Alerting Reaction in Office Blood Pressure and Target Organ Damage: An Innocent Phenomenon?
An alerting reaction is a physician-induced phenomenon which produces a transient blood pressure rise in the office. To determine its relationship with target organ damage in treated hypertensives. We used three different indexes for calculating alerting reaction depending on the first, second or third office blood pressure measurement. We correlated these indexes with glomerular filtration rate, left ventricular mass index and pulse wave velocity. Thereafter, for multivariate analysis, we selected the index which better correlated with each target organ damage subtype. We included 174 adults, mean age 67(±13.7) years. 75% of the patients had some degree of blood pressure fall between measurements 1-3. In multivariate linear regression models, after adjusting for classic risk factors, two out of the three systolic alerting reaction indexes showed an independent association with target organ damage. After further adjusting for office blood pressure and white coat effect (calculated with standardized home blood pressure monitoring), left ventricular mass index maintained a statistically significant association. A higher alerting reaction in the office seems to be related to increased target organ damage in treated hypertensives and should not be considered an innocent phenomenon.


Identification of the extracellular matrix (ECM) binding motifs of tissue inhibitor of metalloproteinases (TIMP)-3 and effective transfer to TIMP-1.
Tissue inhibitor of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent endopeptidases of the matrix metalloproteinase families. There are four mammalian TIMPs (TIMP-1 to -4) but only TIMP-3 is sequestered to the extracellular matrix (ECM). The molecular basis for the TIMP-3:ECM association has never been fully investigated until now. In this report, we identify the unique amino acid configuration that constitutes the basis of the ECM binding motif in TIMP-3. By systematically exchanging the subdomains of the TIMPs and exhaustive mutation of TIMP-3, we have identified the surface residues directly responsible for ECM association. Contrary to the accepted view, we have found that TIMP-3 interacts with the ECM via both its N- and C-terminal domains. The amino acids involved in ECM binding are all basic in nature: Lys-26, Lys-27, Lys-30, Lys-76 of the N-terminal domain and Arg-163, Lys-165 of the C-terminal domain. Replacement of these residues with glutamate (E) and glutamine (Q) (K26/27/30/76E + R163/K165Q) resulted in a soluble TIMP-3 devoid of ECM-adhering ability. Using the ECM binding motif derived from TIMP-3, we have also created a TIMP-1 mutant (K26/27/30 + K76 transplant) capable of ECM association. This is the first instance of TIMPs being intentionally rendered soluble or ECM-bound. The ability to prepare TIMPs in soluble or ECM-bound forms also opens new avenues for future TIMP research.


Inferior vena cava filter ensnarement by central line guide wires--a report of 4 cases and brief review.
Ensnarement of inferior vena cava filters with central line guide wires is an infrequent complication that has been sporadically reported. The authors present 4 patients who experienced this complication. They review the literature, make recommendations to avoid this preventable complication, and recommend what to do once the complication occurs.


A System for Enzymatic Lysine Methylation in a Desired Sequence Context.
A number of lysine-specific methyltransferases (KMTs) are responsible for the post-translational modification of cellular proteins on lysine residues. Most KMTs typically recognize specific motifs in unstructured, short peptide sequences. However, we have recently discovered a novel KMT that appeared to have a more relaxed sequence specificity, namely, valosin-containing protein (VCP)-KMT, which trimethylates Lys-315 in the molecular chaperone VCP. On the basis of this, here, we explored the possibility of using the VCP-KMT/VCP system to obtain specific lysine methylation of desired sequences grafted onto a VCP-derived scaffold. We generated VCP-derived proteins in which three amino acid residues on each side of Lys-315 had been replaced by various sequences representing lysine methylation sites in histone H3. We found that all of these chimeric proteins were subject to efficient VCP-KMT-mediated methylation in vitro, and methylation was also observed in mammalian cells. Thus, we here describe a versatile system for introducing lysine methylation into a desired peptide sequence, and the approach should be readily expandable for generating combinatorial libraries of methylated sequences.


Exosome-Autophagy Crosstalk in Enveloped Virus Infection.
Exosomes, which are extracellular vesicles (EVs) predominantly present in bodily fluids, participate in various physiological processes. Autophagy, an intracellular degradation mechanism, eliminates proteins and damaged organelles by forming double-membrane autophagosomes. These autophagosomes subsequently merge with lysosomes for target degradation. The interaction between autophagy and endosomal/exosomal pathways can occur at different stages, exerting significant influences on normal physiology and human diseases. The interplay between exosomes and the autophagy pathway is intricate. Exosomes exhibit a cytoprotective role by inducing intracellular autophagy, while autophagy modulates the biogenesis and degradation of exosomes. Research indicates that exosomes and autophagy contribute to the infection process of numerous enveloped viruses. Enveloped viruses, comprising viral nucleic acid, proteins, or virions, can be encapsulated within exosomes and transferred between cells via exosomal transport. Consequently, exosomes play a crucial role in the infection of certain viral diseases. This review presents recent findings on the interplay between exosomes and autophagy, as well as their implications in the infection of enveloped viruses, thereby offering valuable insights into the pathogenesis and vaccine research of enveloped virus infection.


A peptide-gated ion channel from the freshwater polyp Hydra.
Chemical transmitters are either low molecular weight molecules or neuropeptides. As a general rule, neuropeptides activate only slow metabotropic receptors. To date, only one exception to this rule is known, the FMRFamide-activated Na(+) channel (FaNaC) from snails. Until now FaNaC has been regarded as a curiosity, and it was not known whether peptide-gated ionotropic receptors are also present in other animal groups. Nervous systems first evolved in cnidarians, which extensively use neuropeptides. Here we report cloning from the freshwater cnidarian Hydra of a novel ion channel (Hydra sodium channel, HyNaC) that is directly gated by the neuropeptides Hydra-RFamides I and II and is related to FaNaC. The cells expressing HyNaC localize to the base of the tentacles, adjacent to the neurons producing the Hydra-RFamides, suggesting that the peptides are the natural ligands for this channel. Our results suggest that neuropeptides were already used for fast transmission in ancient nervous systems.


Extensive gene flow in human populations as revealed by protein and microsatellite DNA markers.
Population genetic studies are mainly based on the description of genetic variability and on interpopulational comparisons using genetic distance measures. The evolutionary dynamics of the populations are inferred from these parameters and accurate estimates of gene flow may be critical. The present study reevaluates the role of gene flow in human populations by different statistical methods from a number of microsatellite and protein polymorphism data. The estimated number of individuals exchanged per generation (Nm) was greater than 1 in all data sets with all statistical methods. The correlation between geographic and genetic distances suggests a pattern of isolation by distance, characteristic of demographic and genetic equilibrium conditions among populations worldwide. Thus the high values of Nm may be interpreted as a reflection of high gene flow between geographically close populations. As expected, gene flow appears to exert a pivotal role in the genetic history of humans.


Orbital trauma: keep an eye for the details!
Orbital injuries are often missed out when they occur concomitantly with other facial bone fractures. Clinical examination and plain radiographic findings alone may prove inadequate in the detection of orbital floor fractures. Refined imaging techniques like CT scans and MRI are immensely helpful in the diagnosis of orbital blowout fractures. A case of 'impure' orbital blowout fracture which went undetected at the time of initial examination and its secondary surgical reconstruction is reported here. This case report emphasizes the importance of careful clinical and radiologic evaluation in orbital injuries.


Computerized static DNA ploidy analysis of prostatic intraepithelial neoplasia.
The microscopic features of prostatic intraepithelial neoplasia (PIN) are said to identify a precursor of prostatic adenocarcinoma (PC). We investigated this sequence of neoplastic progression by studying the relationship of PIN and PC by static ploidy analysis so that PIN and PC nuclei could be distinguished morphologically from each other and separately analyzed. From 51 archival cases of PC with coexistent high-grade PIN (PIN grades II and III) 50 control nuclei, 100 PIN nuclei, and 100 carcinoma nuclei per case were identified and digitized in corresponding Feulgen-stained slides. Control and PIN ploidy histograms fit a log-normal distribution, whereas malignant nuclei fit a rectangular distribution. When the histogram patterns were classified, the incidence of aneuploidy was 25% in PIN and 41% in PC. By case, the concordance of ploidy between PIN and PC was heterogeneous, yet the DNA ploidy of PIN and the corresponding PC was significantly associated. In four cases, PIN was DNA aneuploid while the associated PC was DNA diploid. These results support the hypothesis that high-grade PIN is a neoplastic precursor of prostatic adenocarcinoma and suggest that further karyotypic instability may result in invasive adenocarcinoma with different DNA content detectable by image analysis.


Hippocampal Atrophy Subtypes of Alzheimer's Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications.
One pathological hallmark of Alzheimer's disease (AD) is atrophy of medial temporal brain regions that can be visualized on magnetic resonance imaging (MRI), but not all patients will have atrophy. The aim was to use MRI to categorize patients according to their hippocampal atrophy status and to present prevalence of the subtypes, difference in clinical symptomatology and progression, and factors associated with hippocampal subtypes. We included 215 patients with AD who had been assessed with the clinically available MRI software NeuroQuant (NQ; CorTechs labs/University of California, San Diego, CA, USA). NQ measures the hippocampus volume and calculates a normative percentile. Atrophy was regarded to be present if the percentile was ≤5. Demographics, cognitive measurements, AD phenotypes, apolipoprotein E status, and results from cerebrospinal fluid and amyloid positron emission tomography analyses were included as explanatory variables of the hippocampal subtypes. Of all, 60% had no hippocampal atrophy. These patients were younger and less cognitively impaired concerning global measures, memory function, and abstraction but impaired concerning executive, visuospatial, and semantic fluency, and more of them had nonamnestic AD, compared to those with hippocampal atrophy. No difference in progression rate was observed between the two groups. In mild cognitive impairment patients, amyloid pathology was associated with the no hippocampal atrophy group. The results have clinical implications. Clinicians should be aware of the large proportion of AD patients presenting without atrophy of the hippocampus as measured with this clinical MRI method in the diagnostic set up and that nonamnestic phenotypes are more common in this group as compared to those with atrophy. Furthermore, the findings are relevant in clinical trials.


