Crystal structure of a glutamate/aspartate binding protein complexed with a glutamate molecule: structural basis of ligand specificity at atomic resolution.
The crystal structure of a periplasmic l-aspartate/l-glutamate binding protein (DEBP) from Shigella flexneri complexed with an l-glutamate molecule has been determined and refined to an atomic resolution of 1.0 A. There are two DEBP molecules in the asymmetric unit. The refined model contains 4462 non-hydrogen protein atoms, 730 water molecules, 2 bound glutamate molecules, and 2 Tris molecules from the buffer used in crystallization. The final R(cryst) and R(free) factors are 13.61% and 16.89%, respectively. The structure has root-mean-square deviations of 0.016 A from standard bond lengths and 2.35 degrees from standard bond angles. The DEBP molecule is composed of two similarly folded domains separated by the ligand binding region. Both domains contain a central five-stranded beta-sheet that is surrounded by several alpha-helices. The two domains are linked by two antiparallel beta-strands. The overall shape of DEBP is that of an ellipsoid approximately 55 A x 45 A x 40 A in size. The binding of ligand to DEBP is achieved mostly through hydrogen bonds between the glutamate and side-chain and main-chain groups of DEBP. Side chains of residues Arg24, Ser72, Arg75, Ser90, and His164 anchor the deprotonated gamma-carboxylate group of the glutamate with six hydrogen bonds. Side chains of Arg75 and Arg90 form salt bridges with the deprotonated alpha-carboxylate group, while the main-chain amide groups of Thr92 and Thr140 form hydrogen bonds with the same group. The positively charged alpha-amino group of the L-glutamate forms salt bridge interaction with the side-chain carboxylate group of Asp182 and hydrogen bond interaction with main-chain carbonyl oxygen of Ser90. In addition to these hydrogen bond and electrostatic interactions, other interactions may also play important roles. For example, the two methylene groups from the glutamate form van der Waals interactions with hydrophobic side chains of DEBP. Comparisons with several other periplasmic amino acid binding proteins indicate that DEBP residues involved in the binding of alpha-amino and alpha-carboxylate groups of the ligand and the pattern of hydrogen bond formation between these groups are very well conserved, but the binding pocket around the ligand side chain is not, leading to the specificity of DEBP. We have identified structural features of DEBP that determine its ability of binding glutamate and aspartate, two molecules with different sizes, but discriminating against very similar glutamine and asparagine molecules.


Vector quantization of images using modified adaptive resonance algorithm for hierarchical clustering.
A modified adaptive resonance theory (ART2) learning algorithm, which we employ in this paper, belongs to the family of NN algorithms whose main goal is the discovery of input data clusters, without considering their actual size. This feature makes the modified ART2 algorithm very convenient for image compression tasks, particularly when dealing with images with large background areas containing few details. Moreover, due to the ability to produce hierarchical quantization (clustering), the modified ART2 algorithm is proved to significantly reduce the computation time required for coding, and therefore enhance the overall compression process. Examples of the results obtained are presented, suggesting the benefits of using this algorithm for the purpose of VQ, i.e., image compression, over the other NN learning algorithms.


[Copper metabolic disorder in extravasal stenosis of the celiac trunk].
Copper metabolism was studied in 82 patients with extravasal stenosis of the celiac trunk and in 14 patients with disturbed potency of the celiac trunk and inesenterial arteries of atherosclerotic etiology. The following parameters were analyzed: activity of ceruloplasmin and cytochromoxidase and copper content in the blood serum, copper and cytochromoxidase in the liver. It has been established that the level of the above elements in the blood and liver can be a diagnostic sign of chronic ischemia of the liver in patients with extravasal stenosis of the celiac trunk.


SAGES consensus recommendations on surgical video data use, structure, and exploration (for research in artificial intelligence, clinical quality improvement, and surgical education).
Surgery generates a vast amount of data from each procedure. Particularly video data provides significant value for surgical research, clinical outcome assessment, quality control, and education. The data lifecycle is influenced by various factors, including data structure, acquisition, storage, and sharing; data use and exploration, and finally data governance, which encompasses all ethical and legal regulations associated with the data. There is a universal need among stakeholders in surgical data science to establish standardized frameworks that address all aspects of this lifecycle to ensure data quality and purpose. Working groups were formed, among 48 representatives from academia and industry, including clinicians, computer scientists and industry representatives. These working groups focused on: Data Use, Data Structure, Data Exploration, and Data Governance. After working group and panel discussions, a modified Delphi process was conducted. The resulting Delphi consensus provides conceptualized and structured recommendations for each domain related to surgical video data. We identified the key stakeholders within the data lifecycle and formulated comprehensive, easily understandable, and widely applicable guidelines for data utilization. Standardization of data structure should encompass format and quality, data sources, documentation, metadata, and account for biases within the data. To foster scientific data exploration, datasets should reflect diversity and remain adaptable to future applications. Data governance must be transparent to all stakeholders, addressing legal and ethical considerations surrounding the data. This consensus presents essential recommendations around the generation of standardized and diverse surgical video databanks, accounting for multiple stakeholders involved in data generation and use throughout its lifecycle. Following the SAGES annotation framework, we lay the foundation for standardization of data use, structure, and exploration. A detailed exploration of requirements for adequate data governance will follow.


Adaptation and evaluation of the Family Involvement and Alienation Questionnaire for use in the care of older people, psychiatric care, palliative care and diabetes care.
To adapt the Family Involvement and Alienation Questionnaire (FIAQ) for use in the care of older people, psychiatric care, palliative care and diabetes care and to evaluate its validity and reliability. Involvement in the professional care has proven to be important for family members. However, they have described feelings of alienation in relation to how they experienced the professionals' approach. To explore this issue, a broad instrument that can be used in different care contexts is needed. A psychometric evaluation study, with a cross-sectional design. The content validity of the FIAQ was evaluated during 2014 by cognitive interviews with 15 family members to adults in different care contexts. Psychometric evaluation was then conducted (2015-2016). A sample of 325 family members participated, 103 of whom in a test-retest evaluation. Both parametric and non-parametric methods were used. The content validity revealed that the questionnaire was generally understood and considered to be relevant and retrievable by family members in the contexts of the care of older people, psychiatric care, palliative care and diabetes care. Furthermore, the FIAQ (Revised), demonstrated satisfactory psychometric properties in terms of data quality, homogeneity, unidimensionality (factor structure), internal consistency and test-retest reliability. The study provides evidence that the FIAQ (Revised) is reliable and valid for use in further research and in quality assessment in the contexts of the care of older people, psychiatric care, palliative care and diabetes care.


Linearization of the bradford protein assay.
Determination of microgram quantities of protein in the Bradford Coomassie brilliant blue assay is accomplished by measurement of absorbance at 590 nm. This most common assay enables rapid and simple protein quantification in cell lysates, cellular fractions, or recombinant protein samples, for the purpose of normalization of biochemical measurements. However, an intrinsic nonlinearity compromises the sensitivity and accuracy of this method. It is shown that under standard assay conditions, the ratio of the absorbance measurements at 590 nm and 450 nm is strictly linear with protein concentration. This simple procedure increases the accuracy and improves the sensitivity of the assay about 10-fold, permitting quantification down to 50 ng of bovine serum albumin. Furthermore, the interference commonly introduced by detergents that are used to create the cell lysates is greatly reduced by the new protocol. A linear equation developed on the basis of mass action and Beer's law perfectly fits the experimental data.


Invasion of the canalis sinuosus by dental implants: A report of 3 cases.
The canalis sinuosus (CS) and its accessory canals (ACs) are anatomical structures in the anterior maxilla. These structures are often neglected when planning implant surgery because their clinical significance is still not well-defined. After a retrospective evaluation of 194 patients rehabilitated with dental implants in the anterior maxilla, 3 patients were identified who presented unexpected chronic neurosensory disturbances without any clinical signs supportive of implant failure. Tomographic assessment using cone-beam computed tomography (CBCT) revealed the invasion of the CS and ACs by dental implants, which appeared to explain the patients' symptoms. The purpose of this report was to familiarize practicing dentists and specialists with the CS and its ACs. Unanticipated neurosensory symptoms after implant placement in the anterior maxilla justify the use of CBCT to rule out an injury to this neurovascular bundle.


[The use of sorption therapy in the combined treatment of exudative erythema multiforme].
Polymethylsiloxan, a sorbent, was used in combination with enterosorption with thermal alkaline mineral water in a complex treatment of patients (n = 37) with multiform exudative erythema. During the 45-min therapeutic session the sorbent-applicator was changed three times. The above therapy makes for rapid healing of erosions, reduces treatment time periods, prevents recurrences irrespective of the causative factors of inductors of the disease under study.


Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?
Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.


Small capsid protein pORF65 is essential for assembly of Kaposi's sarcoma-associated herpesvirus capsids.
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for KS tumors, multicentric Castleman's disease, and primary effusion lymphomas. Like other herpesvirus capsids, the KSHV capsid is an icosahedral structure composed of six proteins. The capsid shell is made up of the major capsid protein, two triplex proteins, and the small capsid protein. The scaffold protein and the protease occupy the internal space. The assembly of KSHV capsids is thought to occur in a manner similar to that determined for herpes simplex virus type 1 (HSV-1). Our goal was to assemble KSHV capsids in insect cells using the baculovirus expression vector system. Six KSHV capsid open reading frames were cloned and the proteins expressed in Sf9 cells: pORF25 (major capsid protein), pORF62 (triplex 1), pORF26 (triplex 2), pORF17 (protease), pORF17.5 (scaffold protein), and also pORF65 (small capsid protein). When insect cells were coinfected with these baculoviruses, angular capsids that contained internal core structures were readily observed by conventional electron microscopy of the infected cells. Capsids were also readily isolated from infected cells by using rate velocity sedimentation. With immuno-electron microscopy methods, these capsids were seen to be reactive to antisera to pORF65 as well as to KSHV-positive human sera, indicating the correct conformation of pORF65 in these capsids. When either virus expressing the triplex proteins was omitted from the coinfection, capsids did not assemble; similar to observations made in HSV-1-infected cells. If the virus expressing the scaffold protein was excluded, large open shells that did not attain icosahedral structure were seen in the nuclei of infected cells. The presence of pORF65 was required for capsid assembly, in that capsids did not form if this protein was absent as judged by both by ultrastructural analysis of infected cells and rate velocity sedimentation experiments. Thus, a novel outcome of this study is the finding that the small capsid protein of KSHV, like the major capsid and triplex proteins, is essential for capsid shell assembly.


