Stabilizing and Activating Metastable Nickel Nanocrystals for Highly Efficient Hydrogen Evolution Electrocatalysis.
Exploring high-performance and cost-efficient electrocatalysts with unusual metastable phase offers opportunities for improving the electrochemical hydrogen generation, while it remains a great challenge to achieve them with desirable activity and stability. Herein, we report that the doping engineering in a metastable, hexagonal-close-packed nickel (hcp Ni) electrocatalyst is a largely unrevealed yet important factor in achieving an extremely active and stable electrocatalyst toward alkaline hydrogen evolution reaction (HER). Theoretical predications and experimental results suggest that, while the stability of metastable hcp Ni electrocatalyst can be largely improved via the manganese (Mn) doping due to the lower formation energy and lattice stabilization, the MnO/hcp Ni surface promotes the HER via intrinsic favorable H2O adsorption and fast water dissociation kinetics. Consequently, the Mn-doped hcp Ni electrocatalyst shows a small overpotential of 80 mV at 10 mA/cm2 and a low Tafel slope of 68 mV/dec. The result is even approaching that of the commercial Pt/C, being one of the best reported non-noble metal HER electrocatalysts in alkaline media. Under long-term chronopotentiometry measurement, such electrocatalyst can endure at least 10 h with negligible activity decay and structure change. The present work demonstrates the dimension in boosting the electrocatalysis by doping engineering of metastable electrocatalysts.


Bereavement and Prognosis After a First Acute Myocardial Infarction: A Swedish Register-Based Cohort Study.
BACKGROUND Despite accumulating evidence suggesting that bereavement is associated with increased risks of cardiovascular morbidity and mortality, the association between bereavement and prognosis after acute myocardial infarction (AMI) has not been well documented. We investigated the association by using Swedish register data. METHODS AND RESULTS We studied 266 651 patients with a first AMI included in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) quality register from 1991 to 2018. We obtained information on bereavement (ie, death of a partner, child, grandchild, sibling, or parent), on primary (nonfatal recurrent AMI and death attributed to ischemic heart disease) and secondary outcomes (total mortality, heart failure, and stroke) and on covariates from several national registers. The association was analyzed using Poisson regression. The bereaved patients had a slightly increased risk of the primary outcome; the corresponding risk ratio (RR) was 1.02 (95% CI, 1.00-1.04). An increased risk was noted any time bereavement occurred, except if the loss was in the year after the first AMI. The association was strongest for the loss of a partner, followed by the loss of a child, grandchild, sibling, or parent. We also observed increased risks for total mortality (RR, 1.14 [95% CI, 1.12-1.16]), heart failure (RR, 1.05 [95% CI, 1.02-1.08]), and stroke (RR, 1.09 [95% CI, 1.05-1.13]) following bereavement. CONCLUSIONS Bereavement was associated with an increased risk of poor prognosis after a first AMI. The association varied by the relationship to the deceased.


Mobile source emission inventories--monthly or annual average inputs to MOBILE6?
In many urban areas, on-road vehicles are the biggest contributing source category of volatile organic compounds (VOCs) and nitrogen oxides (NOx). Based on a recently completed emission inventory study for three counties in central Florida, the major source by far of anthropogenic VOCs and NOx was on-road mobile sources, even though other sources (such as construction equipment, lawn and garden equipment, and various point sources) were also significant. Although there is specific guidance for conducting an ozone-season inventory for mobile sources, there is a lack of detailed guidance as to how to employ the U.S. Environmental Protection Agency's (EPA) latest mobile source emission factor program, MOBILE6, for an annual inventory. Several of the MOBILE6 inputs that significantly influence emission factors (e.g., temperature) can vary widely throughout the year, and the annual average value may not be appropriate. Rather, it may be better to utilize monthly values of these parameters. This paper investigated the sensitivity of the annual emission inventory results to using annual or monthly values of temperature, Reid Vapor Pressure of gasoline, and humidity. The results show that, for a three-county area in central Florida representing metropolitan Orlando, the annual emission inventory based on the sum of individual monthly averages is not significantly different from that calculated using one set of annual average inputs to MOBILE6.


Differential Catabolism of an Anthocyanin-Rich Elderberry Extract by Three Gut Microbiota Bacterial Species.
Elderberries are good sources of anthocyanins, which are poorly absorbed in the upper gastrointestinal tract but extensively transformed into phenolic metabolites at the colonic level. Because different gut microbiota strains have different metabolism, the catabolism of anthocyanins may lead to interindividual differences in metabolite production. In this work, an anthocyanin-rich elderberry extract was incubated with three single gut microbial strains (Enterobacter cancerogenous, Bifidobacterium dentium, and Dorea longicatena) up to 4 days, to assess differences in their phenolic metabolism. All of the strains degraded the elderberry anthocyanins, but the metabolic pathways followed were different. Although some metabolites were common for all of the strains, a wide disparity was observed in the kind and amount of several phenolic metabolites produced by each species. These in vitro preliminary results may be of help in the interpretation of the bioavailability of anthocyanins and give a clue to understand interindividual variability in metabolite production.


Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients.
Hypercholesterolemic and hypertensive patients have impaired endothelium-dependent vasorelaxation because of decreased nitric oxide activity, but the mechanism underlying this abnormality is unknown. This study sought to determine whether an increased breakdown of nitric oxide by xanthine oxidase-generated superoxide anions could participate in these forms of endothelial dysfunction. We studied vascular responses to intrabrachial infusion of acetylcholine (an endothelium-dependent vasodilator, 7.5 to 30 microg/min) and sodium nitroprusside (a direct smooth muscle dilator, 0.8 to 3.2 microg/min) by strain-gauge plethysmography before and during the combined administration of oxypurinol (300 microg/min), a xanthine oxidase inhibitor, in 20 hypercholesterolemic patients, 20 essential hypertensive patients, and 20 normal subjects. The vasodilator response to acetylcholine was blunted in hypercholesterolemic (highest flow, 8.2+/-8 mL x min(-1) x dL(-1)) and hypertensive (8.5+/-4 mL x min(-1) x dL(-1)) patients compared with control subjects (13.8+/- 6.6 mL x min(-1) x dL(-1)) (both P<.001); however, no differences were observed in the response to sodium nitroprusside. Oxypurinol did not change the response to acetylcholine in control subjects (P=.26) and improved, but did not normalize, its vasodilator effect in hypercholesterolemic patients (P<.01). Oxypurinol did not affect the response to acetylcholine in hypertensive patients (P=.34) and did not modify the response to sodium nitroprusside in any group. These results suggest that xanthine oxidase-generated superoxide anions are partly responsible for the impaired endothelial vasodilator function of hypercholesterolemic patients. In contrast, this mechanism does not appear to play a significant role in essential hypertension.


I.v. lidocaine worsens histamine-induced bronchoconstriction in dogs.
We have assessed the effect of lidocaine (lignocaine) on histamine-induced bronchoconstriction by direct visualization with a superfine fibreoptic bronchoscope. Seven mongrel dogs were anaesthetized with pentobarbital (pentobarbitone) 30 mg kg-1 followed by 2 mg kg-1 h-1 and pancuronium 200 micrograms kg-1 h-1. The trachea was intubated with a tracheal tube containing a second lumen for insertion of a 2.2-mm fibreoptic bronchoscope. This allowed estimation of the bronchial cross-sectional area (BCA) of the third bronchial bifurcation of the right lung. We used NIH image, a public domain image processing and analysis program. Bronchoconstriction was produced with a bolus dose of histamine 10 micrograms kg-1 i.v. followed by continuous infusion of 500 micrograms kg-1 h-1. After 30 min the following i.v. doses of lidocaine were given: lidocaine 0 (saline), 0.01, 0.1, 1.0 and 10 mg kg-1 at 10-min intervals. BCA was assessed 90 s after each dose. Arterial blood sampling was performed for measurement of plasma catecholamines. Lidocaine 1.0 and 10 mg kg-1 significantly reduced histamine-decreased BCA from 69.7 (SEM 4.1)% to 59.8 (7.3)% and 34.3 (6.8)%, respectively. Plasma concentrations of catecholamines decreased significantly after lidocaine 10 mg kg-1 i.v. In addition, there was a significant correlation between percentage decreases in plasma concentrations of epinephrine (adrenaline) and norepinephrine (noradrenaline) and reduction in %BCA (epinephrine-BCA, P < 0.01, r = 0.674; norepinephrine-BCA, P < 0.01, r = 0.510). This study suggests that i.v. lidocaine may exacerbate histamine-induced bronchoconstriction by a sympatholytic effect. This may have therapeutic implications for patients with acute asthma or anaphylactic shock who may become dependent on circulating catecholamines.


The role of Zn2+ on the structure and stability of murine adenosine deaminase.
Adenosine deaminase (ADA) is a key enzyme in purine metabolism and crucial for normal immune competence. It is a 40 kDa monomeric TIM-barrel protein containing a tightly bound Zn(2+), which is required for activity. In this study, we have investigated the role of Zn(2+) with respect to ADA structure and stability. After removing Zn(2+), the crystallographic structure of the protein remains highly ordered and similar to that of the holo protein with structural changes limited to regions capping the active site pocket. The stability of the protein, however, is decreased significantly in the absence of Zn(2+). Denaturation with urea shows the midpoint to be about 3.5 M for the apo enzyme, compared with 6.4 M for the holo enzyme. ADA contains four tryptophan residues distant from the Zn(2+) site. (19)F NMR studies in the presence and absence of Zn(2+) were carried out after incorporation of 6-(19)F-tryptophan. Chemical shift differences were observed for three of the four tryptophan residues, suggesting that, in contrast to the X-ray data, Zn(2+)-induced structural changes are propagated throughout the protein. Changes throughout the structure as suggested by the NMR data may explain the lower stability of the Zn(2+)-free protein. Real-time (19)F NMR spectroscopy measuring the loss of Zn(2+) showed that structural changes correlated with the loss of enzymatic activity.


[Clinical features of thyroid dysfunction in adult Japanese after allogeneic hematopoietic stem cell transplantation].
We examined the incidence and clinical features of thyroid dysfunction in 661 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital. At a median of 2.5 (1.0-11.3) years, 28 patients (4.2%) developed subclinical hypothyroidism, and 16 patients (2.4%) developed hypothyroidism. Eight of 16 patients (50%) with hypothyroidism were positive for anti-thyroid antibodies. Ten of 44 patients (22.7%) with thyroid dysfunction were discovered more than 5 years after allo-HSCT. Thyroid dysfunction with late onset was common in allo-HSCT recipients, and thyroid function should be monitored on a regular basis.


