Immune status of children with phenylketonuria.
To determine the effect of differences in plasma phenylalanine (Phe) concentrations (< 363 umol/L, 363 to 605 umol/L, and > 605 umol/L) on hematological and immunological parameters in 22 children with phenylketonuria (PKU). Children with PKU were divided into one of three groups based on fasting plasma Phe levels. Hematologic and immunologic parameters of the children with PKU were compared between the groups and also compared with published values from age-matched children without PKU. Hematologic and immunologic parameters did not differ among children with different plasma Phe concentrations. Specifically, no significant differences between groups of PKU children with differing plasma Phe levels were found for plasma levels of albumin, hemoglobin, amino acids, IgM, complement C3, interleukins 1 and 2, erythrocyte, leukocyte and differential cell counts, hematocrit, percentages and numbers of CD4+, CD8+, CD3+ and total lymphocytes, or CD4 to CD8 ratio. Mean plasma IgG and IgA concentrations of the PKU children were, however, significantly lower than values from similar aged children. Moreover, positive correlations were obtained between plasma albumin and percentages and numbers of CD3+ and CD4+, between plasma IgG and interleukins 1 and 2, and between intakes of energy, protein, iron and plasma IgG levels. No correlations were found between plasma Phe and immunological parameters. While differences in plasma Phe concentrations up to concentrations of 866 umol/L do not appear to affect selected immune system parameters, further studies are needed to investigate the relationship between dietary nutrient intake, nutritional status, antibody biosynthesis and cytokine production. Assessment of plasma and cell membrane lipids and trace mineral status of PKU children would be helpful to determine if relationships exist between these nutrients and antibody production.


Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry.
Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses.


Panic disorder and the Defence Mechanism Test.
The aim was to study defence categories according to the modified version of the Defence Mechanism Test (DMTm) and to see if there was a relationship between DMTm and severity of illness. The material consists of 23 patients with panic disorder according to DSM-III-R who participated in a long-term follow-up of two clinical trials. The most common defence categories were repression, denial, disavowal or denial of the threat relation or of the identity of the peripheral person. The patients with denial or polymorphous identification had more severe symptoms and the latter group also were more handicapped by their symptoms. Denial and disavowal or denial of the threat relation may be defence categories, which are not so effective in preventing the individual from experiencing anxiety. Polymorphous identification, although not so common, does not seem to be an appropriate defence among patients with panic disorder.


Human neutrophils as a source of nociceptin: a novel link between pain and inflammation.
Nociceptin is a neuropeptide sharing sequence homology with classical opioid peptides but with a distinct pharmacological profile. Through activation of its receptor, NociR, nociceptin has been linked with several physiological functions in the central nervous system including memory, locomotion, and processing of pain signals. Recently, peripheral blood neutrophils (PMNs) were demonstrated to express a functional NociR, a result suggesting that additional functions of the neuropeptide remain to be elucidated. The present study investigated the possibility that PMNs may be a source of nociceptin and whether the neuropeptide elicits PMN early responses. We observed the presence of nociceptin in the synovial fluids from arthritic patients, an inflammatory milieu typically containing high numbers of PMNs. In addition, freshly isolated PMNs were found to express and secrete nociceptin following degranulation, identifying these inflammatory cells as a novel source of the neuropeptide. Incubation of PMNs with nociceptin elicited a specific pattern of cellular protein phosphorylation on tyrosine residues in a rapid and transient fashion. Moreover, nociceptin prevented intracellular accumulation of cAMP in fMLP-stimulated PMNs, an effect mimicked by the specific NociR synthetic agonist, Ro 64-6198. Taken together, these results show that nociceptin/NociR is present and functional in human neutrophils, and the results identify a novel dialogue pathway between neural and immune tissues.


An unusual case of hematuria in a young female: renal artery embolism, mitral stenosis, and sinus rhythm.
Renal artery embolism (RAE) is an uncommon entity that is most often secondary to a cardiac source. Most reported cases have been in patients with underlying atrial fibrillation (AF), and occurrence of RAE, especially in patients with valvular heart disease, and sinus rhythm is very rare. We describe an unusual case of a young female who presented with sudden onset right flank pain, vomiting, anorexia, and hematuria, and was found to have thrombotic occlusion of the distal right renal artery. Although she denied any previous cardiac history, detailed cardiovascular examination revealed the presence of severe rheumatic mitral stenosis without any evidence of AF or left atrial clot. She was initially managed conservatively using low molecular weight heparin followed by oral anticoagulation with resolution of symptoms. A successful balloon mitral valvotomy was performed six weeks later. The patient is asymptomatic at her last follow-up of six months with preserved renal function. In symptomatic patients, clinicians need to consider the possibility of RAE even in patients of valvular heart disease with underlying sinus rhythm. Appropriate management of the underlying cardiac condition is imperative since embolism may be recurrent leading to compromise of renal function, if left untreated.


Meta-analysis of lipid-lowering therapy in maintenance dialysis patients.
The use of lipid-lowering therapy (LLT) in patients on chronic dialysis is contentious. Here we present an aggregate data meta-analysis of randomised controlled trials (RCTs) comparing long-term LLT versus placebo in dialysis patients. A search of Medline, Google Scholar, COCHRANE database, EMBASE, and cardiovascular and nephrology society proceedings was performed. Criteria for inclusion were RCTs of LLT versus placebo, in which LLT was demonstrated to significantly reduce low-density lipoprotein cholesterol, >12 months of follow-up, and at least one cardiovascular or mortality endpoint in an independently reported dialysis population. Meta-analysis was performed for atherosclerotic cardiovascular events, stroke and mortality using a random-effects method for odds ratio (OR) of risk. Three studies were included with 7,051 patients (3,541 treatment and 3,510 placebo). Twenty-five percent of the LLT patients suffered an atherosclerotic cardiovascular event versus 27% for placebo. The OR was 0.89 (95% CI: 0.80-0.99, p = 0.04). For stroke (haemorrhagic and non-haemorrhagic combined), the figures were 6.2% (LLT) versus 5.7% (placebo) [OR = 1.11 (95% CI: 0.85-1.46, p = 0.45)]. For all-cause mortality, the figures were 40 versus 42% [OR = 0.97 (95% CI: 0.88-1.06, p = 0.49)]. There was an overall significant reduction in risk for atherosclerotic cardiovascular events in dialysis patients treated with LLT compared to placebo. There was a numerical but not a statistical reduction in mortality. There was no statistically significant increase in risk of stroke as has been previously reported.


Genome-wide identification of the ZIP gene family in lettuce (Lactuca sativa L.) and expression analysis under different element stress.
The ZIP protein (ZRT, the IRT-like protein) is an important metal transporter that transports Zn, Fe, and other divalent metal ions in plants. In this study, we identified 20 ZIP genes in lettuce (Lactuca sativa L.). We used bioinformatics methods and renamed them according to their E value in hmmsearch. We also analyzed their gene structure, chromosomal location, constructed a phylogenetic tree, conserved motifs, performed synonymous analysis and responses to abiotic stresses. The results show that these LsZIP genes have 3-11 exons and were distributed unequally on 8 of the 9 chromosomes in lettuce. Based on phylogenetic analyses, the LsZIP gene family can be divided into three subfamilies, and the LsZIP genes within the same subfamily shared similar gene structure. The LsZIP genes contain 12 Motifs, of which Motif1 to Motif8 are widely distributed in group Ⅰ. Furthermore, the LsZIP gene contains numerous hormones and anti-stress response elements. Real-time quantitative PCR demonstrated that most LsZIP genes is up-regulated under the elemental stress in this experiment, indicating that they are positively regulated. But different elemental stressors can induce the expression of LsZIP gene to varying degrees. The LsZIP genes also change in response to different elemental stresses. The present study serves as a basic foundation for future functional studies on the lettuce ZIP family.


The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli.
The cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues. We conducted coordinate-based meta-analyses delineating common and distinct brain activity convergence across cue-reactivity studies (N = 196 articles) involving drug (n = 133) or natural (n = 63) visual stimuli. Across all studies, convergence was observed in limbic, cingulate, insula, and fronto-parieto-occipital regions. Drug-distinct convergence was observed in posterior cingulate, dorsolateral prefrontal, and temporo-parietal regions, whereas distinct-natural convergence was observed in thalamic, insular, orbitofrontal, and occipital regions. We characterized connectivity profiles of identified regions by leveraging task-independent and task-dependent MRI datasets, grouped these profiles into subnetworks, and linked each with putative mental operations. Outcomes suggest multifaceted brain activity during cue-reactivity can be decomposed into elemental processes and indicate that while drugs of abuse usurp the brain's natural-reward-processing system, some regions appear distinct to drug cue-reactivity.


Role of Hepatitis E Virus Infection in North American Patients With Severe Acute Liver Injury.
The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.


