The efficacy of antibiotic treatment versus surgical treatment of uncomplicated acute appendicitis: Systematic review and network meta-analysis of randomized controlled trial.
The efficacy of antibiotics in appendicitis remains controversial, and physicians are not confident in prescribing antibiotics as the first line treatment. This network meta-analysis was conducted to assess the efficacy and safety of individual antibiotics in uncomplicated appendicitis. Randomized controlled trials (RCTs) were identified from MEDLINE and SCOPUS databases since inception to July 2017. Network meta-analysis was applied to estimate treatment effects and safety. Probability of being the best treatment was estimated using surface under the cumulative ranking curve (SUCRA). Among 9 RCTs meeting our inclusion criteria. A network meta-analysis indicated that those receiving antibiotics had about 12-32% lower chance of treatment success and lower risk of complication about 23-86%, especially Beta-lactamase than appendectomy. The overall appendicitis recurrence rate in the antibiotic group was about 18.2%. The SUCRA indicated that appendectomy was ranked first for treatment success and least complications, followed by Beta-lactamase. Appendectomy is still the most effective treatment in uncomplicated appendicitis but it carries complications. Beta-lactamase, might be an alternative treatment if there are any contraindications for operation.


Consequences of smoke inhalation in the 'Epidemiology of Allergic Diseases in Poland' project (ECAP).
This paper presents a risk assessment of individuals with respiratory allergies who are exposed to active and passive tobacco smoke (environmental tobacco smoke or ETS). Smoking tobacco and ETS is a serious environmental hazard known to be harmful to human health. This analysis is based on the results of the Epidemiology of Allergic Diseases in Poland (ECAP) study, which was conducted from 2006-2008 on a sample of approximately 22,500 respondents in 9 areas of Poland, both urban and rural. Data collection was based on individual interviews and a questionnaire employing Computer Assisted Personal Interviewing technology (CAPI). 46.8% of respondents declared themselves as smokers, defined as those who smoke and have done so for at least one year. In this group, 41.5% of respondents were female and 54.3% were male. While differences between various areas of Poland were demonstrated, they did not necessarily correlate with urbanization. Rural Zamość reported 41.4% of smokers while metropolitan Poznań had 41.9% of smokers. These statistics can be contrasted against other urban areas such as Katowice and Gdansk, which had 51.8% and 52.3% of smokers, respectively (n = 9376). 29.6% of rural women reported smoking, while this percentage was higher among urban women, ranging from 36.3% in Poznań to 49.5% in Gdańsk. However, the highest percentage of smokers was among males in Zamość at 56.1%. This percentage was higher than the overall average in this study. The largest percentages of active smoking occurred among laborers, craftsmen, miners, drivers, farmers and fishermen, the self-employed and gardeners. This quantitative assessment of the prevalence of smoking underlines the importance of the consequences of this habit as they relate to asthma and respiratory allergies. The findings demonstrate smoking as a serious social problem associated with allergic diseases, and a habit that differs between place of residence and work environment.


Antitumor activity of titanocene dichloride in xenografted human renal-cell carcinoma.
Titanocene dichloride [(C5H5)2TiCl2] is a new-developed organometallic antitumor agent which is currently being investigated in clinical trials of phases I and II. In the present study, it was tested for antitumor activity in human renal tumors either growing as monolayers in vitro or as xenografts in athymic mice. For comparison, approved cytostatic drugs (in vitro, vinblastine and 5-fluoro-2'-deoxyuridine; in vivo, cyclophosphamide, vinblastine, and 5-fluorouracil) were administered in vitro and in vivo at equivalent or equitoxic dose levels, respectively. Under in vitro conditions, titanocene dichloride was active only moderately. When it was applied at peak plasma level of 10(4) mol/l, it induced cell growth inhibitions by 25-50% in all KTCTL cell lines investigated (KTCTL-1M, KTCTL-2, KTCTL-26A, KTCTL-30, KTCTL-84). In the N-U 2 carcinoma cell strain it was more effective and caused cell growth inhibitions of 70-80% at the 10(-4) mol/l level, the IC50 value amounting to 5 x 10(-6) mol/l. When titanocene dichloride was applied intraperitoneally (i.p.) according to the Q3Dx5 and Q2Dx5 regimens and investigated in the human renal-cell carcinoma N-U 2 growing as xenograft in athymic mice, it brought about significant and dose-dependent growth reductions by 50-75% in relation to untreated controls, whereas cyclophosphamide given as single bolus injection and vinblastine administered both as single and triple doses were slightly less effective in this xenograft. MKT 4 and MKT 5, two formulations of titanocene dichloride which are currently used in clinical trials, showed similar efficacy as titanocene dichloride towards the N-U 2 renal-cell carcinoma xenograft. In the heterotransplanted N-U 26 carcinoma, titanocene dichloride induced relative growth reductions by 50-56% and was similarly active as cyclophosphamide, but less effective than vinblastine applied as a single dose. Titanocene dichloride was again significantly active in the KTCTL-1M carcinoma xenograft and caused relative growth reductions by 50-65%. In the case of the MRI-H 121 renal sarcoma xenograft, however, the organometallic compound showed an only marginal activity which was surpassed by cyclophosphamide, vinblastine and 5-fluorouracil, all three drugs inducing significant relative growth inhibitions by 50-88%. These results confirm a significant and remarkable antitumor activity of titanocene dichloride in three out of four human renal tumors xenografted to athymic mice and suggest that clinical studies of phase II with titanocene dichloride towards renal-cell carcinoma in human patients should be done in the near future.


Hair follicle cycle and shedding in male beagle dogs.
Skin biopsy samples were collected from the thoracolumbar region of 9 male Beagle dogs ranging in age from 2 weeks to 32 months. The highest percentages of anagen hair follicles were present in samples collected during the winter and the summer seasons, and highest percentages of telogen hair follicles were present in samples collected during the fall and the spring seasons. Catagen, never exceeding 7% of the follicles, was found during a brief transitory stage. Peak shedding of hairs combed from the coats of dogs occurred in the spring and fall--these peaks appearing simultaneously with peak percentages of hair follicles in the telogen phase. Dogs younger than 1 year of age had 10% fewer follicles in the telogen stage than did older dogs. In dogs 2 weeks of age, 12 to 16% of the hair follicles were in the telogen stage.


How cells respond to stress.
During emergencies, cells produce stress proteins that repair damage. Inquiry into how they work offers promise for coping with infection, autoimmune disease and even cancer.


Chemistry for All: Advocating Gender Equality.
International Women's Day is celebrated every year on March 8, and this special issue of Angewandte Chemie focussing on Women in Chemistry coincides with International Women's Day 2019. The breadth and quality of content is testament to the excellent research being done in groups being successfully run by female researchers.


Pulmonary embolism: Epidemiology and registries.
Real-life data is important in understanding the needs of patients in routine clinical practice, particularly owing to the fact that almost a quarter of patients with venous thromoboembolism (VTE) have at least one exclusion criterion preventing their recruitment into randomized clinical trials. The Registro Informatizado de Enfermedad Trombo Embólica (RIETE) registry is an ongoing, international, multicentre, prospective registry of consecutive patients presenting with acute VTE. In this chapter, we summarized some of the most relevant data concerning the epidemiology of VTE in the RIETE registry.


Mobile Navigation Using Haptic, Audio, and Visual Direction Cues with a Handheld Test Platform.
This paper reports on a series of user experiments evaluating the design of a multimodal test platform capable of rendering visual, audio, vibrotactile, and directional skin-stretch stimuli. The test platform is a handheld, wirelessly controlled device that will facilitate experiments with mobile users in realistic environments. Stimuli rendered by the device are fully characterized, and have little variance in stimulus onset timing. A series of user experiments utilizing navigational cues validates the function of the device and investigates the user response to all stimulus modes. Results show users are capable of interpreting all stimuli with high accuracy and can use the direction cues for mobile navigation. Tests included both stationary (seated) and mobile (walking a simple obstacle course) tasks. Accuracy and response time patterns are similar in both seated and mobile conditions. This device provides a means of designing and evaluating multimodal communication methods for handheld devices and will facilitate experiments investigating the effects of stimulus mode on device usability and situation awareness.


Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.
Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.


Attitudes and beliefs among Mexican Americans about type 2 diabetes.
Hispanics in the United States have a disproportionately high risk for non-insulin-dependent diabetes mellitus (type 2 diabetes) compared with non-Hispanic whites. Little is known of the attitudes and beliefs about diabetes in this group. Using data from six focus groups of 42 Mexican Americans (14 men and 28 women), we characterized perceptions about the causes of and treatments for type 2 diabetes. Many participants believed diabetes is caused by having a family history of the disease, eating a diet high in fat or sugar, and engaging in minimal exercise. Experiencing strong emotions such as fright (susto), intense anger (coraje), or sadness and depression (tristeza) was also thought to precipitate diabetes. Nearly all participants expressed the belief that it is important to follow doctors' recommendations for diet and exercise, oral medication or insulin; many also cited herbal therapies, such as prickly pear cactus (nopal) and aloe vera (savila) as effective treatments. These findings may be useful in designing interventions to reduce the burden of diabetes in Hispanic populations.


Effects of intranasal administration of the peptide antagonist of type I vaniloid receptor (TRPV1) in the rodent central nervous system.
Intranasal administration of the polypeptide APHC3, an antagonist of the TRPV1 receptor, had acute anxiolytic and antidepressant effects, as well as an ability to modify the microglial response to proinflammatory stress and cytokine profile of the hippocampus. However, the acute antidepressant effect of the polypeptide was not related to the attenuation of neuroiflammation and probably had a different mechanism. The use of intranasal administration of the APHC3 peptide as a therapeutic approach aimed at decreasing depression symptoms needs additional studies in order to find the mechanism of action of this polypeptide in the central nervous system (CNS).


Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.
A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.


