Assembly and spontaneous resolution of the chiral inorganic polyoxometalates-based frameworks via helical chains association.
Two pairs of enantiomerically pure three-dimensional (3D) chiral polyoxometalate (POM) framework materials l,d-[K(H2O)]6·[H2GeW12O40]3·35H2O (1a and 1b) and l,d-[K(H2O)]6·[H2SiW12O40]3·29H2O (2a and 2b) based on inorganic achiral building blocks, have been synthesized and characterized by X-ray crystallography, elemental analysis, powder X-ray diffraction (PXRD), UV-Vis spectroscopy, circular dichroism (CD) spectra. Single-crystal X-ray diffraction analyses revealed that 1a and 1b, 2a and 2b are enantiomers, respectively. In 1a and 1b, 2a and 2b, {K(H2O)}n link terminal oxygen and μ2-bridging oxygen of Keggin-type polyanion moieties to generate 1D 31 helical infinite chiral chains, which are further connected by the achiral Keggin-type polyoxoanions to form 3D 4,8-connected chiral self-assembly frameworks with {4(12)·6(10)·8(6)}{4(6)}2 topology. 1 and 2 are isostructural. They are obtained by spontaneous resolution upon crystallization in the absence of any chiral source. They represent new examples of chiral self-penetrating pure inorganic frameworks known for POM systems. Compounds 1 and 2 display adsorption activity toward volatile organic compounds (VOCs).


The Use of Voriconazole as Primary Prophylaxis for Invasive Fungal Infections in Patients Undergoing Allogeneic Stem Cell Transplantation: A Single Center's Experience.
Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting.


Practical enantioselective process for a chiral phosphodiesterase-4 inhibitor.
L-869298 is a potent and selective phosphodiesterase-4 (PDE4) inhibitor, which is potentially useful in the treatment of asthma and chronic obstructive pulmonary disorder. A catalytic asymmetric synthesis that is suitable for the preparation of kilogram quantities of L-869298, and which does not require the use of chromatography, has been developed to support the on-going drug development program of L-869298 at Merck Research Laboratories. The catalytic asymmetric hydrogenation of an aromatic heteroaromatic ketone afforded the corresponding alcohol in almost perfect enantioselectivity. Activation of the alcohol via formation of the 4-toluenesulfonate, followed by an unprecedented displacement of the tosylate via the lithium enolate of ethyl-3-pyridyl acetate N-oxide, generated the chiral tetra-substituted ethane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Deprotection of the displacement adduct followed by decarboxylation, afforded L-869298 in excellent overall yield. The methodology developed could be readily extended to the synthesis of several other chiral PDE4 inhibitors.


The C-terminal transmembrane domain of Bcl-xL mediates changes in mitochondrial morphology.
We investigate the effect of mitochondrial localization and the Bcl-x(L) C-terminal transmembrane (TM) domain on mitochondrial morphology and subcellular light scattering. CSM 14.1 cell lines stably expressed yellow fluorescent protein (YFP), YFP-Bcl-x(L,) YFP-Bcl-x(L)-DeltaTM, containing the remainder of Bcl-x(L) after deletion of the last 21 amino acids corresponding to the TM domain, or YFP-TM, consisting of YFP fused at its C-terminal to the last 21 amino acids of Bcl-x(L). YFP-Bcl-x(L) and YFP-TM localized to the mitochondria. Their expression decreased the intensity ratio of wide-to-narrow angle forward scatter by subcellular organelles, and correlated with an increase in the proportion of mitochondria with an expanded matrix having greatly reduced intracristal spaces as observed by electron microscopy. Cells expressing YFP-TM also exhibited significant autophagy. In contrast, YFP-Bcl-x(L)-DeltaTM was diffusely distributed in the cells, and its expression did not alter light scattering or mitochondrial morphology compared with parental cells. Expression of YFP-Bcl-x(L) or YFP-Bcl-x(L)-DeltaTM provided significant resistance to staurosporine-induced apoptosis. Surprisingly however, YFP-TM expression also conferred a moderate level of cell death resistance in response to staurosporine. Taken together, our results suggest the existence of a secondary Bcl-x(L) function that is mediated by the transmembrane domain, alters mitochondrial morphology, and is distinct from BH3 domain sequestration.


anti-Oligoannelated THF moieties: synthesis via push-pull-substituted cyclopropanes.
The first synthesis of anti-fused oligoannelated THF moieties is reported. The key transformation of the synthetic sequence, consisting of cyclopropanation, reduction and oxidation, is the expansion of a push-pull-substituted three-membered ring into a five-membered enol ether system. A repetition of the sequence allows the creation of oligoacetals up to a nonacyclic system.


Chemotactic penetration of keratocytes in ePTFE polymer in vitro.
Expanded polytetrafluoroethylene (ePTFE) is used as a support for artificial corneas. Implanted in corneas, most of the time this polymer is colonized by corneal host cells. The absence of colonization often coincides with extrusion of the polymer. Therefore, we decided to introduce keratocytes into ePTFE in vitro before implantation. Because keratocytes do not spontaneously enter ePTFE, we used several chemoattractants, separately and in a mixture, to stimulate the penetration of cultured keratocytes into the polymer. The influence of the passage number on cell penetration was also studied. No significant differences were observed up to the seventh passage, although seventh-passage cells penetrated somewhat more slowly than younger cells. Satisfactory results were obtained with four of the tested chemotactic factors: IL-6, type alpha transforming growth factor (TGF-alpha), platelet derived growth factor isoform BB (PDGF-BB), and fibroblast growth factor-2 (FGF-2). Under our experimental conditions, two to more than six million keratocytes entered the polymer discs with a volume of 706.5 mm(3) in the presence of these four chemoattractants. TGF-alpha was the most efficient and was selected for further in vitro and in vivo studies.


[Effects of flecainide in patients with non-sustained ventricular tachycardia and impaired left ventricular function].
Anti-arrythmia efficacy and effects on left ventricular function of flecainide have been evaluated in 9 patients with symptomatic non sustained ventricular tachycardia (NSVT) and left ventricular ejection fraction (LVEF) lower than 30%, respectively detected by Holter monitoring and radionuclide angiocardiography in basal conditions. Seven to eleven days after starting flecainide therapy (100 mg b.i.d.), Holter and radionuclide angiocardiography were repeated. In 56% of patients a ventricular premature beats (VPB) reduction more than 70% was obtained and total VPB suppression was achieved in 33% of patients. Total suppression of NSVT was obtained in 67% of patients; LVEF did not show significant changes. Thus, antiarrhythmic efficacy of flecainide resulted in agreement with the previous reports, whereas no patient developed signs or symptoms of heart failure or pro-arrhythmia.


Assessment of myocardial injury in the emergency department independently predicts the short-term poor outcome in patients with severe carbon monoxide poisoning receiving mechanical ventilation and hyperbaric oxygen therapy.
Patients with severe carbon monoxide (CO) poisoning are often prone to unconsciousness and respiratory distress and as a result will receive mechanical ventilation and hyperbaric oxygen (MV-HBO) therapy. Factors associated with poor outcome at discharge are less defined in this patient population. This study was conducted to identify the prognostic predictors of short-term poor outcome in severely CO-poisoned patients receiving MV-HBO therapy. The departmental database and the medical records of 81 patients treated with MV-HBO therapy were reviewed. Demographic and clinical data were extracted for analysis. HBO therapy with 2.5 or 2.8 atmosphere absolute (ATA) was administered to these patients. Short-term poor outcome was defined as an in-hospital death or neurologic sequelae at discharge. All patients were divided into two groups: those with a poor outcome and those without a poor outcome. Nine patients died while in the hospital, 32 patients had neurologic sequelae at discharge, and the incidence of poor outcome was 50.6%. Parameters that were assessed in the emergency department (ED) and highly associated with patients with a poor outcome included myocardial injury, typical findings on brain computed tomography related to CO poisoning, and higher serum levels of alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, creatine kinase, creatine kinase-myocardial band, troponin-I, and C-reactive protein. These poor outcomes were also correlated with prolonged lag times from the end of CO exposure to ED arrival and from ED arrival to HBO therapy. In a multivariate analysis, myocardial injury was the only independent predictor of poor outcome (odds ratio, 8.2; 95% confidence interval, 1.012-67.610; p=0.049). The results of this study indicate that myocardial injury assessed at ED arrival independently predicts the short-term poor outcome in severely CO-poisoned patients who receive MV-HBO therapy. Emergency physicians could use this objective marker to identify patients with an increased risk of poor outcome at discharge and refine the treatment protocol by shortening the time of patient transport and administering HBO therapy as soon as possible.


Prevention of the gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs: the role of proton pump inhibitors.
The associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence and complications of gastroduodenal erosions and ulcers are well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimising such damage by acid suppression. Other strategies discussed include avoidance of NSAIDs or minimising their dosage, selecting NSAIDs known to cause less damage, and co-prescription of various agents. Cytoprotection with misoprostol, a prostaglandin analogue, has been shown to be effective in reducing NSAID-related peptic ulcers and their complications. Unfortunately, adverse effects may limit compliance in some patients. Histamine H2 antagonists have only limited efficacy in the prevention of NSAID-induced ulcers in humans, particularly in the stomach, except at higher than standard dosages. This may relate to their relatively modest effect in elevating gastric pH, especially in comparison with proton pump inhibitors. Several studies now confirm the efficacy of proton pump inhibitors in the short and longer term prevention of NSAID-induced upper gastrointestinal injury. Placebo-controlled studies suggest reductions of over 70% in gastric and duodenal ulcer rates over 3 to 6 months. The recent ASTRONAUT (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment) study documented the greater prophylactic efficacy of omeprazole over ranitidine at standard dosages for 6 months. The OMNIUM (Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management) study showed omeprazole to be slightly more effective overall than misoprostol in preventing the upper gastrointestinal adverse effects of NSAIDs, with both substantially more effective than placebo, although misoprostol was somewhat less well tolerated. Although substantial reductions in NSAID ulceration are now achievable when co-therapy with a proton pump inhibitor is given, a few patients will still develop ulcers and their complications. Hence the judicious use of NSAIDs in the first instance cannot be overemphasised.