Adenosine Inhibits Ovarian Cancer Growth Through Regulating RhoGDI2 Protein Expression.
This study aimed to investigate the effect of adenosine (Ado) on the growth of ovarian cancer and to explore the related mechanisms. The effect of Ado on the proliferation of A2780 human ovarian cancer cells was examined according to the MTT method. Moreover, the nude mouse model of subcutaneous A2780 xenograft was constructed, and then, Ado and cisplatin were administered intraperitoneally to investigate the effect of Ado on tumor growth in vivo. Immunohistochemistry (IHC) was carried out to study the effect of Ado on the expression of Rho-specific guanine nucleotide dissociation inhibitor 2 (RhoGDI2) in the subcutaneous xenografts. Afterwards, the commercially constructed RhoGDI2 siRNA plasmid was transfected into A2780 cells, and tube formation assay was conducted to determine the effect of down-regulating RhoGDI2 expression on the regulation of angiogenesis in ovarian cancer by Ado. Besides, Western blotting was performed to detect the effect of RhoGDI2 down-regulation on the regulation of matrix metalloproteinase 2 (MMP-2), MMP-9, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), tumor necrosis factor (TNF-α), and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) expression in ovarian cancer cells by Ado. The relative viability of cells subsequent to Ado treatment proved to be both concentration- and time dependent. IHC results showed that Ado evidently enhanced the RhoGDI2 protein expression. In addition, interference with RhoGDI2 outstandingly attenuated the ability of Ado to suppress tumor cell invasion and induce angiogenesis in vitro. Furthermore, molecular mechanism studies indicated that Ado remarkably inhibited the expression of MMP-2, MMP-9, VEGF, TGF-β, TNF-α, and CD31, while interference with RhoGDI2 restored the expression of the above-mentioned angiogenic factors. Ado inhibits the growth of A2780 human ovarian cancer cells through inhibiting tumor cell invasion and angiogenesis in a RhoGDI2-dependent manner.


2-Amino-4,6-dimethyl-pyrimidin-1-ium chloride.
In the title compound, C6H10N3(+)·Cl(-), the cation is essentially planar with an r.m.s. deviations of the fitted atoms of 0.008 Å. In the crystal, adjacent ions are linked by weak N-H⋯Cl hydrogen bonds involving the pyrimidine and amine N atoms, forming a three-dimensional network. C-H⋯π inter-actions between the methyl and pyrimidine groups and π-π stacking [centroid-centroid distance = 3.474 (1) Å] between parallel pyrimidine ring systems are also observed.


Impact of Ramadan on demographics and frequencies of disease-related visits in the emergency department.
Summary The objective of this study was to determine whether Ramadan is changing frequencies and demographics of visits due to certain diseases. Data obtained from the charts of the adult patients admitted into the emergency department (ED) due to 10 predetermined entities between 2000 and 2004 were analysed. Demographic variables analysed separately for certain entities visiting the ED in Ramadan were not found to be different from visits in other times of year. Visit frequencies for hypertension and uncomplicated headache in Ramadan were significantly higher than in non-Ramadan months (chi(2) test, p = 0.015 for hypertension, p < 0.001 for uncomplicated headache). Mean age of the patients admitted to the ED due to diabetes-related conditions in Ramadan was significantly lower than in pre- and post-Ramadan months (59.91 +/- 14.60 and 62.11 +/- 14.61, respectively) (Mann-Whitney U-test, p = 0.032). The patients with diabetes presenting in Ramadan were found significantly younger than their peers in the rest of the year. For other diseases, Ramadan does not appear to be a risk factor.


The identification and screening of men at high risk for developing prostate cancer.
It is estimated that the lifetime risk of being diagnosed with prostate cancer is 1 in 5. The identification of risk factors, including age, African-American ancestry, family history, and possibly diet and environmental factors, has allowed health care professionals the opportunity to identify, screen, and study men at the greatest risk of developing prostate cancer. The risk factors, current screening tools, and the informed consent process for men participating in a prostate cancer screening program are outlined.


TMEM25 modulates neuronal excitability and NMDA receptor subunit NR2B degradation.
The expression of the transmembrane protein 25 gene (Tmem25) is strongly influenced by glutamate ionotropic receptor kainate type subunit 4, and its function remains unknown. Here, we showed that TMEM25 was primarily localized to late endosomes in neurons. Electrophysiological experiments suggested that the effects of TMEM25 on neuronal excitability were likely mediated by N-methyl-d-aspartate receptors. TMEM25 affected the expression of the N-methyl-d-aspartate receptor NR2B subunit and interacted with NR2B, and both were colocalized to late endosome compartments. TMEM25 induced acidification changes in lysosome compartments and accelerated the degradation of NR2B. Furthermore, TMEM25 expression was decreased in brain tissues from patients with epilepsy and epileptic mice. TMEM25 overexpression attenuated the behavioral phenotypes of epileptic seizures, whereas TMEM25 downregulation exerted the opposite effect. These results provide some insights into TMEM25 biology in the brain and the functional relationship between TMEM25 and epilepsy.


Prevalence of Baseline Erectile Dysfunction (ED) in an Australian Cohort of Men with Localized Prostate Cancer.
Erectile dysfunction (ED) is a common complication following prostate cancer treatment. Post-treatment erectile function (EF) preservation is strongly dependent on the baseline EF prior to treatment. To assess the baseline EF among patients with localized prostate cancer, and the factors associated with baseline EF. All men with clinically localized prostate cancer had their baseline EF assessed prior to brachytherapy at our institution. Six hundred ninety-nine men who completed the International Index of Erectile Function five-item questionnaires pre-treatment between 2001 and 2013 were included in the study. Data on patient factors (medical comorbidities and smoking history) and prostate cancer clinicopathological characteristics were recorded. Ordinal logistic regressions were used to estimate the effects of each variable on the severity of ED. Baseline EF among men with localized prostate cancer, and factors associated with ED. Prior to permanent seed brachytherapy, 335 (48%) patients reported no ED, 129 (17%) mild ED, 42 (6%) mild-moderate ED, 37 (5%) moderate ED, and 165 (24%) severe ED. In multivariate analyses, age, diabetes, and hypertension remained to be independently associated with ED, with diabetes most strongly associated with worse ED (odds ratio = 2.6; 95% confidence interval = 1.3-5.3). ED is common among patients with localized prostate cancer prior to any curative treatment. Assessment of baseline ED is important prior to curative treatment of prostate cancer in order to offer appropriate advise on likelihood of EF preservation post-treatment and avoid patient dissatisfaction with treatment outcomes due to unrealistic expectations.


Lymphotoxin-alpha (LTalpha) supports development of splenic follicular structure that is required for IgG responses.
LTalpha-deficient (LTalpha-/-) mice show altered splenic microarchitecture. This includes loss of normal B cell-T cell compartmentalization, of follicular dendritic cell (FDC) clusters, and of ability to form germinal centers (GC). LTalpha-/- mice immunized with sheep red blood cells (SRBC) produced high levels of antigen-specific IgM but no IgG in either primary or secondary responses, demonstrating failure of Ig class switching. This inability to switch to IgG could have been due to the altered splenic microarchitecture in these mice. Alternatively, it could have been due directly to a requirement for LTalpha expression by lymphocytes cooperating in the antibody response. To investigate this, we performed reciprocal spleen cell transfers. When irradiated LTalpha-/- mice were reconstituted with wild-type splenocytes and immunized immediately with SRBC, splenic microarchitecture remained disturbed and there was no IgG response. In contrast, when irradiated wild-type animals received splenocytes from LTalpha-/- mice, follicle structure and a strong IgG response were retained. These data indicate that LTalpha-deficient B cells and T cells have no intrinsic defect in ability to generate an IgG response. Rather, the altered microenvironment characteristic of LTalpha-/- mice appears to result in impaired ability to switch to a productive IgG response. To investigate whether prolonged expression of LTalpha could alter the structure and function of spleen follicles, reciprocal bone marrow (BM) transplantation was performed. Six weeks after reconstitution of LTalpha-/- mice with wild-type BM, spleen follicle structure was partially restored, with return of FDC clusters and GC. B cell/T cell compartmentalization remained abnormal and white pulp zones were small. This was accompanied by restoration of IgG response to SRBC. Reconstitution of wild-type mice with LTalpha-/- BM resulted in loss of FDC clusters and GC, and loss of the IgG response, although compartmentalized B cell and T cell zones were largely retained. Thus, defective IgG production is not absolutely associated with abnormal B cell and T cell compartmentalization. Rather, expression of LTalpha supports the maturation of spleen follicle structure, including the development and maintenance of FDC clusters, which supports Ig class switching and an effective IgG response.


