Detecting Iodine-Labeled Cells.
The binding of radiolabeled reagents to cells is detected by coating the specimen with a photographic emulsion. When the emulsion is developed, silver grains can be seen at the location of the radiolabel. The silver grains appear as black dots in bright-field microscopy but are most readily detected by dark-field illumination, in which they are seen as intense silver reflections on a black background. The detection of iodine-labeled reagents is extremely sensitive, and the reaction is readily controlled by setting up duplicate samples and varying the exposure time. The method is compatible with histological stains and can be used in double-labeling procedures with enzyme- or fluorochrome-labeled reagents. When iodine-labeled and enzyme-labeled reagents are used together for double labeling, the enzyme-labeled reagents must be developed before the photographic emulsion is added.


CIA-II is associated with lower-grade glioma survival and cell proliferation.
The role of CIA-II has been clarified in several types of tumors; however, whether dysregulated CIA-II expression is also involved in the pathophysiology of lower-grade glioma (LGG) remains undisclosed. A comprehensive pan-cancer analysis of the expression patterns and prognostic significance of CIA-II in miscellaneous tumors was undertaken. Subsequently, a detailed bioinformatics analysis was executed to identify putative correlations between CIA-II expression and clinical features, prognosis, biological functions, immunological characteristics, genomic alterations, and chemotherapeutics in LGG. In vitro studies were implemented to examine the potential roles of CIA-II in LGG. CIA-II expression was found to be abnormally elevated in a variety of tumors, including LGG. Additionally, patients with LGG with higher CIA-II expression owned worse prognosis. Importantly, the results declared that CIA-II expression was an independent prognostic indicator for LGG. Moreover, the expression of CIA-II was tightly interrelated with immune cell infiltration, gene mutations, and chemotherapeutics in LGG. In vitro studies revealed that CIA-II was increased and strongly related to the cell proliferation in LGG. CIA-II may be an independent prognostic factor and a serviceable therapeutic target in LGG.


Eosinophil count in nasal mucosa is more suitable than the number of ICAM-1-positive nasal epithelial cells to evaluate the severity of house dust mite-sensitive allergic rhinitis: a clinical correlation study.
House dust mite (HDM)-sensitive allergic rhinitis is a perennial rhinitis with persistent nasal inflammation. Currently, there are no reliable parameters to monitor the severity of perennial allergic rhinitis. The purpose of this study was to evaluate correlations between clinical and laboratory parameters in patients with HDM-sensitive allergic rhinitis. We measured nasal symptoms, did the Dermatophagoides pteronyssinus (Der P) skin prick test (SPT), evaluated the Der P allergen nasal challenge threshold, and laboratory parameters [(1) inflammatory cell count from nasal mucosal scraping specimens: eosinophils and neutrophils and (2) immunocytochemistry: ICAM-1 expression on nasal epithelial cells] in 20 cases of HDM-sensitive allergic rhinitis and performed correlation tests between all parameters. The wheal diameter induced by Der P SPT was significantly correlated with the Der P allergen nasal challenge threshold (p = 0.001). The number of eosinophils from nasal mucosal scrapping specimens was correlated with the ICAM-1 expression on nasal epithelial cells (p = 0.039), the number of neutrophils from nasal mucosal scrapping specimens (p = 0.001), and nasal stuffiness (p = 0.037) but did not correlate with total nasal symptom scores. Clinical symptoms of HDM-sensitive allergic rhinitis showed a poor correlation with inflammatory parameters. The eosinophil count in nasal mucosa is correlated with ICAM-1 expression and more suitable than ICAM-1 levels to evaluate the severity of HDM-sensitive allergic rhinitis. This study also supports the role of the SPT in the diagnosis of nasal allergy to HDM.


Site-directed mutagenesis and functional analysis of the active-site residues of the E2 component of bovine branched-chain alpha-keto acid dehydrogenase complex.
The catalytic domain of dihydrolipoamide transacylase (E2c) of bovine branched-chain alpha-keto acid dehydrogenase complex (BCKAD) was overexpressed in Escherichia coli. The E2c catalyzes a reversible acyl transfer reaction between acyl-CoA and dihydrolipoamide, which also occurs spontaneously with a much slower rate. The benzene extracts of both the enzyme-catalyzed and the spontaneous reactions mixture have identical ultraviolet absorbance spectra with a maximum at 233-234 nm, which is characteristic of S-acyldihydrolipoamide. The spontaneous reaction rate of various acyl-CoA is in the order of acetoacetyl-CoA > acetyl-CoA > isobutyryl-CoA > isovaleryl-CoA. In other words, the spontaneous acyl transfer is faster when the substituent (R) of acyl-CoA (R-CO-S-CoA) is a more electron-withdrawing group. This result indicates that a negative charge occurs in the substrate during the acyl transfer process. The function of the active-site histidine (His391) and serine (Ser338) of bovine E2c was analyzed by site-directed mutagenesis. Substitution of His391 or Ser338 with alanine caused drastic decreases in catalytic efficiencies by 3-4 orders of magnitude. The residual activity of H391A increased as the pH of the reaction buffer was elevated. These data support the base-catalyzed mechanism inferred from that of chloramphenicol acetyltransferase (CAT). In this reaction, the active-site histidine acts as a general base, and the active-site serine provides a hydrogen bond to the putative negatively charged tetrahedral transition state. Moreover, when Ala348 was changed to valine, the catalytic efficiency for isovaleryl-CoA decreased about 10-fold, and that for acetyl-CoA increased about 3-fold.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of endogenicity and severity on consistency of standard depression rating scales.
Agreement between the clinician-rated Hamilton Depression Rating Scale and the patient-rated Zung Self-Rating Depression Scale was examined in 36 inpatients with major depression during the course of a 4-week antidepressant treatment protocol. Clinician-patient agreement was low when depression was rated as most severe by the clinician. An endogenicity factor extracted from the Zung scale also predicted disagreement, which was greatest for patients with more nonendogenous symptom patterns. Clinicians and researchers should remain aware of the limitations of such standard assessment procedures in the context of changing criteria for the diagnosis of depression.


[Comparison of analgesic effects of electroacupuncture of multi-factor quantitative parameters on inflammatory pain in rats].
To probe into the best parameter of electroacupuncture (EA) for treatment of inflammatory pain in the rat. One hundred and twenty Wistar rats were randomly divided into 12 groups, normal control group, model group and 10 EA groups including A1 B1 C1, A1 B1 C2, A1 B2 C1, A1 B2 C2, A2 B1 C1, A2 B1 C2, A2 B2 C1, A2 B2 C2 (A1 : 2 Hz, A2: 100 Hz; B1 : successive wave; B2: intermittent wave; C1: 0.1 mA, C2: 0.2 mA), A3 B3 C1 (4/20 Hz, disperse-dense wave, 0.1 mA) and A3 B3 C2 (4/20 Hz, disperse-dense wave, 0.2 mA). The rats of adjuvant-induced arthritis in all of the EA groups were treated by EA with selected different parameters once every day for 6 days. Pain thresholds and beta-endorphin (beta-EP) content in the local tissue of inflammation were used as indexes to compare analgesic effects of EA of different frequencies, waveforms and currents by orthogonal experiment design and other methods. The optimized parameters of raising the pain threshold was: 100 Hz, 0.1 mA, intermittent wave. EA at 100 Hz was better than 2 Hz for increasing the content of beta-EP in local tissue of inflammation. The analgesic effect of EA at 4/20 Hz, 0.1 mA, disperse-dense wave on the inflammatory pain in the rat was not significant different with that at 100 Hz, 0.1 mA, intermittent wave (P > 0.05). The best parameters are 100 Hz, 0.1 mA and intermittent wave for EA treatment of inflammatory pain in the rat.


Cancer Worry, Perceived Risk and Cancer Screening in First-Degree Relatives of Patients with Familial Gastric Cancer.
Currently, there is a lack of evidence evaluating the psychological impact of cancer-related risk perception and worry in individuals at high risk for gastric cancer. We examined the relationships between perceived risk, cancer worry and screening behaviors among first-degree relatives (FDRs) of patients with familial gastric cancer. FDRs of patients diagnosed with familial gastric cancer with a non-informative genetic analysis were identified and contacted. Participants completed a telephone interview that assessed socio-demographic information, cancer risk perception, cancer worry, impact of worry on daily functioning, and screening behaviors. Twenty-five FDRs completed the telephone interview. Participants reported high levels of comparative and absolute cancer risk perception, with an average perceived lifetime risk of 54 %. On the other hand, cancer-related worry scores were low, with a significant minority (12 %) experiencing high levels of worry. Study participants exhibited high levels of confidence (median = 70 %) in the effectiveness of screening at detecting a curable cancer. Participants that had undergone screening in the past showed significantly lower levels of cancer-related worry compared to those that had never undergone screening. In conclusion, individuals at high-risk for gastric cancer perceived a very high personal risk of cancer, but reported low levels of cancer worry. This paradoxical result may be attributed to participants' high levels of confidence in the effectiveness of screening. These findings highlight the importance for clinicians to discuss realistic risk appraisals and expectations towards screening with unaffected members of families at risk for gastric cancer, in an effort to help mitigate anxiety and help with coping.


Protection of hepatocytes from Fas-mediated apoptosis by a non-transforming SV40 T-antigen mutant.
Apoptosis is crucial for the normal development of multicellular organisms and is also important for clearing injured cells, such as virus-infected cells or cancer cells. Defective regulation of apoptosis may contribute to viral pathogenesis and aetiology of cancer. Apoptosis of injured cells is principally triggered by the immune system through cytokines such as Fas-ligand and TNF-alpha. Thus, one of the functions of a viral oncogene, such as SV40T-antigen, may be to inhibit cytokine-mediated apoptosis. We previously demonstrated that Fas-mediated apoptosis of hepatocytes is blocked by the wild-type SV40T-antigen during hepatocarcinogenesis. We determined whether this inhibition was directly related to the T-antigen or whether it is a secondary event of cell transformation, by generating transgenic mice expressing a non-transforming T-antigen mutant able to bind endogenous p53 in the liver. This T-antigen mutant cannot induce hepatocarcinoma, unlike the wild-type T-antigen. However, like the wild-type T-antigen, the mutant was a potent inhibitor of apoptosis induced by the Fas-receptor, but not by the TNF-receptor. Therefore, SV40T-antigen has a new property; the inhibition of Fas-mediated apoptosis, which could facilitate the emergence of transformed hepatocytes, but is not sufficient to induce it.