Physical Comorbidity and Health Literacy Mediate the Relationship Between Social Support and Depression Among Patients With Hypertension.
Depression is a common comorbidity among patients with hypertension. Patients with hypertension and depression have worse health outcomes compared to those without depression. The combined effects of social support, physical comorbidity, and health literacy on depression among individuals with hypertension remain unclear. A survey was conducted between December 2017 and May 2018 to investigate the relationships among social support, physical comorbidity, health literacy, and depression in a population of patients with hypertension in rural areas of Sichuan province, China. Multiple linear regression was used to examine factors that influenced depression, and structural equation modeling (SEM) was used to examine the relationships among the four study variables. The mean scores of 549 patients with hypertension were 37.17 ± 6.84 for social support, 14.62 ± 6.26 for health literacy, and 3.56 ± 3.05 for depression; furthermore, 34.2% of participants had physical comorbidity. Gender and per capita annual family income were significantly associated with depression. Physical comorbidity was directly positively related to depression while health literacy was directly negatively related to depression. Social support had an indirect negative association with depression by the mediating effects of health literacy and physical comorbidity. Adequate social support and health literacy, and less physical comorbidity could potentially contribute to reducing depression. The study highlights the importance of social support in maintaining mental health among patients with hypertension. Strategies that target the enhancement of social support and health literacy should be prioritized to relieve depression among patients with hypertension. More attention should be paid to women, low-income individuals, and patients with physical comorbidities.


A decision support process to compare riparian revegetation options in Scheu Creek catchment in north Queensland.
While riparin vegetation can play a major role in protecting land, water and natural habitat in catchments, there are high costs associated with tree planting and establishment and in diverting land from cropping. The distribution of costs and benefits of riparian revegetation creates conflicts in the objectives of various stakeholder groups. Multicriteria analysis provides an appropriate tool to evaluate alternative riparian revegetation options, and to accommodate the conflicting views of various stakeholder groups. This paper discusses an application of multicriteria analysis in an evaluation of riparian revegetation policy options for Scheu Creek, a small sub-catchment in the Johnstone River catchment in north Queensland, Australia. Clear differences are found in the rankings of revegetation options for different stakeholder groups with respect to environmental, social and economic impacts. Implementation of a revegetation option will involve considerable cost for landholders for the benefits of society. Queensland legislation does not provide a means to require farmers to implement riparian revegetation, hence the need for subsidies, tax incentives and moral suasion.


[Frequency of drug resistant tuberculosis in Poland in 2000 as compared to 1997].
Prevalence of drug resistance to one drug and multidrug resistance--MDR in different categories of tuberculosis patients is an important information about the susceptibility pattern of Mycobacterium tuberculosis isolates against antimycobacterial drugs. Poland joined WHO/IUATLD global project on TB drug resistance surveillance, and carried out in 1996/1997 the first prospective survey, simultaneously on primary and acquired drug resistance. This study is repeated in 2000 according to the WHO/IUATLD protocol. The programme covered the whole country. A total of 16 regional centers participated in the co-operative study. 3705 questionnaires and cultures were obtained from patients who excreted TB bacilli during the 12-months from 1 st. January to 31st December 2000. Drug resistance tests to INH, RMP, SM, EMB were performed on Lowenstein-Jensen medium according to the proportion method or/and Bactec 460 TB system. 3705 TB patients (3037 new and 668 treated cases) bacteriologically confirmed by culture were included in one-year study. Primary resistance to any drug was found in 6.12% (CI 5.27-6.56) of new cases. 35 patients (1.15%, CI 0.77-1.35) were infected with MDR strains. Acquired resistance to any drug was found in 16.6% (CI 5.27-6.56), 8.53% (CL 6.41-9.6) of the patients who excreted MDR strains. We have found increased resistance from 3.6% in 1997 to 6.12% (p < 0.001) in 2000 and MDR from 0.6% in 1997 to 1.15% (p < 0.001) in 2000 in untreated tuberculosis patients in Poland. The rate of resistance in the group of treated TB patients was very similar in 1997 (17.0%) and in 2000 (16.6%); except 20% increase of MDR cases--(7.0% in 1997, and 8.53% in 2000). We observed an increase in drug resistant tuberculosis first time during 40 years long period of its monitoring. Regular monitoring of drug resistance in TB patients in Poland is recommended.


Change in primary midwife-led care in the Netherlands in 2000-2008: a descriptive study of caesarean sections and other interventions among 789,795 low risk births.
to study whether an increase in intrapartum referrals in primary midwife-led care births in the Netherlands is accompanied by an increase in caesarean sections. nationwide descriptive study. the Netherlands Perinatal Registry. 789,795 births of nine year cohorts of women with low risk pregnancies in primary midwife-led care at the onset of labour between 2000 and 2008. primary outcome is the caesarean section rate. Vaginal instrumental delivery, augmentation with oxytocin, and pharmacological pain relief are secondary outcomes. Trends in outcomes are described. We used logistic regression to explore whether changes in the planned place of birth and other maternal characteristics influenced the caesarean section rate. the caesarean section rate did not increase and was 5.5 per cent (range 4.9-6.3 per cent) for nulliparous women, and 1.0 per cent (range 0.8-1.1 per cent) for multiparous women. After controlling for the decline in planned home births and other maternal characteristics no increase in the caesarean section rate was found. The vaginal instrumental birth rate showed no increase, and was 18.1 per cent (range 17.9-18.5 per cent) for nulliparous women and 1.5 per cent (range 1.4-1.7 per cent) for multiparous women. Augmentation of labour and/or pharmacological pain relief increased from 24.0 to 38.8 per cent for nulliparous women, and from 5.4 to 10.0 per cent for multiparous women. the rise in intrapartum referrals was not accompanied by an increase in caesarean section rate over the period 2000-2008. Despite a considerable rise in the use of pain relief and augmentation, the rate of spontaneous vaginal birth remained high for low risk women who started labour in primary midwife-led care. the current strict role division between primary care midwives and the obstetrician-led team increasingly results in a change in care provider during labour. In a more integrated care system, more women can receive continuous support of labour from their own primary care midwife, as long as only supportive interventions are needed.


[CT-guided percutaneous endoscopic gastrostomy: a successful method if transillumination is not possible].
If transillumination is not possible, percutaneous endoscopic gastrostomy (PEG) is contraindicated. In these cases the stomach had so far to be punctured directly during radiological monitoring. A new method is described which combines endoscopy and computed tomography (CT) for performing a percutaneous endoscopic gastrostomy. Among 189 patients who were to have the procedure there were eleven (nine men, two women) in whom transillumination was not possible. After endoscopic insufflation of air PEG was done under CT guidance, using the common pull-through technique. The combined method was successful in ten of the eleven patients without complication. In one patient with hepatomegaly and interposition of the transverse colon PEG was not possible even with CT guidance. The combined endoscopic-radiological method is practicable and safe in cases in which transillumination is not possible. There are several advantages compared with direct puncturing: The common pull-through technique can be used; radiological exposure is low and other clinically relevant findings may be revealed by the endoscopy.


Effects of contaminated soil on the growth performance of young Salix (Salix schwerinii E. L. Wolf) and the potential for phytoremediation of heavy metals.
Salix schwerinii was tested in a pot experiment to assess plant growth performance i.e., relative height and dry biomass and the potential for heavy metal uptake in soils polluted with chromium, zinc, copper, nickel and total petroleum hydrocarbons. The soil used in the pot experiment was collected from a landfill area in Finland. Peat soil was added at different quantities to the polluted soil to stimulate plant growth. The plants were irrigated with tap water or processed water (municipal waste water) to further investigate the effects of nutrient loading on plant biomass growth. The soil was treated at two pH levels (4 and 6). The results showed that the addition of 40-70% peat soil at pH 6 to a polluted soil, and irrigation with processed water accelerated plant growth and phytoextraction efficiency. In the pot experiment, Salix grown in chromium, zinc, copper, nickel and total petroleum hydrocarbons -contaminated field soil for 141 days were unaffected by the contaminated soil and took up excess nutrients from the soil and water. Total mean chromium concentration in the plant organs ranged from 17.05 to 250.45 mg kg-1, mean zinc concentration ranged from 142.32 to 1616.59 mg kg-1, mean copper concentration ranged from 12.11 to 223.74 mg kg-1 and mean nickel concentration ranged from 10.11 to 75.90 mg kg-1. Mean chromium concentration in the plant organs ranged from 46 to 94%, mean zinc concentration ranged from 44 to 76%, mean copper concentration ranged from 19 to 54% and mean nickel concentration ranged from 8 to 21% across all treatments. Under the different treatments, chromium was taken up by Salix in the largest quantities, followed by zinc, copper and nickel respectively. Salix also produced a moderate reduction in total petroleum total petroleum hydrocarbons in the polluted soil. The results from the pot experiment suggest that Salix schwerinii has the potential to accumulate significant amounts of chromium, zinc, copper and nickel. However, long term research is needed to verify the phytoextraction abilities of Salix observed in the pot experiment.


Source-goal asymmetries in motion representation: Implications for language production and comprehension.
Recent research has demonstrated an asymmetry between the origins and endpoints of motion events, with preferential attention given to endpoints rather than beginnings of motion in both language and memory. Two experiments explore this asymmetry further and test its implications for language production and comprehension. Experiment 1 shows that both adults and 4-year-old children detect fewer within-category changes in source than goal objects when tested for memory of motion events; furthermore, these groups produce fewer references to source than goal objects when describing the same motion events. Experiment 2 asks whether the specificity of encoding source/goal relations differs in both spatial memory and the comprehension of novel spatial vocabulary. Results show that endpoint configuration changes are detected more accurately than source configuration changes by both adults and young children. Furthermore, when interpreting novel motion verbs, both age groups expect more fine-grained lexical distinctions in the domain of endpoint configurations compared to that of source configurations. These studies demonstrate that a cognitive-attentional bias in spatial representation and memory affects both the detail of linguistic encoding during the use of spatial language and the specificity of hypotheses about spatial referents that learners build during the acquisition of the spatial lexicon.