Neonatal prophylaxis with antibiotic containing ointments does not reduce incidence of chlamydial conjunctivitis in newborns.
Neonatal ocular prophylaxis with silver nitrate does not prevent neonatal conjunctivitis due to Chlamydia trachomatis. The efficacy of antibiotic containing preparations for prevention of neonatal chlamydial conjunctivitis (NCC) has not been established. To examine published literature to determine whether antibiotic containing preparation are efficacious for prevention of NCC and C. trachomatis in the nasopharynx. A literature search of MEDLINE and EMBASE. Articles were selected for review if their content included 4 key criteria: (1) Prospective/comparative study. (2) Prenatal screening of mothers for C. trachomatis with results reported. (3) Follow-up of infants born to chlamydia-positive women. (4) Infants prospectively followed at regular intervals and tested for C. trachomatis in the eye/ nasopharynx (NP). The search yielded 159 studies; 11 were selected for full reviews, eight were excluded; three addressed the four criteria. Rates of C. trachomatis conjunctivitis in infants in included studies who received silver nitrate was 20-33%; positive NP, 1-28% and pneumonia, 3-8%. Rates of C. trachomatis conjunctivitis in neonates who received erythromycin or tetracycline prophylaxis did not differ from silver nitrate; 0-15 and 11%, respectively, who received erythromycin or tetracycline developed NCC. Similarly, 4-33 and 5% of infants who received erythromycin or tetracycline, respectively, had positive NP cultures; 0-4% developed chlamydial pneumonia. Neonatal ocular prophylaxis with erythromycin or tetracycline ophthalmic ointments does not reduce incidence of neonatal chlamydial conjunctivitis or respiratory infection in infants born to mothers with C. trachomatis infection compared to silver nitrate.


Impact of sunitinib on human thyroid cancer cells.
Thyroid cancer accounts for about 1% of all cancer cases. Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid cancer therapy. Therefore, the principal aim of this study was to investigate the impact of sunitinib on the secretion of cytokines of follicular thyroid cancer cells. The effects of irradiation (R), S, and their combination (R+S) on cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were evaluated after two (d2) and four days (d4) of treatment. Multi-Analyte Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN-γ, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-α and TNF-β; ML-1: IFN-γ, IL-4, IL-6, IL-7, IL-8; MIP-1α, MMP-2, MCP-1, TNF-α and TNF-β). R elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2; CGTH W-1: IL-4, TNF-β). In contrast, R+S treatment resulted in a reduction of IFN-γ, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD mRNAs were significantly elevated by R+S. A target-based therapy with R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-α as interesting biomarkers to be investigated in vivo. Different reactions of the cell lines under equal treatment might be due to their different origin and characteristics.


Electrically driven kinklike distorting waves in microsized liquid crystals.
Electrically driven kinklike distortion regimes in a microsized liquid crystal channel have been investigated both experimentally and analytically. Kinklike distortion waves were excited by the interaction between the electric field E and the gradient ∇n[over ̂] of the director field in a homogeneously aligned liquid crystal (HALC) channel. Having obtained the evolution of the normalized light intensity, which was recorded by the high-speed camera, the process of excitation and evolution of the traveling wave in the HALC channel was visualized for the first time. It was shown, based on a nonlinear extension of the classical Ericksen-Leslie theory, that in the case when the electric field E≫E_{th}, the flow of liquid crystal material completely stops and a new mechanism for converting the electric field arises in the form of the electrically driven distorting traveling kinklike wave, which can be excited in the LC channel, composed of 4-n-pentyl-4^{'}-cyanobiphenyl molecules.


Nutrient homeostasis: long-term interrelations between pancreatic hormones, blood glucose and dietary wheat bran in men.
Postprandial plasma somatostatin (SLI), pancreatic glucagon, insulin (IRI) and blood glucose (BG) were measured at 0, 30, 60, 120 and 180 min after a test meal in 10 healthy men before and after 1, 3 and 7 wk of ingestion of a balanced diet supplemented daily with 20 g wheat bran. BG response to the test meal was significantly and consistently lower after the first week of consuming bran, with a maximum drop after 3 wk. After 1 wk of bran, when compared with the prebran values, SLI secretion was decreased, and glucagon response was significantly enhanced at 120 and 180 min after the meal. IRI secretion did not change significantly until the third week. After consuming bran for 7 wk, postprandial SLI concentrations returned to prebran values, and glucagon levels were not significantly different from those of the first meal. IRI during the fourth test meal (after 7 wk of bran consumption) was significantly higher than after the third meal (after 3 wk of bran ingestion), at 60 min and at 120 min. BG levels remained low. Chronic bran ingestion was therefore associated with an improved glucose tolerance. Its effects on pancreatic hormones varied with time for each hormone, and somatostatin was the only one to return to the prebran values.


Friends or foes? A compatibility assessment of bioeconomy-related Sustainable Development Goals for European policy coherence.
In October 2018, the European Union (EU) launched an updated bioeconomy strategy with the aim of encouraging the substitution of fossil carbon with biomass feedstock in the industry and in energy production while preserving ecosystem services. The objective of the paper is to analyse the links between the EU bioeconomy strategy and the Sustainable Development Goals (SDGs), and to assess what could be the main points of synergies and tensions between bioeconomy-related SDG targets. By semantically mapping the action plan of the 2018 EU bioeconomy strategy with the SDG targets, the paper finds that the bioeconomy strategy is aligned with 53 targets distributed in 12 of the 17 SDGs. Ex-post correlation analysis on bioeconomy-related SDGs indicators for 28 EU Member States (1990-2018) shows a predominance of synergies over trade-offs. More intense synergetic past developments (positive correlations) are found among clean energies (SDG 7), recycling (SDG 11), ecosystem preservation (SDG 15) and most of all other bioeconomy-related SDGs. Negative correlations are observed between agro-biodiversity (SDG 2), domestic material consumption of biomass (SDG 8 and 12), agriculture and industrial developments (SDG 2 and SDG 9) and a wide array of bioeconomy-related SDG indicators. The hotspots of strong correlations identified might be useful in further enrichment of ex-ante simulation models. From a policy coherence perspective, a wide range of policy instruments are already in place in the EU to foster synergies and may bring co-benefits. Policies oriented at preventing trade-offs are already in place but they have not overcome the antagonisms observed in this study yet. Change in practices, technical and technological innovations and the application of circular and 'cascading principles' are the most common fields of action.


Early childhood development: an imperative for action and measurement at scale.
Experiences during early childhood shape biological and psychological structures and functions in ways that affect health, well-being and productivity throughout the life course. The science of early childhood and its long-term consequences have generated political momentum to improve early childhood development and elevated action to country, regional and global levels. These advances have made it urgent that a framework, measurement tools and indicators to monitor progress globally and in countries are developed and sustained. We review progress in three areas of measurement contributing to these goals: the development of an index to allow country comparisons of young children's development that can easily be incorporated into ongoing national surveys; improvements in population-level assessments of young children at risk of poor early development; and the production of country profiles of determinants, drivers and coverage for early childhood development and services using currently available data in 91 countries. While advances in these three areas are encouraging, more investment is needed to standardise measurement tools, regularly collect country data at the population level, and improve country capacity to collect, interpret and use data relevant to monitoring progress in early childhood development.


Activation of Sirt1/FXR Signaling Pathway Attenuates Triptolide-Induced Hepatotoxicity in Rats.
Triptolide (TP), a diterpenoid isolated from Tripterygium wilfordii Hook F, has an excellent pharmacological profile of immunosuppression and anti-tumor activities, but its clinical applications are severely restricted due to its severe and cumulative toxicities. The farnesoid X receptor (FXR) is the master bile acid nuclear receptor and plays an important role in maintaining hepatic metabolism homeostasis. Hepatic Sirtuin (Sirt1) is a key regulator of the FXR signaling pathway and hepatic metabolism homeostasis. The aims of this study were to determine whether Sirt1/FXR signaling pathway plays a critical role in TP-induced hepatotoxicity. Our study revealed that the intragastric administration of TP (400 μg/kg body weight) for 28 consecutive days increased bile acid accumulation, suppressed hepatic gluconeogenesis in rats. The expression of bile acid transporter BSEP was significantly reduced and cholesterol 7α-hydroxylase (CYP7A1) was markedly increased in the TP-treated group, whereas the genes responsible for hepatic gluconeogenesis were suppressed in the TP-treated group. TP also modulated the FXR and Sirt1 by decreasing its expression both in vitro and in vivo. The Sirt1 agonist SRT1720 and the FXR agonist obeticholic acid (OCA) were used both in vivo and in vitro. The remarkable liver damage induced by TP was attenuated by treatment with either SRT1720 or OCA, as reflected by decreased levels of serum total bile acids and alkaline phosphatase and increased glucose levels. Meanwhile, SRT1720 significantly alleviated TP-induced FXR suppression and FXR-targets involved in hepatic lipid and glucose metabolism. Based on these results, we conclude that Sirt1/FXR inactivation plays a critical role in TP-induced hepatotoxicity. Moreover, Sirt1/FXR axis represents a novel therapeutic target that could potentially ameliorate TP-induced hepatotoxicity.