Arsenic: opportunity for risk assessment.
Arsenic is a human carcinogen that in small amounts is widely distributed in food and water. It has been regulated for almost 100 years worldwide and in the United States, on the judgment of the Royal Commission on Arsenic that a classical threshold of toxicity exists and that a daily intake of 400 micrograms/day is safe. Modern regulatory thinking in the United States has not accepted safe levels for carcinogens and is thus in conflict with the arsenic standard. Recent epidemics of arsenicism have quantitatively confirmed that threshold not only for the non-cancerous arsenical skin lesions but also for arsenical skin and internal cancers. Research shows that arsenic is a general gene inducer. Genes induced are involved in proliferation, recombination, amplification and the activation of viruses. This characterizes arsenic as an indirect carcinogen and provides a molecular basis for risk assessment and the observed threshold dose response. In the United States at present, about 300 cases of occupational arsenical cancer, declining in numbers, are known. Background arsenic below the drinking water standard is not known to have produced disease. The conspicuous nature of arsenical skin disease presents an unusual opportunity for a simplified survey of arsenical skin disease to support regulatory standards for arsenic.


A simple method for computer quantification of stage REM eye movement potentials.
We describe a simple method for computer quantification of eye movement (EM) potentials during REM sleep. This method can be applied by investigators using either period-amplitude (PA) or Fast Fourier Transform (FFT) spectral EEG analysis without special hardware or computer programming. It provides good correlations with visual ratings of EM in baseline sleep and after administration of GABAergic hypnotics. We present baseline data for both PA and FFT measures for 16 normal subjects, studied for 5 consecutive nights. Both visually rated and computer-measured EM density (EMD) showed high night-to-night correlations across baseline and drug nights and the computer measures detected the EMD suppression that is produced by GABAergic drugs. Measurement of EM in addition to stage REM provides biologically significant information and application of this simple computer method, which does not require pattern recognition algorithms or special hardware, could provide reliable data that can be compared across laboratories.


Effect of exogenous prolactin on ultrastructure of pinealocyte in female pigs during puberty.
Influence of the administration of prolactin to female swine during puberty on the ultrastructure of pinealocytes has been examined by means of morphometric analysis. Prolactin administration for 15 consecutive days resulted in a decrease in the cytoplasmic dense bodies type MBB-2, lysosomes and multivesicular bodies. Some differences in structure of pinealocytes were also observed. Prolactin appeared to stimulate the process of transformation of cytoplasmic dense bodies.


A two pathway model for tonic suppressed-by-contrast cells in the cat retina.
A two pathway spatiotemporal model is proposed to describe the function of tonic suppressed-by-contrast cells of the cat retina. The model is able to describe the experimentally determined responses of such neurons to drifting sinusoidal gratings. It is also able to predict their responses to alternating sinusoidal gratings and flashing or moving spots of light, and these predictions resemble experimental observations, at least qualitatively. The model is physiologically plausible, it can be used to summarize the dynamic responses of the tonic suppressed-by-contrast cells of the cat and potentially to account for the responses of the suppressed-by-contrast cells of other species.


Another Piece of the Puzzle of Podocyte B7-1 Expression: Lupus Nephritis.
Lupus nephritis (LN) is a frequent complication and a major predictor of poor prognosis of systemic lupus erythematosus. Immune complex deposition and T cell infiltration are crucial events in LN pathogenesis. B7-1 (CD80), normally expressed by antigen-presenting cells, is one of the major co-stimulators of T-cell activation through the binding with its counter-receptors CD28 and cytotoxic T-lymphocyte antigen-4. Unexpectedly, B7-1 induction was described at the podocyte level in patients affected by different renal diseases, including LN. These observations suggested a novel exciting function for B7-1 as a biomarker of podocyte injury, and hence that B7-1 inhibitory drugs could serve as podocyte-targeted treatment of intractable renal diseases. However, subsequent studies hardly questioned the reliability of B7-1 detection assays and the therapeutic efficacy of B7-1 blockade in proteinuric patients, casting doubts on B7-1 expression by podocytes. Here, we thoroughly investigated whether B7-1 was indeed expressed by podocytes in LN, before even considering employing B7-1 blockade in patients with severe manifestations of LN and unfavourable prognosis. Applying different immunohistochemical assays with 4 primary antibodies, we analysed kidney biopsies from 42 LN patients at different stages of the disease, and from NZB/NZW mice, an LN model. B7-1 was not induced in podocytes in human and murine LN; instead its expression was confined to infiltrating inflammatory cells. B7-1 is not expressed by podocytes in LN. A renoprotective effect of B7-1 blockade in LN patients cannot be ruled out but, if confirmed, cannot be the result of an effect on podocyte B7-1.


Sources of declarative memory impairment in bipolar disorder: mnemonic processes and clinical features.
There is mounting evidence that declarative memory processes are impaired in patients with bipolar disorder. However, predictors of the observed impairment are not well understood. This study seeks to: (i) better characterize the nature of declarative memory impairment in bipolar disorder, and (ii) determine the relationship between clinical variables and memory function in bipolar disorder. 49 adult patients with bipolar disorder in varying mood states and 38 demographically matched healthy participants completed a comprehensive neurocognitive battery assessing general cognitive functioning, processing speed, and declarative memory. The California verbal learning test was used to characterize learning and memory functions. Although patients with bipolar disorder utilized a similar semantic clustering strategy to healthy controls, they recalled and recognized significantly fewer words than controls, suggesting impaired encoding of verbal information. In contrast, lack of rapid forgetting suggests relative absence of a storage deficit in bipolar patients. While severity of mood symptomatology and illness duration were not associated with task performance, gender and family history significantly affected memory function. Results suggest that declarative memory impairments in bipolar patients: (1) are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and (2) do not appear to be secondary to clinical state, but rather may be associated with the underlying pathophysiology of the illness.


The essential transcription factor, Mcm1, is a downstream target of Sln1, a yeast "two-component" regulator.
In a search for mutants exhibiting altered activity of the yeast transcription factor, Mcm1, we have identified the SLN1 gene, whose product is highly related to bacterial two-component sensor-regulator proteins. sln1 alleles identified in our screen increased Mcm1p-mediated transcriptional activation, while deletion of the SLN1 locus severely reduced Mcm1p activity. Our data establish that Mcm1p is a downstream target of the Sln1 signaling pathway. Yeast Sln1p was recently shown to be involved in osmoregulation and to depend on the Hog1 MAP kinase (Maeda, T., Wurgler-Murphy, S., and Saito, H. (1994) Nature 369, 242-245). We show that SLN1-mediated regulation of Mcm1p activity is independent of the Hog1 MAP kinase, and suggest that the role of SLN1 is not restricted to osmoregulation.


Evidence on the Protective Role of High-Density Lipoprotein (HDL) in HIV-Infected Individuals.
During the last decades, the improvements in the assessment and management of cardiovascular risk have been successful in the reduction of acute cardiovascular outcomes. Among different prevention and therapeutic strategies, treatments targeting HDL increase have been indicated as promising interventions from both basic research and clinical studies. Although this therapeutic approach still requires confirmatory findings from large clinical trials, emerging evidence indicates that it would be particularly useful in some patient categories characterized by accelerated atherosclerotic diseases. In this regard, HIV-infected patients (under antiretroviral treatment or not) have been recently indicated as an appropriate target population. The present review will discuss the promising role of HDL in HIV-related cardiovascular pathophysiology and update novelties from clinical studies targeting HDL increase in HIV patients.


The Amphotericin B-Ergosterol Complex Spans a Lipid Bilayer as a Single-Length Assembly.
Amphotericin B (AmB) is a polyene macrolide antibiotic clinically used as an antifungal drug. Its preferential complexation with ergosterol (Erg), the major sterol of fungal membranes, leads to the formation of a barrel-stave-like ion channel across a lipid bilayer. To gain a better understanding of the mechanism of action, the mode of lipid bilayer spanning provides essential information. However, because of the lack of methodologies to observe it directly, it has not been revealed for the Erg-containing channel assembly for many years. In this study, we disclosed that the AmB-Erg complex spans a lipid bilayer with a single-molecule length, using solid-state nuclear magnetic resonance (NMR) experiments. Paramagnetic relaxation enhancement by Mn2+ residing near the surface of lipid bilayers induced the depth-dependent decay of 13C NMR signals for individual carbon atoms of AmB. We found that both terminal segments, the 41-COOH group and C38-C40 methyl groups, come close to the lipid bilayer surfaces, suggesting that the AmB-Erg complex spans a palmitoyloleoylphosphatidylcholine (POPC) bilayer with a single-molecule length. Molecular dynamics simulation experiments further confirmed the stabilization of the AmB-Erg complex as a single-length spanning complex. These results provide experimental evidence of the single-length complex incorporated in the membrane by making thinner a POPC-Erg bilayer that mimics fungal membranes.


Phylogenetic footprinting reveals extensive conservation of Sonic Hedgehog (SHH) regulatory elements.
Sonic Hedgehog (SHH) plays a fundamental role in numerous developmental processes including morphogenesis of limbs, nervous system, and teeth. Using a Bayesian alignment algorithm for phylogenetic footprinting we analyzed approximately 28 kb of noncoding DNA in the SHH locus of human and mouse. This showed that the length of conserved noncoding sequences (4196 nt) shared by these species was approximately 3 times larger than the SHH coding sequence (1386 nt). Most segments were located in introns (53%) or within 2-kb regions upstream (16%) or downstream (20%) of the first and last SHH codon. Even though regions more than 2 kb upstream or downstream of the first and last SHH codon represented 57% (16 kb) of the sequence compared, they accounted for only 11% (494 nt) of the total length of conserved noncoding segments. One region of 650 nt downstream of SHH was identified as a putative scaffold/matrix attachment region (SMAR). Human-mouse analysis was complemented by sequencing in apes, monkeys, rodents, and bats, thus further confirming the evolutionary conservation of some segments. Gel-shift assays indicated that conserved segments are targeted by nuclear proteins and showed differences between two cell types that expressed different levels of SHH, namely human endothelial cells and breast cancer cells. The relevance of these findings with respect to regulation of SHH expression during normal and pathologic development is discussed.