The role of annexins in tumour development and progression.
The annexins are a super-family of closely related calcium and membrane-binding proteins. They have a diverse range of cellular functions that include vesicle trafficking, cell division, apoptosis, calcium signalling and growth regulation. Many studies have shown the annexins to be among the genes whose expression are consistently differentially altered in neoplasia. Some annexins show increased expression in specific types of tumours, while others show loss of expression. Mechanistic studies relating the changes in annexin expression to tumour cell function, particularly tumour invasion and metastasis, angiogenesis and drug resistance, are now also emerging. Changes in the expression of individual annexins are associated with particular types of tumour and hence the annexins may also be useful biomarkers in the clinic.


Human papillomavirus test with cytology triage in organized screening for cervical cancer.
In randomized studies, testing for high-risk (HR) human papillomavirus (hrHPV) has been more sensitive than conventional cytology in detecting cervical intraepithelial neoplasia (CIN). The aim of this study was to evaluate the performance of HPV testing in the setting of an organized routine screening program. Since 2012, 35- to 60-year-old women living in the city of Tampere have been screened with the Abbott RealTime hrHPV test. HPV-negative women are referred to the next screening round in five years. HPV-positive women are triaged with conventional cytology, and women with at least low-grade squamous intraepithelial lesion (LSIL+ ) are referred to colposcopy. The remaining HPV-positive women are referred for re-testing after 12 months, and then all HPV-positive women are referred to colposcopy. The data from the last cohort with cytological screening (screened in 2011) is presented for comparison. A total 5637 (70%) women attended the first round of HPV screening, and 369 were HPV-positive. Of them, 54 women LSIL+ were referred to colposcopy, resulting in 16 CIN2+ lesions found. Of the remaining HPV-positive women, 66% were still positive one year later, and were referred to colposcopy, with 18 additional CIN2+ lesions found. The attendance rate to the last round of cytological screening was 71% (5814 women). Sixty-four women with LSIL+ cytology were referred to colposcopy, and 11 CIN2+ lesions were found. Of the 777 women with borderline cytology and scheduled for reflex screening in the following year, 109 (19%) had ASC-US+ , and 57 underwent colposcopy, resulting in six additional CIN2+ lesions found. The total detection rate of CIN2+ was significantly higher in the HPV-screened cohort (6.0/1000 vs. 2.9/1000, p = 0.015). However, the total colposcopy rate was 4% vs. 2%, respectively (p < 0.001). Human papillomavirus testing also seems to be more sensitive than cytology in detecting CIN2+ lesions in the setting of a routine organized screening program, besides in the context of randomized trials. The problem of an increased colposcopy rate needs to be addressed in the future.


Adaptive Equalization of Vibrotactile Actuators.
In order to provide convincing artifical touch sensations, humans should be presented with high quality haptic stimuli. In the vibrotactile domain, signals are usually displayed through mechanical actuators. Current high quality actuators exhibit a high dynamic range and have the ability to display a wide range of frequencies. However, fundamentally all actuators introduce distortions into the displayed signals. These distortions are usually nonlinear with additive noise components and they can be detrimental to some vibrotactile application scenarios that require high signal playback precision. To neutralize these distortions, we propose a signal-based equalization setup with adaptive filtering. Such a setup is very general and can be applied to any actuator in a straightforward manner. We introduce a novel adaptive filter based on Volterra and bilinear filter models that is nonlinear and more robust than previous approaches. In simulations and experiments, we show that our filter model is able to consistently outperform existing adaptive filter models and equalize vibrotactile actuators efficiently.


One-stage revision surgery of the infected hip. A minimum 10-year followup study.
Between 1977 and 1983, 24 one-stage revision surgeries were performed for septic failure of a total hip arthroplasty in 24 patients by one surgeon. Twelve patients died and none were lost to followup at a minimum of 10 years after the procedure. Infection reoccurred around two hips (8.3%). If the selected criteria (patients without draining sinuses, without immunocompromise, and with adequate bone quality after debridement) and the standard approach (meticulous debridement, use of antibiotic-impregnated cement, and use of 3 to 6 months postoperative oral antibiotic therapy) used in this study are implemented, direct exchange of an infected total hip arthroplasty construct is a reasonable and cost-effective alternative for some patients with infection after total hip arthroplasty.


Structure of the cobalamin-binding protein of a putative O-demethylase from Desulfitobacterium hafniense DCB-2.
This study describes the identification and the structural and spectroscopic analysis of a cobalamin-binding protein (termed CobDH) implicated in O-demethylation by the organohalide-respiring bacterium Desulfitobacterium hafniense DCB-2. The 1.5 Å resolution crystal structure of CobDH is presented in the cobalamin-bound state and reveals that the protein is composed of an N-terminal helix-bundle domain and a C-terminal Rossmann-fold domain, with the cobalamin coordinated in the base-off/His-on conformation similar to other cobalamin-binding domains that catalyse methyl-transfer reactions. EPR spectroscopy of CobDH confirms cobalamin binding and reveals the presence of a cob(III)alamin superoxide, indicating binding of oxygen to the fully oxidized cofactor. These data provide the first structural insights into the methyltransferase reactions that occur during O-demethylation by D. hafniense.


Few-Mode Fiber Characterization System Based on the Spatially and Spectrally Imaging Technique.
With the widespread use of few-mode fibers, mode characteristics testing becomes essential. In this paper, current few-mode fiber testing techniques are discussed, and the S2 imaging technique is chosen and demonstrated to be capable of few-mode fiber characterization in principle. As a result, the few-mode fiber characterization system with the S2 imaging technique is built and used to obtain accurate mode dispersion of two-mode fibers (a commonly used few-mode fiber) of different lengths. Then, various filters are applied to extract the fundamental and high-order modes to acquire mode coupling components (discrete and distributed mode coupling). The proposed system spectrally characterizes the few-mode fiber by resolving the interference information from the superimposed optical field spatially and has a simple structure and easy operation, which will provide parameter guidance for FMF designing and the FMF sensing experiment optimizing.


Granulocyte colony-stimulating factor induced acute and chronic graft-versus-host disease.
A recent experimental study in mice shed new light on the controversy as to whether granulocyte colony-stimulating factor (G-CSF) increases graft-versus-host disease (GVHD). Total body irradiation and bone marrow were found to be prerequisites for acute GVHD. This study encouraged us to perform a retrospective clinical study. We compared 260 patients given G-CSF prophylaxis after allogeneic hematopoietic stem-cell transplantation with 205 controls transplanted between 1993 and 2003. G-CSF hastened the engraftment of neutrophils, but that of platelets was delayed (P<0.0001). The proportion of acute GVHD of grades II to IV was 29% in the G-CSF group and 19% in the controls (P<0.01) and that of chronic GVHD was 54% and 43%, respectively (P=0.019). G-CSF increased acute and chronic GVHD in patients preferentially conditioned with chemotherapy. Unexpectedly, it exacerbated acute GVHD in recipients of peripheral blood stem cells and enhanced chronic GVHD in bone marrow recipients. A multivariable analysis showed that acute GVHD (hazards ratio=1.52, P=0.03) and chronic GVHD (hazards ratio=1.51, P=0.004) were associated with G-CSF. There was no significant difference between study groups regarding nonrelapse mortality, relapse, or survival. G-CSF increased acute and chronic GVHD in patients treated with chemotherapy but did not affect relapse or survival.


Does being religious help or hinder coping with chronic illness? A critical literature review.
This paper reviews a number of studies relating to religion and coping with chronic illness, emphasizing those aspects relevant to palliative care. After pointing out that religious and existential needs are common in chronic illness, a critical examination is made of those studies which purport to demonstrate associations between spiritual beliefs, religious practices and psychological prognosis. Recommendations are made as to how religious issues can be dealt with in clinical practice, with particular relevance to the multidisciplinary palliative care team.


Identification and validation of methylated differentially expressed miRNAs and immune infiltrate profile in EBV-associated gastric cancer.
The recent discovery of cancer/tissue specificity of miRNA has indicated its great potential as a therapeutic target. In Epstein-Barr virus-associated gastric cancer (EBVaGC), host genes are affected by extensive DNA methylation, including miRNAs. However, the role of methylated miRNA in the development of EBVaGC and immune cell infiltration has largely remained elusive. After crossmatching the DNA methylation and expression profile of miRNA and mRNA in the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas Research Network (TCGA), we discovered that miR-129-2-3p was significantly suppressed due to hypermethylation on its enhancer in EBVaGC. The differentially expressed genes (DEGs) added up to 30, among which AKAP12 and LARP6 were predicted to be the target genes of miR-129-2-3p and negatively correlated with patients' survival. Accordingly, miR-129-2-3p was significantly down-regulated in tumor samples in 26 (65%) out of 40 cases in our cohort (P < 0.0001). The proliferation, migration and invasion functions of GC cells were significantly promoted when transfected with miR-129-2-3p inhibitor and suppressed when transfected with mimics or treated with 5-aza-2'-deoxycytidine. Moreover, a comprehensive regulation network was established by combining the putative transcription factors, miRNA-mRNA and protein-protein interaction (PPI) analysis. Pathway enrichment analysis showed that cytokine activity, especially CCL20, was the most prominent biological process in EBVaGC development. Immune cell infiltration analysis demonstrated CD4+ T cell, macrophage and dendritic cell infiltrates were significantly enriched for the prognostic-indicated hub genes. This study has provided a comprehensive analysis of differentially expressed miRNAs and mRNAs associated with genome-wide DNA methylation by integrating multi-source data including transcriptome, methylome and clinical data from GEO and TCGA, QPCR of tumor samples and cell function assays. It also gives a hint on the relationships between methylated miRNA, DEGs and the immune infiltration. Further experimental and clinical investigations are warranted to explore the underlying mechanism and validate our findings.


