Correlation of Electron Tunneling and Plasmon Propagation in a Luttinger Liquid.
Quantum-confined electrons in one dimension behave as a Luttinger liquid. However, unambiguous demonstration of Luttinger liquid phenomena in single-walled carbon nanotubes (SWNTs) has been challenging. Here we investigate well-defined SWNT cross junctions with a point contact between two Luttinger liquids and combine electrical transport and optical nanoscopy measurements to correlate completely different physical properties (i.e., the electron tunneling and the plasmon propagation) in the same Luttinger liquid system. The suppressed electron tunneling at SWNT junctions exhibits a power-law scaling, which yields a Luttinger liquid interaction parameter that agrees quantitatively with that independently determined from the plasmon velocity based on the near-field optical nanoscopy.


Three methods of estimating births averted nationally by contraception.
This paper compares the performance of three methods applicable to national-level demographic data of estimating births averted as a consequence of contraceptive practice. Two are based on the relationship between the general fertility rate (GFR) or total fertility (TFR) and contraceptive prevalence, while the third uses Bongaarts' proximate determinants (PD) model. Estimates of the number of births averted and the percentage by which the number would have increased in the absence of contraception are consistent between the GFR-based and TFR-based methods, but in general lower than the estimates generated by the PD-based method, except for a few high-contraceptive-prevalence countries. For 156 countries and areas around the world the estimated number of births that would have occurred in a recent year in the absence of contraception--the average of the estimates of the three methods--is approximately 230 million, which is more than the estimated 129 million births that actually occurred.


Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity.


Relationship between esophageal contraction patterns and clearance of swallowed liquid and solid boluses in healthy controls and patients with dysphagia.
Non-obstructive dysphagia patients prove to be a difficult category for clinical management. Esophageal high-resolution manometry (HRM) is a novel method, used to analyze dysphagia. However, it is not yet clear how findings on HRM relate to bolus transport through the esophagus. Twenty healthy volunteers and 20 patients with dysphagia underwent HRM and videofluoroscopy in a supine position. Each subject swallowed five liquid and five solid barium boluses. Esophageal contraction parameters and bolus transport were evaluated with HRM and concurrent videofluoroscopy. Stasis of liquid and solid barium boluses occurred in patients and in healthy volunteers in 64% and 41% and in 84% and 82% of the swallows, respectively. Overall, 70% of the liquid and 72% of the solid bolus swallows were followed by a peristaltic contraction, the difference not being statistically significant. Statistically significant associations were found for transition zone length of liquid and solid boluses, and for DCI and distal contraction amplitudes for liquid stasis. No correlation was found between the degree of stasis and other manometric parameters. Stasis of both liquid and solid boluses occurs frequently in patients and in controls and can be regarded as physiological. Motility patterns can predict the effectiveness of bolus transit and level of stasis to some degree but the relationship between esophageal motility and transit is complex and far from perfect. Esophageal manometry is therefore currently deemed unfit to be used for the prediction of bolus transit, and should rather be used for the identification of treatable esophageal motility disorders.


Family practitioners' knowledge about treatment of depressive illness.
Since nonpsychiatrists, particularly family practitioners, treat a large proportion of patients with depressive illness, their knowledge in this area should be assessed. An audience of 227 family practitioners at a postgraduate symposium were examined on basic principles of treatment of depressive illness, particularly the use of tricyclic antidepressants. Their responses were compared to a group of 17 university psychiatrists. The results showed that the family practitioners knew the right treatment for endogenous depression but tended to prescribe inadequate doses of tricyclics and gave too short a therapeutic trial as compared to psychiatrists. Both the psychiatrists and family practitioners tended to discontinue medications about three to six months after improvement, which is considered a somewhat short treatment span but not inappropriate. Family practitioners need to become better informed about tricyclic dosages and therapeutic trials.


Dancing epilepsy: A stereo encephalography case report.
Ictal semiology is essential to identify the epileptogenic zone (EZ), especially in drug-resistant focal epilepsy (DRE), as its accurate identification determines the surgical prognosis. Dancing is highly unusual ictal semiology, and its underlying neural networks remain somehow unclear since both temporal and frontal lobe (FL) have been implicated in its generation. We present a 21-year-old male with DRE characterized by dancing seizures. Homemade videos were obtained. Through a non-invasive pre-surgical evaluation, the epileptogenic zone was localized within a gross lesion in the left FL. Using stereo electroencephalography (SEEG), we successfully identified the ictal-onset zone in the mesial middle, inferior, and orbito-frontal cortex, with rapid propagation of ictal activity extending backward and laterally to the precentral regions. Subsequently, a left frontal middle and inferior gyrectomy was performed, resulting in seizure freedom for the patient. Pathology results revealed a mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). Atypical seizure semiology, such as dancing, provides an interesting starting point for the analysis of the areas involved in the EZ. Further intracranial recordings are required to fully comprehend the underlying networks and interactions of cerebral areas during dancing seizures.


Thyroxine feed-back on the regulation of thyrotropin [TSH] secretion.
1. The role of thyroid hormone as a feed-back at the hypothalamic level in the control of thyrotrophin (TSH) secretion and release has been investigated by estimating the plasma and pituitary TSH levels following intrahypophysial and intrahypothalamic thyroid autotransplants.2. Thyroidectomized rats bearing thyroid autotransplants in the pituitary had a significantly lower (P < 0.001) plasma TSH than that of controls at 26 degrees C but not at 4 degrees C.3. Thyroidectomized rats bearing thyroid autotransplants in the supraoptic area showed a significantly lower (P < 0.001) level of plasma TSH and higher pituitary TSH at 4 degrees C but not at 26 degrees C.4. Study with both unilaterally and bilaterally thyroidectomized rats bearing thyroid autotransplants either in the pituitary or in the hypothalamus revealed that thyroxine feed-back operates at pituitary level in normal situations (26 degrees C) and there exists a feed-back through higher centres, specifically the TSR secreting area of the hypothalamus, in situations demanding higher thyroid function, as in cold exposure.


The feasibility of a telecommunications service in support of outpatient congestive heart failure care in a diverse patient population.
A home telemonitoring system for patients with congestive heart failure was studied for feasibility and efficacy in a diverse patient population. Fifty patients used the service, in which they weighed themselves and answered yes/no questions about symptoms. Changes in patient weights or symptoms prompted a nurse to call the patient and/or the physician. Patients were given educational and quality of life surveys at enrollment, at 30 days, and at 6 months. The average daily usage rate was 94%. Patients were contacted 57 times--prompting 57 physician notifications, eight medication changes, and 11 nonroutine clinic visits. Patient response to lifestyle surveys showed an improvement in quality of life and improved understanding of prevention measures. Eighty-four percent of patients and 65% of physicians reported satisfaction with the system. This pilot study suggests that home telemonitoring is feasible and has clinical utility in diverse patient groups, and may improve patients' satisfaction and knowledge of self-care. (c)2000 by CHF, Inc.


Reciprocal relationship between pain and depression in elderly Chinese primary care patients.
Pain and depression are common in old age but the reciprocal relationship between pain and depression has not been established in a single study. Moreover, few studies have addressed this issue in a primary care setting. The purposes of this study were to examine the reciprocal relationship between pain and depression and to identify whether social support, functional disability or social functioning mediated the link between pain and depression among Hong Kong Chinese elderly primary care patients. Subjects were 318 patients assessed by a trained assessor with MDS-HC at baseline and these subjects were randomly selected from attendants of three randomly selected elderly health centers in Hong Kong. These patients were re-assessed one year after baseline evaluation. Multiple regression analyses revealed that pain at baseline significantly predicted depression at 12-month follow-up assessment when age, gender, martial status, education, and depression at baseline were adjusted for, but depression at baseline was not associated with pain at 12-months after baseline measure while controlling for age, gender, martial status, education, and pain at baseline. However, depression did predict the onset of pain. Moreover, social support, physical disability or social functioning did not mediate the impact of pain on depression. These data suggest that pain is an important predictor of depression in elderly primary care patients. Therefore, aged care service practitioners must take this risk factor into consideration in their preventive intervention and treatment for psychological well-being.


Activities of amidophosphoribosyltransferase (EC18.104.22.168) and the purine phosphoribosyltransferases (EC22.214.171.124 and 188.8.131.52), and the phosphoribosylpyrophosphate content of rat central nervous system at different stages of development--their possible relationship to the neurological dysfunction in the Lesch-Nyhan syndrome.
(1) This communication reports the amidophosphoribosyltransferase (PRPP-At; EC184.108.40.206), hypoxanthine phosphoribosyltransferase (HPRT; EC188.8.131.52) and adenine phosphoribosyltransferase (APRT; EC188.8.131.52) activities and the phosphoribosylpyrophosphate (PRPP) content of rat brain at different stages of development. The results are not age-related in the foetal and neonatal animals and the data for whole brain homogenates are similar to the average results for the individual regions of the brain at the same stage of development. (2) The enzyme activities and PRPP content are similar in the different regions of the rat central nervous system. PRPP-At has the lowest activity of the 3 enzymes studied and this decreases gradually from birth until 8 weeks. HPRT is the most active of the three enzymes, its activity increases markedly between birth and the end of the third week of life. The time course of these changes shows only minor differences between the regions of the brain studied. The ratio of HPRT activity to PRPP-At activity increases from age 1 week in all parts of the rat brain. (3) The APRT activities in rat brain are intermediate between those of PRPP-At and HPRT and essentially steady except for a decrease in the cerebellum during the first 3 weeks of life. (4) The PRPP concentrations in rat brain decrease between birth and the end of the 3rd week of life. (5) The systemic tissues examined have PRPP-At, HPRT and APRT activities. The relationship between the activities of the different enzymes appears to be characteristic of the tissue concerned. (6) Correlating the observed time course of the changes in the ratio of hypoxanthine phosphoribosyltransferase activity to amidophosphoribosyltransferase activity in the rat with other workers' data on changes in the rate of DNA accretion in human brain during development indicates that the main increase in this ratio is after the major bursts of neuroblast and neuroglia proliferation. We suggest that the neurological dysfunction in the Lesch-Nyhan syndrome is due to lack of a purine derivative with a physiological or neuropharmacological function, rather than to an effect of the biochemical lesion on brain morphogenesis.


Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells.
Thyroid hormone, l-thyroxine (T4), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 and to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2. In this study, we examined the mechanism by which T4 impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T4 inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T4 increased expression and cytoplasmic accumulation of PD-L1, which in turn acted to retain inducible COX-2 in the cytoplasm. Knockdown of PD-L1 by small hairpin RNA (shRNA) relieved the inhibitory effect of T4 on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T4 inhibits COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the antagonizing effect of T4 on resveratrol's anticancer properties.


The Impact of Social Media on Preventive Behavior During the COVID-19 Outbreak in South Korea: The Roles of Social Norms and Self-Efficacy.
Social media are important channels to propagate health information and influence preventive behavior during a public health crisis, as witnessed during the coronavirus pandemic (COVID-19). This study explored the association between social media use and preventive behavior during the outbreak of COVID-19 in South Korea. Using the national survey data (N = 1,500), the study examined the mediating role of social norms in the association between social media use for news and information about COVID-19 and preventive behavior. In addition, the study tested the moderating effect of self-efficacy on the mediating path of social media use for preventive behavior via social norms. Conducting a moderated mediation analysis method, this study found that social norms mediated the relationship between social media use and preventive behavior (b = 0.046). Moreover, the study revealed that the indirect relationship between social media use and preventive behavior through social norms becomes stronger as an individual's level of self-efficacy decreases (low: b = 0.044, middle: b = 0.036, and high: b = 0.030). The study provides empirical evidence of the beneficial impact of social media use on preventive behavior. The findings of the study recommend promoting messages on social norms through social media for facilitating preventive behavior.


Genetic dissection of leaf development in Brassica rapa using a genetical genomics approach.
The paleohexaploid crop Brassica rapa harbors an enormous reservoir of morphological variation, encompassing leafy vegetables, vegetable and fodder turnips (Brassica rapa, ssp. campestris), and oil crops, with different crops having very different leaf morphologies. In the triplicated B. rapa genome, many genes have multiple paralogs that may be regulated differentially and contribute to phenotypic variation. Using a genetical genomics approach, phenotypic data from a segregating doubled haploid population derived from a cross between cultivar Yellow sarson (oil type) and cultivar Pak choi (vegetable type) were used to identify loci controlling leaf development. Twenty-five colocalized phenotypic quantitative trait loci (QTLs) contributing to natural variation for leaf morphological traits, leaf number, plant architecture, and flowering time were identified. Genetic analysis showed that four colocalized phenotypic QTLs colocalized with flowering time and leaf trait candidate genes, with their cis-expression QTLs and cis- or trans-expression QTLs for homologs of genes playing a role in leaf development in Arabidopsis (Arabidopsis thaliana). The leaf gene Brassica rapa KIP-related protein2_A03 colocalized with QTLs for leaf shape and plant height; Brassica rapa Erecta_A09 colocalized with QTLs for leaf color and leaf shape; Brassica rapa Longifolia1_A10 colocalized with QTLs for leaf size, leaf color, plant branching, and flowering time; while the major flowering time gene, Brassica rapa flowering locus C_A02, colocalized with QTLs explaining variation in flowering time, plant architectural traits, and leaf size. Colocalization of these QTLs points to pleiotropic regulation of leaf development and plant architectural traits in B. rapa.


Prognostic factors in renal cell carcinoma.
Renal cell carcinoma (RCC) is a very heterogeneous disease with widely varying prognosis. An accurate knowledge of the individual risk of disease progression and mortality after treatment is essential to counsel patients, plan individualized surveillance protocols and select patients for adapted treatment schedules and new clinical trials. A systematic review of the literature on prognostic factors of localized and metastatic RCC was performed. Prognostic factors in RCC include anatomical (TNM classification, tumor size), histological (Fuhrman grade, histologic subtype), clinical (symptoms and performance status), and molecular features. All these features are not perfectly accurate when used alone. Therefore an increasing number of prognostic models or nomograms that include several combined prognostic features have been designed in order to improve predictive accuracy. UCLA Integrated Staging System (UISS) and the Mayo Clinic's SSIGN score are the two most used prognostic models for localized RCC. In the setting of metastatic RCC the classical anatomical and histological tumor features have little predictive value. However, accurate prognostic models have been designed to predict response to therapy, and progression-free and overall survival. The two most used tools to predict response to immunotherapy are the model designed by the French Group of Immunotherapy and the Motzer's model. The advent of tyrosine kinase inhibitors and antiangiogenic drugs have deeply changed the treatment of metastatic RCC. Predictive tools that are adapted to the modern targeted therapies are now needed. There is increasing knowledge on prognostic factors of localized and metastatic RCC. Several predictive models have been developed by combining different prognostic features and are valuable tools for patient counseling, treatment decision-making and trial design. Further research is needed to assess whether the combination of classical prognostic factors with molecular features and information from gene and protein expression profiling can increase the predictive accuracy of the current prognostic models.


Anatomic Study of Anterior and Posterior Ankle Portal Sites for Ankle Arthroscopy in Plantarflexion and Dorsiflexion: A Cadaveric Study in the Japanese Population.
Arthroscopy is an important and minimally invasive diagnostic and therapeutic tool. However, the risk of injury to the neurovascular structures around the portals exists during arthroscopy of the ankle. In the present study, we measured the distance between each portal and the adjacent neurovascular structures with the foot in plantarflexion and dorsiflexion in the Japanese population. Standard anterolateral (AL), anteromedial, posterolateral (PL), and posteromedial portal positions were identified in 6 fresh adult cadaveric feet. The skin was dissected from the underlying tissue to visualize the adjacent neurovascular structures as noninvasively as possible. The superficial peroneal nerve was the structure closest to an anterior (i.e., AL) portal (3.2 ± 4.2 and 8.3 ± 3.9 mm in plantarflexion and 5.2 ± 4.3 and 10.8 ± 4.1 mm in dorsiflexion), followed by the saphenous nerve and great saphenous vein (SpV). The distance from the superficial peroneal nerve to the AL portal and from the saphenous nerve and great SpV to the anteromedial portal increased significantly with dorsiflexion and decreased significantly with plantarflexion. The sural nerve was the structure closest to the posterior (i.e., PL) portal (10.4 ± 4.8 mm in plantarflexion and 8.5 ± 3.9 mm in dorsiflexion), followed by the lesser SpV. The distance from the sural nerve, saphenous nerve, and lesser SpV to the PL portal and from flexor hallucis longus, posterior tibial artery, and tibial nerve to the posteromedial portal increased significantly in plantarflexion and decreased significantly in dorsiflexion. These findings could help to prevent damage to the neurovascular structures during ankle arthroscopy.


Diamond photonic crystals for the IR spectral range.
2D photonic crystals formed inside monocrystalline diamond to operate in the IR spectral range are reported. The photonic structures consisting of 150-μm-long graphitized wires arranged in a square matrix with a period of 4 μm were produced by laser writing with ultrashort pulses. Transmittance spectra (λ=1-14 μm) measured for the structures with increasing thickness demonstrate the occurrence of few minima being different for TM and TE polarization modes. Complex refraction index of the laser-modified material was evaluated for the first time in order to be used in computer simulation of the structures.