Herpes simplex infection associated with short-term use of a fetal scalp electrode. A case report.
A case of localized neonatal herpes simplex virus (HSV) infection involved a prior fetal scalp electrode site. Rupture of the fetal membranes, placement of the fetal scalp electrode and delivery occurred within 30 minutes. The mother had no previous history of genital lesions, and no herpetic lesions were noted at delivery.


Antimutagenic activity of green tea and black tea extracts studied in a dynamic in vitro gastrointestinal model.
An in vitro gastrointestinal model, which simulates the conditions in the human digestive tract, was used to determine potential antimutagenic activity of extracts of black tea and green tea. In this paper, results are presented on the availability for absorption of potential antimutagenic compounds present in tea and on the influence of the food matrix on this activity. Between 60 and 180min after the tea was introduced into the model, antimutagenic activity was recovered from the jejunal compartment by means of dialysis: the dialysate appeared to inhibit the mutagenicity of the food mutagen MeIQx in the direct plate assay with Salmonella typhimurium (Ames test). The maximum inhibition was measured at 2h after the start of the experiment and was comparable for black tea and green tea extract. To determine the influence of food matrices on the antimutagenic activity of tea, the model was loaded with black tea together with milk or a homogenized standard breakfast. The maximum inhibition observed with black tea was reduced by 22, 42 and 78% in the presence of whole milk, semi-skimmed milk, and skimmed milk, respectively. Whole milk and skimmed milk abolished the antimutagenic activity of green tea by more than 90%; for semi-skimmed milk the inhibition was more than 60%. When a homogenized breakfast was added into the model together with the black tea extract, the antimutagenic activity was completely eliminated. When tea and MeIQx were added together into the digestion model, MeIQx mutagenicity was efficiently inhibited, with green tea showing a slightly stronger antimutagenic activity than black tea. In this case, the addition of milk had only a small inhibiting effect on the antimutagenicity. Antioxidant capacity and the concentration of catechins were also measured in the jejunal dialysates. The reduction in antimutagenic activity corresponded with reduction in antioxidant capacity and with a decrease of concentration of three catechins, viz. catechin, epigallocatechin gallate and epigallocatechin. The in vitro gastrointestinal model appears to be a useful tool to study the antimutagenicity of food components.


Prolyl isomerase as a probe of stability of slow-folding intermediates.
Catalysis of slow folding reactions by peptidyl prolyl cis-trans isomerase (PPI) provides estimates of stabilities of intermediates in folding of normal and mutational variants of yeast iso-2 cytochrome c. A two-state model postulating a rapid preequilibration of intermediates with the unfolded protein is employed to calculate the stabilization free energy of the intermediate from the catalytic efficiency (kcat/Km) of PPI toward slow folding species. Stability measurements have been made for two distinct slow-folding intermediates: the absorbance-detected (IIS) and fluorescence-detected (IIIS) intermediates. Mutation-induced changes in the stability of the intermediates and in the activation free energy for slow folding are compared to changes in equilibrium thermodynamic stability. The results show that (1) for iso-2 the absorbance-detected intermediates (IIS) are slightly more stable than the fluorescence-detected intermediates (IIIS), (2) most mutations have different effects on equilibrium stability and the stability of the IIS or IIIS intermediates, and (3) for both slow folding reactions the mutation-induced changes in the activation free energy are small compared to the magnitude of the activation free energy barrier. Differential effects of mutations on equilibrium stability and the stability of intermediates provides a means of assessing the sequence-encoded structural specificity for folding. Mutations with different effects on intermediate stability and equilibrium stability change the encoded folding information and may alter folding pathways and/or lead to different three-dimensional structures. Identification of mutations which stabilize a folding intermediate relative to the native conformation provides an empirical approach to the design of thermodynamically stable forms of folding intermediates.


Mortality Risk in Alcoholic Patients in Northern Italy: Comorbidity and Treatment Retention Effects in a 30-Year Follow-Up Study.
To analyse the general and cause-specific mortality over the course of 30 years among subjects treated for alcohol use disorders (AUD) in Northern Italy. Cohort of 2499 subjects followed-up for mortality until 31 December 2012. Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were computed to compare the mortality in the cohort with the general population. Cox regression was used to study the effect of psychiatric disorders, burden of physical comorbidity and retention in treatment on mortality, controlling for socio-demographic factors. During the follow-up, 435 deaths occurred. Compared with the general population, alcoholics experienced a 5-fold increased mortality (SMR: 5.53; 95% CI: 5.03, 6.07). Significant excess mortality was observed for a range of specific causes: infections, cancers, cardiovascular, respiratory and digestive system diseases as well as violent causes. In multivariate analysis, the hazard of dying was lower for female gender (hazard ratio [HR]: 0.62; 95% CI: 0.46, 0.84) and for increasing length of retention in treatment (HR for third tertile vs first tertile: 0.43; 95% CI: 0.32, 0.57). Burden of physical comorbidity was associated with increased hazard of dying (HR for 3+ comorbidities vs no comorbidities: 4.40; 95% CI: 2.91, 6.66). Psychiatric comorbidity was not associated with mortality. Despite the harmful effect of AUD, retention in treatment represented a protective factor against death, suggesting that strategies supporting primary medical- and social-care may effectively reduce premature mortality.


NC HealthConnex and Value-based Care: Statewide Health Information Exchange as a Technology Tool for All.
A statewide health information exchange (HIE) can be a vital technology tool and play a pivotal role in driving health care innovation and better health outcomes, especially for providers participating in value-based care models. NC HealthConnex is the state-designated HIE network that gives participating providers secure and timely access to important patient data from more than 4,700 health care facilities spanning geographic locations and care settings.


[Treatment results of comparative study using polyurethane synthografts (author's transl)].
Indication for synthografts is given in open wound treatment as well as in the treatment of infected wounds prior to grafting. Clinical examination of two different synthografts (Epigard and another synthograft) with regard to development of a granulation tissue and cleansing of contaminated wounds in 33 cases. Clinical examinations demonstrated less adhesive power and easier detaching of the other synthograft compared to Epigard; prolonged application of these two materials showed earlier wound debridement and better conditioning effect of Epigard connected with less secretion and better epithelisation. Short application in fresh wounds showed no great difference in granulation tissue except the more secretion under the other synthograft. In our opinion Epigard must be seen as a real synthograft, the other material as a sterile wound dressing.


How do colorectal cancers develop?
The aim of this study was to reveal (1) whether a flat adenoma is the precursor of a flat cancer and (2) the more frequent pathway in colorectal cancer development-a flat cancer or a polypoid cancer. Clinical features and histologic characteristics of 97 flat early cancers, 138 polypoid early cancers, 60 advanced cancers involving the muscularis propria, and 185 flat adenomas were investigated. Of the flat cancers, 89.7% were not accompanied by residual adenoma and are considered to have arisen de novo. The distribution of flat adenomas and flat cancers was significantly different, and a follow-up of flat adenomas did not reveal any rapid growth or carcinomatous changes in the flat adenomas. The shape of advanced cancers involving only the muscularis propria almost matches that of flat early cancers. Fifty-two of 97 flat cancers and 19 of 138 polypoid cancers invaded the submucosal layer. Flat adenomas are not considered to be precursors of flat cancers. Advanced cancers of the large intestine originate mainly from flat cancers arising de novo. The percentage of the advanced cancers that originate from flat cancers is estimated to be 71.2% (52 of 52 +/- 19) at a minimum.


Acute abdominal rhabdomyolysis after body building exercise: is there a "rectus abdominus syndrome?".
Report of a 19-year-old man who was admitted to the hospital after vigorous exercise with signs of the "acute abdomen" syndrome. Since intestinal reasons for the complaints were excluded, a myocardial infarction was considered. However, the excessively increased serum CK levels indicated a disorder of the voluntary muscles. A biopsy taken from the rectus abdominis revealed typical features of acute rhabdomyolysis, which was obviously restricted to the rectus abdominis. Together with a somewhat later observed autopsy case of a young male with acute abdominal rhabdomyolysis, also restricted to the rectus abdominis, this case gives rise to discuss, whether there exists a "rectus abdominis syndrome" analogous to the anterior tibial syndrome.


Toluene Poisoning Presenting as Bilateral Basal Ganglia Haemorrhage.
Toluene is an aromatic hydrocarbon that is often used as a solvent in paints, paint thinners, glues, disinfectants and as an industrial solvent for the manufacturing of pharmaceuticals, paints and chemicals. Metabolic acidosis is a recognized complication of toluene poisoning. However, we here report an unusual case of toluene poisoning presenting with bilateral intracerebral haemorrhage.


Nutritionally Attenuating the Human Gut Microbiome To Prevent and Manage Metabolic Syndrome.
Metabolic syndrome (MSyn) constitutes a litany of pathophysiological conditions, such as central adiposity, hypertension, dyslipidemia, and hyperglycemia. As a result of the epidemic levels of MSyn, several efforts have been made to identify the etiologies of the condition and develop methods by which to reduce its prevalence. The attenuation of the gut microflora ratio of Firmicutes/Bacteroidetes through bioactive compounds found in the Mediterranean diet, dietary polysaccharides, and pre- and probiotics can be used as functional foods to improve derangements in cardiometabolic markers correlated with the development of MSyn. Although more studies are needed to understand the role of manipulating the gut microbiota in health and disease in human models, this review based on current data from epidemiologic studies and clinical trials will serve as a review to elucidate the role nutrition plays in attenuating the gut microbiota in preventing and managing MSyn.


Stress ulcer bleeding.
Although upper gastrointestinal (GI) bleeding from stress-related mucosal disease (SRMD) in critically ill patients is common, significant bleeding with hemodynamic instability is not. Risk factor assessment can assist in identifying patients with a greater likelihood of developing significant SRMD. Prophylaxis against stress ulcer bleeding with luminal agents (eg, antacids and sucralfate) or drugs that inhibit acid secretion (eg, histamine 2-receptor antagonists and proton-pump inhibitors) can reduce major bleeding but has little or no effect on mortality. Currently, the mainstays of prophylactic therapy for SRMD are intravenously administered H2RAs and PPIs. Wider usage of PPIs reflects their enhanced efficacy in suppressing acid secretion as well as lack of tolerance for H2RAs. Guidelines for the prophylactic use of H2RAs or PPIs in treatment of SRMD will require large, randomized studies that also examine cost effectiveness of individual strategies.