Review article: the evolving role of information technology in perioperative patient safety.
The adoption of new technologies in medicine is frequently met with both enthusiasm and resistance. The universal adoption of health information technology (IT) and anesthesia information management systems (AIMS) remains low despite the potential benefits. Electronic medical records, and hence AIMS, are at the intersection of patient safety. This article highlights advantages and barriers to adoption and implementation of IT in general and AIMS in particular, with a focus on clinical decision support systems (CDSS) and computerized physician order entry (CPOE) as hallmarks that may lead to improvement in patient safety and quality in the perioperative setting. The advantages of health IT and AIMS include improved legibility of documentation; the ability to integrate new scientific evidence into practice; enhanced management and exchange of complex health information; the ability to standardize order sets, incorporate computerized physician order entry, and provide clinical decision support; and the ability to capture data for management, research, and quality monitoring and reporting. While not foolproof, AIMS have been shown to improve safety, quality, and patient outcomes. Barriers to the adoption of health IT and AIMS include costs, lack of truly interoperable AIMS components in health-system IT solutions, and lack of clinician involvement in implementation, planning, design, and installation of many IT or AIMS products. Health IT and AIMS are at the intersection of patient safety and technology. Anesthesiologists are perfectly positioned to be the physician leaders of adoption, design, implementation, and integration, not only for AIMS but also for health-system IT solutions in general.


Fear, anger, fruits, and veggies: interactive effects of emotion and message framing on health behavior.
Message framing is a theoretically grounded health communication strategy designed to motivate action by emphasizing either the benefits of engaging in a particular behavior (gains) or the costs of failing to engage in the behavior (losses). This study investigated whether the effectiveness of a framed message depends on the emotional state of the message recipient. We examined effects of fear versus anger, emotions that frequently occur within the context of health decision-making. Undergraduate students (N = 133) were randomly assigned to complete a fear or anger induction task after which they read a gain- or loss-framed pamphlet promoting fruit and vegetable consumption. Fruit and vegetable intake (servings per day) subsequently was assessed over the following 2 weeks. As predicted, a significant frame by emotion interaction was observed, such that participants in the fear condition reported eating more servings of fruits and vegetables after exposure to a loss-framed message than to a gain-framed message. In contrast, participants in the anger condition reported eating (marginally) more servings of fruits and vegetables after exposure to a gain-framed message than to a loss-framed message. Greater increases in fruit and vegetable intake from baseline to follow-up were observed when the message frame was matched to the participant's emotional state. The effectiveness of framed health communications depends on the message recipient's current emotional state. Affective factors that are incidental to the behavior recommended in a health communication can affect the relative success of gain- and loss-framed appeals.


Effects of a hybrid exercise on the activities of myogenic enzymes in plasma.
"Hybrid" exercise uses forces generated by an electrically stimulated muscle to resist the motion of a volitionally contracting agonist. This approach is effective in increasing muscle bulk and strength. Its safety, however, has not been studied and the purpose of this study was to address this lack by assessing the impact of a hybrid strengthening regimen on the serological markers of exercise associated muscle damage. Twelve healthy, sedentary men between the ages of 20 and 27 years were divided into two groups of 6. The members of each group completed an exercise session that consisted of 10 sets of 10 reciprocal elbow flexor and extensor contractions separated by 1-minute rest intervals. In one group, the subjects underwent a hybrid exercise protocol. Subjects in the second group underwent a conventional isometric electrical stimulation program with the same stimulation intensities. Plasma creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were determined immediately before and after the exercise session as well as at follow-up 1, 2, and 7 days later. Secondary variables included active and passive range of motion and the subjects' perceived levels of "soreness" . Evaluation revealed that neither enzymatic activities nor range of motion changed in a statistically significant manner with time within the groups or between the groups. In conclusion, the stimulation intensities involved in hybrid exercise programs of the upper extremity do not appear to be associated with either overt or covert signs of muscle injury.


[International Society of Urological Pathology (ISUP) Consensus Conference on handling and staging of radical prostatectomy specimens].
The 2009 International Society of Urological Pathology (ISUP) consensus conference on handling and staging of radical prostatectomy specimens issued recommendations for standardization of pathology reporting of radical prostatectomy specimens. The conference addressed specimen handling, T2 substaging, prostate cancer volume, extraprostatic extension, lymphovascular invasion, seminal vesicle invasion, lymph node metastases and surgical margins. This review summarizes the conclusions and recommendations resulting from the consensus process.


[Parkinson disease mortality rates in Chile].
Parkinson disease (PD) is the second more common neurodegenerative disorder and determines a loss in quality of life, caregiver burden and increased mortality in those affected. To determine the rates of mortality due to Parkinson disease in Chile. Data were collected from death certificates between 1997 and 2008. Mortality rates were calculated and the mortality trend was established along the study period, and analyzed by age, sex and geographic región of Chile. There was a steady increase in mortality over the years, particularly since 2001 (r²= 0.85, p < 0.01). The increase in mortality rates was 0.25 per 100.000 habitants/year (r²: 0.89, p < 0.01). Mortality was always higher in men and in those older than 80 years. The highest rate (per 100,000 habitants) in Chile was observed in the región of Valparaíso (2.4) while the lowest was in Antofagasta (0.8) (t = 3.72, p < 0.05). Mortality associated with PD has increased progressively, consistent with the expected increase in prevalence of the disease in the population.


Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system.
In Drosophila, male courtship behavior is regulated in large part by the gene fruitless (fru). fru encodes a set of putative transcription factors that promote male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. Little is known about how Fru proteins function at the level of transcriptional regulation or the role that isoform diversity plays in the formation of a male-specific nervous system. To characterize the roles of sex-specific Fru isoforms in specifying male behavior, we generated novel isoform-specific mutants and used a genomic approach to identify direct Fru isoform targets during development. We demonstrate that all Fru isoforms directly target genes involved in the development of the nervous system, with individual isoforms exhibiting unique binding specificities. We observe that fru behavioral phenotypes are specified by either a single isoform or a combination of isoforms. Finally, we illustrate the utility of these data for the identification of novel sexually dimorphic genomic enhancers and novel downstream regulators of male sexual behavior. These findings suggest that Fru isoform diversity facilitates both redundancy and specificity in gene expression, and that the regulation of neuronal developmental genes may be the most ancient and conserved role of fru in the specification of a male-specific nervous system.


Patients' understanding of the reasons for starting and discontinuing inhaled corticosteroids.
Although early discontinuation of treatment in new users of inhaled corticosteroids (ICS) has been widely discussed, the reasons for stopping have not been investigated in depth. We aimed to describe reasons for discontinuation from a patient's perspective in relation to their experience of symptoms at the time of the investigation. A cross-sectional study among new users that discontinued ICS use in the Netherlands was performed. Patients were interviewed by telephone, aiming to identify the symptoms for which they were prescribed ICS, the reasons for discontinuing treatment and the respiratory symptoms patients still experienced at the time of the survey. In addition, automated dispensing records of all patients were retrieved. From 287 eligible patients, 230 (80.1%) were interviewed. Only 22 patients (9.6%) mentioned asthma as the reason for a first ICS prescription. A decrease in symptoms was the main reason for discontinuation (45%). Thirty patients (13%) reported clinically significant residual symptoms. These patients reported more seasonal variation of symptoms and were more often prescribed short-acting beta(2)-agonists. The majority of patients mentioned a wide range of symptoms and conditions, other than asthma or chronic obstructive pulmonary disease, as the reason for the start of ICS therapy. Most of these conditions may be expected to be of short duration. Not surprisingly a decrease in symptoms was the main, and justifiable, reason for discontinuing ICS. However, a non-negligible proportion of patients reported residual symptoms that suggest the need of continued ICS use. Physicians and pharmacists could cooperate in identifying those patients for which ICS are really indicated and motivate them to continue the use of ICS.


DNA end joining by the Klenow fragment of DNA polymerase I.
DNA end joining is a type of illegitimate recombination characterized by the joining of two DNA ends that lack homology. Using oligonucleotides as substrate, we found that an exonuclease-free derivative of the Klenow fragment of Escherichia coli DNA polymerase I can mediate DNA end joining in vitro. DNA sequence analysis of product DNA indicated that overlap products were formed between direct repeat sequences at the termini of the oligonucleotides. Formation of recombinant products was dependent on the strandedness of the substrate DNA, and the rate of product formation was dependent on the size of the potential overlap. With one to three complementary bases available for pairing at the 3' termini, there was an absolute requirement that one of the oligonucleotides be double-stranded, whereas with four complementary bases, products were also formed in reactions with single-stranded oligonucleotides. When noncomplementary nucleotides were added to the terminus of one of the oligonucleotides, product formation was delayed but not blocked. These data indicate that a DNA polymerase can mediate DNA double strand break rejoining in the absence of other proteins.


Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol.
Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.


Contribution of adenosine to arteriolar autoregulation in striated muscle.
The contribution of adenosine to blood flow autoregulation in striated muscle was evaluated by direct in vivo visualization of arterioles in the rat cremaster muscle. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium, and the cremaster muscle was surgically exposed and maintained in a controlled tissue bath environment with pH 7.40, CO2 tension (PCO2) congruent to 40 mmHg, and O2 tension (PO2) at either a high (congruent to 70 mmHg) or a low (congruent to 10 mmHg) value. Local adenosine activity was blocked in some animals by the addition of theophylline (3 X 10(-5) M) to the bath medium. Individual second (2A)- and third (3A)-order arterioles were observed via closed-circuit television microscopy, and blood flow in each arteriole was calculated from simultaneous measurements of arteriolar diameter and red blood cell velocity. Perfusion pressure to the animal's hindquarters was altered by varying the degree of occlusion of the sacral aorta; arteriolar diameter, velocity, and blood flow responses were plotted as a function of the varying pressure. Both 2A and 3A arterioles exhibited vasodilation and substantial superregulation of blood flow (increased blood flow with decreased perfusion pressure) when bath PO2 was low and adenosine activity was not blocked. Addition of theophylline to the cremaster bath medium significantly reduced the dilation and abolished superregulation, although substantial autoregulation remained. When bath PO2 was high, the degree of arteriolar dilation and autoregulation was reduced compared with the low bath PO2 responses, and blocking adenosine activity had no effect on the responses. These results support the concept that changes in local adenosine levels are involved in the autoregulatory responses observed in the rat cremaster muscle and that the magnitude of adenosine's contribution is directly related to the degree of tissue hypoxia. However, blocking adenosine activity did not totally abolish autoregulation, suggesting that other metabolic and/or myogenic factors may also be contributing to blood flow regulation in this tissue.