Thiolation of non-ionic surfactants for the development of lipid-based mucoadhesive drug delivery systems.
The aim of this study was to develop thiolated self-emulsifying drug delivery systems (SEDDS) and nanostructured lipid carriers (NLCs) with improved mucoadhesive properties. Two non-ionic surfactants bearing a short and long PEG chain, namely polyoxyethylene (10) stearyl ether (PSE10) and polyoxyethylene (100) stearyl ether (PSE100), were thiolated for the first time by substituting the terminal hydroxyl group with a thiol group. The synthesis was confirmed by FT-IR, NMR and Ellman's test. SEDDS and NLCs containing these thiolated compounds were investigated for size, polydispersity index (PDI) and ζ potential. Subsequently, mucus diffusion studies, rheological evaluations after mixing the nanocarriers with mucus and mucoadhesion studies on porcine intestinal mucosa were performed. All nanocarriers had a size less than 250 nm, a maximum PDI of 0.3 and a ζ potential < -9.0 mV. Mucus diffusion studies resulted in the rank order of increasing diffusivity: PSE10-SH < PSE100-SH < PSE10-OH < PSE100-OH for NLCs and PSE10-OH < PSE100-OH < PSE100-SH < PSE10-SH for SEDDS. The mucoadhesive properties and increase in viscosity of SEDDS and NLCs ranked: PSE100-OH < PSE10-OH < PSE100-SH < PSE10-SH. In addition, the short chain PSE10-SH showed higher mucus interactions than the long chain PSE100-SH for both SEDDS and NLCs. The thiolated PSE surfactants appeared to be promising excipients for the design of highly mucoadhesive drug delivery systems.


Minor myocardial injury after elective uncomplicated successful PTCA with or without stenting: detection by cardiac troponins.
Cardiac troponins are sensitive and specific markers for the detection of minor myocardial injury. However, they have been rarely used to monitor myocardial injury after coronary stenting. The purpose of the study was to measure cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels after elective uncomplicated successful percutaneous transluminal coronary angioplasty (PTCA) with or without coronary stenting and to compare their results with serum creatinine kinase MB isoenzyme (CKMB). CTnI and cTnT levels were compared with those of CK or CKMB in 98 consecutive patients with stable angina undergoing elective uncomplicated successful PTCA with stenting (n = 71) or without stenting (n = 27). Markers were measured before and 6, 12, 24, and 48 hr after the procedure. Peak postprocedural levels for each marker were compared and related to angiographic and procedural characteristics as well as to the occurrence of side-branch occlusion. None of the patients had abnormal markers before the procedure. Abnormal postprocedural values of one or more markers were observed in 28 patients (29%), 23 after stenting and 5 after PTCA alone. The frequencies of abnormal cTnI and cTnT levels were significantly higher than that of CKMB after coronary intervention (26% and 18% vs. 7%; P = 0.00016 and 0.015, respectively), with cTnI being the most significant. When compared with troponin-negative patients, abnormal cardiac troponin values were significantly related to total time of inflation (223 +/- 128 vs. 170 +/- 105 sec; P = 0.008) and inflation maximal pressure (12.9 +/- 2.3 vs. 12.0 +/- 2.7 atm; P = 0.04). Small side-branch occlusion was noticed in 36% of the troponin-positive patients and in 6% of the troponin-negative group (P = 0.00047). In conclusion, minor myocardial injury is not uncommon after elective uncomplicated successful PTCA with or without stenting. Cardiac troponins, especially cTnI, are more sensitive than CKMB for the detection of this minor myocardial injury. Total time of inflation and inflation maximal pressure are predictors of postprocedural elevation of cardiac troponins. Side-branch occlusion may account for some, but not all, periprocedural minor myocardial injury.


Age and working memory: the role of perceptual speed, the central executive, and the phonological loop.
In a study (N = 61) comparing older (age range = 60-80 years, M = 67) and younger (age range = 20-33 years, M = 25) people, age deficits were observed in working memory, perceptual speed, and central executive functioning but not in phonological loop functioning. Controlling for age differences in central executive performance removed over 50% of the age-related variance in working memory span. However, controlling for perceptual speed removed all of the age-related variance in working memory span. In addition, age differences in central executive functioning were largely eliminated after controlling for age deficits in perceptual speed. These findings suggest that age differences in central executive functioning are primarily attributable to a general slowdown in the rate at which information is activated within the working memory system and that no specific deficits in the central executive occur as a consequence of aging.


Inhibition of Connexin 36 attenuates HMGB1-mediated depressive-like behaviors induced by chronic unpredictable mild stress.
High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1. After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine. Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1-mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.


Cardiovascular pharmacology of ASL-7022. III. Peripheral vascular adrenergic mechanisms.
The peripheral vascular actions of i.v. administered ASL-7022 were investigated in anesthetized, open-chest dogs and in isolated hindlimbs of normal, acute baroreceptor-denervated and spinal dogs. ASL-7022 decreased diastolic arterial blood pressure in open-chest dogs, an effect which was inhibited by ganglion blockade (hexamethonium bromide, 10 mg/kg i.v.). In hindlimbs from control animals, ASL-7022 produced vasodilation. Propranolol (1.0 mg/kg i.v.) reduced but did not eliminate vasodilation in these preparations but combined beta adrenergic and ganglion blockade converted responses to vasoconstriction. ASL-7022 induced greater vasodilation in hindlimbs from acute baroreceptor-denervated animals than in control animals. In acute baroreceptor-denervated preparations ganglion blockade eliminated vasodilation, propranolol partially blocked vasodilation and combined beta adrenergic and ganglion blockade converted responses to vasoconstriction. In spinal dogs i.v. infusion of low doses of ASL-7022 induced small increases in perfusion pressure; higher doses produced small decreases in perfusion pressure. The compound caused only vasoconstriction in propranolol-pretreated hindlimbs and caused only vasodilation in phentolamine-pretreated hindlimbs. ASL-7022 also dose dependently inhibited vasoconstrictor responses to electrical stimulation of the lumbar sympathetic chain and to exogenously administered norepinephrine. The data suggest that ASL-7022 blocks sympathetic vasoconstriction by either inhibiting the sympathetic nervous system or by inducing postsynaptic alpha adrenoceptor blockade. The compound also produces beta adrenoceptor-mediated vasodilation and, under appropriate pharmacological conditions, can be demonstrated to produce alpha adrenoceptor-mediated vasoconstriction.


The many faces of pain for older, dying adults.
An integration of knowledge from the fields of geriatrics, pain management, and palliative care is needed to ensure adequate pain control for the older adult who is dying. An overview is provided of the multiple factors (i.e., chronic illness, malignant disease, care procedures, emotional and cognitive status, response of others) that can cause and exacerbate pain at the end of life for the elderly. Treatment considerations are discussed and an illustrative case study is presented.


Mood Disorders Secondary to Demyelinating and Movement Disorders.
Mood disorders are recognized in several neurologic diseases. This chapter reviews three specific disorders, Parkinson's disease, Huntington's disease, and multiple sclerosis. The demographics of mood disorders and unique clinical characteristics are discussed for each disease. The possible causes for neurobiologically based affective symptoms are explored.


Trends in Gender Differences in Cardiac Care and Outcome After Acute Myocardial Infarction in Western Sweden: A Report From the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).
Cardiovascular disease is the most common cause of death for both genders. Debates are ongoing as to whether gender-specific differences in clinical course, diagnosis, and management of acute myocardial infarction (MI) exist. We compared all men and women who were treated for acute MI at cardiac care units in Västra Götaland, Sweden, between January 1995 and October 2014 by obtaining data from the prospective SWEDEHEART (Swedish Web-System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. We performed unadjusted and adjusted Cox proportional hazards and logistic regression analyses on complete case data and on imputed data sets. Overall, 48 118 patients (35.4% women) were diagnosed with acute MI. Women as a group had better age-adjusted prognosis than men, but this survival benefit was absent for younger women (aged <60 years) and for women with ST-segment elevation MI. Compared with men, younger women and women with ST-segment elevation MI were more likely to develop prehospital cardiogenic shock (adjusted odds ratio 1.67, 95% CI 1.30 to 2.16, P<0.001 and adjusted odds ratio 1.31, 95% CI 1.16 to 1.48, P<0.001) and were less likely to be prescribed evidence-based treatment at discharge (P<0.001 for β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and P2Y12 antagonists). Differences in treatment between the genders did not decrease over the study period (P>0.1 for all treatments). Women on average have better adjusted prognosis than men after acute MI; however, younger women and women with ST-segment elevation MI have disproportionately poor prognosis and are less likely to be prescribed evidence-based treatment.


Morphology of a unique ophidiid, Hypopleuron caninum Radcliffe 1913 (Ophidiiformes, Ophidiidae, Neobythitinae), suggesting a close relationship with the family Carapidae.
Osteological and myological characters of the ophidiid Hypopleuron caninum are described here in detail. In addition to well-known characters of Ophidiidae (e.g., anal-fin origin well posterior to dorsal-fin origin; barbel-like pelvic fin; many scales), many unique or rare conditions were also recognized, including predorsal bone and maxilla condition, and canine teeth on the premaxilla, which were suggestive of a relationship with Carapidae. Furthermore, the predorsal bone appear to be homologous with the vexillar support, a carapid synapomorphy. Although several characters differ from carapid counterparts (e.g., more anterior anal-fin origin and scales absent in Carapidae), some intermediate conditions between Ophidiidae and Carapidae are apparent in Hypopleuron caninum, which may therefore occupy an intermediate phylogenetic position between the two families. A unique morphology of small second infraorbital bone is recognized in all ophidiiform species observed in this study, and it may be a synapomorphic character of the order Ophidiiformes.


Hepatic tuberculosis mimics metastasis revealed by 18F-FDG PET/CT.
Extrapulmonary tuberculosis can affect almost any organ in the body. Here, we report a rare case of primary hepatic tuberculosis presented as multiple hepatic lesions and enlarged lymph nodes in the retroperitoneum and porta hepatis. PET/CT imaging showed avid FDG uptake by these lesions but did not find any definite primary malignancy. Finally, a diagnosis of primary hepatic tuberculosis was made with histopathologic examination.