Long non-coding RNA expression profiles in different severity EV71-infected hand foot and mouth disease patients.
Enterovirus 71 (EV71) is associated with the severe hand foot and mouth disease (HFMD) outcomes, however the host-virus interaction mechanism and the pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs) are involved in variety physiological and pathological processes, but the functions of lncRNAs in EV71 infection remain elusive. Here we profiled the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) from EV71-infected mild patients, severe patients as well as the healthy controls, and identified 8541 lncRNAs were differentially expressed. Focused on the dynamic changed lncRNAs, we performed systematic bioinformatics analysis with Series Test of Cluster (STC) algorithm, Gene Ontology (GO) analysis, pathway analysis and lncRNA-mRNA co-expression network analysis, and revealed the potential functions and related pathways of these lncRNAs were associated with immunity and inflammation during the clinical process of EV71-infected HFMD. Among the significant dynamic changed lncRNAs, ten lncRNAs were screened whose expression were further validated in EV71-infected mild patients, severe patients and healthy control. These results shed light on the potential roles of lncRNAs in EV71-infected HFMD, especially in distinguishing the mild and severe cases for early diagnose and treatment, moreover, provide deeper insight into the mechanism of EV71-induced immune and inflammatory responses, as well as the pathogenesis of the imbalanced inflammation in severe EV71 infection.


Effects of alpha-MSH on sleep, behavior, and brain temperature: interactions with IL 1.
Changes in rabbit sleep-wake activity, brain temperature (Tbr), and behavior were studied after intracerebroventricular injections of a putative endogenous antipyretic, alpha-melanocyte-stimulating hormone (alpha-MSH), and of an endogenous pyrogen, interleukin 1 (IL 1-beta). alpha-MSH (0.1-50.0 micrograms) dose dependently increased wakefulness (W) and decreased Tbr, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). NREMS was more sensitive than REMS to the suppressive effects of low alpha-MSH doses. EEG slow-wave activity in NREMS decreased after alpha-MSH treatment. alpha-MSH elicited stretching, yawning, and signs of sexual excitation. IL 1 (20 and 40 ng) induced fever and excess NREMS. alpha-MSH administered 30 min after IL 1 (40 or 20 ng IL 1 + 0.1, 0.5, or 5.0 micrograms alpha-MSH) significantly attenuated IL 1-induced fever and excess NREMS. IL 1 failed to alter the behavioral effects of alpha-MSH. Despite alpha-MSHs effect on rabbit behavior, total motor activity time did not increase, indicating that increased W after alpha-MSH cannot be attributed to behavioral activation. These results suggest that, besides acting as an endogenous antipyretic, alpha-MSH might be involved in regulation of IL 1-induced sleep.


Clonidine Use for the Treatment of Nightmares in Posttraumatic Stress Disorder.
While clonidine is used clinically for the treatment of nightmares in posttraumatic stress disorder (PTSD), few case reports demonstrating this indication exist, and there have been few studies investigating clonidine's mechanism of action for controlling nightmare symptoms. Case Report. In order to further characterize clonidine's role in treating nightmare symptoms in PTSD, we offer this case report describing one United States veteran who presented to an inpatient psychiatric unit after a suicide attempt. At that time, she described a remote history of PTSD symptoms, including nightmares, flashbacks, hyperarousal, and avoidance behaviors which had been well controlled on sertraline and clonidine. Upon her admission, her home sertraline and alprazolam were continued but her home clonidine was not continued. On day two of her hospital stay, she stated that her nightmares had returned. Her home clonidine was restarted on day two. On day three and thereafter, the patient no longer complained of nightmares. Our patient's nightmare symptoms had been controlled for years after beginning clonidine as an outpatient, but off clonidine, she had a return of her nightmare symptoms. Her nightmares again resolved once clonidine was resumed. Given this pattern in the patient's response to clonidine, this case may serve as additional evidence in the literature that clonidine has a role in treating nightmares in PTSD. Current proposed mechanisms of action for clonidine's ability to control nightmare symptoms in PTSD include that clonidine may alter the proportions of REM and non-REM sleep in a dose-dependent manner or that clonidine may play a role in memory consolidation. Further formal medication trials are the ideal future direction for establishing this role for clonidine.


The role of aldose reductase inhibition in diabetic neutrophil phagocytosis and killing.
This study examines whether an aldose reductase inhibitor (statil, ICI) can enhance neutrophil oxidative killing by diabetic neutrophils. We have examined a radiometric assay of phagocytosis and killing of Candida albicans by neutrophils from 20 controls and 20 subjects with insulin-dependent diabetes under various in vitro glucose concentrations. Glucose was present at 5, 10 and 20 mM in the presence and absence of statil (11 microM). Phagocytosis was unaffected by raised glucose levels in controls and in diabetic subjects. Killing by the diabetic cells was inhibited by increasing concentrations of glucose, killing was 18.9 +/- 2.0, 16.9 +/- 2.4 and 14.8 +/- 2.0% (mean +/- s.e.m.) at 5, 10 and 20 mM glucose, respectively (P less than 0.05). With the addition of statil under the same conditions killing improved to 19.3 +/- 2.0, 23.2 +/- 2.2 and 23.6 +/- 2.4 (P less than 0.01), these values were similar to the controls (P greater than 0.01). We conclude therefore that aldose reductase inhibition restores oxidative killing to normal.


Crashes and crash-surrogate events: exploratory modeling with naturalistic driving data.
There is a need to extend and refine the use of crash surrogates to enhance safety analyses. This is particularly true given opportunities for data collection presented by naturalistic driving studies. This paper connects the original research on traffic conflicts to the contemporary literature concerning crash surrogates using the crash-to-surrogate ratio, π. A conceptual structure is developed in which the ratio can be estimated using either a Logit or Probit formulation which captures context and event variables as predictors in the model specification. This allows the expansion of the crash-to-surrogate concept beyond traffic conflicts to many contexts and crash types. The structure is tested using naturalistic driving data from a study conducted in the United States (Dingus et al., 2005). While the sample size is limited (13 crashes and 38 near crashes), there is reasonable correspondence between predicted and observed crash frequencies using a Logit model formulation. The paper concludes with a summary of empirical results and suggestions for future research.


A combination of two genetic markers is sufficient for restriction fragment length polymorphism typing of Mycobacterium tuberculosis complex in areas with a high incidence of tuberculosis.
The incidence of tuberculosis (TB) in Madagascar is 150 cases per 100,000 people. Because of this endemicity, we studied the genetic diversity of Mycobacterium tuberculosis strains isolated in four big cities in 1994 to 1995 with the aim of monitoring TB transmission. Isolates from 316 cases of pulmonary TB (PTM(+)) were typed by Southern hybridization with genetic markers IS6110 and DR. Of the 316 PTM(+) strains, 66 (20.8%) had a single IS6110 band and were differentiated by the DR marker into 33 profiles. Using both markers, 37.7% (119) of the patients were clustered, a proportion similar to that in countries with a high prevalence of TB. There was no significant difference between clustered and nonclustered patients in age, sex, Mycobacterium bovis BCG status, and drug susceptibility of strains. Clustering was significantly greater in the capital, Antananarivo, than in the other cities, suggesting a higher rate of transmission. However, most of the patients in clusters were living in different areas, and, within a distance of 0.7 km, we did not find epidemiologically unrelated strains with the same restriction fragment length polymorphism profile. Despite an apparently low polymorphism, genetic markers such as IS6110 are potentially valuable for monitoring TB transmission. However, the high proportion of Malagasy isolates with a single IS6110 copy makes this marker alone unsuitable for typing. Additional markers such as DR are necessary for the differentiation of the isolates and for epidemiological surveys.


Inhibition of Acid-Enhanced Elongation of Zea mays Root Segments by Galactose.
The effect of sugars and metabolic inhibitors on the elongation of Zea mays root segments was analyzed by a rhizometer which records the elongation of each of 32 root segments at the same time. Galactose suppressed the acid-enhanced rapid elongation after a lag period of 1.5 hours, but it did not inhibit the slow elongation at pH 7. Mannose was less inhibitory than galactose. Arabinose, xylose, glucose, sucrose, mannitol, and sorbitol caused no inhibition. When galactose was removed after a 1-hour treatment, the elongation was partially recovered. Cycloheximide and 2-deoxyglucose suppressed acid-enhanced elongation when these were applied at the same time as acid treatments, whereas cordycepin (3'-deoxyadenosine) inhibited elongation only if it was applied prior to acid treatment. Over the 9-hour period of elongation studied, the inhibition by galactose was comparable to that of cycloheximide. Since galactose has been reported to suppress the sugar metabolism necessary for the cell wall synthesis, the later phase of acid-enhanced elongation of root segments may at least partially depend on the synthesis or metabolism of cell wall components. The inhibition of root growth by galactose may be partially ascribed to a direct effect on the elongation process in roots, an effect that is enhanced by the acidification of the cell walls.


Bivalent recombinant vaccine for botulinum neurotoxin types A and B based on a polypeptide comprising their effector and translocation domains that is protective against the predominant A and B subtypes.
The botulinum neurotoxins (BoNTs) are a large family of extremely potent, neuroparalytic, dichain proteins which act at the peripheral nervous system. The wide genetic diversity observed with this neurotoxin family poses a significant challenge for the development of an effective botulinum vaccine. The present study describes a vaccine development platform based on protein fragments representing the N-terminal two-thirds of each toxin molecule. These fragments, designated LH(N), comprise the light chain and translocation domains of each neurotoxin and are devoid of any neuron-binding activity. Using codon-optimized genes, LH(N) fragments derived from BoNT serotypes A and B were expressed in Escherichia coli in high yield with >1 g of purified, soluble fragment recoverable from 4.5 liter-scale fermentations. The protective efficacy of LH(N)/A was significantly enhanced by treatment with formaldehyde, which induced intramolecular cross-linking but virtually no aggregation of the fragment. A single immunization of the modified fragment protected mice from challenge with a 10(3) 50% lethal dose (LD(50)) of BoNT/A(1) with an 50% effective dose (ED(50)) of 50 ng of the vaccine. In similar experiments, the LH(N)/A vaccine was shown to protect mice against challenge with BoNT/A subtypes A(1), A(2), and A(3), which is the first demonstration of single-dose protection by a vaccine against the principal toxin subtypes of BoNT/A. The LH(N)/B vaccine was also highly efficacious, giving an ED(50) of approximately 140 ng to a challenge of 10(3) LD(50) of BoNT/B(1). In addition, LH(N)/B provided single-dose protection in mice against BoNT/B(4) (nonproteolytic toxin subtype).


