Prognostic factors in nodular transitional cell bladder tumours.
A cohort of 106 nodular transitional cell bladder cancers (TCC) were followed up for a mean of 9 years. Clinical stage, WHO grade, six morphometric nuclear factors and volume corrected mitotic index (M/V index) were correlated to progression and survival during the follow-up period. Nuclear factors were related to WHO grade with a borderline significance (p = 0.01-0.3) whereas the M/V index showed a highly significant relation to WHO grade. Neither nuclear factors nor the M/V index were related significantly to T-, N- or M-categories at the time of diagnosis. Progression in N- and M-categories was related independently to WHO grade whereas progression in T-category could not be predicted significantly by none of the variables included in this analysis. Survival was predicted by T-category (p = 0.0028), N-category (p = 0.0001), M-category (p = 0.0057) and M/V index (p = 0.010). In T1-T2N0M0 tumours survival was predicted by the Dmax (p = 0.015) and by the M/V index (p = 0.039). In multivariate survival analysis T-category (p < 0.001) had independent prognostic value. In T1-T2N0M0 tumours only the M/V index predicted survival independently (p = 0.007). The results show that only the proliferation rate in addition to T-category have prognostic significance in nodular TCC.


Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives.
Superoxide (O2-.), nitric oxide (.NO), and their reaction product peroxynitrite (ONOO-) have all been shown to independently exert toxic target molecule reactions. Because these reactive species are often generated in excess during diverse inflammatory and other pathologic circumstances, we assessed the influence of .NO on membrane lipid peroxidation induced by O2-., H2O2, and .OH derived from xanthine oxidase (XO) and by ONOO-. Experimental conditions in lipid oxidation systems were adjusted to yield different rates of delivery of .NO, relative to rates of O2-. and H2O2 generation, by infusion of either .NO or via .NO released from S-nitroso-N-acetylpenicillamine or S-nitrosoglutathione. Peroxidation of phosphatidylcholine liposomes was assessed by formation of thiobarbituric acid-reactive products and by liquid chromatography-mass spectrometry. Liposomes exposed to XO-derived reactive species in the presence of .NO exhibited both stimulation and inhibition of lipid peroxidation, depending on the ratio of the rates of reactive oxygen species production and .NO introduction into reaction systems. Nitric oxide alone did not induce lipid peroxidation. Linolenic acid emulsions peroxidized by XO-derived reactive species showed similar dose-dependent regulation of lipid peroxidation by .NO. Mass spectral analysis of oxidation products showed formation of nitrito-, nitro-, nitrosoperoxo-, and/or nitrated lipid oxidation adducts, demonstrating that .NO serves as a potent terminator of radical chain propagation reactions. Electron spin resonance (ESR) analysis of incubation mixtures provided no evidence for formation of paramagnetic iron-lipid-nitric oxide complexes in reaction systems. Peroxynitrite-dependent lipid peroxidation, which predominantly occurs by metal-independent mechanisms, was also inhibited by .NO. Peroxynitrite-mediated benzoate hydroxylation was partially inhibited by .NO, inferring reaction between .NO and ONOOH. It is concluded that .NO can both stimulate O2-./H2O2/.OH-induced lipid oxidation and mediate oxidant-protective reactions in membranes at higher rates of .NO production, with the prooxidant versus antioxidant outcome critically dependent on relative concentrations of individual reactive species. Prooxidant reactions of .NO will occur after O2-. reaction with .NO to yield potent secondary oxidants such as ONOO- and the antioxidant effects of .NO a consequence of direct reaction with alkoxyl and peroxyl radical intermediates during lipid peroxidation, thus terminating lipid radical chain propagation reactions.


A comprehensive analysis of mitochondrial genes variants and their association with antipsychotic-induced weight gain.
Antipsychotic Induced Weight Gain (AIWG) is a common and severe side effect of many antipsychotic medications. Mitochondria play a vital role for whole-body energy homeostasis and there is increasing evidence that antipsychotics modulate mitochondrial function. This study aimed to examine the role of variants in nuclear-encoded mitochondrial genes and the mitochondrial DNA (mtDNA) in conferring risk for AIWG. We selected 168 European-Caucasian individuals from the CATIE sample based upon meeting criteria of multiple weight measures while taking selected antipsychotics (risperidone, quetiapine or olanzapine). We tested the association of 670 nuclear-encoded mitochondrial genes with weight change (%) using MAGMA software. Thirty of these genes showed nominally significant P-values (<0.05). We were able to replicate the association of three genes, CLPB, PARL, and ACAD10, with weight change (%) in an independent prospectively assessed AIWG sample. We analyzed mtDNA variants in a subset of 74 of these individuals using next-generation sequencing. No common or rare mtDNA variants were found to be significantly associated with weight change (%) in our sample. Additionally, analysis of mitochondrial haplogroups showed no association with weight change (%). In conclusion, our findings suggest nuclear-encoded mitochondrial genes play a role in AIWG. Replication in larger sample is required to validate our initial report of mtDNA variants in AIWG.


Uric acid upregulates the adiponectin‑adiponectin receptor 1 pathway in renal proximal tubule epithelial cells.
Adiponectin (APN) is a protein hormone that is primarily derived from adipocytes. It can also be secreted by renal cells. Hypoadiponectinemia has been documented in patients with hyperuricemia, however, whether soluble uric acid (SUA) regulates the expression of APN and APN receptor 1 (AdipoR1) in renal proximal tubule epithelial cells (PTECs) remains to be elucidated. The present study investigated the expression of APN and AdipoR1 in cultured PTECs that were exposed to SUA through immunofluorescence and western blot analysis. In addition, Sprague‑Dawley rats with oxonic acid‑induced hyperuricemia (HUA) with or without febuxostat treatment were employed as an animal model to measure 24 h urine protein, serum creatinine, urea nitrogen, uric acid and homeostasis model assessment of insulin resistance. Renal pathology was evaluated using hematoxylin and eosin and immunohistochemical staining. APN and AdipoR1 expression in the renal cortex were evaluated by western blotting. The results demonstrated that, in PTECs, the expression of APN and AdipoR1 was constant and increased upon SUA exposure. Similar observations were made within the proximal renal tubules of rats, and the oxonic acid‑induced increases in APN and AdipoR1 were offset by febuxostat treatment. Furthermore, SUA‑treated PTECs exhibited an increase in the expression of NLR family pyrin domain‑containing (NLRP) 3, which was dose‑dependent. NLRP3 expression was also significantly increased in the renal cortex of HUA rats compared with control and febuxostat‑treated rats. In conclusion, SUA enhanced the expression of APN and AdipoR1 in PTECs, which was associated with an increase in NLRP3 expression. The APN‑AdipoR1 pathway was demonstrated to have an important role in in vitro and in vivo models of renal proximal tubule inflammatory injury. Therefore, this pathway may be a potential therapy target in urate nephropathy.


[Our experience in the diagnosis of peroxisomal diseases with an abnormal fatty acid profile].
The aetiology and clinical features of peroxisomal diseases vary widely. An altered very-long-chain fatty acid (VLCFA) profile is commonly found in many of these diseases, and this makes it easier to point the diagnosis in the right direction. We review our experience in the diagnosis of cases of peroxisomal diseases with an altered VLCFA pattern; these were determined in serum only when there was a strong clinical suspicion up to the end of 1998, when their quantification by chromatography was introduced into our laboratory. The neuropaediatric database included 10,239 cases between May 1990 and 1st October 2007. Ten cases of peroxisomal disease with an altered VLCFA pattern were identified, all of them males. There were two cases of Zellweger syndrome spectrum, one unclassified peroxisomal oxidation defect and seven X-linked adrenoleukodystrophies (four with neurological compromise and three with no neurological damage; two were identified in siblings of patients and the other due to the presence of Addison's syndrome). In our 10 cases, the diagnosis was guided by the clinical or familial features that led to the determination of VLCFA. Being able to determine VLCFA makes early systematic diagnosis of patients possible. At present, VLCFA determination is performed when there is a clinical suspicion of Zellweger spectrum, suspected X-linked adrenoleukodystrophy/adrenomyeloneuropathy of unclear causation, Addison's disease, both in males and females, and above all in cases of chronic encephalopathy of unknown causation, with or without prenatal onset.


Isolation of a human erythrocyte-adapted substrain of Babesia rodhaini and analysis of the merozoite surface protein gene sequences.
Babesia rodhaini is a rodent hemoparasite closely related to B. microti, the major causative agent of human babesiosis. We tested the infectivity of B. rodhaini for human erythrocytes by using the SCID mouse model in which the circulating erythrocytes were replaced with those of humans. Initially, parasites grew very poorly in the mouse model, but a variant capable of propagating in human erythrocytes emerged after an adaptation period of three weeks. In an attempt to identify parasite proteins involved in the alteration of host cell preference, an expression cDNA library of B. rodhaini was constructed and screened with immune mouse sera. Although we were able to obtain three merozoite surface protein (MSP) genes, sequences of these genes from both the parental strain and human erythrocyte-adapted substrain were identical. Our results suggest that B. rodhaini has potential ability to infect human erythrocytes, but development of this ability may not be brought about by an amino acid change in MSPs.


Homeless "squeegee kids": food insecurity and daily survival.
Current knowledge about food insecurity in North America is largely based on research with low-income households. Much less is known about the food experiences of homeless people, a group who are particularly vulnerable to food insecurity. This study explored the food experiences of street youth, one of the fastest growing segments of the homeless population in Canada. To gain an in-depth understanding of food insecurity within the context of daily life, ethnographic research was undertaken with street youth at one inner-city drop-in centre in Toronto, Canada. Results of this study reveal that street youth's access to food was precarious amidst the instability and chaos of street life. The day-to-day lives of the street youth encountered in this study were characterized by a constant struggle to find safe, secure shelter, generate income, and obtain sufficient food. In this context, food was a precious commodity. Food access was inextricably linked to and contingent upon conditions of health, shelter, and income. Food access was precarious since everyday food sources purchased food and charitable food assistance were ultimately insecure. "Squeegeeing" (washing car windows), the primary source of income for youth in the study, was dependent on the weather, political and public will, and youth's physical health, and thus did not generate enough money to continuously meet basic food needs. Charitable food assistance was considered poor quality and was associated with food sickness. The often unsavoury atmosphere of charitable food programmes, their locations, capacity, and idiosyncratic rules, policies, and hours of operation also affected access. Findings from this study extend the current understanding of food insecurity to homeless youth and offer insight into current responses to hunger and homelessness.