[Respiratory handicap. Recognition, evaluation and social benefits].
The medico-social aspects of respiratory handicap pose some perplexing problems, notably in their recognition, rigorous evaluation and in the granting of social security benefits. The clinical and respiratory function data should be standardised and classified according to type and significance of respiratory disease and also according to the degree of co-operation and understanding of the patient. The respiratory handicap should be evaluated after considering the functional disability engendered by the disorder and their socio-professional repercussions. The abnormality in the lungs should be measured by resting tests; the degree of disability by exercise studies; the socio-professional handicap by ergonometric tests to assess the scale of the demands and requirements of family and social and professional life, indeed the cultural and economic style of the individual concerned. Such combined studies would enable recognition of severe chronic respiratory handicap leading to decisions for exemption certificates, such as cases of severe respiratory failure in patients requiring supplementary treatment for oxygen therapy or assisted ventilation. The benefits and grants offered to those with respiratory handicaps would involve a number of rights relating to: care, work, costs of replacement of workers in the event of prolonged sick leave or the benefits of an invalidity pension. There will be other allowances such as invalidity cards, lodging special studies and other rights particularly relating to lodging and special equipment. The present scale is difficult to use both because of its lack of specificity and its ill-chosen terminology. For better balance between the handicap and the benefits offered, a common and more flexible system, with a printed table should be at hand for the doctor to use for certain decisions: long term illness, period of invalidity or early retirement because of medical incapacity. Within each table a sub-section should exist to allow for certain aspects of legislation (accidents at work, occupational illness or rights under common law) at the same time certain adjustments may be necessary which take into account the patient, degree of autonomy life style and social and cultural level. A pilot study of respiratory handicap, to standardise tests, and co-ordinate the planning of the medical and social interactions for a better grasp of the disorder and greater uniformity of the regulations within each disablement benefit system as well as between various other social security regimes would be desirable.


Phenotypic and functional properties of Th lines and clones recognizing larval antigens of Schistosoma mansoni.
Five T cell clones and two lines were derived from the lymph nodes (LN) of C57BL/6 mice immunized with radiation-attenuated lung-stage larvae of Schistosoma mansoni. All seven clones/lines were CD4+, CD8- and expressed high levels of CD44 and CD45RB surface markers. After prolonged maintenance in-vitro, with soluble antigen from 18 h schistosomula (SSP), five retained the ability to proliferate readily and release IFNg in response to concanavalin A (Con-A) and to SSP and/or soluble adult worm antigen (SWAP). These Th clones/lines induced significant footpad DTH reactions when injected with SWAP, but were unable to confer protective immunity after transfer to naïve recipient mice. This result could be explained by the antigen specificity of the clones/lines, since they were not able to release IFNg when cultured in-vitro with living lung-stage larvae. A second possibility is that the high level of CD45RB expression, which is not seen on the surface of pulmonary CD4+ memory/effector cells isolated directly from protectively-vaccinated mice, alters the ability of the clones/lines to release IFNg and to induce a DTH response in the lungs when they encounter antigen released from migrating schistosomula.


Implication of Kv7 Channels in the Spinal Antinociceptive Actions of Celecoxib.
Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) commonly used to treat pain conditions in humans. In addition to its blocking activity on cyclooxygenase (COX) enzymes, several other targets could contribute to its analgesic activity. Here we explore the spinal antinociceptive actions of celecoxib and the potential implication of Kv7 channels in mediating its effects. Spinal cord in vitro preparations from hind paw-inflamed animals were used to assess the segmental sensory-motor and the early sensory processing of nociceptive information. Electrophysiological recordings of ventral roots and dorsal horn neurones were obtained, and the effects of celecoxib and Kv7 modulators on responses to repetitive dorsal root stimulation at C-fiber intensity were assessed. Celecoxib applied at clinically relevant concentrations produced depressant effects on responses to dorsal root stimulation recorded from both ventral roots and individual dorsal horn neurones; by contrast, the non-nociceptive monosynaptic reflex was unaffected. The NSAID indomethacin had no effect on spinal reflexes, but further coapplication of celecoxib still produced depressant effects. The depressant actions of celecoxib were abolished after Kv7 channel blockade and mimicked by its structural analog dimethyl-celecoxib, which lacks COX-blocking activity. The present results identify Kv7 channels as novel central targets for celecoxib, which may be relevant to its analgesic effect. This finding contributes to better understand the pharmacology of celecoxib and reinforces both the role of Kv7 channels in modulating the excitability of central pain pathways and its validity as target for the design of analgesics.


The conformational states of Mg.ATP in water.
The conformational equilibria of Mg.ATP in solution is studied using molecular dynamics (MD) augmented with umbrella sampling methods. Free energy comparisons show that the Mg(2+) ion is equally likely to coordinate the oxygens of the two end phosphates, or of all three phosphates. The MD trajectories reveal two major degrees of freedom of the Mg.ATP molecule in solution, and we compute the free energy as a function of these variables, and determine its elastic properties. Comparing the free energy function with several crystallographic structures of ATP analogs, we find that the crystal structures correspond to states where ATP would be elastically strained. The average water density around Mg.ATP is investigated to show the average number of hydrogen bonds and the hydrophobicity.


Correlation of corrected flow time in the carotid artery with changes in intravascular volume status.
Assessment of volume status remains a challenge in critical care. Our purpose was to determine if Doppler waveform analysis of carotid artery blood flow correlates with changes in volume status. Dehydrated patients receiving an intravenous fluid bolus were enrolled with exclusions including age less than 18 years, pregnancy, vasopressor administration, or atrial fibrillation. Ultrasound examination with Doppler analysis of the carotid artery was performed with measurements taken to calculate corrected flow time (FTc). Corrected flow time, mean arterial pressure, and pulse rate before and after fluid administration were compared using Wilcoxon matched-pairs signed rank test. Fifty-six patients were enrolled with mean fluid administration of 1110 mL. Corrected flow time increased with fluid resuscitation from prefluid mean of 299 milliseconds (95% confidence interval [CI], 282-317 milliseconds) to a postfluid mean of 340 milliseconds (95% CI, 323-358 milliseconds) (P<.0001). Mean percentage change in FTc was 14.9% (95% CI, 8.4-21.3). There were no significant changes in mean arterial pressure or heart rate from pre- to post-fluid administration. Intravenous fluid administration in dehydrated patients resulted in significant changes in FTc in the carotid artery despite no change in vital signs. Corrected flow time measured from carotid arterial blood flow may be a useful means of assessing volume status in volume-depleted patients.


Error management of emergency transfusions: a surveillance system to detect safety risks in day to day practice.
Acute hemolysis due to AB0-incompatibility caused by transfusion of red blood cell concentrates (RBCC) to the wrong recipient is one of the major causes of transfusion-related death. As part of our policy to improve quality and safety in emergency transfusion, we have developed a standardized surveillance system for supplying RBCC in emergency situations. This surveillance system involves the implementation of a standardized set of basic data transmitted from the requesting unit to the blood bank by phone and a scoring system to check for compliance with guidelines and errors in daily routines. Communication deficiencies and delayed pretransfusion sampling were the most common errors.


Alcohol and the young child.
With the increasing availability of alcohol in modern times, the child neglect and abuse portrayed in Hogarth's engraving Gin Lane may once again be witnessed. Reports occur occasionally of alcohol being given deliberately to infants to quieten them, but alcohol poisoning in the slightly older child is not uncommon. The introduction of child-proof containers has altered poisoning figures recently. However, alcohol poisoning tends to occur at ages 3 and 4, that is, about 2 years after the peak of all poisonings in children. This difference may be an indication that alcohol is taken in imitation of parents' drinking, a suggestion which has some support from reported cases of mouthwash poisoning. Holidays and high days where children and alcohol mix, are potentially dangerous periods. Since alcohol poisoning can be fatal, yet if recognised is relatively easily managed, every child with the slightest degree of drowsiness should be suspect until proven or not by blood alcohol. The prevention of alcohol poisoning in the young child consists in protecting the alcohol by lock and key, not setting an example by drinking or gargling in front of children. Many substances such as mouthwash and perfume should also be under supervision. Once actual poisoning has occurred blood sugar is probably more important than the level of blood ethanol and blood sugar levels should be monitored frequently and the child treated with glucose, preferably intravenously.


Photolabile acetals as profragrances: the effect of structural modifications on the light-induced release of volatile aldehydes on cotton.
Because volatile compounds evaporate from surfaces that are usually exposed to daylight, photoresponsive delivery systems are particularly suitable to control their release. In the present study, we investigated 4,4-diphenyl-4H-benzo[d][1,3]dioxins as profragrances for the light-induced delivery of aldehydes in functional perfumery. The efficiency of fragrance release was investigated on cotton after direct and indirect surface deposition from a fabric softening formulation as a function of the substitution pattern of the profragrance structure. Dynamic headspace analysis above the cotton surface demonstrated that the structure of the profragrance had a much larger effect on the fragrance release than did the amount of deposition on the target surface. Although some trends observed for the photolysis in solution also applied to the reaction on cotton, it is not generally possible to predict the photochemical behaviour of structurally different precursors on surfaces from their solution properties. The fact that the present system performed on a dry surface makes it an interesting light-triggered delivery vehicle for other classes of bioactive volatile compounds, such as pheromones or agrochemicals.


Influence of structure on nickel-titanium endodontic instruments failure.
The purpose of this work was to investigate the process history on fracture life of nickel-titanium endodontics files. The results are based on microstructural investigations of nickel-titanium engine-driven rotary instruments based on X-ray diffraction, scanning electron microscopy, and microhardness tests. Endodontic files are very work-hardened, and there is a high density of defects in the alloy that can disturb the phase transformation. The microhardness Vickers confirmed these observations (dislocations and precipitates). The X-rays show that experimental spectrum lines are extended, typical of a distorted lattice. The surface state of the endodontic files (scanning electron microscopy) is an important factor in failure and fracture initiation.