[Expression and significance of neutrophil surface adhesion molecules in renal transplant recipients with cytomegalovirus infection].
To study the expression and its diagnostic significance of neutrophil surface adhesion molecules including CD11b, CD15 and CD62L after renal transplantation in recipients with cytomegalovirus (CMV) infection. Blood samples were collected from 142 kidney transplant recipients, including 95 males and 47 females, who received allogeneic renal transplantation between September 2009 and January 2015 in 309th Hospital of the PLA. Healthy volunteers (22 males and 9 females) were recruited from physical examination center in 309th Hospital of the PLA from September 2009 to January 2015 as healthy control group. Renal transplant recipients were divided into high active CMV infection group, active CMV infection group and CMV negative control group according to CMV-pp65 antigen detection. Neutrophil surface adhesion molecules CD11b, CD15 and CD62L were detected by flow cytometry and their mean fluorescence intensity compared among the groups. Receiver operating characteristic (ROC) curves of CD11b, CD15 and CD62L in detecting active infection in renal transplant recipients were made. The mean fluorescence intensity of CD15 in high active CMV infection group(n=17) and active CMV infection group(n=65)were 776.31±89.53 and 554.39±67.89, respectively, with significant differences compared with CMV negative control group (n=60, 334.92±44.69) and healthy control group (n=31, 310.56±39.67) (all P<0.05); the expression proportions of CD11b and CD62L in high active CMV infection group and were 42.31%±6.11% and 40.35%±6.47%, respectively, with significant differences compared with active CMV infection group(62.45%±5.67% and 65.65%±5.33%), CMV negative control group(70.74%±6.55% and 70.37%±6.71%) and healthy control group(72.52%±6.48% and 72.43%±6.51%) (all P<0.05). The optimal cut-off values of CD11b and CD62L in diagnosing active CMV infection group were 56.61% and 44.35%, respectively, with the sensitivity being both 100.00%, the specificity being 76.67% and 58.06% respectively, and the area under the curve (AUC) being 0.851 and 0.628 respectively; the optimal cut-off values of CD11b and CD62L in diagnosing high active CMV infection group were 66.57% and 69.56% respectively, with the sensitivity being 81.54% and 87.69% respectively, the specificity being 100.00% and 98.33% respectively, and the AUC being 1.000 and 0.991 respectively; the optimal cut-off values of mean fluorescence intensity of CD15 in diagnosing high active CMV infection group and active CMV infection group were 542.71 and 408.03 respectively, the sensitivity in the two groups being 100.00% and 98.46% respectively, the specificity being both 100.00%, and the AUC being 1.000 and 0.999 respectively. Neutrophils CD15 expression may be up-regulated in renal transplantation recipients with CMV infection, while neutrophils CD11b and CD62L expressions are down-regulated. Such changes in CD15, CD11b and CD62L expression can be used as a basis for laboratory diagnosis of active CMV infection.


How do enzyme activities control metabolite concentrations? An additional theorem in the theory of metabolic control.
A simple theorem is derived relating the extent to which enzymes in a metabolic pathway control the steady-state concentration of metabolites to the kinetic properties of those enzymes. The theorem gives insight into the mechanism by which the concentration of a second messenger is controlled by the enzymes that form and degrade it, and provides an alternative to the 'cross-over theorem'.


Reverse remodeling in a heart failure patient with cardiomegaly treated with sacubitril/valsartan: a case report.
Sacubitril/valsartan (S/V) has shown promise as a tool for decreasing cardiovascular hospitalization and associated mortality among certain patients with heart failure and has been found to exhibit potential renoprotective and antiarrhythmic activity. This report is describing the case of a patient that suffered acute myocardial infarction within one month after undergoing percutaneous coronary intervention (PCI) stent implantation and who underwent standard guideline-directed medical treatment. Upon readmission, echocardiographic evaluation revealed enlargement of the left heart and reduced ejection fraction. While hospitalized, treatment with S/V was begun. Following sustained treatment with this drug for five months, the patient exhibited vascular remodeling, a 30% injection fraction improvement, a 15 mm reduction in left ventricular diastolic diameter, and a significant change in functional class from class III to I. Overall, this case report emphasizes the association between S/V treatment and reverse ventricular remodeling in a patient that experienced cardiomegaly following AMI.


[Factors of antioxidant and prooxidant activities of carotenoids].
The effectiveness of carotenoids as antioxidants is dependent on a number of influencing factors. It is likely that carotenoids exhibit a tendency to lose their effectiveness as antioxidants or act as prooxidants. In this paper, factors influencing the antioxidant or prooxidant activities of carotenoids such as the molecule structure of carotenoids, the location or site of action of the carotenoid molecule within the cell, the concentration of carotenoids, the properties of reactants, the partial pressure of oxygen and the interaction with other antioxidants were reviewed.


Self-Assembled Nanostructures of Homo-Oligopeptide as a Potent Ice Growth Inhibitor.
This study reports the formation of self-assembled nanostructures with homo-oligopeptides consisting of amino acids (i.e., alanine, threonine, valine, and tyrosine), the resulting morphologies (i.e., spherical shape, layered structure, and wire structure) in aqueous solution, and their potential as ice growth inhibitors. Among the homo-oligopeptides investigated, an alanine homo-oligopeptide (n = 5) with a spherical nanostructure showed the highest ice recrystallization inhibition (IRI) activity without showing a burst ice growth property and with low ice nucleation activity. The presence of nanoscale self-assembled structures in the solution showed superior IRI activity compared to an amino acid monomer because of the higher binding affinity of structures on the growing ice crystal plane. Simulation results revealed that the presence of nanostructures induced a significant inhibition of ice growth and increased lifetime of hydrogen bonding compared with unassembled homo-oligopeptide. These results envision extraordinary performance for self-assembled nanostructures as a desirable and potent ice growth inhibitor.


Advancing the Precision Medicine Initiative.
The NIH has approved the framework to build a national research cohort of 1 million Americans, a key part of President Obama's Precision Medicine Initiative.


Diagnostic labelling as determinant of antibiotic prescribing for acute respiratory tract episodes in general practice.
Next to other GP characteristics, diagnostic labelling (the proportion of acute respiratory tract (RT) episodes to be labelled as infections) probably contributes to a higher volume of antibiotic prescriptions for acute RT episodes. However, it is unknown whether there is an independent association between diagnostic labelling and the volume of prescribed antibiotics, or whether diagnostic labelling is associated with the number of presented acute RT episodes and consequently with the number of antibiotics prescribed per patient per year. Data were used from the Second Dutch National Survey of General Practice (DNSGP-2) with 163 GPs from 85 Dutch practices, serving a population of 359,625 patients. Data over a 12 month period were analysed by means of multiple linear regression analysis. Main outcome measure was the volume of antibiotic prescriptions for acute RT episodes per 1,000 patients. The incidence was 236.9 acute RT episodes/1,000 patients. GPs labelled about 70% of acute RT episodes as infections, and antibiotics were prescribed in 41% of all acute RT episodes. A higher incidence of acute RT episodes (beta 0.67), a stronger inclination to label episodes as infections (beta 0.24), a stronger endorsement of the need of antibiotics in case of white spots in the throat (beta 0.11) and being male (beta 0.11) were independent determinants of the prescribed volume of antibiotics for acute RT episodes, whereas diagnostic labelling was not correlated with the incidence of acute RT episodes. Diagnostic labelling is a relevant factor in GPs' antibiotic prescribing independent from the incidence of acute RT episodes. Therefore, quality assurance programs and postgraduate courses should emphasise to use evidence based prognostic criteria (e.g. chronic respiratory co-morbidity and old age) as an indication to prescribe antibiotics in stead of single inflammation signs or diagnostic labels.


Bringing mind-body medicine into the mainstream.
Centuries-old concepts concerning the mind's influence on the body are being examined with renewed interest. As awareness of the health benefits of being able to voluntarily control vital aspects of the metabolic state increases, and as our understanding of the underlying molecular mechanisms of such control also increases, mind-body medicine may move further into the mainstream of Western medical practices.


Trypanosoma brucei growth control by TNF in mammalian host is independent of the soluble form of the cytokine.
Infection of C57Bl/6 mice by pleomorphic African trypanosomes Trypanosoma brucei and T. congolense is characterized by parasitemia waves coupled with the production of systemic levels of TNF. This cytokine is known to control T. brucei growth, but also to contribute to tissue damage, shortening the survival time of infected mice. Using a dominant-negative version of TNF to discriminate between the effects of the membrane-form versus the soluble form of TNF, we show that the second form is involved in neither parasite control nor induction of liver injury. Therefore, soluble TNF is likely not a major contributor to disease outcome. We propose that membrane-bound TNF is responsible for both T. brucei control and host pathology.


Studies on satellite nucleoli in human blastic cells of acute leukaemias.
Blastic cells of acute lymphoid, acute myeloid and acute myelomonocytic leukaemias were studied by means of indirect immunofluorencence to provide more information on the presence of satellite nucleoli in blood cells. According to results, satellite nucleoli were found in a small but constant number of blastic cells disregarding their type and type of acute leukaemia. Satellite nucleoli exhibited a positive immunoreaction for fibrillarin and protein B23 which are characteristic for main nucleolar components. These findings suggest that satellite nucleoli contain fibrillar centers as well as dense fibrillar and granular components or at least proteins characteristic for these nucleolar components. Similarly as in normal and pathological cells of completely different origin, in blastic cells of acute leukaemias the number of satellite nucleoli per cells ranged between 1 and 2.


RBF network-based adaptive sliding mode control strategy for the tendon-sheath driven joint of a prosthetic hand.
The complex in-hand manipulation puts forward higher requirements for the dexterity and joint control accuracy of the prosthetic hand. The tendon-sheath drive has important application potential in the fields of prosthetic hand to obtain higher dexterity. However, the existing control methods of tendon-sheath driven joint are mainly open-loop compensation based on friction model, which makes it difficult to achieve high-precision joint control. The purpose of this work is to improve the position control accuracy of the tendon-sheath driven joint for the prosthetic hand. The structure of the prosthetic hand is introduced, and the encoder and potentiometer are mounted on the driving motor and joint respectively. Then, the transfer function of the joint is established based on the dynamic model. The adaptive sliding mode control strategy based on RBF network is applied to realize the closed-loop feedback position control of the prosthetic hand joint. The stability of the system is demonstrated by Lyapunov theorem. Under the condition of constant and variable sheath curvature, the effectiveness of the controller is demonstrated by simulation and joint motion experiments, respectively. The results show that the closed-loop control has better position tracking ability than the open-loop control, and the designed controller can reduce the tracking error more obviously than the traditional algorithm. The high-precision position control can be realized by designing the controller based on the joint angle feedback. The research content has certain theoretical and practical significance for the development of joint high-precision control of tendon-sheath driven prosthetic hand. This is beneficial to the implementation of complex in-hand manipulation for prosthetic hand.