Unraveling the potential mechanisms of the anti-osteoporotic effects of the Achyranthes bidentata-Dipsacus asper herb pair: a network pharmacology and experimental study.
Background: Osteoporosis is a prevalent bone metabolism disease characterized by a reduction in bone density, leading to several complications that significantly affect patients' quality of life. The Achyranthes bidentata-Dipsacus asper (AB-DA) herb pair is commonly used in Traditional Chinese Medicine (TCM) to treat osteoporosis. This study aimed to investigate the therapeutic compounds and potential mechanisms of AB-DA using network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. Methods: Identified compounds of AB-DA were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCM-ID), TCM@Taiwan Database, BATMAN-TCM, and relevant literature. The main bioactive ingredients were screened based on the criteria of "OB (oral bioavailability) ≥ 30, DL (drug-likeness) ≥ 0.18." Potential targets were predicted using the PharmMapper and SwissTargetPrediction websites, while disease (osteoporosis)-related targets were obtained from the GeneCards, DisGeNET, and OMIM databases. The PPI network and KEGG/GO enrichment analysis were utilized for core targets and pathway screening in the STRING and Metascape databases, respectively. A drug-compound-target-pathway-disease network was constructed using Cytoscape software to display core regulatory mechanisms. Molecular docking and dynamics simulation techniques explored the binding reliability and stability between core compounds and targets. In vitro and in vivo validation experiments were utilized to explore the anti-osteoporosis efficiency and mechanism of sitogluside. Results: A total of 31 compounds with 83 potential targets for AB-DA against osteoporosis were obtained. The PPI analysis revealed several hub targets, including AKT1, CASP3, EGFR, IGF1, MAPK1, MAPK8, and MAPK14. GO/KEGG analysis indicated that the MAPK cascade (ERK/JNK/p38) is the main pathway involved in treating osteoporosis. The D-C-T-P-T network demonstrated therapeutic compounds that mainly consisted of iridoids, steroids, and flavonoids, such as sitogluside, loganic acid, and β-ecdysterone. Molecular docking and dynamics simulation analyses confirmed strong binding affinity and stability between core compounds and targets. Additionally, the validation experiments showed preliminary evidence of antiosteoporosis effects. Conclusion: This study identified iridoids, steroids, and flavonoids as the main therapeutic compounds of AB-DA in treating osteoporosis. The underlying mechanisms may involve targeting core MAPK cascade (ERK/JNK/p38) targets, such as MAPK1, MAPK8, and MAPK14. In vivo experiments preliminarily validated the anti-osteoporosis effect of sitogluside. Further in-depth experimental studies are required to validate the therapeutic value of AB-DA for treating osteoporosis in clinical practice.


Consumers' purchase decisions for products with nutrition and health claims: What role do product category and gaze duration on claims play?
Labeling food packages with nutrition and health claims is a widely used practice. This study aims to contribute to the literature by examining the gaze and purchase behavior of consumers regarding food products with nutrition and health claims. A close-to-realistic purchase situation with three-dimensional food packages with nutrition, health, and taste claims was simulated while the participants' eye movements were measured using head-mounted eye tracking glasses. In the purchase situation, two food categories with differing perceived healthiness were offered, orange juice and milk chocolate. In total, 156 consumers participated in this study which was undertaken in Germany. The findings indicate that each claim was noticed by at least 85% of the participants and health claims were looked at longer than nutrition or taste claims. Furthermore, when compared to other participants, the longer a participant looked at a specific claim, the more likely the participant was to purchase the respective product. Even though the product category had no effect on the gaze duration on claims, it affected the purchase behavior. Nutrition claims were preferred for orange juice while taste claims were preferred for milk chocolate. Health claims were preferred for neither. Marketers can benefit from this study, as it shows the gaze duration on claims influenced the purchase likelihood. Another important finding is that there are great differences between product categories regarding the type of claim consumers prefer.


The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up.
To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.


Functional compartmentalization of the neuronal growth cone: determining calcium's place in signaling cascades.
The growth cone is generally regarded as the basic unit of neuronal organization concerned with development of connections within the nervous system. The discussion below illustrates that the growth cone itself can be subdivided into distinct units of organization. It is this functional compartmentalization which enables the growth cone to read the molecular terrain it traverses and to convert this information into precise motor events. Our discussion will focus on the flow of information from the environment to the growth cone. In particular, we will follow signaling events from their remote processing within filopodia to the biological equivalent of a central processing unit in the core of the growth cone.


Pressure Ulcer Prevalence and Care in Indonesian Hospitals: A Multicenter, Cross-sectional Evaluation Using an Extended Donabedian Model.
Although the number of studies on pressure ulcer (PU) occurrence continues to grow, research regarding the quality of PU care and its effect on outcomes is limited. Using an extended Donabedian model, a 1-day, multicenter, cross-sectional evaluation of the quality of PU care was conducted in a convenience sample of Indonesian hospitals among patients ≥18 years of age in the medical, surgical, and intensive care units. Structure (ie, hospital attributes), process (recommended PU preventive measures), and outcome indicators (nosocomial PU prevalence excluding nonblanchable erythema), along with patient characteristics (age, gender, ethnicity, admission days, diseases [per ICD-10], recent surgery, PU categorization [4 categories according to National Pressure Ulcer Advisory Panel-European Pressure Ulcer Advisory Panel guidelines], PU history, care dependency, and Braden score) were examined. Patient data were collected by 2 nurses -1 from the patient's unit and 1 from another unit - using the Landelijke Prevalentiemeting Zorgproblemen-International questionnaire, a paper-and-pencil survey translated into Indonesian. Heads of wards and nursing units completed the questionnaires at institutional and ward levels, respectively. The data were analyzed using descriptive and bivariate analyses, and multilevel logistic regression modeling was applied according to the generalized estimating equation approach. Among the 4 participating hospitals, 66 care units, 36 pairs of nurses, and 1132 adult patients (mean age 48.7 ± 17.4 years, 40.9% women) were involved. Ninety-one (91) patients developed 1 or more PUs; the nosocomial PU prevalence (excluding nonblanchable erythema, category I) was 3.6%. The most frequently used PU preventive measures were patient education (329, 29.1%), repositioning (269, 23.8%), and skin moisturizing (266, 23.5%). The factors most associated with nosocomial PU rate excluding category I were the inclusion of PU care in patient care files (P = .001), repositioning (P = .002), skin moisturizing (P = .009), age (P = .013), admission days (P = .001), care dependency scores (P = .047), immobility (P = .001), sensory perception limitation (P = .001), moist skin (P = .032, OR 13.74), and friction and shear problem (P = .001). The prevalence of nosocomial PUs in this study was comparable to previous research in the Netherlands and rather low, even though limited structural indicators and suboptimal preventive measures were noted. Also, outdated preventive measures such as massage, donuts, and water-filled gloves were still used. The quality of PU care in these hospitals may be improved by addressing the absence of structural factors, including protocols/guidelines. Future research is needed for guideline implementation programs in Indonesian hospitals.


Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials.
Symptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms. This study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset. In each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman's rho; p < 0.01, all comparisons listed here): FEV1% predicted (-0.19, -0.14, -0.15); St. George's Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (-0.30, -0.14) and incremental shuttle walk (ISWT) (-0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed. Results suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials. MPEX: NCT00739648 ; AZ1: NCT00949975 ; AZ 2: NCT01023516.


Imipenem use in serious childhood infections.
Imipenem plus cilastatin is a beta-lactam antibiotic with a broad spectrum and good tolerance. For this its use is indicated in serious infections even in children. The authors carried out a preliminary bacteriological study in patients affected by serious infection, cystic fibrosis, tumors, neutropenia, subjects undergoing intensive therapy and those with abdominal surgical infection. Isolated microorganism sensitivity in these patients, towards imipenem was very high (89%-100%). With these premises, 35 patients with serious infections in various locations were treated only with imipenem. Of these, 15 were oncologic neutropenic and 20 normal. In the first group therapeutic success was 66.6% and in the second one 80%. Local and systemic tolerance always showed good results.


Early detection and successful therapy of fulminant chlamydia pneumoniae myocarditis.
We report a case involving a young female patient with Chlamydia pneumoniae myocarditis who required assist device therapy for acute heart failure. Early diagnosis was provided by endomyocardial biopsy, and tailored antibiotic therapy facilitated quick recovery of myocardial function. This is the first case to report detecting C pneumoniae as the pathogen responsible for fulminant myocarditis while the patient was still alive and to report long-term follow-up data.


Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases.
Nucleotide sequence analysis of two cDNA clones, one shown to direct the synthesis in Escherichia coli of the pI 6.7 form of the 20,000-molecular-weight class of Chinese hamster lung cell dihydrofolate reductase, and the other shown to direct the synthesis of the pI 6.5 form of the 21,000-molecular-weight class of the enzyme, has revealed the following: (i) the differences in physical and enzymatic properties displayed by these two proteins are due to two variations in their respective amino acid sequences with the conversion of Leu to Phe at position 22 probably responsible for the differential sensitivity of these two enzymes to methotrexate and methasquin; (ii) the multiple mRNAs responsible for the synthesis of each of these proteins differ in size due, at least in part, to a length heterogeneity at their 3' ends; (iii) these two proteins are encoded by different genes; and (iv) the sequence AAATATA appears to be a major polyadenylation signal in one Chinese hamster lung cell dihydrofolate reductase gene and a minor signal in another.


Inhibiting MMP activity prevents the development of endometriosis in the chicken chorioallantoic membrane model.
Matrix metalloproteinases (MMPs) are essential for extracellular matrix remodelling and may contribute to the development of endometriosis. Transplantation of endometrium onto the chicken chorioallantoic membrane (CAM) results in endometriosis-like lesion formation, a process that requires extensive tissue remodelling. We investigated the expression of a wide range of MMPs in menstrual endometrium, endometriosis-like lesions in CAMs, in peritoneal endometriosis and in endometriosis in the rectovaginal space, as well as the function of MMPs in early lesion formation in the CAM model. Expression of MMPs was evaluated by immunohistochemistry and MMP function was studied in the CAM by inhibiting MMP activity during lesion formation. Nearly all MMPs were present in all tissues studied. No significant differences in the expression of a majority of MMPs were found in endometriosis-like lesions in CAMs when compared with human endometriosis. Inhibition of MMP-1, -2, -3, -7 and -13 activities significantly impaired endometriosis-like lesion formation in CAMs. The MMP expression profiles of experimentally induced endometriosis in CAMs and human endometriosis are similar. The prevention of endometriosis-like lesion formation in the CAM by inhibiting MMP activity strongly suggests that MMPs have a function in the early development of endometriotic lesions.