An economic method for synthesis of highly ordered porous silica.
We report an economic method for synthesis of highly ordered silica with a mixing surfactant system containing short-chain cationic surfactant (decyltrimethyl ammonium bromide, denoted C10TMAB) and short-chain anionic surfactant (sodium octyl sulfate, denoted SOS) as the templating agents. Highly ordered supermicroporous silica was synthesized by judiciously chosen mixing ratio of surfactants. The samples were characterized by small-angle X-ray diffraction, transmission electron microscopy, and N2 adsorption-desorption. The results showed that the pore structure of the resulting silica belongs to the two-dimensional hexagonal structure (space group 2D-p6mm) with a pore size of ca. 2.2nm. Moreover, the method proposed herein is expected to facilitate the synthesis of not only porous silicas but also materials with other framework compositions.


Highly Stretchable and Transparent Supercapacitor by Ag-Au Core-Shell Nanowire Network with High Electrochemical Stability.
Stretchable and transparent electronics have steadily attracted huge attention in wearable devices. Although Ag nanowire is the one of the most promising candidates for transparent and stretchable electronics, its electrochemical instability has forbidden its application to the development of electrochemical energy devices such as supercapacitors. Here, we introduce a highly stretchable and transparent supercapacitor based on electrochemically stable Ag-Au core-shell nanowire percolation network electrode. We developed a simple solution process to synthesize the Ag-Au core-shell nanowire with excellent electrical conductivity as well as greatly enhanced chemical and electrochemical stabilities compared to pristine Ag nanowire. The proposed core-shell nanowire-based supercapacitor still possesses fine optical transmittance and outstanding mechanical stability up to 60% strain. The Ag-Au core-shell nanowire can be a strong candidate for future wearable electrochemical energy devices.


Some comments on respiratory quotient (RQ) determination from the analysis of exit gas from a fermentor.
Recently, the respiratory quotient (RQ) of microbes measured in situ in a fermentor by exit-gas analysis has been used successfully, for instance, in a fed-batch culture of baker's yeast as a criterion to control the feeding rate.(1-3) It is significant here to keep RQ values close to unity throughout; any deviations of RQ from unity give rise to deterioration of the cell growth yield.However easy it might be to keep RQ values around unity by controlling the feeding rate, the question of whether or not RQ values determined by gas analysis at the fermentor exit could generally represent those in vivo deserves attention. Indeed, for a fermentation carried out at an alkaline side, gas analysis would give RQ values that differ remarkably from true values because of the medium's "storage" of CO(2) released from microbes. The purpose of this communication is to make clear those factors that would affect true RQ values in the analysis of exit gas from a fermentor.


[Health-related quality of life measurement: a critical reading guide].
Quality of life is rarely assessed in the pulmonary function laboratory. Quality of life, or at least some of its domains, should be directly measured. Quality-of-life questionnaires developed according to established protocols can be very useful in clinical practice. In clinical studies, the choice of a questionnaire depends on its function (evaluative or discriminative) which should be supported by its measurement properties (validity, reliability, responsiveness). The methodology of critical appraisal of an article about quality of life proposed in this reading guide are in keeping with the principles of evidence-based medicine.


Racial/Ethnic-Specific Reference Intervals for Common Laboratory Tests: A Comparison among Asians, Blacks, Hispanics, and White.
Reference intervals (RIs) for common clinical laboratory tests are usually not developed separately for different subpopulations. The aim of this study was to investigate racial/ethnic differences in RIs of common biochemical and hematological laboratory tests using the National Health and Nutrition Examination Survey (NHANES) 2011-2012 data. This current study included 3,077 participants aged 18-65 years who reported their health status as "Excellent," "Very good," or "Good," with known race/ethnicity as white, black, Hispanic, or Asian. Quantile regression analyses adjusted for sex were conducted to evaluate racial/ethnic differences in the normal ranges of 38 laboratory tests. Significant racial/ethnic differences were found in almost all laboratory tests. Compared to whites, the normal range for Asians significantly shifted to higher values in globulin and total protein and to lower values in creatinine, hematocrit, hemoglobin, mean cell hemoglobin, mean cell hemoglobin concentration, and mean platelet volume. These results indicate that racial/ethnic subpopulations have unique distributions in the labortoary tests and race/ethnicity may need to be incorporated in the development of their RIs. Establishment of racial/ethnic-specific RIs may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment to improve quality of patient care, especially for a state with diverse racial/ethnic subpopuations such as Hawai'i.


Anterior cruciate ligament tear in Hong Kong Chinese patients.
To investigate the associations between patient sex, age, cause of injury, and frequency of meniscus and articular cartilage lesions seen at the time of the anterior cruciate ligament reconstruction. University affiliated hospital, Hong Kong. Medical notes and operating records of 672 Chinese patients who had received anterior cruciate ligament reconstruction between January 1997 and December 2010 were reviewed. Data concerning all knee cartilage and meniscus injuries documented at the time of surgery were analysed. Of the 593 patients, meniscus injuries were identified in 315 (53.1%). Patients older than 30 years were more likely to suffer from meniscal injury compared with those younger than 30 years (60% vs 51%, P=0.043). Longer surgical delay was observed in patients with meniscal lesions compared with those without (median, 12.3 months vs 9.1 months, P=0.021). Overall, 139 cartilage lesions were identified in 109 (18.4%) patients. Patients with cartilage lesions were significantly older than those without the lesions (mean, 27.6 years vs 25.1 years, P=0.034). Male patients were more likely to have chondral injuries than female patients (20.1% vs 10.9%, P=0.028). The risk of cartilage lesions was increased by nearly 3 times in the presence of meniscal tear (P<0.0001; odds ratio=2.7; 95% confidence interval, 1.7-4.2). Increased age and surgical delay increased the risk of meniscal tears in patients with anterior cruciate ligament tear. Increased age, male sex, and presence of meniscal tear were associated with an increased frequency of articular lesions after an anterior cruciate ligament tear.


Immunolocalization of fetal aldolase isoenzymes in rat regenerating liver after carbon tetrachloride intoxication.
Light and electron microscopic immunolocalization of adult and fetal aldolase isoenzymes has been studied in rat liver 72 h after CCL4 intoxication. As in rat regenerating liver after partial hepatectomy, fetal aldolases A and C were located in sinusoidal cells (Kupffer and endothelial cells) whereas adult aldolase B was present in hepatocytes only. Our results are different from those obtained with fetal and cancerous livers; they suggest that control mechanisms of gene regulation different in liver regeneration and in cancer.


Emergence of gentamicin- and methicillin-resistant Staphylococcus aureus strains in New York City hospitals.
Gentamicin- and methicillin-resistant strains of Staphylococcus aureus have been isolated from Spring 1979 to the present from many hospitals in New York City. A large proportion of the strains were resistant to the majority of antistaphylococcal antibiotics. The ratio of multiply resistant strains was highest among tetracycline-resistant strains. There were significant differences in phage susceptibility patterns and the resistance spectrum of strains isolated at different hospitals, whereas strains isolated at the same hospital often showed a marked degree of similarity. This suggests multiple origins of gentamicin- and methicillin-resistant strains isolated in New York City.


A uniformly cleaved epitaxically grown diamond crystal for synchrotron radiation.
A homoepitaxic single-crystal diamond (111) film grown by microwave-assisted chemical vapour deposition (CVD) and fractured along the [110] directions to form small triangles was investigated by X-ray double-crystal topography. The X-ray topographic image showed that all parts of the cleaved CVD diamond film sections uniformly reflected X-rays at the peak position of the rocking curve, which was measured in the Bragg case. Furthermore, no bending effect was observed and the CVD diamond film appeared to be more perfect than and showed higher integrated intensity than the natural diamond substrate.


Selection and phenotype characterization of potassium antimony tartrate-resistant populations of four New World Leishmania species.
In the present study, we selected in vitro populations of Leishmania Viannia guyanensis, L.V. braziliensis, L. Leishmania amazonensis and L.L. infantum chagasi that were resistant to potassium antimony tartrate (SbIII). The resistance index of these populations varied from 4- to 20-fold higher than that of their wild-type counterparts. To evaluate the stability of the resistance phenotype, these four resistant populations were passaged 37 to 47 times in a culture medium without SbIII. No change was observed in the resistance indexes of L.V. guyanensis (19-fold) and L.L. infantum chagasi (4-fold). In contrast, a decrease in the resistance index was observed for L.V. braziliensis (from 20- to 10-fold) and L.L. amazonensis (from 6- to 3-fold). None of the antimony-resistant populations exhibited cross-resistance to amphotericin B and miltefosine. However, the resistant populations of L.V. braziliensis, L.L. amazonensis and L.L. infantum chagasi were also resistant to paromomycin. A drastic reduction was observed in the infectivity in mice for the resistant L.V. guyanensis, L.L. amazonensis and L.V. braziliensis populations. The SbIII-resistant phenotype of L.V. braziliensis was stable after one passage in mice. Although the protocol of induction was the same, the SbIII-resistant populations showed different degrees of tolerance, stability, infectivity in mice and cross-resistance to antileishmanial drugs, depending on the Leishmania species.