Prophylaxis against Pneumocystis pneumonia in patients with inflammatory bowel disease: toward a standard of care.
Patients with Crohn's Disease and ulcerative colitis are increasingly treated with a host of immunomodulatory and immunosuppressive medications, including thiopurines and antibody-based biologic agents. Despite the known infectious complications associated with these therapies from the HIV and solid organ transplant literature, there are currently no well-defined concise guidelines to assist gastroenterologists and other physicians in the utility and indication for prophylaxis against Pneumocystis pneumonia and other infections in inflammatory bowel disease (IBD) patients. In this article, we discuss the evidence of various infections associated with immunocompromise in HIV/AIDS, organ transplantation, and in other immunocompromised states, and discuss the evidence for the efficacy and safety of various infectious prophylaxis protocols. In addition, we discuss the evidence for Pneumocystis and other infections in IBD patients treated with corticosteroids, azathioprine/6-MP, biologic agents and other therapies, and we present the case for various antibiotic (and antiviral) regimens to prevent such infections. Based on the review of the literature, this discussion represents a true call for guidelines for infection prophylaxis, to help guide gastroenterologists and all practitioners who care for the challenging population of IBD patients.


Measurement of absolute transition dipole moment functions of the 3 (1)Pi --> 1(X) (1)Sigma+ and 3 (1)Pi --> 2(A) (1)Sigma+ transitions in NaK using Autler-Townes spectroscopy and calibrated fluorescence.
We describe a two-laser experiment using optical-optical double resonance fluorescence and Autler-Townes (AT) splittings to determine the NaK 3 (1)Pi-->1(X)(1)Sigma(+), 2(A)(1)Sigma(+) absolute transition dipole moment functions. Resolved 3 (1)Pi-->A (1)Sigma(+) and 3 (1)Pi-->X (1)Sigma(+) fluorescence was recorded with the frequencies of a titanium-sapphire laser (L1) and a ring dye laser (L2) fixed to excite particular 3 (1)Pi(upsilon = 19,J = 11,f)<--A (1)Sigma(+)(upsilon('),J(') = J = 11,e)<--X (1)Sigma(+)(upsilon("),J(") = J(')+/-1,e) double resonance transitions. The coefficients of a trial transition dipole moment function mu(e)(R) = a(0)+a(1)(R(eq)/R)(2)+a(2)(R(eq)/R)(4)+... were adjusted to match the relative intensities of resolved spectral lines terminating on the lower A (1)Sigma(+)(upsilon('),11,e) and X (1)Sigma(+)(upsilon("),11,e) levels. These data provide a relative measure of the functions mu(e)(R) over a broad range of R. Next, L2 was tuned to either the 3 (1)Pi(19,11,f)<--A (1)Sigma(+)(10,11,e) or 3 (1)Pi(19,11,f)<--A (1)Sigma(+)(9,11,e) transition and focused to an intensity large enough to split the levels via the AT effect. L1 was scanned over the A (1)Sigma(+)(10,11,e)<--X (1)Sigma(+)(1,10,e) or A (1)Sigma(+)(9,11,e)<--X (1)Sigma(+)(0,12,e) transition to probe the AT line shape, which was fit using density matrix equations to yield an absolute value for mu(ik) = integral psi(vib) (i)(R)mu(e)(R)psi(vib)(k)(R)dR, where i and k represent the upper and lower levels, respectively, of the coupling laser (L2) transition. Finally, the values of mu(ik) were used to place the relative mu(e)(R) functions obtained with resolved fluorescence onto an absolute scale. We compare our experimental transition dipole moment functions to the theoretical work of Magnier et al. [J. Mol. Spectrosc. 200, 96 (2000)].


Earthworm diversity in Rio Grande do Sul, Brazil.
The knowledge regarding earthworm species richness in subtropical Brazil is limited, particularly in the state of Rio Grande do Sul (RS), where only a few sites have been sampled. In this study we assessed earthworm richness in different ecosystems of RS, prioritizing un-sampled regions. Fifteen ecosystems, including native vegetation and other ecosystems with variable levels of disturbance were sampled in 30 counties in RS, totaling 77 sampling points, mainly in the Pampa biome. Qualitative sampling was performed by handsorting soil monoliths and fixing the earthworms in 4% formalin solution. Species identification was based on morphological characters, and species richness and Shannon (H) and McIntosh (U) diversity indices were calculated for each ecosystem. Twenty-one earthworm species were identified, belonging to seven families: Glossoscolecidae (8), Rhinodrilidae (2), Ocnerodrilidae (4), Megascolecidae (4), Acanthodrilidae (1), Lumbricidae (1) and Criodrilidae (1). From these, ten are new species belonging to the genera: Glossoscolex (6), Fimoscolex (1), Kerriona (1), Eukerria (1), and one aquatic species of the Criodrilidae family, belonging to a new genus. Most of the native species (Urobenus brasiliensis, Fimoscolex n.sp.1 and the Glossoscolex spp.) predominated in ecosystems little altered by human activity, while exotic (Amynthas gracilis, Amynthas rodericensis, Metaphire californica, Aporrectodea trapezoides) and peregrine species (Pontoscolex corethrurus) predominated in areas with more human disturbance. Native ecosystems with lower disturbance, particularly forests and native pastures had higher diversity than disturbed sites. This is the first record of A. rodericencis for Brazil and most sites represent new collection records for the known species in RS.


Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: Another Provisional Entity Emerging From the Papillary Renal Cell Carcinoma Pandora's Box.
Papillary renal cell carcinoma (especially type 2) is a Pandora's box with many newly described renal cell carcinomas emerging from it as a result of enhanced molecular techniques. Biphasic hyalinizing psammomatous renal cell carcinoma (BHPRCC) is the latest addition, which was first described a few months ago. Here, we report a case of BHPRCC to supplement the very limited literature available about this entity, and to highlight the characteristic morphology as well as the recurring molecular alterations in the neurofibromatosis 2 gene.


EU nurse figures in decline long before Brexit vote.
The falling number of European Union (EU) nurses applying to work in the UK has been widely blamed on Brexit. But figures obtained by Nursing Standard reveal interest from EU nurses was waning months before the June 2016 referendum, a trend experts say could be due to tougher language requirements introduced by the Nursing and Midwifery Council (NMC).


Prostaglandin-induced diarrhoea.
A child with chronic diarrhoea since birth responded to the prostaglandin synthetase inhibitors aspirin and indomethacin. During a period without treatment, raised levels of prostaglandins F2alpha and E2 were observed. No source for these raised prostaglandins was shown, and it is suggested that she may have an inborn defect of prostaglandin metabolism.


Alkyne-Functionalized Coumarin Compound for Analytic and Preparative 4-Thiouridine Labeling.
Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on post-transcriptional modification. This work focuses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA and is used as a metabolic label and for cross-linking purposes in eukaryotic RNA. A newly designed coumarin compound named 4-bromomethyl-7-propargyloxycoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via "click chemistry", thereby offering a wide range of preparative and analytical options. We applied PBC to quantitatively monitor the metabolic incorporation of s4U as a label into RNA and for site-specific introduction of a fluorophore into bacterial tRNA at position 8, allowing the determination of its binding constant to an RNA-modification enzyme.


Prediction of key milk biomarkers in dairy cows through milk MIR spectra and international collaborations.
At the individual cow level, sub-optimum fertility, mastitis, negative energy balance and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were: 1) to assess the potential of milk Mid Infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6P, free glucose), ketosis (BHB and acetone), mastitis (NAGase and LDH), and fertility (progesterone); 2) to test alternative methodologies to partial least square regression (PLS) to better account for the specific asymmetric distribution of the biomarkers; and 3) to create robust models by merging large data sets from 5 international or national projects. Benefiting from this international collaboration, the data set comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents while the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. PLS was used as the reference basis, and compared with a random modification of distribution associated with PLS (Random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS) and Support Vector Machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low vs high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation data set. The remaining 80% of herds were used as the calibration data set. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS provided the best results for isocitrate, glucose-6P, free glucose and LDH (R2v = 0.48, 0.58, 0.28, and 0.24). For other molecules, PLS-Random-downsampling and PLS-KennardStone-downsampling outperformed PLS in the majority of cases, but the best results were provided by SVM for citrate, BHB, acetone, NAGase and progesterone (R2v = 0.94, 0.58, 0.76, 0.68, and 0.15). Hence, PLS and SVM based on the entire data set provided the best results for normal and skewed distributions, respectively. Complementary to the quantitative methods, the qualitative discriminant models enabled the discrimination of high and low values for BHB, acetone, and NAGase with a global accuracy around 90%, and glucose-6P with an accuracy of 83%. In conclusion, MIR spectra of milk can enable quantitative screening of citrate as a biomarker of energy deficit and discrimination of low and high values of BHB, acetone, and NAGase, as biomarkers of ketosis and mastitis. Finally, progesterone could not be predicted with sufficient accuracy from milk MIR spectra to be further considered. Consequently, MIR spectrometry can bring valuable information regarding the occurrence of energy deficit, ketosis and mastitis in dairy cows, which in turn have major influences on their fertility and survival.


Transforming growth factor-{beta} gene polymorphisms in different phenotypes of sarcoidosis.
The aetiology of sarcoidosis is unclear. Single nucleotide polymorphisms (SNPs) in transforming growth factor (TGF)-β2 and -β3 have been reported to be associated with the development of lung fibrosis in patients with sarcoidosis. SNPs in TGF-β2 (rs1891467) and TGF-β3 (rs3917200) were investigated in 296 patients with sarcoidosis (acute/self remitting, n = 70 (including 62 patients with Löfgren's syndrome); chronic, n = 168; acute/chronic, n = 58) by real-time PCR. 32 patients showed radiological signs of lung fibrosis. The genotype frequencies were compared among the sarcoidosis groups as well as to 377 healthy controls. We found a significant association with the G-allele in rs1891467 in TGF-β2 and an acute/self remitting course of sarcoidosis compared to a chronic course (p = 0.001). The results were even more evident for patients with Löfgren's syndrome (p<0.001). Moreover, we could demonstrate a borderline significance between TGF-β3 (rs3917200) and lung fibrosis (p = 0.050). Carriers of the G-allele in rs1891467 might be protected from developing a chronic course. Moreover, there is evidence that rs3917200 is involved in the development of lung fibrosis in sarcoidosis. This study is the first in sarcoidosis patients to suggest a genetic implication of TGF-β2 as a protective factor in the course of sarcoidosis.