Oriented LiMn2O4 Particle Fracture from Delithiation-Driven Surface Stress.
The insertion and removal of Li+ ions into Li-ion battery electrodes can lead to severe mechanical fatigue because of the repeated expansion and compression of the host lattice during electrochemical cycling. In particular, the lithium manganese oxide spinel (LiMn2O4, LMO) experiences a significant surface stress contribution to electrode chemomechanics upon delithiation that is asynchronous with the potentials where bulk phase transitions occur. In this work, we probe the stress evolution and resulting mechanical fracture from LMO delithation using an integrated approach consisting of cyclic voltammetry, electron microscopy, and density functional theory (DFT) calculations. High-rate electrochemical cycling is used to exacerbate the mechanical deficiencies of the LMO electrode and demonstrates that mechanical degradation leads to slowing of delithiation and lithiation kinetics. These observations are further supported through the identification of significant fracturing in LMO using scanning electron microscopy. DFT calculations are used to model the mechanical response of LMO surfaces to electrochemical delithiation and suggest that particle fracture is unlikely in the [001] direction because of tensile stresses from delithiation near the (001) surface. Transmission electron microscopy and electron backscatter diffraction of the as-cycled LMO particles further support the computational analyses, indicating that particle fracture instead tends to preferentially occur along the {111} planes. This joint computational and experimental analysis provides molecular-level details of the chemomechanical response of the LMO electrode to electrochemical delithiation and how surface stresses may lead to particle fracture in Li-ion battery electrodes.


Two instances of Chinese herbal medicine poisoning in Singapore.
Datura metel L. (Yangjinghua) is a toxic herb that contains anticholinergic compounds. Inappropriate consumption of this herb could result in anticholinergic poisoning. Clinical features of such poisoning have not been previously described. We report two such cases. Both patients had taken brews of Datura metel L., and developed poisoning soon afterwards. Prominent clinical features included confusion, dilated pupils, absence of sweating, and the absence of sluggish bowel sounds. No flushing of the face or skin was detected in either case. Both patients recovered fully within 12 hours with supportive measures, and no gastric elimination or antidote was used. The different names ascribed to Datura metel L. in chinese medicine can be confusing; this confusion resulted in the poisoning of one of our patients. The clinical features of Datura metel L. poisoning and concerns over inappropriate uses of herbal medicine are discussed.


Precision behavioral medicine: Implications of genetic and genomic discoveries for behavioral weight loss treatment.
This article reviews the concept of precision behavioral medicine and the progress toward applying genetics and genomics as tools to optimize weight management intervention. We discuss genetic, epigenetic, and genomic markers, as well as interactions between genetics and the environment as they relate to obesity and behavioral weight loss to date. Recommendations for the conditions under which genetics and genomics could be incorporated to support clinical decision-making in behavioral weight loss are outlined and illustrative scenarios of how this approach could improve clinical outcomes are provided. It is concluded that there is not yet sufficient evidence to leverage genetics or genomics to aid the treatment of obesity but the foundations are being laid. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


[Clinical and immunological criteria of the activity of inflammatory reaction and autolymphokine therapy in penetrating wounds of the eye].
Clinical and immunological criteria of an unfavorable course of posttraumatic process were defined and the efficacy of autolymphokine therapy in the postoperative treatment of patients with penetrating wounds to the eye assessed. A total of 119 patients were examined. Autolymphokine therapy supplemented the traditional postoperative treatment in 38 of them. An unfavorable course of the posttraumatic period was associated with high levels of tumor necrosis factor-alpha and interleukin-1-beta in the blood serum and lacrimal fluid, with accumulation and long persistence of high titers of antibodies to lens antigens and retinal S-antigen in the lacrimal fluid, with intensive cellular immune response to these antigens in the leukocyte migration inhibition test, and with a deficit of tissue-specific anticorneal antibodies in the lacrimal fluid during the first 3-4 weeks after the injury. In the event of a favorable outcome the cytokines were detected in the minimal amounts, and antibody titers were moderate. Autolymphokine therapy 2 to 3 times decreased the concentration of cytokines in the lacrimal fluid, maintained the moderate level of autoantibodies in the lacrimal fluid, decreased the incidence of the leukocyte migration inhibition and the duration of its detection, and shortened the period of autoantibody detection in the blood serum.


[For an interdisciplinary museology. The particular case of anatomical waxes].
Nowadays, the anatomical models in three dimensions are often showed in Museums devoted to the History of Medicine. Due to their historical importance and the major role they played as scientific education tool, they are essentials to understand the heritage of the anatomical knowledge. Historically, within all materials used to cast the body, wax has been the most frequently used, so that the ceroplastical collection has become a part of the medical education before leading to a general public pedagogy. This paper has a double purpose. In one hand, it aims to survey the formal evolution and the uses of this production, from his creation on, in the other, to study this cultural heritage within the museology issue.


Recombination and nondisjunction in humans and flies.
Recent studies of Drosophila and humans indicate that aberrant genetic recombination is an important component of nondisjunction in both species. In both, a proportion of nondisjunction is associated with failure to pair and/or recombine and in both, exchanges which are either too distal or too proximal increase the likelihood of malsegregation. In this review we provide two perspectives on these observations: first, a review of exchange and chromosome segregation in model organisms, focusing on Drosophila, and secondly an overview of nondisjunction in humans. This format allows us to describe the paradigms developed from studies of model organisms and to ask whether these paradigms apply to the human situation.


Prolyl isomerase Pin1 promotes autophagy and cancer cell viability through activating FoxO3 signalling.
Pin1-directed prolyl isomerization is a central common oncogenic mechanism to drive tumorigenic processes. However, the role of Pin1 in cellular autophagy is still poorly understood. Here we report that pharmacological inhibition of Pin1 decreased the formation of autophagosome/autolysosomes upon nutrient starvation. Inhibition of Pin1 reduced, whereas forced expression of Pin1 increased, the level of LC3 and viability of U2OS and PANC-1 cells. Pin1 could augment the accumulation of LC3 upon chloroquine treatment, while chloroquine also disturbed its function on cell viability. RNA-Seq and qPCR identified altered autophagic pathway upon Pin1 silencing. Mechanistically, FoxO3 was identified critical for Pin1-mediated autophagy. Knockdown of FoxO3 could rescue the changes of LC3 level and cellular viability caused by Pin1 overexpression. In xenograft mouse model, Pin1 reduced the sensitivity of PANC-1 to chloroquine while FoxO3 silencing could inhibit Pin1's function. Moreover, Pin1 could bind FoxO3 via its pS284-P motif, reduce its phosphorylation at T32, facilitate its nuclear retention, and therefore increased its transcriptional activity. S284A mutation of FoxO3 interfered with its T32 phosphorylation, reduced its nuclear localization and disrupted its function to support cell viability upon nutrient starvation. Furthermore, the protein level of Pin1 positively correlated with FoxO3 nuclear localization and LC3 level in pancreatic adenocarcinoma and osteosarcoma samples. Together, this study highlights an important role for Pin1-FoxO3 axis in regulating autophagy and cancer cell viability. Intervening in the Pin1-FoxO3 interaction would serve as an effective therapeutic strategy and the pS284-P motif of FoxO3 provides a potential target for drug design.


[Quality management in histopathology. "From biopsy to diagnosis"].
The University Institute of Pathology (IUP), Lausanne, has established a system designed to continuously document and manage the quality of its diagnostic activity in surgical pathology. To realize the system a few tools were created. Several "free codes" were introduced into the general computer system in order to register and evaluate (1) the quality of frozen section diagnoses, (2) the relevance of the use of this type of examination and (3) the frequency of spontaneous "official" internal consultations in search of a second opinion. Further, an evaluation checklist including all steps leading to the diagnosis (some of which were facultative*) was established. Eleven items were evaluated and registered in this way: quality of slides and staining, reporting time, selection of tissue blocks*, macro- and microscopic descriptions*, appropriateness of special stains and/or techniques and their quality*, final diagnosis, accuracy of codes for invoicing and diagnoses, quality of the final report. The relevance of the furnished clinical data was also evaluated and recorded. Of all registered frozen section examinations (397), 86.6% showed identity of provisional and definitive diagnoses. In 11.6% of cases there was a difference between the two diagnoses without clinical relevance, and in 1.8% the discrepancy was clinically significant. These percentages are comparable with those published in the literature. Internal consultation for second opinion is a current habit in our institution, and 980 cases (4%) were registered as such. Among the 25,249 cases received for histopathological examination during 1998 (each case may concern more than one specimen from the same patient), 495 (2% = 2-3 cases/day) were evaluated in detail by two reviewers throughout the year. The statistical results obtained demonstrate that our diagnostic performance in histopathology is very satisfactory: 43% of the analysed cases bear no deficit and 67.3% present two or less points in deficit; no diagnostic error was evidenced; 70% of the reports are signed-out within 3 days after reception of the material (mean delay < 3 days). The adopted system represents an excellent tool by which to continuously document and manage the quality of our diagnostic performances. It is reliable, efficient, sensitive and also feasible, as it does not require significant or exaggerated additional investments. The results obtained after one year confirm the high quality of the IUP's diagnostic activity.