Reversal of biological age in multiple rat organs by young porcine plasma fraction.
Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young adult pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clock, which is a highly accurate molecular biomarker of aging. To address this question, we developed and validated six different epigenetic clocks for rat tissues that are based on DNA methylation values derived from n = 613 tissue samples. As indicated by their respective names, the rat pan-tissue clock can be applied to DNA methylation profiles from all rat tissues, while the rat brain, liver, and blood clocks apply to the corresponding tissue types. We also developed two epigenetic clocks that apply to both human and rat tissues by adding n = 1366 human tissue samples to the training data. We employed these six rat clocks to investigate the rejuvenation effects of a porcine plasma fraction treatment in different rat tissues. The treatment more than halved the epigenetic ages of blood, heart, and liver tissue. A less pronounced, but statistically significant, rejuvenation effect could be observed in the hypothalamus. The treatment was accompanied by progressive improvement in the function of these organs as ascertained through numerous biochemical/physiological biomarkers, behavioral responses encompassing cognitive functions. An immunoglobulin G (IgG) N-glycosylation pattern shift from pro- to anti-inflammatory also indicated reversal of glycan aging. Overall, this study demonstrates that a young porcine plasma-derived treatment markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.


The influence of personal tobacco smoking on the clinical practice of Italian chest physicians.
Tobacco smoking (TS) is a major cause of lung diseases. This study aimed to determine: 1) the prevalence of TS among chest physicians; 2) the influence of the personal smoking habit on clinical practice; and 3) what training about tobacco-related issues (TI) doctors received in medical school. A total of 983 attendees at the National Meeting of the Italian National Thoracic Society (AIPO) received a questionnaire about TI, which also contained the Fagerstroem Tolerance Questionnaire, and 605 (61.5%) answered. An independent assessment of the prevalence of smokers was carried out to minimize the bias of self-selection. The numbers of smokers was 151 (25%), never-smokers 246 (40.7%) and exsmokers 208 (34.4%). Smoking chest physicians underestimate the health hazards of smoking (p<0.001) and disregard their educational role (p=0.005) more than nonsmoking chest physicians. Compliance with smoking restrictions inside hospitals is frequently poor (30.1% smoke in clinics). In 33.1% of smokers a high nicotine addiction was found, which influenced their behaviour in hospital but not their ability to cope with tobacco-related problems. This ability was generally low: 39.1% of responders reported no training about TI. Smoking is frequent among Italian chest physicians, who are poorly trained about the health effects of tobacco smoking and are poorly skilled in treating smokers.


Cyclic AMP differentiates two separate but interacting pathways of phosphoinositide hydrolysis in the DDT1-MF2 smooth muscle cell line.
The activation of adenosine A1 receptors in DDT1-MF2 smooth muscle cells resulted in both the inhibition of agonist-stimulated cAMP accumulation and the potentiation of norepinephrine-stimulated phosphoinositide hydrolysis. Pharmacological analysis indicated the involvement of an A1 adenosine receptor subtype in both of these responses. In the absence of norepinephrine, the activation of the adenosine receptor did not directly stimulate phosphoinositide hydrolysis. The adenosine receptor-mediated augmentation of norepinephrine-stimulated phosphoinositide hydrolysis was pertussis toxin sensitive and was selectively antagonized by agents that mimicked cAMP (8-bromo-cAMP) or raised cellular cAMP levels (forskolin). This initially suggested that cAMP might partially regulate the magnitude of the phospholipase C response to norepinephrine and that adenosine agonists might enhance the phospholipase C response by reducing cAMP levels. However, neither the reduction of cellular cAMP levels by other agents nor the inhibition of cAMP-dependent protein kinase was sufficient to replicate the action of adenosine receptor activation on phosphoinositide hydrolysis. Thus, in the presence of norepinephrine, adenosine receptor agonists appear to stimulate phosphoinositide hydrolysis via a pathway that is separate from, but dependent upon, that of norepinephrine. This second pathway can be distinguished from that which is stimulated by norepinephrine on the basis of its sensitivity to inhibition by both cAMP and pertussis toxin.


Molecular characterization of a novel immune receptor restricted to the monocytic lineage.
Homology basic local alignment search tool search was conducted using a sequence encoding for a novel inhibitory receptor (IREM-1) cloned in our laboratory and a previously described homologous sequence termed CMRF-35. On the basis of this information, we cloned a full length cDNA corresponding to a novel member of this family, termed immune receptor expressed by myeloid cells 2 (IREM-2). The gene, located in chromosome 17q25.1, encodes for a protein of 205 aa that contains an extracellular region comprising an Ig-like domain and a transmembrane region with a positively charged amino acid residue (lysine), that predicted its putative association with an adapter molecule. Indeed, the interaction between IREM-2 and DAP-12 was confirmed in transfected COS-7 cells. By generating specific Abs and using bone marrow and PBMCs, we observed that IREM-2 expression appeared to be restricted to mature hemopoietic cells of the monocytic and myeloid dendritic cell lineages. In vitro differentiation to macrophages or immature dendritic cells down-regulated IREM-2 expression. Upon engagement with the specific mAbs, IREM-2 expressed in rat basophilic leukemia cells together with DAP-12, induced NFAT transcriptional activity; moreover, IREM-2 engagement on monocytes induced TNF-alpha production. Taken together, our results indicate that IREM-2 is a novel activating receptor of the Ig-superfamily in the monocytic lineage.


C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.
New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene.According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation.Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.


[Effects of covering the windowpane with plastic film on microclimate and sunshine of the living room in a cold region].
Experiments were made to ascertain the effects of covering windowpane with plastic film in Hulunbeir region on microclimate and sunshine intensity in the living room. It was found that a good regulative effect on the room microclimate resulted by covering the windowpane with plastic film in the cold region. The room temperature rose distinctly. No evident effects were found on ultra-violet radiation and illumination. But the concentration of carbon dioxide increased to some extent. Attention should be paid to ventilation of the room.


North Carolina internists' and endocrinologists' knowledge, opinions, and behaviors regarding periodontal disease and diabetes: need and opportunity for interprofessional education.
The aim of this study was to determine the knowledge and practice behaviors of one state's internists and endocrinologists who treat patients with any type of diabetes. A thirty-five-item questionnaire was mailed to 1,000 internists and 115 endocrinologists in North Carolina. Questions were open and closed ended and Likert-scaled. Descriptive statistics and bivariate analysis were utilized. The response rate was 34 percent (N=378). The overall usable response rate was 23 percent (N=254). Over half of the respondents (66 percent) were males. Internists' and endocrinologists' knowledge about periodontal disease was high. The majority of the respondents agreed that physicians should be taught about periodontal disease (88 percent) and should be trained to screen for periodontal disease in their patients (78 percent). However, when asked if they are confident in providing an oral health screening for their patients, the responses were evenly distributed from strongly agree to strongly disagree. This study suggests that internists and endocrinologists have some knowledge about oral health and believe that there is a link between periodontal disease and diabetes mellitus; however, the majority do not have sufficient familiarity with the studies that link periodontal disease and diabetes mellitus. They agree with the idea of collaboration with dental professionals to reduce the number of patients at risk for developing periodontal disease. Perhaps the time is conducive to promote interprofessional education and collaboration between medical and dental health care providers to prepare for the future increase in patient and treatment needs.


Robust predictive control strategy applied for propofol dosing using BIS as a controlled variable during anesthesia.
This paper presents the application of predictive control to drug dosing during anesthesia in patients undergoing surgery. The performance of a generic predictive control strategy in drug dosing control, with a previously reported anesthesia-specific control algorithm, has been evaluated. The robustness properties of the predictive controller are evaluated with respect to inter- and intrapatient variability. A single-input (propofol) single-output (bispectral index, BIS) model of the patient has been assumed for prediction as well as for simulation. A set of 12 patient models were studied and interpatient variability and disturbances are used to assess robustness of the controller. Furthermore, the controller guarantees the stability in a desired range. The applicability of the predictive controller in a real-life environment via simulation studies has been assessed.


Expectations vs. actual behavior of a social robot: An experimental investigation of the effects of a social robot's interaction skill level and its expected future role on people's evaluations.
Since social robots are increasingly entering areas of people's personal lives, it is crucial to examine what affects people's perceptions and evaluations of these robots. In this study, three potential influences are examined: 1) the robot's level of interaction skills, 2) the robot's expected future role as a helpful assistant or a threatening competitor, and 3) people's individual background with regard to robots and technology in general. In an experimental lab study with a 2x2 between-subjects-design (N = 162), people read a vignette describing the social robot Nao either as assistant or competitor and subsequently interacted with Nao, which either displayed high or low interaction skills. Results of a structural equation model show that the robot's interaction skill level had the strongest effect, with a low level leading to a negative evaluation of the robot's sociability and competence and subsequently a negative general evaluation of the interaction with the robot. A robot which was expected to become a competitor was also evaluated as less sociable than a robot expected to become an assistant. Overall, in case of an actual interaction with a social robot, the robot's behavior is more decisive for people's evaluations of it than their expectations or individual backgrounds.