Orotidine-5'-phosphate decarboxylase and pyrophosphorylase of bean leaves.
This report includes results demonstrating the existence of orotidine-5'-phosphate decarboxylase and orotidine-5'-phosphate pyrophosphorylase in plant leaves. The decarboxylase enzyme, purified 8 fold from leaves of etiolated pinto beans (Phaseolus vulgaris L.), had a pH optimum of 6.3. It was strongly inhibited by 6-azauridine-5'-phosphate; a concentration of 12 mum decreased the reaction rate 60%. The enzyme was not dependent upon magnesium ions or inhibited by p-chloromercuribenzoate. It was present in other parts of the bean plant and was found in young leaves of tomato (Lycopersicon esculentum Mill.) and Canada thistle (Cirsium arvense L.)The enzyme orotidine-5'-phosphate pyrophosphorylase, which catalyzes the formation of orotidine-5'-phosphate from orotic acid and 5-phosphoribosyl-1-pyrophosphate, was found in the etiolated bean leaves, and was also present in the leaves of tomato and Canada thistle. It was stimulated by manganous or magnesium ions and had a pH optimum of 7.2. The K(m) value obtained by varying the concentrations of 5-phosphoribosyl-1-pyrophosphate was 75 mum, and when orotic acid was varied the resulting K(m) was 3.5 mum. The presence of these 2 enzymes in higher plants, combined with previous results with inhibitors and labeled metabolites, indicates that the normal pathway of pyrimidine nucleotide synthesis in higher plants proceeds through orotic acid and OMP.


The Sizes and Composition of HDL-Cholesterol Are Significantly Associated with Inflammation in Rheumatoid Arthritis Patients.
Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.


[Intraoperative monitoring of motor evoked potentials during glioma removal].
To determine whether motor evoked potentials(MEPs)provide reliable monitoring of the motor system during resection of gliomas in or adjacent to the motor cortex or pyramidal tract. MEP recording was performed during 64 operations in 55 patients harboring gliomas. Intraoperative MEP findings were classified into 3 groups:Group A was defined as having no significant MEP changes, Group B as having reversible MEP changes(?50% amplitude decrease or loss), and Group C as having irreversible changes. Postoperative motor function was evaluated according to the presence/absence of deterioration immediately after surgery and 1 month later, as compared to preoperative motor status Immediately after surgery, 13 of 39(33%)patients in Group A, 6 of 17(35%)in Group B, and 7 of 8(88%)in Group C experienced deterioration of motor function. One month after surgery, 4 of 39(10%)patients in Group A, 3 of 17(18%)in Group B, and 4 of 8(50%)showed deterioration of motor function. Both immediately(χ2=8.3, p<0.05)and 1 month(χ2=6.9, p<0.05)after surgery, MEP alterations correlated significantly with postoperative deterioration of motor function. Despite MEPs being stable throughout surgery(Group A), there were some patients with deterioration of motor function initially appearing to represent false negative monitoring. However, these deteriorations were confirmed to have been caused by secondary hemorrhage, venous return dysfunction, postoperative convulsion, or resection of the supplementary motor area. MEP monitoring provides reliable information on the motor system during glioma surgery. Although false negative MEP results may exist in some patients, most data were not influenced by intraoperative manipulation but rather were attributable to secondary postoperative events.


High Prevalence of Sterile Pyuria in the Setting of Sexually Transmitted Infection in Women Presenting to an Emergency Department.
The clinical presentations for sexually transmitted infections (STI) and urinary tract infections (UTI) often overlap, and symptoms of dysuria and urinary frequency/urgency occur with both STIs and UTIs. Abnormal urinalysis (UA) findings and pyuria are common in both UTIs and STIs, and confirmatory urine cultures are not available to emergency clinicians to aid in decision-making regarding prescribing antibiotics for UTIs. The objective of this study was to determine the frequency of sterile pyuria in women with confirmed STIs, as well as whether the absolute number of leukocytes on microscopy or nitrite on urine dipstick correlated with positive urine cultures in patients with confirmed STIs. We also sought to determine how many patients with STIs were inappropriately prescribed a UTI antibiotic. We performed a retrospective chart review of patients aged 18-50 who had a urinalysis and pelvic examination in the emergency department (including cervical cultures), and tested positive for Neisseria gonorrhoeae, Chlamydia trachomatis, and/or Trichomonas vaginalis. Descriptive statistics were obtained for all variables, and associations between various findings were sought using the Fisher's exact test for categorical variables. We calculated comparison of proportions using the N-1 chi-squared analysis. A total of 1,052 female patients tested positive for Neisseria gonorrhoeae, Chlamydia trachomatis, and/or Trichomonas vaginalis and were entered into the database. The prevalence of pyuria in all cases was 394/1,052, 37% (95% confidence interval [CI] [0.34-0.40]). Of the cases with pyuria, 293/394, 74% (95% CI [0.70-0.78]) had sterile pyuria with negative urine cultures. The prevalence of positive urine cultures in our study population was 101/1,052, 9.6% (95% CI [0.08-0.11]). Culture positive urines had a mean of 34 leukocytes per high-power field, and culture negative urines had a mean of 24 leukocytes per high-power field, with a difference of 10, (95% CI [3.46-16.15]), which was statistically significant (p=0.003). Only 123 cases tested positive for nitrite on the urinalysis dipstick; 50/123, 41% (95% CI [0.32-0.49]) had positive urine cultures, and 73/123, 59% (95% CI [0.51-0.68]) had negative urine cultures. Nitrite-positive urines were actually 18% more likely to be associated with negative urine cultures in the setting of positive STI cases, (95% CI [4.95-30.42], p=0.0048). Antibiotics were prescribed for 295 patients with suspected UTI. Of these, 195/295, 66% (95% CI [0.61-0.71]) had negative urine cultures, and 100/295, 34% (0.33, 95% CI [0.28-0.39]) had positive urine cultures. Chi-square analysis yielded a difference of these proportions of 32% (95% CI [23.92-39.62], p<0.0001). This study demonstrated that in female patients with STIs who have pyuria, there is a high prevalence of sterile pyuria. Our results suggest that reliance on pyuria or positive nitrite for the decision to add antimicrobial therapy empirically for a presumed urinary tract infection in cases in which an STI is confirmed or highly suspected is likely to result in substantial over-treatment.


Hepatitis B associated fulminant polyarteritis nodosa: successful treatment with pulse cyclophosphamide, prednisolone and lamivudine following emergency surgery.
For hepatitis B virus associated polyarteritis nodosa, alpha interferon and plasma exchanges have been proposed to be the first-line treatment. We report a case of hepatitis B surface antigen (HBsAg)-positive fulminant polyarteritis nodosa with predominant gastrointestinal involvement who showed good response to pulse cyclophosphamide, prednisolone, and lamivudine therapy. The patient, a 22-year-old man, presented with a short history of epigastric pain. Initial upper gastrointestinal endoscopy revealed gastritis and duodenal erosions. His pain did not respond to H2-receptor antagonists. He had slightly impaired liver function tests, and was HBsAg and hepatitis B e antigen (HBeAg) positive. Around 3 weeks after initial presentation, he developed massive gastrointestinal haemorrhage requiring resuscitation and emergency laparotomy. Microscopic examination of the resection specimens revealed necrotizing vasculitis of small and medium-sized arteries in the submucosa compatible with polyarteritis nodosa. The patient was treated with pulse cyclophosphamide and prednisolone, with lamivudine being added when he showed an acute rise in liver enzymes. He subsequently developed HBeAg seroconversion, and remained well 18 months after cessation of all immunosuppressives. We believe that the efficacy of pulse cyclophosphamide, prednisolone, and lamivudine in the treatment of hepatitis B virus associated polyarteritis nodosa, especially in comparison with interferon and plasma exchanges, deserves further evaluation.


Botulinum toxin type A in refractory chronic migraine: an open-label trial.
Botulinum toxin type A (BT-A) has been described as an important strategy to various types of pain such as cervical dystonia, myofascial pain syndrome and headache. Although BT-A efficacy has not been proven in tension type headache, its use in migraine continues controversial. In this open trial, we evaluated the efficacy of BT-A in refractory migraine. BT-A was injected in patients diagnosed with migraine who had previously used three classes of prophylactic drugs by at least one year with no response. The most important improvement was observed within 30 days, but pain intensity and frequency of headache had been decreased until the end of three months of follow up. Side effects of BT-A were mild and self limited. We conclude that BT-A seems to be a safe and effective treatment to refractory migraine patients.


The Acute Impact of Smoking One Cigarette on Cardiac Hemodynamic Parameters.
The acute impact of tobacco smoking on the cardiac hemodynamic parameters and its pathological implication in the process of arterial atherosclerosis need further exploration. This investigation was purposed to assess the acute impact of tobacco smoke on blood pressure and cardiac hemodynamic parameters. Using an Ultrasonic Cardiac Output Monitor, and DINAMAP Pro 400 Series V2 blood pressure monitor, several cardiac hemodynamic parameters and the blood pressure were assessed in 14 smokers, 11 females and 3 males, at 2 time points, before and after smoking of one cigarette. Data, in terms of ratio of the means and 95% confidence interval were analyzed using ANOVA. Single-subject design in which the subject has served as his/her own control has been used. Tobacco smoking led to statistically significant acute increase in the means of all hemodynamic parameters, except for heart rate in female subjects, as compared to the means obtained before smoking. Cigarette smoking induces acute non-physiologic alteration in cardiac outflow forces, exposing the aortic valve and arch to mechanical injury that might be implicated in initiating and promoting the process of aortic arch atherosclerosis and associated pathological lesions.


African American English speaking 2nd graders, verbal-s, and educational achievement: Event related potential and math study findings.
A number of influential linguistic analyses hold that African American English (AAE) has no verbal-s, the-s that, for example, turns drink into drinks in more mainstream English varieties.On such accounts, sentences like Mary drinks coffee are ungrammatical in AAE. Previous behavioral studies suggest that in addition to being ungrammatical, AAE speaking children find these sentences cognitively demanding, and that their presence in mathematical reasoning tests can depress scores. Until now, however, no online sentence processing study nor investigation of neurophysiological markers has been done to support these findings. Aimed at addressing this gap in the literature, the auditory ERP experiment described herein revealed two different processes associated with AAE speaking 2nd graders listening to this type of sentence: a morphosyntactic structure building problem, reflected in a bilateral early anterior-central negativity; and an increase in working memory load, indicated by a bilateral late long-lasting anterior-central negativity. Study participants also took an orally administered test of math word problems. Consistent with previous findings, results showed they answered fewer questions correctly when those questions contained verbal-s than when they did not.