Assessing oxidative pathway genes as risk factors for bipolar disorder.
There is a growing body of evidence implicating oxidative stress and the glutathione system in the pathogenesis of major psychiatric illnesses, including schizophrenia and bipolar disorder. Here we investigate whether genes involved in oxidative stress regulation are associated with increased risk for bipolar disorder. Four candidate genes were selected a priori from two different steps in the oxidative stress pathway, specifically the synthesis of glutathione [catalytic subunit of glutamate cysteine ligase (GCLC) and regulatory subunit of glutamate cysteine ligase (GCLM)] and the removal of reactive oxygen species [superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3)]. Haplotype tagging and functional nucleotide polymorphisms were selected in each gene and tested for association with bipolar disorder under narrow (n = 240) and broad (n = 325) phenotypic models, compared to healthy controls (n = 392, comprising 166 psychiatrically assessed unaffected controls plus 226 healthy individuals). Single marker association analysis did not reveal significant association with bipolar disorder; however, haplotypes in the SOD2 gene showed nominal association (global chi(2) = 8.94, p = 0.03; broad model). Interaction analysis revealed a significant interaction between SOD2 and GPX3 haplotypes, which further increases risk for bipolar disorder (odds ratio = 2.247, chi(2) = 9.526, p = 0.002, corrected p = 0.029). Further characterization of the SOD2 and GPX3 interaction using larger cohorts is required to determine the role of these oxidative pathway genes as risk factors for bipolar disorder.


Clinical evaluation of a novel method for the measurement of prostate-specific antigen, AccuPSA(TM) , as a predictor of 5-year biochemical recurrence-free survival after radical prostatectomy: results of a pilot study.
Study Type - Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Nadir Ultrasensitive PSA levels has some value for predicting BCR following RD. AccuPSA assays lower limit of PSA quantification of <0.01 pg/ml greatly enhances sensitivity and specificity of nadir PSA to predict BCR following RP. Our pilot study shows an AccuPSA of 3 pg/ml has a sensitory and specificity of 100% and 75% respectively for predicting 5 year BCR following RP. OBJECTIVES • To conduct a proof of concept study to evaluate a novel digital single molecule immunoassay (AccuPSA(TM) ) that detects prostate-specific antigen (PSA) a thousandfold more sensitively than current PSA detection methods. • To determine the ability of the AccuPSA(TM) assay to predict 5-year biochemical recurrence (BCR)-free survival after radical prostatectomy (RP). PATIENTS AND METHODS • A total of 31 frozen serum specimens were obtained from specimen logs maintained at New York University Langone Medical Center and the Johns Hopkins University School of Medicine on men who had undergone RP. Those men without evidence of BCR had a minimum of 5 years' PSA follow-up. • In all cases, preoperative and pathological information were available, as was a serum specimen 3-6 months after RP, with a PSA level of <0.1 ng/mL measured by conventional PSA methods at the time of serum collection. • Specimens were tested using the AccuPSA(TM) method. • A Cox proportional hazard model and Kaplan-Meier analysis were used to determine whether AccuPSA(TM) predicted the risk of BCR. RESULTS • Overall, 11/31 (35.5%) men developed BCR. • Mean AccuPSA(TM) nadir levels were significantly different (P < 0.001) between the non-BCR group (2.27 pg/mL) and the BCR group (46.99 pg/mL). • Using a multivariate Cox proportional hazard model, AccuPSA(TM) nadir level was a significant predictor of BCR-free survival (P < 0.01). • Kaplan-Meier analysis of up to 5 years follow-up showed that 100% of men with AccuPSA(TM) nadir values <3 pg/mL did not develop BCR, whereas 62.5% of men with values >3 pg/mL developed BCR (P= 0.00024). • The sensitivity, specificity, positive predictive value and negative predictive value of the AccuPSA(TM) method was 100%, 75%, 69% and 100%, respectively. CONCLUSIONS • AccuPSA(TM) assay predicts 5-year BCR- free survival after RP. • Identifying a reliable predictor of BCR soon after RP has important implications for frequency of PSA testing, selection of candidates for adjuvant therapy, and reassuring a large subset of men that they are not at risk of recurrence. • Larger studies are needed to validate these findings.


Levels of serum eosinophil cationic protein are associated with hookworm infection and intensity in endemic communities in Ghana.
The eosinophil cationic protein (ECP) is a cytotoxic protein mainly secreted by eosinophils granulocytes and plays a role in host defense against parasitic infections. Infection with Necator americanus (hookworm) is traditionally diagnosed by the Kato-Katz method which is inherently tedious, subjective and known to underestimate infection intensity. This study aimed to assess levels of serum ECP in relation to hookworm infection intensity. Stool samples from 984 (aged 4 to 80 years) participants in a cross-sectional study conducted in the Kintampo North Municipality of Ghana were examined using the Kato-Katz and formol-ether concentration methods. Serum ECP levels were measured by ECP assay kit and compared between 40 individuals infected with hookworm only, 63 with hookworm- Plasmodium falciparum co-infection, 59 with P. falciparum infection and 36 with no infection. Hookworm infection prevalence was 18.1% (178/984). ECP levels were significantly higher in individuals infected with hookworm only (β = 2.96, 95%CI = 2.69, 3.23, p<0.001) or co-infected with P. falciparum (β = 3.15, 95%CI = 2.91, 3.39, p<0.001) compared to the negative control. Levels of ECP were similar between those with only P. falciparum infection and the uninfected control (p>0.05). Increased hookworm intensity was associated with a significant increase in ECP level (β = 4.45, 95%CI = 2.25, 9.11, rs = 0.193, n = 103, p<0.01). ECP threshold of 84.98ng/ml was associated with a positive predictive value (PPV) of 98% (95% CI = 92, 100), and negative predictive value (NPV) of 76% (95% CI = 62, 87) in classifying hookworm infection status with an AUROC of 96.3%. Serum ECP level may be a good biomarker of hookworm infection and intensity and warrant further investigations to help improve current hookworm diagnosis.


Biotransformation of Tetracyclines by Fungi: Challenges and Future Research Perspectives.
Tetracycline antibiotics are used worldwide in human and veterinary medicine. On the basis of low metabolization and through organic fertilizers, tetracyclines enter the environment in a biologically active form. This can have toxic effects on microbial communities and promote the selection of resistant strains. The use of fungi could be a promising approach to deactivate tetracyclines by degradation or derivatization as a result of their particular enzyme endowment. Here, we highlight the current analytical and biotechnological challenges associated with the bioconversion of tetracyclines by fungi and propose research approaches to advance the technology for wastewater and manure treatment.


A novel Pd-catalyzed N-dealkylative carbonylation of tertiary amines for the preparation of amides.
A novel and convenient protocol for the formation of amides via palladium-catalyzed N-dealkylative carbonylation of alkyl tertiary amines has been developed. In the presence of PdCl2(PhCN)2, CuO, PhCN and CO, a range of substituents on both aryl iodides and alkyl tertiary amines were compatible with the reaction to afford a series of N,N-disubstituted amides in moderate to excellent yields.


Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects.
1. Stereoselectivity in the pharmacokinetics of nitrendipine was investigated by reanalysing plasma samples of a previously published study (Soons et al., 1989). 2. Racemic nitrendipine was administered intravenously (40 micrograms kg-1) and orally, both as plain tablet (20 mg) and in an osmotic pump device (40 mg Osmet) to nine healthy male subjects. Nitrendipine enantiomers were measured with a stereoselective assay. 3. Upon oral administration (tablet) the bioavailability of (S)-(-)-nitrendipine (13.4% +/- 5.6%) was 75% (50% - 98%) higher than that of (R)-nitrendipine (7.9% +/- 4.0%) (mean +/- s.d. (95% confidence interval)). Values of AUC and Cmax for (S)-nitrendipine were 90% (55% - 121%) and 77% (51% - 100%) higher respectively, than those for (R)-nitrendipine. Similar results were obtained with the osmotic system. 4. The clearance of intravenously administered (S)-nitrendipine was slightly (7%) lower than that of (R)-nitrendipine, but elimination half-lives and volumes of distribution were similar. 5. The difference in disposition of nitrendipine enantiomers is most likely related to a difference in activity of the cytochrome P-450 system towards the enantiomers, giving rise to a two-fold difference in first-pass elimination. 6. Stereoselectivity in the first pass metabolism of nitrendipine exhibited little intersubject variability and therefore is not a major factor in the wide variability in systemic availability of the more-potent (S)-enantiomer.


More than Carbazole Derivatives Activate Room Temperature Ultralong Organic Phosphorescence of Benzoindole Derivatives.
The mechanism of carbazole (Cz)-based phosphors is still unclear since its isomer (1H-benzo[f]indole, Bd) is discovered in 2020. Herein, the successful synthesis of four Cz/Bd derivatives is reported, named as 2CzBr, CzBdBr, 2BdBr, and 3Bd, and the general mechanism for their ultralong organic phosphorescence (UOP) is provided. Bd and its derivatives give double groups of phosphorescence, including the short-wavelength phosphorescence with a short lifetime and the ultralong phosphorescence at long wavelengths, assigned to their neutral molecules and radical cations, respectively. Interestingly, the doped poly(methyl methacrylate) (PMMA) films of CzBdBr and 2BdBr show photo-activated ultralong phosphorescence at room temperature. The activation of Bd derivatives 'UOP involves three factors: 1) well dispersion in the matrix with limited amount, 2) generation of their radical cations and 3) the matrix-mediated stabilization of radical cations. The function of Cz derivatives to activate the Bd derivatives' UOP could be replaced by photo-activation or using other matrixes. Significantly, the application of the doped PMMA films is practiced and gives an exciting result that the high-resolution QR code could be reversibly printed and erased on the film. This research has expanded the understanding in the field of organic phosphorescence and it may pave a new way for its development.


Laboratory-acquired meningococcemia--California and Massachusetts.
Although Neisseria meningitidis is commonly isolated in clinical laboratories, laboratory-acquired infection is rare (1). This report describes two fatal cases of meningococcal infection in laboratory workers; both of these cases probably were laboratory acquired.