Insulin receptor substrate-1 is the predominant signaling molecule activated by insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor-positive human breast cancer cells.
Because insulin-like growth factor-I (IGF-I), insulin, and interleukin-4 (IL-4) have known biological effects in breast cancer cells and signal through insulin-receptor substrate (IRS) adaptor proteins, we examined the expression and function of IRS-1 and IRS-2 in breast tumors and cell lines. IRS-1 and IRS-2 were expressed by cell lines and primary breast tumor specimens. IGF-I, insulin, and IL-4 treatment of MCF-7 and ZR-75, and IGF-I treatment of T47-D breast cancer cells, resulted in much greater tyrosine phosphorylation of IRS-1 compared with IRS-2. Furthermore, IGF-I stimulated greater tyrosine phosphorylation of IRS-1 than either insulin or IL-4. IGF-I treatment also enhanced association of the p85 regulatory subunit of phosphatidylinositol 3-kinase with IRS-1 and stimulated increased enzymatic activity compared with IL-4 and insulin in all three cell lines. Similarly, mitogen-activated protein kinase activity was greater in IGF-I-stimulated cells. To determine the functional significance of the activation of these pathways, we inhibited activation of phosphatidylinositol 3-kinase with wortmannin and mitogen-activated protein kinase with PD098059. Both compounds inhibited IGF-stimulated growth, suggesting that both pathways contributed to the mitogenic response to IGF-I. We conclude that IRS-1, and not IRS-2, is the predominant signaling molecule activated by IGF-I, insulin, and IL-4. Furthermore, enhanced tyrosine phosphorylation of IRS-1 by IGF-I, compared with either insulin or IL-4, is associated with greater activation of mitogenic downstream signaling pathways resulting in enhanced cell growth.


Calcitonin gene-related peptide and reperfusion injury.
Calcitonin gene-related peptide is a potent intrinsic vasodilator, can induce prostacyclin release, and may inhibit membrane lipid peroxidation. This study examines the effect of calcitonin gene-related peptide on vessel diameters, capillary perfusion, and contractile function of skeletal muscle after 4 or 5 hours of ischemia and during immediate reperfusion using the rat cremaster muscle model. Forty-two male rats were used; half of these received 0.2 ml of 10(-7) M calcitonin gene-related peptide after 0, 15, and 30 minutes of reperfusion, while the other half received normal saline as a control. By means of intravital videomicroscopy, the diameters of 10 vessels per muscle were measured prior to ischemia and during reperfusion. The fluorescein filling area was determined at 15, 30, and 60 minutes of reperfusion. After 1 hour of reperfusion, muscle function was examined in vitro by quantifying the contractile response to electric field stimulation of the muscles in an organ bath system. There was a significant increase in the diameter of the arterioles, but not the small arteries, at every time point from 10 to 60 minutes of reperfusion. The fluorescein filling area was increased in treated muscles at every time point. Contractile function was not significantly preserved. In light of the ability of calcitonin gene-related peptide to relieve vasospasm and improve capillary perfusion, it may be useful in reducing reperfusion injury in the future.


[History and Current Status of Birth Cohort Studies in the UK, and Feasibility in Japan].
Birth cohort studies are conducted by prospectively following the participants with a spe- cific characteristic background from their birth or prenatal birth, and can explore the causal relationship of various factors with outcomes. In the UK, birth cohort studies with long-term follow-ups have been launched every ten years, which have provided many significant results and related useful policy recommendation. However, these have not necessarily intended to be launched as the national project with long-term observations, rather existing birth cohorts are accept to continue because of the excellent results and survey condition. In 1990s, birth cohort studies have been revalued as national resources, and widely used by domestic and international researchers. As the contribution to psychiatry and mental health, most of the cohort studies have been conducted to identify risk factors for onset of psychiatric diseases such as schizophrenia. Nowadays, broader studies were conducted and highly evaluated for the relationships between physical and psychological illnesses, and biological studies. Recent cohort studies also showed that cognitive abilities in childhood or adolescence was similar between those who later developed schizophrenia and those who experienced psychotic symptoms, sug- gesting that a spectrum in psychiatric diseases would be useful for elucidating the pathophysiology. In Japan, birth cohort studies which findings could be reflected on policy implications have been required as national resources. However, as there have been no birth cohort studies that have conducted for long-term follow-ups, there are little techniques and knowledge for launching and continuing a birth cohort study with low attrition, and providing evidences to society. It is necessary to establish these techniques and knowledge by learning from the UK cases within the cultural and social contexts in Japan. High quality routine studies including examination have been implemented in Japan in various fields such as perinatal and infant care, schools, work places, medical care, and the central and local governments. Supplementation of those data will be needed for high quality birth cohort studies. Until now, there has been no relevant law to conduct any data linkage between the data from various fields in research settings and it is necessary to be prepared.


[Autosomal dominant polycystic kidney disease (ADPKD). in Morocco. Multicenter study about 308 families].
Autosomal dominant polycystic kidney disease (ADPKD) has aroused great interest these last years, especially after the discovery of the genes responsible for this disease. It remains a frequent cause of chronic renal failure (CRF). In this work we report the results of a multi-centre retrospective study. The data relates to 41 centres of nephrology and dialysis in Morocco, 308 Moroccan families and 420 observations. We have tried to determine the frequency of this pathology in Morocco, its complications and difficulties in taking care of it. The average age of the discovery of ADPKD was 46 +/- 3 years and the sex ratio was of 1.08. The ADPKD frequency among Moroccans who undergo dialysis was 6.5%. Pain was the most frequent symptom which revealed the disease (21%); while renal failure at different stages was found in 17% of the patients and high blood pressure (HBP) in 11%. The clinic diagnosis was confirmed by echography in 95% of cases. The association with a hepatic cysts was found in 17.8% of the cases. In addition, to HBR and urinary tract infection, the complications were largely dominated by renal chronic failure and the difficulties in taking care of it because of economic problems. Through this the authors discuss and report the profile and the prognostics of this infection in our society, with a special focus on the evolution of the renal function, the delay in the diagnosis and the management.


Holding Animal-Based Research to Our Highest Ethical Standards: Re-seeing Two Emergent Laboratory Practices and the Ethical Significance of Research Animal Dissent.
"Animal-based research should be held to the highest ethical standards" is becoming an increasingly common refrain. Though I think such a commitment is what we should expect of those using animals in science, much as we would if the participants were humans, some key insights of discussions in applied ethics and moral philosophy only seem to slowly impact what reasonably qualifies as the highest standards in animal research ethics. Early in my paper, I will explain some of these insights and loosely tie them to animal research ethics. Two emergent practices in laboratory animal science, positive reinforcement training and "rehoming," will then be discussed, and I will defend the view that both should be mandatory on no more ethical grounds than what is outlined in the first section. I will also provide reasons for foregrounding the moral significance of dissent and why, most of the time, an animal research subject's sustained dissent should be respected. Taken together, what I will defend promises to change how at least some animals are used in science and what happens to them afterwards. But I will also show how an objective ethics requires nothing less. Ignoring these constraints in the scientific use of animals comes at the cost of abandoning any claim to adhering to our highest ethical standards and, arguably, any claim to the moral legitimacy of such scientific use.


Reporting sodium channel activity using calcium flux: pharmacological promiscuity of cardiac Nav1.5.
Voltage-gated sodium (Nav) channels are essential for membrane excitability and represent therapeutic targets for treating human diseases. Recent reports suggest that these channels, e.g., Nav1.3 and Nav1.5, are inhibited by multiple structurally distinctive small molecule drugs. These studies give reason to wonder whether these drugs collectively target a single site or multiple sites in manifesting such pharmacological promiscuity. We thus investigate the pharmacological profile of Nav1.5 through systemic analysis of its sensitivity to diverse compound collections. Here, we report a dual-color fluorescent method that exploits a customized Nav1.5 [calcium permeable Nav channel, subtype 5 (SoCal5)] with engineered-enhanced calcium permeability. SoCal5 retains wild-type (WT) Nav1.5 pharmacological profiles. WT SoCal5 and SoCal5 with the local anesthetics binding site mutated (F1760A) could be expressed in separate cells, each with a different-colored genetically encoded calcium sensor, which allows a simultaneous report of compound activity and site dependence. The pharmacological profile of SoCal5 reveals a hit rate (>50% inhibition) of around 13% at 10 μM, comparable to that of hERG. The channel activity is susceptible to blockage by known drugs and structurally diverse compounds. The broad inhibition profile is highly dependent on the F1760 residue in the inner cavity, which is a residue conserved among all nine subtypes of Nav channels. Both promiscuity and dependence on F1760 seen in Nav1.5 were replicated in Nav1.4. Our evidence of a broad inhibition profile of Nav channels suggests a need to consider off-target effects on Nav channels. The site-dependent promiscuity forms a foundation to better understand Nav channels and compound interactions.


Oxaliplatin-induced Pulmonary Toxicity: A Rare but Serious Complication.
The FOLFOX regimen (oxaliplatin, leucovorin, and 5-fluorouracil) is FDA approved for use in patients with colorectal cancer and other gastrointestinal malignancies. The initial phase III randomized controlled trials that led to FDA approval of oxaliplatin with leucovorin and 5-fluorouracil showed a less than 1% incidence of pulmonary fibrosis and grade IV pulmonary toxicities. Here we describe two cases of pulmonary toxicity in patients with metastatic colorectal cancer treated with FOLFOX and briefly review the literature regarding oxaliplatin-induced pulmonary toxicity.


Graphene quantum dot sensitized leaf-like InVO4/BiVO4 nanostructure: a novel ternary heterostructured QD-RGO/InVO4/BiVO4 composite with enhanced visible-light photocatalytic activity.
Leaf-like InVO4/BiVO4 nanostructures with sizes of 2-5 μm were synthesized by a simple hydrothermal method. Graphene quantum dots (QD-RGO) were then deposited onto the surfaces of the leaf-like InVO4/BiVO4 crystals through a facile deposition-precipitation technique. Under visible light irradiation (λ > 420 nm), the QD-RGO/InVO4/BiVO4 photocatalyst degraded rhodamine B (Rh B) efficiently and displayed a much higher photocatalytic activity than pure BiVO4, InVO4, RGO/InVO4, RGO/BiVO4 or an InVO4/BiVO4 hybrid. The InVO4/BiVO4 photocatalyst with 3 wt% of QD-RGO exhibited the highest photocatalytic efficiency. The quenching effects of different scavengers demonstrated that O2˙(-) played a major role in Rh B degradation. It was elucidated that the excellent photocatalytic activity of QD-RGO/InVO4/BiVO4 for the degradation of Rh B under visible light (λ > 420 nm) can be ascribed to the extended absorption in the visible light region resulting from the QD-RGO loading, the high specific surface area, and the efficient separation of photogenerated electrons and holes through the QD-RGO/InVO4/BiVO4 heterostructure.