Glycoprotein Synthesis in Plants: II. Structure of the Mannolipid Intermediate.
This paper reports the purification and structural determination of the mannolipid shown previously (Ericson and Delmer 1977 Plant Physiol 59: 341-347) to serve as an intermediate in glycoprotein synthesis in cotyledons of Phaseolus vulgaris. The mannolipid was purified by chromatography in organic solvents on diethylaminoethyl-cellulose, followed by repeated steps of deacylation and rechromatography on Sephadex LH-20. Binding and elution behavior on diethylaminoethyl-cellulose was consistent with the presence of a monophosphate residue. Lability of the mannolipid to mild acid treatment as well as its resistance to hot phenol treatment or catalytic hydrogenation are consistent with the structure of a polyprenol having a saturated alpha-residue. After methanolysis, the chloroform-methanol-soluble portion of the mannolipid was analyzed by mass spectrometry. The fragmentation pattern obtained was nearly identical to that obtained from standard dolichol-phosphate. An intense ion at m/e 69 represented the omega-terminal isoprenoid residue, and repeating fragments separated by 68 mass units were observed up to m/e of > 1,200. All evidence supports the conclusion that the mannolipid is dolichol-monophosphate-mannose and thus provides further support for the concept that the processes involved in the glycosylation of protein in higher plants are similar to those known to occur in the animal kingdom.


Association between gait variability, falls and mobility in people with multiple sclerosis: A specific observation on the EDSS 4.0-4.5 level.
We previously demonstrated that gait variability increases throughout the disease process in people with multiple sclerosis (PwMS). While gait variability tends to remain steady in the lower levels of disability, a significant increase occurs once patients reach the moderate neurological level. To examine the relationship between variability of major spatio-temporal parameters of gait and falls, in PwMS with an expanded disability status scale score of 4.0 and 4.5. The study included 91 PwMS, 50 women. Gait variability was studied using an electronic mat. Clinical gait measures included the Two-minute walk test, Timed Up and Go test and the Timed 25-foot walk. Fifty patients were classified as fallers, 41, non-fallers. The MS fallers presented a higher variability score in the step length (37.3% increase) and single support (28.2% increase) compared to participants in the non-fallers. Additionally, gait variability scores were significantly correlated with clinical walking tests. The strongest correlation scores were for variability of the step length. Pearson's rho scores for the Timed Up and Go test, 2-min walk and Timed 25-foot walk were 0.541, - 0.448 and 0.425, respectively. This study confirms that gait variability is a potential treatment target for PwMS moderately disabled, in order to decrease risk of falls.


Effects of amphotericin B, nystatin, and other polyene antibiotics on chitin synthase.
The effects of amphotericin B (AmB), nystatin, filipin, and pimaricin were tested chitin synthase (EC 220.127.116.11) (chitosomes from yeast cells of Mucor rouxii). AmB and nystatin inhibited the enzyme at concentrations greater than or equal to 10 micrograms/ml, filipin was weakly inhibitory, and pimaricin had no effect. The inhibition of chitin synthase by AmB appears to be noncompetitive, with a Ki value of about 0.13 mM. the effect of nystatin was more complex and included a sharp stimulation of chitin synthase activity at approximately 50 micrograms/ml. Our findings suggest the existence of binding sites (sterols?) on the chitosome that are selective for certain polyenes and that play a role in the operation of chitin synthase. Because the minimal growth inhibitory concentrations of AmB or nystatin are lower than the concentrations that inhibit chitin synthase in vitro, the possibility of chitosomal chitin synthase being a primary target for the antifungal action of these polyenes seems unlikely.


NewWave: a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA-seq data.
We present NewWave, a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA sequencing data. To achieve scalability, NewWave uses mini-batch optimization and can work with out-of-memory data, enabling users to analyze datasets with millions of cells. NewWave is implemented as an open-source R package available through the Bioconductor project at https://bioconductor.org/packages/NewWave/. Supplementary data are available at Bioinformatics online.


Ethanolic Extract of Salvia hispanica L. Regulates Blood Pressure by Modulating the Expression of Genes Involved in BP-Regulatory Pathways.
Hypertension (HT) is considered to be a potential risk factor for cardiovascular diseases and has been directly related to pathologies such as obesity and dyslipidemias. Angiotensin-converting enzyme inhibitors (ACEIs) blocked the renin-angiotensin-aldosterone cascade diminishing the production of angiotensin II and the level of bradykinin, produced by the kallikrein-kinin system. Although ACEIs are effective therapeutics in regulating HT, they present several side-effects that can be due to their mechanism of action (as hypotension, cough, dizziness, light-headedness or hyperkalemia) to specific drug molecular structure (skin rash, neutropenia and tasting disorders) or due to associated pathologies in the patients (it has been considered a possible nephrotoxic effect when ACEIs are administered in combination with angiotensin receptor blockers, in patients that present comorbidities as diabetes, acute kidney injury or chronic kidney disease). Therefore, it is necessary the searching for new products with ACEI activity that do not produce side effects. Interestingly, species of the plant genus Salvia have been found to possess hypotensive effects. In the present study, we analyzed the effects of the ethanolic extract of Salvia hispanica L. seeds (EESH) on the expression of genes involved in pathways regulating HT. Administration of EESH to hypertensive rats inhibited the angiotensin-converting enzyme (ACE) activity along with a decrease in Ace and elevation of Agtr1a and Nos3 gene expression, as compared to that in healthy rats. Moreover, these results were similar to those observed with captopril, an antihypertensive drug used as a control. No significant change in the expression of Bdkrb2 gene was observed in the different groups of rats. To conclude, our results demonstrate that EESH regulates blood pressure (BP) in hypertensive rats through transcriptionally regulating the expression of genes that participate in different pathways involving ACE.


Overexpression of human Ku70/Ku80 in rat cells resulting in reduced DSB repair capacity with appropriate increase in cell radiosensitivity but with no effect on cell recovery.
The effect of an overexpression of human Ku70/80 was studied using cells of the rat cell lines Rat-1 and R7080, the latter being transfected with the human cDNAs for Ku70 and Ku80. The overexpression was found to result in a 20% reduction of the DNA-PK activity. The kinetics of DSB repair, which was studied after exposure of the cells to 30 Gy of X rays, was biphasic and had identical half-times for Rat-1 and R7080 cells (tfast = 7 min and tslow = 135 min). However, there was a significant difference between the cell lines in the fractions of DSBs repaired with slow and fast kinetics. In R7080 cells, about twice as many DSBs were repaired with slow kinetics compared to Rat-1 cells (34% compared to 16%). A similar difference was found in the number of residual DSBs (3.6% compared to 2.0%). R7080 cells also showed a reduced capacity to repair chromosome damage as detected by the PCC technique. Concerning cell killing, R7080 cells were clearly more radiosensitive than Rat-1 cells (D0.1 = 6.4 compared to 10.5 Gy), and this increase in sensitivity correlated well with the increase in residual DSBs. The two cell lines, however, did not vary in cell recovery. For sublethal as well as potentially lethal damage, Rat-1 and R7080 cells showed identical recovery ratios. These data demonstrate that the overexpression of human Ku70/Ku80 led to a reduced capacity for DSB repair with an associated increase in cell sensitivity but with no effect on cell recovery.


Antihypertensive effect of felodipine combined with beta-blockade. A comparison between 2 and 3 daily dosages.
24 hypertensive patients, who were not satisfactorily controlled (diastolic blood pressure greater than 95 mm Hg) with beta-blockers alone were randomised to 2 treatment groups where felodipine was administered for 2 weeks in a total daily dose of 15 mg divided in 2 or 3 doses. Following a 2-week placebo washout period, the patients were switched to the alternative dose regimen in a double-blind crossover manner. Blood pressure was measured with standard techniques and was also non-invasively monitored for 24 hours at the end of each dose regimen period and at the end of the intermediate placebo period. Mean arterial blood pressure at the end of the placebo run-in period was 169/105 mm Hg. Felodipine 5 mg thrice daily reduced blood pressure by 20/9 mm Hg and felodipine 7.5 mg twice daily by 17/9 mm Hg (p less than 0.05). The difference between the 2 dose regimens was not statistically significant. When 24-hour blood pressure measurements for the 2 dose regimens were compared, there were no statistically significant differences. Both regimens reduced the 24-hour blood pressure significantly compared with placebo. Two patients were withdrawn during the study, 1 before felodipine treatment started and the other due to diarrhoea and flushing related to felodipine. Otherwise felodipine was generally well tolerated.


Detection and management of associated atherothrombotic locations in patients with a recent atherothrombotic ischemic stroke: results of the DETECT survey.
Cerebral infarction (CI), myocardial infarction, peripheral artery disease (PAD) and aortic atheroma are the main clinical manifestations of atherothrombosis. Long-term prevention after CI of atherothrombotic origin may require preventive measures at other sites, such as specific drug therapies, surgery, or angioplasty. Therefore the detection of other locations is potentially important. The primary objective was to describe the other locations of atherothrombosis in patients hospitalized for a recent cerebral infarct of atherothrombotic origin. Secondary objectives were to describe their vascular risk factor profiles, and their management before and after the cerebral event. This prospective, observational, multicenter survey was conducted in France between September 2003 and July 2004, mainly in neurological departments and stroke units. 753 patients were included (74% men; mean age 69.3 years). Previous coronary events had occurred in 119 (16%). Previous stroke or transient ischemic attacks had occurred in 233 (31%). PAD was already known in 109 (15%). A search for other atherothrombotic locations was positive in 216 patients (29%). The minimum prevalence for any associated atherothrombotic location (either present before or identified during hospitalization) was 47.5% for any location, 33.7% for coronary artery disease, 16.6% for aortic atheroma, and 22.7% for PAD. Fifty percent of the patients with recent atherothrombotic CI have other locations of atherothrombosis. For this reason, a systematic search for these other locations is recommended because of the possible therapeutic consequences. However, the question of the most appropriate period for this search after the cerebral event remains unsettled.