All-trans-retinoic acid blocks cell cycle progression of human ovarian adenocarcinoma cells at late G1.
We prepared single cell clones from two ovarian carcinoma cell lines, CA-OV3 and SK-OV3, and analyzed the effect of all-trans-RA treatment on cell division, DNA synthesis, and cell cycle stage distribution of these single cell clones. Our results show that despite the well-known heterogeneous nature of these cell lines, all single cell clones of SK-OV3 cells are resistant to the growth inhibitory effects of all-trans-RA. In contrast, all single cell clones of CA-OV3 cells were growth inhibited by all-trans-RA. However, the extent of growth inhibition did vary somewhat from clone to clone. Additional studies employing flow cytometry showed that all-trans-RA blocked CA-OV3 cell cycle progression in the G1 stage. Finally, all-trans-RA was able to inhibit G1 progression in growth-arrested CA-OV3 cells following stimulation with fetal bovine serum, insulin, IGF-1, or estrogen. Since each of these growth factors is known to act via distinct signal transduction pathways, our results suggest that all-trans-RA blocks G1 progression by targeting a downstream process or event which occurs at a point after the insulin/IGF-1, estrogen, and serum signal transduction pathways converge.


EVOLUTION OF MORTALITY FOR COLORECTAL CANCER IN BRAZIL AND REGIONS, BY SEX, 1996-2015.
Colorectal cancer is among the three most frequent neoplasms in Brazil, being a public health problem. To describe distribution pattern of colorectal cancer mortality in Brazil and regions, according to sex, between 1996 and 2015. Values of standardized and stratified mortality rates by sex between 1996 and 2015 were used, through polynomial regression models and joinpoint analysis. It was observed that, for linear trends in mortality rates, for both sexes, there is a statistically significant trend increasing in both models, with rates and trends, and higher for men than for women, respectively, 7.3% per year (R2=0.95, P<0.001) and 6.5% per year (R2=0.87, P<0.001). It is observed a difference in magnitude and behavior of trend between the regions. It is understood that it is important to know the trend of rates in order to define priority populations for early interventions that increase survival and reduce mortality.


[Effects of sympathetic nerve stimulation on connexin43 and ventricular arrhythmias during acute myocardial ischemia: experiment with rats].
To investigate the effects of sympathetic nerve stimulation (SNS) on connexin43 (Cx43) and ventricular arrhythmias during acute myocardial ischemia (MI). Ninety five Wistar rats were randomly divided into four groups: MI group (n=25), undergoing: ligation of the anterior descending coronary; MII-SNS group (n=25); undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary and lasting till 30 min after the ligation, sympathetic nerve stimulation preconditioning + myocardial ischemia (pSNS-MI) group (n=25), undergoing electric stimulation of sympathetic nerve since the beginning of ligation of the anterior descending coronary that ended just after the ligation; and sham operation (SO) group (n=20), without coronary ligation. Ventricular arrhythmias were monitored by electrocardiography. Western blotting and RT-PCR were used to detect the protein and mRNA expression of Cx43 respectively. Immunofluorescence analysis was used to observe the changes of Cx43 protein distribution. One and 3 rate died due to ventricular fibrillation in the MI group and MI-SS group respectively. The incidence of ventricular tachycardia (VT)/VF within 30-minute after ligation in the MI-SNS group was 80.0%, significant higher than that of the MI group (52.0%, P < 0.05). The incidence of VT/VF within 30-minute after ligation of the pSNS-MI group was 20.0%, significantly lower than that of the MI-SNS group (P < 0.05). 30 minutes after the ligation, the percentage of phosphorylated Cx43 of the pSNS-MI and MI-SNS groups were 71.2% +/- 7.0% and 73.4% +/- 6.7% respectively, both significantly higher than that of the MI group (46.7% +/- 6.3%) (both P < 0.05). The total contents of Cx43 of the MI and pSNS-MI groups were 1.29 +/- 0.14 and 1.25 +/- 0.13 respectively, both similar to that of the SO group [(1.30 +/- 0.10), both P > 0.05], while the total Cr43 content of the MI-SNS group was 0.73 +/- 0. 12, significantly lower than that of the SO group [(1.30 +/- 0.10), P < 0.05]. The Cx43 mRNA levels of the 3 experimental groups were all significantly lower than that of the SO group (all P < 0.05). Immunofluorescence analysis confirmed that ischemia and sympathetic nerve stimulation induced the changes of connexin43 distribution and sympathetic nerve stimulation preconditioning inhibited the changes of connexin43 distribution induced by ischemia. SNS promotes ventricular arrhythmias by promoting Cx43 degradation, and sympathetic nerve stimulation preconditioning inhibits ventricular arrhythmias by preventing Cx43 dephosphorylation.


[Extra- and paravasation of cytotoxic drugs. Pathomechanisms and current preventive measures].
Defined anticancer drugs are able to induce severe local damages in cases of accidental extravasation. The underlying pathomechanisms differ from each other, e.g. vincristine and conventional doxorubicin, when the corresponding intervention needs hyaluronidase and dexrazoxane, respectively. Whether an intensified diagnostic measure may help to assume extent and severity of local drug extravasation more accurately, needs further clinical investigation.


Influences on infant feeding decisions of first-time mothers in five European countries.
Infant feeding decisions made by new parents have significant health implications. The study aimed to investigate: influences on infant feeding decisions; characteristics of mothers reporting reliance on alternative information sources; associations between reliance on different sources and intentions to exclusively breastfeed and introduce complementary foods later; and subsequent breastfeeding and weaning behaviours. First-time mothers in five European countries (England, Finland, Germany, Hungary, Spain) completed questionnaires about the importance of 17 influences on infant feeding choices at birth and 8 months later, during 2007-2008. Use of individual sources and reliance on four categories (family and friends, health professionals, written materials, audio-visual media) were compared between countries. Associations between information sources used and mother characteristics, feeding intentions and behaviours were investigated using appropriate statistical tests. In all, 2071 first-time mothers provided baseline data; 78% at 8 months. Variation exists between countries in the influence of different sources on feeding decisions of first-time mothers. Across all countries, the most important influences at both time points were books, partner and antenatal midwife. Mothers in higher income quintiles and remaining at school beyond age 16 years reported greater reliance on written sources (P<0.0005). Mothers relying most on written sources reported longer exclusive breastfeeding (P=0.002), and a tendency to introduce foods other than milk later (P=0.079) than mothers relying most on personal or professional contacts. Further research is required about which dissemination strategies are most effective at improving infant feeding behaviours in varied cultural settings, and for different socio-economic groups.


Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors.
An in vitro culture and assay system was used to determine whether cytotoxic lymphocytes are generated in humans after rickettsial infection. Peripheral blood mononuclear cells (PBMC) were obtained from six individuals with serologic evidence of prior infection with typhus group rickettsiae and from six nonimmune individuals. After PBMC from immune individuals were stimulated in vitro for 7 days with rickettsial antigen, they were capable of lysing typhus group rickettsia-infected, autologous phytohemagglutinin (PHA)-induced blasts, but not uninfected PHA-blasts. No cytotoxic effector cells were generated when either PBMC from immune individuals were placed in culture for 7 days without antigenic stimulation, or when PBMC from nonimmune individuals were stimulated in vitro with antigen for 7 days. Freshly isolated PBMC from immune donors were also unable to lyse typhus group rickettsia-infected autologous PHA-blasts or an autologous rickettsia-infected lymphoblastoid cell line (LCL). Neither supernatants from antigen-stimulated cultures of PBMC from immune donors nor recombinant human interferon-gamma were capable of significantly lysing typhus group rickettsia-infected PHA blasts by this assay. Populations of cytotoxic effector cells depleted of OKT3, OKT4, or OKT8-positive cells by treatment with the respective monoclonal antibodies and complement were assayed for their cytotoxic capacity. The results suggest that the cytotoxic effector cell population is predominantly OKT3 and OKT8-positive, but OKT4-negative. Positive selection with the use of a fluorescence-activated cell sorter also suggested that most of the cytotoxic effector cells are OKT8-positive. PBMC from immune donors after in vitro stimulation with rickettsial antigen were capable of significantly lysing infected autologous LCL or infected HLA-mismatched LCL as compared with the respective uninfected controls. In addition, PBMC from either immune donors or nonimmune donors after stimulation in vitro for 7 days with media containing purified lymphokines were capable of significantly lysing autologous infected LCL as compared with the uninfected autologous control. We conclude that lysis of cells infected with typhus group rickettsiae is mediated by a lymphokine-activated killer.


Magnolol prevented brain injury through the modulation of Nrf2-dependent oxidative stress and apoptosis in PLP-induced mouse model of multiple sclerosis.
Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS). The aim of the current study was to investigate the effects of magnolol in an experimental autoimmune encephalomyelitis (EAE) model of MS in female mice. Magnolol (0.1, 1, and 10 mg/kg) was administered once daily for 21 days after immunization of mice. Magnolol post-immunization treatment significantly reversed clinical scoring, EAE-associated pain parameters, and motor dysfunction in a dose-dependent manner. Magnolol treatment significantly inhibited oxidative stress by reducing malondialdehyde (MDA), nitric oxide (NO) production, and myeloperoxidase (MPO) activity while enhancing the level of antioxidants such as reduced glutathione (GSH), glutathione-S-transferase (GST), catalase, and superoxide dismutase (SOD) in the brain and spinal cord. It reduced cytokine levels in the brain and spinal cord. It suppressed CD8+ T cells frequency in the spleen tissue. Magnolol remarkably reversed the EAE-associated histopathology of the brain and spinal cord tissue. Magnolol significantly intensifies the antioxidant defense system by enhancing the expression level of nuclear factor erythroid 2-related factor (Nrf2) while decreasing the expression of inducible nitric oxide synthase (iNOS) and cleaved-caspase-3 in the brain. Molecular docking results showed that magnolol possesses a better binding affinity for Nrf2, iNOS, and caspase-3 proteins. Taken together, the present study demonstrated that magnolol has significant neuroprotective properties in EAE via inhibition of oxidative stress.