Co-Delivery of Curcumin and Cisplatin to Enhance Cytotoxicity of Cisplatin Using Lipid-Chitosan Hybrid Nanoparticles.
Lipid-polymer hybrid nanoparticles (LPHNP) are suitable for co-delivery of hydrophilic and lipophilic drugs. The structural advantages of polymers and biomimetic properties of lipids enable higher encapsulation of drugs and controlled release profile. Lipid-polymer hybrid nanoparticles have been prepared for co-delivery of curcumin and cisplatin for enhanced cytotoxicity against ovarian cancer. Chitosan, cisplatin, curcumin, Lipoid S75 were selected as structural components and ionic gelation method was used for preparation of LPHNPs. Nanoparticles were formed via ionic interaction of positively charged chitosan and negatively charged lipid. The optimized nanoparticles were of 225 nm with cationic charge. The encapsulation efficiency was greater than 80% with good drug loading. The drug release profile showed controlled release behavior of both curcumin and cisplatin simultaneously and the absence of burst release. The in vitro therapeutic efficacy and cellular association was evaluated using A2780 ovarian cell lines. To further investigate therapeutic efficacy, we developed 3D spheroids as tumor model to mimic the in vivo conditions. The cytotoxicity and uptake of co-loaded LPHNPs were evaluated on 3D spheroids and results indicated increased chemosensitization and enhanced therapeutic efficacy of co-loaded LPHNPs. Lipid-polymer hybrid nanoparticles could be a suitable platform for co-delivery of curcumin and cisplatin for enhanced cytotoxic effect on ovarian cell lines.


Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency.
Low serum 25-hydroxyvitamin D [25(OH)D] levels remain a challenge worldwide. While some in vitro studies show a caffeine-induced decrease in vitamin D receptor expression, there is a paucity of research to define the extent of caffeine intake and effects on 25(OH)D levels. Therefore, we aimed to associate dietary caffeine intake with 25(OH)D deficiency through a recognized dataset. Using data collected from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), 25(OH)D levels and dietary caffeine intake were extracted from 13134 individuals (30-47 years, interquartile range). We used one-way ANOVA and chi-square tests for quantitative and qualitative variables, respectively, and performed multivariate logistic regression for four models to assess the odds ratio (OR) of 25(OH)D deficiency (<20 ng/ml or <50 nmol/L) based on quartiles of dietary caffeine intake. Both crude and multivariable models detected higher OR for 25(OH)D deficiency according to the highest intakes of caffeine (15.8±9.5, 51.9±11.9, and 177±156 mg/d) when compared to the reference category (2.19±1.04 mg/d), in which the OR in the highest category of caffeine intake was 1.24 (95% CI: 1.12 to 1.37) and 1.48 (95% CI: 1.16 to 1.78) for the crude model and the most complete multivariable analysis (adjustment for age, sex, race, body mass index, smoking, physical activity, occupation, energy intake, protein intake, and fat intake), respectively. In conclusion, higher dietary intakes of caffeine were associated with 25(OH)D deficiency in a representative sample of the American population, but further investigation is warranted to determine causation.


Nutrient-Poor Breeding Substrates of Ambrosia Beetles Are Enriched With Biologically Important Elements.
Fungus-farming within galleries in the xylem of trees has evolved independently in at least twelve lineages of weevils (Curculionidae: Scolytinae, Platypodinae) and one lineage of ship-timber beetles (Lymexylidae). Jointly these are termed ambrosia beetles because they actively cultivate nutritional "ambrosia fungi" as their main source of food. The beetles are obligately dependent on their ambrosia fungi as they provide them a broad range of essential nutrients ensuring their survival in an extremely nutrient-poor environment. While xylem is rich in carbon (C) and hydrogen (H), various elements essential for fungal and beetle growth, such as nitrogen (N), phosphorus (P), sulfur (S), potassium (K), calcium (Ca), magnesium (Mg), and manganese (Mn) are extremely low in concentration. Currently it remains untested how both ambrosia beetles and their fungi meet their nutritional requirements in this habitat. Here, we aimed to determine for the first time if galleries of ambrosia beetles are generally enriched with elements that are rare in uncolonized xylem tissue and whether these nutrients are translocated to the galleries from the xylem by the fungal associates. To do so, we examined natural galleries of three ambrosia beetle species from three independently evolved farming lineages, Xyleborinus saxesenii (Scolytinae: Xyleborini), Trypodendron lineatum (Scolytinae: Xyloterini) and Elateroides dermestoides (Lymexylidae), that cultivate unrelated ambrosia fungi in the ascomycete orders Ophiostomatales, Microascales, and Saccharomycetales, respectively. Several elements, in particular Ca, N, P, K, Mg, Mn, and S, were present in high concentrations within the beetles' galleries but available in only very low concentrations in the surrounding xylem. The concentration of elements was generally highest with X. saxesenii, followed by T. lineatum and E. dermestoides, which positively correlates with the degree of sociality and productivity of brood per gallery. We propose that the ambrosia fungal mutualists are translocating essential elements through their hyphae from the xylem to fruiting structures they form on gallery walls. Moreover, the extremely strong enrichment observed suggests recycling of these elements from the feces of the insects, where bacteria and yeasts might play a role.


Vestibular disease in dogs: association between neurological examination, MRI lesion localisation and outcome.
To determine whether the neurological examination correctly distinguishes between central and peripheral vestibular lesions in dogs. Retrospective study on dogs with vestibular disease presenting to two referral clinics in Germany. Ninety-three dogs were included; neurological examination suggested central vestibular disease in 62 and a peripheral lesion in 31. MRI diagnosis was central vestibular disease in 68 dogs and peripheral in 25. Of the 62 dogs with a lesion localisation diagnosed as central vestibular by neurological exam, 61 were correctly identified (98.4%). Twenty-four of the 31 dogs diagnosed with a peripheral lesion by neurological exam had a consistent lesion on MRI (77.4%). The neurological examination is efficient at identifying lesions in the central vestibular system but less so for peripheral lesions. Therefore it is prudent to recommend imaging in dogs that show signs of peripheral vestibular syndrome but do not rapidly respond to treatment.


Prime time for G-protein-coupled receptor heteromers as therapeutic targets for CNS disorders: the dopamine D₁-D₃ receptor heteromer.
A number of G-protein-coupled receptors (GPCRs) are currently under consideration as potential therapeutic targets for drugs acting in the central nervous system (CNS). Attempts to discover new medications have operated under the assumption that GPCRs are monomers and that a specific drug activates one single receptor coupled to one single signal transduction mechanism. In the neuronal membrane, GPCRs are now known to be arranged into homo- and hetero-oligomers; drugs acting on a single receptor within a specific heteromer context are thought to induce a particular downstream signaling. However, there is recent evidence showing that heteromer-tailored drugs can be designed that display different affinities for a given receptor depending on the receptor partners contained within the heteromer. It can therefore be predicted that customized drugs targeting a specific receptor heteromer in the CNS might improve safety and efficacy for their therapeutic targets. Finally, it will be important to identify receptor heteromers that are involved in the pathogenesis of diseases, such as the recently discovered dopamine D₁-D₃ receptor heteromer, which might play a key role in L-DOPA-induced dyskinesia in Parkinson's disease.


A diluent containing coconut water, fructose, and chicken egg yolk increases rooster sperm quality at 5°C.
The present study was conducted to evaluate the quality of rooster sperm at 5°C after treatment with a diluent containing coconut water, fructose, and chicken egg yolk and stored the semen sample at 5°C. Ten semen samples from 10 healthy roosters were subjected to four different treatments. For the treatments, 0.2 ml fresh semen with a sperm concentration of 5.2×109 cell/ml was mixed with T0 (no diluent), T1 (0.34 ml coconut water and 6 µl fructose), T2 (0.274 ml coconut water, 0.12 ml egg yolk, and 6 µl fructose), and T3 (0.34 ml egg yolk and 6 µl fructose) solutions. Each treated solution was stored at 5°C and evaluated both macroscopically and microscopically. Macroscopically, semen volume, pH, and sperm concentration were evaluated. The microscopic sperm characteristics examined included total motility (i.e., rapid, medium, or slow), progressive and non-progressive motility, viability, and spermatozoa abnormalities noted at different storage times. The results showed that spermatozoa motility was under 40%. The results indicated that sperm viability significantly affected (p<0.05). The highest mean value of sperm viability on day 7 of storage was found after treatment with the T2 solution (46.100±0.5677%). Similarly, spermatozoa abnormalities were significantly lower after treatment with the T2 solution (6.680±1.702%). The addition of a diluent containing coconut water, egg yolk, and fructose helped in the better preservation spermatozoa motility, as well as viability for up to 7 days when the semen samples were stored at 5°C.


A High-Throughput Interbacterial Competition Screen Identifies ClpAP in Enhancing Recipient Susceptibility to Type VI Secretion System-Mediated Attack by Agrobacterium tumefaciens.
The type VI secretion system (T6SS) is an effector delivery system used by Gram-negative bacteria to kill other bacteria or eukaryotic hosts to gain fitness. The plant pathogen Agrobacterium tumefaciens utilizes its T6SS to kill other bacteria, such as Escherichia coli. We observed that the A. tumefaciens T6SS-dependent killing outcome differs when using different T6SS-lacking, K-12 E. coli strains as a recipient cell. Thus, we hypothesized that the A. tumefaciens T6SS killing outcome not only relies on the T6SS activity of the attacker cells but also depends on the recipient cells. Here, we developed a high-throughput interbacterial competition platform to test the hypothesis by screening for mutants with reduced killing outcomes caused by A. tumefaciens strain C58. Among the 3,909 strains in the E. coli Keio library screened, 16 mutants with less susceptibility to A. tumefaciens C58 T6SS-dependent killing were identified, and four of them were validated by complementation test. Among the four, the clpP encoding ClpP protease, which is universal and highly conserved in both prokaryotes and eukaryotic organelles, was selected for further characterizations. We demonstrated that ClpP is responsible for enhancing susceptibility to the T6SS killing. Because ClpP protease depends on other adapter proteins such as ClpA and ClpX for substrate recognition, further mutant studies followed by complementation tests were carried out to reveal that ClpP-associated AAA+ ATPase ClpA, but not ClpX, is involved in enhancing susceptibility to A. tumefaciens T6SS killing. Moreover, functional and biochemical studies of various ClpP amino acid substitution variants provided evidence that ClpA-ClpP interaction is critical in enhancing susceptibility to the T6SS killing. This study highlights the importance of recipient factors in determining the outcome of the T6SS killing and shows the universal ClpP protease as a novel recipient factor hijacked by the T6SS of A. tumefaciens.