Shear-wave elasticity imaging of a liver fibrosis mouse model using high-frequency ultrasound.
The objective of this study was to develop a high-frequency imaging platform for evaluating liver fibrosis in mice based on shear-wave elasticity imaging (SWEI). Although SWEI has been used to diagnose hepatic fibrosis clinically, it is performed at relatively low frequencies (<20 MHz). For preclinical ultrasound imaging in small animals, a high-frequency (>30 MHz) single-element transducer with mechanical scanning is often used. In this study we developed a new SWEI system based on a 40-MHz single-element transducer for imaging and a separate 20-MHz excitation transducer for producing the radiation force and the associated shear waves. Liver fibrosis was induced in ten C57BL/6 (B6) mice using carbon tetrachloride; the other ten mice served as the control group. Synchronizing the excitation beam (i.e., the beam from the excitation transducer) and the detection beam sequence (i.e., the beam from the imaging transducer) allows this mechanical-scanning setup to analyze the shear-wave dispersion relation. The liver viscoelastic properties were determined in vivo by measuring the shear-wave dispersion curve followed by fitting to the Voigt model. The mice were then killed and the fibrosis stage was evaluated (from F0 to F4) based on the METAVIR score. The measured mean values of liver elasticity and viscosity, respectively, ranged from 1.06 to 1.89 kPa and from 1.29 to 1.75 Pa∙s for normal F0 and fibrosis stages of F3 and F4. The Spearman coefficients for the correlations between the measured elasticity and viscosity at various fibrosis stages as assessed by the METAVIR score were 0.73 (p < 0.001) and 0.634 (p = 0.0013), respectively. We also found that the collagen content in the liver was linearly correlated with the measured elasticity (r(2) = 0.54, p < 0.001) and less strongly with the viscosity (r2 = 0.26, p = 0.022). Finally, the diagnosis performance of high-frequency SWEI was evaluated using multivariate receiver operating characteristic curve (ROC) analysis. The areas under the multivariate ROC curve for diagnosing fibrosis stages of F ≥ 3, F = 4, F0 vs. F3, F0 vs. F4, and F3 vs. F4 were 0.9, 0.98, 0.83, 1.0, and 0.96, respectively. Compared with traditional ROC analysis, an improved diagnosis performance was found for diagnosing fibrosis stages of F ≥ 3 and F0 vs. F3. These results demonstrate that the developed high-frequency SWEI platform can yield quantitative viscoelastic properties for diagnosing various fibrosis stages in mice. It is a promising tool for studying the progression of liver fibrosis in preclinical animal models both noninvasively and quantitatively.


Development of a self-replicating plasmid system for Mycoplasma hyopneumoniae.
Mycoplasma hyopneumoniae is a prevalent swine respiratory pathogen that is a major cause of economic loss to pig producers. Control is achieved by a combination of antimicrobials, vaccination and management practices, but current vaccines offer only partial control and there is a need for improved preventative strategies. A major barrier to advances in understanding the pathogenesis of M. hyopneumoniae and in developing new vaccines is the lack of tools to genetically manipulate the organism. We describe the development and optimisation of the first successful plasmid-based system for the genetic manipulation of M. hyopneumoniae. Our artificial plasmids contain the origin of replication (oriC) of M. hyopneumoniae along with tetM, conferring resistance to tetracycline. With these plasmids, we have successfully transformed M. hyopneumoniae strain 232 by electroporation, generating tetracycline resistant organisms. The persistence of extrachromosomal plasmid and maintenance of plasmid DNA over serial passages shows that these artificial plasmids are capable of self-replication in M. hyopneumoniae. In addition to demonstrating the amenability of M. hyopneumoniae to genetic manipulation and in optimising the conditions necessary for successful transformation, we have used this system to determine the minimum functional oriC of M. hyopneumoniae. In doing so, we have developed a plasmid with a small oriC that is stably maintained over multiple passages that may be useful in generating targeted gene disruptions. In conclusion, we have generated a set of plasmids that will be valuable in studies of M. hyopneumoniae pathogenesis and provide a major step forward in the study of this important swine pathogen.


Can El Niño-Southern Oscillation Increase Respiratory Infectious Diseases in China? An Empirical Study of 31 Provinces.
Respiratory infectious diseases (RID) are the major form of infectious diseases in China, and are highly susceptible to climatic conditions. Current research mainly focuses on the impact of weather on RID, but there is a lack of research on the effect of El Niño-Southern Oscillation (ENSO) on RID. Therefore, this paper uses the system generalized method of moments (SYS-GMM) and the data of 31 provinces in China from 2007 to 2018 to construct a dynamic panel model to empirically test the causality between ENSO and RID morbidity. Moreover, this paper considers the moderating effects of per capita disposable income and average years of education on this causality. The results show that ENSO can positively and significantly impact RID morbidity, which is 5.842% higher during El Niño years than normal years. In addition, per capita disposable income and average years of education can effectively weaken the relationship between ENSO and RID morbidity. Thus, this paper is of great significance for improving the RID early climate warning system in China and effectively controlling the spread of RID.


Improved survival of primary cadaveric renal allografts in blacks with quadruple immunosuppression.
Black recipients of cadaveric kidneys have been shown to have a lower rate of allograft survival than whites. Data were reviewed from 642 primary cadaveric transplants: results in 276 patients (163 white and 113 black) (group 1) who had received triple therapy (azathioprine-CsA-prednisone, 1985-87) were compared with those in 366 patients (180 white and 186 black) (group 2) receiving quadruple immunosuppression (MALG-azathioprine-CsA-prednisone, 1987-90). Blacks in group 2 had better patient (97% vs. 91%, P = 0.03) and graft (77% vs. 55%, P = 0.0002) survival at 1 year than in group 1. There was no difference in these parameters among whites in either group. Racial differences in graft survival noted in group 1 disappeared in group 2. While HLA BDR matching improved in group 2 patients (P = 0.0001), whites received better matched kidneys than blacks in both groups (P = 0.001). HLA matching was associated with improved graft survival only in white recipients of 4 BDR-matched kidneys. In group 1, more blacks than whites had at least one episode of acute rejection (76% vs. 57%, P = 0.001); blacks also lost more grafts to acute and chronic rejection. In group 2, there were no racial differences in the number of rejection episodes or immunologic graft losses. Of 14 potential variables examined by parametric analysis, only quadruple therapy significantly reduced risk of graft loss in blacks. Quadruple immunosuppression improved primary cadaveric renal allograft survival in black recipients, abrogating previously noted racial differences.


Real-time controller for foot-drop correction by using surface electromyography sensor.
Foot drop is a disease caused mainly by muscle paralysis, which incapacitates the nerves generating the impulses that control feet in a heel strike. The incapacity may stem from lesions that affect the brain, the spinal cord, or peripheral nerves. The foot becomes dorsiflexed, affecting normal walking. A design and analysis of a controller for such legs is the subject of this article. Surface electromyography electrodes are connected to the skin surface of the human muscle and work on the mechanics of human muscle contraction. The design uses real surface electromyography signals for estimation of the joint angles. Various-speed flexions and extensions of the leg were analyzed. The two phases of the design began with surface electromyography of real human leg electromyography signal, which was subsequently filtered, amplified, and normalized to the maximum amplitude. Parameters extracted from the surface electromyography signal were then used to train an artificial neural network for prediction of the joint angle. The artificial neural network design included various-speed identification of the electromyography signal and estimation of the angles of the knee and ankle joints by a recognition process that depended on the parameters of the real surface electromyography signal measured through real movements. The second phase used artificial neural network estimation of the control signal, for calculation of the electromyography signal to be stimulated for the leg muscle to move the ankle joint. Satisfactory simulation (MATLAB/Simulink version 2012a) and implementation results verified the design feasibility.


Identifying palliative care needs of patients with non-communicable diseases in Indonesia using the SPICT tool: a descriptive cross-sectional study.
In Indonesia, Non-Communicable Diseases (NCD) are a contributing factor to mortality with most cases involving heart disease, cancer, chronic lung disease and diabetes. Accordingly, the identification of palliative care needs is very important as a first step in providing palliative care for these patients with NCD. However, currently there is no national standardized tool nor guidance system for identifying palliative care needs of NCD patients in Indonesia. The Supportive and Palliative Care Indicators Tool (SPICT) has been used worldwide for screening palliative care needs. This study aimed to identify palliative care needs in NCD patients using the SPICT tool. This descriptive study used a cross-sectional design. Sampling technique used convenience sampling with a total sample of 124 adult patients with NCD in Dr. Sardjito Hospital Yogyakarta. Data collection used the Indonesian version of the SPICT. Data analyses used descriptive statistics and chi-square tests with p < 0,05 set as significant. Additionally, the prevalence of patients requiring palliative care was also calculated. The patients with NCD requiring palliative care who were screened using the SPICT tool were 61.3%. The nurses identified only 17.7%, while the physicians identified only 9.7%. The overall agreement of the clinician's assessments to the researchers was < 32%. Meanwhile, agreement with nurses was 31 and 25% with the physicians. These results highlight that by using the SPICT tool, recognition of hospitalized patients with NCD needing palliative care increased from 10 to 18% to > 61%. The Indonesian version of the SPICT tool can help the clinicians to reach meet agreement in identifying hospitalized patients who need palliative care as the first step in addressing palliative interventions for patients with NCD. It can provide several benefits in screening patients with NCD from the beginning of diagnosis.


Boston keratoprosthesis type 1 surgery: use of frozen versus fresh corneal donor carriers.
This study aims to determine whether frozen corneas can be successfully used as carriers of the Boston keratoprosthesis (KPro). Prospective study of 37 patients undergoing KPro surgery with fresh or frozen corneas as carriers. Patients were randomized to receive either a fresh corneal graft or a frozen corneal graft during implantation of the Boston KPro. The randomization depended on availability of fresh versus frozen corneas offered by the local eye bank. All surgeries were performed by the same experienced surgeon. Outcome measures included retention of the device, level of preoperative and postoperative visual acuities (VAs), and complications. The indication for Boston KPro was corneal graft failure in 24 eyes; 13 patients had KPro as a primary procedure. The assembly of the Boston KPro and surgery were uneventful in all cases. Mean follow-up was 9.65 months. Median preoperative VA was counting fingers (range, 20/100 to light perception) in the fresh cornea group (19 eyes) and hand motions (range, 20/150 to light perception) in the frozen cornea group (18 eyes). Median postoperative VA were 20/150 (range, 20/30 to hand motions) and 20/150 (range, 20/40 to counting fingers) in the fresh and frozen cornea groups, respectively. Inflammation and retroprosthetic membrane formation were the most common complications with similar rates between the 2 groups. The device retention rate was 100% at the end of the follow-up period. Frozen and fresh corneal donors seem equally efficient and safe as carriers of the Boston KPro with similar recuperation of VA and no untoward complications, such as melt, leaks, or endophthalmitis.