Effect of neurotrophin-3 genetically modified olfactory ensheathing cells transplantation on spinal cord injury.
Transplantation of olfactory ensheathing cells (OECs) has emerged as a very promising therapy for spinal cord injury (SCI). Also, local delivery of NT-3 can counteract pathological events and induce a regenerative response after SCI. Supplement of exogenetic NT-3 might be a new approach to SCI repair. In this study, we examined the therapeutic effect of rat NT-3 gene-modified OECs transplantation on SCI. Rat NT-3 gene was transfected into OECs using a retroviral system. The engineered NT-3-OECs were tested for their ability to express and secrete biologically active NT-3 in vitro. Then NT-3-OECs were implanted into contused T9 spinal cord of the adult rats. Their ability of survival and NT-3 production was examined. The effect of axon regeneration was evaluated at the morphological level and promotion of locomotor functional recovery were assessed. The result showed that genetically modified OECs were capable of surviving and producing NT-3 in vivo to significantly improve the recovery after SCI.


Advances in adult pulmonary tuberculosis.
The immune response is able to contain but not eliminate Mycobacterium tuberculosis. Antigens that are specific to M. tuberculosis can identify latent infection accurately even after BCG vaccination. Genes that are required for persistence of the organism have been identified and new drugs are being developed to disrupt their function. This offers the hope of shortened courses of therapy. New drugs are urgently needed for multidrug-resistant tuberculosis, particularly as some areas are reporting a high prevalence of fluoroquinolone resistance. The sputum smear is the standard rapid diagnostic test for pulmonary tuberculosis, but is frequently negative in HIV infection. The yield of smear can be increased by sputum induction and by concentration. Innovative methods of providing directly observed therapy have been devised. Preventive therapy is effective in HIV infection and probably improves survival. However, the duration of benefit of preventive therapy seems to be relatively short-lived. Effective long-term reduction of tuberculosis risk in HIV-infected patients can be achieved with highly active antiretroviral therapy.


Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication.
Enterovirus 71 is an enterovirus of the family Picornaviridae. The 2C protein of poliovirus, a relative of enterovirus 71, is essential for viral replication. The poliovirus 2C protein is associated with host membrane vesicles, which form viral replication complexes where viral RNA synthesis takes place. We have now identified a host-encoded 2C binding protein called reticulon 3, which we found to be associated with the replication complex through direct interaction with the enterovirus 71-encoded 2C protein. We observed that the N terminus of the 2C protein, which has both RNA- and membrane-binding activity, interacted with reticulon 3. This region of interaction was mapped to its reticulon homology domain, whereas that of 2C was encoded by the 25th amino acid, isoleucine. Reticulon 3 could also interact with the 2C proteins encoded by other enteroviruses, such as poliovirus and coxsackievirus A16, implying that it is a common factor for such viral replication. Reduced production of reticulon 3 by RNA interference markedly reduced the synthesis of enterovirus 71-encoded viral proteins and replicative double-stranded RNA, reducing plaque formation and apoptosis. Furthermore, reintroduction of nondegradable reticulon 3 into these knockdown cells rescued enterovirus 71 infectivity, and viral protein and double-stranded RNA synthesis. Thus, reticulon 3 is an important component of enterovirus 71 replication, through its potential role in modulation of the sequential interactions between enterovirus 71 viral RNA and the replication complex.


Determining the Nutrient Content of Hydroponically-Cultivated Microgreens with Immersible Silicon Photonic Sensors: A Preliminary Feasibility Study.
Microgreens have gained attention for their exceptional culinary characteristics and high nutritional value. The present study focused on a novel approach for investigating the easy extraction of plant samples and the utilization of immersible silicon photonic sensors to determine, on the spot, the nutrient content of microgreens and their optimum time of harvest. For the first time, it was examined how these novel sensors can capture time-shifting spectra caused by the molecules' dynamic adhesion onto the sensor surface. The experiment involved four types of microgreens (three types of basil and broccoli) grown in a do-it-yourself hydroponic installation. The sensors successfully distinguished between different plant types, showcasing their discriminative capabilities. To determine the optimum harvest time, this study compared the sensor data with results obtained through standard analytical methods. Specifically, the total phenolic content and antioxidant activity of two basil varieties were juxtaposed with the sensor data, and this study concluded that the ideal harvest time for basil microgreens was 14 days after planting. This finding highlights the potential of the immersible silicon photonic sensors for potentially replacing time-consuming analytical techniques. By concentrating on obtaining plant extracts, capturing time-shifting spectra, and assessing sensor reusability, this research paves the way for future advancements in urban farming.


Distribution of eukaryotic serine racemases in the bacterial domain and characterization of a representative protein in Roseobacter litoralis Och 149.
Two distinct bacterial and eukaryotic serine racemases (SRs) have been identified based on phylogenetic and biochemical characteristics. Although some reports have suggested that marine heterotrophic bacteria have the potential to produce d-serine, the gene encoding bacterial SRs is not found in those bacterial genomes. In this study, using in-depth genomic analysis, we found that eukaryotic SR homologues were distributed widely in various bacterial genomes. Additionally, we selected a eukaryotic SR homologue from a marine heterotrophic bacterium, Roseobacter litoralis Och 149 (RiSR), and constructed an RiSR gene expression system in Escherichia coli for studying the properties of the enzyme. Among the tested amino acids, the recombinant RiSR exhibited both racemization and dehydration activities only towards serine, similar to many eukaryotic SRs. Mg2+ and MgATP enhanced both activities of RiSR, whereas EDTA abolished these enzymatic activities. The enzymatic properties and domain structure of RiSR were similar to those of eukaryotic SRs, particularly mammalian SRs. However, RiSR showed lower catalytic efficiency for L-serine dehydration (kcat/Km=0.094 min(-1) mM(-1)) than those of eukaryotic SRs reported to date (kcat/Km=0.6-21 min(-1) mM(-1)). In contrast, the catalytic efficiency for L-serine racemization of RiSR (kcat/Km=3.14 min(-1) mM(-1)) was 34-fold higher than that of l-serine dehydration. These data suggested that RiSR primarily catalysed serine racemization rather than dehydration.


Evaluation of seroepidemiological toxoplasmosis in HIV/AIDS patients in the south of Brazil.
Toxoplasmosis is considered one of the opportunistic infections for individuals with the Acquired Immunodeficiency Syndrome (AIDS), and is also a major cause of morbidity and mortality. The aim of this study was to evaluate the prevalence of neurotoxoplasmosis, ocular toxoplasmosis and antibodies for Toxoplasma gondii in HIV-positive patients attending the SAE (Specialized Assistance Service for HIV/AIDS), as well as to associate their serological profile with epidemiological and clinical data. A total of 250 patients participated in the study from December, 2009 to November, 2010. Serological analysis was performed using the indirect immunofluorescent technique; epidemiological data were gathered by a questionnaire, and clinical history was based on the analysis of medical charts. Prevalence of seropositivity was 80%, with history of neurotoxoplasmosis in 4.8% and of ocular toxoplasmosis in 1.6% of the patients. The Highly Active Antiretroviral Treatment (HAART) was not used by 32% of the patients, 18.4% of the patients had CD4+ T- lymphocyte count less than 200 cells/mm³ and 96.8% of them were not aware of the modes of disease transmission. These findings led us to conclude that the study population is at high risk of clinical toxoplasmosis, because of both reactivation of infection in the seropositive patients who do not make a regular use of HAART, and primo-infection in seronegative patients worsened by an unawareness of the modes of infection reported in this study.


Clinical Utility of Potassium-Sparing Diuretics to Maintain Normal Serum Potassium in Peritoneal Dialysis Patients.
♦ BACKGROUND: Hypokalemia is a vexing problem in end-stage renal disease patients on peritoneal dialysis (PD), and oral potassium supplements (OPS) have limited palatability. Potassium-sparing diuretics (KSD) (spironolactone, amiloride) may be effective in these patients. ♦ METHODS: We performed a cross-sectional review of 75 current or past (vintage > 6 months) PD patients with regard to serum potassium (K+), OPS, and KSD utilization. We reviewed charts for multiple clinical and laboratory variables, including dialysis adequacy, residual renal function, nutritional status and co-existing medical therapy. ♦ RESULTS: The cohort was middle-aged with a mean age of 49.2 years (standard deviation [SD] = 14.7) and overweight with a body mass index of 29.5 (6.7) kg/m2. Of all the participants, 57.3% were female, 73.3% African-American, and 48% diabetic with an overall PD vintage of 28.2 (24.3) months at the time of enrollment. Weekly Kt/V was 2.12 (0.43), creatinine clearance was 73.5 (33.6) L/week/1.73 m2 with total daily exchange volume of 10.8 (2.7) L. Residual urine output (RUO) measured at 440 (494) mL (anuric 30.6%). Three-month averaged serum K+ measured at 4 (0.5) mmol/L with 36% of the participants receiving K+ supplements (median: 20 [0;20] mmol/day) and 41.3% KSD (spironolactone dose: 25 - 200 mg/day; amiloride dose: 5 - 10 mg/day). Serum K+ correlated positively with weekly Kt/V (r = 0.239; p = 0.039), PD vintage (r = 0.272; p = 0.018) but not with PD modality, daily exchange volume, RUO, or KSD use. However, KSD use was associated with decreased use of OPS (r = -0.646; p < 0.0001). ♦ CONCLUSIONS: Potassium-sparing diuretics were effective in this cohort of PD patients and decreased the need for OPS utilization.


