Mobile intervention to promote correct hand hygiene at key times to prevent COVID-19 in the Swiss adult general population: study protocol of a multiphase optimisation strategy.
Behaviour change is key to the public health measures that have been issued in many countries worldwide to contain COVID-19. Public health measures will only take preventive effect if people adhere to them. Interventions taking health psychology approaches may promote adherence to public health measures. However, evidence from randomised controlled behaviour change trials is scarce during an ongoing pandemic. We aim to use the example of hand washing with soap to optimise and test a digital, theory-based and evidence-based behaviour change intervention to prevent the spread of COVID-19. This protocol describes the multiphase optimisation strategy for the preparation, optimisation and evaluation of a theory-based and evidence-based intervention delivered via app. The app aims to promote correct hand hygiene at key times in the adult general population. The study will be conducted in German-speaking Switzerland. The preparation phase has identified relevant behavioural determinants of hand hygiene during a pandemic from health behaviour theories and formative research with focus groups (n=8). The optimisation phase will identify the most effective and acceptable combination and sequence of three intervention modules in a parallel randomised trial (n=387) with analysis of variance (ANOVA) and regression analysis. Additionally, thematic analysis of qualitative interview data (n=15) will be used to gain insights on the feasibility, usability and satisfaction of the intervention. The evaluation phase will test the optimised intervention against an active control group in a randomised controlled trial (n=205), analysing pre-post differences and 6-month follow-up effects with ANOVA and regression analysis. The trial was approved by the Cantonal Ethics Commission Bern of the Swiss Association of Research Ethics Committees (protocol ID: 2021-00164). Final results will be presented in peer-reviewed journals and at conferences. NCT04830761.


Thermally activated breakdown in a simple polymer model.
We consider the thermally activated fragmentation of a homopolymer chain. In our simple model the dynamics of the intact chain is a Rouse one until a bond breaks and bond breakdown is considered as a first passage problem over a barrier to an absorbing boundary. Using the framework of the Wilemski-Fixman approximation we calculate activation times of individual bonds for free and grafted chains. We show that these times crucially depend on the length of the chain and the location of the bond yielding a minimum at the free chain ends. Theoretical findings are qualitatively confirmed by Brownian dynamics simulations.


[Impact of fenestration on early outcome in patients undergoing modified Fontan operation].
To compare the impact of fenestration on early outcome in patients undergoing modified Fontan operation. Data from 90 consecutive patients underwent modified Fontan operation from November 2008 to June 2013 were retrospectively analyzed. Patients were divided into fenestrated group (49 patients) and non-fenestrated group (41 patients) and early outcome post operation was compared between the two groups. Anatomy, age, gender, body weight and disease classifications were similar between the two groups (all P > 0.05). Postoperative central venous pressure was (11.4 ± 4.1) mmHg (1 mmHg = 0.133 kPa) in fenestrated group and (12.1 ± 3.8) mmHg in non-fenestrated group (P = 0.894). The duration of chest tube drainage was (11.1 ± 9.2) day in fenestrated group and (15.0 ± 10.7) day in non-fenestrated group (P = 0.160). Volume of pleural drainage was 772.0 (411.5-1 971.5) ml in fenestrated group and 1 259.0 (571.0-2 647.5) ml in non-fenestrated group (P = 0.214). Duration of ICU stay was 24.0 (18.0-40.0) day in fenestrated group and 24.0 (19.0-36.0) day in non-fenestrated group (P = 0.751). The time of respirator use was 9.0 (6.0-15.0) hours in fenestrated group and 8.0 (6.0-16.0) hours in non-fenestrated group (P = 0.951). Duration of hospital stay was significantly longer in fenestrated group than in non-fenestrated group ((32.7 ± 23.0) day vs. (27.8 ± 12.6) day, P = 0.025). One patient (2.0%) died of low cardiac output syndrome in fenestrated group and 1 patient (2.4%) experienced hydropericardium in non-fenestrated group. The incidence rate of complications (P = 0.898) and mortality (P = 1.000) were similar between the two groups. Early outcome is similar for patients undergoing the modified Fontan operation with or without fenestration.


Population movements and the HIV cascade in recently diagnosed patients at the French Guiana -Suriname border.
Border areas are particular "hot spots" generating high levels of HIV vulnerability and facing great challenges to control epidemics. The objective of this study is to describe the sociodemographic, clinical and biological profiles of newly HIV diagnosed people at the French Guiana - Suriname border, to construct an HIV care cascade and compare it with the Surinamese one. HIV-patients aged over 15 years newly diagnosed in western French Guiana in 2011 and 2012 were included in a retrospective cohort study. Patients were identified using different sources (n = 121). The male-to-female ratio was 0.8, 85% of the patients were of foreign origin, 72% were undocumented migrants, 21% were living in Suriname and 48% had baseline CD4 cell counts <200 cells/mm3. After one year, 34% were lost to follow-up, 54% received treatment, 34% had controlled viremia and 6% died. We observed a disappointing HIV cascade, like that of Suriname, requiring to develop a coordinated healthcare offer on both sides of the border. Targeted efforts through a bi-national collaboration are needed to address the specific issues of cross-border patients to reach the 90*3 UNAIDS's diagnosis, link to care and treatment targets and better control the local epidemic.


M2 Polarization of Monocytes-Macrophages Is a Hallmark of Indian Post Kala-Azar Dermal Leishmaniasis.
The high level of functional diversity and plasticity in monocytes/macrophages has been defined within in vitro systems as M1 (classically activated), M2 (alternatively activated) and deactivated macrophages, of which the latter two subtypes are associated with suppression of cell mediated immunity, that confers susceptibility to intracellular infection. Although the Leishmania parasite modulates macrophage functions to ensure its survival, what remains an unanswered yet pertinent question is whether these macrophages are deactivated or alternatively activated. This study aimed to characterize the functional plasticity and polarization of monocytes/macrophages and delineate their importance in the immunopathogenesis of Post kala-azar dermal leishmaniasis (PKDL), a chronic dermatosis of human leishmaniasis. Monocytes from PKDL patients showed a decreased expression of TLR-2/4, along with an attenuated generation of reactive oxidative/nitrosative species. At disease presentation, an increased mRNA expression of classical M2 markers CD206, ARG1 and PPARG in monocytes and lesional macrophages indicated M2 polarization of macrophages which was corroborated by increased expression of CD206 and arginase-1. Furthermore, altered vitamin D signaling was a key feature in PKDL, as disease presentation was associated with raised plasma levels of monohydroxylated vitamin D3 and vitamin D3- associated genes, features of M2 polarization. Taken together, in PKDL, monocyte/macrophage subsets appear to be alternatively activated, a phenotype that might sustain disease chronicity. Importantly, repolarization of these monocytes to M1 by antileishmanial drugs suggests that switching from M2 to M1 phenotype might represent a therapeutic opportunity, worthy of future pharmacological consideration.


Extradural administration of morphine and bupivacaine. A controlled comparison.
Analgesia, following operation, was provided by the extradural administration of morphine or bupivacaine in 24 patients, in a double-blind, randomized, cross-over study. Observations were made of vital signs, peak expiratory flow rate (PEFR), quality and duration of pain relief and the occurrence of adverse effects. Vital signs were little affected by morphine, but hypotension requiring active treatment occurred in three patients following the administration of bupivacaine. The PEFR was improved about equally by each drug, and the improvement was significant compared with control values (P less than 0.001). Pain relief as judged by the linear analogue scale was significantly better following bupivacaine than after morphine (P less than 0.001), but the pain score system, while showing effective pain relief in most patients with both drugs, did not demonstrate a significant difference between them. The duration of effect of morphine was significantly longer (P less than 0.05) than that of bupivacaine. Adverse effects, other than bupivacaine-induced hypotension, were not serious.


Hemorrhagic necrosis of pheochromocytoma associated with phentolamine administration.
A case of ruptured pheochromocytoma is presented, the pathophysiology discussed, and the literature reviewed. Evidence is presented that the use of alpha-adrenergic blockade in general, and phentolamine in particular, may predispose to this complication. Twelve cases of massive hemorrhagic necrosis with or without rupture were found in the literature, including the present case. Six had no operation; one survived. Six had immediate operation; 4 survived. An additional case of hemorrhage into a small pheochromocytoma following phentolamine is presented. This tumor was neither ruptured nor massively necrotic, but the case supports the hypothesis that alpha-adrenergic blockade may cause hemorrhage within the pheochromocytoma.


Surgical management of bilateral diaphragmatic paralysis in a dog.
Bilateral diaphragmatic paralysis of uncertain cause developed in a 3-month-old Golden Retriever. A surgical procedure for tightening the diaphragmatic muscle was used to help alleviate the dog's respiratory distress. During thoracotomy, the central tendon of the diaphragm was plicated, using an interlocking suture pattern. The dog improved after surgery, and although complete recovery from paralysis was achieved only on one side, the dog has remained clinically normal 1 year after surgery.