Insight into ribonuclease A domain swapping by molecular dynamics unfolding simulations.
Bovine pancreatic ribonuclease (RNase A) deserves a special place among the numerous proteins that form oligomers by three-dimensional domain swapping. In fact, under destabilizing conditions and at high protein concentrations, it can swap two different domains, the N-terminal alpha-helix or the C-terminal beta-strand, leading to dimers with different quaternary structures. With the change in the unfolding conditions, the relative abundance of the two dimers varies, and the prevalence of one dimer over the other is inverted. To investigate the dynamic behavior of the termini, four independent 10 ns high-temperature molecular dynamics simulations of RNase A were carried out at two different pH values in an attempt to reproduce the experimental conditions of neutral and very low pH that favor the formation of the N- and C-terminal domain-swapped dimers, respectively. In agreement with experimental data, under mild unfolding conditions, a partial or complete opening of the N-terminal arm is observed, whereas the dislocation of the C-terminus away from the core of the structure occurs only during the low-pH simulations. Furthermore, the picture emerging from this study indicates that the same protein can have different pathways for domain swapping. Indeed, in RNase A the C-terminal swapping requires a substantial unfolding of the monomers, whereas the N-terminal swapping can occur through only partial unfolding.


Selective preparation of benzyltitanium compounds by the metalative Reppe reaction. Its application to the first synthesis of alcyopterosin A.
Dialkoxytitanacyclopentadienes, prepared from two different acetylenes and a divalent titanium alkoxide reagent, Ti(O-i-Pr)4/2 i-PrMgCl, reacted with propargyl bromide to give directly benzyltitanium compounds. The resultant benzyltitanium compounds underwent deuteriolysis, iodinolysis (with I2), or oxygenation (with O2 gas) to give the corresponding deuterium-labeled compounds, iodides, or alcohols, illustrating their synthetic versatility. The first synthesis of alcyopterosin A, a bicyclic aromatic sesquiterpenoid recently isolated and characterized, has been achieved by this method, starting with an appropriate combination of an acetylene and a diyne.


Development and validation of a hydrophilic interaction chromatography-tandem mass spectrometry method with on-line polar extraction for the analysis of urinary nucleosides. Potential application in clinical diagnosis.
The present paper describes the development, validation and application of a quantitative method for the determination of endogenous nucleosides and nucleobases in urine based on the on-line coupling of a solid-phase extraction step with hydrophilic interaction chromatography-tandem mass spectrometry. The method combines the use of a highly polar restricted-access material (RAM), based on an N-vinylacetamide copolymer, for efficient analyte extraction and matrix removal, with separation by zwitterionic hydrophilic interaction chromatography (ZIC-HILIC), that revealed a satisfactory retention of the polar analytes studied. Detection using a triple quadrupole analyser allowed reliable identification and high-sensitivity quantitation of the target compounds. The on-line configuration developed, RAM-ZIC-HILIC-MS/MS, provides a convenient approach to automate the application to urine analysis, with minimum sample manipulation. The whole method was validated according to European Legislation for bioanalytical methods. The validation steps included the verification of matrix effects, calibration curve, precision, accuracy, selectivity, stability and carry-over in real samples. The results of the validation process revealed that the proposed method is suitable for the reliable determination of nucleosides and nucleobases in human urine, showing limits of detection from 0.1 to 1.3 ng mL(-1). The application to clinical samples was also checked; the results obtained in analyses of urine samples from healthy volunteers and cancer patients using Principal Component Analysis, Hierarchical Cluster Analysis and Soft Independent Modeling of Class Analogy are also shown.


[Bronchiolitis caused by graft versus host reaction after bone marrow allograft].
Graft versus host reaction (GVH) is a major complication of allogenic marrow transplants. The GVH present is a pluri-visceral syndrome in which certain pulmonary disorders are recognised. Amongst these respiratory failure by bronchiolitis is not an exceptional presentation. The case reported here is of an 18 year old man who developed, immediately following a marrow graft for acute lymphoblastic leukaemia, a lethal obstructive respiratory failure after progression for 2 1/2 years. The respiratory function data (TVO with elevated residual volume (VR) and VR/Total lung capacity (CT) hypoxia which corrected on exercise with normocapnia then hypoxic hypercapnia; compliance normal at low frequency but fell at high frequency and inspiratory and expiratory resistance was raised: DLCO/VA was normal) allowed the confirmation of obstructive respiratory failure by disease of the small airways. The pathogenesis of CVH is equivocal. Recurring infections seem to play a role, favoured by iatrogenic factors such as chemotherapy and total body irradiation. In the case reported here the first pulmonary signs followed an episode of influenza with sero-conversion.


PHBV/PLLA-based composite scaffolds fabricated using an emulsion freezing/freeze-drying technique for bone tissue engineering: surface modification and in vitro biological evaluation.
Tissue engineering combines living cells with biodegradable materials and/or bioactive components. Composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramic with suitable properties are promising for bone tissue regeneration. In this paper, based on blending two biodegradable and biocompatible polymers, namely poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(L-lactic acid) (PLLA) with incorporated nano hydroxyapatite (HA), three-dimensional composite scaffolds with controlled microstructures and an interconnected porous structure, together with high porosity, were fabricated using an emulsion freezing/freeze-drying technique. The influence of various parameters involved in the emulsion freezing/freeze-drying technique was studied for the fabrication of good-quality polymer scaffolds based on PHBV polymers. The morphology, mechanical properties and crystallinity of PHBV/PLLA and HA in PHBV/PLLA composite scaffolds and PHBV polymer scaffolds were studied. The scaffolds were coated with collagen in order to improve wettability. During in vitro biological evaluation study, it was observed that SaOS-2 cells had high attachment on collagen-coated scaffolds. Significant improvement in cell proliferation and alkaline phosphatase activity for HA-incorporated composite scaffolds was observed due to the incorporation of HA. After 3 and 7 days of culture on all scaffolds, SaOS-2 cells also had normal morphology and growth. These results indicated that PHBV/PLLA-based scaffolds fabricated via an emulsion freezing/freeze-drying technique were favorable sites for osteoblastic cells and are promising for the applications of bone tissue engineering.


Ultrasonographic diagnosis of pancreatic carcinoma supplemented with CT or ERCP.
The practicability of ultrasonography as the primary imaging method for pancreatic carcinoma was studied in a series of 64 patients with pancreatic carcinoma examined and operated on more than 2 years previously, and CT and ERCP were compared for their expedience in the further examination of uncertain sonographic findings. Ultrasound revealed 42 carcinomas definitely and 8 carcinomas uncertainly (78%) and further indicated dilatation of bile and/or pancreatic ducts in 10 patients. Three sonographic examinations failed, and one resulted in a false negative finding (error of interpretation). ERCP proved to be a little more informative than CT in the further examinations.


[Homonymous lateral quadranopsia disclosing cerebral toxoplasmosis in a patient with AIDS].
A case of Homonymous lateral quadranopsia revealing cerebral toxoplasmosis is reported in AIDS patient. Neuro-ophthalmologic manifestations must be explored by neuro-radiologic examination. Nuclear magnetic resonance would rather be performed than CT scan. Frequencies of cerebral and ocular toxoplasmosis localisations are compared. Severity of toxoplasmosis localisation justifies an early diagnosis based on immunological assay detecting the infection. Prophylactic treatment has to be instored.


Effect of gap junction uncoupler heptanol on resistance arteries reactivity in experimental models of diabetes, hyperlipemia and hyperlipemia-diabetes.
The understanding of the involvement of the gap junctions (GJ) in the vascular reactivity is an ongoing effort. In this study we questioned on impact of pathologies such as diabetes, hyperlipemia, and simultaneous hyperlipemia-diabetes on GJ involvement in the contractile/relaxant response of the mesenteric resistance arteries. To this purpose, four groups of Golden Syrian hamsters were used: (i) diabetics (D), injected by streptozotocin, (ii) hyperlipemics (H), fed the standard chow of the species supplemented with 3% cholesterol and 15% butter, (iii) simultaneously hyperlipemic-diabetics (HD), and (iv) controls (C), age-matched normal healthy animals. At 24 weeks after the beginning of the experiment, the vascular reactivity of the resistance arteries was measured by the myograph technique in the presence/absence of 1 mM Heptanol (Hep) and of vasoconstrictors and vasodilators. The results showed that: (i) in pathological conditions 1 mM Hep significantly impaired the constrictor response of the hamster resistance arteries to both 10(-5) M NA (noradrenaline, agonist of alpha(1)-adrenoceptors) and 64.1 mM K+ (potassium ion, the major intracellular cation). The impairment occur in the group range: HD < H < D < C being the highest at the simultaneous insult of hyperlipemia and diabetes; (ii) independently of the pathological condition, 1 mM Hep abolishes both endothelium-dependent and independent relaxation of the hamster resistance arteries. At 1 mM Hep we noticed a reversible effect on endothelium-dependent relaxation that may be partially restored (in normal) in the presence of L-arginine. It is hoped that these results may contribute to understanding of the involvement of GJ in vascular pathology/dysfunction.


Vascular trauma as a result of therapeutic procedures for the treatment of malignancy.
Twenty-two iatrogenic vascular injuries caused by resection of tumors with local recurrences or adjuvant chemotherapy were treated over a 42-month period in 11 female and 8 male patients with cancer (58% had documented metastases). Sixteen of 22 vascular injuries were caused by intraarterial administration of chemotherapy (8 emboli; 8 direct catheter trauma), and six were caused by resection of tumors with local invasion. The injuries were extremity ischemia (15 extremities in 13 patients), pseudoaneurysm (4), expanding hematoma (3 injuries in 2 patients). Twenty-two surgical repairs included bypass of severely damaged arteries in five, embolectomy in five, interposition grafts in three, pseudoaneurysm resection and primary repair in three, primary repair of three vascular injuries, and one patch angioplasty. Leg amputation was required in two patients. Seventeen of 19 patients had successful vascular repairs with resolution of preoperative indications for vascular repair without intraoperative or postoperative deaths. Long term follow-up (mean, 17 months) showed no recurrence of vascular problems; however, two patients died of metastatic cancer at 6 and 24 weeks after vascular repair. This study supports an aggressive approach to the management of vascular injuries caused by therapeutic interventions for malignancy despite the presence of metastatic disease.