Protection by pentoxifylline of diazinon-induced toxic stress in rat liver and muscle.
ABSTRACT The effects of diazinon, pentoxifylline, and their combination therapy on plasma glucose, the key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress were studied in rat liver and muscle. Oxidative stress was determined by measuring the concentration of lipid peroxides and assessing total antioxidant capacity. Diazinon (60 mg/kg) and pentoxifylline (100 mg/kg) were administrated by gavage. Administration of diazinon increased blood glucose, hepatic glycogen phosphorylase (GP), and phosphoenol pyruvate carboxykinase (PEPCK) by 160.65%, 117.2%, and 93.5%, respectively, while it decreased plasma cholinesterase (ChE) by 53.82%. Diazinon-induced oxidative stress was demonstrated by decreased total antioxidant capacity and enhanced lipid peroxidation by 52.61% and 280% in liver and by 40.02% and 46.6% in muscle, respectively. Pentoxifylline increased plasma glucose, hepatic GP, and PEPCK by 98.65%, 60%, and 79.86%, respectively, while it did not change plasma ChE, liver and muscle lipid peroxides, and total antioxidant capacity. In combination therapy, pentoxifylline did not alter diazinon-induced change in muscle GP activity but restored a diazinon-induced increase in hepatic and muscle lipid peroxides by 39.18% and 42.35%, respectively. Pentoxifylline also recovered a diazinon-induced decrease in liver and muscle total antioxidant capacity and plasma ChE by 122.33%, 56.44%, and 115.62%, respectively. Pentoxifylline did not affect diazinon-induced hyperglycemia and increased hepatic GP and PEPCK or muscle GP activities. It is concluded that pentoxifylline is a good choice for the alleviation of acute toxic stress of diazinon in muscle and liver and ChE in plasma, while it is unable to recover diazinon-induced hyperglycemia.


Alpha-Synuclein Suppresses Retinoic Acid-Induced Neuronal Differentiation by Targeting the Glycogen Synthase Kinase-3β/β-Catenin Signaling Pathway.
Alpha-synuclein (α-SYN) is expressed during neuronal development and is mainly involved in the modulation of synaptic transmission. Missense mutations and amplifications of this gene have been associated with the pathogenesis of Parkinson's disease. Here, we evaluate whether α-SYN plays a detrimental role in the phenotypic and morphological regulation of neurons. We also identify the underlying mechanisms of this process in all-trans-retinoic acid (RA)-induced differentiated SH-SY5Y cells, which represents dopaminergic (DAergic) phenotype. Our results indicate that overexpression of wild-type or mutant A53T α-SYN attenuated the RA-induced upregulation of tyrosine hydroxylase and dopamine transporter as well as neurite outgrowth in SH-SY5Y cells. In addition, GSK-3β inactivation and downstream β-catenin stabilization were associated with RA-induced differentiation, which was attenuated by α-SYN. Moreover, protein phosphatase 2A was positively regulated by α-SYN and was implicated in the α-SYN-mediated interference with RA signaling. The results obtained from SH-SY5Y cells were verified in primary cultures of mesencephalic DAergic neurons from A53T α-SYN transgenic mice, which represent high levels of α-SYN and protein phosphatase 2A in the midbrain. The number and length of neurites in tyrosine hydroxylase-positive as well as Tau-positive cells from A53T α-SYN transgenic mice were significantly lower than those in littermate controls. The current results provide novel insight into the role of α-SYN in the regulation of neuronal differentiation, including DAergic neurons. Identifying the signaling pathway involved in the α-SYN-mediated dysregulation of neuronal differentiation could lead to a better understanding of the developmental processes underlying α-SYN-related pathologies and facilitate the discovery of specifically targeted therapeutics.


Content and delivery of pre-operative interventions for patients undergoing total knee replacement: a rapid review.
Total knee replacement (TKR) is a common operation typically performed for end-stage knee osteoarthritis. Patients awaiting TKR often have poor health-related quality of life. Approximately 20% of patients experience persistent pain post-TKR. Pre-operative TKR interventions could improve pre- and post-operative outcomes, but future research is required to inform their design. This review aimed to identify and synthesize recent literature on the content and delivery of pre-operative TKR interventions to help guide future research and clinical practice. This rapid review included randomized trials of pre-operative TKR interventions ("outcomes studies") and primary studies exploring patients' and/or health professionals' views of pre-operative TKR interventions ("views studies"). Medline, Embase, PsycINFO, CINAHL and the Cochrane Central Register of Controlled Trials were searched for English language studies published between January 2009 and December 2020. Eligible studies' reference lists were screened. Studies were appraised using the Mixed Methods Appraisal Tool. The findings were narratively synthesized using a convergent segregated approach. From 3263 records identified, 52 studies were included (29 outcomes studies, 21 views studies, two outcomes/views studies). The studies' methodological quality varied but was generally highest in qualitative studies. The outcomes studies investigated education (n=5), exercise (n=20), psychological (n=2), lifestyle (n=1), and/or other interventions (n=5). The views studies addressed education (n=20), exercise (n=3), psychological (n=1), lifestyle (n=4), and/or other interventions (n=1). Only three outcomes studies (two randomized controlled trials (RCTs) and a pilot study) compared the effectiveness of intervention components/delivery approaches. The two RCTs' results suggest that pre-operative TKR exercise interventions are equally effective regardless of whether they include strength or strength plus balance training and whether they are hospital- or home-based. Personal tailoring and using more than one delivery format were associated with improved outcomes and/or perceived as beneficial for multiple intervention types. Definitive evidence on the optimal design of pre-operative TKR interventions is lacking. Personal tailoring and employing multiple delivery formats appear to be valuable design elements. Preliminary evidence suggests that including balance training and hospital versus home delivery may not be critical design elements for pre-operative TKR exercise interventions. PROSPERO CRD42019143248 FUNDER: National Institute for Health and Care Research (ICA-CDRF-2018-04-ST2-006).


Evolutionary aspects of transmitter molecules, their receptors and channels.
Classical transmitters are present in all phyla that have been studied; however, our detailed understanding of the process of neurotransmission in these phyla is patchy and has centred on those neurotransmitter receptor mechanisms which are amenable to study with the tools available at the time, for example, high-affinity ligands, tissues with high density of receptor protein, suitable electrophysiological recording systems. Studies also clearly show that many neurones exhibit co-localization of classical transmitters and neuropeptides. However, the physiological implications of this co-localization have yet to be elucidated in the vast majority of examples. The application of molecular biological techniques to the study of neurotransmitter receptors (to date mainly in vertebrates) is contributing to our understanding of the evolution of these proteins. Striking similarities in the structure of ligand-gated receptors have been revealed. Thus, although ligand-gated receptors differ markedly in terms of the endogenous ligands they recognize and the ion channels that they gate, the structural similarities suggest a strong evolutionary relationship. Pharmacological differences also exist between receptors that recognize the same neurotransmitter but in different phyla, and this may also be exploited to further the understanding of structure-function relationships for receptors. Thus, for instance, some invertebrate GABA receptors are similar to mammalian GABAA receptors but lack a modulatory site operated by benzodiazepines. Knowledge of the structure and subunit composition of these receptors and comparison with those that have already been elucidated for the mammalian nervous system might indicate the functional importance of certain amino acid residues or receptor subunits. These differences could also be exploited in the development of new agents to control agrochemical pests and parasites of medical importance. The study of the pharmacology of receptor proteins for neurotransmitters in invertebrates, together with the application of biochemical and molecular biological techniques to elucidate the structure of these molecules, is now gathering momentum. For certain receptors, e.g. the nicotinic receptor, we can expect to have fundamental information on the function of this receptor at the molecular level in both invertebrates and vertebrates in the near future.


Fruit Intake to Prevent and Control Hypertension and Diabetes.
Fruits are considered healthy because of their high antioxidant, vitamin, mineral, fiber, and phytochemical contents. However, their high sugar content is a concern for glucose, lipid, and uric acid metabolism. We reviewed related articles published in the last 10 years and summarized evidence that relates fruit intake to the prevention and control of hypertension and diabetes mellitus. Clinicians should familiarize themselves with appropriate fruit intake to counsel at-risk patients on hypertension and diabetes.


Spectrographic temperature measurement of a high power breakdown arc in a high pressure gas switch.
A procedure for obtaining an approximate temperature value of conducting plasma generated during self-break closure of a RIMFIRE gas switch is described. The plasma is in the form of a breakdown arc which conducts approximately 12 kJ of energy in 1 μs. A spectrographic analysis of the trigger-section of the 6-MV RIMFIRE laser triggered gas switch used in Sandia National Laboratory's "Z-Machine" has been made. It is assumed that the breakdown plasma has sufficiently approached local thermodynamic equilibrium allowing a black-body temperature model to be applied. This model allows the plasma temperature and radiated power to be approximated. The gas dielectric used in these tests was pressurized SF(6). The electrode gap is set at 4.59 cm for each test. The electrode material is stainless steel and insulator material is poly(methyl methacrylate). A spectrum range from 220 to 550 nanometers has been observed and calibrated using two spectral irradiance lamps and three spectrograph gratings. The approximate plasma temperature is reported.


Density and the journey to work.
"This paper evaluates the influence of residential density on commuting behavior across U.S. cities while controlling for available opportunities, the technology of transportation infrastructure, and individual socio-economic and demographic characteristics. The measures of metropolitan and local density are addressed separately.... Regressions are conducted to predict commuting time, speed, and distance, by mode of travel on a cross-section of individuals nationally and city by city. The results indicate that residential density in the area around the tripmaker's home is an important factor: the higher the density the lower the speed and the shorter the distance.... The paper suggests a threshold density at which the decrease in distance is overtaken by the congestion effects resulting in a residential density between 7,500 and 10,000 persons per square mile (neither the highest nor lowest) with the shortest duration auto commutes."