What is the clinical utility of DNA testing in patients with familial hypercholesterolaemia?
Familial hypercholesterolaemia is a common genetic disorder of lipid metabolism in which patients have a significantly elevated risk of early coronary heart disease, which can be substantially lowered by treatment with the statin class of drugs. In many countries in Europe, tracing of relatives using DNA information, once the family mutation has been identified, is being actively carried out. The present review examines the specificity and clinical utility of DNA testing in patients with familial hypercholesterolaemia. Technological progress has improved the detection rate in patients with the strongest clinical suspicion of familial hypercholesterolaemia to more than 70-80%. Patients carrying a mutation have, on average, higher low-density lipoprotein cholesterol levels and greater risk of early coronary heart disease, and studies have reported the utility of DNA information in the identification of affected relatives. More than 1000 different molecular causes of familial hypercholesterolaemia are documented in the University College London database, and although more than 90% of these clearly cause familial hypercholesterolaemia, the remainder require careful interpretation. DNA testing, as an adjunct to the measurement of plasma low-density lipoprotein cholesterol levels, has clinical utility in providing an unequivocal diagnosis in patients and in identifying affected relatives at an early age so that they can be offered lifestyle advice and appropriate lipid-lowering therapies. Researchers and DNA diagnostic laboratories need to interpret novel sequence changes with caution in order to avoid a false positive diagnosis.


Laser Sintered Porous Ti-6Al-4V Implants Stimulate Vertical Bone Growth.
The objective of this study was to examine the ability of 3D implants with trabecular-bone-inspired porosity and micro-/nano-rough surfaces to enhance vertical bone ingrowth. Porous Ti-6Al-4V constructs were fabricated via laser-sintering and processed to obtain micro-/nano-rough surfaces. Male and female human osteoblasts were seeded on constructs to analyze cell morphology and response. Implants were then placed on rat calvaria for 10 weeks to assess vertical bone ingrowth, mechanical stability and osseointegration. All osteoblasts showed higher levels of osteocalcin, osteoprotegerin, vascular endothelial growth factor and bone morphogenetic protein 2 on porous constructs compared to solid laser-sintered controls. Porous implants placed in vivo resulted in an average of 3.1 ± 0.6 mm3 vertical bone growth and osseointegration within implant pores and had significantly higher pull-out strength values than solid implants. New bone formation and pull-out strength was not improved with the addition of demineralized bone matrix putty. Scanning electron images and histological results corroborated vertical bone growth. This study indicates that Ti-6Al-4V implants fabricated by additive manufacturing to have porosity based on trabecular bone and post-build processing to have micro-/nano-surface roughness can support vertical bone growth in vivo, and suggests that these implants may be used clinically to increase osseointegration in challenging patient cases.


A carbon nanotube-based Raman-imaging immunoassay for evaluating tumor targeting ligands.
Herein, we describe a versatile immunoassay that uses biotinylated single-walled carbon nanotubes (SWNTs) as a Raman label, avidin-biotin chemistry to link targeting ligands to the label, and confocal Raman microscopy to image whole cells. Using a breast tumor cell model, we demonstrate the usefulness of the method to assess membrane receptor/ligand systems by evaluating a monoclonal antibody, Her-66, known to target the Her2 receptors that are overexpressed on these cells. We present two-dimensional Raman images of the cellular distribution of the SWNT labels corresponding to the distribution of the Her2 receptors in different focal planes through the cell with validation of the method using immunofluorescence microscopy, demonstrating that the Her-66-SWNT complexes were targeted to Her2 cell receptors.


[Evolution of angiogenesis following anthracycline-based neoadjuvant chemotherapy in breast cancer].
The impact of chemotherapy on the extent of breast cancer angiogenesis is unknown. The aim of this study was to investigate the effect of primary chemotherapy on tumor microvessel density and vascular endothelial growth factor (VEGF), and correlate this changes with tumor response, post-chemotherapy changes and other biological variables. In 41 consecutive patients with breast cancer stages II and III, treated with anthracycline-based neoadjuvant chemotherapy, immunohistochemical analysis of microvessel density and VEGF were performed before and after the administration of neoadjuvant chemotherapy. Microvessel density was the same in post-chemotherapy that in pre-chemotherapy samples (p = 0.29). There were no changes in the expression of VEGF (p = 0.23). The expression of VEGF and microvessel density did not show any relationship with the response in the pre-chemotherapy analysis (p = 0.60 and p = 0.30 respectively), nor in the post-chemotherapy analysis (p = 0.50 and p = 0.65 respectively). Changes post-chemotherapy were not associated with VEGF expression (p = 0.53 in the pre-chemotherapy samples and p = 0.43 in the post-chemotherapy samples) nor microvessel density (p = 0.72 in the pre-chemotherapy samples and p = 0.65 in the post-chemotherapy samples). Anthracycline-based neoadjuvant chemotherapy does not cause a reduction of the density of microvessel nor of the expression of VEGF in breast cancer.


On the effect of streamwise disturbance on the airfoil-turbulence interaction noise.
Usually the prediction of airfoil-gust interaction noise is mainly based on the flat plate solution, and only the transverse velocity disturbance that is perpendicular to the flat plate surface is considered. However, the solution might underestimate the sound generation in non-uniform mean flows for finite thickness airfoils, in which the velocity disturbance in the streamwise direction could probably produce sound as well. The effect is studied in this work by using both numerical simulations and theoretical analysis. To highlight the effect of streamwise disturbance, the anisotropic turbulences with constant transverse velocity components while varying streamwise components are employed, which can be realised by adjusting the integral length scales in the Gaussian energy spectra. The simulation results explicitly show that more sound is produced by the streamwise components for airfoils at higher Mach numbers when the flow non-uniformities are more significant. An analytical model based on acoustic analogy to account for the sound generation by the coupling between the gust and non-uniform mean flows is proposed, which explains the observations in the numerical simulation well. Also, a correction to Amiet's flat plate solution using the proposed model yields better agreement with the numerical results, especially for anisotropic turbulences with larger integral length scale in the streamwise direction.


Mammalian prions: tolerance to sequence changes-how far?
Upon prion infection, abnormal prion protein (PrP (Sc) ) self-perpetuate by conformational conversion of α-helix-rich PrP (C) into β sheet enriched form, leading to formation and deposition of PrP (Sc) aggregates in affected brains. However the process remains poorly understood at the molecular level and the regions of PrP critical for conversion are still debated. Minimal amino acid substitutions can impair prion replication at many places in PrP. Conversely, we recently showed that bona fide prions could be generated after introduction of eight and up to 16 additional amino acids in the H2-H3 inter-helix loop of PrP. Prion replication also accommodated the insertions of an octapeptide at different places in the last turns of H2. This reverse genetic approach reveals an unexpected tolerance of prions to substantial sequence changes in the protease-resistant part which is associated with infectivity. It also demonstrates that conversion does not require the presence of a specific sequence in the middle of the H2-H3 area. We discuss the implications of our findings according to different structural models proposed for PrP (Sc) and questioned the postulated existence of an N- or C-terminal prion domain in the protease-resistant region.


Prognostic significance of flow cytometric immunophenotyping in acute myeloid leukemia.
The prognostic significance of flow cytometric immunophenotyping (FCI) in acute myeloid leukemia (AML) has been controversial. In this study, we re-investigated the possible role of FCI in the prediction of AML relapse following standard chemotherapy. A total of 209 AML cases with follow-up information were analyzed. Among those, 78 cases were in remission (M:F=44/34; mean age of 48.9 years) and 131 had relapse (M:F=71/60; mean age of 51.3 years). The expression of CD34, HLA-DR or a combination of both was significantly different between the remission and relapse groups for all AML as well as AML without t(15;17). None of the pammyeloid markers or their combinations analyzed was found to correlate with treatment outcomes. Complex cytogenetic abnormalities were more likely associated with relapse group than with remission group, but were not statistically significant after excluding AML with t(15;17). In conclusion, FCI is useful in predicting treatment outcome and disease relapse in AML.


Apoptotic insults impair Na+, K+-ATPase activity as a mechanism of neuronal death mediated by concurrent ATP deficiency and oxidant stress.
The Na+, K+-ATPase (Na+, K+-pump) plays critical roles in maintaining ion homeostasis. Blocking the Na+, K+-pump may lead to apoptosis. By contrast, whether an apoptotic insult may affect the Na+, K+-pump activity is largely undefined. In cultured cortical neurons, the Na+, K+-pump activity measured as a membrane current Ipump was time-dependently suppressed by apoptotic insults including serum deprivation, staurosporine, and C2-ceramide, concomitant with depletion of intracellular ATP and production of reactive oxygen species. Signifying a putative relationship among these events, Ipump was highly sensitive to changes in ATP and reactive oxygen species levels. Moreover, the apoptosis-associated Na+, K+-pump failure and serum deprivation-induced neuronal death were antagonized by pyruvate and succinate in ATP- and reactive-oxygen-species-dependent manners. We suggest that failure of the Na+, K+-pump as a result of a combination of energy deficiency and production of reactive oxygen species is a common event in the apoptotic cascade; preserving the pump activity provides a neuroprotective strategy in certain pathological conditions.


Self-paced intermittent-sprint performance and pacing strategies following respective pre-cooling and heating.
This study examined the effects of pre-exercise cooling and heating on neuromuscular function, pacing and intermittent-sprint performance in the heat. Ten male, team sport athletes completed three randomized, counterbalanced conditions including a thermo-neutral environment (CONT), whole body submersion in an ice bath (ICE) and passive heating in a hot environment (HEAT) before 50 min of intermittent-sprint exercise (ISE) in the heat (31 + 1°C). Exercise involved repeated 15 m maximal sprints and self-paced exercise of varying intensities. Performance was measured by sprint times and distance covered during self-paced exercise. Maximal isometric contractions were performed to determine the maximal voluntary torque (MVT), activation (VA) and contractile properties. Physiological measures included heart rate (HR), core (T (core)) and skin (T (skin)) temperatures, capillary blood and perceptual ratings. Mean sprint times were slower during ICE compared to HEAT (P < 0.05). Total distance covered was not different between conditions, but less distance was covered during HEAT in 31-40 min compared to CONT, and 41-50 min compared to ICE (P < 0.05). MVT was reduced post-exercise compared to post-intervention in CONT and HEAT. VA was reduced post-intervention in HEAT compared to CONT and ICE, and post-exercise compared to ICE (P < 0.05). HR, T (core) and T (skin) during exercise were lower in ICE compared to CONT and HEAT (P < 0.05). Sprint times and distance covered were not affected by ICE and HEAT conditions compared to CONT. However, initial sprint performance was slowed by pre-cooling, with improvements following passive heating possibly due to altered contractile properties. Conversely, pre-cooling improved exercise intensities, whilst HEAT resulted in greater declines in muscle recruitment and ensuing distance covered.