The effects of NaNbO3 particle size on the photocatalytic activity for 2-propanol photodegradation.
The effects of NaNbO3 particle size on the photocatalytic activity were investigated by taking gaseous 2-propanol photodegradation as a model reaction. By varying the loading amount of precursors onto mesoporous SBA-15, nanocrystalline NaNbO3 samples with particle sizes ranging from 3 to 50 nm were successfully synthesized. The particle size and surface area value of templated NaNbO3 change systematically with the change in loading amount of the precursors. The physicochemical characteristics of the samples were examined by techniques such as XRD, SEM, TEM, Raman spectroscopy, and UV-visible diffuse reflectance spectroscopy. The optimum NaNbO3 particle size for the highest photocatalytic activity was found to be 30 nm. The current study also revealed that the NaNbO3 photocatalyst is structure sensitive for 2-propanol photodegradation. The density of active sites on the sample surface decreases as the particle size decreases. Competing effects of factors such as the surface area, changes in electronic structure, defect density, and concentration of reaction active sites determine the optimum particle size of NaNbO3.


1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP)-Cysteine Conjugates: Metabolic Formation and Binding to Cellular DNA.
1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that the reaction of 1-CHO-DHP with cysteine generated four identified products. By mass and 1H NMR spectral analyses, these products are cysteinyl-[2'-S-7]-1-CHO-DHP (P2), cysteinyl-[3'-N-7]-1-CHO-DHP (P3), 7-keto-DHP (P4), and 1-cysteinylimino-DHP (P5). These four compounds were also formed from the incubation of 1-CHO-DHP in HepG2 cells. Compounds P3 and P5 were interconvertible in acetonitrile and water. Incubation of P2 in HepG2 cells generated the four DHP-dG and -dA adducts that we propose to be potential common biomarkers of pyrrolizidine alkaloids exposure and pyrrolizidine alkaloids-induced liver tumor initiation. These four DHP-DNA adducts were also formed from the incubation of a mixture of P3 and P5 in HepG2 cells but not from the incubation with 7-keto-DHP. From the reaction of 1-CHO-DHP with glutathione, only trace amounts of the glutathione-1-CHO-DHP adduct were detected, with the structure unable to be characterized.


Scanning tunneling microscopy study of the possible topological surface states in BiTeCl.
Recently, the non-centrosymmetric bismuth tellurohalides such as BiTeCl are being studied as possible candidates for topological insulators. While some photoemission studies showed that BiTeCl is an inversion asymmetric topological insulator, others showed that it is a normal semiconductor with Rashba splitting. Meanwhile, first-principle calculations have failed to confirm the existence of topological surface states in BiTeCl so far. Therefore, the topological nature of BiTeCl requires further investigation. Here we report a low-temperature scanning tunneling microscopy study on the surface states of BiTeCl single crystals. On the tellurium (Te) -terminated surfaces with relatively low defect density, evidence for topological surface states is observed in the quasi-particle interference patterns, both in the anisotropy of the scattering vectors and the fast decay of the interference near the step edges. Meanwhile, on the samples with much higher defect densities, we observed surface states that behave differently. Our results may help to resolve the current controversy on the topological nature of BiTeCl.


Wegener's granulomatosis manifested as a perirectal abscess.
Wegener's granulomatosis is a serious systemic vasculitis that needs to be diagnosed promptly to limit morbidity and mortality. Atypical presentations of this disease are not uncommon. This case illustrates a rare manifestation of Wegener's granulomatosis (ie, perirectal abscess) and the value of the antineutrophil cytoplasmic antibody in conjunction with supporting pathology.


[An unusual case of Kartagener's syndrome associated with rheumatoid arthritis].
We observed a 56-year-old woman with Kartagener's syndrome and severe seropositive rheumatoid arthritis. This is the third case of such association in the world literature and a second one being diagnosed in our Department. The patient was also as the previous one a carrier of HLA DR1 and B27 antigens. An electromicroscopic study showed normal bronchial cilia in contrast to classical course of the disease. A number of immunological disturbances were observed, especially defective granulocyte function. We suggest that the severe course of rheumatoid arthritis may be related to the chronic stimulation of immune system by microbes continuously present in the patients airways.


Regional ventricular dysfunction in coronary artery disease.
Percentage asynergy, ejection fraction (EF), left ventricular end diastolic pressure (LVEDP) and the site of coronary artery narrowing or obstruction were measured in 69 patients with significant coronary artery disease. Complete obstruction in the first third of the left anterior descending artery (LAD) produced a mean asynergy of 49% associated with an ejection fraction of 40% and a LVEDP of 19mm Hg. The extent of asynergy was modified by the nature of the underlying coronary artery anatomy and the protective circulation. Complete obstruction in the main right coronary artery produced a mean asynergy of 20% associated with an EF of 67% and LVEDP of 6 mm Hg. Complete obstruction in the first third of the circumflex artery produced a mean asynergy of 15% associated with an EF or 74% and LVEDP of 14mm Hg. Subtotal obstruction in the first third of the LAD produced a mean asynergy of 25% associated with an EF of 62% and LVEDP of 7mm Hg. The damage produced by a LAD obstruction was extensive while that of a right or circumflex obstruction was mild. Patients always had a high percentage asynergy after two episodes of myocardial infarction. A negative linear relationship was found between percentage asynergy and EF. There was a rough positive linear relationship between LVEDP and percentage asynergy.


Chromatin mapping identifies BasR, a key regulator of bacteria-triggered production of fungal secondary metabolites.
The eukaryotic epigenetic machinery can be modified by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. We discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster in the fungus Aspergillus nidulans. Using this model, we aim understanding mechanisms of microbial communication based on bacteria-triggered chromatin modification. Using genome-wide ChIP-seq analysis of acetylated histone H3, we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus and relate changes in the acetylation to that in the fungal transcriptome. Differentially acetylated histones were detected in genes involved in secondary metabolism, in amino acid and nitrogen metabolism, in signaling, and encoding transcription factors. Further molecular analyses identified the Myb-like transcription factor BasR as the regulatory node for transduction of the bacterial signal in the fungus and show its function is conserved in other Aspergillus species.


Urinary cadmium levels in active and retired coal miners.
A meta-analysis, based upon 24 publications, showed a significantly elevated risk for urinary bladder cancer amongst miners. In European underground hard coal mining areas, an increased risk for urinary bladder cancer development was noted among hard coal miners, in particular in three investigations in the greater Dortmund area. However, the cause remains unclear. As cadmium (Cd), which was reported to be a bladder carcinogen in humans and is a constituent of coal, the aim of this study was to determine urinary Cd levels in active and retired hard coal miners and assess whether hard coal miners demonstrated elevated metal levels. In total, 103 retired and 25 active hard coal miners as well as 18 controls without any history of hard coal mining were investigated for urinary Cd levels. Urinary Cd concentrations, in addition to other elements, were analyzed in spot urines by ICP-MS-based multi-element analysis in a Department for Forensic and Clinical Toxicology. Limit of detection (LOD) for Cd was 0.5 μg/L. Reference value for occupationally non-exposed working age population was 0.8 μg/L. In total, 49% of all underground coal miners were exposed to coal dust, 12% to grinded rock, and 39% to both. Urinary Cd levels in retired as well as active coal miners and controls were clearly below the Biological Exposure Index. Urinary Cd concentration is a suitable biomarker to evaluate the metallic load of the body, as the half-life is > than 10 years. The detected urinary Cd levels in retired and active coal miners indicated underground hard coal miners were not apparently exposed to Cd to a occupationally-relevant concentration.


Single-dose antimicrobial therapy for urinary tract infections in women.
Single-dose antimicrobial therapy for uncomplicated urinary tract inductions in women has been reported and evaluated by several investigators. A review of the results of these studies suggest that amoxicillin, sulfisoxazole, and trimethoprim-sulfamethoxazole are effective single-dose regimens in this setting. These results should not be extrapolated to other populations, such as pregnant women or children, or to other antimicrobial agents. The limited data available suggest that cephalosporins are less effective than the regimens recommended. When the infecting organism is sensitive, failure to eradicate bacteriuria with one of these single-dose regimens may be indicative of a more invasive infection, perhaps in the kidney.


TransgeneOmics--A transgenic platform for protein localization based function exploration.
The localization of a protein is intrinsically linked to its role in the structural and functional organization of the cell. Advances in transgenic technology have streamlined the use of protein localization as a function discovery tool. Here we review the use of large genomic DNA constructs such as bacterial artificial chromosomes as a transgenic platform for systematic tag-based protein function exploration.


Alternative remedies for insomnia: a proposed method for personalized therapeutic trials.
Insomnia is a common symptom, with chronic insomnia being diagnosed in 5-10% of adults. Although many insomnia patients use prescription therapy for insomnia, the health benefits remain uncertain and adverse risks remain a concern. While similar effectiveness and risk concerns exist for herbal remedies, many individuals turn to such alternatives to prescriptions for insomnia. Like prescription hypnotics, herbal remedies that have undergone clinical testing often show subjective sleep improvements that exceed objective measures, which may relate to interindividual heterogeneity and/or placebo effects. Response heterogeneity can undermine traditional randomized trial approaches, which in some fields has prompted a shift toward stratified trials based on genotype or phenotype, or the so-called n-of-1 method of testing placebo versus active drug in within-person alternating blocks. We reviewed six independent compendiums of herbal agents to assemble a group of over 70 reported to benefit sleep. To bridge the gap between the unfeasible expectation of formal evidence in this space and the reality of common self-medication by those with insomnia, we propose a method for guided self-testing that overcomes certain operational barriers related to inter- and intraindividual sources of phenotypic variability. Patient-chosen outcomes drive a general statistical model that allows personalized self-assessment that can augment the open-label nature of routine practice. The potential advantages of this method include flexibility to implement for other (nonherbal) insomnia interventions.