Influence of salivary components and extracellular polysaccharide synthesis from sucrose on the attachment of Streptococcus mutans 6715 to hydroxyapatite surfaces.
The adsorption of (3)H-labeled Streptococcus mutans 6715 cells to disks of hydroxyapatite (HA) was studied. The number of streptococci that adsorbed was logarithmically related to the concentration of cells available up to at least 2 x 10(8) per ml; equilibrium occurred within 45 min. Assay reliability was verified by direct scanning electron microscopic counts. Untreated HA disks exposed to buffered saline (PBS)-suspended streptococci at a concentration of 1.1 x 10(8) per ml absorbed 3.2 x 10(6) cells per cm(2); approximately 3% of the surface area was, therefore, occupied by adsorbed organisms. The presence of adsorbed salivary components on HA reduced the number of attaching S. mutans cells by half. When S. mutans cells were suspended in saliva to mimic conditions existing in the mouth, the number of streptococci adsorbing to saliva-treated HA was reduced more than 30-fold compared to untreated HA. Approximately one-half of the streptococci adsorbed to untreated or to saliva-treated HA disks could be desorbed over a 4-h period with 0.067 M phosphate buffer. S. mutans cells exposed to sucrose to permit extracellular polysaccharide synthesis before or during adsorption attached in fewer numbers to both saliva-treated and untreated HA than PBS-treated organisms. When S. mutans cells adsorbed on untreated HA were exposed to sucrose, fewer organisms could be desorbed; thus, in situ polysaccharide synthesis promoted their more firm attachment to untreated HA. However, when saliva-suspended streptococci were adsorbed to saliva-treated HA surfaces, exposure to sucrose before or subsequent to adsorption did not promote more firm attachment. Evidently, the powerful adherence-inhibiting and desorptive effects of salivary components overshadowed any promoting effects attributable to glucan synthesis from sucrose. Similarly, no differences were noted in the desorption of S. mutans cells from human teeth after exposure to sucrose, glucose, or PBS relative to a strain of Streptococcus mitis (S. mitior). Thus, no evidence was obtained to support the hypothesis that glucan synthesis from sucrose was essential for, or promoted, the attachment of S. mutans cells to HA surfaces exposed to saliva or to the smooth surfaces of human teeth.


Surgical residents' perceptions of the effects of the ACGME duty hour requirements 1 year after implementation.
In July 2003, the Accreditation Council for Graduate Medical Education implemented nationwide requirements on resident duty hours with the aim of improving quality of care. Our objectives were (1) to determine the extent and means of compliance with the ACGME requirements within general surgery residency programs and (2) to examine general surgery residents' perceptions of the effects of the ACGME requirements on patient care and residents' training experience. A survey was mailed to residents in 19 New England general surgery programs in spring 2004 (n=238). The overall response rate was 36%. More than 89% of respondents reported that the requirements generally were being enforced, and respondents' mean work hours (80.8 +/- 11.7 per week) supported this claim. Forty-three percent felt that quality of care had deteriorated. Although 70% perceived decrements in continuity of care, only 32% believed that the risk of patient management errors had increased. Sixty percent reported doing fewer operations, and half felt that residents missed out on too many learning opportunities. Yet, only 39% reported that the requirements had worsened the quality of training. Residents consistently reported an improved quality of life. Seventy-five percent felt that, overall, the requirements were a good thing. Most surgical residents do not believe that the ACGME duty hour requirements have had their intended effect of improving quality of care and are ambivalent about effects on the quality of their training. However, they report an improved quality of life, and most residents do support the requirements overall.


Role of organisational factors on the 'weekend effect' in critically ill patients in Brazil: a retrospective cohort analysis.
Higher mortality for patients admitted to intensive care units (ICUs) during the weekends has been occasionally reported with conflicting results that could be related to organisational factors. We investigated the effects of ICU organisational and staffing patterns on the potential association between weekend admission and outcomes in critically ill patients. We included 59 614 patients admitted to 78 ICUs participating during 2013. We defined 'weekend admission' as any ICU admission from Friday 19:00 until Monday 07:00. We assessed the association between weekend admission with hospital mortality using a mixed logistic regression model controlling for both patient-level (illness severity, age, comorbidities, performance status and admission type) and ICU-level (decrease in nurse/bed ratio on weekend, full-time intensivist coverage, use of checklists on weekends and number of institutional protocols) confounders. We performed secondary analyses in the subgroup of scheduled surgical admissions. A total of 41 894 patients (70.3%) were admitted on weekdays and 17 720 patients (29.7%) on weekends. In univariable analysis, weekend admitted patients had higher ICU (10.9% vs 9.0%, P<0.001) and hospital (16.5% vs 13.5%, P<0.001) mortality. After adjusting for confounders, weekend admission was not associated with higher hospital mortality (OR 1.05, 95% CI 0.99 to 1.12, P=0.095). However, a 'weekend effect' was still observed in scheduled surgical admissions, as well as in ICUs not using checklists during the weekends. For unscheduled admissions, no 'weekend effect' was observed regardless of ICU's characteristics. For scheduled surgical admissions, a 'weekend effect' was present only in ICUs with a low number of implemented protocols and those with a reduction in the nurse/bed ratio and not applying checklists during weekends. ICU organisational factors, such as decreased nurse-to-patient ratio, absence of checklists and fewer standardised protocols, may explain, in part, increases in mortality in patients admitted to the ICU mortality on weekends.


Transmitter release in botulinum-poisoned muscles.
Examination of miniature end-plate potentials (m.e.p.ps) in rat skeletal muscle poisoned in vivo by botulinum toxin type A reveals the presence of two populations of potentials. One population which corresponds to m.e.p.ps in unpoisoned muscles and to quantal end-plate potentials. The frequency of these m.e.p.ps is greatly reduced by botulinum toxin. The second population of m.e.p.ps has quite different characteristics. These m.e.p.ps have a more variable, but generally much larger amplitude, and their time to peak is longer than normal m.e.p.ps. The frequency of these m.e.p.ps increases during poisoning and reaches 0.3-1 Hz after 10-14 days. In addition to the variability in amplitude and time-to-peak these m.e.p.ps differ from those at unpoisoned junctions by being unaffected by procedures which alter extra- or intracellular Ca2+ concentrations. The appearance of this Ca2+-insensitive spontaneous quantal secretion of acetylcholine is apparently not a direct effect of the toxin but secondary to blockade of impulse transmission since it also appears at unpoisoned end-plates when transmission is impaired for other reasons. Procedures which increase the intracellular Ca2+ concentration in nerve terminals restore transmitter release from botulinum toxin poisoned nerves. Furthermore, the block caused by the toxin is very temperature-dependent, a reduction in temperature relieving the block. Since presynaptic Ca2+ currents are unaltered by the toxin it is proposed that the block of transmission is due to a reduction in the calcium content of the nerve terminal to a level where the amount of Ca2+, which normally enters, is insufficient to activate transmitter release.


Indium(III)-induced fluorescent excimer formation and extinction in calix[4]arene-fluoroionophores.
New fluorogenic or/and chromogenic calix[4]arenes 1-3 with two facing amide groups linked to fluorescent pyrene units are synthesized. Orientations of the pyrene units are remote from each other in 1 and face-to-face pi-stacked in 2, which produces different photophysical properties. In the excited state, the two pyrene units of 2 form a strong intramolecular excimer displaying an emission at 472 nm with a relatively weak monomer emission at 395 nm. In contrast, 1 exhibits only a monomer emission at 398 nm because intramolecular hydrogen bonding between the phenolic OH oxygens and the amide hydrogens prevents pi-stacking of the two pyrene groups. Fluorescence changes upon addition of various metal ions show that 1 has a remarkably high selectivity for In(3+) over the other metal ions tested. Compound 1 forms 2:1 (metal:ligand), as well as 1:1 complexes, with In(3+), with fluorescence varying uniquely with the complex stoichiometry. Compound 3, which possess two pyrene units and two chromogenic azo groups, shows almost the same binding behavior toward metal ions as does 1, together with additional bathochromic shifts of the absorption maximum. Compared with 1, compound 3 emits a considerably weaker fluorescence, which is attributed to electron transfer from the pyrene units to the nitro groups of the phenylazo moieties.


Laparoscopic Biopsies in Pancreas Transplantation.
As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney-pancreas biopsies and 14 pancreas-only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields.


Gonadotrophin hormone releasing tests in women receiving hormonal contraception.
Gonadotrophin secretion by the pituitary was tested by i.v. injections of synthetic LH and FSH releasing hormone (LHRH) in five normal women between day 21 and day 25 of the luteal phase of the cycle, in twelve women receiving contraception with i.m. injection of medroxyprogesterone acetate and in eight women taking combined oral contraceptives of different varieties. Treatment with oral contraceptives led to a decrease or even to complete suppression of the response and possibly the reserve capacity of both LH and FSH secretions. Treatment with medroxyprogesterone acetate for several years lowered basal serum LH and FSH as did oral contraceptives but had much less effect on the responses to LRH. In long-term steroid contraception, progestogens alone seem to exert much less deleterious effect on gonadotrophin function than when used in combination with an oestrogen.


Standard anti-tuberculosis treatment and hepatotoxicity: do dosing schedules matter?
A nested case-control study was conducted in order to examine whether dosing schedules of standard pyrazinamide-containing anti-tuberculosis (TB) treatment (standard treatment) might affect hepatotoxicity. The present authors retrospectively identified all patients with hepatitis using biochemical criteria from a cohort of 3,007 clinic patients who commenced anti-TB treatment from January 1 to June 30, 2001. Each case with hepatitis between 1-9 weeks post-TB treatment was compared using conditional logistic regression analysis with two controls selected randomly from patients without hepatitis in the same period and matched by sex, age and standard treatment. Impacts of sex and age were examined by logistic regression analysis of cases and patients without hepatitis. Hepatitis occurred in 167 patients, of whom 96 qualified as cases. A conditional logistic risk model identified hepatitis B surface antigen carriage as the only risk factor (odds ratio (95% confidence interval (CI)) 1.8 (1.1-3.1)). Logistic regression analysis showed that sex was nonsignificant but ageing increased the odds of hepatitis. The risk of hepatitis increased from 2.6% (1.9-3.5%) to 4.1% (3.2-5.3%) as age exceeded 49 yrs. Dosing schedules in the first 9 weeks have little impact on hepatotoxicity. If patients at risk of both hepatitis and relapse receive standard treatment, daily dosing is preferable.