Management of Priapism: Results of a Nationwide Survey and Comparison with International Guidelines.
The aim of this study is to evaluate current urologic practice regarding the management of priapism in Turkey and compare with international guidelines. Urologists and urology residents were invited to an online survey consisting of 30 multiple-choice questions on priapism-related clinical practices that were consid- ered most important and relevant to practices by using Google Forms. Total number of responses was 340. Respondents reported that they recorded a detailed patient's medical history and physical examination findings (n = 340, 100%) and laboratory testing, which includes corporal blood gas analysis (n=323, 95%). Participants announced that they performed Doppler ultrasound for 1/4 cases (n = 106, 31%), but 22% of the participants (n=75) replied that they performed in >75% of cases. Participants (n=311, 91%) responded that the first-line treatment of ischemic priapism is decompression of the corpus cavernosum. Moreover, most respondents (n = 320, 94%) stated that sympathomimetic injection drugs should be applied as the second step. About three-quarters of respondents (n = 247, 73%) indicated adrenaline as their drug of choice. Phosphodiesterase type 5 inhibitors seems to be the most pre- ferred drug for stuttering priapism (n=141, 41%). Participants (n=284, 84%) replied that corpora-glanular shunts should be preferred as the first. A large number of par- ticipants (n = 239, 70%) declared that magnetic resonance imaging can be performed in cases with delayed (>24 hours) priapism to diagnose corporal necrosis. Most of the participants (84%) responded that penile prosthesis should be preferred to shunts in cases with delayed (>48 hours) priapism. It would be appropriate to improve the training offered by professional associations and to give more training time to the management of priapism during residency.


Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks.
We studied the immunological responses in the lung, brain and spleen of ducks and chickens within the first 7 days after infection with H7N1 highly pathogenic avian influenza (HPAI). Infection with HPAI caused significant morbidity and mortality in chickens, while in ducks the infection was asymptomatic. The HPAI viral mRNA load was higher in all investigated tissues of chickens compared with duck tissues. In the lung, brain and spleen of HPAI-infected chickens, a high, but delayed, pro-inflammatory response of IL-6 and IL-1β mRNA was induced, including up-regulation of IFN-β, IFN-γ, TLR3 and MDA-5 mRNA from 1 day post infection (p.i.). Whereas in ducks already at 8 h p.i., a quicker but lower response was found for IL-6, IL-1β and iNOS mRNA followed by a delayed activation of TLR7, RIG-I, MDA5 and IFN-γ mRNA response. Virus-infected areas in the lung of chickens co-localized with KUL-01⁺ (macrophages, dendritic cells), CD4⁺, and CD8α⁺ cells, during the first day after infection. However, only KUL-01⁺ cells co-localized with the virus after 1 day p.i. In ducks, CVI-ChNL-68.1⁺ (macrophage-like cells), CD4⁺ and CD8α⁺ cells and apoptosis co-localized with the virus within 8 h p.i. Apoptosis was detected in the brain and lung of HPAI-infected chickens after 2 days p.i. and apoptotic cells co-localized with virus-infected areas. In conclusion, excessive delayed cytokine inflammatory responses but inadequate cellular immune responses may contribute to pathogenesis in chickens, while ducks initiate a fast lower cytokine response followed by the activation of major pattern recognition receptors (TLR7, RIG-I, MDA5) and a persistent cellular response.


In search of oculomotor capture during film viewing: Implications for the balance of top-down and bottom-up control in the saccadic system.
In the laboratory, the abrupt onset of a visual distractor can generate an involuntary orienting response: this robust oculomotor capture effect has been reported in a large number of studies (e.g. Ludwig & Gilchrist, 2002; Theeuwes, Kramer, Hahn, & Irwin, 1998) suggesting it may be a ubiquitous part of more natural visual behaviour. However the visual stimuli used in these experiments have tended to be static and had none of the complexity, and dynamism of more natural visual environments. In addition, the primary task in the laboratory (typically visual search) can be tedious for the participants with participant's losing interest and becoming stimulus driven and more easily distracted. Both of these factors may have led to an overestimation of the extent to which oculomotor capture occurs and the importance of this phenomena in everyday visual behaviour. To address this issue, in the current series of studies we presented abrupt and highly salient visual distractors away from fixation while participants watched a film. No evidence of oculomotor capture was found. However, the distractor does effect fixation duration: we find an increase in fixation duration analogous to the remote distractor effect (Walker, Deubel, Schneider, & Findlay, 1997). These results suggest that during dynamic scene perception, the oculomotor system may be under far more top-down control than traditional laboratory based-tasks have previously suggested.


Are prophylactic haematopoietic growth factors of value in the management of patients with aggressive non-Hodgkin's lymphoma?
Combination chemotherapy used to treat patients with aggressive non-Hodgkin's lymphoma is associated with neutropenia and subsequent infection, hospital admission and treatment delays. Haematopoietic growth factors (HGF) can prevent neutropenia and improve quality of life. We undertook a meta-analysis of six randomised and one nonrandomised trials to quantify the effect in previously untreated patients, and a simple cost-effectiveness analysis. The trials compared HGF plus chemotherapy with chemotherapy alone. In total, there were 779 patients aged between 15 and 82 years. Haematopoietic growth factors was associated with a statistically significant 44% reduction in the incidence of severe neutropenia (neutrophil count <0.5 x 10(9) l(-1)), a 60% reduction in the number of hospital admissions due to infection, an 80% reduction in the number of patients who had a treatment delay due to neutropenia and a 50% reduction in hospital stay. These data together with UK G-CSF drug costs were combined to develop a simple cost-effectiveness model, based on direct costs. Given the current cost of G-CSF, it would only be cost-effective among patients in which high rates of hospital stay due to neutropenia or infection are expected. Alternatively, if the cost could be reduced then all patients may be able to obtain the benefits. However, the evidence that prophylactic HGFs are clinically worthwhile is clear.


Lead poisoning and brain cell function.
Exposure to excessive amounts of inorganic lead during the toddler years may produce lasting adverse effects upon brain function. Maximal ingestion of lead occurs at an age when major changes are occurring in the density of brain synaptic connections. The developmental reorganization of synapses is, in part, mediated by protein kinases, and these enzymes are particularly sensitive to stimulation by lead. By inappropriately activating specific protein kinases, lead poisoning may disrupt the development of neural networks without producing overt pathological alterations. The blood-brain barrier is another potential vulnerable site for the neurotoxic action of lead. Protein kinases appear to regulate the development of brain capillaries and the expression of the blood-brain barrier properties. Stimulation of protein kinase by lead may disrupt barrier development and alter the precise regulation of the neuronal environment that is required for normal brain function. Together, these findings suggest that the sensitivity of protein kinases to lead may in part underlie the brain dysfunction observed in children poisoned by this toxicant.


Neural-network control of nonaffine nonlinear system with zero dynamics by state and output feedback.
This paper focuses on adaptive control of nonaffine nonlinear systems with zero dynamics using multilayer neural networks. Through neural network approximation, state feedback control is firstly investigated for nonaffine single-input-single-output (SISO) systems. By using a high gain observer to reconstruct the system states, an extension is made to output feedback neural-network control of nonaffine systems, whose states and time derivatives of the output are unavailable. It is shown that output tracking errors converge to adjustable neighborhoods of the origin for both state feedback and output feedback control.


Computing smallest intervention strategies for multiple metabolic networks in a boolean model.
This article considers the problem whereby, given two metabolic networks N1 and N2, a set of source compounds, and a set of target compounds, we must find the minimum set of reactions whose removal (knockout) ensures that the target compounds are not producible in N1 but are producible in N2. Similar studies exist for the problem of finding the minimum knockout with the smallest side effect for a single network. However, if technologies of external perturbations are advanced in the near future, it may be important to develop methods of computing the minimum knockout for multiple networks (MKMN). Flux balance analysis (FBA) is efficient if a well-polished model is available. However, that is not always the case. Therefore, in this article, we study MKMN in Boolean models and an elementary mode (EM)-based model. Integer linear programming (ILP)-based methods are developed for these models, since MKMN is NP-complete for both the Boolean model and the EM-based model. Computer experiments are conducted with metabolic networks of clostridium perfringens SM101 and bifidobacterium longum DJO10A, respectively known as bad bacteria and good bacteria for the human intestine. The results show that larger networks are more likely to have MKMN solutions. However, solving for these larger networks takes a very long time, and often the computation cannot be completed. This is reasonable, because small networks do not have many alternative pathways, making it difficult to satisfy the MKMN condition, whereas in large networks the number of candidate solutions explodes. Our developed software minFvskO is available online.