In vitro interaction of aminoglycosides with beta-lactam penicillins.
The aminoglycosides are used clinically in combination with beta-lactam antibiotics. The combined use, however, produces an interaction and inactivation of the antibiotics. A study was designed to investigate the kinetics of the interaction in vitro. Four concentrations of aminoglycosides (5 to 20 micrograms of gentamicin and tobramycin per ml) and penicillins (100 to 600 micrograms of carbenicillin and ticarcillin per ml) were incubated in plasma (3 days, 37 degrees C). Samples taken at 12-h intervals were analyzed for both aminoglycosides (radioimmunoassay) and penicillin (high-pressure liquid chromatography). In controls, degradation of all four antibiotics were by first-order reactions. In incubation mixtures of two antibiotics, the rate of loss of the aminoglycosides was greater than that in the controls, whereas the rate of loss of penicillins was not significantly increased. The loss of penicillins in incubation mixtures still appeared to be by first-order reactions. However, semilogarithmic plots of aminoglycoside concentrations were curvilinear, suggesting a second-order reaction. Aminoglycoside concentrations in incubation mixtures were fitted by computer to a model incorporating a second-order interaction between aminoglycosides and penicillins and the first-order loss of penicillin from the mixture. The interaction rate constant averaged 2.2 X 10(-4) (micrograms/ml h)-1 for interaction of both carbenicillin and ticarcillin with gentamicin and 1.6 X 10(-4) (micrograms/ml h)-1 for interaction of the penicillins with tobramycin. The effect of the interaction in vivo was examined by computer simulation using the kinetic parameters determined in vitro.


Modeling the role of the close-range effect and environmental variables in the occurrence and spread of Phragmites australis in four sites on the Finnish coast of the Gulf of Finland and the Archipelago Sea.
Phragmites australis, a native helophyte in coastal areas of the Baltic Sea, has significantly spread on the Finnish coast in the last decades raising ecological questions and social interest and concern due to the important role it plays in the ecosystem dynamics of shallow coastal areas. Despite its important implications on the planning and management of the area, predictive modeling of Phragmites distribution is not well studied. We examined the prevalence and progression of Phragmites in four sites along the Southern Finnish coast in multiple time frames in relation to a number of predictors. We also analyzed patterns of neighborhood effect on the expansion and disappearance of Phragmites in a cellular data model. We developed boosted regression trees models to predict Phragmites occurrences and produce maps of habitat suitability. Various Phragmites spread figures were observed in different areas and time periods, with a minimum annual expansion rate of 1% and a maximum of 8%. The water depth, shore openness, and proximity to river mouths were found influential in Phragmites distribution. The neighborhood configuration partially explained the dynamics of Phragmites colonies. The boosted regression trees method was successfully used to interpolate and extrapolate Phragmites distributions in the study sites highlighting its potential for assessing habitat suitability for Phragmites along the Finnish coast. Our findings are useful for a number of applications. With variables easily available, delineation of areas susceptible for Phragmites colonization allows early management plans to be made. Given the influence of reed beds on the littoral species and ecosystem, these results can be useful for the ecological studies of coastal areas. We provide estimates of habitat suitability and quantification of Phragmites expansion in a form suitable for dynamic modeling, which would be useful for predicting future Phragmites distribution under different scenarios of land cover change and Phragmites spatial configuration.


Determination of Association Constants for Cyclodextrin-Surfactant Inclusion Complexes: A Numerical Method Based on Surface Tension Measurements
Inclusion complexes of beta-cyclodextrin (beta-CD) with sodium octyl sulfonate (C8As), sodium dodecyl sulfonate (C12As), and sodium hexadecyl sulfonate (C16As) in aqueous solutions are studied by surface tension measurement at the air/water interface at different temperatures. At fixed concentrations of the surfactants, the surface tension increases with an increase in beta-CD concentration to a maximum value, at which it holds. The surface tension curves of the surfactants in the presence of beta-CD are higher than those in the absence of beta-CD. The curves rise higher with the increase in beta-CD concentration for each surfactant. The apparent critical micelle concentrations (CMC*) of the surfactants vary linearly with beta-CD concentration. The CMC* and surface tension values (including those after the CMC*) for the same system decrease with increase in temperature. A numerical method based on surface tension measurements is developed to determine the association constants for 1:1 inclusion complexes. This method is very reliable and easy to perform. The results demonstrate that the longer the hydrophobic tail of the surfactant, the greater the association constant with beta-CD, and that for the same surfactant the association constant is higher at lower temperatures.


A Case Study of a New State Model for Assessing Local Wellness Policies.
In 2016, the United States Department of Agriculture issued a final rule to strengthen local wellness policies (LWPs). As school districts pursue compliance, states can provide critical guidance by leveraging support from intermediary programs such as the Supplemental Nutrition Assistance Program-Education (SNAP-Ed). After Arizona SNAP-Ed piloted a statewide model for assessing LWPs, we evaluated that model by exploring local SNAP-Ed agency experiences with the pilot. Our case study objectives were to determine the model's feasibility and utility from the perspective of local agencies supporting school districts during LWP review and revision. We used open-ended semistructured interviews with the 13 local SNAP-Ed agencies who engaged in each LWP assessment phase and analyzed data using constant comparative analysis. Participants found the model feasible and useful. Five themes emerged, 3 of which tracked strongly with successful LWP review and revision: local agency staff comprehension, the openness of local agency staff and district/school personnel to the process, and the local agency's engagement of the district/school throughout the process. Leveraging local agency support can be an effective strategy to improving LWPs, given understanding, buy-in, and staff engagement. Findings can inform agencies seeking to engage intermediaries in LWP assessment and revision.


AMPA receptors in epilepsy and as targets for antiepileptic drugs.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are key mediators of seizure spread in the nervous system and represent promising targets for antiepileptic drugs. There is emerging evidence that AMPA receptors may play a role in epileptogenesis and in seizure-induced brain damage. This evidence suggests that AMPA receptor antagonists could have broad utility in epilepsy therapy. Regional, developmental, and disease-associated variations in AMPA receptors produced by differential expression of AMPA receptor subunits and variations in posttranscriptional processing, including alternative splicing and pre-mRNA editing, provide a diversity of functionally distinct AMPA receptor isoforms that allow opportunities for selective drug targeting. Four types of AMPA receptor antagonist are discussed in this chapter: (a) competitive AMPA recognition site antagonists, including those of the quinoxalinedione and newer nonquinoxalinedione classes, (b) 2,3-benzodiazepine noncompetitive (allosteric) antagonists, (c) desensitization enhancing antagonists, exemplified by SCN-, and (d) antagonists of Ca(2+)-permeable AMPA receptors, including polyamine amide arthropod toxins and their synthetic analogues. Competitive and noncompetitive AMPA receptor antagonists are broad-spectrum anticonvulsants in animal seizure models. Their effectiveness and safety for humans remain to be determined. There is evidence that these antagonists can potentiate the antiseizure activity of N-methyl-D-aspartate (NMDA) receptor antagonists and conventional antiepileptic drugs. This evidence suggests that the preferred use of AMPA receptor antagonists may be in combination therapies. Agents that enhance desensitization may have advantages in comparison with other AMPA receptor antagonists to the extent that they preferentially block high-frequency synaptic signaling and avoid depressing AMPA receptors on interneurons, which would lead to disinhibition and enhanced excitability. Evidence has accumulated that Ca(2+)-permeable AMPA receptors (those lacking the edited GluR2 subunit) may play a role in epileptogenesis and the brain damage occurring with prolonged seizures. Because Ca(2+)-permeable AMPA receptors are predominately expressed in gamma-aminobutyric acid (GABA)ergic interneurons, it is hypothesized that some forms of epilepsy might be caused by reduced GABA inhibition resulting from Ca(2+)-permeable AMPA receptor-mediated excitotoxic death of interneurons. It is further proposed that drugs that selectively target Ca(2+)-permeable AMPA receptors might have antiepileptogenic and neuroprotective properties. Certain polyamine toxins and their analogues are channel-blocking AMPA receptor antagonists that selectively inhibit Ca(2+)-permeable AMPA receptors. These substances might give clues to the development of such antagonists.