Communication in Health Professions: A European consensus on inter- and multi-professional learning objectives in German.
Communication is object of increasing attention in the health professions. Teaching communication competencies should already begin in undergraduate education or pre-registration training. The aim of this project was to translate the Health Professions Core Communication Curriculum (HPCCC), an English catalogue of learning objectives, into German to make its content widely accessible in the German-speaking countries. This catalogue lists 61 educational objectives and was agreed on by 121 international communication experts. A European reference framework for inter- and multi-professional curriculum development for communication in the health professions in German-speaking countries should be provided. The German version of the HPCCC was drafted by six academics and went through multiple revisions until consensus was reached. The learning objectives were paired with appropriate teaching and assessment tools drawn from the database of the teaching Committee of the European Association for Communication Health Care (tEACH). The HPCCC learning objectives are now available in German and can be applied for curriculum planning and development in the different German-speaking health professions, the educational objectives can also be used for inter-professional purposes. Examples for teaching methods and assessment tools are given for using and implementing the objectives. The German version of the HPCCC with learning objectives for communication in health professions can contribute significantly to inter- and multi-professional curriculum development in the health care professions in the German-speaking countries. Examples for teaching methods and assessment tools from the materials compiled by tEACH supplement the curricular content and provide suggestions for practical implementation of the learning objectives in teaching and assessment. The relevance of the German HPCCC to the processes of curriculum development for the various health professions and inter-professional approaches should be the subject of further evaluation.


Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model.
There is accumulating evidence that functional alteration(s) of the bone marrow (BM) microenvironment contribute to the development of some myeloid disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In addition to a cell-intrinsic role of WNT activation in leukemia stem cells, WNT activation in the BM niche is also thought to contribute to the pathogenesis of MDS and AML. We previously showed that the Apc-haploinsufficient mice (Apcdel/+ ) model MDS induced by an aberrant BM microenvironment. We sought to determine whether Apc, a multifunctional protein and key negative regulator of the canonical β-catenin (Ctnnb1)/WNT-signaling pathway, mediates this disease through modulating WNT signaling, and whether inhibition of WNT signaling prevents the development of MDS in Apcdel/+ mice. Here, we demonstrate that loss of 1 copy of Ctnnb1 is sufficient to prevent the development of MDS in Apcdel/+ mice and that altered canonical WNT signaling in the microenvironment is responsible for the disease. Furthermore, the US Food and Drug Administration (FDA)-approved drug pyrvinium delays and/or inhibits disease in Apcdel/+ mice, even when it is administered after the presentation of anemia. Other groups have observed increased nuclear CTNNB1 in stromal cells from a high frequency of MDS/AML patients, a finding that together with our results highlights a potential new strategy for treating some myeloid disorders.


Experimental and Theoretical Study of the Time-Effect-Based Instability Characteristics of the Gas Drainage Borehole Sealing Section in a Soft Coal Seam.
The instability and sealing difficulty confronted by gas drainage boreholes in a soft coal seam weakens the drainage efficiency. To address this problem, the instability characteristics of the sealing section of boreholes are investigated. On the basis of the findings of the mechanical properties of the borehole around the sealing section and in view of the physical and mechanical properties of the soft coal seam, a theoretical analysis was performed. A system consisting of the YYL200 electronic persistent creep test system and the DNS-200 electronic universal tester was used to observe the borehole under different filling conditions. The samples were subjected to a graded loading test, and the Kelvin-Voigt model was selected for parameter inversion and law analysis of the test results. The results show that the collapse of the broken area and the stress concentration and instability of the sealing section after the sealing of the soft coal seam are directly attributable to the instability of the soft coal seam and the sealing difficulty. The mechanical properties of the grouting sealing material are directly related to the loading of the hole-containing sample and dead load displacement. The maximal overall displacement of the sample in group B is close to 1.4 mm. The instantaneous deformation capacity and deformation space reflected by the generalized Kelvin model parameters E 1, E 2, and η are closely related to the mechanical properties of the filling material. The highly stress- and deformation-resistant sealing material can ensure the relative time-effect-based stability within the stress concentration area of the sealing section.


[Henry Foley and Lyautey, and the medical activities in Morocco during the initial phase of the protectorate].
In June 1912, Lyautey was called to Marocco as "Résident général". His first decision, before his arrival in Marocco, at Fès, was to require an important additional quota of physicians. He received each of them, in order to verify their moral and professional capacity to assume their charge. Lyautey knew that he must contribute to the modernization and development of this very old, fascinating and glorious nation, which was no longer suited to the modern time. Among the necessary and urgent actions, the medical one seemed to be the more important. Lyautey had found with Henry Foley, all the essential qualities to manage the medical assistance service for marocan populations. But Foley refused to be with Lyautey in Marocco, because he was working in the saharian city of Beni-Ounif, on different subjects as exanthematous typhus, recurrent fever ... He had discovered in 1908, the role of lice in the transmission of recurrent fever in Beni-Ounif, one year before the discovery of this role in exanthematic typhus by Charles Nicolle. But the relation proved by not yet published correspondence, was not broken off between Foley and Lyautey.


Evidence for robots.
Robots have been successfully used in commercial industry and have enabled humans to perform tasks which are repetitive, dangerous and requiring extreme force. Their role has evolved and now includes many aspects of surgery to improve safety and precision. Orthopaedic surgery is largely performed on bones which are rigid immobile structures which can easily be performed by robots with great precision. Robots have been designed for use in orthopaedic surgery including joint arthroplasty and spine surgery. Experimental studies have been published evaluating the role of robots in arthroscopy and trauma surgery. In this article, we will review the incorporation of robots in orthopaedic surgery looking into the evidence in their use.


A gigantic marine ostracod (Crustacea: Myodocopa) trapped in mid-Cretaceous Burmese amber.
The mid-Cretaceous Burmese amber (~99 Ma, Myanmar), widely known for exquisite preservation of theropods, also yields microfossils, which can provide important contextual information on paleoenvironment and amber formation. We report the first Cretaceous ostracod in amber-the gigantic (12.9 mm) right valve of an exclusively marine group (Myodocopa: Myodocopida) preserved in Burmese amber. Ostracods are usually small (0.5-2 mm), with well-calcified carapaces that provide an excellent fossil record extending to at least the Ordovician (~485 million years ago), but they are rarely encountered in amber. The new specimen effectively doubles the age of the ostracod amber record, offering the first representative of the Myodocopa, a weakly calcified group with a poor fossil record. Its carapace morphology is atypical and likely plesiomorphic. The preserved valve appears to be either a moulted exuvium or a dead and disarticulated specimen, and subsequent resin flows contain forest floor inclusions with terrestrial arthropods, i.e., fragmentary remains of spiders, and insect frass. These features resolve an enigmatic taphonomic pathway, and support a marginal marine setting for resin production.


Nasal reconstruction: our experience.
The nose is a critically important aesthetic and functional portion of the face. We can explore nasal defects following trauma or tumor resections. Reconstructive techniques based on primary closure, skin graft, local flap, regional flap and microvascular free tissue transfer provides an algorithmic framework applicable to any reconstructive problem. From 2010 to 2016, 33 patients were treated with nasal reconstruction. Malignant tumor resection was the main cause of nasal defect. The most common tumor resected was BCC (basal cell carcinoma) followed by SCC (squamous cell carcinoma). Recurrence of malignant tumor were also treated. As described in the literature, we used the most common reconstructive techniques to handle post-resection defects. Most of the defects involved the dorsum and the ala of the nose, only rarely had the skeleton been affected by the resection. When the cartilage had been sacrificed, a graft from the septum or from the ear flap was harvested. All patients resulted in optimal reconstruction. In any case, a second surgery was needed. All the surgical procedures were performed in one single stage except for the paramedian forehead flap that required a second stage for division and inset of the flap. All donor sites did not show functional and aesthetic damage. All patients resulted in a morpho-functional restoration of the area affected by the resection with a high success rate. Following the algorithm when restoring the anatomical subunit is the base purpose has determined satisfactory results.


[Dynamic electrocardiography evaluation of the effectiveness of prajmalium bitartrate, disopyramide and procainamide in patients with stabilized ventricular extrasystole].
20 patients with chronic premature ventricular contractions (P.V.Cs) underwent several Holter ECG monitorings to assess clinical effectiveness of three antiarrhythmic drugs: Prajmalium Bitartrate (P.B.) 80 mg/daily, Disopyramide (D.) 600 mg/daily and Procainamide (P.) 2400 mg/daily, to assess the most effective antiarrhythmic medication in every patient. Clinical effectiveness was considered as 80% reduction of P.V.Cs or 50% reduction with suppression of all complex ventricular ectopy (repetitive, polymorph, bigeminy). These results were observed respectively, for 80% reduction, in 5/20 patients for P.B., in 9/20 for D., and in 3/19 for P; and for 50% reduction in 11/20 for P.B., in 18/20 for D., and in 9/19 for P. Comparison in the same patient, using Holter ECG monitoring with a computer assisted analysis, of the effects of different antiarrhythmic medications, is a rational procedure to assess clinical efficacy of new antiarrhythmic drugs and to choose the most effective in each case.


[Sequential analysis of effectiveness of diazepam, a tranquilizer, on stress in swine (author's transl)].
To study the effectiveness of diazepam, a tranquilizer, in alleviating the problems resulting from the mixing and moving of weaned piglets from one piggery to another, two procedures, one of short-duration transport and the other of long-duration transport, are used in a double blind clinical trial. Both followed mixing the pigs, but before they entered the new piggery. Results from both groups of pigs (treated and control) are sequentially analyzed. Measurements used are growth rate and feed conversion curves during the first 18-20 days of the prefattening period. Diazepam (I mg/kg IM) reduces feed conversion when used to alleviate the effects of the long journey, but increases feed conversion after the short journey when compared to controls injected with a placebo. Worsening effects seem related to increased aggressiveness in animals treated and transported. These results indicate that a better understanding of the action mechanisms of psychotropic drugs is necessary, and they should be used with caution in husbandry.