Clinical Characteristics of the Suicide Attempters Who Refused to Participate in a Suicide Prevention Case Management Program.
Case management interventions for suicide attempters aimed at helping adjust their social life to prevent reattempts have high nonparticipation and dropout rates. We analyzed the clinical characteristics of the group who refused to participate in the suicide prevention program in Korea. A total of 489 patients with a suicide attempt who visited Uijeongbu St. Mary's Hospital, the Catholic University of Korea, from December 2009 to December 2013 were analyzed. All patients were divided into the participation group (n = 262) and the refusal group (n = 227) according to their participation in the case management program. Demographic and clinical characteristics of each group were examined. Results showed that the refusal group had low risks for suicide in terms of risk factors related with psychopathologies and presenting suicide behavior. That is, the refusal group had less patients with co-morbid medical illnesses and more patients with mild severity of depression compared to the participation group. However, the refusal group had more interpersonal conflict, more isolation of social integrity, and more impaired insight about suicide attempt. The results suggest that nonparticipation in the case management program may depend upon the patient's impaired insight about the riskiness of suicide and lack of social support.


Right frontal EEG and pregnancy/neonatal outcomes.
Fifty-two pregnant women recruited during their second trimester were given EEGs and divided into greater relative right and left frontal EEG activation groups. The greater relative right frontal EEG women had lower dopamine levels during their second trimester and lower dopamine and higher cortisol levels during the neonatal period. The newborns of the right frontal EEG mothers also showed greater relative right frontal EEG, had lower dopamine and serotonin levels, spent more time in indeterminate sleep and had inferior Brazelton scores. A discriminant function analysis based on the mothers' prenatal depression scores and biochemical measures correctly classified 74% of the women as greater relative right or left frontal EEG group members.


Relation among plant growth, carbohydrates and flowering time in the Arabidopsis Landsberg erecta x Kondara recombinant inbred line population.
Arabidopsis thaliana natural variation was used to study plant performance viewed as the accumulation of photo-assimilates, their allocation and storage, in relation to other growth-related features and flowering-related traits. Quantitative trait locus (QTL) analysis using recombinant inbred lines derived from the cross between Landsberg erecta (originating from Poland) and Kondara (originating from Tajikistan) grown on hydroponics, revealed QTLs for the different aspects of plant growth-related traits, sugar and starch contents and flowering-related traits. Co-locations of QTLs for these different aspects were detected at different regions, mainly at the ER locus; the top of chromosomes 3, 4 and 5; and the bottom of chromosome 5. Increased plant growth was associated with early flowering and leaf transitory starch, and correlated negatively with the levels of soluble sugar at early phases of development. From the significant correlations and the co-locations of the QTLs for these aspects, we conclude that there is a complex relationship between plant growth-related traits, carbohydrate content and flowering-related traits.


Critical role of CDK11(p58) in human breast cancer growth and angiogenesis.
A capillary network is needed in cancer growth and metastasis. Induction of angiogenesis represents one of the major hallmarks of cancer. CDK11(p58), a Ser/Thr kinase that belongs to the Cell Division Cycle 2-like 1 (CDC2L1) subfamily is associated with cell cycle progression, tumorigenesis, sister chromatid cohesion and apoptotic signaling. However, its role in breast cancer proliferation and angiogenesis remains unclear. Tumorigenicity assays and blood vessel assessment in athymic mice were used to assess the function of CDK11(p58) in tumor proliferation and angiogenesis. CCK-8 assay was used to detect breast cancer cell growth. Immunohistochemistry was used to detect the expression of vascular endothelial growth factor (VEGF), CD31 and CD34 in CDK11 positive patient breast cancer tissues. Dual-Luciferase array was used to analyze the function of CDK11(p58) in the regulation of VEGF promoter activity. Western blot was used to detect related protein expression levels. CDK11(p58) inhibited breast cancer growth and angiogenesis in breast cancer cells and in nude mice transplanted with tumors. Immunohistochemistry confirmed that CDK11(p58) was negatively associated with angiogenesis-related proteins such as VEGF, CD31 and CD34 in breast cancer patients. Real-time PCR and dual-luciferase assay showed CDK11(p58) inhibited the mRNA levels of VEGF and the promoter activity of VEGF. As CDK11(p58) is a Ser/Thr kinase, the kinase-dead mutant failed to inhibit VEGF mRNA and promoter activity. Western blot analysis showed the same pattern of related protein expression. The data suggested angiogenesis inhibition was dependent on CDK11(p58) kinase activity. This study indicates that CDK11(p58) inhibits the growth and angiogenesis of breast cancer dependent on its kinase activity.


The technique and early results of high gastric reduction for obesity.
The high gastric reduction operation has been performed on one hundred and nine obese patients over a sixteen-month period. Patient selection, preoperative care, operative technique and postoperative care are described. Our early results show that a satisfactory initial and continuing weight loss can be sustained for a twelve-month period with a low morbidity and mortality. Further follow-up of these patients is required before the ultimate place of this procedure is established.


Scarpa fascia preservation during abdominoplasty: randomized clinical study of efficacy and safety.
Scarpa fascia preservation has been suggested as a way of reducing complications associated with conventional abdominoplasty. A prospective randomized study was conducted to evaluate the effect on results and complications of preserving the Scarpa fascia during a full abdominoplasty. This was a single-center study conducted from August of 2009 to February of 2011. Patients were assigned randomly to one of two procedures: classic full abdominoplasty (group A) or a similar type of abdominoplasty except for the preservation of the Scarpa fascia and the deep fat compartment in the infraumbilical area (group B). Four surgeons were involved in the study. Several variables were determined: general characteristics, time to suction drain removal, total volume of drain output, length of hospital stay, systemic complications, local complications, and aesthetic result. A total of 160 full abdominoplasties were performed in women (group A, 80 patients; group B, 80 patients) equally divided by the four involved surgeons. There were no statistically significant differences between groups with respect to general characteristics, complications (except for the seroma rate), and aesthetic result. The Scarpa fascia preservation group had a highly significant reduction of 65.5 percent on the total drain output, 3 days on the time to drain removal, and 86.7 percent on the seroma rate. Preservation of the Scarpa fascia during an abdominoplasty had a beneficial effect on patient recovery, as it reduced the total drain output, time to drain removal, and seroma rate without compromising the aesthetic result.


Mechanical properties of the superficial biofilm layer determine the architecture of biofilms.
Cells in biofilms sense and interact with their environment through the extracellular matrix. The physicochemical properties of the matrix, particularly at the biofilm-environment interface, determine how cells respond to changing conditions. In this study we describe the application of atomic force microscopy and confocal imaging to probe in situ the mechanical properties of these interfacial regions and to elucidate how key matrix components can contribute to the physical sensing by the cells. We describe how the Young's modulus of microcolonies differs according to the size and morphology of microcolonies, as well as the flow rate. The Young's modulus increased as a function of microcolony diameter, which was correlated with the production of the polysaccharide Psl at later stages of maturation for hemispherical or mushroom shaped microcolonies. The Young's modulus of the periphery of the biofilm colony was however independent of the hydrodynamic shear. The morphology of the microcolonies also influenced interfacial or peripheral stiffness. Microcolonies with a diffuse morphology had a lower Young's modulus than isolated, circular ones and this phenomenon was due to a deficiency of Psl. In this way, changes in the specific polysaccharide components imbue the biofilm with distinct physical properties that may modulate the way in which bacteria perceive or respond to their environment. Further, the physical properties of the polysaccharides are closely linked to the specific architectures formed by the developing biofilm.


Effect of histamine H3 receptor blockade on venous return and splanchnic hemodynamics in experimental bacteremia.
In the heart, histamine H3 receptors may function as inhibitory presynaptic receptors that decrease adrenergic neural norepinephrine release in conditions of enhanced sympathetic tone. In a previous study, we found that H3 receptor blockade improved cardiac contractility and systemic hemodynamics in experimental bacteremia in dogs. Because histamine H3 receptors have been found in the splanchnic circulation in other animal models, it was not clear the extent to which H3 receptor blockade may have altered splanchnic hemodynamics, and variables of venous return, that in turn contributed to the overall improvement in systemic hemodynamics observed in the previous experiment. In the present study, we examined splanchnic hemodynamics in the presence of H3 receptor blockade in a canine model of Escherichia coli bacteremia. Bacteremia was produced by intravenous infusion of live E. coli administered throughout the experiment. Variables of venous return included mean systemic pressure, resistance to venous return, and mean right atrial pressure. Splanchnic measurements included hepatic and portal pressures and flows. Measurements were obtained before and after H3 receptor blockade with thioperamide maleate. The animals were studied while ventilated and anesthetized. H3 receptor blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect mean systemic pressure or resistance to venous return. There were no changes in portal or hepatic flows after H3 receptor blockade. The cardiac function curve after H3 receptor blockade was shifted upward and to the left compared with the pretreatment curve. The results showed that the primary effect of H3 receptor blockade in experimental bacteremia was attributable to an increase in inotropy. There was no evidence to indicate that H3 receptor activation contributed to altered splanchnic hemodynamics in this model.


Tetranuclear Manganese Models of the OEC Displaying Hydrogen Bonding Interactions: Application to Electrocatalytic Water Oxidation to Hydrogen Peroxide.
Toward the development of structural and functional models of the oxygen evolving complex (OEC) of photosystem II, we report the synthesis of site-differentiated tetranuclear manganese complexes featuring three six-coordinate and one five-coordinate Mn centers. To incorporate biologically relevant second coordination sphere interactions, substituents capable of hydrogen bonding are included as pyrazolates with arylamine substituents. Complexes with terminal anionic ligands, OH- or Cl-, bound to the lower coordinate metal center are supported through the hydrogen-bonding network in a fashion reminiscent of the enzymatic active site. The hydroxide complex was found to be a competent electrocatalyst for O-O bond formation, a key transformation pertinent to the OEC. In an acetonitrile-water mixture, at neutral pH, electrochemical water oxidation to hydrogen peroxide was observed, albeit with low (15%) Faradaic yield, likely due to competing reactions with organics. In agreement, 9,10-dihydroanthracene is electrochemically oxidized in the presence of this cluster both via H-atom abstraction and oxygenation with ∼50% combined Faradaic yield.