[Effects of Chaihu Shugan Powder on the Cytoactivity of Rat Interstitial Cells of Cajal and Intracellu- lar Ca²+ Concentration].
Objective To observe effects of Chaihu Shugan Powder (CSP) on the cytoactivity and intracellular Ca²⁺ concentration of rat interstitial cells of Cajal (ICCs). Methods CSP containing serum was prepared according to common methods of seropharmacology, which was then divided into three CSP groups (5%,10%, 20% CSP containing serum) , 10% Domperidone containing serum group, and the blank control group. ICCs in gastric antrum were rapidly isolated and extracted to perform routine culture. ICCs were identified by immunofluorescence staining. The logarithmic growth curve of ICCs was determined by MTT method. After 3 days culture of ICCs at the logarithmic phase, the cytoactivity of ICCs was detected by CCK-8 method. Intracellular Ca²⁺ changes of ICCs were tested by Fluo-3 fluorescence with laser scanning confocal microscope. Effects of drug containing serums in each group on the growth of ICCs in gastric an- trum were compared. Results After successful isolation, culture, and identification of ICCs, the cytoac- tivity of ICCs and intracellular Ca²⁺ fluorescence intensity were significantly enhanced in the Domperidone group and the CSP groups, as compared with the blank group at the same time point (P <0. 05). Compared with the Domperidone group at the same time point, the cytoactivity of ICCs and intracellular Ca²⁺ fluorescence intensity were significantly enhanced in 10% and 20% CSP groups (P <0. 05). Compared with 5% CSP group at the same time point, the cytoactivity of ICCs (48 and 72 h respectively) and intracellular Ca²⁺ fluorescence intensity were significantly enhanced in 10% and 20% CSP groups (P <0. 05). Conclu- sion CSP could promote cytoactivity and growth of ICCs by enhancing intracellular Ca²⁺ concentration.


Schizophrenia and Nicotine Dependence: What Psychopharmacological Treatment Options are Available for the Duo Perturbationes?
Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.


Clinical Evaluation of the Concussed Athlete: A View From the Sideline.
The sideline assessment of concussion is challenging, given its variable presentations, the limited sensitivity and specificity of sideline assessment tools, and how the presentation of the injury evolves over time. In addition, the diagnostic process, as well as the tools used to assess and manage concussion, continue to progress as research and what we know about concussion advance. This paper focuses on the initial assessment on the sideline by reviewing the concussion-evaluation literature, drawing from clinical experience to emphasize a standardized approach, and underscoring the importance of both familiarity with the athlete and clinical judgment. To review the evidence regarding the clinical assessment of sport-related concussion on the sideline. Additional considerations included making same-day return-to-play decisions, the sensitivity and specificity of sideline testing, and the importance of ongoing assessment and follow-up of injured athletes. I conducted a systematic literature review of the assessment of concussion on the sideline. The PubMed and MEDLINE databases were searched using the key term athletic injuries with concussion and mild traumatic brain injury. The search was refined by adding the key terms sideline assessment and on-field assessment. In addition, select additional position statements and guidelines on concussion were included in the review. The PubMed search using athletic injuries and concussion as key terms produced 1492 results. Refining the search by sideline assessment and on-field assessment produced 29 and 35 results, respectively. When athletic injuries and traumatic brain injury were combined, 1912 results were identified. Refining the search by sideline assessment and on-field assessment led to 28 and 35 results, respectively. Only papers that were English-language titles, original work, and limited to human participants and included sideline assessments of sport-related concussion in athletes older than 13 years were considered for this discussion. A total of 96 papers were reviewed, including systematic reviews, consensus guidelines, and position statements. The sideline assessment of sport-related concussion is challenging given the elusiveness and variability of presentation, reliance on athlete-reported symptoms, and the varying specificity and sensitivity values of sideline assessment tools. In addition, the recognition of injury and assessment often occur in a time-pressured environment, requiring rapid disposition and decision making. Clinicians should begin the evaluation by assessing for cervical spine injury, intracranial bleeding, and other injuries that can present in a similar fashion or in addition to concussion. The sideline concussion evaluation should consist of a symptom assessment and a neurologic examination that addresses cognition (briefly), cranial nerve function, and balance. Emerging tools that assess visual tracking may provide additional information. The sensitivity and specificity of commonly implemented sideline assessment tools are generally good to very good, especially for symptom scores and cognitive evaluations performed within 48 hours of injury, and they are improved when a baseline evaluation is available for comparison. Serial assessments are often necessary as objective signs and symptoms may be delayed. A standardized assessment is paramount in evaluating the athlete with a suspected concussion, but there is no replacement for being familiar with the athlete and using clinical judgment when the athlete seems "not right" despite a "normal" sideline assessment. Ultimately, the clinician should err on the side of caution when making a return-to-play decision.


Monodentate Phosphorus Ligand-Enabled General Palladium-Catalyzed Allylic C-H Alkylation of Terminal Alkenes.
Monodentate phosphorus ligands have been found to enable the palladium-catalyzed allylic C-H alkylation reaction of terminal alkenes with a wide variety of carbon nucleophiles. Moreover, an asymmetric allylic C-H alkylation of terminal alkenes with pyrazol-5-ones has been established in the presence of chiral phosphoramidite ligand and chiral phosphoric acid as co-catalyst. Mechanistic studies suggest that a ternary Pd(0) complex, coordinated with a monodentate phosphorus ligand, benzoquinone, and alkene, is most likely to be an active species.


Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases.
The inadequate nature of the microenvironment is one of several factors considered in the failure of tumor engraftment in athymic mice; in the present work, we have tried to more adequately reconstitute it by injecting tumor cells together with fibroblasts. We have demonstrated that the s.c. co-inoculation of fibroblasts with different kinds of tumor cells of animal origin [rat rhabdomyosarcoma (RMS) 9-4/0, rat hepato-carcinoma FAO] or human origin (colonic adenocarcinoma HT29, Ewing's sarcoma pleural metastasis EW-S1) is necessary for tumor take and growth when the number of tumor cells alone is below the tumorigenic dose. We have shown that the s.c. coinoculation of 10(6) fibroblasts and 10(2) RMS 9-4/0 tumor cells induced a tumor take in all the recipient mice, while 10(2) tumor cells alone never gave any tumor. With a tumorigenic number of RMS 9-4/0 tumor cells (10(4), addition of 10(6) fibroblasts decreased the delay between cell injection and tumor appearance, thereby increasing tumor take and growth rate. These results were observed not only in nude animals (mice and rats) used as recipient animals but also in normal WAG rats receiving the syngeneic RMS 9-4/0 tumor cells, and they were independent of the nature or origin of the different fibroblasts cells. This helper effect has also been observed in the normal WAG rats. I.v. injection of tumor cells from a poorly metastatic 9-4/8 subline, derived from the RMS 9-4/0 line and mixed with 10(6) fibroblasts, gave a high number of lung colonies. Addition of 10(6) irradiated 9-4/8 tumor cells instead of fibroblasts did not increase the lung colonizing potential. Fibroblast-conditioned medium mixed with tumor cells instead of fibroblasts also enhanced tumor take and size but to a lesser extent than did the fibroblasts themselves. Only endothelial cells cultured from porcine aorta had a similar helper effect among the cells tested. It is argued in the discussion that the proliferating state of cultivated fibroblasts is a determinant factor conferring upon them the ability to promote tumor cell growth, while fibroblasts very numerous at the implantation site but quiescent might not be efficient in cooperation. Changes in fibroblast morphology and physiology may be necessary in order for tumor cells to express their tumorigenicity.


[Initial characteristics and isolation of bacterial mutants with altered ability to transpose Tn9].
The method allowing the induction of bacterial mutations affecting Tn9 transposition from the bacteriophage genome to the Escherichia coli chromosome is described. Neither impaired ability of cells to adsorb bacteriophages, nor phage DNA degradation in the mutant cells were observed in the transposition-defective mutants isolated by the method. This led us to the conclusion that the isolated mutants were indeed defective in the transposition of Tn9.


The Transposition Flap for the Reconstruction of Lower Cutaneous Lip Defects.

The lower cutaneous lip is a highly visible and functionally sensitive unit, and numerous factors must be considered when deciding on the optimal repair for defects in this area. The transposition flap represents an excellent option in the reconstruction of larger lower cutaneous lip defects. We describe the use of random pattern transposition flaps for the repair of lower lateral cutaneous lip defects.

J Drugs Dermatol. 2017;16(4):385-387.
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Relationship between vitamin D, calcium and parathyroid hormone in Cape Town.
The aim of this study was to test the hypothesis that vitamin D deficiency is associated with abnormal levels of calcium and parathyroid hormone (PTH). Vitamin D requests at a tertiary hospital in South Africa over 2 years were retrospectively analysed along with calcium and PTH levels. Only when the 25-hydroxyvitamin D (25(OH)D) level dropped below 25 nmol/l, was there a significant rise in PTH. A subnormal 25(OH)D level was also not always related to hypocalcaemia, as more than half of patients with their 25(OH)D level below 25 nmol/l had calcium levels in the reference range. However, all patients with calcium levels below 1.8 mmol/l were shown to have vitamin D insufficiency. Hypovitaminosis D may co-exist with a blunted PTH response. Therefore, assumptions about vitamin D status should not be made based on PTH and calcium values. 25(OH)D measurements should be requested when vitamin D deficiency is clinically suspected, irrespective of biochemical results.