[Reconstruction and application of genome-scale metabolic network model].
The exploitation of microbial manufacture process (MMP) in industrial biotechnology requires a comprehensive understanding and an efficient modification of microorganism physiology. The availability of genome sequences and accumulation of -omics data allow us to understand of microbial physiology at the systems level, and genome-scale metabolic model (GSMM) represents a valuable framework for integrative analysis of metabolism of microorganisms. Genome scale metabolic models are reconstructed based on a combination of genome sequence and the more detailed biochemical knowledge, and these reconstructed models can be used for analyzing and simulating the operation of metabolism in response to different perturbations. Here we describe the reconstruction protocols for GSMM in further detail and provide the perspective of GSMM.


Pollen dispersal in spatially aggregated populations.
We perform a theoretical study of effective pollen dispersal within plant populations exhibiting intraspecific spatial aggregation. We simulate nonuniform distributions of individuals by means of a Poisson cluster process and use an individual-based spatially explicit model of pollen dispersal to assess the effects of different aggregation patterns on the effective pollen pool size (N(ep)) and the axial variance of pollen dispersal (sigma (p)). Results show clear interactions between clumping and both N(ep) and sigma (p), whose precise form and intensity depend on the relative spatial scale of aggregation to pollen dispersal range. If clump size is small relative to dispersal range, clumping results in lower N(ep) and sigma (p) than in randomly distributed populations. Interestingly, by contrast, aggregation may actually enlarge N(ep) and has minimum impact on sigma (p) if clump size is near or above the scale of dispersal. High intraclump to global density ratios enhance the sensitivity of both N(ep) and sigma (p) to clumping, while leptokurtic pollen dispersal generates sharper reductions of both N(ep) and sigma (p) for small clump sizes and stronger increments of N(ep) for larger clump sizes. Overall, our results indicate that isolation-by-distance models in plants should not ignore the effects of intraspecific spatial aggregation on effective dispersal.


Geometric classification of scalp hair for valid drug testing, 6 more reliable than 8 hair curl groups.
Curly hair is reported to contain higher lipid content than straight hair, which may influence incorporation of lipid soluble drugs. The use of race to describe hair curl variation (Asian, Caucasian and African) is unscientific yet common in medical literature (including reports of drug levels in hair). This study investigated the reliability of a geometric classification of hair (based on 3 measurements: the curve diameter, curl index and number of waves). After ethical approval and informed consent, proximal virgin (6cm) hair sampled from the vertex of scalp in 48 healthy volunteers were evaluated. Three raters each scored hairs from 48 volunteers at two occasions each for the 8 and 6-group classifications. One rater applied the 6-group classification to 80 additional volunteers in order to further confirm the reliability of this system. The Kappa statistic was used to assess intra and inter rater agreement. Each rater classified 480 hairs on each occasion. No rater classified any volunteer's 10 hairs into the same group; the most frequently occurring group was used for analysis. The inter-rater agreement was poor for the 8-groups (k = 0.418) but improved for the 6-groups (k = 0.671). The intra-rater agreement also improved (k = 0.444 to 0.648 versus 0.599 to 0.836) for 6-groups; that for the one evaluator for all volunteers was good (k = 0.754). Although small, this is the first study to test the reliability of a geometric classification. The 6-group method is more reliable. However, a digital classification system is likely to reduce operator error. A reliable objective classification of human hair curl is long overdue, particularly with the increasing use of hair as a testing substrate for treatment compliance in Medicine.


Hydroxyapatite ceramics for continuous delivery of heparin.
The goal of this investigation is to develop a ceramic system for delivering therapeutic amounts of heparin continuously from subcutaneous implants. Hydroxyapatite (HA) ceramic reservoirs were used for the continuous delivery of heparin in both in vitro and in vivo environments. Each reservoir was loaded with heparin. The open end was then sealed with a silastic medical adhesive and sterilized by ethylene oxide. A total of 15 capsules were used for conducting the in vitro experiments. Each capsule (control, sham, 1400, 2800, 4200 units heparin) was suspended in a vial containing 100 ml phosphate buffered saline (pH 7.4) at 37 degrees C. A one ml aliquot was withdrawn from each serum bottle at fixed intervals for three weeks, and assayed for heparin by the Sigma Heparin Clotting Assay. The largest amount of heparin was released from the capsule containing 4200 units of heparin and the smallest amount was released from the capsule containing 1400 units of heparin. Thirty Holtzman rats (140 +/- 15 g.) were used in the in vivo experiment. The rats were equally distributed into five groups (control, sham, 1400, 2800, and 4200 units of heparin). Animals in four of the five groups were implanted with HA capsules containing various amounts of heparin. Capillary tube clotting times were observed at regular intervals. Six days following implantation, the clotting times of the blood obtained from rats implanted with heparin-containing capsules was significantly higher (6.3 +/- 0.07 minutes) than the clotting times of blood obtained from shams and controls (4.3 +/- 0.03 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)


Cancer cachexia syndrome: pathogenesis, diagnosis, and new therapeutic options.
Cancer anorexia-cachexia syndrome (CACS) is the most frequent paraneoplastic syndrome occurring in half of all oncologic patients and is considered as a poor prognosticator. Patients usually present with weight loss, lipolysis, muscle wasting, anorexia, chronic nausea, inflammation, and asthenia. The etiopathogenesis of CACS is still poorly understood, although several factors and biological pathways are known to be involved. Because of the complexity of this multifactorial condition, a single agent therapy may not be sufficient. Indeed, there is a tendency toward an integrated multiple approach including nonpharmacological and pharmacological treatments. However, despite encouraging preliminary results, currently there is not enough evidence to support a change in clinical practice. This review provides a brief and practical summary of the diagnosis, pathogenesis, and treatment of CACS. Future perspectives will also be discussed.


The neural cell adhesion molecule-derived peptide, FGL, attenuates lipopolysaccharide-induced changes in glia in a CD200-dependent manner.
Fibroblast growth loop (FGL) is a neural cell adhesion molecule (NCAM)-mimetic peptide that mimics the interaction of NCAM with fibroblast growth factor receptor (FGFR). FGL increases neurite outgrowth and promotes neuronal survival in vitro, and it has also been shown to have neuroprotective effects in vivo. More recent evidence has indicated that FGL has anti-inflammatory effects, decreasing age-related changes in microglial activation and production of inflammatory cytokines. These changes have been associated with an FGL-induced increase in expression of the glycoprotein, CD200, which interacts with its receptor to help maintain microglia in a quiescent state. However whether the FGL-induced anti-inflammatory effects are CD200-dependent has not been examined. The objective of this study was to address this question. Mixed glia were prepared from brain tissue of neonatal wildtype and CD200-deficient mice and preincubated with FGL prior to stimulation with lipopolysaccharide (LPS). Cells were assessed for mRNA expression of markers of microglial activation, CD11b, CD40 and intercellular adhesion molecule 1 (ICAM-1) and also the inflammatory cytokines, interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, while supernatant concentrations of these cytokine were also assessed. LPS significantly increased all these parameters and the effect was greater in cells prepared from CD200-deficient mice. Whereas FGL attenuated the LPS-induced changes in cells from wildtype mice, it did not do so in cells from CD200-deficient mice. We conclude that the FGL-induced changes in microglial activation are CD200-dependent and demonstrate that the interaction of astrocytes with microglia is critically important for modulating microglial activation.


Thoracoscopic management of oesophageal mucocele: Old complication, new approach.
Oesophageal mucocele is an uncommon complication of bipolar exclusion of oesophagus. Traditionally, this condition is managed through thoracotomy which is associated with significant morbidity. The present report outlines the thoracoscopic management of oesophageal mucocele following surgical exclusion for oesophageal perforation. Left thoracoscopic oesophagectomy for oesophageal mucocele described in this report has not been published earlier.


The human haptoglobin gene promoter: interleukin-6-responsive elements interact with a DNA-binding protein induced by interleukin-6.
Transcription of the human haptoglobin (Hp) gene is induced by interleukin-6 (IL-6) in the human hepatoma cell line Hep3B. Cis-acting elements responsible for this response are localized within the first 186 bp of the 5'-flanking region. Site-specific mutants of the Hp promoter fused to the chloramphenicol acetyl transferase (CAT) gene were analysed by transient transfection into uninduced and IL-6-treated Hep3B cells. We identified three regions, A, B and C, defined by mutation, which are important for the IL-6 response. Band shift experiments using nuclear extracts from untreated or IL-6-treated cells revealed the presence of IL-6-inducible DNA binding activities when DNA fragments containing the A or the C sequences were used. Competition experiments showed that both sequences bind to the same nuclear factors. Polymers of oligonucleotides containing either the A or the C regions confer IL-6 responsiveness to a truncated SV40 promoter. The B region forms several complexes with specific DNA-binding proteins different from those which bind to the A and C region. The B region complexes are identical in nuclear extracts from IL-6-treated and untreated cells. While important for IL-6 induction in the context of the haptoglobin promoter, the B site does not confer IL-6 inducibility to the SV40 promoter. Our results indicate that the IL-6 response of the haptoglobin promoter is dependent on the presence of multiple, partly redundant, cis-acting elements.


A Crosslinked Polytetrahydrofuran-Borate-Based Polymer Electrolyte Enabling Wide-Working-Temperature-Range Rechargeable Magnesium Batteries.
A polymer-based magnesium (Mg) electrolyte is vital for boosting the development of high-safety and flexible Mg batteries by virtue of its enormous advantages, such as significantly improved safety, potentially high energy density, ease of fabrication, and structural flexibility. Herein, a novel polytetrahydrofuran-borate-based gel polymer electrolyte coupling with glass fiber is synthesized via an in situ crosslinking reaction of magnesium borohydride [Mg(BH4 )2 ] and hydroxyl-terminated polytetrahydrofuran. This gel polymer electrolyte exhibits reversible Mg plating/stripping performance, high Mg-ion conductivity, and remarkable Mg-ion transfer number. The Mo6 S8 /Mg batteries assembled with this gel polymer electrolyte not only work well at wide temperature range (-20 to 60 °C) but also display unprecedented improvements in safety issues without suffering from internal short-circuit failure even after a cutting test. This in situ crosslinking approach toward exploiting the Mg-polymer electrolyte provides a promising strategy for achieving large-scale application of Mg-metal batteries.


Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate transitions.
Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The mechanisms that maintain pluripotency, or that cause its destabilization to initiate development, are complex and incompletely understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to input signals. Our strategy used random asynchronous Boolean simulations (R-ABS) to simulate single-cell fate transitions and strongly connected components (SCCs) strategy to represent population heterogeneity. This framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) and used to simulate cellular responses to combinations of five signaling pathways. Our simulations predicted experimentally verified cell population compositions and input signal combinations controlling specific cell fate transitions. Extending the model to PSC differentiation, we predicted a combination of signaling activators and inhibitors that efficiently and robustly generated a Cdx2+Oct4- cells from naïve mESCs. Overall, this platform provides new strategies to simulate cell fate transitions and the heterogeneity that typically occurs during development and differentiation.


Views of healthcare professionals on recruiting to a psychosocial randomised controlled trial: a qualitative study.
Randomised controlled trials, and in particular those of psychosocial interventions, often fail to recruit to target, resulting in underpowered trials with poor generalisability of findings. The objectives of this study were to explore the views of healthcare professionals on recruiting to psychosocial research studies, and to explore their views on factors that may hinder or facilitate recruitment. We conducted 14 semi-structured interviews, with healthcare professionals who had been involved in recruitment into a randomised controlled trial of a talking therapy for depression in patients with advanced cancer. Interviews were transcribed and analysed using thematic analysis. Five primary themes were identified, comprised of 11 subthemes. Attitudes towards research were largely positive. Health care professionals identified lack of time and narrow screening criteria as barriers to recruitment, and also noted the tendency to withhold participants from research for reasons other than eligibility (e.g., gatekeeping). The engagement of the study team with the clinical recruitment site, and the frequent presence of a researcher in clinics, were noted as facilitating recruitment. Healthcare professionals involved in recruiting to trials of psychosocial interventions hold generally positive views of psychosocial research. However, they report that constraints including space and time limit their ability to recruit, and express anxieties about approaching patients for trial recruitment in the palliative phase of their illness. The findings from this study can inform how best to design trials, and in particular trials of psychosocial interventions, and train health care professionals for the study, to maximise recruitment.


An efficient and numerically stable procedure for generating sextic force fields in normal mode coordinates.
In this paper, we outline a general, scalable, and black-box approach for calculating high-order strongly coupled force fields in rectilinear normal mode coordinates, based upon constructing low order expansions in curvilinear coordinates with naturally limited mode-mode coupling, and then transforming between coordinate sets analytically. The optimal balance between accuracy and efficiency is achieved by transforming from 3 mode representation quartic force fields in curvilinear normal mode coordinates to 4 mode representation sextic force fields in rectilinear normal modes. Using this reduced mode-representation strategy introduces an error of only 1 cm(-1) in fundamental frequencies, on average, across a sizable test set of molecules. We demonstrate that if it is feasible to generate an initial semi-quartic force field in curvilinear normal mode coordinates from ab initio data, then the subsequent coordinate transformation procedure will be relatively fast with modest memory demands. This procedure facilitates solving the nuclear vibrational problem, as all required integrals can be evaluated analytically. Our coordinate transformation code is implemented within the extensible PyPES library program package, at http://sourceforge.net/projects/pypes-lib-ext/.


Consequences of herpes simplex virus in pregnancy and their prevention.
New findings reveal that first-time infection of the mother is the most important factor for the transmission of genital herpes from mother to fetus/newborn. Interventions based on these findings will lead to new management of the pregnant patient with genital herpes prior to pregnancy and measures to prevent the acquisition of herpes during pregnancy. Risk factors for the transmission of herpes from mother to newborn have been detailed. It is the pregnant woman who acquires genital herpes as a primary infection in the latter half of pregnancy, rather than prior to pregnancy, who is at greatest risk of transmitting this virus to her newborn. This is true for both herpes simplex virus type-1 and herpes simplex virus type-2. Additional risk factors for neonatal herpes simplex virus infection include the use of a fetal-scalp electrode and maternal age of less than 21 years. Risk factors for the transmission of herpes from mother to newborn are detailed. Antiviral suppressive therapy initiated in the late third trimester has been shown to decrease viral shedding and the need for cesarean section.


Emerging Hubs in Plant Light and Temperature Signaling.
Due to their nature as sessile organisms, plants must accurately sense their surroundings and then translate this information into efficient acclimation responses to maximize development. Light and temperature are two major stimuli that provide immediate cues regarding energy availability, daylength, proximity of other species and seasonal changes. Both cues are sensed by complex systems and the integration of these signals is of very high value to properly respond to environmental changes without being disguised by random changes. For instance a cold day has a different significance if it occurs during the illuminated phase of the day or during the night, or when days are shortening during the fall instead of a long-day in spring. Here, we summarize recent advances in the nature of signaling components that operate as connectors of light and temperature signaling, with emphasis on the emerging hubs. Despite the nature of the thermosensors is still in its infancy compared to an important body of knowledge about plant sensory photoreceptors, the interaction of both types of signaling will not only bring clues of how plants integrate environmental information, but also will help in leading research in the nature of the thermosensors themselves.


Tandem oxidation/rearrangement of beta-ketoesters to tartronic esters with molecular oxygen catalyzed by calcium iodide under visible light irradiation with fluorescent lamp.
It was found that beta-ketoesters were directly transformed to the corresponding alpha-hydroxymalonic esters, tartronic esters, with molecular oxygen catalyzed by calcium iodide under visible light irradiation from fluorescent lamp. This reaction includes tandem oxidation/rearrangement and has received much attention from the viewpoint of reduction of energy consumption, labor, and solvents.


Herbivore-induced plant volatiles as cues for habitat assessment by a foraging parasitoid.
1. Animals usually require information about the current state of their habitat to optimize their behaviour. For this, they can use a learning process through which their estimate is continually updated according to the cues they perceive. Identifying these cues is a long-standing but still inveterate challenge for ecologists. 2. The use of plant cues by aphid parasitoids for the assessment of habitat profitability and the adaptation of patch exploitation was studied. Grounding on predictions from optimal foraging theory, we tested whether parasitoids exploited host patches less intensively after visiting heavily infested plants than after visiting plants bearing fewer aphids. 3. As predicted, after visiting heavily infested plants parasitoids reduced their residence time and attacked fewer hosts in the next patch. This was the case regardless of whether the aphids were actually present on the first plant, indicating that the cue came from the plant. Moreover, the level of infestation of a plant at some distance from the first plant visited affected parasitoid patch exploitation on the second plant in a similar manner, indicating that the cue was volatile. 4. These results highlight a novel role of herbivore-induced volatiles in parasitoid foraging behaviour, different from the widely studied attraction at a distance.


Tsw - A case study on structure-function puzzles in plant NLRs with unusually large LRR domains.
Plant disease immunity heavily depends on the recognition of plant pathogens and the subsequent activation of downstream immune pathways. Nod-like receptors are often crucial in this process. Tsw, a Nod-like resistance gene from Capsicum chinense conferring resistance against Tomato spotted wilt virus (TSWV), belongs to the small group of Nod-like receptors with unusually large LRR domains. While typical protein domain dimensions rarely exceed 500 amino acids due to stability constraints, the LRR of these unusual NLRs range from 1,000 to 3,400 amino acids and contain over 30 LRR repeats. The presence of such a multitude of repeats in one protein is also difficult to explain considering protein functionality. Interactions between the LRR and the other NLR domains (CC, TIR, NBS) take place within the first 10 LRR repeats, leaving the function of largest part of the LRR structure unexplained. Herein we discuss the structural modeling limits and various aspects of the structure-function relation conundrums of large LRRs focusing on Tsw, and raise questions regarding its recognition of its effector NSs and the possible inhibition on other domains as seen in other NLRs.


IFN-gamma sensitizes MIN6N8 insulinoma cells to TNF-alpha-induced apoptosis by inhibiting NF-kappaB-mediated XIAP upregulation.
Although X-linked inhibitor of apoptosis protein (XIAP) is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic beta-cell apoptosis remains unclear. Here, we found that: (i) XIAP level was inversely correlated with tumor necrosis factor (TNF)-alpha-induced apoptosis in MIN6N8 insulinoma cells; (ii) adenoviral XIAP overexpression abrogated the TNF-alpha-induced apoptosis through inhibition of caspase activity; (iii) downregulation of XIAP by antisense oligonucleotide or Smac peptide sensitized MIN6N8 cells to TNF-alpha-induced apoptosis; (iv) XIAP expression was induced by TNF-alpha through a nuclear factor-kappaB (NF-kappaB)-dependent pathway, and interferon (IFN)-gamma prevented such an induction in a manner independent of NF-kappaB, which presents a potential mechanism underlying cytotoxic IFN-gamma/TNF-alpha synergism. Taken together, our results suggest that XIAP is an important modulator of TNF-alpha-induced apoptosis of MIN6N8 cells, and XIAP regulation in pancreatic beta-cells might play an important role in pancreatic beta-cell apoptosis and in the pathogenesis of type 1 diabetes.


Combination therapy of tanshinone IIA and puerarin for pulmonary fibrosis via targeting IL6-JAK2-STAT3/STAT1 signaling pathways.
Efficient therapy of idiopathic pulmonary fibrosis (IPF) is still a major challenge. The current studies with single-target drug therapy are the pessimistic approaches due to the complex characteristics of IPF. Here, a combination therapy of Tanshinone IIA and Puerarin for IPF was proposed to alleviate IPF due to their antiinflammatory and anti-fibrotic effects. In vivo, the combination therapy could significantly attenuate the area of ground glass opacification that was presented by 85% percentile density score of the micro-CT images when compared to single conditions. In addition, the combination therapy enormously improved the survival rate and alleviated pathological changes in bleomycin (BLM)-induced IPF mice. By using a wide spectrum of infiltration biomarkers in immunofluorescence assay in pathological sections, we demonstrate that fewer IL6 related macrophage infiltration and fibrosis area after this combination therapy, and further proved that IL6-JAK2-STAT3/STAT1 is the key mechanism of the combination therapy. In vitro, combination therapy markedly inhibited the fibroblasts activation and migration which was induced by TGF-β1 or/and IL6 through JAK2-STAT3/STAT1 signaling pathway. This study demonstrated that combination therapeutic effect of TanIIA and Pue on IPF may be related to the reduced inflammatory response targeting IL6, which could be an optimistic and effective approach for IPF.