Enhanced expression of insulin-like growth factor-binding protein-I in the fasted rat: the effects of insulin and growth hormone administration.
The effect of fasting on insulin-like growth factor-binding protein-1 (IGFBP-1) expression was examined in the rat. Food deprivation for a period of 24 h resulted in a 9.5 +/- 2.0-fold increase in hepatic IGFBP-1 mRNA abundance (P less than 0.001). An increase in circulating IGFBP-1 in sera from fasted rats was demonstrated by immunoblotting, and an increased abundance of a 30-kDa IGFBP in sera from fasted rats was apparent when [125I]IGF-I was used in ligand blotting experiments. Refeeding resulted in a prompt decline in hepatic IGFBP-1 mRNA. Administration of insulin (0.5-4 U, ip) to fasted rats resulted in profound hypoglycemia, but either increased or had no significant effect on hepatic IGFBP-1 mRNA abundance. In contrast, administration of human GH (hGH; 100 micrograms, ip) resulted in a prompt decline in hepatic IGFBP-1 mRNA, followed by a late rebound in IGFBP-1 mRNA to levels greater than those in fasted controls. Furthermore, hepatic IGFBP-1 mRNA levels were significantly lower in hGH-treated (100 micrograms every 8 h) food-deprived rats than in saline-treated food-deprived rats (2.25 +/- 1.55- vs. 8.99 +/- 3.80-fold increase; P less than 0.005). Similar changes were observed when serum IGFBP-1 was quantitated by immunoblotting. The effects of GH could not be explained by secondary hyperinsulinism, since no significant increase in insulin levels was observed in GH-treated rats. From these observations we conclude the enhanced expression of IGFBP-1 in the food-deprived rat may be a consequence of GH deficiency rather than insulin deficiency.


Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress.
Hypoxia is increasingly recognized as an important physiological driving force. A specific transcriptional program, induced by a decrease in oxygen (O2) availability, for example, inspiratory hypoxia at high altitude, allows cells to adapt to lower O2 and limited energy metabolism. This transcriptional program is partly controlled by and partly independent of hypoxia-inducible factors. Remarkably, this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise, leading to a relative decrease in O2 supply, compared to the acutely augmented O2 requirement. We have coined the term "functional hypoxia" for this important demand-responsive, relative reduction in O2 availability. Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial "brain hardware upgrade," underlying advanced performance. Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes, which can be imitated by recombinant human erythropoietin treatment. This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function. It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease. Finally, it sketches a planned multistep pilot study in healthy volunteers and first patients, about to start, aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.


Embryonic development of the mammalian caudal neural tube.
In the literature, some controversy still exists about the embryonic developmental processes involved in the formation of the caudal neural tube. Therefore, a three-dimensional and histological study concerning the normal development of the caudal neural tube was performed on both mouse and human embryos. Three developmental processes can be distinguished in caudal neural tube development: caudal neuropore closure, secondary neurulation, and degeneration and differentiation of the secondary neural tube. Caudal neuropore closure occurs at the level of somite 32-34 in both species. Therefore, primary neurulation leads to the formation of all spinal cord segments and ganglia. Secondary neurulation involves cell deposition from a cluster of neurectodermal cells at the caudal end of the closed neural tube, directly around a lumen, the lumen always in contact with the lumen of the primary neural tube. This process leads only to the formation of the primordia of the filum terminale and ventriculus terminalis and, possibly, part of the conus medullaris. Secondary neurulation is followed by a period characterized by degeneration and differentiation of the secondary neural tube. Its lumen and neural tissue will disappear, whereas part of the secondary neurectodermal cells differentiate to a fibrous layer comparable and continuous with the marginal layer of the primary neural tube. This fibrous layer represents the future filum terminale. The embryological processes indicated above can be helpful in the interpretation of congenital anomalies affecting the caudal spinal cord and spine.


Analysis of multisite surface electromyography characteristics of pelvic floor muscles in postpartum patients with diastasis recti abdominis.
To explore the electrophysiological characteristics of the independent muscles in the pelvic floor muscle (PFM) group of postpartum women with diastasis recti abdominis (DRA) and analyze the correlation between the rectus abdominis interval and PFM function. A total of 133 women who underwent postpartum re-examination from August 2021 to July 2022 were collected. The participants were divided into DRA and control groups based on the occurrence of DRA on ultrasonography. General data of the participants were collected, and the multisite surface electromyography (sEMG) assessment of the PFMs was performed using a intravaginal novel airbag-type stretchable electrode array device developed by the team. The sEMG characteristics of the different PFMs in the two groups were compared, and the correlation between the maximum rectus abdominis interval and the sEMG parameters of different PFMs was analyzed. There were no differences in the baseline demographics and incidence of pelvic floor dysfunction between the two groups (p > 0.05). The mean amplitude of vaginal sphincter endurance contraction in the DRA group was significantly lower than that in the control group (28.44 ± 15.59 vs. 22.03 [12.22, 28.00], p < 0.05). Spearman's rank correlation analysis showed a weak negative correlation between the maximum rectus abdominis interval and the endurance contraction mean amplitude of the urethral and external anal sphincters (r = -0.173, -0.217, p < 0.05). Patients with DRA had weakened PFM endurance, and there was a weak negative correlation between the maximum rectus abdominis interval and the endurance contraction mean amplitude of the PFM.


Monocyte chemotactic protein-1 regulates voltage-gated K+ channels and macrophage transmigration.
Progressive human immunodeficiency virus (HIV)-1 infection and virus-induced neuroinflammatory responses effectuate monocyte-macrophage transmigration across the blood-brain barrier (BBB). A key factor in mediating these events is monocyte chemotactic protein-1 (MCP-1). Upregulated glial-derived MCP-1 in HIV-1-infected brain tissues generates a gradient for monocyte recruitment into the nervous system. We posit that the inter-relationships between MCP-1, voltage-gated ion channels, cell shape and volume, and cell mobility underlie monocyte transmigration across the BBB. In this regard, MCP-1 serves both as a chemoattractant and an inducer of monocyte-macrophage ion flux affecting cell shape and mobility. To address this hypothesis, MCP-1-treated bone marrow-derived macrophages (BMM) were analyzed for gene and protein expression, electrophysiology, and capacity to migrate across a laboratory constructed BBB. MCP-1 enhanced K+ channel gene (KCNA3) and channel protein expression. Electrophysiological studies revealed that MCP-1 increased outward K+ currents in a dose-dependent manner. In vitro studies demonstrated that MCP-1 increased BMM migration across an artificial BBB, and the MCP-1-induced BMM migration was blocked by tetraethylammonium, a voltage-gated K+ channel blocker. Together these data demonstrated that MCP-1 affects macrophage migratory movement through regulation of voltage-gated K+ channels and, as such, provides a novel therapeutic strategy for neuroAIDS.


Anthrax vaccination in a military population before the war in Iraq: side effects and informed choice.
To assess any health consequences of the anthrax vaccination programme in UK Armed Forces deployed to Iraq. Data were collected from two samples simultaneously. The first was 5302 randomly selected UK service personnel. The second was 607 service personnel involved in a longitudinal study, where pre-vaccination health had previously been collected. Both samples were offered the anthrax vaccination before they deployed to Iraq in 2003 and subsequently following their service in Iraq. Participants completed a detailed questionnaire, including a range of health outcomes, receipt of the anthrax vaccination and quality of choice. Seventy-two percent of the combined sample had the anthrax vaccination. Being a member of the Army, a commissioned officer or a reservist was associated with higher uptake. No differences in self-reported health were observed between those who did and did not receive the vaccination. For participants who accepted the vaccination, we found an association between making an uninformed choice and adverse health. After adjustment for baseline health in the longitudinal cohort these associations remained significant. Anthrax vaccination used by the UK Armed Forces in preparation for the Iraq War has not resulted in adverse health outcomes. However, of those who did accept the vaccination, reported side effects were related to whether acceptance of vaccination was perceived to be informed. Improving the quality of choice may improve self-reported ill health.


p38MAPK, ERK and PI3K signaling pathways are involved in C5a-primed neutrophils for ANCA-mediated activation.
The complement system is one of the important contributing factors in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). C5a and the neutrophil C5a receptor play a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. The current study further investigated the signaling pathways of C5a-mediated priming of human neutrophils for ANCA-induced neutrophil activation. The effects of the p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190), extracellular signal-regulated kinase (ERK) inhibitor (PD98059), c-Jun N-terminal kinase (JNK) inhibitor (6o) and phosphoinositol 3-kinase (PI3K) inhibitor (LY294002) were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on C5a-induced increase in expression of membrane-bound PR3 (mPR3) on neutrophils. For C5a-primed neutrophils for MPO-ANCA-induced respiratory burst, the mean fluorescence intensity (MFI) value was 254.8±67.1, which decreased to 203.6±60.3, 204.4±36.7, 202.4±49.9 and 188±47.9 upon pre-incubation with SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.05), respectively. For PR3-ANCA-positive IgG, the MFI value increased in C5a-primed neutrophils, which decreased upon pre-incubation with above-mentioned inhibitors. The lactoferrin concentration increased in C5a-primed neutrophils induced by MPO or PR3-ANCA-positive IgG supernatant and decreased upon pre-incubation with above-mentioned three inhibitors. mPR3 expression increased from 923.3±182.4 in untreated cells to 1278.3±299.3 after C5a treatment and decreased to 1069.9±188.9, 1100±238.2, 1092.3±231.8 and 1053.9±200.3 by SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.01), respectively. Activation of p38MAPK, ERK and PI3K are important steps in the translocation of ANCA antigens and C5a-induced activation of neutrophils by ANCA.