Paget's disease of bone.
To review recent advance in understanding the causation and management of Paget's disease. We review recent publications concerning the aetiology of the disease and the use of biochemical markers of bone turnover in diagnosis and treatment. Epidemiologic studies suggest that Paget's disease is decreasing in prevalence and severity (implying that environmental factors are important) but there is also strong evidence of a genetic predisposition particularly through the SQSTM1 gene. Genome-wide association studies have identified polymorphisms at several other loci that are associated with the disease. Plasma alkaline phosphatase activity (ALP) is widely used, but less helpful in patients with disease of limited extent. Of the newer markers, plasma procollagen-1 N-peptide (PINP) performs best. Treatment with potent bisphosphonates usually produces long-term remission. Both genetic and environmental factors appear to be important in the aetiology of Paget's disease. Effective long-term disease suppression can be achieved with bisphosphonate treatment.


Hypoechoic testicular mass: a case of testicular and epididymal sarcoidosis.
We present a case of testicular and epididymal sarcoidosis in a man with a hypoechoic testicular mass. Radical orchiectomy was averted by use of intraoperative frozen section analysis.


Paget's disease of bone: the anatomical distribution.
Osteitis deformans has hitherto been regarded as a bone disease of unknown aetiology, but epidemiological studies have raised the possibility of an environmental factor. From the epidemiological studies, X-Rays of 1864 patients with Paget's disease were available for examination of the skeletal distribution of the disease. The epidemiological surveys were based upon examinations of X-Rays covering the lumbar spine, pelvis and upper ends of the femora, and all other X-Ray examinations on the patients showing Paget's disease were also studied for evidence of the disease outside the primary sites. There is a preference for the lower half of the body, and a distribution of the disease in the lumbar and dorsal vertebrae similar to spondylosis; a peri-articular origin of the disease is apparent in long bones, and there is a tendency for the right side of the body to be affected more than the left. The radiological distribution has been supported by radio-nucleide studies in a further 50 patients. In general, the vascular axial skeleton is affected, and it is postulated that an environmental factor is being transported by the blood to bone. Bone stress may then stimulate the changes of osteitis deformans.


Long-term Clinical Outcome of Aortic Arch Calcification in Kidney Transplant Recipients.
Cardiovascular disease is the most common cause of death in kidney transplant recipients (KTRs). Aortic arch calcification (AoAC) is a major risk factor for cardiovascular disease in KTRs. This study aimed to evaluate the long-term outcomes of AoAC in KTRs. We retrospectively evaluated AoAC in KTRs between 2000 and 2010 using chest radiography. AoAC was semiquantitatively estimated by calculating calcification score. Associations between clinical and biochemical parameters were evaluated. A total of 258 patients were enrolled; the mean age was 40.7 years, and 135 (52.3%) were males. Diabetes mellitus was present in 28 (10.9%), and deceased donor kidney transplantation (KT) had been performed in 95 (36.8%). Fifty-three (20.5%) patients had AoAC at the time of KT, with an AoAC score of 0.8 ± 2.0. The proportion of KTRs with AoAC gradually increased to 23.3%, 26.4%, and 28.7% at 1, 3, and 5 years, respectively, after KT. The AoAC score also gradually increased to 1.0 ± 2.3, 1.2 ± 2.8, and 1.6 ± 3.1, respectively, at 1, 3, and 5 years after KT. The 10-year graft survival rate was 83.2% in the AoAC group and 85.1% in the non-AoAC group. The 10-year patient survival rate was 90.6% in the AoAC group and 95.7% in the non-AoAC group. In multivariate analysis, age at KT, deceased-donor KT, and diabetes mellitus were independent predictors for all-cause mortality. AoAC is an independent predictor of poor cardiovascular outcome in KTRs. Age and dialysis duration were independent risk factors for AoAC. Age at KT, deceased-donor KT, and diabetes mellitus were independent predictors for all-cause mortality. Regular follow-up by chest radiography could be a simple and useful method to screen for AoAC and reduce cardiovascular mortality.


Matching documented training needs with practical capacity: lessons learned from Project Public Health Ready.
The Upper Midwest offers a distinct environment for identifying and addressing threat and preparedness scenarios. The population is often scattered, with residents using urban centers periodically. This has also led to the challenge of providing specific skills and cross-disciplinary awareness and coordination to the public health community. The Upper Midwest Center for Public Health Preparedness was established by a grant from the Centers for Disease Control and Prevention to assist in meeting the challenge of adding capacity to develop the preparedness workforce in the Upper Midwest. Project Public Health Ready (PPHR) provides an example of the role academic preparedness centers can play in partnering with local public health agencies to strengthen the public health workforce. The purpose of this article is to present the Iowa Systems Model for Workforce Development being utilized for workforce training and education, describe how the model has been applied in the example of PPHR, and discuss lessons learned from the PPHR experience.


Assessment of personal integrated exposure to fine particulate matter of urban residents in Hong Kong.
Metropolitan residents are concerned about their exposure to airborne pollutants. But establishing these exposures is challenging. A compact personal exposure kit (PEK) was developed to evaluate personal integrated exposure (PIE) from time-resolved data to particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) in five microenvironments, including office, home, commuting, other indoor activities (other than home and office), and outdoor activities experienced both on weekdays and weekends. The study was conducted in Hong Kong. The PEK measured PM2.5, reported location and several other factors, stored collected data, as well as reported the data back to the investigators using global system for mobile communication (GSM) telemetry. Generally, PM2.5 concentrations in office microenvironment were found to be the smallest (13.0 μg/m3), whereas the largest PM2.5 concentration microenvironments were experienced during outdoor activities (54.4 μg/m3). Participants spent more than 85% of their time indoors, including in offices, homes, and other public indoor venues. On average, 42% and 81% of the time were spent in homes, which contributed 52% and 79% of PIE (during weekdays and weekends, respectively), suggesting that improvement of air quality in homes may reduce overall exposures and indicating the need for actions to mitigate possible public health burdens in Hong Kong. This study also found that various indoor/outdoor microenvironments experienced by urban office workers cannot be accurately represented by general urban air quality data reported from the regulatory monitoring. Such personalized air quality information, especially while in transit or in offices and homes, may provide improved information on population exposures to air pollution. Implications: A newly developed personal exposure kit (PEK) was used to monitor PM2.5 exposure of metropolitan citizens in their daily life. Different microenvironments and time durations caused various personal integrated exposure (PIE). The stationary monitoring method for PIE was also compared and evaluated with PEK. Positive protection actions can be taken after understanding the major contribution to PM2.5 exposure.


Intensifying embroilments: Technosciences, imaginaries and publics.
A common thread in the contributions to this special issue can be found in the Foucauldian notion of intensification. Technoscientific imaginaries and publics have long been embroiled; yet, elements of novelty in their relationship can be detected in the ambivalence of the overcoming of traditional purification work; the expanding production of 'prototypical' truths; the uncertain threshold between publics of enquirers, witnesses and lookouts; and the growing indistinction of the everyday and the sublime, of trivial and non-trivial futures. The intensification of old patterns and recent trends determines a critical moment in a literal sense of the word: novel potentialities for a democratic governance of technosciences are opening up, but novel dominative opportunities are disclosing as well.


Modeling analysis of myosin-based meridional X-ray reflections from frog skeletal muscles in relaxed and contracting states.
Analysis of the myosin-based meridional intensity data in the X-ray diffraction patterns of live frog skeletal muscles was performed to propose a more precise model for a myosin crown periodicity and an axial disposition of two-headed crossbridges along the thick filament in a sarcomere. Modeling studies revealed that the thick filament has a mixed structure of two different periodicities of the myosin crossbridge crown arrangement and that the crown periodicity and the axial disposition of crossbridges are altered when muscle goes from the relaxed state to the contracting state. Factors that primarily affect the meridional intensities were examined.


Identification of P-glycoprotein/multidrug resistance genes from model organisms.
Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, several new members of this gene superfamily have been cloned from Drosophila, Saccharomyces cerevisiae, and E. coli DNA. The Drosophila and E. coli genes contain two sets of transmembrane domains and two ATP-binding domains, whereas the yeast gene contains single transmembrane and ATP-binding domains. All three genes show a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The E. coli sequence is the only known transporter gene containing both ATP and transmembrane domains in a single open reading frame. While the function of these sequences has not been determined, they may prove to be useful for developing a model to study the function of P-glycoproteins.


Pain assessment in younger and older pain patients: psychometric properties and patient preference of five commonly used measures of pain intensity.
To study the psychometric properties and preference for five different pain intensity scales (horizontal visual analog scale [VAS], vertical VAS, Box-11, Box-21, and verbal descriptor scale) across different age groups. Chronic pain patients rated their present, average, weakest, and strongest pain on five different scales, and indicated scale preference. Outpatient pain facility. The number of mistakes on all scales increased with increasing age, and the VAS appeared to be most prone to making mistakes. All scales appeared to be sufficiently valid, but the verbal descriptor scale was less related to the common underlying pain factor than the other scales. The Box-21 was the most preferred scale overall, although patients aged >75 years especially preferred the verbal descriptor scale. The numerical Box-21 scale is an excellent choice for pain intensity assessment in heterogeneous patient groups. The verbal descriptor scales may be considered when the study population consists of a majority of older persons.