The Impact of Homelessness on Mortality of Individuals Living in the United States: A Systematic Review of the Literature.
This systematic review assessed peer-reviewed research studies on mortality rates of the homeless population within the United States. Extrapolated data included definitions of homelessness, mortality data sources, findings on mortality rates, and causes of premature mortality. Results demonstrate that individuals experiencing homelessness die earlier than comparison groups not experiencing homelessness. Methodology and findings varied across studies. Subpopulations included veterans, families, youth, and unsheltered. Causes of death varied across subpopulations and changed over time. Top causes of death, predominantly determined by ICD codes, stemmed from neoplasms, heart disease, and substance use disorder. Sources used for mortality data included the National Death Index (NDI), the Social Security Death Index (SSDI), state death occurrence files, and city vital statistics. Important research foci include standardization, subpopulation variations, policy implications, and the influence of mortality risk factors, such as poverty and racism.


POSTERIOR VERSUS ANTERIOR APPROACH TO TOTAL HIP ARTHROPLASTY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.
To perform a systematic review and meta-analysis to compare clinical and surgical outcomes of posterior versus anterior approach to primary total hip arthroplasty (THA). This study followed the standard methodology established by the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two independent reviewers searched for randomized controlled trials comparing posterior an anterior approach to primary THA with at least one quantifiable functional outcome published in the PubMed, Cochrane, and Virtual Health Library databases. The analysis included ten randomized controlled trials conducted with 774 patients. The posterior approach was associated with shorter operative time (mean of 15.98 minutes shorter, 95% CI 11.21 to 20.76, p < 0.00001) while the anterior approach was associated with shorter length of hospital stay (0.31 days or about eight hours shorter, 95% CI 0.12 to 0.51, p = 0.002) and greater earlier improvement in functional outcomes up to six months from the procedure (mean Harris Hip Score of 4.06 points greater, 95% CI 2.23 to 5.88, p < 0.0001). Whereas the posterior approach to primary THA is associated with a shorter operative time, the anterior approach has the potential to decrease the length of stay and provide greater short-term functional restoration. Level of evidence I, Systematic Review and Meta-Analysis.


Production of D-tagatose, a functional sweetener, utilizing alginate immobilized Lactobacillus fermentum CGMCC2921 cells.
D-tagatose is a ketohexose that can be used as a novel functional sweetener in foods, beverages, and dietary supplements. This study was aimed at developing a high-yielding D-tagatose production process using alginate immobilized Lactobacillus fermentum CGMCC2921 cells. For the isomerization from D-galactose into D-tagatose, the immobilized cells showed optimum temperature and pH at 65 °C and 6.5, respectively. The alginate beads exhibited a good stability after glutaraldehyde treatment and retained 90% of the enzyme activity after eight cycles (192 h at 65 °C) of batch conversion. The addition of borate with a molar ratio of 1.0 to D-galactose led to a significant enhancement in the D-tagatose yield. Using commercial β-galactosidase and immobilized L. fermentum cells, D-tagatose was successfully obtained from lactose after a two-step biotransformation. The relatively high conversion rate and productivity from D-galactose to D-tagatose of 60% and 11.1 g l⁻¹ h⁻¹ were achieved in a packed-bed bioreactor. Moreover, lactobacilli have been approved as generally recognized as safe organisms, which makes this L. fermentum strain an attracting substitute for recombinant Escherichia coli cells among D-tagatose production progresses.


Monitoring smoking behaviour using a wearable acoustic sensor.
Smoking is a cause of multiple health problems resulting in diseases which can also be fatal. It is well known that smoking has long-term impact on the health of an individual as well. While a number of studies have looked at the impact of smoking on health and its economic impacts, most of these rely on input from smokers in the form of questionnaires and surveys. Long-term monitoring of smoking habits and behaviour is thus not possible because of the lack of means to do so. This paper proposes the use of a wearable device to monitor breathing signals of subjects. It is shown that the acoustic properties of a smoking breath are different from a non-smoking breath. To encapsulate these differences, several features from a breath segment are extracted and used with a simple classifier to automatically identify smoking breaths. The proposed algorithm detected smoking and non-smoking breaths with average accuracy of 66% and 99% respectively.


Discriminating males alter sperm production between species.
Prezygotic reproductive isolation and its importance in speciation is traditionally approached from the viewpoint of those events that occur before mating. However, recent interest in sperm competition theory has shown that prezygotic isolation can be affected by mechanisms that occur after mating but before fertilization. One neglected aspect of these studies is how the cost of sperm production might play a role in species isolation. We examined differential sperm production in a species whose males are sexually parasitized by a unisexual gynogenetic species. Gynogens are clonal females that require sperm from males of closely related bisexual species to initiate embryogenesis. We tested for differential sperm production by male sailfin mollies (Poecilia latipinna) when they were in the presence of either a heterospecific, gynogenetic female (Poecilia formosa, Amazon molly) or a conspecific female. We found that previously demonstrated male mate choice for conspecific over heterospecific females also is revealed in sperm production. Males from both an allopatric and a sympatric population produce more sperm when in the presence of a conspecific female than when in the presence of a heterospecific female. We suggest that differential sperm production also could play a role in prezygotic reproductive isolation in bisexual species complexes that occur in sympatry.


[Basidiomycetous laccase gene diversity in two subtropical forest soils].
As one of the key enzymes involved in lignin decomposition of forest litter, laccase plays an important role in the carbon cycling in forest ecosystem. By using TA cloning and sequencing, a comparative study was conducted on the basidiomycetous laccase gene diversity in the O horizon (litter layer) and A horizon (surface soil layer, 0-20 cm) in two subtropical forests (a primeval evergreen deciduous broadleaved mixed forest and an artificial masson pine forest). For the same soil horizons, the basidiomycetous laccase gene diversity and richness were higher in the primeval forest than in the masson pine forest; for the same forest ecosystems, the basidiomycetous laccase gene diversity and richness in the primeval forest were slightly higher in O horizon than in A horizon, but those in the masson pine forest were apparently lower in O horizon than in A horizon. The two forest soils had the same dominant laccase gene-containing basidiomycetous populations, and most of the populations had high similarity of amino acid sequence to Mycena sp. or Pleurotus sp. belonging to Agaricales. Comparing with the A horizon in primeval forest and the O horizon in masson pine forest, the O horizon in primeval forest and the A horizon in masson pine forest had a relatively uniform distribution of basidiomycetous populations. The nucleotide sequence similarity of basidiomycetous laccase gene between the O and A horizons in the masson pine forest was higher than that in the primeval forest. This study showed that vegetation and soil horizon had significant effects on the basidiomycetous laccase gene diversity and community structure, and the discrepancies in the substrate availability for basidiomycetes and in the soil pH induced by the vegetation and soil horizon could be the driving forces.


Relationship of Chronic Rhinosinusitis with Asthma, Myocardial Infarction, Stroke, Anxiety, and Depression.
Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the nose and paranasal sinuses. It often has a high burden and is difficult to treat because of comorbidities. However, no population-based, long-term longitudinal study has investigated the relationship between CRS and its comorbidities. To investigate the potential relationship between CRS and its comorbidities-asthma, acute myocardial infarction (AMI), stroke, anxiety disorder, and depression-using a representative sample. Data for a total of 1,025,340 patients from the Korean National Health Insurance Service database from 2002 to 2013, including 14,762 patients with CRS and 29,524 patients without CRS, were used for this study. A 1:2 propensity score matching was performed using the nearest-neighbor matching method and sociodemographic factors and enrollment year. Cox proportional hazards model was used to analyze the hazard ratio (HR) of CRS for asthma, AMI, stroke, anxiety disorder, and depression. The incidence rates of asthma, AMI, and stroke were 71.1, 3.1, and 7.7 per 1000 person-years in patients with CRS, respectively. The adjusted HRs of asthma, AMI, and stroke were 2.06 (95% CI, 2.00-2.13), 1.29 (95% CI, 1.15-1.44), and 1.16 (95% CI, 1.08-1.24), respectively, in patients with CRS versus patients without CRS. The incidence rates of anxiety disorder and depression in patients with CRS were 42.1 and 24.2 per 1000 person-years, respectively. The adjusted HRs of anxiety disorder (HR, 1.54; 95% CI, 1.49-1.60) and depression (HR, 1.50; 95% CI, 1.44-1.57) were significantly greater in patients with CRS versus patients without CRS. CRS is associated with an increased incidence of asthma, AMI, stroke, anxiety disorder, and depression. Therefore, we suggest that clinicians should monitor patients with CRS carefully, and optimize management as a means to potentially decrease these other associated comorbid conditions.


Solitary fibrous tumor of the pleura: a report of five cases diagnosed by transthoracic cutting needle biopsy.
Five patients had a solitary fibrous tumor of the pleura; a well-known but rare entity. In all cases, biopsy by a transthoracic cutting needle (Tru-Cut; Travenol; Deerfield, IL) yielded specimens adequate for histologic analysis and gave the clue to the diagnosis. In four patients, surgical resection confirmed the diagnosis. The opportunity for and interest in diagnosing these tumors by transthoracic cutting needle biopsy before surgery are discussed. An accurate diagnosis of solitary fibrous tumors of the pleura can be made by a minimally invasive procedure; this allows for a more informed allocation of surgical resources.