Mandible, tongue, and airway in Pierre Robin sequence: a longitudinal cephalometric study.
The purpose of this retrospective longitudinal cephalometric study was to analyze size, growth, and relations of the mandible, tongue, and airway in the isolated, nonsyndromic Pierre Robin Sequence (PRS) infant. The objective was to understand better the early morphologic changes that occur in these structures. The data were obtained from lateral cephalometric radiographs taken in the first 2 years of life on 17 PRS infants, 26 isolated cleft palate (CP), and 26 normal control (N) infants. Mean values of each variable were compared using a univariate analysis of variance. A multivariate discriminant function analysis (DFA) was also used to characterize group differences. The three groups were distinct throughout the period of study. Differences were greater at the earliest age and the distinction was greater between the PRS and N infants with the CP infant in between, but having more similarity to the PRS infant. Initially, the PRS infant had a shorter tongue and mandibular length, narrower airway, smaller tongue area and the hyoid position was more posterior and inferior as compared to N. The tongue shape and position were specific to the PRS infants. This group distinction diminished with age and resulted from an increased mandibular growth rate in the PRS infant. These findings support the hypothesis of "partial mandibular catch-up growth" in the PRS infant. The increased growth rate in the PRS infant improved the airway dimension, which might be partly responsible for the natural resolution of the respiratory distress. This increased growth rate did not allow for the various structures to reach values equal to normal.


[Impact of a profound change in the structure of a society on the evolution of an endemic disease: leprosy in French Polynesia].
In French Polynesia the cases of leprosy are individually severe but the endemy itself always stood in low limits. The intensive use of modern treatments since 1950 have been making the eredication reasonably possible in the future. However the brutal demographic increase, the deep upsetting of the society and the important migrations made propitious conditions in the urbanized area for the advent of a new centre of infection. The result seems to be an increase of leprosy in the territory.


Charging systems and PAYT experiences for waste management in Spain.
Municipal waste charges in Spain are very widespread, although their application varies significantly among different municipalities. Most commonly, waste charges are implemented as a flat rate, but some of them depend on indicators such as household water consumption, the land area of the property or the value of the real estate. Only one residential pay-as-you-throw scheme has been applied so far. It was a pay-per-bag scheme implemented in Torrelles de Llobregat, Barcelona. A number of other systems focussing only on commercial waste have been implemented in Spain. Several factors suggest that new pay-as-you-throw schemes will be adopted in the near future. In 2000 no municipalities had door-to-door collection schemes; since then over 70 municipalities have implemented them. In addition to this, some regions encourage the separate collection of commercial waste, by means of doorstep schemes. In all of these areas, variable charging systems could be easily adopted. Additionally, regarding waste charges, the National Waste Plan (2000-2006) advocated for the implementation of "pilot experiences for the quantitative application of the polluter-pays-principle". The tendency towards these variable charging systems in Europe will also favour their introduction in Spain.


Methodological pipeline for monitoring post-harvest quality of leafy vegetables.
Plants are primary source of nutrients for humans. However, the nutritional value of vegetables tends to decrease once organ and tissue sinks are detached from the plant. Minimal processing of leafy vegetables involves cutting and washing before packaging and storage. These processing procedures result in stressful conditions and post-harvest disorders senescence-related can also occur. The aim of this work is to define a methodological pipeline to evaluate the "quality" changes of fresh cut leafy vegetables over their shelf-life. At this purpose, intra-species variability has been investigated considering two varieties of Lactuca sativa (var. longifolia and capitata), showing different susceptibility to browning. Since browning mainly depends on phenol oxidation, redox parameters as well as the activity of the enzymes involved in phenol biosynthesis and oxidation have been monitored over storage time. At the same time, the metabolic changes of the lettuce leaves have been estimated as response patterns to chemical sensors. The obtained sensor outputs were predictive of browning-related biological features in a cultivar-dependent manner. The integration of the results obtained by this multivariate methodological approach allowed the identification of the most appropriate quality markers in lettuce leaves from different varieties. This methodological pipeline is proposed for the identification and subsequent monitoring of post-harvest quality of leafy vegetables.


Development and validation of a sensitive spectrofluorimetric method for the determination of amoxapine in human plasma and urine.
A selective and sensitive spectrofluorimetric method was developed and validated for the determination of amoxapine in human plasma and urine. The developed method is based on labeling with 5-dimethylaminonaphthalene-1-sulfonyl chloride (dansyl chloride) and monitoring at 397 nm (excitation)/514 nm (emission). The method was validated for linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, recovery and robustness. The calibration curves were linear over a concentration range of 250-2500 and 50-1250 ng/mL for plasma and urine, respectively. The LOD values were calculated to be 13.31 and 13.17 ng/mL for plasma and urine, respectively. The proposed method was applied to study of amoxapine in human plasma and urine.


Successful Radiofrequency Ablation of Recurrent Supraventricular Tachycardia in a Patient with Complex Congenital Heart Disease.
BACKGROUND Radiofrequency ablation (RFA) is the criterion standard treatment for patients with atrioventricular nodal reentrant tachycardia (AVNRT). Knowledge about RFA in patients with dextrocardia and situs inversus is limited due to their rare incidence and complexity. The incidence of dextrocardia is reported to be 1 in 12 000 births, with situs inversus occurring in one-third of the cases. The incidence of congenital heart disease is about 5% in these patients. However, data on rhythm and conduction disorders in this group of patients are currently limited, making management more difficult owing to their individual anatomy. CASE REPORT We report the case of an obese 21-year-old man with complex congenital heart disease (CCHD) (situs inversus dextrocardia, pulmonary atresia, single ventricle, common atrium with single atrioventricular valve), asplenia, and multiple cardiac-corrective surgeries (Fontan repair, bidirectional Glenn anastomosis, and Blalock-Taussig shunt) who underwent successful RFA of recurrent supraventricular tachycardia. CONCLUSIONS Supraventricular arrhythmias are common in the setting of CCHD. Although catheter ablation procedures are technically challenging to perform in patients with CCHD, they remain the best therapeutic option for these arrhythmias. To our knowledge, this case is the first to be described in the literature of successful ablation of AVNRT in a patient with situs inversus dextrocardia, pulmonary atresia, a single ventricle, a common atrium with a single atrioventricular valve, and multiple cardiac-corrective surgeries.


Gene expression-based risk score in diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression-based risk score (GERS) predictive for patient's overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS was shown to be an independent predictor of survival when compared to the previously published prognostic factors, including the International Prognostic Index (IPI). GERS displayed a prognostic value in germinal-center B-cell-like subgroup (GCB) and activated B cell-like (ABC) molecular subgroups of patients as well as in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or rituximab-CHOP (R-CHOP) regimens. Combination of GERS and IPI lead to a potent prognostic classification of DLBCL patients. Finally, a genomic instability gene signature was highlighted in gene expression profiles of patients belonging to the high-risk GERS-defined group.


DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity.
Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together, these results indicate that HIV-1 IN is a shape-readout DNA binding protein.


Directed Evolution: Past, Present and Future.
Directed evolution, the laboratory process by which biological entities with desired traits are created through iterative rounds of genetic diversification and library screening or selection, has become one of the most useful and widespread tools in basic and applied biology. From its roots in classical strain engineering and adaptive evolution, modern directed evolution came of age twenty years ago with the demonstration of repeated rounds of PCR-driven random mutagenesis and activity screening to improve protein properties. Since then, numerous techniques have been developed that have enabled the evolution of virtually any protein, pathway, network or entire organism of interest. Here we recount some of the major milestones in the history of directed evolution, highlight the most promising recent developments in the field, and discuss the future challenges and opportunities that lie ahead.


Monoether-Tagged Biodegradable Polycarbonate Preventing Platelet Adhesion and Demonstrating Vascular Cell Adhesion: A Promising Material for Resorbable Vascular Grafts and Stents.
We developed a biodegradable polycarbonate that demonstrates antithrombogenicity and vascular cell adhesion via organocatalytic ring-opening polymerization of a trimethylene carbonate (TMC) analogue bearing a methoxy group. The monoether-tagged polycarbonate demonstrates a platelet adhesion property that is 93 and 89% lower than those of poly(ethylene terephthalate) and polyTMC, respectively. In contrast, vascular cell adhesion properties of the polycarbonate are comparable to those controls, indicating a potential for selective cell adhesion properties. This difference in the cell adhesion property is well associated with surface hydration, which affects protein adsorption and denaturation. Fibrinogen is slightly denatured on the monoether-tagged polycarbonate, whereas fibronectin is highly activated to expose the RGD motif for favorable vascular cell adhesion. The surface hydration, mainly induced by the methoxy side chain, also contributes to slowing the enzymatic degradation. Consequently, the polycarbonate exhibits decent blood compatibility, vascular cell adhesion properties, and biodegradability, which is promising for applications in resorbable vascular grafts and stents.