The role of natural product chemistry in drug discovery.
Although traditionally natural products have played an important role in drug discovery, in the past few years most Big Pharma companies have either terminated or considerably scaled down their natural product operations. This is despite a significant number of natural product-derived drugs being ranked in the top 35 worldwide selling ethical drugs in 2000, 2001, and 2002. There were 15 new natural product-derived drugs launched from 2000 to 2003, as well as 15 natural product-derived compounds in Phase III clinical trials or registration at the end of 2003. Recently, there has been a renewed interest in natural product research due to the failure of alternative drug discovery methods to deliver many lead compounds in key therapeutic areas such as immunosuppression, anti-infectives, and metabolic diseases. To continue to be competitive with other drug discovery methods, natural product research needs to continually improve the speed of the screening, isolation, and structure elucidation processes, as well addressing the suitability of screens for natural product extracts and dealing with issues involved with large-scale compound supply.


The effect of dietary energy:protein ratio, protein quality and food allocation on the efficiency of utilisation of protein by broiler chickens.
1. Various theories have been proposed to explain the reduced performance of broilers when given feeds excessively high in protein, but a satisfactory solution to this problem had, up to now, not been found. Three experiments were conducted to test the hypothesis that the efficiency of utilisation of protein (ep) is a linear-plateau function of the ratio between the feed apparent metabolisable energy and digestible crude protein contents (AMEn:DCP) and that dietary protein quality, feed allocation and sex do not influence this relationship. 2. A 'linear-plateau' model successfully described the efficiency of protein utilisation (ep) as a function of AMEn:DCP in all three experiments. In Experiment 1, with both sexes being both ad libitum and control fed, the breakpoint was at 58.6 MJ AMEn/kg DCP. In Experiment 2, both sexes were fed balanced and unbalanced protein series, and at different rates, the slopes of the ascending part of the linear-plateau relationships for the different treatments were the same for all treatments (0.0204), and the inflection point was at 71 MJ AMEn/kg DCP. Using similar treatments in Experiment 3, the breakpoint for the balanced protein was 72 MJ/kg and for the unbalanced, 64, with a combined slope of 68 MJ AMEn/kg DCP. 3. The three experiments provide adequate evidence that ep is a linear-plateau function of the dietary AMEn:DCP ratio with a breakpoint of around 66.2 ± 1.98 MJ AMEn/kg DCP. Below this critical ratio, food intake declines as does protein and lipid retention. 4. That broilers, like pigs, exhibit an energy-dependent phase when high-protein feeds are offered is of practical importance when formulating pre-starter feeds for broilers and starter feeds for turkey poults as the ep of such feeds may well fall below the maximum due to the lack of dietary energy required to process the high dietary protein contained in such feeds resulting in poorer performance than expected.


The protein and lipid composition of the membrane of milk fat globules depends on their size.
In bovine milk, fat globules (MFG) have a heterogeneous size distribution with diameters ranging from 0.1 to 15 µm. Although efforts have been made to explain differences in lipid composition, little is known about the protein composition of MFG membranes (MFGM) in different sizes of MFG. In this study, protein and lipid analyses were combined to study MFG formation and secretion. Two different sized MFG fractions (7.6±0.9 µm and 3.3±1.2 µm) were obtained by centrifugation. The protein composition of MFGM in the large and small MFG fractions was compared using mass-spectrometry-based proteomics techniques. The lipid composition and fatty acid composition of MFG was determined using HPLC-evaporative light-scattering detector and gas chromatography, respectively. Two frequently studied proteins in lipid droplet biogenesis, perilipin-2 and TIP47, were increased in the large and small MFG fractions, respectively. In the large MFG fraction, besides perilipin-2, cytoplasmic vesicle proteins (heat shock proteins, 14-3-3 proteins, and Rabs), microfilaments and intermediate filament-related proteins (actin and vimentin), host defense proteins (cathelicidins), and phosphatidylinositol were higher in concentration. On the other hand, cholesterol synthesis enzymes [lanosterol synthase and sterol-4-α-carboxylate 3-dehydrogenase (decarboxylating)], cholesterol, unsaturated fatty acids, and phosphatidylethanolamine were, besides TIP47, higher in concentration in the small MFG fraction. These results suggest that vesicle proteins, microfilaments and intermediate filaments, cholesterol, and specific phospholipids play an important role in lipid droplet growth, secretion, or both. The observations from this study clearly demonstrated the difference in protein and lipid composition between small and large MFG fractions. Studying the role of these components in more detail in future experiments may lead to a better understanding of fat globule formation and secretion.


Incidence rates of hepatocellular carcinoma in the U.S. and Denmark: recent trends.
Hepatocellular carcinoma (HCC) incidence rates vary by gender, age, time and place. Geographic differences in gender-, age- and time-specific HCC incidence rates may improve the understanding of HCC risk factors. We computed annual standardized HCC incidence rates for the United States (U.S.) 1978-2004 and for Denmark 1978-2003. Among U.S. white men aged 45-59 the HCC incidence rates were comparable to the Danish rates until 1995, but more than tripled over the following 8 years to become over 2.5-fold higher than the Danish rate by 2003, with an additional small increase in 2004. HCC rates in black U.S. men aged 45-59 also increased sharply after 1995. Among women aged 45-59 the U.S. HCC rates were elevated in recent years, but did not show the sharp increase after 1995 observed among men; the Danish rates showed a decreasing trend throughout 1978-2003. U.S. rates in the 60-74 years age groups showed a protracted and gradual increase with no evidence of a sharp increase after 1995. In the 60-74 years age group, rates for Danish men were comparable to those for U.S. white men, but rates for Danish women decreased. The U.S. prevalence rates of hepatitis C virus (HCV) infection are 2.1 and 1.1% for men and women, respectively, the Danish 0.2%. The disparity in HCV prevalence is the most likely explanation for the differences between Danish and U.S. trends in HCC incidence. Intravenous drug use and blood transfusions are the major sources of HCV, and we suggest that increased HCV infection prevalence among Vietnam era military veterans may contribute to the earlier and steeper HCC incidence increase for U.S. men than for U.S. women.


Recent Developments in Oral Appliance Therapy of Sleep Disordered Breathing.
Oral appliances are increasingly gaining a place in the treatment of sleep disordered breathing caused by upper airway obstruction. This review of publications since 1995 documents substantial progress in the scientific basis for this therapy. Imaging by several techniques has shown that mandibular advancing oral appliances open the airway in awake and anaesthetized subjects, creating the presumption that this effect is maintained in sleep. Three controlled cross-over treatment trials have shown that patients consistently prefer oral appliance over continuous positive airway pressure therapy, especially when the treatment effect is strong. Appliance design and use indicates a preference for adjustable mandibular advancing appliances. Complications of therapy appear to be infrequent, but evidence for safety of long-term use is still limited. Oral appliance therapy can be an effective therapy for sleep disorders caused by upper airway obstruction. Considering the accumulated evidence, it is no longer tenable to label oral appliance therapy an OexperimentalO procedure.


Pregnancy outcomes in Lebanese-born women in western Sydney.
A sample of 400 Lebanese-born women who gave birth at Auburn District Hospital in 1987-1988 was compared with a sample of 400 Australian-born women who gave birth in the same time period. The Lebanese-born women were found to be older and of higher parity than were their Australian-born counterparts; and to have booked their hospital admission significantly later in pregnancy than did the Australian-born women. Lebanese-born women also had frequently made a consanguineous marriage. Certain antenatal and intrapartum complications were more common in the Lebanese-born women, and perinatal mortality and morbidity rates were higher among their infants. The particular problems of pregnancy in Lebanese-born women, and possible ways of overcoming these, are discussed.


Monitoring Pb in Aqueous Samples by Using Low Density Solvent on Air-Assisted Dispersive Liquid-Liquid Microextraction Coupled with UV-Vis Spectrophotometry.
In this study, AA-DLLME combined with UV-Vis spectrophotometry was developed for pre-concentration, microextraction and determination of lead in aqueous samples. Optimization of the independent variables was carried out according to chemometric methods in three steps. According to the screening and optimization study, 86 μL of 1-undecanol (extracting solvent), 12 times syringe pumps, pH 2.0, 0.00% of salt and 0.1% DDTP (chelating agent) were chosen as the optimum independent variables for microextraction and determination of lead. Under the optimized conditions, R = 0.9994, and linearity range was 0.01-100 µg mL-1. LOD and LOQ were 3.4 and 11.6 ng mL-1, respectively. The method was applied for analysis of real water samples, such as tap, mineral, river and waste water.


Interferon-γ decreases chondroitin sulfate proteoglycan expression and enhances hindlimb function after spinal cord injury in mice.
Glial cells, including astrocytes and macrophages/microglia, are thought to modulate pathological states following spinal cord injury (SCI). In the present study, we evaluated the therapeutic effects of interferon-γ (IFN-γ), which is one of the cytokines regulating glial function, in a mouse contusive SCI model. We found that intraperitoneal injection of IFN-γ significantly facilitated locomotor improvement following SCI. Immunohistochemistry demonstrated that IFN-γ decreased the accumulation of chondroitin sulfate proteoglycans (CSPGs), which are critical axon outgrowth inhibitors produced by reactive astrocytes in the injured central nervous system (CNS). Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting demonstrated that neurocan, one of several CSPGs, was reduced in the spinal cords of IFN-γ-treated mice compared to vehicle-treated mice. Consistently, IFN-γ inhibited the production of neurocan from activated astrocytes in vitro. In addition, IFN-γ treatment enhanced the number of serotonin-positive nerve fibers and myelinated nerve fibers around the lesion epicenter. We also found that glial cell line-derived neurotrophic factor (GDNF) and insulin-like growth factor-1 (IGF-1) were upregulated post-SCI following IFN-γ treatment. Our results indicate that IFN-γ exhibits therapeutic effects in mouse contusive SCI, presumably by reducing CSPG expression from reactive astrocytes and increasing the expression of neurotrophic factors.