Evaluation with receptor binding assay on the water extracts of ten CNS-active Chinese herbal drugs.
In the present study, we established receptor binding assays to evaluate the water extracts of ten central nervous system (CNS)-active Chinese herbal drugs. These ten herbal drugs are Chaihu (Radix Bupleuri), Chuanxiong (Rhizoma Chuanxiong), Danggui (Radix Angelicae sinensis), Danshen (Radix Salviae miltiorrhizae), Duhuo (Radix Angelicae pubescentis), Hangqin (Radix Scutellariae), Qinjiao (Radix Gentianae macrophyllae), Shengma (Rhizoma Cimicifugae), Suanzaoren (Semen Zizphi spinose), and Yangjihua (Flos Daturae). The results indicated that these water extracts contained the principles acting on the dopamine (D1 & D2), muscarinice acetylcholine (M1), or 5-HT (5-HT1A & 5-HT2) receptors, or the benzodiazepine and the gamma-amino-n-butyric acid (GABA) binding sites of GABAA receptors as determined by receptor binding assays. The receptors or binding sites which predominantly acted by each water extract are listed as follows: Chaihu: D2, 5-HT1A, GABA; Chuanxiong: GABA, 5-HT1A; Danggui: GABA, 5-HT1A; Danshen: BDZ; Duhuo: GABA, 5-HT1A, D2, D1; Hangqin: BDZ, D1, 5-HT1A; Qinjiao: GABA, BDZ, 5-HT1A, D2; Shengma: 5-HT1A; Suanzaoren: 5-HT1A, 5-HT2, GABA; Yangjihua: M1, 5-HT1A, 5-HT2. These results provided evidence to explain the CNS effects of these herbal drugs at the receptor level. Furthermore, these results provided information to direct the isolation and purification of receptor-interactive compounds from these herbal drugs.


Physiologic inhibitors of coagulation in patients on chronic hemodialysis.
Patients on hemodialysis are at increased risk for bleeding and thromboses. The intriguing balance between these risks is more complex than once thought, as endogenous clotting factors and their regulators come into contact with bioincompatible dialyzer membranes, in the setting of an extracorporeal circuit of blood flow, in the face of the uremic state. In this review, we summarize the current data on the interaction between the physiologic inhibitors of coagulation and hemodialysis. Data sources and study selection were obtained from research and review articles related to the endogenous anticoagulation pathway published in English on MEDLINE from 1972 to 2002. While protein C activity and protein S antigen concentrations are increased, there is no change in antithrombin III levels during hemodialysis in relation to predialysis levels. Plasma protein Z, which has only recently been studied in uremic subjects, is increased as well. In addition, hemodialysis leads to elevated tissue factor plasminogen inhibitor, thrombomodulin, tissue plasminogen activator, and plasminogen activator inhibitor-1 activities. The potential functional significance of these observations is discussed. Finally, as erythropoietin is commonly prescribed to uremic patients and is recognized to be prothrombotic, an appraisal of its interaction with the naturally occurring anticoagulants is presented. It is apparent that we are only beginning to realize the complexity of the interplay between this myriad of serum factors and hemodialysis. Further research is needed to shed light on this underexplored area of hemodialysis.


The use of biomarkers in the diagnosis and treatment of obstruction of the upper urinary tract in children.
Antenatal hydronephrosis, dilatation of the upper urinary tract (UUTD), is a common finding on prenatal ultrasound. One of the most common causes is ureteropelvic junction (UPJ) obstruction. Although such prenatally diagnosed UUTD resolves spontaneously in most newborns, further examination of these children is advocated to prevent possible irreversible kidney damage, and ultrasound is mainly used for this. If the dilatation persists or becomes symptomatic, it is necessary to proceed to other relatively demanding and invasive diagnostic examinations for these small patients, where the question of the right timing of indications for possible surgical solutions is still unclear. For this reason, various biomarkers have been investigated in a number of clinical trials as potential mini-invasive diagnostic tools for determining when upper urinary tract dilatation in such children poses a threat to the developing kidneys and they should be operated on, and vice versa, when to proceed conservatively. The aim of this article is to review the findings on and current issues with the use of biomarkers in the diagnosis and treatment of UPJ obstruction in children.


The pore-forming protein Cry5B elicits the pathogenicity of Bacillus sp. against Caenorhabditis elegans.
The soil bacterium Bacillus thuringiensis is a pathogen of insects and nematodes and is very closely related to, if not the same species as, Bacillus cereus and Bacillus anthracis. The defining characteristic of B. thuringiensis that sets it apart from B. cereus and B. anthracis is the production of crystal (Cry) proteins, which are pore-forming toxins or pore-forming proteins (PFPs). Although it is known that PFPs are important virulence factors since their elimination results in reduced virulence of many pathogenic bacteria, the functions by which PFPs promote virulence are incompletely understood. Here we study the effect of Cry proteins in B. thuringiensis pathogenesis of the nematode Caenorhabditis elegans. We find that whereas B. thuringiensis on its own is not able to infect C. elegans, the addition of the PFP Cry protein, Cry5B, results in a robust lethal infection that consumes the nematode host in 1-2 days, leading to a "Bob" or bag-of-bacteria phenotype. Unlike other infections of C. elegans characterized to date, the infection by B. thuringiensis shows dose-dependency based on bacterial inoculum size and based on PFP concentration. Although the infection process takes 1-2 days, the PFP-instigated infection process is irreversibly established within 15 minutes of initial exposure. Remarkably, treatment of C. elegans with Cry5B PFP is able to instigate many other Bacillus species, including B. anthracis and even "non-pathogenic" Bacillus subtilis, to become lethal and infectious agents to C. elegans. Co-culturing of Cry5B-expressing B. thuringiensis with B. anthracis can result in lethal infection of C. elegans by B. anthracis. Our data demonstrate that one potential property of PFPs is to sensitize the host to bacterial infection and further that C. elegans and probably other roundworms can be common hosts for B. cereus-group bacteria, findings with important ecological and research implications.


Pollen-Specific Aquaporins NIP4;1 and NIP4;2 Are Required for Pollen Development and Pollination in Arabidopsis thaliana.
In flowers with dry stigmas, pollen development, pollination, and pollen tube growth require spatial and temporal regulation of water and nutrient transport. To better understand the molecular mechanisms involved in reproductive processes, we characterized NIP4;1 and NIP4;2, two pollen-specific aquaporins of Arabidopsis thaliana. NIP4;1 and NIP4;2 are paralogs found exclusively in the angiosperm lineage. Although they have 84% amino acid identity, they displayed different expression patterns. NIP4;1 has low expression levels in mature pollen, while NIP4;2 expression peaks during pollen tube growth. Additionally, NIP4;1pro:GUS flowers showed GUS activity in mature pollen and pollen tubes, whereas NIP4;2pro:GUS flowers only in pollen tubes. Single T-DNA mutants and double artificial microRNA knockdowns had fewer seeds per silique and reduced pollen germination and pollen tube length. Transport assays in oocytes showed NIP4;1 and NIP4;2 function as water and nonionic channels. We also found that NIP4;1 and NIP4;2 C termini are phosphorylated by a pollen-specific CPK that modifies their water permeability. Survival assays in yeast indicated that NIP4;1 also transports ammonia, urea, boric acid, and H2O2 Thus, we propose that aquaporins NIP4;1 and NIP4;2 are exclusive components of the reproductive apparatus of angiosperms with partially redundant roles in pollen development and pollination.


Trap geometry in three giant montane pitcher plant species from Borneo is a function of tree shrew body size.
*Three Bornean pitcher plant species, Nepenthes lowii, N. rajah and N. macrophylla, produce modified pitchers that 'capture' tree shrew faeces for nutritional benefit. Tree shrews (Tupaia montana) feed on exudates produced by glands on the inner surfaces of the pitcher lids and defecate into the pitchers. *Here, we tested the hypothesis that pitcher geometry in these species is related to tree shrew body size by comparing the pitcher characteristics with those of five other 'typical' (arthropod-trapping) Nepenthes species. *We found that only pitchers with large orifices and lids that are concave, elongated and oriented approximately at right angles to the orifice capture faeces. The distance from the tree shrews' food source (that is, the lid nectar glands) to the front of the pitcher orifice precisely matches the head plus body length of T. montana in the faeces-trapping species, and is a function of orifice size and the angle of lid reflexion. *Substantial changes to nutrient acquisition strategies in carnivorous plants may occur through simple modifications to trap geometry. This extraordinary plant-animal interaction adds to a growing body of evidence that Nepenthes represents a candidate model for adaptive radiation with regard to nitrogen sequestration strategies.


Bioconverted Jeju Hallabong tangor (Citrus kiyomi × ponkan) peel extracts by cytolase enhance antioxidant and anti-inflammatory capacity in RAW 264.7 cells.
Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi × ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or 200 µg/ml of citrus peel extracts for 4 h, followed by stimulation with 1 µg/ml lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin E2 (PGE2) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and PGE2 production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only 200 µg/ml of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and 200 µg/ml of CKP-C notably inhibited mRNA levels of interleukin-1β (IL-1β) and IL-6, whereas 200 µg/ml CKP-C significantly inhibited mRNA levels of TNF-α. This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones of citrus peels and provide more potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by increasing radical scavenging activity and suppressing pro-inflammatory mediators and cytokines.


Characteristics of a propagating gaussian beam.
From diffraction theory, an expression is derived for the radius of a gaussian beam, in an output plane of a single lens, on-axis optical system, as a function of input waist radius, lens focal length, input waist to lens spacing, and lens to output plane spacing. Several special cases are discussed and plots of the important cases are included. The choice of the plots, and their scaling, was made on the basis of providing useful information to those people involved with typical problems in laser scanning systems, such as the location and size of the focused spot. The derivation includes a discussion of truncation effects.


Postoperative complications and clinical outcomes among patients undergoing thoracic and gastrointestinal cancer surgery: A prospective cohort study.
This study sought to determine the influence of postoperative complications on the clinical outcomes of patients who underwent thoracic and gastrointestinal cancer surgery. A prospective cohort study was conducted regarding 179 consecutive patients who received thorax or digestive tract surgery due to cancer and were admitted to an oncological intensive care unit. The Postoperative Morbidity Survey was used to evaluate the incidence of postoperative complications. The influence of postoperative complications on both mortality and length of hospital stay were also assessed. Postoperative complications were found for 54 patients (30.2%); the most common complications were respiratory problems (14.5%), pain (12.9%), cardiovascular problems (11.7%), infectious disease (11.2%), and surgical wounds (10.1%). A multivariate logistic regression found that respiratory complications (OR = 18.68; 95%CI = 5.59 - 62.39; p < 0.0001), cardiovascular problems (OR = 5.06, 95%CI = 1.49 - 17.13; p = 0.009), gastrointestinal problems (OR = 26.09; 95%CI = 6.80 - 100.16; p < 0.0001), infectious diseases (OR = 20.55; 95%CI = 5.99 - 70.56; p < 0.0001) and renal complications (OR = 18.27; 95%CI = 3.88 - 83.35; p < 0.0001) were independently associated with hospital mortality. The occurrence of at least one complication increased the likelihood of remaining hospitalized (log-rank test, p = 0.002). Postoperative complications are frequent disorders that are associated with poor clinical outcomes; thus, structural and procedural changes should be implemented to reduce postoperative morbidity and mortality.