Agomelatine treatment of major depressive disorder.
To review the efficacy, safety, pharmacologic, and pharmacokinetic data of agomelatine to better understand its potential role in the treatment of patients with major depressive disorder. A MEDLINE search (1966-October 2008) was conducted using the following terms: agomelatine, antidepressant, S20098, melatonin, serotonin, 5-HT(2C), MT, efficacy, safety, adverse effect, pharmacology, pharmacokinetic, receptor binding, depression, major depressive disorder, and mood disorder. All articles in English identified from the data sources were evaluated. Randomized, controlled trials involving humans were prioritized in the review. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. Agomelatine, a potent agonist at type 1 and 2 melatonin receptors, selectively inhibits serotonin. It is extensively metabolized via cytochrome P450 isoenyzmes 1A1, 1A2, and 2C9 to metabolites with less activity than the parent drug. Five randomized controlled studies were identified that examined the efficacy and safety of agomelatine in major depressive disorder. In general, agomelatine was found to produce significant improvements in depressive symptoms compared with placebo on many, but not all, rating scales. Three of the trials had active comparator arms (ie, venlafaxine, paroxetine). In these 3 investigations, agomelatine produced effects on depressive symptoms similar to those of the comparator drugs. A small number of studies have demonstrated sleep benefits with the use of agomelatine in depressed patients. Positive findings also exist for the use of agomelatine in seasonal affective disorder and bipolar depression. The most common adverse effects reported with agomelatine use were headache, nasopharyngitis, and gastrointestinal complaints. The magnitude of agomelatine-related adverse effects appears to be at least similar to some currently marketed antidepressants. Overall, agomelatine is a promising and well-tolerated medication for the treatment of major depressive disorder. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy and safety of agomelatine.


Dietary Intake and Obesity among Filipino Americans in New Jersey.
The prevalence of obesity is a public concern and is linked to chronic diseases. Filipino Americans have a high prevalence rate of hypertension and diabetes. This study investigated the dietary intake of first-generation Filipino Americans (n=210). In addition, it provides a comparison of the obesity rates using the International guideline and the WHO Asian recommendation. The dietary intake included caloric, carbohydrate, and fat intake and was determined using the Block Brief Food Frequency Questionnaire. The anthropometric measurements included actual height, weight, and waist measurements. The body mass index (BMI) and waist circumference were categorized using the International guideline and the WHO Asian recommendation to determine obesity. The caloric and carbohydrate intake were normal; however, fat intake was increased. The BMI and waist circumference showed substantial difference when using the International and Asian guidelines to determine obesity. The results highlight the increased health risks of Filipino American immigrants including a high dietary fat intake and an increased obesity rate.


Preparation of mixed ligand immobilized artificial membranes for predicting drug binding to membranes.
Mixed ligand immobilized artificial membranes (IAMs) are surfaces that contain at least two immobilized membrane phospholipids which are designated as either the primary phospholipid or the secondary phospholipid. The primary immobilized phospholipid refers to the immobilized phospholipid that has the highest surface density. For this work, the primary immobilized phospholipid was a single-chain ether phosphatidylcholine (PC) analog. Four mixed-ligand IAMs were prepared by use of immobilized PC as the primary immobilized phospholipid. The secondary immobilized phospholipid ligand was either phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, or phosphatidic acid. All of these secondary phospholipids are bonded at approximately 6-10 mol % relative to the molar amount of immobilized PC. Each secondary phospholipid contains functional groups in the polar head group region that require protecting groups during the immobilization process. The four-step synthetic strategy to prepare mixed-ligand IAMs involves (i) immobilization of the PC analog at high density to silica propylamine (SPA), (ii) immobilization of the second phospholipid (PL) analog at low density, (iii) end capping residual amines with a long-chain anhydride followed by end capping with a short-chain anhydride, and (iv) deprotection of the polar head group protecting groups. The surface density of the mixed PLs bonded to the silica support was approximately 130 mumol of PLs/g of SPA. High-performance liquid chromatography using these mixed lipid IAMs can be exploited to rapidly predict the membrane binding properties of drugs.


Sequence divergence, functional constraint, and selection in protein evolution.
The genome sequences of multiple species has enabled functional inferences from comparative genomics. A primary objective is to infer biological functions from the conservation of homologous DNA sequences between species. A second, more difficult, objective is to understand what functional DNA sequences have changed over time and are responsible for species' phenotypic differences. The neutral theory of molecular evolution provides a theoretical framework in which both objectives can be explicitly tested. Development of statistical tests within this framework has provided insight into the evolutionary forces that constrain and in some cases change DNA sequences and the resulting patterns that emerge. In this article, we review recent work on how functional constraint and changes in protein function are inferred from protein polymorphism and divergence data. We relate these studies to our understanding of the neutral theory and adaptive evolution.


The Shifting Landscape in Utilization of Inpatient, Observation, and Emergency Department Services Across Payers.
Recent policies by public and private payers have increased incentives to reduce hospital admissions. Using data from four states from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project, this study compared the payer-specific population-based rates of adults using inpatient, observation, and emergency department (ED) services for 10 common medical conditions in 2009 and in 2013. Patients had an expected primary payer of private insurance, Medicare, Medicaid, or no insurance. Across all four payer populations, inpatient admissions declined, and care shifted toward treat-and-release observation stays and ED visits. The percentage of hospitalizations that began with an observation stay increased. Implications for quality of care and costs to patients warrant further examination. Journal of Hospital Medicine 2017;12:443-446.


Adsorption and scattering of H2 and D2 by NiAl(110).
We present quasiclassical dynamics calculations of H2 and D2 scattering by the NiAl(110) surface using a recently proposed six-dimensional potential-energy surface (PES) obtained from density-functional theory calculations. The results for dissociative adsorption confirm several experimental predictions using (rotationally hot) D2 beams, namely, the existence of a dissociation barrier, the small isotopic effect, the importance of vibrational enhancement, and the existence of normal energy scaling. The latter conclusion shows that normal energy scaling is not necessarily associated with weak corrugated surfaces. The results for rotationally elastic and inelastic diffractions are also in reasonable agreement with experiment, but they show that many more diffractive transitions are responsible for the observed structures than previously assumed. This points to the validity of the PES recently proposed [P. Riviere, H. F. Busnengo, and F. Martin, J. Chem. Phys. 121, 751 (2004)] to describe dissociative adsorption as well as rotationally elastic and inelastic diffractions in the H2NiAl(110) system.


[Comparative dimensions of propriospinal neurons of different structuro-functional groups in the cat].
Profile areas of somata and proximal dendrites and conventional diameters (c.d.--diameter of a circle equiareal to this profile) of descending propriospinal interneurons labelled by horseradish peroxidase were measured in cat spinal cord. C.d. of different units varied approximately from 12 to 80 micron. Mean values of c.d. for neurons located in cervical, thoracic and lumbar segments and sending axons to L6-7 level were 39.9, 30.8 and 36.9 micron; therefore, direct correlation of the dimensions of a neuron and the length of its axon was not observed. C. d. distribution at cervical level was bimodal indicating the existence of two populations of long-axon propriospinal neurons; large units concentrated only at cervical level and small ones distributed throughout cervical and thoracic segments. Mean c. d. of neurons in cervical segments labelled by peroxidase injection at lower cervical levels was 44.2 micron indicating larger dimensions of short-axon cervical propriospinal units. The smallest (mean c.d. 20-22 micron) propriospinal neurons were located in the dorsal layers of dorsal horn, the largest ones--in the ventral horns. No substantial difference between dimensions of neurons with uncrossed and crossed axons was found.


Mycology of Onychomycosis: A 5-year retrospective review (2011 - 2015) in Hospital Kuala Lumpur.
Onychomycosis is a common nail disease with numerous etiological pathogens. In order to determine and trend the local mycological pattern of culture-positive diseased nail samples sent from the Department of Dermatology, Hospital Kuala Lumpur, a five-year retrospective audit was carried out, which revealed that non-dermatophyte molds were the predominant fungi isolated, followed by yeasts and dermatophytes. This is similar to two previous studies in Malaysia, but varies greatly from other studies around the world which showed a dermatophyte-predominant prevalence. This could be due to the nature of the environment our patients encountered.


Protein quality of two varieties of high-lysine maize fed alone and with black beans or milk to normal and depleted weanling rats.
Opaque-2 corn, modified high-lysine corn with vitreous endosperm, and common corn were compared in rat growth studies. Corn alone supplied 8.6% protein; and at both 8.6 and 11.4% protein, corn furnished 60% of the protein and either milk or black beans supplied 40%. The modified corn, which also was high in both lysine and tryptophan, did not differ significantly from Opaque-2 corn in its ability to stimulate growth and nitrogen deposition in both well-nourished and partially protein-depleted rats; and both were significantly superior to common corn when fed alone. Milk was a more effective supplement for corn than black beans, especially when high-lysine varieties were fed, whereas beans exerted a similar effect on all varieties of corn. The depleted rats deposited more nitrogen as a result of eating most diets than did well nourished rats. Implications of these findings for preschool children are discussed.