Development of a patient-reported outcome: the Neck OutcOme Score (NOOS)--Content and construct validity.
To develop a patient-reported outcome evaluating the impact of neck pain. The results of item generation and reduction and subscale structure in support of the content and construct validity of the measure are reported. Items were generated from the literature and through focus groups including patients with neck pain and healthcare professionals, respectively. Item reduction was based on focus groups and field-tested questionnaire data. Construct validity was assessed using exploratory factor analysis. Focus groups containing 24 patients (mean age 57.2 (standard deviation (SD) 15.9) years, range 24-85 years); 19 women) and 12 healthcare professionals were conducted before data saturation was achieved. A total of 196 patients with neck pain (mean age 47.8 (SD 13.7) years), range 18-89 years; 146 women) completed the preliminary questionnaire. Overall 35 items were removed from the original 69. A multidimensional questionnaire, divided into five subscales, was developed from the remaining 34 items: mobility; symptoms; sleep disturbance; everyday activity and pain; and participation in everyday life. Exploratory factor analysis supported a 5-subscale structure. The Neck OutcOme Score has excellent content validity and preliminary results support a 5-subscale structure. Additional work is needed to assess the reliability, further construct validity and responsiveness.


Neoplastic superior vena caval obstruction: diagnosis with percutaneous needle aspiration.
Obstruction of the superior vena cava arises from a spectrum of etiologies that include both benign and malignant conditions. Therefore, management of this serious disorder varies and depends on the underlying cause. Pursuit of a histologic diagnosis with invasive procedures has been associated with a wide range of diagnostic yields and complications. Percutaneous fine-needle aspiration biopsy has been shown to be highly reliable and well tolerated in the diagnosis of a variety of mediastinal and lung masses. Three patients are presented with obstruction of the superior vena cava in whom computed tomography safely guided percutaneous needle biopsy in obtaining a correct histologic diagnosis. It appears that transthoracic percutaneous needle aspiration biopsy is safe and efficacious in patients with superior vena cava syndrome, but further experience with this increasingly available procedure is warranted.


Further evidence for the reliability and validity of the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ).
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) was developed to assess clinically relevant cognitive and physical symptoms associated with depression that are not adequately assessed by traditional measures. Although the CPFQ has been shown previously to be a reliable and valid measure, the purpose of the present study was to provide additional evidence using larger samples from 4 independent clinical trials that were designed to test the efficacy and safety of different antidepressants. The psychometric analyses were based on data from 4 independent clinical trials that were designed to test the safety and efficacy of different antidepressants. Reliability of the items and of the overall questionnaire was evaluated with principal components analysis, whereas validity was assessed by associations of the questionnaire scores with convergent and divergent external criteria. Overall, the results have replicated previous findings that the CPFQ has good internal reliability. Validation also is strengthened by the demonstration of predictive differences among known groups as well as a sensitivity to change with antidepressant treatment. Results support the use of the CPFQ as a valuable instrument for the detection of clinically relevant symptoms that are not captured by typical measures of depression used for the assessment of treatment outcomes.


The Delphi technique: a worthwhile research approach for nursing?
Since its introduction as a research approach in the late 1940s the Delphi technique has had over 1000 published research utilizations. Most of these have been in the field of social policy. However, a review of contemporary nursing literature suggests that it is becoming a popular choice among nurse researchers. With its focus on maximizing participant's judgements and decision-making abilities the Delphi technique is a useful tool in the research armoury of a young profession. However, questions remain about its scientific respectability. This paper gives an overview of what the Delphi technique is, the criteria for selecting it as a research approach, the studies where it has been used and its advantages and disadvantages.


[Clinical and experimental studies on treatment of menopausal syndrome with geng nian shu].
370 cases of menopausal syndrome (MS)patients with the Syndrome Differentiation of "Excessive Fire in the Heart and Liver" were studied and divided into 4 groups randomly, 3 of them were treated with Geng-Nian-Shu(GNS) of different forms administered double-blindly with placebo. The effective rates of 3 therapeutic groups were 80.3-91.3% and the placebo group 48.6%, the difference was statistically significant. FSH, LH, E2, Te, ACTH, corticosteroid, CA, TSH, FT3, FT4, and beta-EP were assayed before and after treatment. The results were as follows:ACTH, FT3, FT4 lowered after treatment (P < 0.05, P < 0.05, P < 0.01) respectively, CA and corticosteroid in urine and beta-EP in plasma somewhat lowered (P < 0.05). Assays of the vegetative nerve balance factors (Y) showed that patients changed from the state of sympathetic hyperfunction to normal after treatment. No statistical difference of FSH, LH, E2, Te before and after treatment was observed. Animal experiment: mono-amino-neurotransmitter in hypothalamus, beta-EP in pituitary gland and blood plasma, plasma ACTH, cAMP and serum TSH, FT3, FT4, FSH, E2, Te of normal and ovariectomized white rats were studied, and the effect of GNS on these parameters were observed. In ovariectomized white rats: (1) The amount of NE in the hypothalamus increased, and NE, 5-HT, DA, plasma cAMP, ACTH, serum FT3, beta-EP in pituitary gland markedly lowered in the treatment group. The differences were statistically Significant (P < 0.05-0.001). (2) Serum TSH increased with no statistical difference, it was not lowered in the treatment group. (3) No significant difference for FT4, plasma beta-EP was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural studies on centromeres in the yeast Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae, circular or linear plasmids containing a functional centromere (CEN) and a chromosomal replicator (ARS) are mitotically stable and segregate as ordinary yeast chromosomes in the first and second meiotic divisions. A centromere in S. cerevisiae consists of a region of DNA, approximately 150 bp in length, containing three important sequence elements, which are folded with proteins into a specific conformation in the chromatin (the yeast kinetochore). Each of the functional CEN sequences contains a high (91% to 95%) AT region (element II), 78 to 86 bp in length, flanked on one side by the common sequence PuTCACPuTG (element I), and on the other by the sequence TGTTT.TG.TTTCCGAAA....AAA (element III). Deletions in the element II region partially inactivate mitotic function and cause precocious separation of the sister chromatids in meiosis I. Element III appears to be a protein binding site, as evidenced by the following observations. Various point mutations in element III inactivate centromere function, especially in the central CCG (17). One or more protein binding sites in the element III region can be demonstrated by an exonuclease III blocking assay. Wild-type CEN sequences compete strongly in this binding assay, whereas certain functionally inactive mutant CEN sequences do not. In addition, various DNA segments containing either CEN3 or the element III region strongly repress expression of the yeast GAL1 gene when inserted immediately upstream from the transcriptional start site. Helical DNA segments containing CEN3 or CEN14 are shown to be bent or distorted in shape in the high-AT element II region.


A Novel Riemannian Metric Based on Riemannian Structure and Scaling Information for Fixed Low-Rank Matrix Completion.
Riemannian optimization has been widely used to deal with the fixed low-rank matrix completion problem, and Riemannian metric is a crucial factor of obtaining the search direction in Riemannian optimization. This paper proposes a new Riemannian metric via simultaneously considering the Riemannian geometry structure and the scaling information, which is smoothly varying and invariant along the equivalence class. The proposed metric can make a tradeoff between the Riemannian geometry structure and the scaling information effectively. Essentially, it can be viewed as a generalization of some existing metrics. Based on the proposed Riemanian metric, we also design a Riemannian nonlinear conjugate gradient algorithm, which can efficiently solve the fixed low-rank matrix completion problem. By experimenting on the fixed low-rank matrix completion, collaborative filtering, and image and video recovery, it illustrates that the proposed method is superior to the state-of-the-art methods on the convergence efficiency and the numerical performance.


Bioelectric observations on adult and newborn hypothalamic dendrites.
Bioelectric activities of hypothalamic dendrites of newborn kittens and adult cats were recorded in vivo. Stimulation of various hypothalamic areas with electrical stimuli, or by injection of norepinephrine, generated propagated spikes in both newborn and adult neurons. The morphologically immature hypothalamic dendrites were hypersensitive to stimuli and were able to generate propagated spikes not only of axon hillock (adults) but also of dendritic membrane origin. Some mechanisms responsible for the two types of spike formation (newborn and adult) have been identified.


Attitudes regarding drug abuse among a group of ex-addict staff members.
Thirteen male and 11 female ex-addict staff members of a therapeutic community were surveyed to assess their attitudes on nine factors related to drug abuse and the drug abuser. Each factor was assessed according to the critieria established by Marcus. Both male and female groups held positive beliefs that psychological problems were contributing factors in the development of addiction. Among the remaining eight factors there was considerable variation in agreement regarding these male and female ex-addicts' attitudes toward drug abuse and the drug abuser.


Fluid-phase endocytosis in yeasts other than Saccharomyces cerevisiae.
A FITC-dextran internalization assay with Saccharomyces cerevisiae as positive control was used to determine whether fluid-phase endocytosis is a general characteristic of yeasts. Schizosaccharomyces pombe, Pichia polymorpha, Kluyveromyces phaseolosporus, Yarrowia lipolytica and Candida albicans were clearly positive, whereas results obtained with Debaryomyces marama were inconclusive. In all cases internalized FITC-dextran was found to be localized in the vacuoles and the process was always time- and temperature-dependent. Lower eucaryotes, particularly yeasts, appear to have the ability to incorporate substances from the extracellular medium through fluid-phase endocytosis.