Therapeutic potential of phytoconstituents of edible fruits in combating emerging viral infections.
Plant-derived bioactive molecules display potential antiviral activity against various viral targets including mode of viral entry and its replication in host cells. Considering the challenges and search for antiviral agents, this review provides substantiated data on chemical constituents of edible fruits with promising antiviral activity. The bioactive constituents like naringenin, mangiferin, α-mangostin, geraniin, punicalagin, and lectins of edible fruits exhibit antiviral effect by inhibiting viral replication against IFV, DENV, polio, CHIKV, Zika, HIV, HSV, HBV, HCV, and SARS-CoV. The significance of edible fruit phytochemicals to block the virulence of various deadly viruses through their inhibitory action against the entry and replication of viral genetic makeup and proteins are discussed. In view of the antiviral property of active constituents of edible fruits which can strengthen the immune system and reduce oxidative stress, they are suggested to be diet supplements to combat various viral diseases including COVID-19. PRACTICAL APPLICATIONS: Considering the increasing threat of COVID-19, it is suggested to examine the therapeutic efficacy of existing antiviral molecules of edible fruits which may provide prophylactic and adjuvant therapy with their potential antioxidant, anti-inflammatory, and immune-modulatory effects. Several active molecules like geraniin, naringenin, (2R,4R)-1,2,4-trihydroxyheptadec-16-one, betacyanins, mangiferin, punicalagin, isomangiferin, procyanidin B2, quercetin, marmelide, jacalin lectin, banana lectin, and α-mangostin isolated from various edible fruits have showed promising antiviral properties against different pathogenic viruses. Especially flavonoid compounds extracted from edible fruits possess potential antiviral activity against a wide array of viruses like HIV-1, HSV-1 and 2, HCV, INF, dengue, yellow fever, NSV, and Zika virus infection. Hence taking such fruits or edible fruits and their constituents/compounds as dietary supplements could deliver adequate plasma levels in the body to optimize the cell and tissue levels and could lead to possible benefits for the preventive measures for this pandemic COVID-19 situation.


The permeability of EUDRAGIT RL and HEMA-MMA microcapsules to glucose and inulin.
Measurement of the rate of glucose diffusion from EUDGRAGIT RL and HEMA-MMA microcapsules coupled with a Thiele modulus/Biot number analysis of the glucose utilization rate suggests that pancreatic islets and CHO (Chinese hamster ovary) cells (at moderate to high cell densities) should not be adversely affected by the diffusion restrictions associated with these capsule membranes. The mass transfer coefficients for glucose at 20 degrees C were of the same order of magnitude for both capsules, based on release measurements: approximately 5 x 10(-6) cm/s for EUDRAGIT RL and approximately 2 x 10(-6) for HEMA-MMA. Inulin release from EUDRAGIT RL was slower than for glucose (mass transfer coefficient 14 +/- 4 x 10(-8) cm/s). The Thiele moduli were much less than 1, either for a single islet at the center of a capsule or CHO cells uniformly distributed throughout a capsule at 10(-6) cells/ mL, so that diffusion restrictions within the cells in EUDRAGIT RL or 800 microm HEMA-MMA capsules should be negligible. The ratio of external to internal diffusion resistance (Biot number) was less than 1, so that at most, only a small diffusion effect on glucose utilization should be expected (i.e., the overall effectiveness factors were greater than 0.8). These calculations were consistent with experimental observation of encapsulated islet behavior but not fully with CHO cell behavior. Permeability restricted cell viability and growth is potentially a major limitation of encapsulated cells; further analysis is warranted.


Peptides and proteins as a continuing exciting source of inspiration for peptidomimetics.
Despite their enormous diversity in biological function and structure, peptides and proteins are endowed with properties that have induced and stimulated the development of peptidomimetics. Clearly, peptides can be considered as the "stem" of a phylogenetic molecular development tree from which branches of oligomeric peptidomimetics such as peptoids, peptidosulfonamides, urea peptidomimetics, as well as β-peptides have sprouted. It is still a challenge to efficiently synthesize these oligomeric species, and study their structural and biological properties. Combining peptides and peptidomimetics led to the emergence of peptide-peptidomimetic hybrids in which one or more (proteinogenic) amino acid residues have been replaced with these mimetic residues. In scan-like approaches, the influence of these replacements on biological activity can then be studied, to evaluate to what extent a peptide can be transformed into a peptidomimetic structure while maintaining, or even improving, its biological properties. A central issue, especially with the smaller peptides, is the lack of secondary structure. Important approaches to control secondary structure include the introduction of α,α-disubstituted amino acids, or (di)peptidomimetic structures such as the Freidinger lactam. Apart from intra-amino acid constraints, inter-amino acid constraints for formation of a diversity of cyclic peptides have shaped a thick branch. Apart from the classical disulfide bridges, the repertoire has been extended to include sulfide and triazole bridges as well as the single-, double- and even triple-bond replacements, accessible by the extremely versatile ring-closing alkene/alkyne metathesis approaches. The latter approach is now the method of choice for the secondary structure that presents the greatest challenge for structural stabilization: the α-helix.


Anthracycline-induced cardiotoxicity: comparison of recommendations for monitoring cardiac function during therapy in paediatric oncology trials.
The use of anthracyclines is limited by a dose-dependent cardiotoxicity (A-CT). The aim of this study was to gain insight in the currently available guidelines for monitoring cardiotoxicity during anthracycline therapy in children and in the monitoring recommendations currently used in European paediatric oncology trials. An extensive literature search to identify guidelines was performed and one guideline was identified. Twelve protocols including anthracycline therapy were evaluated. With regard to the minimally required diagnostic tests, parameters and definitions of A-CT most protocols roughly followed the guideline. However, both monitoring schedules and recommendations to prevent further cardiac damage in case A-CT was diagnosed varied widely between protocols and only a minority of the protocols followed the recommendations of the guideline. In conclusion, despite an existing guideline, there is a wide variation in the recommendations for monitoring cardiac function during anthracycline therapy in the currently used European paediatric oncology protocols. A possible explanation could be the lack of rigorous evidence on the most optimal way to monitor cardiac function in children treated with anthracyclines. There is a strong need for evidence from clinical research which can support recommendations for monitoring cardiac function during anthracycline therapy for childhood cancer. In the meantime, it is important to standardize the used cardiac monitoring schedules.


Computer evaluation of reference limits.
Reference limits are necessary for medical laboratory to provide objective information on health in concrete characteristics. With respect to changeability of some factors influencing upon homeostasis, reference limits must be determined and redetermined in each clinical laboratory with the high degree of the internal quality control system. The presented program computing reference limits and providing expert consultations facilitates solution.


Peptide nanotube aligning side chains onto one side.
A novel pseudo cyclic penta-β-peptide composed of a β-naphthylalanine, two β-alanines, and a sequence of ethylenediamine-succinic acid (CP5ES) is synthesized and investigated on peptide nanotube (PNT) formation. When the PNT is formed with the maximum number of intermolecular hydrogen bonds between the cyclic peptides, the sequence enables the alignment of the side chains, naphthyl groups, on one side of the PNT. Microscopic and spectroscopic observations of CP5ES crystals reveal that CP5ES forms rod- or needle-shaped molecular assemblies showing exciton coupling of the Cotton effect and predominant monomer emission, which are different from a reference cyclic tri-β-peptide composed of a β-naphthylalanine and two β-alanines. Insertion of a sequence of ethylenediamine-succinic acid into β-amino acids in the cyclic skeleton is therefore suggested to be effective to make the side chains aligning on one side of the PNT. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.


Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV.
To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV). All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software. Recurrence and metastasis were classified into early (< or =2 years) and late phase (>2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed. Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which "HBsAg, HBeAb, HbcAb" positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC) evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P<0.05). The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor's clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma de novo. HBV replication takes a great role in this process. From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.


Neural Basis of Video Gaming: A Systematic Review.
Background: Video gaming is an increasingly popular activity in contemporary society, especially among young people, and video games are increasing in popularity not only as a research tool but also as a field of study. Many studies have focused on the neural and behavioral effects of video games, providing a great deal of video game derived brain correlates in recent decades. There is a great amount of information, obtained through a myriad of methods, providing neural correlates of video games. Objectives: We aim to understand the relationship between the use of video games and their neural correlates, taking into account the whole variety of cognitive factors that they encompass. Methods: A systematic review was conducted using standardized search operators that included the presence of video games and neuro-imaging techniques or references to structural or functional brain changes. Separate categories were made for studies featuring Internet Gaming Disorder and studies focused on the violent content of video games. Results: A total of 116 articles were considered for the final selection. One hundred provided functional data and 22 measured structural brain changes. One-third of the studies covered video game addiction, and 14% focused on video game related violence. Conclusions: Despite the innate heterogeneity of the field of study, it has been possible to establish a series of links between the neural and cognitive aspects, particularly regarding attention, cognitive control, visuospatial skills, cognitive workload, and reward processing. However, many aspects could be improved. The lack of standardization in the different aspects of video game related research, such as the participants' characteristics, the features of each video game genre and the diverse study goals could contribute to discrepancies in many related studies.


Binding energy and geometry of e+ A (A=Li,Na) by the hyperspherical approach.
We calculate the binding energy and geometry of the weakly bound e(+)Li and e(+)Na systems within the framework of hyperspherical coordinates. The Schrodinger equation in hyperangular coordinates is solved at a series of fixed hyper-radii using B-splines and the resulting coupled hyper-radial equation is solved using the slow variable discretization method developed by Tolstikhin et al. [J. Phys. B 29, L389 (1996)]. Great efforts are made in optimizing the distribution of B-splines to overcome the slow convergence of the binding energy and geometrical quantities. This approach allows us to obtain the results with improved convergence that are in good agreement with the best values reported to date. In addition, an analysis of the structure of the two systems is also made and the e(+)Na system is seen to exhibit quantum halo features.