Effect of cytokinins on in vitro multiplication, volatiles composition and rosmarinic acid content of Thymus leucotrichus Hal. shoots.
An efficient in vitro multiplication protocol was designed to Thymus leucotrichus, a subshrub and perennial herb growing naturally in the Northwest of Turkey. Of all basal media studied, Murashige and Skoog medium was found to be superior to the others, providing higher shoot formation and the maximum shoot length. Varying concentrations of cytokinins, i.e., 6-benzyladenine, thidiazuron, 2-isopentenyladenine and kinetin were supplemented in the nutrient media to observe their effects on shoot development and biomass. Rosmarinic acid content and volatile compositions of both naturally growing plants and in vitro multiplied plantlets were also evaluated. 6-benzyladenine (1.0 mg/L) and kinetin (0.5 mg/L) were found to be optimum for shoot number and shoot elongation, respectively. Thidiazuron (1.0 mg/L) was superior for biomass production. Rosmarinic acid content of in vitro multiplied plants was found to be higher than that of wild plants, reaching a maximum with 0.5 mg/L 2-isopentenyladenine, which yielded 10.15 mg/g dry weight. The highest thymol content was obtained with 1.0 mg/L kinetin (55.82%), while thidiazuron (0.1 mg/L) increased carvacrol production (12.53%). Overall, Murashige and Skoog medium supplemented with 1.0 mg/L kinetin was determined to be the most favorable medium studied.


Immunopathogenesis and immunotherapy of multiple myeloma.
Despite the advent of novel therapies and improvements in survival, multiple myeloma (MM) remains an incurable disease. Thus, new treatment strategies including immunotherapies are needed for MM patients with stable disease after induction chemotherapy as well as for disease control in patients with advanced disease. However, profound immune dysregulation not only of B cells, but also of other immune cells such as natural killer cells, T cells, and dendritic cells and increase in the number of immunosuppressive cells, i.e., regulatory T and B cells and myeloid-derived suppressor cells, have been demonstrated in advanced MM patients, which may be involved in disease progression. Because of immune dysfunction, immunotherapies have not shown clinical efficacy in MM patients. It is therefore crucial to resolve immunosuppressive mechanisms and improve immune responses, especially in advanced MM patients. Recently, excellent clinical efficacy of new immunotherapeutic strategies such as immunomodulatory drug-intensified monoclonal antibody treatment, immune checkpoint inhibitors, and chimeric antigen receptor T-cell therapy targeting B cell maturation antigen has been reported in advanced-stage MM patients. Those new treatments or their combination will improve prognosis and possibly point toward a cure for myeloma.


Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2.
1. We investigated the response to pressure (myogenic tone) and flow of rat mesenteric resistance arteries cannulated in an arteriograph which allowed the measurement of intraluminal diameter for controlled pressures and flows. Rats were treated for 3 weeks with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1 day-1) or L-NAME plus the angiotensin I converting enzyme inhibitor (ACEI) quinapril (10 mg kg-1 day-1). 2. Mean blood pressure increased significantly in chronic L-NAME-treated rats (155 +/- 4 mmHg, n = 8, vs control 121 +/- 6 mmHg, n = 10; P < 0.05). L-NAME-treated rats excreted significantly more dinor-6-keto prostaglandin F1 alpha (dinor-6-keto PGF1 alpha), the stable urinary metabolite of prostacyclin, than control rats. The ACEI prevented the rise in blood pressure and the rise in urinary dinor-6-keto PGF1 alpha due to L-NAME. 3. Isolated mesenteric resistance arteries, developed myogenic tone in response to stepwise increases in pressure (42 +/- 6 to 847 +/- 10 mN mm-1, from 25 to 150 mmHg, n = 9). Myogenic tone was not significantly affected by the chronic treatment with L-NAME or L-NAME + ACEI. 4. Flow (100 microliters min-1) significantly attenuated myogenic tone by 50 +/- 6% at 150 mmHg (n = 10). Flow-induced dilatation was significantly attenuated by chronic L-NAME to 22 +/- 6% at 150 mmHg (n = 10, p = 0.0001) and was not affected in the L-NAME + ACEI group. 5. Acute in vitro NG-nitro-L-arginine (L-NOARG, 10 microM) significantly decreased flow-induced dilation in control but not in L-NAME or L-NAME + ACEI rats. Both acute indomethacin (10 microM) and acute NS 398 (cyclo-oxygenase-2 (COX-2) inhibitor, 1 microM) did not change significantly flow-induced dilatation in controls but they both decreased flow-induced dilatation in the L-NAME and L-NAME + ACEI groups. Acute Hoe 140 (bradykinin receptor inhibitor, 1 microM) induced a significant contraction of the isolated mesenteric arteries which was the same in the 3 groups. 6. Immunofluorescence analysis of COX-2 showed that the enzyme was expressed in resistance mesenteric arteries in L-NAME and L-NAME + ACEI groups but not in control. COX-1 expression was identical in all 3 groups. 7. We conclude that chronic inhibition of nitric oxide synthesis is associated with a decreased flow-induced dilatation in resistance mesenteric arteries which was compensated by an overproduction of vasodilator prostaglandins resulting in part from COX-2 expression. The decrease in flow-induced dilatation was prevented by the ACEI, quinapril.


[Textual research on decipher of"prescriptions for treating children's head sore"from Zhi re bing yao lun (Essentials on Treatment of Febrile Diseases) in the Western Xia regime].
There were 3 prescriptions for treating children's head sore, инв6476-28, 29, 30 preserved in Russia, included in the Zhi re bing yao lun (Essentials on Treatment of Febrile Diseases), a medical literature of the Western Xia regime. Based on the correlated relationship between the Tangut language and the Chinese characters, the 3 prescriptions were translated into Chinese, and then compared with Chinese medical documents. It could be seen that medical system in the Western Xia regime had an inseparable relationship with that of the Han nationality, while keeping the features of the northwestern nomadic nationalities at the same time.


Near Point of Convergence and Gait Deficits in Adolescents After Sport-Related Concussion.
To prospectively examine gait characteristics of participants acutely after concussion with and without receded near point of convergence (NPC), compared with healthy controls. Cross-sectional study. Sports-medicine clinic. Patients examined after concussion (n = 33; mean ± SD = 7.2 ± 3.1 days) and a group of uninjured athletes (n = 31) completed a Postconcussion Symptom Scale, underwent NPC testing, and single/dual-task gait assessments. Near point of convergence was defined as the patient-reported diplopia distance when a fixation target moved toward the nose. Receded NPC was defined as a distance >5 cm from the tip of the nose. Spatiotemporal gait characteristics in single-task and dual-task conditions were evaluated with analysis of variance; correlations were calculated between NPC and gait measures. Eighteen of 33 (55%) patients with concussion presented with receded NPC. Those with receded NPC exhibited slower gait speed (single-task = 1.06 ± 0.14 m/s vs 1.19 ± 0.15 m/s; dual-task = 0.80 ± 0.13 m/s vs 0.94 ± 0.13 m/s; P = 0.003) and shorter stride lengths (single-task = 1.11 ± 0.10 m vs 1.24 ± 0.11 m; dual-task = 0.97 ± 0.11 m vs 1.09 ± 0.11 m; P = 0.001) than healthy controls. Near point of convergence was moderately correlated with dual-task average walking speed for the normal NPC group (ρ = -0.56; P = 0.05). Postconcussion Symptom Scale scores did not significantly differ between groups (27 ± 18 vs 28 ± 16). After concussion, adolescents with receded NPC exhibited significant gait-related deficits compared with healthy controls, whereas those with normal NPC did not. Vergence and gross motor system dysfunction may be associated after concussion. Gait and vergence measures may contribute useful information to postconcussion evaluations.


Microtubule-associated protein tau is hyperphosphorylated during mitosis in the human neuroblastoma cell line SH-SY5Y.
A phosphorylated tau epitope specific for paired helical filaments in Alzheimer's disease is recognized by monoclonal antibody PHF-1. Healthy adult brains lack the PHF-1 epitope (PHF-1 tau), but it is transiently expressed by immature neurons during development. We have found that proliferating SH-SY5Y human neuroblastoma cells also express PHF-1 tau. Consistent with the recent finding that cell-cycle-dependent kinases can phosphorylate tau in vitro, flow cytometry showed that mitotic SH-SY5Y cells were up to 18-fold more PHF-1 immunoreactive than nonmitotic cells. On immunoblots, PHF-1 tau in mitotic and nonmitotic cells also was strikingly different. First, mitosis induced a prominent PHF-1 reactive band at 120 kDa, which likely accounted for the large increase in PHF-1 signal seen at mitosis. Although the size of the 120-kDa band is consistent with it being the high-molecular-weight form of tau, other antibodies to tau did not recognize it. Second, mitosis caused a hyperphosphorylation of the PHF-1 immunoreactive tau band normally seen at 50 kDa. In mitotic cells this band had an increased intensity and molecular weight. Alkaline phosphatase treatment abolished tau M(r) heterogeneity, verifying that the variations in mobility were due to phosphorylation. These data show that cell-cycle-dependent hyperphosphorylation of tau occurs in intact cells, and they support the hypothesis that aberrant activity of cell-cycle-dependent kinases may contribute to tau phosphorylation and PHF formation in Alzheimer's disease.


Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features.
Dermatomyositis (DM) is a major clinical subset of autoimmune myositis (AIM). The characteristic DM rash (Gottron papules, heliotrope rash) and perifascicular atrophy at skeletal muscle biopsy are regarded as specific features for this diagnosis. However, new concepts are challenging the current definition of DM. A modified Bohan and Peter classification of AIM was proposed in which the core concept was the inclusion of the diagnostic significance of overlap connective tissue disease features. In this clinical classification, a DM rash in association with myositis in the absence of overlap features indicates a diagnosis of pure DM. However, overlap features in association with myositis allow a diagnosis of overlap myositis (OM), irrespective of the presence or absence of the DM rash. Perifascicular atrophy may be present in both pure DM and OM. Recently, the presence of perifascicular atrophy in myositis without a DM rash was proposed as diagnostic of a novel entity, adermatopathic DM. We conducted the present study to evaluate these new concepts to further differentiate pure DM from OM.Using the modified Bohan and Peter classification, we performed a follow-up study of a longitudinal cohort of 100 consecutive adult French Canadian patients with AIM, including 44 patients with a DM phenotype, defined as a DM rash, and/or DM-type calcinosis, and/or the presence of perifascicular atrophy on muscle biopsy. A detailed evaluation was performed for overlap features, the extent and natural history of the DM rash, adermatopathic DM, DM-specific and overlap autoantibodies by protein A immunoprecipitation on coded serum samples, and associations with cancer and survival.Two distinct subsets were identified in patients with a DM phenotype: pure DM (n = 24) and OM with DM features, or OMDM (n = 20). In pure DM, the DM rash was a dominant finding. It was the first disease manifestation, was always present at the time of myositis diagnosis, and was associated with a high cutaneous score and chronicity. Concurrent heliotrope rash and Gottron papules (positive predictive value [PPV] 91%), as well as the V-sign and/or shawl sign (PPV 100%), were diagnostic of pure DM. Anti-Mi-2, anti-MJ, and anti-p155 autoantibodies were present in 50% of pure DM patients and were restricted to this subset (PPV 100%). Cancer was present in 21% of pure DM patients. The 15-year survival was excellent (92%).In contrast, in patients with OMDM, the first manifestation was proximal muscle weakness or other skeletal muscle-related complaints. The DM rash appeared at diagnosis or at follow-up, was associated with a low cutaneous extent score and was transient. Adermatopathic DM, which was absent in pure DM, was highly predictive (PPV 100%) of OMDM. Overlap autoantibodies (including anti-Jo-1, anti-PL-7, anti-PM-Scl, anti-U1RNP, and/or anti-U5-RNP) were found in 70% of OMDM patients. OMDM was not associated with cancer, but the 15-year survival was significantly decreased (65%).Perifascicular atrophy occurred as commonly in OMDM (n = 6/20, 30%) as in pure DM (n = 4/24, 17%) patients. These 6 OMDM patients had adermatopathic DM at myositis diagnosis, and only 1 of them developed a DM rash at follow-up, emphasizing the lack of specificity of perifascicular atrophy for pure DM.In conclusion, using the modified Bohan and Peter classification of AIM allowed identification of OMDM, a new clinical subset of OM. Furthermore, identification of OMDM allowed recognition of pure DM as a new entity that was distinct from OMDM or from OM without DM features. However, the absolute specificity of a DM rash and perifascicular muscle atrophy for the diagnosis of pure DM was lost. The distinctive clinical manifestations and autoantibody profiles presented are proposed as diagnostic criteria to differentiate pure DM from OMDM.


Is there really a link between exact-number knowledge and approximate number system acuity in young children?
Although everyone perceives approximate numerosities, some people make more accurate estimates than others. The accuracy of this estimation is called approximate number system (ANS) acuity. Recently, several studies have reported that individual differences in young children's ANS acuity are correlated with their knowledge of exact numbers such as the word 'six' (Mussolin et al., 2012, Trends Neurosci. Educ., 1, 21; Shusterman et al., 2011, Connecting early number word knowledge and approximate number system acuity; Wagner & Johnson, 2011, Cognition, 119, 10; see also Abreu-Mendoza et al., 2013, Front. Psychol., 4, 1). This study argues that this correlation should not be trusted. It seems to be an artefact of the procedure used to assess ANS acuity in children. The correlation arises because (1) some experimental designs inadvertently allow children to answer correctly based on the size (rather than the number) of dots in the display and/or (2) young children with little exact-number knowledge may not understand the phrase 'more dots' to mean numerically more. When the task is modified to make sure that children respond on the basis of numerosity, the correlation between ANS acuity and exact-number knowledge in normally developing children disappears.


Population dynamics of anophelines in a malathion treated village in the intermediate zone of Sri Lanka.
As part of research programme on malaria transmission in Sri Lanka, a study was made of man-biting anophelines at Nikawehera, a village on the border of the intermediate and dry rainfall zones. Weekly mosquito collections by night human bait (NHB) were performed inside and outside four fixed stations from October 1992 till March 1993. Houses in the village were treated with malathion by the Anti-Malaria Campaign in October and at the end of January 1993. An. culicifacies and An. tesselatus were the most abundant species. An. culicifacies was probably the only species responsible for malaria transmission. An. culicifacies densities varied between stations and reflected differences in availability of breeding places. An. culicifacies aggressivity is closely related to the rainfall pattern, increasing after the first monsoon rains in November and reaching a peak in late December--early January. Vectorial capacity, however, decreased during the first weeks of the rainy season. The maximum vectorial capacity was found in January. The night biting cycle of An. culicifacies showed a peak between 20.00 and 23.00 h. Since the introduction of electricity in the village, people go to bed later. This might reduce the impact of impregnated bednets on malaria transmission. The results show that malathion spraying as performed now is not very effective. The timing of the spray rounds should be improved. In order to limit malaria transmission, we suggest to advance the malathion spraying campaign of January with one month.


Algebraic harmony and probabilities in genomes. Long-range coherence in quantum code biology.
According to the founders of quantum mechanics and quantum biology P. Jordan and E. Schrödinger, the main difference between living and inanimate objects is the dictatorial influence of genetic molecules on the whole living organism. Code biology can make a valuable contribution to understanding this dictatorial influence of genetic molecules whose ensemble is endowed with many interconnected alphabets and codes. The paper is devoted to probability rules of nucleotide sequences of single-stranded DNA in eukaryotic and prokaryotic genomes. These rules are connected with n-plets alphabets of DNA whose nucleotide sequences are considered as bunches of many parallel texts written in interconnected n-plets alphabets. The rules draw attention to genomic phenomena of special tetragroupings of n-plets and new genomic symmetries. A generalization of the second Chargaff's rule is described. They show the existence of long-range coherence in genomic DNA sequences and reveal new connections of structural features of genomic sequences with formalisms of quantum mechanics and quantum informatics. The author supposes that the received results are related to the known vibration-resonance theory of G. Frohlich about long-range coherence in biological systems, that is, about collective quantum effects there. The possible influence of the described genetiс probability phenomena on the genetically inherited physiological structures is noted and discussed.


The relationship between least-cost and resistance distance.
Least-cost modelling and circuit theory are common analogs used in ecology and evolution to model gene flow or animal movement across landscapes. Least-cost modelling estimates the least-cost distance, whereas circuit theory estimates resistance distance. The bias added in choosing one method over the other has not been well documented. We designed an experiment to test whether both methods were linearly related. We also tested the sensitivity of these metrics to variation in Euclidean distance, spatial autocorrelation, the number of pixels representing the landscape, and data aggregation. We found that least-cost and resistance distance were not linearly related unless a transformation was applied. Resistance distance was less sensitive to the number of pixels representing a landscape and was also less sensitive than least-cost distance to the Euclidean distance between nodes. Spatial autocorrelation did not affect either method or the relationship between methods. Resistance distance was more sensitive to aggregation in any form compared to least-cost distance. Therefore, the metric used to infer movement or gene flow and the manipulations applied to the data used to calculate these metrics may govern findings.


Purification and characterization of a primary-secondary alcohol dehydrogenase from two strains of Clostridium beijerinckii.
Two primary alcohols (1-butanol and ethanol) are major fermentation products of several clostridial species. In addition to these two alcohols, the secondary alcohol 2-propanol is produced to a concentration of about 100 mM by some strains of Clostridium beijerinckii. An alcohol dehydrogenase (ADH) has been purified to homogeneity from two strains (NRRL B593 and NESTE 255) of 2-propanol-producing C. beijerinckii. When exposed to air, the purified ADH was stable, whereas the partially purified ADH was inactivated. The ADHs from the two strains had similar structural and kinetic properties. Each had a native M(r) of between 90,000 and 100,000 and a subunit M(r) of between 38,000 and 40,000. The ADHs were NADP(H) dependent, but a low level of NAD(+)-linked activity was detected. They were equally active in reducing aldehydes and 2-ketones, but a much lower oxidizing activity was obtained with primary alcohols than with secondary alcohols. The kcat/Km value for the alcohol-forming reaction appears to be a function of the size of the larger alkyl substituent on the carbonyl group. ADH activities measured in the presence of both acetone and butyraldehyde did not exceed activities measured with either substrate present alone, indicating a common active site for both substrates. There was no similarity in the N-terminal amino acid sequence between that of the ADH and those of fungi and several other bacteria. However, the N-terminal sequence had 67% identity with those of two other anaerobes, Thermoanaerobium brockii and Methanobacterium palustre. Furthermore, conserved glycine and tryptophan residues are present in ADHs of these three anaerobic bacteria and ADHs of mammals and green plants.