Choice of LECS Procedure for Benign and Malignant Gastric Tumors.
Laparoscopic endoscopic cooperative surgery (LECS) refers to the endoscopic dissection of the mucosal or submucosal layers with laparoscopic seromuscular resection. We recommend a treatment algorithm for the LECS procedure for gastric benign tumors according to the protruding type. In the exophytic type, endoscopic-assisted wedge resection can be performed. In the endophytic type, endoscopic-assisted wedge resection of the anterior wall is relatively easy to perform, and endoscopic-assisted transgastric resection, laparoscopic-assisted intragastric surgery, or single-incision intragastric resection in the posterior wall and esophagogastric junction (EG Jx) can be attempted. We propose an algorithm for the LECS procedure for early gastric cancer according to the tumor location. The endoscopic submucosal dissection (ESD) procedure can be adapted for all areas of the stomach, and single-incision ESD can be performed in the mid to high body and the EG Jx. In full-thickness gastric resection, laparoscopy-assisted endoscopic full-thickness resection can be adapted for the entire area of the stomach, but it cannot be applied to the pyloric and EG Jx. In conclusion, surgeons need to select the LECS procedure according to tumor type, tumor location, the surgeon's individual experience, and the situation of the institution while also considering the advantages and disadvantages of each procedure.


The cryo-EM structure of the Plasmodium falciparum 20S proteasome and its use in the fight against malaria.
Plasmodium falciparum is the parasite responsible for the most severe form of malaria. Its increasing resistance to existing antimalarials represents a major threat to human health and urges the development of new therapeutic strategies to fight malaria. The proteasome is a protease complex essential in all eukaryotes. Accordingly, inhibition of the Plasmodium 20S proteasome is highly toxic for the parasite at all of its infective and developmental stages. Proteasome inhibitors have antimalarial potential both as curative and transmission blocking agents, but in order to have therapeutic application, they must specifically target the Plasmodium proteasome and not its human counterpart. X-ray crystallography has been widely used to determine structures of yeast and mammalian 20S proteasomes with ligands. However, crystallisation of the Plasmodium proteasome is challenging, as only small quantities of the complex can be directly purified from the parasite. Furthermore, most X-ray structures of proteasome-inhibitor complexes require soaking of crystals with high concentrations of ligand, thus preventing analysis of inhibitor subunit specificity. Instead we chose to determine the Plasmodium falciparum 20S proteasome structure, in the presence of a new rationally designed parasite-specific inhibitor, by high-resolution electron cryo-microscopy and single particle analysis. The resulting map, at a resolution of about 3.6 Å, allows a direct molecular analysis of inhibitor/enzyme interactions. Here we present an overview of this structure, and how it provides valuable information that can be used to assist in the design of improved proteasome inhibitors with the potential to be developed as next-generation antimalarial drugs.


A forward modelling approach for the estimation of oxygen extraction fraction by calibrated fMRI.
The measurement of the absolute rate of cerebral metabolic oxygen consumption (CMRO2) is likely to offer a valuable biomarker in many brain diseases and could prove to be important in our understanding of neural function. As such there is significant interest in developing robust MRI techniques that can quantify CMRO2 non-invasively. One potential MRI method for the measurement of CMRO2 is via the combination of fMRI and cerebral blood flow (CBF) data acquired during periods of hypercapnic and hyperoxic challenges. This method is based on the combination of two, previously independent, signal calibration techniques. As such analysis of the data has been approached in a stepwise manner, feeding the results of one calibration experiment into the next. Analysing the data in this manner can result in unstable estimates of the output parameter (CMRO2), due to the propagation of errors along the analysis pipeline. Here we present a forward modelling approach that estimates all the model parameters in a one-step solution. The method is implemented using a regularized non-linear least squares approach to provide a robust and computationally efficient solution. The proposed framework is compared with previous analytical approaches using modelling studies and in vivo acquisitions in healthy volunteers (n=10). The stability of parameter estimates is demonstrated to be superior to previous methods (both in vivo and in simulation). In vivo estimates made with the proposed framework also show better agreement with expected physiological variation, demonstrating a strong negative correlation between baseline CBF and oxygen extraction fraction. It is anticipated that the proposed analysis framework will increase the reliability of absolute CMRO2 measurements made with calibrated BOLD.


An integrated wave-effects model for an underwater explosion bubble.
A model for a moderately deep underwater explosion bubble is developed that integrates the shock wave and oscillation phases of the motion. A hyperacoustic relationship is formulated that relates bubble volume acceleration to far-field pressure profile during the shock-wave phase, thereby providing initial conditions for the subsequent oscillation phase. For the latter, equations for bubble-surface response are derived that include wave effects in both the external liquid and the internal gas. The equations are then specialized to the case of a spherical bubble, and bubble-surface displacement histories are calculated for dilational and translational motion. Agreement between these histories and experimental data is found to be substantially better than that produced by previous models.


A new administration form of the nasal decongestant oxymetazoline: a study on the change of ostial patency in healthy individuals.
A new administration form of the nasal decongestant oxymetazoline and the effect on patency of the maxillary ostium was investigated in five healthy volunteers. Registration and comparison of the equivalent diameter after administration of placebo spray and oxymetazoline spray, placebo solution and oxymetazoline solution were performed. It is our impression that administration of solution with the new spring-bellows container compared to spray oxymetazoline, is a more effective way of increasing the equivalent diameter of the maxillary ostium.


Bifurcation of conical magnetic field.
A strong magnetic field develops via bifurcation in a flow with accretion, as analytical and numerical solutions of magnetohydrodynamic equations show. Examples are swirl-free and swirling jets, and thermal convection near a point source of heat and gravity. The features of the resulting conical similarity magnetic flows are analogous to those observed in cosmic jets.


Relationship between oxygen saturation, gestational age, and level of oral feeding skills in preterm infants.
To correlate the peripheral oxygen saturation with gestational age and the level of oral feeding skills in the introduction of oral feeding in preterm infants. This is a cross-sectional, quantitative study whose sample was composed of 169 clinically stable preterm infants. Peripheral oxygen saturation was assessed before and after introduction of oral feeding. The preterm infants were stratified into three groups based on their gestational age at birth: 26-29, 30-33, and 34-36 weeks. The preterm infants were classified into four levels according to their oral feeding skill and resistance. No differences in oxygen saturation were observed between the strata of gestational age and between the levels of oral feeding skill. Differences were observed in the groups of preterm infants aged 30-33 weeks (p=0.04) and 34-36 weeks (p=0.02) and on the level I of oral feeding skills (p=0.04) when oxygen saturation was compared at pre- and post-first oral feeding. Significant correlations (p<0.001) were found between gestational age and the levels of oral feeding skills (r=0.38); in Group A, between gestational age and oxygen saturation before the first oral feeding (r=0.83); in Group B, between the level of oral feeding skill and oxygen saturation before the first oral feeding (r=0.26) and between level of oral feeding skill and gestational age (r=0.26). Correlation was found for peripheral oxygen saturation when compared with gestational age and with the level of oral feeding skills.


Building a Scaffold for Arteriovenous Fistula Maturation: Unravelling the Role of the Extracellular Matrix.
Vascular access is the lifeline for patients receiving haemodialysis as kidney replacement therapy. As a surgically created arteriovenous fistula (AVF) provides a high-flow conduit suitable for cannulation, it remains the vascular access of choice. In order to use an AVF successfully, the luminal diameter and the vessel wall of the venous outflow tract have to increase. This process is referred to as AVF maturation. AVF non-maturation is an important limitation of AVFs that contributes to their poor primary patency rates. To date, there is no clear overview of the overall role of the extracellular matrix (ECM) in AVF maturation. The ECM is essential for vascular functioning, as it provides structural and mechanical strength and communicates with vascular cells to regulate their differentiation and proliferation. Thus, the ECM is involved in multiple processes that regulate AVF maturation, and it is essential to study its anatomy and vascular response to AVF surgery to define therapeutic targets to improve AVF maturation. In this review, we discuss the composition of both the arterial and venous ECM and its incorporation in the three vessel layers: the tunica intima, media, and adventitia. Furthermore, we examine the effect of chronic kidney failure on the vasculature, the timing of ECM remodelling post-AVF surgery, and current ECM interventions to improve AVF maturation. Lastly, the suitability of ECM interventions as a therapeutic target for AVF maturation will be discussed.