Ionic Liquids Functionalized MOFs for Adsorption.
Metal-organic frameworks (MOFs) and ionic liquids (ILs) represent promising materials for adsorption separation. ILs incorporated into MOF materials (denoted as IL/MOF composites) have been developed, and IL/MOF composites combine the advantages of MOFs and ILs to achieve enhanced performance in the adsorption-based separation of fluid mixtures. The designed different ILs are introduced into the various MOFs to tailor their functional properties, which affect the optimal adsorptive separation performance. In this Perspective, the rational fabrication of IL/MOF composites is presented, and their functional properties are demonstrated. This paper provides a critical overview of an emergent class of materials termed IL/MOF composites as well as the recent advances in the applications of IL/MOF composites as adsorbents or membranes in fluid separation. Furthermore, the applications of IL/MOF in adsorptive gas separations (CO2 capture from flue gas, natural gas purification, separation of acetylene and ethylene, indoor pollutants removal) and liquid separations (separation of bioactive components, organic-contaminant removal, adsorptive desulfurization, radionuclide removal) are discussed. Finally, the existing challenges of IL/MOF are highlighted, and an appropriate design strategy direction for the effective exploration of new IL/MOF adsorptive materials is proposed.


Metabolomic analysis of the effects of polychlorinated biphenyls in nonalcoholic fatty liver disease.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants and have been associated with abnormal liver enzymes and suspected nonalcoholic fatty liver disease (NAFLD), obesity, and the metabolic syndrome in epidemiological studies. In epidemiological surveys of human PCB exposure, PCB 153 has the highest serum levels among PCB congeners. To determine the hepatic effects of PCB 153 in mice, C57BL/6J mice were fed either a control diet (CD) or a high fat diet (HFD) for 12 weeks, with or without PCB 153 coexposure. The metabolite extracts from mouse livers were analyzed using linear trap quadrupole-Fourier transform ion cyclotron resonance mass spectrometer (LTQ-FTICR MS) via direct infusion nanoelectrospray ionization (DI-nESI) mass spectrometry. The metabolomics analysis indicated no difference in the metabolic profile between mice fed the control diet with PCB 153 exposure (CD+PCB 153) and mice fed the control diet (CD) without PCB 153 exposure. However, compared with CD group, levels of 10 metabolites were increased and 15 metabolites were reduced in mice fed HFD. Moreover, compared to CD+PCB 153 group, the abundances of 6 metabolites were increased and 18 metabolites were decreased in the mice fed high fat diet with PCB 153 exposure (HFD+PCB 153). Compared with HFD group, the abundances of 2 metabolites were increased and of 12 metabolites were reduced in HFD+PCB 153 group. These observations agree with the histological results and indicate that the metabolic effects of PCB 153 were highly dependent on macronutrient interactions with HFD. Antioxidant depletion is likely to be an important consequence of this interaction, as this metabolic disturbance has previously been implicated in obesity and NAFLD.


Flexbar 3.0 - SIMD and multicore parallelization.
High-throughput sequencing machines can process many samples in a single run. For Illumina systems, sequencing reads are barcoded with an additional DNA tag that is contained in the respective sequencing adapters. The recognition of barcode and adapter sequences is hence commonly needed for the analysis of next-generation sequencing data. Flexbar performs demultiplexing based on barcodes and adapter trimming for such data. The massive amounts of data generated on modern sequencing machines demand that this preprocessing is done as efficiently as possible. We present Flexbar 3.0, the successor of the popular program Flexbar. It employs now twofold parallelism: multi-threading and additionally SIMD vectorization. Both types of parallelism are used to speed-up the computation of pair-wise sequence alignments, which are used for the detection of barcodes and adapters. Furthermore, new features were included to cover a wide range of applications. We evaluated the performance of Flexbar based on a simulated sequencing dataset. Our program outcompetes other tools in terms of speed and is among the best tools in the presented quality benchmark. https://github.com/seqan/flexbar. firstname.lastname@example.com or email@example.com.


Platelet-Derived Extracellular Vesicle Functionalization of Ti Implants.
Extracellular Vesicles (EVs) are biological nanovesicles that play a key role in cell communication. Their content includes active biomolecules such as proteins and nucleic acids, which present great potential in regenerative medicine. More recently, EVs derived from Platelet Lysate (PL) have shown an osteogenic capability comparable to PL. Besides, biomaterials are frequently used in orthopedics or dental restoration. Here, we provide a method to functionalize Ti surfaces with PL-derived EVs in order to improve their osteogenic properties. EVs are isolated from PL by size exclusion chromatography, and afterward Ti surfaces are functionalized with PL-EVs by drop casting. Functionalization is proven by EVs release and its biocompatibility by the lactate dehydrogenase (LDH) release assay.


Neuromusculoskeletal model that walks and runs across a speed range with a few motor control parameter changes based on the muscle synergy hypothesis.
Humans walk and run, as well as change their gait speed, through the control of their complicated and redundant musculoskeletal system. These gaits exhibit different locomotor behaviors, such as a double-stance phase in walking and flight phase in running. The complex and redundant nature of the musculoskeletal system and the wide variation in locomotion characteristics lead us to imagine that the motor control strategies for these gaits, which remain unclear, are extremely complex and differ from one another. It has been previously proposed that muscle activations may be generated by linearly combining a small set of basic pulses produced by central pattern generators (muscle synergy hypothesis). This control scheme is simple and thought to be shared between walking and running at different speeds. Demonstrating that this control scheme can generate walking and running and change the speed is critical, as bipedal locomotion is dynamically challenging. Here, we provide such a demonstration by using a motor control model with 69 parameters developed based on the muscle synergy hypothesis. Specifically, we show that it produces both walking and running of a human musculoskeletal model by changing only seven key motor control parameters. Furthermore, we show that the model can walk and run at different speeds by changing only the same seven parameters based on the desired speed. These findings will improve our understanding of human motor control in locomotion and provide guiding principles for the control design of wearable exoskeletons and prostheses.


Does bone morphogenetic protein change the operative nonunion rates in spine fusions?
A retrospective cohort study with medical record review. To determine if there is difference in the operative nonunion rates with and without the use of bone morphogenetic protein (BMP) after spinal fusions by analyzing data from an integrated health care system's spine registry. BMP was first approved in 2002 for use in single-level anterior lumbar fusions. Follow-up studies have advocated its use in reducing the need for reoperations for nonunions. Recent studies, however, have questioned these conclusions and the usefulness of BMP in spinal fusions has been highly debated. We identified 9425 spinal fusion cases between 2009 and 2011 from a spine registry in a large integrated health care organization. Patient characteristics, diagnosis, operative times, length of stay, and reoperations were extracted from the registry. Reoperations for nonunions were adjudicated via medical record review. Cox regression models were used to evaluate the risk of reoperation while adjusting for confounders. In our cohort, there were 5456 BMP cases and 3969 non-BMP cases. The mean age was 60.4 years (standard deviation: 12.9 yr), with the majority being females (53%). The median follow-up time was 1.2 years (interquartile range: 0.6-2.0 yr). Reoperation rates for BMP versus non-BMP nonunions for all fusion cases with follow-up of 1 year or more (1.9% vs. 2.2%) and follow-up of 2 years or more (2.3% vs. 2.6%) were not statistically significantly different. Operative nonunion rates did not reach statistical significance for different spine regions and for different fused columns (anterior only, posterior only, or combined). After controlling for differences in patient characteristics, operative times, levels fused, and spinal regions, the risk of reoperation in the BMP versus non-BMP groups was 0.67 (95% CI: 0.42-1.06). In this large cohort of spinal fusions at all spine regions involving all fused columns with and without BMP, we found no statistically significant difference in operative nonunion rates. 3.


Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro.
In the disorder leukocyte adhesion deficiency III (LAD-III), integrins on platelets and leukocytes are expressed but fail to function and this leads to severe bleeding and infections at an early age. Mutation in the KINDLIN3 (FERMT3) gene is the cause of LAD-III in patients from the Middle East, Malta, and Turkey. We describe 2 novel homozygous mutations in the KINDLIN3 gene of a new African-American patient that destabilize KINDLIN3 mRNA leading to loss of kindlin-3 protein. Transfection of wild-type (WT) KINDLIN3 cDNA restored integrin-related adhesion and migration in the LAD-III patient's T and B lymphocytes. We analyzed the individual mutations separately in vitro to learn more about the function of the kindlin-3 protein. The first G>A mutation gives rise to a Gly308Arg change at the end of FERM (protein 4.1, ezrin, radixin, moesin) subdomain 2, and the second mutation is a base deletion causing early termination within the pleckstrin homology (PH) domain. This second mutation prevented membrane association of kindlin-3 and did not restore either adhesion or migration, whereas the FERM subdomain 2 mutation affected only migration. Thus, these LAD-III patient mutations have highlighted functionally important regions of kindlin-3 that alter leukocyte integrin-dependent function in 2 distinct ways.


Nutrition and clinical manifestations of pulmonary tuberculosis: A cross-sectional study in Shandong province, China.
The aim is to investigate the association between nutritional status and clinical picture of pulmonary tuberculosis (PTB). A total of 613 pulmonary tuberculosis patients in Weifang city, Shandong province, China were included. Clinical and nutritional history, anthropometry, nutritionally relevant indicators including serum total protein and albumin, hemoglobin and lymphocyte count were measured. Adjustments were made for confounders in multivariable logistic models where tuberculosis activity (clinical symptoms and signs, sputum-smear tests or chest computerized tomography (CT)) was the dependent variable. Hypoalbuminemia (OR=2.61; 95% CI, 1.69-4.03), anemia (OR=1.62; 95% CI, 1.04-2.51) and lymphocytopenia (OR=1.92; 95% CI, 1.21-3.05) were associated with a higher TB score (a clinical severity measure for pulmonary tuberculosis based on typical signs and symptoms); hypoalbuminemia (OR=1.75; 95% CI, 1.08-2.84) and anemia (OR=1.87; 95% CI, 1.14-3.08) were associated with a positive sputum smear; anemia (OR=3.58; 95% CI, 1.85-6.94) was associated with cavitation in CT. Hypoalbuminemia, anemia and lymphocytopenia were positively associated with the severity of clinical manifestation of PTB. Nutritional status may be a marker for the severity of the clinical manifestations of PTB.


Absolute calibration of a soft X-ray spectrograph for X-ray laser research using white beam.
Absolute calibration of a soft X-ray spectrograph has been performed using a white beam of synchrotron radiation. The calibrated spectrograph was a flat-field grazing-incidence spectrograph with an X-ray CCD detector for X-ray laser research. Absolute sensitivity of the spectrograph system can be obtained from transmitted spectra using filters made of several different materials, each providing an absorption-edge wavelength standard. The absolute sensitivity determined in this work shows nearly the same behaviour with wavelength as that in another calibration experiment using a laser-produced plasma as an X-ray source.