Bilateral Internal Thoracic Artery Minimally Invasive CABG Management in COPD.
Background Off-pump multi-arterial minimally invasive coronary surgery via anterolateral mini-thoracotomy has become a feasible and safe procedure. Case Description We report on a 61-year-old patient with a coronary one-vessel disease with severely stenotic left anterior descending artery and diagonal branch, additionally suffering from chronic obstructive pulmonary disease with severely impaired lung function. Using a fan technique allowing for double lung ventilation, the patient was successfully operated grafting both internal thoracic arteries via a left anterolateral mini-thoracotomy. Conclusion Anaortic, minimally invasive off-pump coronary artery bypass grafting is an excellent technique to achieve myocardial revascularization with both internal thoracic arteries even in patients with impaired lung function.


Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy.
Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer.


Predictors of mortality in patients with geriatric trauma in the emergency service.
In our study, it was aimed to compare the power of trauma scores (Glasgow Coma Score, Revised Trauma Score, Abbreviated Injury Scale, Injury Severity Score, and Trauma Score-Injury Severity Score) in order to predict mortality in patients with geriatric trauma and to determine the predictive values of these scores in mortality. Demographic data, clinical features, etiological causes, laboratory results, and trauma scores of the patients were statistically analyzed. SPSS 20 for Windows was used for this evaluation. It was determined that as the Glasgow Coma Score value of the patients increased, the Abbreviated Injury Scale and Injury Severity Score scores decreased and the Trauma Score-Injury Severity Score score increased. Abbreviated Injury Scale and Injury Severity Score values increased and Revised Trauma Score and Trauma Score-Injury Severity Score values decreased as the lactate levels of the patients increased. It was determined that the Abbreviated Injury Scale and Injury Severity Score scores of the patients hospitalized in the intensive care unit were significantly higher, while their Trauma Score-Injury Severity Score scores were lower. Glasgow Coma Score, Revised Trauma Score, Trauma Score-Injury Severity Score, Abbreviated Injury Scale, and Injury Severity Score scores and blood lactate levels are important parameters that can be used in the emergency department for the early detection of high-risk patients in geriatric trauma and the evaluation of the prognosis of geriatric trauma patients.


Light microscopic identification of vagal nerve innervation of the rat stomach using methylene blue.
Using a methylene blue staining techique, the innervation in the rat stomach has been studied. Several distinctive patterns of beaded and unbeaded nerves were seen. Axons in the muscle coat gave branches which ramified in connective tissue and were occasionally related to blood vessels. Further nerve fibres passed directly between the muscularis mucosae and muscle coat whilst others ran between the epithelium and muscularis mucosae. A few fine terminal axons were observed close to cells throughout the epithelial layer. This method of identifying nerves will be useful in studying the consequences of vagal denervation and reinnervation following vagotomy in man and animals.


Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tails of adhesion molecules CD43 and PSGL-1.
Radixin is a member of the ERM proteins that cross-link plasma membranes and actin filaments. The FERM domains located in the N-terminal regions of ERM proteins are responsible for membrane association through direct interaction with the cytoplasmic tails of integral membrane proteins. Here, crystals of the radixin FERM domain bound to the cytoplasmic peptides of two adhesion molecules, CD43 and PSGL-1, have been obtained. Crystals of the radixin FERM domain bound to CD43 belong to space group P4(3)22, with unit-cell parameters a = b = 68.72, c = 201.39 A, and contain one complex in the crystallographic asymmetric unit. Crystals of the radixin FERM domain bound to PSGL-1 belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 80.74, b = 85.73, c = 117.75 A, and contain two complexes in the crystallographic asymmetric unit. Intensity data sets were collected to a resolution of 2.9 A for the FERM-CD43 complex and 2.8 A for the FERM-PSGL-1 complex.


Radiographically guided percutaneous catheter drainage of pleural fluid collections.
We reviewed the outcome of guided percutaneous catheter drainage of pleural fluid collections in 18 patients over a 5-year period. Catheter positioning was guided by fluoroscopy in 10 (56%) cases, CT in seven (39%), and sonography in one (6%). Included were 16 patients with empyemas and one each with a sterile hematoma and transudate. In nine of the patients, previous surgical chest tube drainage had been unsuccessful. The majority of collections were treated with a 12- or 14-French catheter and closed underwater seal drainage. Twelve (80%) of the 15 patients who had an adequate trial of guided drainage were cured. Propyliodone oil suspension contrast sinography after catheter placement showed two clinically unsuspected bronchopleural fistulas. Although an extensive multilocular pleural collection was a contraindication to percutaneous catheter drainage, the thick fibrous peel of a chronic empyema was not. Drainage of pleural fluid collections with radiographic guidance ensures proper catheter placement and is successful in a high percentage of cases.


Regulation of plant defense responses in Arabidopsis by EDR2, a PH and START domain-containing protein.
We have identified an Arabidopsis mutant that displays enhanced disease resistance (edr2) to the biotrophic powdery mildew pathogen Erysiphe cichoracearum. Inhibition of fungal growth on edr2 mutant leaves occurred at a late stage of the infection process and coincided with formation of necrotic lesions approximately 5 days after inoculation. Double-mutant analysis revealed that edr2-mediated resistance is suppressed by mutations that inhibit salicylic acid (SA)-induced defense signaling, including npr1, pad4 and sid2, demonstrating that edr2-mediated disease resistance is dependent on SA. However, edr2 showed normal responses to the bacterial pathogen Pseudomonas syringae pv. tomato strain DC3000. EDR2 appears to be constitutively transcribed in all tissues and organs and encodes a novel protein, consisting of a putative pleckstrin homology (PH) domain and a steroidogenic acute regulatory protein-related lipid-transfer (START) domain, and contains an N-terminal mitochondrial targeting sequence. The PH and START domains are implicated in lipid binding, suggesting that EDR2 may provide a link between lipid signaling and activation of programmed cell death mediated by mitochondria.


Fetal biophysical profile score in triplet pregnancies.
Assessment of the last fetal biophysical profile score (BPS) (excluding nonstress test) prior to delivery was carried out in 35 triplet pregnancies. A normal BPS was found to be reliable in predicting nondistressed fetuses in triplets (specificity, 94.9%), while an equivocal BPS (6/8) had low sensitivity (14.3%) in predicting distressed fetuses. Two stillbirths were not detected by ultrasound prior to delivery. No correlation was found between the BPS and either neonatal morbidity or perinatal mortality. The BPS could not differentiate between distressed and nondistressed fetuses in the same pregnancy. These results suggest that an equivocal BPS has limited value in predicting fetal distress in triplet pregnancies, but a normal one could be used to predict nondistressed fetuses.


Early and late stage processing abnormalities in autism spectrum disorders: An ERP study.
This research assessed event-related potentials (ERPs) elicited during the processing of different kinds of visual stimuli among children with Autism Spectrum Disorder (ASD) (n = 15) and typically developing (TD) children (n = 19). Within a simple visual oddball paradigm, participating children passively viewed fruit and vegetable images that were used as standard stimuli in addition to images of these foods with their usual colors modified to create novel stimuli and cartoon depictions of these images (i.e., "deviant" stimuli). Analyses revealed significant main effect differences between the groups for P100, N100 and P300 components; ASD group children showing longer P100 latencies, weaker N100 amplitudes and larger P300 amplitudes than did the TD group. A Group x Hemisphere interaction also emerged for N400 amplitudes but differences were not significant in simple-effects analyses. Together these results suggested children with ASD may be characterized by lower attention resource allocation and engagement during early stages of processing visual stimuli. However, ERPs in later processing stages suggested children with ASD and TD children have similar neural responses in attending to visual images as stimulus presentations continue.


Modeling hazard functions in families.
A genetic frailty model is presented for censored age of onset data in nuclear families where individuals carrying a genetic susceptibility gene have an increased risk of becoming affected. We use maximum likelihood via the EM algorithm to estimate the genetic relative risk and the allele frequency under a dominant susceptibility type and a proportional hazards model. When sampling is from a disease registry, likelihood corrections are necessary for reducing bias in the parameter estimates. In these biased samples, the full conditional likelihood is approximated by a likelihood conditional on the proband's age of onset. For unbiased samples, simulations show the distributions of the estimates are similar under both a semiparametric and the correctly specified parametric likelihoods. For biased samples, simulations under the approximate conditional likelihood show the median estimates of the allele frequency and genetic relative risk tend to under- and overestimate, respectively, the true values; however, the approximation is better for rarer allele frequencies (0.0033 vs. 0.01). In practice, large samples or more complex ascertainment corrections are recommended. Using the approximate conditional likelihood on familial breast cancer onset data collected as part of a case-control study at the Fred Hutchinson Cancer Research Center in Seattle, Washington, we estimate an allele frequency of 0.0009 (approximate 95% CI 0.0006-0.002) and a genetic relative risk of 104 (approximate 95% CI 55-181).