Mindfulness-based cognitive therapy for Japanese breast cancer patients-a feasibility study.
Mindfulness-based intervention has been receiving growing attention in cancer care. This study aimed to examine feasibility and to preliminary explore effectiveness of mindfulness-based cognitive therapy (MBCT) in Japanese breast cancer patients, and to explore possible modification of the program so that it fits better with this population. Twelve participants with diagnosis of Stage I-III breast cancer received an eight session, weekly MBCT intervention in a group therapy format. The participants were followed up until 3 months after the completion of the program. All the participants completed the program with high attendance rate (mean number of attended sessions = 7.7). Significant improvement in anxiety (Hospital Anxiety and Depression Scale (HADS) - anxiety subscale; effect size Cohen's d = 0.88, P < 0.05), trauma-related psychological symptoms (Impact of Event Scale-revised; d = 0.64, P < 0.01) and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer: FACT-B; d = 0.72, P < 0.01), and trend-level improvement in depression (HADS - depression subscale; d = 0.53, P = 0.054) were observed. Qualitative analyses suggested the program may be beneficial for alleviating fear of cancer recurrence and for increasing spiritual well-being. Some recommended modification of the program was indicated from the post-intervention interviews. Mindfulness-based cognitive therapy was well accepted by Japanese breast cancer patients and yielded favorable effect on their psychological status and quality of life. Further effectiveness study in a randomized-control design is warranted.


Retailing research: increasing the role of evidence in clinical services for childbirth.
A current review of the structures and assumptions of research transfer for clinical care reveals some progress from "passive diffusion" to "active dissemination" models, but little or no progress has been made toward targeting local influences on practitioner behavior for "coordinated implementation" of clinically relevant research into childbirth (or other) medical practices. The implementation of scientifically valid research syntheses, such as Effective Care in Pregnancy and Childbirth (ECPC), is therefore constrained by a poorly developed marketplace for retailing research information to practitioners. A survey in Canada of the four most significant potential retailing groups demonstrated that whereas clinical and community groups were adopting the necessary knowledge and attitudes, public policy makers and administrators trailed well behind them. To increase the probability of thorough retailing of ECPC, a three-phase plan could be instituted that would identify product champions within potential retailing groups, develop implementation activities for each retailing group, and convene annual conferences.


Combining functional imaging with brain stimulation in Parkinson's disease.
Brain stimulation techniques such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS) constitute promising clinical and research tools to investigate neural mechanisms underlying neurological and psychiatric diseases. They have enormous potential in modifying brain activity and subsequent function. However, it is still a matter of debate how either of these stimulation approaches operates to produce the clinical outcomes observed in patients. The combination of these techniques with functional neuroimaging is contributing significantly to disentangle the mechanisms through which brain stimulation affects neuronal activity and related networks. In the present review we outline the research done to date on the effects of DBS and TMS on motor, cognition and behaviour in Parkinson's disease (PD) with particular emphasis on neuroimaging.


Infection with Bacillus cereus after close-range gunshot injuries.
Three patients were admitted with close-range gunshot wounds of the knee and lower leg, inflicted in all three cases through clothing. At admission, all of the patients were given antibiotics (cefuroxime and metronidazole) to prevent streptococcal and anaerobic infection. All of the patients developed severe tissue infection with Bacillus cereus within days of admission. In one case, the organism was also recovered from the blood. B. cereus is capable of causing severe infection after trauma and its ubiquity in the environment allows it easy access to gunshot wounds. Its potent production of beta-lactamase renders penicillins and cephalosporins predictably ineffective. The early administration of a non-beta-lactam drug (such as ciprofloxacin) should be considered in cases where Bacillus cereus is isolated from traumatic wounds.


Perovskite Solar Cells and Devices at EPFL Valais Wallis.
Stability required! Perovskite solar cells have emerged as one of the most exciting fields of research, owing to their impressive rise in power conversion efficiency surpassing 22% in six short years of research. Current research is focused on ways to improve stability of perovskite-based devices, a key characteristic required to bring this technology from the lab into the market. In this Editorial, guest editor Prof. Mohammad Khaja Nazeeruddin describes the context of this Special Issue, and summarizes the work being performed in his research group toward this low-cost near-future photovoltaic technology.


Considerations for multi-centre conditioned pain modulation (CPM) research; an investigation of the inter-rater reliability, level of agreement and confounders for the Achilles tendon and Triceps Surae.
This study aimed to investigate the inter-rater reliability of the conditioned pain modulation (CPM) effect. The reliability between two examiners assessing the CPM effect via pressure pain thresholds and induced using the cold pressor test of 28 healthy volunteers at the mid-portion Achilles tendon (AT) and Triceps Surae musculotendinous junction was performed. Reliability was calculated using intraclass correlation coefficient (ICC). Confounders were assessed using multivariable generalised estimating equations (GEEs). Bias in the level of agreement was assumed if the confidence intervals (CIs) of the mean difference in Bland-Altman plots did not cross the line of equality. The inter-rater reliability of the CPM effect was poor to moderate in the AT (ICC 95% CI = 0.00-0.66) and Triceps Surae (ICC 95% CI = 0.00-0.69). However, when accounting for confounders within the GEE, there were no differences between testers and Bland-Altman plots reported good agreement between testers. Habitual completion of running-related physical activity was a confounder for both the AT parallel-paradigm (p = 0.017) and sequential-paradigm (p = 0.029). Testing order was a confounder for the AT (p = 0.023) and Triceps Surae (p = 0.014) parallel-paradigm. This study suggests the CPM effect may be site specific (i.e. differences between the AT and Triceps Surae exist). In addition, differences in the reliability between examiners are likely due to the influence of confounders and not examiner technique and therefore appropriate analysis should be used in research investigating the CPM effect.


Social and institutional factors that affect breastfeeding duration among WIC participants in Los Angeles County, California.
Hospital practices and early maternal return to work are associated with breastfeeding duration; however, research has not documented the long-term effects of many hospital policies or the effect of early return to work on breastfeeding outcomes of WIC participants. This study investigated the impact of in-hospital breastfeeding, receipt of a formula discharge pack, and maternal return to work on the long-term breastfeeding outcomes of 4,725 WIC participants in Los Angeles County, California. Multivariate logistic regression analyses were used to assess determinants of exclusive breastfeeding at 6 months and breastfeeding at 6, 12, and 24 months. In-hospital initiation of breastfeeding, exclusive breastfeeding in the hospital, receipt of a formula discharge pack, and maternal return to work before 3 months were all significantly associated with breastfeeding outcomes after controlling for known confounders. Mothers who exclusively breastfed in the hospital were eight times as likely as mothers who did not breastfeed in the hospital to reach the AAP recommendation of breastfeeding for 12 months or longer (P < .01). Only 6.9% of the sample reported exclusively breastfeeding for 6 months or more, and just one-third reported any breastfeeding at 12 months. Nine in ten respondents received a formula discharge pack in the hospital. Mothers who received a discharge pack were half as likely to exclusively breastfeed at 6 months as those who did not receive one (P < .01). Medical providers should educate, encourage, and support WIC mothers to breastfeed in the hospital and refrain from giving formula discharge packs.


Low-Energy Pulsed Ion Beam Technology with Ultra-High Material Removal Resolution and Widely Adjustable Removal Efficiency.
High-precision optical component manufacturing by ion beam machining tools with ultra-high material removal resolution and dynamically adjustable removal efficiency is important in various industries. In this paper, we propose a low-energy pulsed ion beam (LPIB) technology that can obtain a single pulse with high-resolution material removal by adjusting the pulse frequency and duty cycle, and enable the dynamic adjustment of the removal efficiency. The pulse frequency is 1-100 Hz, and the duty cycle is 0-100%. For monocrystalline silicon, the pulse frequency and duty cycle are set to 100 Hz and 1%, respectively; thus, the single-shot pulse depth removal resolution of material is 6.7 × 10-4 nm, which means every 21 pulses can remove one silicon atom layer. Compared with IBF, where the removal resolution of the maximum depth is about 0.01 nm, the controllable resolution is one to two orders of magnitude higher. There is a linear relationship between the removal efficiency of the pulsed ion beam removal function and the pulse duty ratio. The material removal of a single pulse can be adjusted in real time by adjusting the pulse duty cycle and frequency. Owing to its high resolution and wide adjustable removal efficiency, LPIB has broad application prospects in the field of sub-nano-precision surface modification, quality tuning of inertial resonant devices, and so on. This technology is expected to advance surface processing and ultra-precision manufacturing.


Infantile colic: incidence and treatment in a Norfolk community.
In a prospective study of 1019 infant and mother pairs, 268 infants suffered with 'infantile colic'. Significantly more of these were breast fed, supporting the proposed theory of a colic-producing factor in breast milk. Social class and maternal education were not related to the incidence of colic. Seventy-two percent of our infants with colic suffered from classical evening colic. The symptoms did not disappear from all the infants by 3 months - over 38% continued to have symptoms after 3 1/2 months of age. Treatment is limited, but merbentyl helped to relieve symptoms to a varying degree in over 60% of the infants who tried it. The family relationships are often strained during this period and this appears to persist when at one year of age significantly more of these infants were described as demanding, miserable and bad-tempered by their mothers.


Antiobesity effects of Kaempferia parviflora in spontaneously obese type II diabetic mice.
Kaempferia parviflora Wall. Ex Baker (KP) has been used as a folk medicine in Laos and Thailand to lower blood glucose levels, improve blood flow, and increase vitality. This study investigated the preventive effects of KP on obesity and its downstream symptoms (various metabolic disorders) using Tsumura, Suzuki, Obese Diabetes (TSOD) mice, a multifactorial genetic disease animal model in which metabolic diseases develop spontaneously, similar to metabolic syndrome in humans, and Tsumura, Suzuki, Non-Obesity (TSNO) mice as the corresponding control mice. When feed that was mixed with KP (1 or 3%) was given ad libitum to TSOD and TSNO mice for 8 weeks, body weight increase, visceral fat accumulation, lipid metabolism abnormalities, hyperinsulinemia, glucose intolerance, insulin resistance, hypertension, and peripheral neuropathy were suppressed in TSOD mice, but no marked differences were observed in TSNO mice. Because KP had preventive effects on metabolic diseases, including antiobesity effects, only in obese animals, we propose that KP will be extremely valuable as a medicine or component of food in alternative health care.