From staff-mix to skill-mix and beyond: towards a systemic approach to health workforce management.
Throughout the world, countries are experiencing shortages of health care workers. Policy-makers and system managers have developed a range of methods and initiatives to optimise the available workforce and achieve the right number and mix of personnel needed to provide high-quality care. Our literature review found that such initiatives often focus more on staff types than on staff members' skills and the effective use of those skills. Our review describes evidence about the benefits and pitfalls of current approaches to human resources optimisation in health care. We conclude that in order to use human resources most effectively, health care organisations must consider a more systemic approach--one that accounts for factors beyond narrowly defined human resources management practices and includes organisational and institutional conditions.


Identifying Drug Therapy Problems Through Patient Consultation at Community Pharmacies: A Quality Improvement Project.
This study aimed to identify drug therapy problems during patient counseling at prescription pickup in the community pharmacy setting. This descriptive quality improvement project assessed the number of drug therapy problems identified during patient consultation. Data were collected for 2 months at 6 community pharmacies in Arizona. The criterion for inclusion was any patient new or transferred prescription consultation provided by a pharmacist or pharmacy intern. Three doctor of pharmacy candidates collected data on a standardized form. The percentage and type of drug therapy problems identified during patient consultation were calculated. Data collectors counseled patients on 1305 prescriptions, and of those, 29 drug therapy problems (2.2%) were identified after the pharmacists' final check. The most common problems involved patient drug allergy or sensitivity (20.7%). This project suggests that drug therapy problems in a community pharmacy setting can be identified via patient counseling at the time of prescription pickup.


Enterovirus heart disease of adults: a persistent, limited organ infection in the presence of neutralizing antibodies.
Detection of enterovirus RNA in endomyocardial biopsies (EMB) by reverse transcription/polymerase chain reaction (RT-PCR) is currently the preferred diagnostic procedure in suspected enterovirus heart disease (EHD), which can present clinically as myocarditis, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). EMB and peripheral blood mononuclear cells (PBMC) of 44 patients with suspected EHD were examined by nested RT-PCR to investigate whether the myocardial enterovirus infection is limited to the heart or is generalized. Enterovirus RNA was detected in EMB, but not in PBMC, of 8 patients (3 of these suffered from ARVC), whereas EMB of 16 controls and PBMC of 45 controls were negative. In addition, enterovirus RNA was demonstrated in PBMC, but not in EMB, of a single patient with suspected EHD. A high sequence homology of the amplicons to coxsackievirus B3 was demonstrated in 7 patients, and to coxsackievirus B2 in two patients. In order to evaluate whether the myocardial enterovirus infection was acute or persistent, neutralization and complement fixation tests were performed for antibodies against the serotypes indicated by the nucleic acid sequences. Neutralizing antibodies were detected in the sera of all 9 patients, but complement fixing antibodies were demonstrated only in one EHD patient and in the patient positive for enterovirus RNA in PBMC. In conclusion, the molecular and serological data demonstrate that CVB3 predominates as cardiotropic enterovirus, and that the enterovirus replication is limited to the heart in EHD. Serological results support the hypothesis of myocardial enterovirus RNA persistence in spite of neutralizing antibodies.


Historical development of the dopamine hypothesis of schizophrenia.
This review examines the history of discoveries that contributed to development of the dopamine hypothesis of schizophrenia. The origin of the hypothesis is traced to the recognition that neuroleptic drugs interfere with brain dopamine function. This insight was derived from two distinct lines of research. The first line originated from the discovery in 1956 that reserpine depletes brain serotonin. This finding resulted in a sequence of studies that led to the discovery that brain dopamine is involved in neuroleptic-induced extrapyramidal motor disturbances. The second line of research was aimed at determining the mechanism of action of psychomotor stimulants. This research produced evidence that stimulants directly or indirectly activate brain dopamine receptors. Because nonreserpine neuroleptics such as chlorpromazine block stimulant-induced movement, these findings suggested that neuroleptics were dopamine antagonists. Most previous accounts of the development of the dopamine hypothesis of schizophrenia emphasize the first line of research and ignore the second.


Morphological changes caused by exposure of rabbit oesophageal mucosa to hydrochloric acid and sodium taurocholate.
The present authors have studied the light and electron microscopic changes in rabbit oesophageal mucosa which has been exposed to solutions of hydrochloric acid and sodium taurocholate (ST). In an in vivo model the oesophagus was perfused with saline, acid (0.1-40 mmol/l of H+) or taurocholate (0.1-1.0 mmol/l at pH 2.0 or 1.0 mmol/l at neutral pH). At the end of each perfusion experiment the oesophagus was removed and assessed by the naked eye, light and electron microscopy. Some desquamation of superficial stratum corneum cells occurred in all specimens perfused for 5 h. Injury was more evident to the stratum spinosum and basal cell layers. Damage was more severe in the bile salt plus acid perfused specimens, varying between margination of nuclear chromatin in the basal cells to complete necrosis and separation of the overlying layers. Taurocholate in neutral solution did not damage the oesophageal epithelium. Electron microscopy revealed that damage to cells in the basal layers and stratum granulosum occurred within 30 min of exposure to acidified taurocholate, this damage increasing with time. It is concluded that taurocholate is able to damage oesophageal mucosa, that the damage first occurs in the deeper layers of the oesophageal mucosa and that the damage may occur in the absence of gross or light microscopic changes in the mucosa.


Physiological, kinematic, and electromyographic responses to kinesiology-type patella tape in elite cyclists.
Kinesiology-type tape (KTT) has become popular in sports for injury prevention, rehabilitation, and performance enhancement. Many cyclists use patella KTT; however, its benefits remain unclear, especially in uninjured elite cyclists. We used an integrated approach to investigate acute physiological, kinematic, and electromyographic responses to patella KTT in twelve national-level male cyclists. Cyclists completed four, 4-minute submaximal efforts on an ergometer at 100 and 200 W with and without patella KTT. Economy, energy cost, oxygen cost, heart rate, efficiency, 3D kinematics, and lower-body electromyography signals were collected over the last minute of each effort. Comfort levels and perceived change in knee stability and performance with KTT were recorded. The effects of KTT were either unclear, non-significant, or clearly trivial on all collected physiological and kinematic measures. KTT significantly, clearly, and meaningfully enhanced vastus medialis peak, mean, and integrated electromyographic signals, and vastus medialis-to-lateralis activation. Electromyographic measures from biceps femoris and biceps-to-rectus femoris activation ratio decreased in either a significant or clinically meaningful manner. Despite most cyclists perceiving KTT as comfortable, increasing stability, and improving performance, the intervention exerted no considerable effects on all physiological and kinematic measures. KTT did alter neuromuscular recruitment, which has potential implications for injury prevention.


Sophoridine from Sophora Flower Attenuates Ovariectomy Induced Osteoporosis through the RANKL-ERK-NFAT Pathway.
An imbalance in osteogenesis and osteoclastogenesis is a crucial pathological factor in the development of osteoporosis. Osteoclasts (OCs) play a pivotal role in osteoporosis, whose new therapy exploration has been focused on the suppression of OC formation. Sophoridine is found from the Chinese traditional food sophora flower to exhibit anti-osteoporosis capacity by screening. This study is focused on its anti-osteoporosis mechanism evaluation. The anti-osteoporosis effect of sophoridine, (15 mg kg-1 body), was evaluated in ovariectomized (OVX) mice by monitoring changes in bone histomorphometry index, formation of osteoclasts from blood-derived mononuclear cells, and changes in the synthesis of pro-osteoclastogenic cytokines. Signal pathways were investigated by QPCR, Western blot, and immunofluorescence. Sophoridine has a significant anti-osteoporosis effect in vivo, which can inhibit RANKL-induced OC formation, the appearance of OC-specific marker genes, and OC marker protein in vitro. Mechanistically, sophoridine dose- and time-dependently blocks the RANKL-induced OC formation and the activation of ERK and c-Fos as well as the induction and nucleus translocation of NFATc1. Sophora flower might be a useful alternative functional food in preventing or treating osteoporosis.


Full recovery of the NADH:ubiquinone activity of complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica by the addition of phospholipids.
NADH:ubiquinone oxidoreductase (complex I) is the largest multiprotein complex of the mitochondrial respiratory chain. His-tagged complex I purified from the strictly aerobic yeast Yarrowia lipolytica exhibited electron transfer rates from NADH to n-decylubiquinone of less than 2% when compared to turnover numbers calculated for native mitochondrial membranes from this organism. Reactivation was observed upon addition of asolectin, purified phospholipids and different phospholipid mixtures. Maximal activities of 6-7 micromol NADH min(-1) mg(-1) were observed following incubation with a mixture of 76% phosphatidylcholine, 19% phosphatidylethanolamine and 5% cardiolipin. For full reactivation, 400-500 phospholipid molecules per complex I were needed. This demonstrated that the inactivation of complex I from Y. lipolytica by general delipidation could be fully reversed simply by returning the phospholipids that had been removed during the purification procedure. Thus, our homogeneous and highly pure complex I preparation had retained its full catalytic potential and no specific, functionally essential component had been lost. As the purified enzyme was also found to contain only substoichiometric amounts of ubiquinone-9 (0.2-0.4 mol/mol), a functional requirement of this endogeneous ubiquinone could also be excluded.