The timeline and risk factors of clinical progression of COVID-19 in Shenzhen, China.
The novel coronavirus disease 2019 (COVID-19) broke out globally. Early prediction of the clinical progression was essential but still unclear. We aimed to evaluate the timeline of COVID-19 development and analyze risk factors of disease progression. In this retrospective study, we included 333 patients with laboratory-confirmed COVID-19 infection hospitalized in the Third People's Hospital of Shenzhen from 10 January to 10 February 2020. Epidemiological feature, clinical records, laboratory and radiology manifestations were collected and analyzed. 323 patients with mild-moderate symptoms on admission were observed to determine whether they exacerbated to severe-critically ill conditions (progressive group) or not (stable group). We used logistic regression to identify the risk factors associated with clinical progression. Of all the 333 patients, 70 (21.0%) patients progressed into severe-critically ill conditions during hospitalization and assigned to the progressive group, 253 (76.0%) patients belonged to the stable group, another 10 patients were severe before admission. we found that the clinical features of aged over 40 (3.80 [1.72, 8.52]), males (2.21 [1.20, 4.07]), with comorbidities (1.78 [1.13, 2.81]) certain exposure history (0.38 [0.20, 0.71]), abnormal radiology manifestations (3.56 [1.13, 11.40]), low level of T lymphocytes (0.99 [0.997, 0.999]), high level of NLR (0.99 [0.97, 1.01]), IL-6 (1.05 [1.03, 1.07]) and CRP (1.67 [1.12, 2.47]) were the risk factors of disease progression by logistic regression. The potential risk factors of males, older age, with comorbidities, low T lymphocyte level and high level of NLR, CRP, IL-6 can help to predict clinical progression of COVID-19 at an early stage.


Haemodilution with medium molecular weight hydroxyethyl starch in patients with peripheral arterial occlusive disease stage IIb.
The basic therapy of peripheral arterial occlusive disease stage IIb, according to Fontaine, is exercise. It should be determined whether a mild hypervolaemic haemodilution with hydroxyethyl starch or Ringer lactate can produce a further increase in walking distance. For this purpose, three groups of 25 patients each were formed. One group exercised three times weekly and the second group, in addition to exercise, underwent a mild hypervolaemic to isovolaemic dilution therapy with HES for a period of 6 weeks. In the final group the haematocrit was reduced to the same extent by venesections and volume substitution using Ringer lactate. The walking distance in the HES group increased from 216 m to 311 m (44%), in the Ringer lactate group from 214 m to 258 m (20%), and in the exercise group from 213 m to 242 m (14%). On comparison of the groups, the increase in pain-free walking distance in the HES group differs significantly (P less than 0.05) from that achieved in the other groups. It was demonstrated that haemodilution with HES in combination with exercise brings about a clinical effect three times that achieved by exercise alone. Venesection with subsequent administration of Ringer lactate and exercise is superior to exercise alone but markedly inferior to the combination therapy with HES.


Spontaneous transfection of mammalian cells with plasmid DNA.
A simple method for spontaneous transfection into mammalian cells (both adherent and suspension in culture) with plasmid DNA is described. This method does not require any specific DNA carrier or technical device and can be applied for obtaining both transient and stably transfected cells. The efficiency of spontaneous transfection is slightly lower in comparison with that of the conventional calcium phosphate and lipofectin transfection methods and does not depend on the type of cell culture used.


NanoSIMS: insights into the organization of the proteinaceous scaffold within Hexactinellid sponge spicules.
The giant basal spicules (GBS) from Monorhaphis chuni (Porifera [sponges], Hexactinellida) represent the largest biosilica structures on Earth and can reach lengths of 300 cm (diameter of 1.1 cm). The amorphous silica of the inorganic matrix is formed enzymatically by silicatein. During this process, the enzyme remains trapped inside the lamellar-organized spicules. In order to localize the organic silicatein scaffold, the inside of a lamella has been analyzed by nano-secondary ion mass spectrometry (NanoSIMS). It is shown that the GBSs are composed of around 245 concentrically arranged individual siliceous lamellae. These surround an internal siliceous axial cylinder. The lamellae adjacent to the cylinder are thicker (10-30 mum) than the more peripheral lamellae (2-10 microm). One lamella of a thickness of 18 mum has been selected for further analysis. This lamella itself is composed of three sublamellae with an individual thickness of 2-6 microm each, which are then further organized into three cylindrical slats (thickness: 1.6-1.8 microm). Other than the main lamellae, the sublamellae are not separated from each other by gaps. The element analysis of the sublamellae by NanoSIMS revealed that the siliceous matrix is embedded in an organic matrix that consists of up to 6-10 wt/% of C. The pattern of C distribution reflects a distinct zonation of the organic material within the solid intralamellar biosiliceous material. A growth model for the lamella starting from nanosized silica particles is proposed: During formation of a lamella nanosized silica particles fuse, through biosintering processes, to slats that build the individual sublamellae, which then finally form the lamellae. In turn, those lamellae may form the higher structural entity, the axial cylinder.


Impact of high atmospheric carbon dioxide on the biotic stress response of the model cereal species Brachypodium distachyon.
Losses due to disease and climate change are among the most important issues currently facing crop production. It is therefore important to establish the impact of climate change, and particularly of high carbon dioxide (hCO2), on plant immunity in cereals, which provide 60% of human calories. The aim of this study was to determine if hCO2 impacts Brachypodium distachyon immunity, a model plant for temperate cereals. Plants were grown in air (430 ppm CO2) and at two high CO2 conditions, one that is relevant to projections within the coming century (1000 ppm) and a concentration sufficient to saturate photosynthesis (3000 ppm). The following measurements were performed: phenotyping and growth, salicylic acid contents, pathogen resistance tests, and RNAseq analysis of the transcriptome. Improved shoot development was observed at both 1000 and 3000 ppm. A transcriptomic analysis pointed to an increase in primary metabolism capacity under hCO2. Alongside this effect, up-regulation of genes associated with secondary metabolism was also observed. This effect was especially evident for the terpenoid and phenylpropanoid pathways, and was accompanied by enhanced expression of immunity-related genes and accumulation of salicylic acid. Pathogen tests using the fungus Magnaporthe oryzae revealed that hCO2 had a complex effect, with enhanced susceptibility to infection but no increase in fungal development. The study reveals that immunity in B. distachyon is modulated by growth at hCO2 and allows identification of pathways that might play a role in this effect.


Chromosomal regions with quantitative trait loci controlling cadmium concentration in brown rice (Oryza sativa).
A novel mapping population consisting of 39 chromosome segment substitution lines (CSSLs) was used to locate the putative quantitative trait loci (QTLs) for cadmium (Cd) concentration in brown rice (Oryza sativa). The mapping population carried a single chromosome segment of 'Kasalath' (indica) in each line overlapping with neighbouring segments in a 'Koshihikari' (japonica) genetic background. The parents and CSSLs were grown in pots filled with Cd-polluted soil until grain filling. The brown rice of three of the 39 CSSLs had significantly lower Cd concentrations than that of Koshihikari, and the brown rice of a further three had significantly higher concentrations. On the basis of graphical genotypes of CSSLs, putative QTLs controlling the Cd concentration in brown rice were detected on chromosomes 3, 6 and 8. Each of the CSSLs was nearly isogenic to Koshihikari, which is the most popular rice cultivar in Japan: they carried > 90% of the Koshihikari genetic background. Therefore, the development of a new Koshihikari with less Cd concentration in brown rice would be feasible in the near future.


Mild Epicureanism: notes toward the definition of a therapeutic attitude.
Psychotherapists generally feel uncomfortable addressing patients' beliefs, particularly religious beliefs, because of the desire to respect client subjectivity and to avoid the abuse of therapeutic authority. This paper's first contention is that at some junctures, investigation of the client's belief structure can be an important catalyst for change, as exemplified by an extended case example. This stance assumes that much of the individual and collective damage rigid belief systems inflict derives from their function as a defense against death awareness, as described by terror management theory. The paper develops the concept of a therapeutic meta-attitude towards belief mild Epicureanism, related to the classical Greek philosopher Epicurus (341-270 BC). Mild Epicureanism means to soften attachments to all belief systems, even therapeutic theories, to lower their potential inhibition of personal growth. The paper presents the argument that mild Epicureanism is consistent with most therapeutic approaches, and allows addressing clients' belief without interfering with their right to make up their own minds.


Affective self-report during the intracarotid sodium amobarbital test.
Changes in internal affective state were investigated in patients undergoing the intracarotid sodium amobarbital test. It was found that when the left hemisphere was inactivated, patients rated their mood as significantly more negative than during baseline conditions. No significant change in affective state was observed during the inactivation of the right hemisphere. The findings are interpreted in terms of a differential lateralization model of emotion, in which the right hemisphere is more involved in the more powerful and salient negative affects.


Substances as Self-Treatment for Cognitive Test Anxiety among Undergraduate Students.
This research investigates associations between cognitive test anxiety (CTA) and use of alcohol, tobacco, cannabis, and medical and non-medical prescription stimulants (MNPS) among undergraduate students in Israel. A structured, self-report, anonymous questionnaire was distributed to 814 undergraduate students in Israel. According to the test anxiety questionnaire, 16.6% of participants were found to experience CTA. CTA was higher among users of MNPS than among students who did not use MNPS. Students with CTA were 2.21 times more likely to engage in use of MNPS than students who did not have CTA (OR 2.21, 95% CI: 1.50-3.26; P < 0.001). A significant association was found between CTA and use of MNPS among the entire sample and among non-medical use of prescription stimulants (NPS). In addition, a significant negative correlation was found between CTA and attitudes toward cannabis and MNPS, such that students with higher CTA had more positive attitudes towards MNPS. A logistic regression model was found to be significant, predicting about 24.7% of the variance in MNPS use. Counseling services for students should be focused on consulting and treatment programs for students with CTA. In addition, preventive educational programs should be formed to target substance habits, especially NPS use.