5,5'-Diphenylhydantoin (dilantin) decreases cytosol and specific nuclear 3,5,3'-triiodothyronine binding in rat anterior pituitary in vivo and in cultured GC cells.
To study the effect of 5,5'-diphenylhydantoin (DPH) on cellular and specific nuclear T3 binding, we have studied the effect of DPH on binding of T3 by rat anterior pituitary in vivo and in cultured GC cells, a rat pituitary tumor cell line that secretes GH. As determined by in vivo displacement techniques, DPH (10 mg/100 g BW daily for 3 days or as a single dose of 20 mg/100 g BW) resulted in a significant decrease in T3 binding by cytosol and specific nuclear sites in rat anterior pituitary. In cultured GC cells, the addition of 400 muM DPH resulted in a 70-80% decrease in specific nuclear T3 binding and a 40-50% decrease in cytosol T3 binding without affecting the rate of T3 equilibration. The effect of DPH was dose dependent between 10 and 400 muM. Similar effects, but of a smaller magnitude, were noted in studies of isolated GC cell nuclei. The maximum percent decrease in specific T3 binding in isolated nuclei was 22% at 400 muM DPH. Scatchard analysis suggested that the DPH-induced decrease in specific nuclear T3 binding was competitive when measured in intact cells; the interaction between DPH and T3 appeared noncompetitive in studies of isolated GC cell nuclei. Other experiments indicated that DPH did not affect the exit rate of T3 from either the cytosol or specific nuclear compartments. The present studies suggest that DPH may decrease the fractional rate of entry of T3 into cultured cells and also inhibit binding of T3 by nuclear receptors. The similarity of effects observed in cultured GC cells and in rat anterior pituitary in in vivo studies suggests that studies in GC cells should be useful for examination of biological changes that result from the interaction between DPH and T3 at nuclear binding sites.


Vitamin D status in renal transplant recipients.
Vitamin D plays an important role in calcium homeostasis. Renal transplant recipients may be more susceptible to reduced levels because of decreased sun exposure and steroid therapy. This study aimed to determine vitamin D status after renal transplantation and its effect on parathyroid hormone (PTH) and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D levels (25-OHD) in 244 renal transplant recipients, divided into two groups, 104 recently transplanted (less than 1 year) and 140 long-term. Vitamin D status was defined according to NKF/KDOQI guidelines. Mean 25-OHD levels were 33 +/- 19 nmol/L and 42 +/- 20 nmol/L, respectively, for the recent and long-term transplant recipients. Vitamin D insufficiency was present in 29% and 43%, deficiency in 56% and 46% and severe deficiency in 12% and 5%, respectively. An inverse correlation was found between logPTH and 25-OHD (r=-0.2, p= 0.019) in long-term but not in recently transplanted patients. No correlation was found between 25-OHD levels and BMD. Hypercalcaemia was present in 40% of the recently transplanted recipients and 25% of the long-term. In conclusion 25-OHD was low in virtually all of our renal transplant recipients and may aggravate secondary hyperparathyroidism, but its correction may be difficult in patients with hypercalcaemia.


Acute Cartilage Injury Induced by Trans-Articular Sutures.
To determine the extent of acute cartilage injury by using trans-articular sutures. Five different absorbable sutures, monofilament polydioxanone (PDS) and braided polyglactin (Vicryl), were compared on viable human osteochondral explants. An atraumatic needle with 30 cm of thread was advanced through the cartilage with the final thread left in the tissue. A representative 300 μm transversal slice from the cartilage midportion was stained with Live/Dead probes, scanned under the confocal laser microscope, and analyzed for the diameters of (a) central "Black zone" without any cells, representing in situ thread thickness and (b) "Green zone," including the closest Live cells, representing the maximum injury to the tissue. The exact diameters of suture needles and threads were separately measured under an optical microscope. The diameters of the Black (from 144 to 219 µm) and the Green zones (from 282 to 487 µm) varied between the different sutures (P < 0.001). The Green/Black zone ratio remained relatively constant (from 1.9 to 2.2; P = 0.767). A positive correlation between thread diameters and PDS suturing material, toward the Black and Green zone, was established, but needle diameters did not reveal any influence on the zones. The width of acute cartilage injury induced by the trans-articular sutures is about twice the thread thickness inside of the tissue. Less compressible monofilament PDS induced wider tissue injury in comparison to a softer braided Vicryl. Needle diameter did not correlate to the extent of acute cartilage injury.


Abnormal patterns of colonic mucin secretion after ureterosigmoidostomy.
Colonic epithelial mucin was investigated histochemically in biopsy specimens from a group of patients who had undergone ureterosigmoidostomy. For comparison, colonic biopsy samples from uninvolved mucosa adjacent to carcinomas from another group of patients and from a group of patients undergoing sigmoidoscopy for hemorrhoids were also studied. The high-iron diamine-alcian blue (HID-AB; pH 2.5) method was used, and the proportions of HID-positive and AB-positive cells were assessed semiquantitatively. In both ureterosigmoidostomy and cancer groups, highly significant increases in the proportions of AB-positive cells (sialomucins) were observed, particularly in the middle and lower segments of the crypts. Ureterosigmoidostomy introduces a high risk for the development of colonic carcinoma. Morphologic features that could account for such a high risk were investigated, and an abnormal pattern of colonic mucin secretion after ureterosigmoidostomy was demonstrated. Although this abnormality cannot be related specifically to ureterosigmoidostomy, data from the present investigation suggest that histochemical studies of colonic specimens from patients who have undergone ureterosigmoidostomy may provide a useful tool for follow-up studies.


[A retrospective study of the perioperative complications following whole lung lavage in the treatment of pulmonary alveolar proteinosis].
Objective: To evaluate the safety of the procedures of whole lung lavage(WLL) for pulmonary alveolar proteinosis(PAP) in perioperative period. Methods: In this retrospective study, we collected clinical data from 78 WLL procedures of PAP patients from January 2006 to June 2016 in Guangzhou Institute of Respiratory Disease. The causes of perioperative complications were analyzed. Results: Eighteen (23.07%) of the 78 procedures developed complications, including pleural effusion(n=4), pneumonia(n=4), cardiac failure(n=2), cardiac arrhythmia (n=2), pneumothorax(n=2), atelectasis(n=1), lung edema(n=1), laryngeal edema(n=1), pleural effusion and pneumonia(n=1). All complications were mild and easy to treat. Seventy-four procedures had successful extubation, but 4 procedures developed a prolonged time of extubation. Age, DSS, PaCO(2,)FEV(1,)lavage volume, lavage times and underlying diseases were not predictors for any complications(each P>0.05). High fluid recovering rate had a protective effect against the occurring of complications (Wald=7.672, OR<0.01, P<0.05). Conclusions: Whole lung lavage was a safe procedure in the treatment of PAP. Complications could recovery after proper therapy. The perioperative complications showed a correlation with low fluid recover rate. Operation under guideline was the key to avoid complications.


Calculating magnification differences in monocular aphakia.
The calculation of magnification differences is treated well in a number of texts, 1, 3, 4, 5, 7 but the formulas are not always presented in their most convenient form. Because of this, many complex schemes have been illustrated 2 and many different versions have been published. 3, 4, 5. The purpose of this paper is to present the pertinent equations in a simplified manner and to illustrate them by a specific example, namely, the case of monocular aphakia.


Reverse Monte Carlo simulations, Raman scattering, and thermal studies of an amorphous Ge30Se70 alloy produced by mechanical alloying.
The short- and intermediate-range orders of an amorphous Ge30Se70 alloy produced by mechanical alloying were studied by reverse Monte Carlo simulations of its x-ray total structure factor, Raman scattering, and differential scanning calorimetry. The simulations were used to compute the G(Ge-Ge) (RMC)(r), G(Ge-Se) (RMC)(r), and G(Se-Se) (RMC)(r) partial distribution functions and the S(Ge-Ge) (RMC)(K), S(Ge-Se) (RMC)(K), and S(Se-Se) (RMC)(K) partial structure factors. We calculated the coordination numbers and interatomic distances for the first and second neighbors and the bond-angle distribution functions Theta(ijl)(cos theta). The data obtained indicate that the structure of the alloy has important differences when compared to alloys prepared by other techniques. There are a high number of Se-Se pairs in the first shell, and some of the tetrahedral units formed seemed to be connected by Se-Se bridges.