[Urinary incontinence in the elderly].
Urinary Incontinence (UI) is a cardinal geriatric syndrome that has an impact on the health and quality of life of the elderly and those living around them. The etiology is often multifactorial. Physical, cognitive, functional, and psychological factors contribute to the appearance of UI. In most patients, the clinical history and a good physical examination are enough to diagnose UI accurately; although to confirm and classify UI further more complex tests are needed. The fields of pharmacology, endoscopy, neurophysiology, and surgery are making significant progress to manage UI; therefore, is useful for all practicing physicians that attend elderly patients to learn about the new therapeutic options.


Randomized trial of leuprorelin and flutamide in male patients with hepatocellular carcinoma treated with tamoxifen.
The growth of hepatocellular carcinoma (HCC) is thought to be dependent on androgens, as androgen receptors are present in most of these tumors. The aim of this multicenter trial was to assess the effect of antiandrogens in patients who have advanced HCC. Male patients with advanced HCC were randomized into 2 groups treated with (1) leuprorelin (3.75 mg/mo subcutaneously), flutamide (750 mg/d orally), and tamoxifen (30 mg/d orally) or (2) tamoxifen alone (30 mg/d orally) administered until death. Survival was the main end point (log-rank test). The required sample size was 375 patients (alpha, 5%; beta, 10%; 1-year survival, 45% in treated group and 30% in controls). Between February 1994 and January 1998, 376 male patients (mean age, 66 years; treated group, n = 192; control group, n = 184) were included. No baseline imbalance was found between the groups. At the reference date (January 1, 2003), 183 deaths (95.3%) were observed in the treated group and 177 deaths (96.2%) were observed in controls. Thirteen patients were lost to follow-up. Median survival time was estimated to be 135.5 days (95% CI, 112-189) and 176 days (95% CI, 141-227) in treated and control groups, respectively (P = .21). Crude and adjusted relative risks of death in the treated group were estimated at 1.14 (95% CI, 0.93-1.40) and 1.08 (95% CI, 0.87-1.33; P = .48) respectively. Premature interruption of treatment was more frequent in the treated group (n = 45) than in controls (n = 22; P = .0045), mainly because of digestive side effects. In conclusion, no benefit in survival was found with antiandrogenic treatment in male patients with advanced HCC.


Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer.
The beta-chemokine RANTES was measured in plasma in 43 patients with breast cancer and in 23 patients with cervical cancer, and the RANTES content in primary tumors, tumor metastatic to lymph nodes, and clinically normal skin or pelvic mucosa was measured. In addition, plasma levels were determined in all of the patients for the platelet-derived chemokine beta-thromboglobulin (beta-TG) and for IFN-gamma, interleukin (IL)-2, IL-4, IL-5, and IL-10, along with serum IgE levels and blood eosinophils. Plasma RANTES levels were found to be higher in order of stages IV, III, II, and I of each cancer except for stage I. A marked increase in plasma RANTES level (> 10,000 pg/ml) was found in 27% of patients with progressive malignancy but in none of those in clinical remission. The platelet RANTES content was correspondingly decreased in those patients with increased plasma RANTES levels. Beta-TG showed a pattern similar to RANTES both in plasma and platelets, but with much less dramatic differences between patients with different stages of disease. Other allergic parameters, IgE, eosinophils and plasma IFN-gamma, IL-2, -5, and -10, were not elevated in the cancer patients. The RANTES content was markedly elevated in the primary tumor and metastatic lesions (lymph node or skin) from all of the patients with breast or cervical cancer, irrespective of the plasma RANTES level. In addition, in patients with progressive breast or cervical cancer, but not in patients thought to be cured of these tumors, the RANTES content was markedly increased in clinically normal tissue taken from near the operative site several months postoperatively, as well as in intact skin or mucosa taken perioperatively near the excised tumor. This study suggests an as-yet-undefined but important role played by RANTES in carcinogenesis, as well as the possibility that a RANTES assay in tissue surrounding a tumor or postoperative tumor site may help predict prognosis in these patients.


Abnormal level of arousal as a predictor of delirium and inattention: an exploratory study.
Abnormal level of arousal (LoA) and inattention are key features of delirium. However, the extent to which abnormal LoA alone might predict delirium and inattention is unclear. Here we tested the hypotheses that (1) patients with abnormal LoA have delirium, and (2) abnormal LoA is associated with worse performance on tests of attention. Thirty acute hip fracture patients aged 64-97 years underwent assessments of LoA, delirium status, and attentional functioning in the 24 hours before surgery and at 2-4 and 7-10 days after surgery. The Observational Scale of Level of Arousal (OSLA) and the Richmond Agitation-Sedation Scale (RASS) were used to assess LoA. Sustained attention was measured with the Edinburgh Delirium Test Box. Delirium was assessed with the Confusion Assessment Method and the Delirium Rating Scale-Revised-98. Ten patients (33%) were diagnosed with delirium. Abnormal LoA as measured by the OSLA was strongly associated with the presence of delirium. The area under the receiver operating characteristic curve was 0.89 (95% confidence interval: 0.81-0.97), with a sensitivity of 0.87 and a specificity of 0.81. Area under the curve, sensitivity, and specificity for the RASS were 0.81 (95% confidence interval: 0.68-0.94), 0.80, and 0.79, respectively. Abnormal LoA was associated with worse attentional deficits preoperatively and at postoperative days 2-4 (p <0.01). These exploratory findings suggest that abnormal LoA is a strong indicator of delirium. Also, abnormal LoA is strongly associated with inattention as measured by an objective cognitive test. These findings suggest that acute-onset abnormal LoA could be used as a trigger for delirium assessment in routine clinical practice. Future work will help to clarify further the interrelationships among abnormal LoA, inattention, and delirium.


Benign rolandic epilepsy: neuropsychological findings.
Benign rolandic epilepsy (BRE) is a partial idiopathic epilepsy of childhood presenting with a nocturnal seizure and with a typical EEG showing centrotemporal spike and multifocal or generalized sharp slow waves. Although normal neurological and intellectual development are expected in BRE, it is not infrequent to detect subtle defects in neuropsychological functions and neuromotor development. This study included 20 cases of BRE diagnosed according to the criteria of ILAE. The patients underwent several tests of neuropsychological functions as well as detailed neurological examination and the results were compared statistically to normal controls. In the patient group, a family history of language delay or learning disability (P < 0.005), presence of consanguinity (P < 0. 05), dyspraxia in the lower extremities (to imitation) (P < 0.05), difficulties in go-no-go test (P < 0.001), as well as some problems related to language such as dysprosody (P = 0.05), minor motor deficits in the left (P < 0.05) and right upper extremity (P < 0.05) were significantly more frequent compared to the control group. One should be rather guarded against the prognosis in BRE with respect to the higher cortical functions and neurodevelopmental problems.


Preparation of Rat Whole-kidney Acellular Matrix via Peristaltic Pump.
To design a whole-kidney a cellular matrix scaffold using peristaltic pump perfusion and to ascertain the retention of extra cellular proteins by the scaffold. Male Sprague-Dawley (SD) rats weighing 200-250 g were used. Intravenous catheters were inserted into the renal artery followed by perfusion of decellularization solution using a peristaltic pump. After decellularization, the acellular matrix was observed under a microscope after hematoxylin and eosin (H&E) staining and a fluorescence microscope after 4′,6-diamidino-2-phenylindole (DAPI) staining. Immunohistochemistry was used to identify the composition of kidney acellular matrix. The result of H&E and DAPI staining demonstrate the removal of cellular material in kidney a cellular matrix. Immunohistochemistry confirmed the conservation of the natural expression of extra cellular matrix proteins including collagen types I and IV, fibrin and laminin. Peristaltic pump perfusion enables successful preparation of renal a cellular matrix, to retainthe criticalproteins of natural extra cellular matrix. The resulting kidney a cellular matrix represents an ideal natural scaffold for renal tissue engineering.


Can the risk of obstetric anal sphincter injuries (OASIs) be predicted using a risk-scoring system?
Perineal trauma involving the anal sphincter is an important complication of vaginal delivery. Prediction of anal sphincter injuries may improve the prevention of anal sphincter injuries. Our aim was to construct a risk scoring model to assist in both prediction and prevention of Obstetric Anal Sphincter Injuries (OASIs). We carried out an analysis of factors involved with OASIs, and tested the constructed model on new patient data. Data on all vaginal deliveries over a 5 year period (2004-2008) was obtained from the electronic maternity record system of one institution in the UK. All risk factors were analysed using logistic regression analysis. Odds ratios for independent variables were then used to construct a risk scoring algorithm. This algorithm was then tested on subsequent vaginal deliveries from the same institution to predict the incidence of OASIs. Data on 16,920 births were analysed. OASIs occurred in 616 (3.6%) of all vaginal deliveries between 2004 and 2008. Significant (p < 0.05) variables that increased the risk of OASIs on multivariate analysis were: African-Caribbean descent, water immersion in labour, water birth, ventouse delivery, forceps delivery. The following variables remained independently significant in decreasing the risk of OASIs: South Asian descent, vaginal multiparity, current smoker, home delivery. The subsequent odds ratios were then used to construct a risk-scoring algorithm that was tested on a separate cohort of patients, showing a sensitivity of 52.7% and specificity of 71.1%. We have confirmed known risk factors previously associated with OASIs, namely parity, birth weight and use of instrumentation during delivery. We have also identified several previously unknown factors, namely smoking status, ethnicity and water immersion. This paper identifies a risk scoring system that fulfils the criteria of a reasonable predictor of the risk of OASIs. This supersedes current practice where no screening is implemented other than examination at the time of delivery by a single examiner. Further prospective studies are required to assess the clinical impact of this scoring system on the identification and prevention of third degree tears.