The Burch-Schneider cage for reconstruction after metastatic destruction of the acetabulum: outcome and complications.
The Burch-Schneider cage is an established implant in revision surgery after hip arthroplasty that is used for reconstructing osseous defects in the acetabulum. However, there are only a few reports about the use of cages in patients with metastatic destruction of the acetabulum. The aim of this retrospective study was to assess the outcome and complications of this procedure. The records of 15 patients with metastatic acetabular defects using the Burch-Schneider cage were examined pre- and postoperatively. X-rays were analyzed, clinical and functional outcome was assessed by the Harris hip score (HHS) and the visual analogue scale (VAS) for subjective pain perception. The follow-up of 14 months was due to the underlying disease. The overall revision rate was 26%. The HHS improved from 33 (range 25-39) to 69 (range 35-93). The VAS improved from 7.5 to 3.2. The life expectancy of patients with bone metastasis can be short and patients should be carefully selected for a surgical treatment. The implantation of a protrusio cage can improve the quality of life in these patients by increasing their mobility and reducing pain. The complication rate is comparable with the rates for other surgical methods for metastatic acetabular lesions. For surgeons who are familiar with this implant, it seems to be a good option in treating such cases.


Effects of AFO use on walking in boys with Duchenne muscular dystrophy: a pilot study.
Although bracing in the late ambulatory stage of Duchenne muscular dystrophy (DMD) has been described, the effects of ankle-foot orthoses (AFOs) in earlier stages have not been evaluated. The aim of this pilot study was to describe the effects of dynamic response AFO (DR-AFO) use in boys with DMD who are ambulatory. Using a crossover design, 3 boys were randomly assigned to either a 2-week DR-AFO or a placebo intervention. Phases were separated by a 1-week washout period. Primary outcomes were time to walk 10 m and a 6-Minute Walk Test. With DR-AFO use, declines in 10-m walk time (median decline = 0.8 s) and 6-Minute Walk Distance (median = 25.0 m) occurred. Parental report suggested that the use of DR-AFOs increased falls in 2 of 3 participants. This pilot study does not support the use of DR-AFOs by boys with DMD who are ambulatory.


A case of systemic amyloidosis associated with cyclic neutropenia.
Reactive AA amyloidosis is caused by the accumulation of the acute phase reactant, serum amyloid A (SAA), as a complication of chronic inflammatory conditions. Cyclic neutropenia is a rare hereditary disorder characterized by repeated episodes of neutropenia at regular intervals, with or without concurrent infection, and is known to be a rare cause of AA amyloidosis. Here, we report a case of a patient who developed systemic AA amyloidosis following a prolonged course of undiagnosed cyclic neutropenia. The patient had a history of recurrent infections since infancy and developed goiter, proteinuria, and azotemia at age 14 years. Her SAA level was markedly increased (601.8 μg/mL, normal range <8 μg/mL), and a thyroid and kidney biopsy revealed typical lesions of AA amyloidosis. Amyloid deposits were also detected in the myocardium, colon, and gallbladder. She had repeated episodes of neutropenia regularly at 3-week intervals and a pathogenic mutation in the ELA2 gene. After 10 months of treatment with recombinant human granulocyte colony-stimulating factor, her SAA level normalized (<2.5 μg/mL), but her renal function did not recover. This case clearly shows that cyclic neutropenia can be complicated by AA amyloidosis unless it is detected early and treated adequately.


Photochemical reaction containers as energy and electron-transfer agents.
Two deep cavity cavitands, octa acid and resorcinol-capped octa acid, have been established to be good triplet energy donors in the excited state and electron donors in the ground state to excited acceptors. This property endows them the capacity to be "active" reaction containers. The above recognition provides opportunities to investigate the excited state chemistry of host-encapsulated guests without the use of secondary triplet energy and electron donors.


The PET and LIM1-2 domains of testin contribute to intramolecular and homodimeric interactions.
The focal adhesion protein testin is a modular scaffold and tumour suppressor that consists of an N-terminal cysteine rich (CR) domain, a PET domain of unknown function and three C-terminal LIM domains. Testin has been proposed to have an open and a closed conformation based on the observation that its N-terminal half and C-terminal half directly interact. Here we extend the testin conformational model by demonstrating that testin can also form an antiparallel homodimer. In support of this extended model we determined that the testin region (amino acids 52-233) harbouring the PET domain interacts with the C-terminal LIM1-2 domains in vitro and in cells, and assign a critical role to tyrosine 288 in this interaction.


Limiting factors to oxygen transport on Mount Everest.
The effect of a sudden increase of the inspired oxygen tension on the maximal aerobic performance was studied on 23 subjects acclimated to high altitude (5,350-8,848 m above sea level) in the course of a 4-mo expedition to Mt. Everest. Inhalation of 100% O2 at 390 mmHg or a rapid descent (20 min) by helicopter to 2,850 m (Pio2 = 117 mmHg) raised maximal oxygen consumption (Vo2 max) from an average 0.7 of the control sea-level value, respectively, to 0.92 and 0.97. The failure of acclimated subjects to increase markedly or even to resume the preexisting sea-level Vo2mxa while breathing O2 in the presence of a 40% increase of blood Hb concentration and of a limited reduction of maximal cardiac output (Qmax), is attributed to changes in the peripheral circulation. These may consist of a) a hindrance of O2 diffusion due to erythrocytes packing secondary to increased hematocrit (Hct up to 70%); b) a bypass of arterial blood from the high-resistance working areas of the body aimed at reducing the load on the heart caused by increased blood viscosity. A 11.6% increase above normal controls of Hb concentration still found in 13 subjects 25 days after leaving altitude does not increase significantly maximum O2 consumption.


Exploring genetic susceptibility to cancer in diverse populations.
Incidence rates for many cancers differ markedly by race/ethnicity and furthering our understanding of the genetic and environmental causes of such disparities is a scientific and public health need. Genome-wide association studies (GWAS) are widely acknowledged to provide important information about the etiology of common cancers. To date, these studies have been primarily conducted in European-derived populations. There are important reasons for extending the reach of GWAS studies to other groups and for conducting multiethnic genetic studies involving multiple populations and admixed populations. These include a (1) need to discover the full scope of variants that affect risk of disease in all populations, (2) furthering the understanding of disease pathways, and (3) to assist in fine-mapping of genetic associations by exploiting the differences in linkage disequilibrium between populations to narrow the range of marker alleles demarking regions that contain a true biologically relevant variant. Challenges to multiethnic studies relating to study power, control for hidden population structure, imputation, and use of shared controls for multiple cancer endpoints are discussed.


Analysis of the precision of modulation transfer function measurements with a circular edge: influence of object circularity.
To measure the modulation transfer function (MTF) using a circular edge, we generate a synthesized edge spread function from multiple profiles radiating from the center, assuming that the circular object is perfectly round. Therefore, this study aimed to quantify the influence of the shape change of the circular edge on the measurement precision of the MTF. To examine this relationship, we generated simulated images with intentionally distorted circular edges and analyzed the correlation between circularity and the calculated MTF. This simulation was designed to replicate the MTF properties of an actual computed tomography image and was applied to isolate the effect of shape distortion on MTF measurements. MTF measurements were conducted on 11 different circularity images to determine the spatial frequencies at which the MTF values are 50% (f50) and 10% (f10), and the error rates to the true value were calculated. Our findings revealed a correlation between circularity and the measured MTF value. Specifically, an 1% decrease in circularity from the perfect circle condition resulted in an approximately -35% change in f50. This decrease in MTF values was attributed to the presence of rectangular spatial blurring, which occurs when a distorted circular image is used to generate the synthetic edge profile. This study provided insights into the influence of the shape changes in the circular edge on MTF measurements. The present findings contribute to a better understanding of the evaluation results and measurement errors when describing the image quality characteristics modalities using the circular edge technique.


Organohydrogel Actuators with Adjustable Stimulus Responsiveness for On-Demand Morphing.
Hydrogel actuators showing shape morphing in response to external stimuli are of significant interest for their applications in soft robots, artificial muscles, etc. However, there is still a lack of hydrogel actuators with adjustable stimulus responsiveness for on-demand driving. In this study, an organohydrogel actuator was prepared by a two-step interpenetrating method, resulting in the coexistence of poly(N-isopropylacrylamide-co-4-(2-sulfoethyl)-1-(4-vinylbenzyl) pyridinium betaine) (p(NIPAM-SVBP)) hydrophilic networks and poly(lauryl methacrylate) (pLMA) hydrophobic networks with gradient distribution. In the initial state, the organohydrogel actuator can be driven globally under thermal stimulation. Owing to the unique alkali-chromic performance of SVBP, the organohydrogel actuator can be endowed with photothermal properties and actuate locally under the stimulus of NIR light. More importantly, the organohydrogel will return to the original colorless state after being treated with acid solution. Our work provides a new insight into designing and fabricating novel actuators with adjustable stimulus responsiveness for on-demand morphing.


Factors and interactions affecting the performance of polyurethane elastomers in medical devices.
Polyurethanes offer the greatest versatility in compositions and properties of any family of polymers. For implantable medical devices, a few specific elastomeric polyurethane compositions have demonstrated a combination of toughness, durability, biocompatibility and biostability not achieved by any other available material. Because of the complex behavior of implantable polyurethanes in the body environment, designers and fabricators of polyurethane-containing devices must pay particular attention to the choice of composition and design of components. Subsequent treatment during qualification, fabrication, sterilization, storage, implantation, in vivo operation and explantation also determine the performance and provide the means for assessing the efficacy of the polyurethane in the implanted device.


Seasonal variation of kaurenoic acid, a hypoglycemic diterpene present in Wedelia paludosa (Acmela brasiliensis) (Asteraceae).
We evaluated the variation of the concentration of kaurenoic acid (1), which is a bioactive diterpene, in leaves, flowers, stems and roots from Wedelia paludosa (Acmela brasiliensis) for different seasons using the HRGC/FID method. The results indicated that the concentration of 1 is higher in the roots and stems during the autumn. The pharmacological results suggested that kaurenoic acid is responsible, at least in part, for the hypoglycemic potential detected in this plant.