Characteristics of training and motivation of physicians working in emergency medicine.
Emergency medicine is an area in which correct decisions often need to be made fast, thus requiring a well-prepared medical team. There is little information regarding the profile of physicians working at emergency departments in Brazil. To describe general characteristics of training and motivation of physicians working in the emergency departments of medium and large hospitals in Salvador, Brazil. A cross-sectional study with standardized interviews applied to physicians who work in emergency units in 25 medium and large hospitals in Salvador. At least 75% of the professionals at each hospital were interviewed. One hospital refused to participate in the study. A total of 659 physicians were interviewed, with a median age of 34 years (interquartile interval: 29-44 years), 329 (49.9%) were female and 96 (14.6%) were medical residents working at off hours. The percentage of physicians who had been trained with Basic Life Support, Advanced Cardiovascular Life Support and Advanced Trauma Life Support courses was 5.2, 18.4 and 11.0%, respectively, with a greater frequency of Advanced Cardiovascular Life Support training among younger individuals (23.6% versus 13.9%; p<0.001). Thirteen percent said they were completely satisfied with the activity, while 81.3% expressed a desire to stop working in emergency units in the next 15 years, mentioning stress levels as the main reason. The physicians interviewed had taken few emergency immersion courses. A low motivational level was registered in physicians who work in the emergency departments of medium and large hospitals in Salvador.


The Dutch consumer quality index: an example of stakeholder involvement in indicator development.
Like in several other Western countries, in the Dutch health care system regulated competition has been introduced. In order to make this work, comparable information is required about the performance of health care providers in terms of effectiveness, safety and patient experiences. Without further coordination, external actors will all try to force health care providers to be transparent. For health care providers this might result in a situation in which they have to deliver data for several sets of indicators, defined by different actors. Therefore, in the Netherlands an effort is made to define national sets of performance indicators and related measuring instruments. In this article, the following questions are addressed, using patient experiences as an example:- When and how are stakeholders involved in the development of indicators and instruments that measure the patients' experiences with health care providers?- Does this involvement lead to indicators and instruments that match stakeholders' information needs? The Dutch experiences show that it is possible to implement national indicator sets and to reach consensus about what needs to be measured. Preliminary evaluations show that for health care providers and health insurers the benefits of standardization outweigh the possible loss of tailor-made information. However, it has also become clear that particular attention should be given to the participation of patient/consumer organisations. Stakeholder involvement is complex and time-consuming. However, it is the only way to balance the information needs of all the parties that ask for and benefit from transparency, without frustrating the health care system.


Supraspinal pain processing: distinct roles of emotion and attention.
Attentional and emotional states alter the way we perceive pain. Recent findings suggest that the mechanisms underlying these two forms of pain modulation are at least partially separable. This concept is supported by the observation that attention and emotions differentially alter the sensory and affective dimensions of pain perception and apparently implicate different brain circuits. In this review, we will examine those recent findings within the broader cognitive neuroscience conceptualization of human attention and emotion and the corresponding functional neuroanatomy.


Centrosomes in cellular regulation.
Centrosomes, spindle pole bodies, and related structures in other organisms are a morphologically diverse group of organelles that share a common ability to nucleate and organize microtubules and are thus referred to as microtubule organizing centers or MTOCs. Features associated with MTOCs include organization of mitotic spindles, formation of primary cilia, progression through cytokinesis, and self-duplication once per cell cycle. Centrosomes bind more than 100 regulatory proteins, whose identities suggest roles in a multitude of cellular functions. In fact, recent work has shown that MTOCs are required for several regulatory functions including cell cycle transitions, cellular responses to stress, and organization of signal transduction pathways. These new liaisons between MTOCs and cellular regulation are the focus of this review. Elucidation of these and other previously unappreciated centrosome functions promises to yield exciting scientific discovery for some time to come.


Sense of coherence, hope, and home demolition are differentially associated with anger and anxiety among Bedouin Arab adolescents in recognized and unrecognized villages.
This research investigated how coping resources explain emotional reactions of anger and anxiety, in the context of threat of house demolition, among adolescents in three groups: Adolescents living in a recognized village with no demolition, adolescents living in an unrecognized village (by the Israeli government as legal) with no demolition, and adolescents living in an unrecognized village with demolition. The framework of this research is based on Antonovsky's salutogenic theory, which suggests examining ability to cope with stressful situations. Multi-group cross-sectional study. The study was carried out during 2010-2011 and included 910 participants, of whom 411 adolescents lived in unrecognized villages where 193 of them experienced home demolition. Participants filled out a questionnaire including demographics, coping resources and emotional reactions. Findings showed that stress reactions were the highest among adolescents from unrecognized villages with demolition. Personal sense of coherence (SOC) was related to fewer emotional reactions among the adolescents from recognized villages; among adolescents from unrecognized villages, especially adolescents living in an unrecognized village with demolition, a stronger SOC was linked to stronger emotional reactions. These findings have important implications for understanding the role of coping among youth from different cultural groups.


Role of arms in somersaulting from compliant surfaces: a simulation study of springboard standing dives.
The role of arms in compliant-surface jumping for maximizing backward somersault rotations is studied using multi-segment models and is applied to springboard diving. The surface (springboard) is modeled by a rigid bar with a rotational spring with a hinged end and point mass at the tip. Planar four- and five-segment human models are used (with the fifth segment representing the arms) and are driven by torque actuators at the ankle, knee, hip, and shoulder. Each joint torque is the product of maximum isometric torque and three variable functions depending on instantaneous joint angle, angular velocity, and activation level, respectively. Movement simulation starts from a balanced initial posture and ends at jump takeoff. The objective is to find joint torque activation patterns during board contact so that the number of backward rotations in flight is maximized. Kinematic differences in jumps with and without arms are mainly in smaller takeoff vertical velocity and more flexed knee and hip in the former. In both jumps, joint torque/activations are similar in their minor flexion-full extension patterns. Maximum hip torque is larger with arms but maximum knee torque is larger without arms. Except at the knee, more joint work can be done with arm swing. Total angular momentum is increased considerably by arm motion because of its remote contribution. Consequently segment remote contributions to total angular momentum are much larger in jumping with arms. Shoulder strength helps generate angular momentum only to a certain limit. If more work is used to generate horizontal velocity away from the board, the amount of total angular momentum is reduced.


The feasibility of using a conventional flexible RF coil for an online MR-guided radiotherapy treatment.
The purpose of this paper is to evaluate the impact of a flexible radiofrequency coil on the treatment delivery of an online MR-guided radiotherapy treatment. For this study, we used a Synergy MR body coil (Philips, Best) in combination with the current MRL prototype of the UMC Utrecht. The compatibility of the coil is evaluated in two steps. First, we evaluated the dosimetric impact of the MR coil on both a simple and a complex irradiation strategy for treating spinal bone metastases. This tumor site will likely be chosen for the first in-man treatments with the UMC Utrecht MRL system. Second, we investigated the impact of the treatment beam on the MRI performance of the body coil. In case a single posterior-anterior rectangular field was applied, dose to the target volume was underestimated up to 2.2% as a result of beam attenuation in the MR coil. This underestimation however, decreased to 1% when a stereotactic treatment strategy was employed. The presence of the MR coil in or near the distal site of the treatment beam decreased the exit dose when a magnetic field was present. The MRI performance of the coil was unaffected as the result of the radiation. It is feasible to use the Synergy MR body coil for an online MR-guided radiotherapy treatment without any modification to the coil or attenuation correction methods in the planning stage. The effect of the MRI coil on the dose delivery is minimal and there is no effect of the treatment beam on the SNR of the acquired MRI data.


C-terminal domain of rodent intestinal mucin Muc3 is proteolytically cleaved in the endoplasmic reticulum to generate extracellular and membrane components.
Although human MUC3 and rodent Muc3 are both membrane-associated intestinal mucins, the present study has explored the possibility that rodent Muc3 might exist in soluble as well as membrane forms. No evidence was obtained for the existence of soluble splice variants; however, experiments with heterologous cells transfected with cDNA encoding the 381-residue C-terminal domain of rodent Muc3 showed that a definitive proteolytic cleavage occurs during processing in the endoplasmic reticulum. The products consisted of a V5-tagged 30 kDa extracellular glycopeptide and a Myc-tagged 49 kDa membrane-associated glycopeptide. Throughout their cellular transport to the plasma membrane, the two fragments remained associated by non-covalent SDS-sensitive interactions. Site-specific mutagenesis pinpointed the need for glycine and serine residues in the cleavage sequence Leu-Ser-Lys-Gly-Ser-Ile-Val-Val, which is localized between the two epidermal-growth-factor-like motifs of the mucin. A similar cleavage sequence (Phe-Arg-Pro-Gly downward arrow Ser-Val-Val-Val, where downward arrow signifies the cleavage site) has been reported in human MUC1 and analogous sites are present in human MUC3, MUC12 and MUC17. Thus early proteolytic cleavage may be a conserved characteristic of many membrane-associated mucins, possibly as a prelude to later release of their large extracellular domains at cell surfaces.


Context-aware fall detection using inertial sensors and time-of-flight transceivers.
Automatic detection of falls is important for enabling people who are older to safely live independently longer within their homes. Current automated fall detection systems are typically designed using inertial sensors positioned on the body that generate an alert if there is an abrupt change in motion. These inertial sensors provide no information about the context of the person being monitored and are prone to false positives that can limit their ongoing usage. We describe a fall-detection system consisting of a wearable inertial measurement unit (IMU) and an RF time-of-flight (ToF) transceiver that ranges with other ToF beacons positioned throughout a home. The ToF ranging enables the system to track the position of the person as they move around a home. We describe and show results from three machine learning algorithms that integrate context-related position information with IMU based fall detection to enable a deeper understanding of where falls are occurring and also to improve the specificity of fall detection. The beacons used to localize the falls were able to accurately track to within 0.39 meters of specific waypoints in a simulated home environment. Each of the three algorithms was evaluated with and without the context-based false alarm detection on simulated falls done by 3 volunteer subjects in a simulated home. False positive rates were reduced by 50% when including context.