Regulation of tyrosine phosphorylation during the CD40-mediated rescue of Ramos-BL B cells from BCR-triggered apoptosis.
The regulation of tyrosine phosphorylation is essential for BCR-triggered cellular responses during the selection process in the germinal centres. We were interested in examining the temporal regulation of tyrosine phosphorylation following CD40 cross-linking of anti-IgM-triggered Ramos-BL B cells. CD40 co-stimulation of anti-IgM-treated Ramos-BL B cells rescued them from growth inhibition and apoptosis, even when anti-CD40 Abs were added up to 12 h after the cross-linking of the BCR. The initial up-regulation of tyrosine phosphorylation triggered by BCR cross-linking is followed by tyrosine dephosphorylation after 12 h of stimulation, coinciding with pro-caspase-3 processing and PARP cleavage. We find that CD40 co-stimulation rescues BCR-triggered Ramos-BL B cells only before the irreversible inhibition of tyrosine kinase activity after 12 h of BCR cross-linking and that this is coupled with up-regulation of tyrosine phosphorylation; thus demonstrating the importance of the late regulation of tyrosine phosphorylation for CD40-mediated rescue of Ramos-BL B cells from BCR-triggered G1 growth arrest and apoptosis.


The type locality of Pan troglodytes vellerosus (Gray, 1862), and implications for the nomenclature of West African chimpanzees.
We show that, in 1862, Richard Burton collected the type specimen of Pan troglodytes vellerosus not on Mount Cameroon, as has been generally assumed, but in Gabon. Therefore, P. t. vellerosus is not the correct name for the chimpanzee population of western Cameroon and southern Nigeria, if that population is taxonomically distinct. As First Reviser, we choose the name Pan troglodytes ellioti for this population of chimpanzees, based on Anthropopithecus ellioti named by Matschie [Matschie P (1914) Neue Affen aus Mittelafrika. Sitzungsber Ges Naturforsch Freunde Berlin 1914:323-342] from a specimen in the Humboldt Museum, Berlin, collected in Bascho (=Basho), Cameroon, and given to the museum in 1905.


"Fibromyalgia and quality of life: mapping the revised fibromyalgia impact questionnaire to the preference-based instruments".
The revised version of the Fibromyalgia Impact Questionnaire (FIQR) is one of the most widely used specific questionnaires in FM studies. However, this questionnaire does not allow calculation of QALYs as it is not a preference-based measure. The aim of this study was to develop mapping algorithm which enable FIQR scores to be transformed into utility scores that can be used in the cost utility analyses. A cross-sectional survey was conducted. One hundred and 92 Spanish women with Fibromyalgia were asked to complete four general quality of life questionnaires, i.e. EQ-5D-5 L, 15D, AQoL-8D and SF-12, and one specific disease instrument, the FIQR. A direct mapping approach was adopted to derive mapping algorithms between the FIQR and each of the four multi-attribute utility (MAU) instruments. Health state utility was treated as the dependent variable in the regression analysis, whilst the FIQR score and age were predictors. The mean utility scores ranged from 0.47 (AQoL-8D) to 0.69 (15D). All correlations between the FIQR total score and MAU instruments utility scores were highly significant (p < 0.0001) with magnitudes larger than 0.5. Although very slight differences in the mean absolute error were found between ordinary least squares (OLS) estimator and generalized linear model (GLM), models based on GLM were better for EQ-5D-5 L, AQoL-8D and 15D. Mapping algorithms developed in this study enable the estimation of utility values from scores in a fibromyalgia specific questionnaire.


The relationship between communication competence and exercise participation type: focusing on joining clubs and using fitness applications.
The purpose of this study was to determine the effects of the differences in subfactors of communication competence on exercise participation types (clubs, applications use). Communication competence focus on the communication part of the individual's interpersonal competence. Therefore, communication competence can be predicted to be related to the type of exercise participation. Accordingly, the targets of this study were clubs, which had group characteristics, and fitness applications, which had individual characteristics. There was a significant difference as a result of the association between communication competence and the type of exercise participation. In terms of club membership, significant differences were found in communication competence skills according to exercise participation types in that self-disclosure of subjects who joined clubs was significant, social relaxation of subjects who intend to join a club was significant, and the immediacy of fitness applications users was significant.


Relapsing bacteremia after blood transmission of Bartonella henselae to cats.
To determine persistence of bacteremia, pathogenicity, and immunoglobulin kinetics after blood transmission of Bartonella henselae in cats. 18 specific-pathogen-free (SPF) cats (16 weeks old) received blood or urine from 4 adult cats (2 SPF, 2 naturally infected with B henselae). SPF cats were inoculated with blood IV (n = 4), blood IM (n = 4), or urine sediment IM (n = 4) from 2 bacteremic cats (donors A and B). Control cats (2/route) received inoculum from culture-negative, seronegative SPF cats (donors C and D). 6 cats (5 blood, 1 urine) were transiently febrile during the 213-day observation period. Two bacteremic cats developed CNS abnormalities. Transient anemia was the only hematologic abnormality. Bacteremia was induced in 7 of 8 blood recipients by postinoculation day (PID) 11. Urine recipients (n = 6) did not become bacteremic or seroconvert by PID 108, but when challenge exposed IV with blood, 4 of 6 became infected. All infected cats developed relapsing bacteremia. Initially, colony counts for donor-A recipients were 10(3) greater than those for donor-B recipients; however, during relapses, counts were similar. Polymerase chain reaction-restriction fragment length polymorphism analysis of 16S rRNA gene and the intergenic spacer region revealed no differences among isolates derived from recipient cats. Bartonella henselae-specific antibodies were detected between PID 15 and 18 in donor-A, compared with PID 46 and 181 in donor-B recipients. The peak geometric mean titer of donor-A recipients was 1,448, versus 406 for donor-B recipients. Blood transmission of B henselae induced subtle clinical abnormalities; the biological behavior of the 2 donor strains differed; and relapsing bacteremia can persist in conjunction with variably high antibody titers.


Prevalence and causes of blindness in Otibhor Okhae Teaching Hospital, Irrua, Edo State, Nigeria.
This hospital-based retrospective study was aimed at providing baseline information on the causes of blindness in the locality. The case notes of all new patients attending the Eye Clinic of Otibhor Okhae Teaching Hospital, Irrua, Edo State, Nigeria, over a six-year period (January 1995-December 2000) were retrieved and analyzed. Over 6% (555) of new patients seen during this period were uniocularly blind while 3.9% (354) were binocularly blind. The leading causes of uniocular blindness were cataract, open-angle glaucoma and corneal ulceration/leucoma. Binocular blindness was mainly due to cataract, open-angle glaucoma and aphakia. The prevalence of blindness in the study population is high. Cataract, as the main cause of blindness, will require surgical relief, either in the teaching hospital or preferably in the patient's locality. Appropriate interventions need to be evolved (in the form of either mobile clinics or a series of surgical eye camps) to stem the present trend toward high prevalence of avoidable blindness. Prevention of ocular trauma is an essential factor in the reduction of blindness in children. Health education and bringing ophthalmological care to the doorstep of underprivileged rural dwellers will improve their level of awareness.


[Should resistance to methicillin of RH mutant staphylococci be necessarily attributed to cephalosporins?].
The resistance to cephalosporins of 48 heterogeneous methicillin-resistant strains ("RH" mutants) of Staphylococcus pyogenes var. aureus is studied in vitro with various methods: sensitivity discs test on Mueller-Hinton medium with 5 per cent NaCl at 37 degrees C; M.I.C. in solid medium by spots medium with two inocula: a light inoculum (10(7) bacterial/ml) and a heavy inoculum (10(9) bacteria/ml). With light inoculum all strains have M.I.C. to cephaloridin less than 2 meg/ml and seem sensitive. With heavy inoculum 45 sc. equal or superior to 64 meg/ml and then are resistant. These resistances occur after 3 degrees C. The varied methods of detection of mutants to cephalosporins are discussed in this paper.


Futility: a concept in search of a definition.
The simplistic concepts of futility and autonomy, then, cannot adequately inform society about the kinds of health care services that are appropriately provided to patients. Health care professionals, patients, and their surrogates are left with the arduous but necessary task of communicating effectively and of searching for an equitable resolution to the treatment conflict. With these introductory remarks to help frame the discussion, we invite you to read LMHC's mini-symposium on futility [articles by Steven H. Miles; Betty Dew; Kathryn A. Koch, Bruce W. Myers and Stephen Sandroni; Ann Alpers and Bernard Lo; Edward R. Grant; and Troyen A. Brennan], and to decide for yourself about this relatively new, extremely important, but also highly dangerous, concept of medical futility.


[Effects of ulinastatin on interleukin-8 during one-lung ventilation in surgery].
Ulinastatin is a kind of broad- spectrum hydrolase inhibitors purified from urine of healthy males.There was no data showing whether ulinastatin could affect alveolar inflammatory reactions.This study was designed to investigate the changes of pulmonary alveolar interleukin-8 during one lung ventilation (OLV) in surgery and the effects of ulinastatin on alveolar IL-8. Sixty patients,ASA II- III,who underwent lobectomy, were randomly divided into two groups [30 patients in each group,surgery group(II) and control group (I)].Patients in surgery group were treated with ulinastatin 5,000 u/kg preoperatively. Alveolar IL-8 was harvested by bronchoalveolar lavage at 0, 1, and 2 hours after one lung ventilation and at the end of surgery. The changes of concentration of IL-8 in bronchoalveolar lavage fluid were analyzed statistically. (1)Alveolar interleukin 8 was significantly higher at 2 hours after OLV [(160.85+/-46.58)ng/L] than before OLV [(128.26+/-35.35)ng/L] in control group. The results indicated that OLV and/or the stimulation of surgery could induce the pulmonary inflammatory reaction. (2)The concentrations of alveolar IL-8 at 2 hours [(140.32+/-41.25)ng/L] after OLV and at the end of surgery [ (156.74+/-43.58) ng/L] were significantly lower in surgery group than those in control group [(160.85+/-46.58)ng/L and (172.41+/-52.60)ng/L] respectively(P< 0.05). Ulinastatin could alleviate the pulmonary alveolar inflammatory reactions in OLV.