Serum fragmented cytokeratin 18 levels reflect the histologic activity score of nonalcoholic fatty liver disease more accurately than serum alanine aminotransferase levels.
Reliable noninvasive biomarkers to assess the histologic activity of nonalcoholic fatty liver disease (NAFLD) have not been established. As the frequency of Mallory bodies is known to be closely associated with the disease severity, we hypothesized that serum levels of Mallory body-related proteins were correlated with NAFLD histologic activity and evaluated this possibility. Serum levels of total and fragmented cytokeratin (CK) 18, heat shock protein (Hsp) 70, Hsp90alpha, ubiquitin+1, and p38alpha at the time of liver biopsy were measured in 118 NAFLD patients and their association with histologic findings and NAFLD histologic activity score (NAS) was investigated. Serum levels of both forms of CK18 and Hsp90alpha were markedly higher in patients having nonalcoholic steatohepatitis (NASH) compared with non-NASH ones. Both forms of CK18 significantly correlated with degree of steatosis, lobular inflammation, and ballooning, and showed stronger positive correlations with NAS than serum aspartate and alanine aminotransferase (AST and ALT). Multiple regression analysis further revealed that fragmented CK18 and AST were effective predictors of NAS, with the former being the more definitive of the two (P<0.001 vs. 0.005). In 20 NAFLD patients who received a follow-up biopsy, changes in fragmented CK18 levels, but not AST or ALT levels, closely paralleled those in NAS. These results establish the usefulness of fragmented CK18 measurement for assessing and monitoring the histologic activity of NAFLD.


Water Researchers Do Not Have a Strategic Plan for Gathering Evidence to Inform Water Intake Recommendations to Prevent Chronic Disease.
Confusion has persisted for decades in the United States (U.S.) over how much plain water to drink, despite national water intake recommendations which are based on high quality scientific evidence. This editorial summarizes the definition, alignment and coordination of evidence that informs the current U.S. adequate intake (AI) recommendations for water. It highlights gaps in the evidence that perpetuate confusion and opportunity to address the gaps through strategic planning.


Are People Becoming More Entitled Over Time? Not in New Zealand.
It is a common conception that entitlement is increasing among younger generations over time. However, although there is some evidence for this trend, other findings are less conclusive. The current research investigated change in psychological entitlement across the adult lifespan for men and women (ages 19-74), using six annual waves of data (2009-2014) from the New Zealand Attitudes and Values Study ( N = 10,412). We employed Cohort-Sequential Latent Growth Modeling to assess mean-level change in entitlement. Entitlement was found to be generally unchanging over time for both men and women, with only those aged 65 and above showing increasing entitlement. Entitlement showed a steady downward trend across age. These findings from a large national probability sample suggest that change in entitlement may follow a decreasing developmental trend across the lifespan. In New Zealand, at least, there is no evidence for a narcissism epidemic.


Immunohistochemical staining for DNA topoisomerase I, DNA topoisomerase II-alpha and p53 in gastric carcinomas.
New anticancer drugs targeting DNA topoisomerase I (topo I) are showing activity against gastric carcinomas. Laboratory studies have indicated that cells responsive to topo I targeted drugs have elevated levels of topo I, require active DNA replication and may require a functional apoptotic pathway. In this study, we evaluated these potential markers of topo I targeted drug sensitivity in 22 cases of primary gastric carcinoma. By immunohistochemical staining, we observed elevated topo I expression in 15 of 22 neoplasms (68%). By immunohistochemical staining for the proliferation marker DNA topoisomerase II-alpha (topo II-alpha), we observed that 16 of 22 neoplasms (73%) had topo II-alpha indices > than 50 indicating a large number of actively cycling tumor cells. Abnormal p53 expression was observed in 7 of the 22 cases (32%). Of the 22 cases of gastric carcinoma, 8 (36%) had high levels of topo I, a large number of cycling tumor cells and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I.


Pipeline sampled-delay focusing in ultrasound imaging systems.
A sampled-delay focusing technique was recently proposed by the authors which completely eliminates the use of analog L-C delay lines for beam focusing in completely eliminates the use of analog L-C delay lines for beam focusing in ultrasound B-mode imaging systems. With this approach, the product of sampling rate and maximum time delay is required to be less than unity. To remove this constraint, we propose in this paper a first-in-first-out pipelining technique. This allows one to perform beam steering and dynamic focusing simultaneously on a resolution-cell basis and in a completely digital fashion without the use of analog L-C delay lines.


Physiologic +Gz tolerance responses over successive +Gz exposures in simulated air combat maneuvers.
Fighter aircraft pilots are exposed to repetitive headward acceleration (+Gz) during air combat maneuvering. The objective of this study was to compare physiologic responses and the calculated +Gz tolerances of multiple successive +Gz exposures with the responses of the first +Gz exposure. There were 13 subjects who performed simulated air combat maneuvering (SACM) profiles composed of 10 rapid-onset rate +Gz cycles with different combinations of short- or long-duration +Gz plateaus (8 or 20 s) and +Gz pauses (1 or 15 s). +Gz, plateaus were individually set at levels inducing strong physiologic responses while the +Gz pause was set at 1.4 Gz. Head-level systolic pressure, ear opacity, and vision quality were measured. The nadirs of head-level systolic pressure, ear opacity, and visual quality during each +Gz plateau were higher in subsequent cycles compared to the first +Gz cycle. There was an average increase in calculated +Gz tolerance of 0.35 +/- 0.21 Gz following the first +Gz cycle. SACMs with short +Gz pauses produced greater increases in +Gz tolerance than SACMs with long +Gz pauses. Cardiovascular and visual responses were improved over the course of successive +Gz cycles, indicating that the risk of +Gz-induced loss of consciousness was not increased beyond the first +Gz cycle. The increase in +Gz tolerance beginning with the second cycle is attributed to a carryover of compensatory responses, primarily vasoconstriction, with possible contribution from greater venous return and baroreflex enhancement.


Atopic dermatitis.
Atopic dermatitis (AD) is an eczematous, highly pruritic chronic inflammatory skin disease. It usually begins early in life and often occurs in people with a personal or family history of asthma and allergic rhinitis. The prevalence is high, especially in children,and it has been rising in recent decades, in parallel with asthma prevalence. Although AD is often described as an "allergic" dis-ease, allergic causation is difficult to document, and AD is increasingly viewed as a skin disease that predisposes to allergies. This interpretation, based on clinical, epidemiologic, and animal stu-dies, may greatly influence our approach to therapy and prevention of atopic diseases in the coming years.


Effects of aeration and storage temperature on Campylobacter concentrations in poultry semen.
Campylobacter is one of the most commonly reported bacterial causes of human foodborne infections in the United States. Recent evidence has demonstrated that Campylobacter is present in poultry semen and may contribute to the vertical transmission between the breeder hen and offspring. As Campylobacter is considered sensitive to oxygen and cold temperature, the objective of this study was to determine if aeration and storage temperature could reduce or eliminate Campylobacter in poultry semen. In 4 separate trials, pooled semen samples were collected from roosters or toms, diluted with a commercial poultry semen extender, and inoculated with an average of 10(7) cells/mL of a wild-type C. jejuni or C. coli semen isolate. Pooled ejaculates were then divided into 3 aeration treatments: Control (no aeration), air, or oxygen (gently bubbled for 20 min with atmospheric air or oxygen, respectively). Immediately after aeration, pooled semen samples were further divided to 3 test storage temperatures: 4, 23, or 42 degrees C. At 0, 2, 6, and 24 h of storage, samples were enumerated for Campylobacter. Aeration of the semen alone, or aeration with reduced temperatures (4 or 23 degrees C), did not reduce the amount of Campylobacter compared with the controls. Campylobacter concentrations were, however, reduced when stored at 42 degrees C for 24 h. This effect is associated with reduced sperm viability and is therefore not a practical treatment of reducing Campylobacter in semen. It appears alternative methods will be needed to eliminate Campylobacter from poultry semen.


Comparison of direct and standardized antibiotic susceptibility testing in bacteriuria.
In clinical isolates of bacteria from urine, the antibiotic susceptibility was tested with a direct disc diffusion method in which the inoculum was not primarily standardized. The results were compared with those from parallel tests using standardized inoculum. Of a total 2,272 urine specimens, 700 were accepted for direct susceptibility testing, 189 were not accepted because of mixed culture or indistinct inhibition zones. The overall concordance between the direct and the standardized tests was 95.8% (2,800 observations with 118 discordant results). The direct diffusion method used in this way is time saving and economical and can reliably be used in a clinical microbiological laboratory serving mainly outpatients.


Heparin is essential for a single keratinocyte growth factor molecule to bind and form a complex with two molecules of the extracellular domain of its receptor.
Keratinocyte growth factor (KGF or FGF-7) is a member of the heparin binding fibroblast growth factor (FGF) family and is a paracrine mediator of proliferation and differentiation of a wide variety of epithelial cells. To examine the stoichiometry of complexes formed between KGF and its receptor, we have utilized a soluble variant of the extracellular region of the KGF receptor containing two tandem immunoglobulin-like loops, loops II and III (sKGFR). Ligand-receptor complexes were examined by size exclusion chromatography, light scattering, N-terminal protein sequencing, and sedimentation velocity. In the presence of low-molecular mass heparin ( approximately 3 kDa), we demonstrate the formation of complexes containing two molecules of sKGFR and one molecule of KGF. In the absence of heparin, we were unable to detect any KGF-sKGFR complexes using the above techniques, and additional studies in which sedimentation equilibrium was used show that the binding is very weak (Kd >/= 70 microM). Furthermore, using heparin fragments of defined size, we demonstrate that a heparin octamer or decamer can promote formation of a 2:1 complex, while a hexamer does not. Utilizing the highly purified proteins and defined conditions described in this study, we find that heparin is obligatory for formation of a KGF-sKGFR complex. Finally, 32D cells, which appear to lack low-affinity FGF binding sites, were transfected with a KGFR-erythropoeitin receptor chimera and were found to require heparin to achieve maximal KGF stimulation. Our data are consistent with the previously described concept that cell- or matrix-associated heparan sulfate proteoglycans (HSPGs) and FGF ligands participate in a concerted mechanism that facilitates FGFR dimerization and signal transduction in vivo.