Kinetic transport of pesticide from contaminated fabric through a model skin.
Most protective clothing research for workers exposed to pesticides has focused on the primary dermal exposure that results from direct contact with the pesticide and on the penetration, versus repellency, of protective materials. The role of absorption and retention in the function of traditional clothing materials to limit pesticide exposure has received less attention. This project investigates the transfer of pesticides from contaminated work clothing in the dry state to human skin with the goal of furthering our understanding of the role of absorption and retention in the function of traditional clothing materials. Our objective was to study the use of synthetic membrane to evaluate the kinetic transport of pesticide from contaminated clothing through human skin. Transport of pesticide through the test system with and without the presence of fabric was characterized by a three-parameter single exponential rise to maximum equation. The synthetic membrane system was an appropriate model for human skin in this situation. Starching applied to the fabric gave additional absorption and retention, reducing pesticide transport from the fabric to the skin, and heavier weight fabric, such as denim, provided protection through absorption and retention of the pesticide.


Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
Transvaginal sonography (TVS) is core to any ovarian cancer screening strategy. General-population screening involves older postmenopausal women in whom ovarian visualization is difficult because of decreasing ovarian size and lack of follicular activity. We report on factors affecting the visualization of postmenopausal ovaries in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). The UKCTOCS is a randomized controlled trial of 202 638 postmenopausal women with 50 639 women in the ultrasound scan arm. TVS is the primary screening modality in the ultrasound scan arm. Age, education, ethnicity, body mass index (BMI), previous pelvic surgery, lifestyle and reproductive factors, and a personal/family history of cancer were assessed for their effects on ovarian visualization at the initial TVS. Between 11 June 2001 and 18 August 2007, 43 867 women underwent TVS. The median age and BMI of the women were 60.6 (interquartile range (IQR), 9.9) years and 25.7 (IQR, 5.8), respectively. The right ovary was visualized in 29 297 (66.8%) and the left ovary was visualized in 28 726 (65.5%). Visualization of ovaries decreased with previous hysterectomy (odds ratio (OR) = 0.534; 95% CI, 0.504-0.567), previous tubal ligation (OR = 0.895; 95% CI, 0.852-0.940), increasing age (OR = 0.953; 95% CI, 0.950-0.956), unilateral oophorectomy (OR = 0.224; 95% CI, 0.186-0.269) and being overweight (OR = 0.918; 95% CI, 0.876-0.962) or obese (OR = 0.715; 95% CI, 0.677-0.755). Increased visualization was observed with a history of infertility (OR = 1.134; 95% CI, 1.005-1.279) and increasing age (in years) at menopause (OR = 1.005; 95% CI, 1.001-1.009). Several factors affect the visualization of postmenopausal ovaries. Their impact needs to be taken into consideration when developing quality assurance for ovarian ultrasound scanning or comparing study results as their prevalence may differ between populations.


Computed tomography of the brain in subacute sclerosing panencephalitis.
Twenty-four computed tomographic scans of 12 patients with confirmed subacute sclerosing panencephalitis were studied using standardized techniques of radiological assessment. Abnormalities encountered were of four types--(1) lateral ventricular dilatation, (2) cerebral cortical atrophy and sylvian fissure widening, (3) low parenchymal attenuation, and (4) brainstem atrophy and cerebellar atrophy--and of varying degrees. The abnormalities correlated best with the stage and duration of disease, but not necessarily well with the patient's mental state. The fewest radiological abnormalities were encountered in the acute or early stages, whereas more signs of parenchymal disturbances in the form of low attenuations emerged during intermediate periods. Chronic periods were accompanied by atrophic changes in the form of cortical atrophy, ventricular dilatation, and brainstem cerebellar atrophy.


Mortality in Children Receiving Growth Hormone Treatment of Growth Disorders: Data From the Genetics and Neuroendocrinology of Short Stature International Study.
Although pediatric growth hormone (GH) treatment is generally considered safe for approved indications, concerns have been raised regarding potential for increased risk of mortality in adults treated with GH during childhood. To assess mortality in children receiving GH. Prospective, multinational, observational study. Eight hundred twenty-seven study sites in 30 countries. Children with growth disorders. GH treatment during childhood. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) using age- and sex-specific rates from the general population. Among 9504 GH-treated patients followed for ≥4 years (67,163 person-years of follow-up), 42 deaths were reported (SMR, 0.77; 95% CI, 0.56 to 1.05). SMR was significantly elevated in patients with history of malignant neoplasia (6.97; 95% CI, 3.81 to 11.69) and borderline elevated for those with other serious non-GH-deficient conditions (2.47; 95% CI, 0.99-5.09). SMRs were not elevated for children with history of benign neoplasia (1.44; 95% CI, 0.17 to 5.20), idiopathic GHD (0.11; 95% CI, 0.02 to 0.33), idiopathic short stature (0.20; 95% CI, 0.01 to 1.10), short stature associated with small for gestational age (SGA) birth (0.66; 95% CI, 0.08 to 2.37), Turner syndrome (0.51; 95% CI, 0.06 to 1.83), or short stature homeobox-containing (SHOX) gene deficiency (0.83; 95% CI, 0.02 to 4.65). No significant increases in mortality were observed for GH-treated children with idiopathic GHD, idiopathic short stature, born SGA, Turner syndrome, SHOX deficiency, or history of benign neoplasia. Mortality was elevated for children with prior malignancy and those with underlying serious non-GH-deficient medical conditions.


Synthesis of chiral helical 1,3-oxazines.
A series of novel 1,3-oxazines were prepared to construct a helical framework. The 1,3-oxazine attached to the phenanthrene unit showed a small bite angle θ (∼12°), while the units attached to [4]helicene showed a larger θ (∼35°) and exhibited helical isomers at ambient conditions. The diastereomers of the third type of helicene-like bis-oxazine attached to binaphthyl were easily separable and showed good thermal stability. All four diastereomers of bis-helicene were synthesized, and their absolute configuration was established.


Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends.
Effective serodiagnosis of systemic fungal infections is of increasing importance, particularly with regard to the identification of infection with Histoplasma capsulatum, Paracoccidioides brasiliensis and Penicillium marneffei. Methodology has been based either around antibody or antigen detection, although there is clear overlap between the two. Antibody-based detection systems for the diagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei have now begun to incorporate a range of highly purified and well-characterized antigens, in contrast to the situation of a few years ago when relatively crude preparations derived from either whole cells or culture filtrate were used. The application of such antigens offers improvements in reproducibility and specificity, although the detection of meaningful antibody responses in immunosuppressed individuals remains a problem. Partly as a consequence of this a great deal of attention has focused on the development of antigen detection assays, and such methods have proved particularly successful, as for instance in the serodiagnosis of histoplasmosis in AIDS patients. The recent utilization of monoclonal antibodies in the development of antigen detection methods for the diagnosis of histoplasmosis and paracoccidioidomycosis offers further scope for improvement in this area.


A xenogeneic-free protocol for isolation and expansion of human adipose stem cells for clinical uses.
Human adipose stem cells (HASCS) play a crucial role in the fields of regenerative medicine and tissue engineering for different reasons: the abundance of adipose tissue, their easy harvesting, the ability to multipotent differentiation and the fact that they do not trigger allogeneic blood response or secrete cytokines that act as immunosuppressants. The vast majority of protocols use animal origin reagents, with the underlying risk of transmitting infections by non-human pathogens. We have designed a protocol to isolate and maintain the properties of hASCs avoiding xenogeneic reagents. These changes not only preserve hASCs morphology, but also increase cell proliferation and maintain their stem cell marker profile. On the other hand, human serum albumin (HSA), Tryple® and human Serum (HS), do not affect hASCs multipotent differentiation ability. The amendments introduced do not trigger modifications in the transcriptional profile of hASCs, alterations in key biochemical pathways or malignization. Thus, we have proven that it is possible to isolate and maintain hASCs avoiding animal reagents and, at the same time, preserving crucial culture parameters during long term culture. Thereby we have revealed a novel and effective tool for the improvement of clinical, cell-based therapies.


Determination of 12 pueraria components by high-performance liquid chromatography-mass spectrometry.
Puerariae radix, a commonly used Chinese herb drug derived from the dried root of legume plant, contains a series of isoflavones as its chief pharmacologically active constituents. Using 12 pueraria components as markers, an LC-UV-MS method requiring less than 60 min, was developed for estimating the quality of pueraria samples within 60 min. Extracts were analyzed using a Cosmosil 5C18-MS column, by gradient elution with an aqueous solution of acetic acid and methanol-ACN at a flow-rate of 1.0 mL/min. Peaks were detected at 254 nm and each peak was identified by LC/MS. The reproducibilities (RSD) of this proposed method, on the basis of peak-area ratios from six replicate injections, were 0.93-1.42% (intraday) and 1.05-1.63% (interday) at a detection limit of 0.12-0.78 microg/mL. Most of the markers used in this study can be classified, respectively, into three major categories, namely, isoflavones, O-glycosidic isoflavones, and C-glycosidic isoflavones. The structures of the compounds were determined from LC-MS fragmentation data and data from the literature.