Active Flexion in Weight Bearing Better Correlates with Functional Outcomes of Total Knee Arthroplasty than Passive Flexion.
Correlations between maximum flexion and functional outcomes in total knee arthroplasty (TKA) patients are reportedly weak. We investigated whether there are differences between passive maximum flexion in nonweight bearing and other types of maximum flexion and whether the type of maximum flexion correlates with functional outcomes. A total of 210 patients (359 knees) underwent preoperative evaluation and postoperative follow-up evaluations (6, 12, and 24 months) for the assessment of clinical outcomes including maximum knee flexion. Maximum flexion was measured under five conditions: passive nonweight bearing, passive weight bearing, active nonweight bearing, and active weight bearing with or without arm support. Data were analyzed for relationships between passive maximum flexion in nonweight bearing by Pearson correlation analyses, and a variance comparison between measurement techniques via paired t test. We observed substantial differences between passive maximum flexion in nonweight bearing and the other four maximum flexion types. At all time points, passive maximum flexion in nonweight bearing correlated poorly with active maximum flexion in weight bearing with or without arm support. Active maximum flexion in weight bearing better correlated with functional outcomes than the other maximum flexion types. Our study suggests active maximum flexion in weight bearing should be reported together with passive maximum flexion in nonweight bearing in research on the knee motion arc after TKA.


Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor-coupled phencyclidine binding site.
Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycl ohepten-5,10 - imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[3H]-3 binding sites, compared to 20 microM needed for its optical antipode (-)-8a and the 2-isothiocyanate (+)-8b. The apparent Ki values for reversible inhibition of (+)-[3H]-3 binding by (+)- and (-)-8a and (+)-8b were 37,838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[3H]-3 binding sites at 100 microM and 250 nM, respectively, with apparent Ki values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 microM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 microM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma 1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system.


Cholecystokinin (CCK)-33 stimulates insulin secretion from the perfused rat pancreas: studies on the structure-activity relationship.
Cholecystokinin (CCK)-33 is known to stimulate insulin secretion. Presently, using the perfused rat pancreas, we have characterized the active site in the CCK-33 molecule that is responsible for this effect by the use of different CCK fragments. We found that CCK-33, CCK-8 and CCK-7 (1 nM) all significantly stimulated insulin secretion in the presence of 4.4 mM or 6.7 mM glucose. However, CCK-7 was much less potent than the longer forms. In contrast, CCK-4, CCK-6 and CCK-33 (1-21) had no effect on insulin secretion. We conclude that the shortest CCK-form that stimulates insulin secretion at 1 nM is the C-terminal heptapeptide CCK-7. However, CCK-8 is much more potent than CCK-7 in this respect.


Complete genome sequence of Thermovibrio ammonificans HB-1(T), a thermophilic, chemolithoautotrophic bacterium isolated from a deep-sea hydrothermal vent.
Thermovibrio ammonificans type strain HB-1(T) is a thermophilic (Topt: 75°C), strictly anaerobic, chemolithoautotrophic bacterium that was isolated from an active, high temperature deep-sea hydrothermal vent on the East Pacific Rise. This organism grows on mineral salts medium in the presence of CO2/H2, using NO3(-) or S(0) as electron acceptors, which are reduced to ammonium or hydrogen sulfide, respectively. T. ammonificans is one of only three species within the genus Thermovibrio, a member of the family Desulfurobacteriaceae, and it forms a deep branch within the phylum Aquificae. Here we report the main features of the genome of T. ammonificans strain HB-1(T) (DSM 15698(T)).


Evolving Role of Autologous Stem Cell Transplantation for Light Chain Amyloidosis in the Modern Era.
Muhamed Baljevic, MD, considers the role of autologous stem cell transplantation for light chain amyloidosis in a peer perspective accompanying an article by Iuliana Vaxman, MD, and Angela Dispenzieri, MD.


Elevated serum human growth hormone and decreased serum insulin in prediabetic males after intravenous tolbutamide and glucose.
Serum human growth hormone (HGH), serum immunoreactive insulin (IRI), plasma free fatty acids, and blood glucose were measured during intravenous glucose and intravenous tolbutamide tolerance tests in 13 normal and 13 prediabetic (offspring of two diabetic parents) males, closely matched for weight and age. Only prediabetics with normal glucose tolerance during oral, intravenous, and cortisone-primed glucose tolerance tests were evaluated. Mean serum HGH levels were significantly higher in prediabetics in response to intravenous tolbutamide and at the end of the 3-hr intravenous glucose tolerance tests (IVGTT). This is interpreted as a hyperresponsiveness of the growth hormone-releasing mechanisms in prediabetic subjects. The insulin response during the first 10 min of an IVGTT was significantly reduced in prediabetic males as compared to normal controls, whereas the insulin response to intravenous tolbutamide was not significantly different at the same time intervals in the same subjects.It appears, therefore, that measuring IRI during an IVGTT can be valuable in detecting the earliest signs of diabetes even before any disturbance of blood glucose homeostasis is seen. The possibility that growth hormone hypersecretion in prediabetics might play a role in the pathogenesis of human diabetes mellitus is discussed.


Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.
Human thymidylate synthase (hTS) provides the sole de novo intracellular source of thymidine 5'-monophosphate (dTMP). hTS is required for DNA replication prior to cell division, making it an attractive target for anticancer chemotherapy and drug discovery. hTS binds 2'-deoxyuridine 5'-monophosphate (dUMP) and the folate co-substrate N5,N10-methylenetetrahydrofolate (meTHF) in a pocket near the catalytic residue Cys195. The catalytic loop, which is composed of amino-acid residues 181-197, can adopt two distinct conformations related by a 180° rotation. In the active conformation Cys195 is close to the active site, while in the inactive conformation it is rotated and Cys195 is too distant from the active site for catalysis. Several hTS structures, either native or engineered, have been solved in the active conformation in complex with ligands or inhibitors and at different salt concentrations. However, apo hTS structures have been solved in an inactive conformation in high-salt and low-salt conditions (PDB entries 1ypv, 4h1i, 4gyh, 3egy and 3ehi). Here, the structure of apo hTS crystallized in the active form with sulfate ions coordinated by the arginine residue that binds dUMP is reported.


Comparison of femtosecond laser-assisted descemetic and predescemetic lamellar keratoplasty for keratoconus.
The purpose of this study is to compare the outcomes following femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) with 75% of stromal dissection (predescemetic group) and femtosecond laser-assisted DALK using big-bubble technique with total stromal resection (descemetic group) for the treatment of keratoconus. Twenty eyes of 17 patients with keratoconus were studied. There were 10 eyes of 9 patients in predescemetic group and 10 eyes of 8 patients in descemetic group. The postoperative best-corrected visual acuity (BCVA), manifest refraction, keratometry, endothelial cell density (ECD), and central corneal thickness (CCT) were analyzed. All surgeries were performed uneventfully. At 1 year after surgery, the BCVA, corneal astigmatism, keratometry, CCT, and ECD between two groups were not statistically significant (all P > 0.05). However, the mean manifest refraction was -9.43 ± 7.44 diopter (D) and -1.03 ± 1.13D in predescemetic and descemetic groups, respectively, which was statistically significant between two groups (P < 0.05). The results of BCVA and corneal astigmatism, keratometry, ECD, and CCT were comparable between two groups. However, the mean postoperative manifest refraction was lower in descemetic group.


CAAT/enhancer binding protein homologous protein-dependent death receptor 5 induction is a major component of SHetA2-induced apoptosis in lung cancer cells.
The flexible heteroarotinoids (Flex-Het) represent a novel type of atypical retinoids lacking activity in binding to and transactivating retinoid receptors. Preclinical studies have shown that Flex-Hets induce apoptosis of cancer cells while sparing normal cells and exhibit anticancer activity in vivo with improved therapeutic ratios over conventional retinoid receptor agonists. Flex-Hets have been shown to induce apoptosis through activation of the intrinsic apoptotic pathway. The present study has revealed a novel mechanism underlying Flex-Het-induced apoptosis involving induction of death receptor 5 (DR5). The representative Flex-Het SHetA2 effectively inhibited the growth of human lung cancer cells in cell culture and in mice. SHetA2 induced apoptosis, which could be abrogated by silencing caspase-8 expression, indicating that ShetA2 triggers a caspase-8-dependent apoptosis. Accordingly, SHetA2 up-regulated DR5 expression, including cell surface levels of DR5, and augmented tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Importantly, small interfering RNA (siRNA)-mediated blockade of DR5 induction conferred cell resistance to SHetA2-induced apoptosis, as well as SHetA2/TRAIL-induced apoptosis. These results show that DR5 induction is a key component of apoptosis induced by SHetA2 or by SHetA2 combined with TRAIL. SHetA2 exerted CAAT/enhancer-binding protein homologous protein (CHOP)-dependent transactivation of the DR5 promoter. Consistently, SHetA2 induced CHOP expression, which paralleled DR5 up-regulation, whereas siRNA-mediated blockage of CHOP induction prevented DR5 up-regulation, indicating CHOP-dependent DR5 up-regulation by SHetA2. Collectively, we conclude that CHOP-dependent DR5 up-regulation is a key event mediating SHetA2-induced apoptosis.


Traumatic cholecystectomy.
Injury to the gallbladder following blunt abdominal trauma is an unusual finding at laparotomy, with a reported incidence of less than 2%. Avulsion from the liver and detachment from both the cystic duct and artery is an extremely rare finding. The condition of the patient and the extent of injuries will dictate the procedure performed. In the case presented, total avulsion of the gallbladder was successfully treated with identification and ligation of the cystic duct, and coagulation of small bleeding points, followed by placement of a Penrose drain.