"Pseudo-Circumscribed Palmar or Plantar Hypokeratosis (Pseudo-CPH)": a Histologic Pattern Secondary to Trauma; Further Characterization of a Known Entity.
Circumscribed palmar or plantar hypokeratosis (CPH) is defined clinically as well-circumscribed areas of erythematous eroded skin mostly over thenar or hypothenar eminences of the palms and less commonly soles. Histologically, lesions demonstrate a characteristic abrupt drop-off in the cornified layer leading to broad areas of hypokeratosis. In the original description in 2002, Perez et al favored these lesions to be a distinctive epidermal malformation. Since then, some reports implicate trauma; however, the exact etiology remains uncertain. The authors present 11 cases in which the histologic changes of CPH are present as an incidental finding that they favor to represent a reaction pattern to trauma. The changes of CPH overly traumatized neoplasms [ie, a poroma, squamous cell carcinoma (2), dermatofibroma], verruca vulgaris (3), inflammatory processes (lichen amyloid and granulomatous inflammation secondary to a ruptured infundibular cyst), and scar and fibrosing granulation tissue from previous procedures. Classic clinical findings of CPH are not present. The changes most commonly but not exclusively occur on acral skin (8/11), both volar (4) and dorsal skin (4). Six patients are female and 5 are male. Ages range from 21 to 87 years (median 64 years). The authors propose that, in some instances, the histologic changes of CPH are present as a secondary phenomenon and represent a reaction pattern to trauma. They name this finding of secondary histologic change of CPH as "pseudo-CPH" to distinguish it from primary lesions of CPH ("primary CPH") with classic clinical and histologic features.


The Cost of Ankylosing Spondylitis in the UK Using Linked Routine and Patient-Reported Survey Data.
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis which typically begins in early adulthood and impacts on healthcare resource utilisation and the ability to work. Previous studies examining the cost of AS have relied on patient-reported questionnaires based on recall. This study uses a combination of patient-reported and linked-routine data to examine the cost of AS in Wales, UK. Participants in an existing AS cohort study (n = 570) completed questionnaires regarding work status, out-of-pocket expenses, visits to health professionals and disease severity. Participants gave consent for their data to be linked to routine primary and secondary care clinical datasets. Health resource costs were calculated using a bottom-up micro-costing approach. Human capital costs methods were used to estimate work productivity loss costs, particularly relating to work and early retirement. Regression analyses were used to account for age, gender, disease activity. The total cost of AS in the UK is estimated at £19016 per patient per year, calculated to include GP attendance, administration costs and hospital costs derived from routine data records, plus patient-reported non-NHS costs, out-of-pocket AS-related expenses, early retirement, absenteeism, presenteeism and unpaid assistance costs. The majority of the cost (>80%) was as a result of work-related costs. The major cost of AS is as a result of loss of working hours, early retirement and unpaid carer's time. Therefore, much of AS costs are hidden and not easy to quantify. Functional impairment is the main factor associated with increased cost of AS. Interventions which keep people in work to retirement age and reduce functional impairment would have the greatest impact on reducing costs of AS. The combination of patient-reported and linked routine data significantly enhanced the health economic analysis and this methodology that can be applied to other chronic conditions.


[Neuropsychological analysis in 2 cases of infarction in the left precentral gyrus--with special reference to apraxia of speech and agraphia].
It remains controversial whether agraphia can coexist in a case with apraxia of speech, and whether an apraxia of speech can be classified into a category of aphasia. We examined the presence of agraphia in 2 right-handed patients of apraxia of speech. Case 1 of mild agraphia showed an infarcted lesion in the left precentral gyrus extending to the neighboring white matter, which involving the arcuate fasciculus on MRI. Positron emission tomography (PET) indicated decrease of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the infarcted lesion, but no decrease of CBF and CMRO2 in the Broca's area. In this case, agraphia was more conspicuous in "kanji" than in "kana" and severity of the agraphia was not correlated to that of speech disturbance on naming test. Case 2 without agraphia showed a small infarcted lesion in the left precentral gyrus, which did not extend to the deep white matter on MRI. Agraphia can coexist with apraxia of speech in a case with the lesion in the left precentral gyrus, in which the cortical lesion is relatively widespread or extends to the deep white matter. However, lack of etiological connection between the agraphia and the apraxia of speech was suggested. We could not confirm the location in the left precentral gyrus which is responsible for the agraphia.


Usefulness of ultrasound in the management of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is a life-threatening disease. Different imaging techniques have been used to diagnose and guide the ventilatory management of patients with ARDS. Chest ultrasound is a reliable tool to identify interstitial syndrome, lung consolidation, lung collapse, and pleural effusion. In addition, echocardiography is essential in the diagnosis of diastolic left ventricle dysfunction and the estimation of elevated ventricle filling pressures, which is necessary before diagnosing ARDS. Therefore, combining chest and heart ultrasound assessment is useful to diagnose ARDS and guide the ventilatory management of the disease. Available data in the literature suggest that protocol-based approaches should be implemented for the purposes of diagnosis and management.


Role of implantable cardioverter defibrillator therapy in patients with acquired long QT syndrome: a long-term follow-up.
The use of implantable cardioverter defibrillators (ICD) in patients with torsade de pointes (TdP) and ventricular fibrillation in the presence of acquired long QT syndrome (aLQTS) is under debate, partly due to the fact that aLQTS is potentially reversible and currently no long-term follow-up data are available. We aimed to evaluate the long-term follow-up of patients with acquired long QT syndrome (aLQTS) who had received an implantable cardioverter defibrillator (ICD) for secondary prevention of sudden cardiac arrest (SCA). Over a 10 year period, 43 patients with an ICD after survived cardiac arrest (SCA) due to an aLQTS were included [female n= 27 (63%); mean age 61 ± 16 years]. There was no clinical evidence for congenital LQTS (Schwartz score 1.25 ± 0.8). Structural heart disease was present in 29 patients (47%; ischaemic n= 13; dilated cardiomyopathy n= 9; mean EF 41%± 12). The most common proarrhythmic trigger happened to be antiarrhythmic drugs (n= 34; 79%). Other triggers included contrast agent (n= 1), haloperidol (n= 2), severe hypokalaemia (n= 2), drug abuse/alcohol (n= 2), and mere severe bradycardia (n= 2). Under trigger QTc interval measured 536 ± 58 vs. 438 ± 33 ms without trigger (P< 0.001). During a mean follow-up of 84 ± 55 months, appropriate shocks occurred in 19 patients (44%); inappropriate shocks in 13 patients (30%; only inappropriate n= 3). Appropriate shocks were almost as common in patients without as in those with structural heart disease (35 vs. 48%; P= 0.32). None of the patients were re-exposed to the initial trigger during the follow-up period. Beta-blocker medication did not prevent ICD shocks (12 of 19 vs. 11 of 24 on medication). Appropriate ICD shocks are a common finding in patients with aLQTS and SCA irrespective of the underlying cause or structural heart disease. Thus, even in the presence of relevant acquired proarrhythmia ICD may be beneficial.


Assessment of pain and other symptoms in Mexican patients with advanced illness.
Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. During this stage, several symptoms appear and contribute to a decrement in the quality of life. We performed a retrospective study evaluating medical records of terminally ill patients who attended a specialized pain and palliative medicine service. The Edmonton Symptom Assessment Scale (ESAS) was used to document symptoms intensity. Data analysis was carried out at two times: the initial assessment and the last visit before death. We analyzed thirty-eight cases of which 58% were women (22 cases) and the mean age of the sample was 60.7 years (SD: 15.6). All cases had an oncologic disease classified as end-stage cancer and were considered as palliative patients. Symptom intensity was documented by the ESAS in two different moments: pain 3.7 (SD: 3.2) vs. 4.1 (SD: 3.4), nausea 1.4 (SD: 3.2) vs. 1.8 (SD: 3.3), depression 3.4 (SD: 3.4) vs. 4.3 (SD: 3.7), anxiety 3 (SD: 3.5) vs. 2.4 (SD: 3.6), weakness 4.8 (SD: 3.5) vs. 6.2 (SD: 3.6), dyspnea 1.1 (SD: 2.7) vs. 2.8 (SD: 3.4), anorexia 3.5 (SD: 3.7) vs. 4.7 (SD: 3.8), and somnolence 2.6 (SD: 3.5) vs. 4.9 (SD: 3.5). Statistical significance was found in weakness, dyspnea, and somnolence. We found the ESAS a useful tool for symptom assessment. In this study, we document the prevalence of symptoms at the end of life in a Spanish-speaking country. Physicians trained in pain and palliative medicine managed those symptoms, and we observed that symptoms maintained the same intensity. There is the possibility that the intervention made by those clinicians modified the symptomatic outcome in those patients. Evaluation of effective protocols for symptom management at the end of life is needed.


[Expression and clinical significance of surfactant protein D mRNA in peripheral blood of lung cancer patients].
The sensitive detection of circulating tumor cells in lung cancer patients is very important for prognosis and selection of appropriate treatment modalities. Based on recent promising data, the authors established reverse transcriptase (RT)-PCR with primers specific for surfactant protein D (SP-D) gene to detect circulating tumor cells in the peripheral blood of lung cancer patients, and to initiatively discuss its clinical significance. The expression of SP-D mRNA was analyzed by an improved nested RT-PCR in the peripheral blood of 26 lung cancer patients with metastases, 37 lung cancer patients without metastases, 15 benign pneumonia patients, and 15 healthy volunteers. 1) The sensitivity of the method was 1 x 10(-6), with high level of specificity. 2) Using this method, the positive detection rate of the expression of SP-D mRNA was 92.3% (24/26) and 24.3% (9/37) in the peripheral blood of lung cancer patients with and without metastases, respectively. While no sample was positive for SP-D mRNA expression in the benign pneumonia patients and in the healthy volunteers. SP-D mRNA might be a valuable marker to detect circulating tumor cells in the peripheral blood of lung cancer patients. This method may be a valuable tool for early identification of metastases in asymptomatic lung cancer patients. Furthermore, it can also provide important clinical information for the evaluation of prognosis and in the selection of appropriate treatment strategies.


Pathophysiological Evaluation in a Case of Wernicke's Encephalopathy by Multimodal MRI.
To report a patient with Wernicke's encephalopathy (WE) using multimodal magnetic resonance imaging (MRI) including conventional MRI, diffusion-weighted MRI (DWI), arterial spin labeling (ASL), and proton MR spectroscopy (MRS). A 50-year-old woman of WE with a history of cholecystectomy and acute pancreatitis was given MRI scans including DWI, MRS, and ASL pre- and post-thiamine treatment. Two weeks after admission, the patient's condition rapidly improved. The typical MRI findings and lesions in the frontal cortex at baseline disappeared or resolved partially. The reduced apparent diffusion coefficient value in part of the thalamus lesion, the elevated cerebral blood flow in the frontal cortex, the lactate doublet peak in the right thalamus lesion, and in cerebral spinal fluid, all resolved after treatment. The combination of conventional MRI with DWI, proton MRS, and ASL, offers a powerful diagnostic tool and a better understanding of the pathophysiological and hemodynamic mechanisms.