Antiarrhythmic drug therapy and all-cause mortality after catheter ablation of atrial fibrillation: A propensity-matched analysis.
It is not clear if antiarrhythmic drug therapy (AAD) after catheter ablation (CA) of atrial fibrillation (AF) increases mortality. To determine whether there is an association between AAD therapy and mortality after CA of AF. There were 3624 consecutive patients with AF (mean age: 59 ± 11 years, women: 27%, paroxysmal AF: 58%). An AAD was used in 2253 patients (62%, AAD group) for a mean duration of 1.3 ± 0.8 years, during a mean follow-up of 6.7 ± 2.2 years after CA of AF. Using propensity score matching, with every 2 patients using an AAD matched to 1 patient who did not use AAD (NO-AAD group), Cox regression models were utilized to assess the association between AAD use (as a time-variable covariate) and all-cause mortality. There were a total of 50 deaths (2.2%) in the AAD and 62 deaths (4.5%) in the NO-AAD groups, respectively (P = .02). At the time of death, 46 of 50 patients (92%) who died in the AAD cohort were still using an AAD (P = .21, compared to baseline use). On multivariate analysis, although the risk of death was not statistically significant between the AAD and NO-AAD cohorts, there was a trend towards mortality benefit with AAD therapy (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.43-1.00, P = .05), regardless of the rhythm or anticoagulation status. AAD use after CA of AF is not associated with an increased risk of mortality, suggesting that when carefully chosen and monitored, AADs appear to be safe after CA of AF.


Group counseling to prevent sexually transmitted disease and HIV: a randomized controlled trial.
To compare prevention effectiveness of multisession group counseling with standard HIV prevention counseling for reducing risk behaviors and new sexually transmitted diseases (STDs). Small groups of consenting STD clinic patients were randomized to four 1-hour small group counseling interventions based on the information-motivation-behavioral skills (IMB) model with a booster session at 2 months or to the standard two 20-minute individual counseling sessions. Follow-up interviews and examinations were 2, 6, 9, and 12 months after enrollment. From March 1992 through June 1993, 996 (59%) of 1,681 eligible persons were enrolled; 32 (3%) tested HIV-positive and were excluded. Intervention attendance was 98% for one session, and 47% attended four or five counseling sessions. Follow-up was similar for both groups: 72% attended at least once; 47% returned at 12 months. Both groups had similar increases in condom use and decreases in number of partners, and similar number of new infections with gonorrhea (14%), chlamydia (10%), or syphilis (2%). Two 20-minute counseling sessions were as effective as four 1-hour group sessions for reducing risk behavior and STD incidence in an STD clinic patient population.


Hepatitis G virus infection in screened Chinese blood donors.
To determine the prevalence of the recently identified hepatitis G virus (HGV)/GBV-C in screened Chinese paid blood donors. Two hundred and seventy-nine plasma samples were tested for HGV RNA by RT-PCR with nested primers from the 5'-noncoding region of GBV-C. All samples were obtained from plasma or blood bags that had been screened twice by routine selection tests (ALT, HBsAg, Anti-HCV, anti-HIV, and syphilis) and were available for clinical use. HGV RNA was detected in 2 (4%) of 50 paid plasma donors from the Beijing Red Cross Blood Center, 1 (2%) of 50 paid blood donors from Taiyuan, and 9 (5%) of 179 paid blood donors from Hebei, a total HGV detection rate of 4.3% (12/279). Our data suggest that HGV infection is relatively frequent even in screened donors, at least in paid screened donors, although larger-scale studies are required.


Social vulnerability as a predictor of mortality and disability: cross-country differences in the survey of health, aging, and retirement in Europe (SHARE).
Social factors are important for health; the concept of social vulnerability considers them holistically and can be quantified using a social vulnerability index (SVI). Investigate the SVI in relation to mortality and disability, independent of frailty, in middle-aged and older European adults, and examine how this relationship differs across countries. 18,289 community-dwelling participants 50 years and older from SHARE wave 1 (2004) were included in our sample. A 32-item SVI and a 57-item frailty index were calculated for individuals as the proportion of deficits present out of the total number considered. Countries were grouped based on their social model: Nordic (Denmark, Netherlands, Sweden), Continental (France, Austria, Belgium, Germany) and Mediterranean (Greece, Italy, Spain). Outcome measures were 5-year mortality and disability (≥1 dependency with activities of daily living) at wave 4 (2011-2012). High social vulnerability (highest quartile) predicted mortality (HR = 1.25, 95 % CI 1.07-1.45), and disability (OR = 1.36, 95 % CI 1.15-1.62) after controlling for age, sex, baseline disability and frailty level. When analyses were split by social model, social vulnerability remained a significant predictor of mortality for Continental (HR = 1.36, CI 1.05-1.77) and Mediterranean (HR = 1.33, CI 1.03-1.72) countries, but not the Nordic (HR = 1.02, CI 0.76-1.37) countries; the same pattern was observed for disability (Nordic OR = 1.06, CI 0.72-1.55; Continental OR = 1.53, CI 1.20-1.96; Mediterranean OR = 1.58, CI 1.13-2.23). Social vulnerability was a significant predictor of mortality and disability, though when controlling for frailty, this relationship varied by the social model of the country.


Expression of the rat amylin (IAPP/DAP) gene.
We have used the polymerase chain reaction with mixed sequence primers to generate a probe for rat amylin and have used this to detect expression in various rat tissues. Amylin mRNA is found in greatest concentrations in the pancreas where a single mRNA species can be detected giving a hybridisation signal intensity approximately 10% that of insulin mRNA. When the beta cell population was depleted with streptozotocin, both amylin and insulin mRNAs were reduced to a similar extent. Consistent with its supposed role in the control of carbohydrate metabolism, amylin mRNA was also found in the stomach. Unlike the related peptide, CGRP, amylin mRNA is not present in the thyroid and is not widely distributed in the central nervous system. The only nervous tissue in which it could be detected was the dorsal root ganglion. Surprisingly, amylin mRNA was also found in the lung though only at very low levels.


Surface-plasmon-resonance-based biosensor with immobilized bisubstrate analog inhibitor for the determination of affinities of ATP- and protein-competitive ligands of cAMP-dependent protein kinase.
Interactions between adenosine-oligoarginine conjugates (ARC), bisubstrate analog inhibitors of protein kinases, and catalytic subunits of cAMP-dependent protein kinase (cAPK Calpha) were characterized with surface-plasmon-resonance-based biosensors. ARC-704 bound to the immobilized kinase with subnanomolar affinity. The immobilization of ARC-704 to the chip surface via streptavidin-biotin complex yielded a high-affinity surface (K(D)=16nM). The bisubstrate character of ARC-704 was demonstrated with various ligands targeted to ATP-binding pocket (ATP and inhibitors H89 and H1152P) and protein-substrate-binding domain of Calpha (RIIalpha and GST-PKIalpha) in competition assays. The experiments performed on surfaces with different immobilization levels of ARC-704 produced similar results. The closeness of the obtained affinities of the tested compounds to the inhibitory potencies and affinities of the compounds measured with other methods demonstrates the applicability of the chip with the immobilized biligand inhibitor for the characterization of both ATP- and substrate protein-competitive ligands of basophilic protein kinases.


The cytotoxicity of 3-bromopyruvate in breast cancer cells depends on extracellular pH.
Although the anti-cancer properties of 3BP (3-bromopyruvate) have been described previously, its selectivity for cancer cells still needs to be explained [Ko et al. (2001) Cancer Lett. 173, 83-91]. In the present study, we characterized the kinetic parameters of radiolabelled [14C] 3BP uptake in three breast cancer cell lines that display different levels of resistance to 3BP: ZR-75-1 < MCF-7 < SK-BR-3. At pH 6.0, the affinity of cancer cells for 3BP transport correlates with their sensitivity, a pattern that does not occur at pH 7.4. In the three cell lines, the uptake of 3BP is dependent on the protonmotive force and is decreased by MCTs (monocarboxylate transporters) inhibitors. In the SK-BR-3 cell line, a sodium-dependent transport also occurs. Butyrate promotes the localization of MCT-1 at the plasma membrane and increases the level of MCT-4 expression, leading to a higher sensitivity for 3BP. In the present study, we demonstrate that this phenotype is accompanied by an increase in affinity for 3BP uptake. Our results confirm the role of MCTs, especially MCT-1, in 3BP uptake and the importance of cluster of differentiation (CD) 147 glycosylation in this process. We find that the affinity for 3BP transport is higher when the extracellular milieu is acidic. This is a typical phenotype of tumour microenvironment and explains the lack of secondary effects of 3BP already described in in vivo studies [Ko et al. (2004) Biochem. Biophys. Res. Commun. 324, 269-275].


Intra- and interganglionic synaptic connections in the CNS of Aplysia.
Synaptic connections were found between two groups of neurons in the CNS of Aplysia, the cerebral ganglion A and B cluster neurons which are involved in the control of pedal and parapodial movements and neurons in the pleural ganglion which has been shown to modulate locomotion. The A and B neurons made synaptic connections in both the cerebral and pleural ganglia. Pleural neurons had synaptic connections among themselves and with A and B neurons. The A neurons made excitatory monosynaptic connections with the B neurons and a minimum of 6 pleural neurons including the left giant cell (LGC). All of the A neuron synapses found were excitatory. The B neurons received excitatory synaptic input from two other groups of neurons in the cerebral ganglion and both excitatory and inhibitory input from pleural neurons. The latter were identified on the basis of their synaptic connections with the LGC and A neurons. The B neurons and LGC had several common synaptic inputs. The A neurons received monosynaptic input from only 2 pleural neurons. Complex synaptic circuits between A and B neurons and pleural neurons were found. These included recurrent inhibition of B neurons by A neurons via a pleural interneuron, feedforward summation of A neuron synaptic input to the LGC, and reciprocal excitatory synaptic connections between B and the pleural neurons. The activity of the B neurons was modulated by direct inhibitory and excitatory synaptic connections from pleural neurons. The A neurons were modulated primarily by a polysynaptic pathway through the B neurons. The modulation of cerebral A and B neurons by pleural neurons is consistent with behavioral results obtained studying locomotion.