Does physical activity induce DNA damage?
The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity. Blood was taken before and several times during and after the run. In a first multiple step test, the volunteers ran as long as possible with increasing speed. In a second test they had to run for 45 min with a fixed individual speed which was defined to ensure an aerobic metabolism. In the first test, the white blood cells of all subjects showed increased DNA migration in the SCG assay. The effect was seen 6 h after the end of the exercise and reached its maximum 24 h later. After 72 h, DNA migration decreased to about control level. The distribution of DNA migration among cells clearly demonstrated that the majority of white blood cells exhibited increased DNA migration and that the effect was not only due to a small fraction of damaged cells. From the same blood samples, blood cultures were set up to study a possible effect on the frequency of sister chromatid exchanges (SCE), another indicator for genotoxic effects. However, there was no significant increase in SCE in any of the cultures. In the second exercise, during aerobic metabolism, the effect on DNA migration was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)


Furoquinoline Alkaloids from the Leaves of Evodia lepta as Potential Cholinesterase Inhibitors and their Molecular Docking.
Nine furoquinoline alkaloids (1-9) were isolated from the leaves of Evodia lepta based on bioassay-guided fractionation and chromatographic techniques. All isolates were evaluated for their cholinesterase (ChEs) inhibitory activities, in which kokusaginine (7) and melineurine (5) exhibited the highest activity toward AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were mixed mode inhibitors of both ChE enzymes. Molecular docking studies on the binding sites of AChE and BChE were performed in order to afford a molecular insight into the mode of action of these active compounds. From this study these compounds have emerged as promising molecules for Alzheimer's disease therapy.


Recursive segment-wise peak alignment of biological (1)h NMR spectra for improved metabolic biomarker recovery.
Chemical shift variation in small-molecule (1)H NMR signals of biofluids complicates biomarker information recovery in metabonomic studies when using multivariate statistical and pattern recognition tools. Current peak realignment methods are generally time-consuming or align major peaks at the expense of minor peak shift accuracy. We present a novel recursive segment-wise peak alignment (RSPA) method to reduce variability in peak positions across the multiple (1)H NMR spectra used in metabonomic studies. The method refines a segmentation of reference and test spectra in a top-down fashion, sequentially subdividing the initial larger segments, as required, to improve the local spectral alignment. We also describe a general procedure that allows robust comparison of realignment quality of various available methods for a range of peak intensities. The RSPA method is illustrated with respect to 140 (1)H NMR rat urine spectra from a caloric restriction study and is compared with several other widely used peak alignment methods. We demonstrate the superior performance of the RSPA alignment over a wide range of peaks and its capacity to enhance interpretability and robustness of multivariate statistical tools. The approach is widely applicable for NMR-based metabolic studies and is potentially suitable for many other types of data sets such as chromatographic profiles and MS data.


[Diagnostic value of the H-reflex index in alcoholic polyneuropathy].
We examined the H-reflex-index of triceps surae muscle (HI) and the motor nerve conduction velocity of the tibial nerve (mNLG) of 56 alcohol dependent patients. The results were compared with neurologic disorders, duration of the dependency and the type of alcoholism according to Jellinek. The HI showed significant more pathological changes than the mNLG.


Gas-particle partitioning of semivolatile organic compounds (SOCs) on mixtures of aerosols in a smog chamber.
The partitioning behavior of a set of diverse SOCs on two and three component mixtures of aerosols from different sources was studied using smog chamber experimental data. A set of SOCs of different compound types was introduced into a system containing a mixture of aerosols from two or more sources. Gas and particle samples were taken using a filter-filter-denuder sampling system, and a partitioning coefficient Kp was estimated using Kp = Cp/(CgTSP). Particle size distributions were measured using a differential mobility analyzer and a light scattering detector. Gas and particle samples were analyzed using GCMS. The aerosol composition in the chamber was tracked chemically using a combination of signature compounds and the organic matter mass fraction (f(om)) of the individual aerosol sources. The physical nature of the aerosol mixture in the chamber was determined using particle size distributions, and an aggregate Kp was estimated from theoretically calculated Kp on the individual sources. Model fits for Kp showed that when the mixture involved primary sources of aerosol, the aggregate Kp of the mixture could be successfully modeled as an external mixture of the Kp on the individual aerosols. There were significant differences observed for some SOCs between modeling the system as an external and as an internal mixture. However, when one of the aerosol sources was secondary, the aggregate model Kp required incorporation of the secondary aerosol products on the preexisting aerosol for adequate model fits. Modeling such a system as an external mixture grossly overpredicted the Kp of alkanes in the mixture. Indirect evidence of heterogeneous, acid-catalyzed reactions in the particle phase was also seen, leading to a significant increase in the polarity of the resulting aerosol mix and a resulting decrease in the observed Kp of alkanes in the chamber. The model was partly consistent with this decrease but could not completely explain the reduction in Kp because of insufficient knowledge of the secondary organic aerosol composition.


Cloning and characterization of the Haemophilus influenzae Rd rec-1+ gene.
The Haemophilus influenzae Rd rec-1+ gene was cloned from a partial chromosomal digest into a plasmid vector as a 20-kilobase-pair (kbp) BstEII fragment and then subcloned. The smallest subclone with rec-1+ activity carried a 3.1-kbp EcoRI fragment. The identity of the rec-I gene in these clones was confirmed by transforming an Rd strain carrying a leaky rec-1 mutation (recA4) to resistance to methyl methanesulfonate (MMS) by using whole or digested plasmids. It was demonstrated that the Rec+ phenotype of the MMSr transformants was linked to the strA, novAB, and mmsA loci, as expected if the recA4 allele had been replaced by rec-1+. In growing cultures (rec-1 or rec+), all rec-1+-carrying plasmids induced near-maximal levels of transformability when their hosts reached stationary phase; these levels are 100 to 1,000 times higher than the values seen with strains not carrying a Rec plasmid. Transfer of the 3.1-kbp subclone was greatly reduced compared with transfer of similarly sized vector plasmids, and the resulting transformants grew slowly; this suggests an explanation of my failure to directly clone this fragment from chromosomal DNA digests. Transfer of a rec-1+ plasmid to a very poorly genetically transformable H. influenzae Rb strain resulted in greatly increased transformability. Transfer of such plasmids to a noncompetent H. influenzae Rc strain did not render this strain competent. It is suggested that transformability of Rd and Rb strains is limited by rec-1 expression but that the noncompetence of Rc has some other basis.


Emphysematous cholecystitis following routine colonoscopy.
Cholecystitis is a rare sequela of colonoscopy, the relationship between which has not yet been defined. This case study reviews a rural elderly patient who developed right upper quadrant pain following routine colonoscopy. He developed emphysematous cholecystitis, which required laparoscopy with conversion to open via Kocher's incision and underwent a subtotal cholecystectomy due to the severity of necrosis and inflammation. He had an uncomplicated recovery. Colonoscopy is an important diagnostic procedure, the most common complications of which are haemorrhage and perforation. There are less than 10 cases of associated cholecystitis and no reports of emphysematous cholecystitis. The hypothesized pathogenesis is dehydration and lithogenesis associated with traumatic translocation of organisms, however, no definitive correlation has been determined. Due to the potential health impact, cholecystitis cannot be excluded regarding post-colonoscopy abdominal pain, however, the correlation between procedure and pathology remains unclear.


Extracellular Cardiolipin Modulates Select Immune Functions of Astrocytes in Toll-Like Receptor (TLR) 4-Dependent Manner.
Alzheimer's disease (AD) is characterized by chronic neuroinflammation, which is partially mediated by dysregulated functions of glial cells. Cardiolipin (CL) is a phospholipid normally confined to the inner mitochondrial membrane; however, it has been detected in human sera, indicating that it can exist in the extracellular space where it may interact with nearby cells. Although CL has been shown to modulate several functions of microglia in a toll-like receptor (TLR) 4-dependent manner, the effects of extracellular CL on astrocytes are unknown. In addition to their homeostatic functions, astrocytes participate in neuroimmune responses of the brain and express TLR 4. Therefore, we hypothesized that extracellular CL (1) modulates the secretion of cytokines and cytotoxins by astrocytes, as well as their phagocytic activity, and (2) acts by interacting with astrocyte TLR 4. We demonstrate that CL inhibits the lipopolysaccharide- (LPS-) induced secretion of cytotoxins and expression of glial fibrillary acidic protein (GFAP) by human U118 MG astrocytic cells. CL alone upregulates the phagocytic activity of human astrocytic cells and primary murine astrocytes. CL in combination with LPS upregulates secretion of interleukin (IL)-1β by astrocytic cells. Furthermore, CL alone increases the secretion of monocyte chemoattractant protein (MCP)-1 by astrocytic cells, which is blocked by the TLR 4-specific antagonist TAK-242. We demonstrate that CL upregulates MCP-1 secretion in the absence of its natural carrier protein, β2-glycoprotein 1, indicating that CL may be bioactive in the brain where this protein is not present. Lastly, we show that CL downregulates the expression of astrocytic TLR 4, implying that CL engages this receptor, as its activation has been shown to lead to its degradation. Overall, our study extends the list of cell type functions of which CL modulates and provides evidence that CL, or liposomes containing this phospholipid can be used to modulate specific neuroimmune functions of astrocytes.


[Palm oil and cardiovascular health: considerations to evaluate the literature critically].
Palm oil is obtained from Elaeis guineensis, E. oleifera or the hybrid OxG palm fruits. When crude, it contains high carotenoid concentrations (responsible for the red color), tocopherols and tocotrienols, but most of them are eliminated during its refining. Palm oil main components are palmitic and oleic acids, both near 50%, but their proportion changes depending on the fraction used. Fatty acids absorption and the effect on blood lipid profile depend on the position in the triacylglycerol, especially in the sn-2 position. The location of the monounsaturated or saturated fatty acids varies depending on the type of palm oil or fraction used. We critically review the two main reviews published about palm oil, which analyze 67 publications, and several studies that are more recent. Most of the studies were performed in non-European countries where palm oil is the main culinary oil. The effect on cardiovascular risk factors depends on the fat used as counterpart. Palm oil improves lipid profile after a diet rich in trans and saturated fats, while it impairs lipid profile after a diet rich in monounsaturated and polyunsaturated fats. Relevant methodological errors have been identified, such as not differentiating between palm oil, palm kernel oil and their fractions, comparing single fatty acids with whole oils or fats, or not considering physical activity or other factors that can affect blood lipids. No studies considering palm oil as an ingredient in a Mediterranean diet context, where olive oil is the main culinary oil, were found, so extrapolation of data is currently very difficult.