Using the T2-weighted magnetic resonance imaging signal intensity ratio and clinical manifestations to assess the prognosis of patients with cervical ossification of the posterior longitudinal ligament.
The aim of this study was to investigate the clinical significance of both the signal intensity ratio obtained from MR imaging and clinical manifestations on the prognosis of patients with cervical ossification of the posterior longitudinal ligament. The authors retrospectively reviewed the records of 58 patients with cervical ossification of the posterior longitudinal ligament who underwent cervical laminoplasty from February 1999 to July 2007. Magnetic resonance imaging (1.5-T) was performed in all patients before surgery. Sagittal T2-weighted images of the cervical spinal cord compressed by the ossified posterior longitudinal ligament showed increased intramedullary signal intensity, whereas the sagittal images obtained at the C7-T1 disc levels were of normal intensity. The signal intensity ratio between regions of intramedullary increased signal intensity and the normal C7-T1 disc level was calculated based on the signal intensity values generated from the MR imaging workstation. Patients were divided into 3 groups according to their signal intensity ratio (high, intermediate, and low signal intensity groups). There were significant differences between the 3 groups regarding recovery rate (p < 0.001), age (p = 0.022), duration of disease (p = 0.001), Babinski sign (p < 0.001), ankle clonus (p < 0.001), and both pre- and postoperative Japanese Orthopaedic Association score (p < 0.001). There was no significant difference in sex among the 3 groups (p = 0.391). Patients with low signal intensity ratios that changed on T2-weighted imaging experienced a good surgical outcome. Low increased signal intensity might reflect mild neuropathological alteration in the spinal cord and greater recuperative potential. An increased signal intensity ratio with positive pyramidal signs indicates less recuperative potential of the spinal cord and a poor surgical outcome.


Human glutathione S-transferases.
Human glutathione S-transferases (GSTs) are a functionally diverse family of soluble enzymes of detoxification that use reduced glutathione (GSH) in conjugation and reduction reactions. Toxic electrophiles, including a variety of carcinogens, are substrates for the GSTs and after conjugation or reduction they are more easily excreted into bile or urine. Many of the GSTs have been cloned, and the three-dimensional structures of GSTs from several species, including humans, have been determined. These data have provided significant insight into how the GSTs function as enzymes. Many GST substrates are inducers of GST gene expression; nonsubstrate inducers include H2O2 and other reactive oxygen species. The regulatory elements of several human GST genes have been partially characterized, and the regulation of the GSTs in humans appears to be very different from that in rodents. Several polymorphisms of GST expression occur commonly in humans and have been associated with an increased susceptibility to certain cancers, particularly when combined with other genetic and environmental factors such as smoking. The role of GSTs in protecting cells from injury by toxic electrophiles continues to be developed.


Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study.
Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs), which consist of proteins called connexins (Cxs). GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of colorectal tumours. Tissue samples (50 cases) were collected from normal colon, at the maximum distance from the tumor. Using antibodies for Cx26, Cx32 and Cx43, immunohistochemical detection was made. In epithelial cells, strong Cx26 immunoreactivity was found, whereas Cx32 and Cx43 were sparsely distributed. Strong Cx43 immunostaining in muscularis mucosae was observed. In the circular layer of muscularis externa, expression of Cx43 and Cx26 was seen, but only in the portion closest to the submucosa. No immunoreactivity was found in the longitudinal muscle layer. Small vessels stained positively only for Cx43. Furthermore, there was no difference in staining between samples derived from various sections of the colon. This study showed immunohistochemically for the first time the expression of Cx26 in human colon mucosa.


Validation of the International Adjustment Disorder Questionnaire in Israel and Switzerland.
The ICD-11 has introduced a new conceptualization of adjustment disorder (AjD) as a stress response syndrome with core symptoms of preoccupations and failure to adapt to the stressor. The current study aimed to assess the reliability and validity of the International Adjustment Disorder Questionnaire (IADQ) in two culturally distinct samples from Israel and Switzerland. Two samples were recruited in Israel (N = 1142) and Switzerland (N = 699) during the initial stages of the COVID-19 pandemic. Confirmatory factor analysis indicated that a correlated two-factor model provided an excellent fit to the Israeli and Swiss sample data. The IADQ scores correlated strongly with another measure of AjD symptoms and with symptoms of depression, anxiety, acute stress and negative emotions, whereas correlations with posttraumatic stress disorder, complex posttraumatic stress disorder and positive emotions were weaker. In the Swiss sample, 18.8% met diagnostic criteria for probable AjD and 10.2% in the Israeli sample. The current study provides the first evidence of the validity of the German and Hebrew versions of the IADQ and can be used for the screening of this debilitating condition.


[The results of the introduction of a protocol of preventive activities in a primary care center].
A sample of 360 people was analyzed. They had received the protocol of preventive activities of the "Unitat Docent de Medicina Familiar i Comunitària de Barcelona" during 1989. The results of those activities directed to the prevention of cardiovascular risk and to the detection of excessive alcohol intake are reported, as they are those with the easiest and widest implementation. Overall results include hypercholesterolemia in 43.9%, abnormal blood pressure in 10.5%, a rate of smokers of 31.7%, 7.7% with an excessive alcohol intake, and 51.9% of obese individuals. The results are also shown by age and sex groups. In the discussion, the results are compared with those expected for our population. It is concluded that preventive measures should be encouraged by primary health are teams.


Effects of ethanol-based fuel contamination: microbial community changes, production of regulated compounds, and methane generation.
Ethanol-based fuels are becoming more heavily used, increasing the likelihood of ethanol-based fuel spills during transportation and storage. Although ethanol is well-known to be readily biodegradable, very little is known about the effects that such a spill might have on an indigenous microbial community. Of particular concern is that ethanol contamination could stimulate the growth of organisms that can generate regulated compounds and/or produce explosive quantities of methane gas. A column-based study was performed to elucidate the potential impacts of ethanol-based fuel (E85) on the indigenous microbial community during a simulated fuel spill. A continuous dilute supply of E85 resulted in profound shifts in both the bacterial and archaeal communities. The shift was accompanied by the production of high concentrations of volatile fatty acids and butanol, a compound that is regulated in groundwater by some states. Results also indicated that a continuous feed of dilute E85 generated explosive levels of methane within one month of column operation. Quantitative PCR data showed a statistically significant increase in methanogenic populations when compared to a control column. The elevated population numbers correlated to areas of the column receiving a sustained carbon load. Toxicity data indicated that microbial growth was completely inhibited (as evidenced by absence of ethanol breakdown products) at ethanol levels above 6% (v/v). These data suggest that ethanol from ethanol-based fuel can be readily degraded, but can also produce metabolic products that are regulated as well as explosive levels of methane. The core of an E85 spill may serve as a long-term source of contamination as it cannot be degraded until significant dilution has occurred.


Effects of passive smoking on prenatal and infant development: Lessons from the past.
This paper studies the effect of passive smoking on child development. We use data from a time when the adverse effects of smoking on health were not known and when tobacco was not an inferior good. This allows us to disentangle the effect on foetuses and infants of smoking from that of other indicators of social and economic conditions. We exploit a set of unique longitudinal historical datasets defined at a detailed level of geographical disaggregation, namely the 69 Italian provinces. The datasets record precise information on the per capita consumption of tobacco products, the heights of twenty-year old conscripts in the second half of the 19th century Italy, and other relevant controls. We find a strong negative effect of smoking in the period immediately before and after birth on the height at age 20. Results are robust to changes in specification and consistent across the height distribution.


The influenza A virus host shutoff factor PA-X is rapidly turned over in a strain-specific manner.
The influenza A endoribonuclease PA-X regulates virulence and transmission of the virus by reducing host gene expression and thus regulating immune responses to influenza A virus. Despite this key function in viral biology, the levels of PA-X protein remain markedly low during infection, and previous results suggest that these low levels are not solely the result of regulation of the level of translation and RNA stability. How PA-X is regulated post-translationally remains unknown. We now report that the PA-X protein is rapidly turned over. PA-X from multiple viral strains are short-lived, although the half-life of PA-X ranges from ∼30 minutes to ∼3.5 hours depending on the strain. Moreover, sequences in the variable PA-X C-terminal domain are primarily responsible for regulating PA-X half-life, although the N-terminal domain also accounts for some differences among strains. Interestingly, we find that the PA-X from the 2009 pandemic H1N1 strain has a longer half-life compared to the other variants we tested. This PA-X isoform has been reported to have a higher host shutoff activity, suggesting a role for protein turnover in regulating PA-X activity. Collectively, this study reveals a novel regulatory mechanism of PA-X protein levels that may impact host shutoff activity during influenza A virus infection.IMPORTANCE The PA-X protein from influenza A virus reduces host immune responses to infection through suppressing host gene expression, including genes encoding the antiviral response. Thus, it plays a central role in influenza A virus biology. Despite its key function, PA-X was only discovered in 2012 and much remains to be learned including how PA-X activity is regulated to promote optimal levels of viral infection. In this study, we reveal that PA-X protein levels are very low likely because of rapid turnover. We show that instability is a conserved property among PA-X variants from different strains of influenza A virus, but that the half-lives of PA-X variants differ. Moreover, the longer half-life of PA-X from the 2009 pandemic H1N1 strain correlates with its reported higher activity. Therefore, PA-X stability may be a way to regulate its activity and may contribute to the differential virulence of influenza A virus strains.


Backscattering properties of topographic targets in the visible, shortwave infrared, and mid-infrared spectral ranges for hard-target lidars.
Hard-target lidars rely on the reflectivity and backscattering properties of topographic targets, which are rather difficult to evaluate, resulting in uncertainties when assessing the performance of the instrument. In this work, backscattering properties and hemispherical reflectance of topographic targets are measured in the visible, near-infrared, and mid-infrared spectral ranges. A laboratory setup mimicking a hard-target lidar is used to measure the backscattered signals at various angles of incidence, which are then fitted using a bidirectional reflectance distribution function Phong model. We show that these results are useful for optimizing active stand-off detection and hard-target lidars and for increasing their overall efficiency.