Synchronization of genetic oscillators.
Synchronization of genetic or cellular oscillators is a central topic in understanding the rhythmicity of living organisms at both molecular and cellular levels. Here, we show how a collective rhythm across a population of genetic oscillators through synchronization-induced intercellular communication is achieved, and how an ensemble of independent genetic oscillators is synchronized by a common noisy signaling molecule. Our main purpose is to elucidate various synchronization mechanisms from the viewpoint of dynamics, by investigating the effects of various biologically plausible couplings, several kinds of noise, and external stimuli. To have a comprehensive understanding on the synchronization of genetic oscillators, we consider three classes of genetic oscillators: smooth oscillators (exhibiting sine-like oscillations), relaxation oscillators (displaying jump dynamics), and stochastic oscillators (noise-induced oscillation). For every class, we further study two cases: with intercellular communication (including phase-attractive and repulsive coupling) and without communication between cells. We find that an ensemble of smooth oscillators has different synchronization phenomena from those in the case of relaxation oscillators, where noise plays a different but key role in synchronization. To show differences in synchronization between them, we make comparisons in many aspects. We also show that a population of genetic stochastic oscillators have their own synchronization mechanisms. In addition, we present interesting phenomena, e.g., for relaxation-type stochastic oscillators coupled to a quorum-sensing mechanism, different noise intensities can induce different periodic motions (i.e., inhomogeneous limit cycles).


Effect of relaxin on bound cAMP in rat uterus.
Relaxin was able to elevate uterine bound cAMP in the presence of 3-isobutyl-1-xanthine in buffers of low or high (0.5 M NaCl) ionic strength. Significant elevation was observed 10 min after exposure to the hormone. The peak in bound cAMP preceded that in total cAMP (15 vs 20 min, respectively, under isometric conditions). The response was concentration-dependent, with maximal elevation in bound cAMP observed at 0.1-0.4 microgram/ml relaxin. The effect of relaxin on bound cAMP represented a change in a sizable proportion of the total available binding sites. However, relaxin did not elevate bound cAMP in the absence of phosphodiesterase inhibitors under conditions where it clearly inhibited contractile activity. These data suggest that although relaxin can alter the level of bound cAMP in the rat uterus under some conditions, these effects may not be involved in the acute changes elicited by this hormone which result in the rapid inhibition of spontaneous contractile activity.


Regulation mechanisms of muscle contraction at subcellular level.
The relaxation phase of contraction under voltage clamp conditions was analysed. It was shown that relaxation can be described by at least two exponentials. These can be explained as contributions of Ca uptake and Ca redistribution between the Ca specific sites on troponin C. The analysis has brought evidence in support of the hypothesis concerning unhomogenous distribution of Ca occupied sites during the activation of contraction.


Bacterial repopulation of drinking water pipe walls after chlorination.
The short-term kinetics of bacterial repopulation were evaluated after chlorination of high-density polyethylene (HDPE) colonized with drinking water biofilms and compared with bare HDPE surfaces. The effect of chlorination was partial as a residual biofilm persisted and was time-limited as repopulation occurred immediately after water resupply. The total number of bacteria reached the same levels on both the bare and chlorinated biofilm-fouled HDPE after a seven-day exposure to drinking water. Due to the presence of a residual biofilm, the hydrophobicity of chlorinated biofilm-fouled surface exhibited much lower adhesion forces (2.1 nN) compared to bare surfaces (8.9 nN). This could explain the rapid repopulation after chlorination, with a twofold faster bacterial accumulation rate on the bare HDPE surface. γ-Proteobacteria dominated the early stages of repopulation of both surfaces and a shift in the dominance occurred over the colonization time. Such observations define a timescale for cleaning frequency in industrial environments and guidelines for a rinsing procedure using drinking water.


Protecting Personhood: A Classic Grounded Theory.
The importance of perceiving and considering patients as healthcare partners has been increasingly promoted. Healthcare systems around the world are now highly interested in patient engagement, participation, collaboration, and partnership. Healthcare professionals are advised that patients, as autonomous beings, should be active in and responsible for a portion of their own care. The study presented here focused on patients' perceptions of interprofessional collaboration. It was conducted using the classic grounded theory methodology. The theory of protecting personhood emerged as the core concept of hospitalized patients, cared for by interprofessional healthcare teams. This theory encapsulates the process hospitalized patients go through to find balance in their sense of self, oscillating between personhood and patienthood in the unfamiliar hospital environment. The process consists of four stages: the stage of introspection, during which hospitalized patients become aware of their self as a person and as a patient; the stage of preservation, when patients find a balance between the sense of personhood and patienthood; the stage of rupture, wherein patients experience an imbalance between their sense of personhood and patienthood; and the stage of reconciliation, in which personhood is restored. The theory of protecting personhood offers insights into a better understanding of hospitalized patients' experiences and strategies, revealing the importance of relationships, and the driving force of empowerment. This study is about patients' perspectives of interprofessional healthcare teams. A grounded theory process allowed the emergence of patients' concerns and expectations, leading to a substantive theory grounded in the patients' data.


Early career researchers: an interview with Jeremy Goldbogen.
Jeremy Goldbogen is an Assistant Professor at the Hopkins Marine Station, Stanford University, USA, where he studies the integrative biology of vertebrate filter feeders from forage fish to baleen whales. He received his Bachelor's degree in Zoology from the University of Texas, Austin, USA, before moving to the Scripps Institution of Oceanography and then the University of British Columbia for his PhD, which he completed in 2010 in the laboratory of Bob Shadwick. After a short postdoc at Scripps, Goldbogen moved to continue his postdoc training at the Cascadia Research Collective in Olympia, Washington.


Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes.
New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Saccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset. Cross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets from Ancylostoma caninum and Haemonchus contortus--two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools. The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.


Diabetes and Cirrhosis Are Risk Factors for Hepatocellular Carcinoma After Successful Treatment of Chronic Hepatitis C.
Successful treatment of hepatitis C virus (HCV) infection reduces the risk for hepatocellular carcinoma (HCC), but a risk remains. Current guidelines recommend continued HCC surveillance after sustained virologic response (SVR) has been achieved. This study aimed to investigate risk factors and incidence rates for HCC after SVR in HCV patients with pretreatment advanced liver disease (Metavir stage F3/F4). All patients with advanced liver disease successfully treated for HCV at Karolinska University Hospital during 1992-2013 (n = 399) were followed up for a median of 7.8 years. Data from national registries were used to minimize loss to follow-up. Incidence rates and hazard ratios (HRs) for development of HCC were calculated by Cox regression analysis. Seventeen patients developed HCC during 3366 person-years (PY) of follow-up. The HCC incidence rate was 0.95 (95% confidence interval [CI], .57-1.6) and 0.15 (95% CI, .05-.49) per 100 PY for patients with pretreatment F4 and F3, respectively. Patients with pretreatment cirrhosis and diabetes had a HR to develop HCC of 6.3, and an incidence rate of 7.9 per 100 PY (95% CI, 3.3-19) during the first 2 years of follow-up. The risk for HCC decreased significantly 2 years after SVR had been achieved. Diabetes mellitus and cirrhosis are strong risk factors for HCC development after SVR has been achieved. The risk to develop HCC diminishes significantly 2 years after SVR. Patients without cirrhosis have a low risk to develop HCC after SVR, and the benefit of HCC surveillance for this group is questionable.


Closed-Loop Controlled Photopolymerization of Hydrogels.
Here, we present a closed-loop controlled photopolymerization process for fabrication of hydrogels with controlled storage moduli. Hydrogel crosslinking was associated with a significant change in the phase angle of a piezoelectric cantilever sensor and established the timescale of the photopolymerization process. The composition, structure, and mechanical properties of the fabricated hydrogels were characterized using Raman spectroscopy, scanning electron microscopy (SEM), and dynamic mechanical analysis (DMA). We found that the storage moduli of photocured poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(N-isopropylacrylamide) (PNIPAm) hydrogels could be controlled using bang-bang and fuzzy logic controllers. Bang-bang controlled photopolymerization resulted in constant overshoot of the storage modulus setpoint for PEGDMA hydrogels, which was mitigated by setpoint correction and fuzzy logic control. SEM and DMA studies showed that the network structure and storage modulus of PEGDMA hydrogels were dependent on the cure time and temporal profile of UV exposure during photopolymerization. This work provides an advance in pulsed and continuous photopolymerization processes for hydrogel engineering based on closed-loop control that enables reproducible fabrication of hydrogels with controlled mechanical properties.


Electrochemical synthesis of selenyl-dihydrofurans via anodic selenofunctionalization of allyl-naphthol/phenol derivatives and their anti-Alzheimer activity.
Herein, we report an eco-friendly, electrosynthetic approach for the intramolecular oxyselenylation of allyl-naphthol/phenol derivatives. This reaction proceeds with 0.2 equiv. of nBu4NClO4 as an electrolyte and Pt working electrodes in an undivided cell, resulting in the selenyl-dihydrofurans in good to excellent yields. Furthermore, several of the synthesized products presented a high percentage of acetylcholinesterase (AChE) inhibition, highlighting their potential anti-Alzheimer activity.


Does nursing education promote ageism?
The literature is replete with diverse studies about gerontological nursing education on the attitudes of nursing students. This study examined the effect of a 3-year curriculum on ageism over all 3 years. Students were exposed first to well elderly subjects, then hospitalized older subjects, then severely ill older subjects. They were tested with the Kogan's Old People Scale and a semantic differential scale to see how their attitudes towards older people changed according to their experiences. The Kogan scale was most sensitive and showed that older students and those with grandparent role models had better attitudes towards older adults. Also, there were great increases in positive attitudes towards ageing in year 1 that slowly decreased by the end of year 3.