Characterization of carbon dioxide concentrating chemolithotrophic bacterium Serratia sp. ISTD04 for production of biodiesel.
Proteomics and metabolomics analysis has become a powerful tool for characterization of microbial ability for fixation of Carbon dioxide. Bacterial community of palaeoproterozoic metasediments was enriched in the shake flask culture in the presence of NaHCO3. One of the isolate showed resistance to NaHCO3 (100mM) and was identified as Serratia sp. ISTD04 by 16S rRNA sequence analysis. Carbon dioxide fixing ability of the bacterium was established by carbonic anhydrase enzyme assay along with proteomic analysis by LC-MS/MS. In proteomic analysis 96 proteins were identified out of these 6 protein involved in carbon dioxide fixation, 11 in fatty acid metabolism, indicating the carbon dioxide fixing potency of bacterium along with production of biofuel. GC-MS analysis revealed that hydrocarbons and FAMEs produced by bacteria within the range of C13-C24 and C11-C19 respectively. Presence of 59% saturated and 41% unsaturated organic compounds, make it a better fuel composition.


Synthesis of ribonucleic acid in the venom gland of Crotalus durissus terrificus (Ophidia, Reptilia) after manual extraction of tne venom.
1. The incorporation of [5-(3)H]uridine into RNA of the venom gland of Crotalus durissus terrificus was studied after manual extraction (;milking') of the venom. The labelled precursor was injected immediately after milking. 2. The RNA was extracted 1, 2, 4, 6 and 8h after injection of the label and analysed by sucrose-density-gradient centrifugation. 3. The sedimentation analysis showed that 18S rRNA synthesis is higher than 28S rRNA at all time-intervals. The specific radioactivities of both ribosomal components did not reach a plateau even at 8h after injection. 4. An RNA fraction was detected sedimenting between 18S rRNA and 4S tRNA and was called the 10-14S fraction. The specific radioactivity was always higher than that of both classes of rRNA and reached the maximum value at 6h of labelling. 5. The incorporation of the precursor was also studied by radioautography, which helped to elucidate the intracellular origin of the RNA analysed by sucrose-density-gradient centrifugation.


Mechanical Properties of Organic Semiconductors for Stretchable, Highly Flexible, and Mechanically Robust Electronics.
Mechanical deformability underpins many of the advantages of organic semiconductors. The mechanical properties of these materials are, however, diverse, and the molecular characteristics that permit charge transport can render the materials stiff and brittle. This review is a comprehensive description of the molecular and morphological parameters that govern the mechanical properties of organic semiconductors. Particular attention is paid to ways in which mechanical deformability and electronic performance can coexist. The review begins with a discussion of flexible and stretchable devices of all types, and in particular the unique characteristics of organic semiconductors. It then discusses the mechanical properties most relevant to deformable devices. In particular, it describes how low modulus, good adhesion, and absolute extensibility prior to fracture enable robust performance, along with mechanical "imperceptibility" if worn on the skin. A description of techniques of metrology precedes a discussion of the mechanical properties of three classes of organic semiconductors: π-conjugated polymers, small molecules, and composites. The discussion of each class of materials focuses on molecular structure and how this structure (and postdeposition processing) influences the solid-state packing structure and thus the mechanical properties. The review concludes with applications of organic semiconductor devices in which every component is intrinsically stretchable or highly flexible.


Movement of an imperiled esocid fish in an agricultural drain.
Animal movement is increasingly affected by human alterations to habitat and climate change. In wetland systems, widespread hydrologic alterations from agriculture have changed the shape, function, and stability of shallow streams and wetland habitats. These changes in habitat quality and quantity may be especially consequential for freshwater fishes such as Grass Pickerel (Esox americanus vermiculatus), a small predatory fish found in disjunct populations across southern Ontario and listed as Special Concern under Canada's Species at Risk Act. To characterize Grass Pickerel movement response to stream-channel alterations, Fisheries and Oceans Canada implemented a tracking study to monitor the movements of a Grass Pickerel population in an agricultural drain on the Niagara Peninsula (Ontario, Canada). From 2009 to 2013, 2007 Grass Pickerel were tagged and tracked in the 37.3 km2 Beaver Creek watershed using a combination of mark-recapture surveys and eight fully automated passive integrated transponder tag antennas. Most individuals moved within 500 m (i.e., stationary fish) while 16% of the fish moved > 500 m (i.e., mobile fish), with a maximum median movement distance of 1.89 km and a maximum movement distance of 13.5 km (a long-tail distribution). Most movements occurred near the largest confluence where only a few were long-distance upstream or downstream movements. Mobile fish were larger than their stationary counterparts. Grass Pickerel in sites with higher abundance had more mobile fish, implying potential density dependence. Our results highlight that, while a long-distance dispersal ability exists in extant Grass Pickerel populations, the current conditions of riverscapes may prevent these dispersals from occurring. For declining Grass Pickerel populations, limitations to their movement ecology may substantially increase the likelihood of local extirpations.


Topical treatment of tinea pedis using 6% coriander oil in unguentum leniens: a randomized, controlled, comparative pilot study.
The antifungal activity of coriander oil has already been demonstrated in vitro. Evaluation of the efficacy and tolerability of 6% coriander oil in unguentum leniens in the treatment of interdigital tinea pedis. Half-side comparative pilot study on subjects with symmetric, bilateral interdigital tinea pedis. Active drug and placebo control were applied twice daily on the affected areas, and follow-up visits were performed on days 14 and 28. 40 participants (mean age 52.5 years, 60% male) were included in the study. For 6% coriander oil in unguentum leniens, a highly significant improvement of the clinical signs (p < 0.0001) was observed during the entire observation period; the number of positive fungal cultures also tended to decrease (p = 0.0654). The tolerability of the tested substances was good. Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis.


Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori.
Ginger root (Zingiber officinale) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness, dyspepsia and hyperemesis gravidarum, and is also reported to have chemopreventative activity in animal models. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since Helicobacter pylori (HP) is the primary etiological agent associated with dyspepsia, peptic ulcer disease and the development of gastric and colon cancer, the anti-HP effects of ginger and its constituents were tested in vitro. A methanol extract of the dried powdered ginger rhizome, fractions of the extract and the isolated constituents, 6-,8-,10-gingerol and 6-shogoal, were tested against 19 strains of HP, including 5 CagA+ strains. The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a minimum inhibitory concentration range of 6.25-50 micrograms/ml. One fraction of the crude extract, containing the gingerols, was active and inhibited the growth of all HP strains with an MIC range of 0.78 to 12.5 micrograms/ml and with significant activity against the CagA+ strains. These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagA+ strains in vitro and this activity may contribute to its chemopreventative effects.


The yeast EDC1 mRNA undergoes deadenylation-independent decapping stimulated by Not2p, Not4p, and Not5p.
A major mechanism of eukaryotic mRNA degradation initiates with deadenylation followed by decapping and 5' to 3' degradation. We demonstrate that the yeast EDC1 mRNA, which encodes a protein that enhances decapping, has unique properties and is both protected from deadenylation and undergoes deadenylation-independent decapping. The 3' UTR of the EDC1 mRNA is sufficient for both protection from deadenylation and deadenylation-independent decapping and an extended poly(U) tract within the 3' UTR is required. These observations highlight the diverse forms of decapping regulation and identify a feedback loop that can compensate for decreases in activity of the decapping enzyme. Surprisingly, the decapping of the EDC1 mRNA is slowed by the loss of Not2p, Not4p, and Not5p, which interact with the Ccr4p/Pop2p deadenylase complex. This indicates that the Not proteins can affect decapping, which suggests a possible link between the mRNA deadenylation and decapping machinery.


Ultrastructural studies of primary congenital glaucoma in rabbits.
The cause of congenital glaucoma is unknown. To determine whether the site of impaired aqueous outflow is the entrance to the trabecular meshwork (TM), within the TM, the aqueous drainage plexus, or a combination thereof, the process of TM development was examined by scanning and transmission electron microscopy on postnatal day 3 and weeks 1, 2, 3, 4, and 6 in New Zealand rabbits homozygous for the buphthalmic (bu/bu) gene compared with age-matched controls. Openings to the entrance of the TM in congenital glaucoma were observed, and there was no evidence of an endothelial membrane occluding aqueous flow to the TM. The morphology of the congenital glaucoma TM was abnormal in all bu/bu rabbits by 2 weeks and was characterized by a smaller entrance to the TM at the iris base, smaller intertrabecular openings within and between the trabecular lamellae, and at 6 weeks, iris pillars with extensive lateral extensions in the angle recess. Most intertrabecular spaces were open, however, the inner intertrabecular spaces adjacent to the aqueous plexus were compressed. These results suggest the development of congenital glaucoma, which involves a mutation in an autosomal recessive gene and leads to loss of function of a gene(s) required for the differentiation of the TM.


Single Low Dose Primaquine (0.25 mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.
Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic. The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria. ClinicalTrials.gov NCT01872702.