Prognostic factors for respiratory sickness absence and return to work among blue collar workers and office personnel.
To analyze factors that determine the occurrence of sickness absence due to respiratory disorders and the time it takes to return to work. A longitudinal study with 2 year follow up was conducted among 326 male blue collar and white collar workers. The survey started with an interview on respiratory complaints and spirometry. Sixty six (21%) workers were lost to follow up. Complete data on sickness absence among 251 workers during the follow up were collected from absence records and self reports. Regression analysis based on a proportional hazards model was applied to identify risk factors for the occurrence and duration of sickness absence due to respiratory disorders. During the follow up 35% workers attributed at least one period of sickness absence to respiratory complaints, which accounted for 14.2% of all days lost. A history of chronic obstructive pulmonary disease (COPD) did not predict sickness absence for COPD; the same was true for chronic non-specific lung disease (CNSLD). Complaints about asthma contributed significantly to absence due to asthma (relative risk (RR) 3.96; 95% confidence interval (95% CI) 1.99 to 7.90). Job title was a significant predictor of sickness absence due to respiratory complaints. Decrease in forced vital capacity (FVC, <80% of the reference value) was also a significant predictor of absence due to asthma (RR 4.03; 95% CI 1.41 to 11.54) and of respiratory absence (RR 2.49; 95% CI 1.07 to 5.79). Absence with respiratory complaints was not associated with age, height, body mass index, or smoking. Duration of employment was a weak almost significant predictor against respiratory absenteeism (RR 0.94; 95% CI 0.91 to 0.97). Return to work after respiratory absence was worse for blue collar workers than office personnel (RR 5.74; 95% CI 1.90 to 17.4 for welders, and RR 6.43; 95% CI 2.08 to 19.85 for metal workers). Asthmatic complaints in the 12 months before the study were associated with sickness absence for these complaints during the follow up. An abnormal level of FVC also influenced respiratory absenteeism. Blue collar workers had more often and more prolonged absences due to respiratory disorders than white collar workers. Workers with absence due to respiratory complaints were at higher risk of subsequent sickness absence in the next year.


Mechanical complications of central venous catheterisation in trauma patients.
INTRODUCTION Central venous catheterisation (CVC) is a commonly performed procedure in a wide variety of hospital settings and is associated with appreciable morbidity. There is a paucity of literature focusing on mechanical complications specifically in the trauma setting. The aim of our study was to determine the spectrum of mechanical complications in a high-volume trauma centre in a developing world setting where ultrasound guidance was not available. METHODS A retrospective study was performed analysing data from a four-year period at the Pietermaritzburg Metropolitan Trauma Service in South Africa. RESULTS A total of 178 mechanical complications (18%) occurred in 1,015 patients undergoing CVC: 117 pneumothoraces, 25 malpositions, 18 catheter dislodgements, 14 arterial cannulations, one air embolism, one chylothorax, one pleural cannulation and one retained guide-wire. The internal jugular vein (IJV) approach was associated with a higher overall complication rate than the subclavian vein (SCV) approach (24% vs. 13%, p<0.001). Pneumothorax (73% vs. 57%, p<0.001) and arterial cannulation (15% vs. 0%, p<0.001) were more common with the IJV. Catheter dislodgement (21% vs. 0%, p<0.001) was more common with the SCV. Junior doctors performed 66% of the CVCs and this was associated with a significantly higher complication rate (20% vs. 12%, p<0.001). CONCLUSIONS CVC carries appreciable morbidity, with pneumothorax being the most frequent mechanical complication. The SCV was the most commonly used approach at our institution. The majority of CVCs were performed by junior doctors and this was associated with a considerable complication rate.


Induced non-enzymatic browning of soybean meal. III. Digestibility and efficiency of protein utilization by ruminants of soybean meal treated with xylose or glucose.
Trials were conducted to evaluate effects of non-enzymatic browning of soybean meal (SBM) on efficiency of protein utilization and N digestibility. In trial 1, 48 Suffolk-Finnsheep lambs (22 kg) were fed 80 d to evaluate efficiency of protein utilization for growth when supplemental protein was fed as urea (U), commercial SBM (CS), or commercial SBM (pH 8.5, 83% dry matter) containing xylose (3 mol/mol SBM-lysine) and heated 30 min (XTS-30) or 55 min (XTS-55). Diets containing graded levels of N from CS, XTS-30 and XTS-55 were fed. Response criterion was efficiency of protein utilization, plotted as gains of lambs fed test proteins minus gain of lambs fed U vs supplemental test protein fed. Efficiencies of protein utilization were .62, 1.27 and .91 for CS, XTS-30 and XTS-55, respectively. Protein from XTS-30 was used more efficiently (P less than .05) than that from CS. In trial 2, apparent digestibility of N from CS (97%) was higher (P less than .01) than XTS-30 (77%) and XTS-55 (82%) by Suffolk-Finnsheep lambs (27 kg). In trial 3, 60 mixed-breed steers (218 kg) were fed individually for 105 d to evaluate glucose as a reducing sugar. Glucose-treated SBM (GTS) was prepared by mixing glucose (3 mol/mol SBM lysine) with SBM, adjusting pH and dry matter content to 8.5 and 80%, respectively, and heating at 150 C for 60 min. Supplemental N sources were U, CS, GTS and a 50:50 mixture (protein basis) of corn gluten meal and blood meal (CGM/BM).(ABSTRACT TRUNCATED AT 250 WORDS)


Review: modifications of human serum albumin and their binding effect.
Human serum albumin (HSA) regulates the transport and availability of numerous chemical compounds and molecules in the blood vascular system. While previous HSA research has found that HSA interacts with specific varieties of ligands, new research efforts aim to expand HSA's ability to interact with more different drugs in order to improve the delivery of various pharmacological drugs. This review will cover fatty acid chain and posttranslational modifications of HSA that potentially modulate how HSA interacts with various pharmacological drugs, including glycation, cysteinylation, S-nitrosylation, S-transnitrosation and S-guanylation.


Work-family conflict and job burnout among correctional staff: a comment on Lambert and Hogan (2010)1.
Lambert and Hogan (2010) examined the relations between work-family conflict, role stress, and other noted predictors, on reported emotional exhaustion among a sample of 272 correctional staff at a maximum security prison. Using an ordinary least squares (OLS) regression model, the authors found work-on-family conflict, perceived dangerousness of the job, and role strain to have positive relations with emotional exhaustion. However, contrary to expectation they found that custody officers reported lower exhaustion than did their noncustody staff counterparts. Suggestions are provided for follow-up efforts designed to extend this line of research and correct methodological issues.


Identification of differentially expressed genes in shrimp (Penaeus stylirostris) infected with White spot syndrome virus by cDNA microarrays.
White spot syndrome virus (WSSV) is currently the most important viral pathogen infecting penaeid shrimp worldwide. Although considerable progress has been made in characterizing the WSSV genome and developing detection methods, information pertaining to host genes involved in WSSV pathogenesis is limited. We examined the potential of cDNA microarray analysis to study gene expression in WSSV-infected shrimp. Shrimp cDNAs were printed as low-density arrays on glass slides and were hybridized with Cy3/Cy5 labeled probes derived from RNA isolated from healthy and WSSV-infected shrimp. Genes that code for proteins that are relevant to crustacean immunity, structural proteins, as well as proteins of unknown function were among those whose mRNA expression was altered upon WSSV infection. To validate the microarray data, the temporal expression of three differentially expressed genes, an immune gene (C-type lectin-1), a structural gene (40S ribosomal protein), and a gene involved in lipid metabolism (fatty acid binding protein) was measured in healthy and WSSV-infected shrimp by real-time RT-PCR. The data suggest that WSSV infection alters the expression of a wide array of cellular genes, and provides a framework for further studies aimed at identifying genes whose function may provide insight into the mechanism of WSSV infection in shrimp.


Juxtaglomerular apparatus tumor: a rare but curable cause of secondary hypertension.
We have reported our experience at Duke University Medical Center with juxtaglomerular apparatus tumor, a rare but remediable cause of significant hypertension. Our three cases illustrate markedly different clinical courses and diagnostic difficulties. Results of the usual diagnostic studies, including intravenous pyelogram and renal angiogram with selective renal vein renin assessment, may be normal, but abdominal CT with contrast can show even small lesions. Thus we propose the addition of CT in evaluating all cases of high-renin hypertension when renal artery stenosis has been excluded. Periodic reevaluation of these patients is mandatory to increase diagnostic accuracy and avoid unnecessary morbidity and mortality. Local resection, rather than total nephrectomy, should be considered because the tumors have low invasive potential.


[Clinical aspects of using extremely high frequency electromagnetic radiation in the complex treatment of occlusive vascular diseases of the lower extremities].
A method of local influencing with the extremely high frequency electromagnetic irradiation on the points of acupuncture was used in the complex treatment of 44 patients with obliterative diseases of the vessels of the lower extremities at the age of 34-75 years. Obliterative atherosclerosis was diagnosed in 15 of them, obliterative endarteritis --in 29. A high effectiveness of the method even in late stages of vascular pathology was noted. No complications were observed.


Thinking about the past, present, and future: Time perspective and self-esteem in adolescents, young adults, middle-aged adults, and older adults.
We examined time perspective and self-esteem in adolescents, young adults, middle-aged adults, and older adults. Time perspective was measured with scales that assess relative orientations and relationships among the past, present, and future. Age effects were examined with standard analytic strategies to determine categorical differences between age groups and with new statistical techniques designed to show continuous age patterns. Findings indicated that (1) thinking about the future was greatest for adolescents and young adults and lowest for middle-aged and older adults, and thinking about the present increased across ages; (2) fewer adolescents and middle-aged participants perceived that the time periods were interrelated compared to younger and older adults; and (3) across ages, a greater emphasis towards the past compared to other time periods was associated with lower self-esteem, whereas emphasizing the present and the future jointly was associated with higher self-esteem.