Using a web-based image quality assurance reporting system to improve image quality.
The purpose of this study is to show the impact of a web-based image quality assurance reporting system on the rates of three common image quality errors at our institution. A web-based image quality assurance reporting system was developed and used beginning in April 2009. Image quality endpoints were assessed immediately before deployment (period 1), approximately 18 months after deployment of a prototype reporting system (period 2), and approximately 12 months after deployment of a subsequent upgraded department-wide reporting system (period 3). A total of 3067 axillary shoulder radiographs were reviewed for correct orientation, 355 shoulder CT scans were reviewed for correct reformatting of coronal and sagittal images, and 346 sacral MRI scans were reviewed for correct acquisition plane of axial images. Error rates for each review period were calculated and compared using the Fisher exact test. Error rates of axillary shoulder radiograph orientation were 35.9%, 7.2%, and 10.0%, respectively, for the three review periods. The decrease in error rate between periods 1 and 2 was statistically significant (p < 0.0001). Error rates of shoulder CT reformats were 9.8%, 2.7%, and 5.8%, respectively, for the three review periods. The decrease in error rate between periods 1 and 2 was statistically significant (p = 0.03). Error rates for sacral MRI axial sequences were 96.5%, 32.5%, and 3.4%, respectively, for the three review periods. The decrease in error rates between periods 1 and 2 and between periods 2 and 3 was statistically significant (p < 0.0001). A web-based system for reporting image quality errors may be effective for improving image quality.


Nikolaevskiy equation with dispersion.
The Nikolaevskiy equation was originally proposed as a model for seismic waves and is also a model for a wide variety of systems incorporating a neutral "Goldstone" mode, including electroconvection and reaction-diffusion systems. It is known to exhibit chaotic dynamics at the onset of pattern formation, at least when the dispersive terms in the equation are suppressed, as is commonly the practice in previous analyses. In this paper, the effects of reinstating the dispersive terms are examined. It is shown that such terms can stabilize some of the spatially periodic traveling waves; this allows us to study the loss of stability and transition to chaos of the waves. The secondary stability diagram ("Busse balloon") for the traveling waves can be remarkably complicated.


Keratocystic odontogenic tumor with an ectopic tooth in maxilla.
The term odontogenic keratocyst was first used by Philipsen in the year 1956. The lesion was renamed by him as keratocystic odontogenic tumor (KCOT) and reclassified as odontogenic neoplasm in the World Health Organization's 2005 edition that occurs commonly in the jaws having a predilection for the angle and ascending ramus of mandible. In contrast, KCOTs arising in the maxillary premolar region are relatively rare. Here, we discuss a rare case of keratocystic odontogenic tumor occurring in the maxilla with an ectopic tooth position.


Experimental and simulation study on chatter stability region of integral impeller with non-uniform allowance.
In order to accurately improve and predict chatter stability region of machining process, an optimization method of machining process with non-uniform allowance of integral impeller was proposed. The modal parameters of the workpiece process system were obtained using the finite element analysis. Based on the regenerative chatter analysis theory, a limit comparison diagram of the stability with uniform allowance and non-uniform allowance was established. The simulation results showed that the non-uniform allowance natural frequency is about 1.43 times as much as the uniform allowance natural frequency, and the machining system stiffness non-uniform allowance is twice as much as the uniform allowance, while the limit of chatter stability region is increased by 3 times. This article studied uniform allowance and non-uniform allowance of milling chatter stability with experimental method. Tool path for five-axis machining and machine tool simulation based on NX CAM were planned. The comparisons of cutting processing uniform allowance and non-uniform allowance were done, and the surface profile detection of the test part with the three-dimensional scanning was carried out. The experimental results showed that the average optimization rate for manufacturing precision of blade suction surface after optimization and pressure surface was 63.8% and 48.84%. The total experiment showed that this process optimization strategy could effectively improve the stiffness of the integral impeller blade and reduce the cutting chatter of the blade during the cutting process.


Feeding patterns before 6 months of age: the relative validity of recall from interviews of mothers of Guatemalan infants and toddlers.
The WHO recommends exclusive breastfeeding during the first 6 mo of life; however, deviations from this recommendation are widespread. The objective of the current study was to evaluate exclusive and predominant breastfeeding rates, as defined by the WHO, in a cross-sectional sample of Guatemalan children using retrospective records on the temporal pattern of introducing foods and beverages before 6 mo. Mothers of 150 infants, aged 6 to 23 mo, attending a public health clinic were interviewed about early life feeding practices with a structured questionnaire. In addition, the plausibility of the reported offering of liquids and foods, other than breast milk, since birth was checked against reported current feeding practices. We observed that estimated exclusive breastfeeding was rare with 14% of infants receiving exclusive breastfeeding for 5 mo, and only 9% for the recommended 6 mo. The proportion of infants with predominant breastfeeding, which allows certain liquids such as water, juices and ritual fluids, was 33% through 5 mo and 23% through 6 mo. One-quarter of mothers (n=38) reported implausible answers concerning age-of-introduction of liquids and foods. Nevertheless, retrospective reports at up to 2 y give credible outcomes for estimations of feeding pattern at 6 mo of age. Our findings match the findings of other studies conducted in Guatemala. Overall adherence to the WHO guidelines for feeding in the first semester of infancy was much less than ideal and in need of strengthening.


Catalytic mechanism and substrate selectivity of aldo-keto reductases: insights from structure-function studies of Candida tenuis xylose reductase.
Aldo-keto reductases (AKRs) constitute a large protein superfamily of mainly NAD(P)-dependent oxidoreductases involved in carbonyl metabolism. Catalysis is promoted by a conserved tetrad of active site residues (Tyr, Lys, Asp and His). Recent results of structure-function relationship studies for xylose reductase (AKR2B5) require an update of the proposed catalytic mechanism. Electrostatic stabilization by the epsilon-NH3+ group of Lys is a key source of catalytic power of xylose reductase. A molecular-level analysis of the substrate binding pocket of xylose reductase provides a case of how a very broadly specific AKR achieves the requisite selectivity for its physiological substrate and could serve as the basis for the design of novel reductases with improved specificities for biocatalytic applications.


Theoretical insights into the separation of Am(III)/Eu(III): designing ligands based on a preorganization strategy.
Separation of trivalent actinide (An(III)) and lanthanide (Ln(III)) is a worldwide challenge of nuclear waste treatment. Designing ligands with efficient An(III)/Ln(III) separation performance is still one of the key issues for the disposal of accumulated radioactive waste and the recovery of minor actinides. Recently, N-heterocyclic ligands modified with amide groups have shown excellent An(III)/Ln(III) separation performance. The preorganized structure of the ligands has a great impact on the An(III)/Ln(III) separation performance. We theoretically investigated the extraction behaviors of Am(III) and Eu(III) using phenanthroline (L1 and L2) and bipyridine (L3 and L4) based ligands with a completely or partially preorganized structure. The properties of these ligands and their coordination structures, bonding nature and thermodynamic behaviors with the Am(III) and Eu(III) complexes have been systematically studied in a theoretical fashion. The analyses of the bonding nature suggest that the Am-N bonds possess more covalence than the Eu-N bonds. The thermodynamic results indicate that L2 with a completely preorganized structure has the strongest extraction ability and the best Am(III)/Eu(III) selectivity, while L3 with the most flexible skeleton appears to have the weakest extraction ability and the lowest Am(III)/Eu(III) selectivity. And L1 and L4 have similar performances with regard to Am(III)/Eu(III) selectivity. The results suggest that a certain degree of preorganization of the ligand structure can enhance the extraction ability and Am(III)/Eu(III) selectivity. This work provides valuable information for designing efficient ligands for An(III)/Ln(III) separation by the preorganization strategy.


[Fibrinolytic treatment of peripheral artery disease and phlebothrombosis (author's transl)].
Standardised streptokinase-heparin treatment was used in 30 patients with stenoses or occlusions of the large arteries and phlebothrombosis. Apart from three cases of occlusion of the popliteal artery it was possible to revascularise all occluded vessels and markedly widen any haemodynamically effective stenoses.


Postoperative delirium in 47 379 individuals undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.
The study aims to discuss the assessment methods used for the incidence of in-hospital postoperative delirium (IHPOD) in transcatheter aortic valve replacement (TAVR) patients and explore possible strategies for preventing and reducing postoperative complications in the geriatric population. An electronic search of PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials was conducted up to August 2021, to identify studies on the IHPOD following TAVR in patients above 70 years. The primary objective of the study was to determine the incidence of delirium following TAVR and procedures like transfemoral (TF) and non-TF approaches. The secondary objectives were to determine the incidence of stroke and incidence according to the confusion assessment method (CAM) diagnostic tool. The authors only included studies published in English and excluded patients with comorbidities and studies with inaccessible full-text. Among the selected 42 studies with 47 379 patients, the incidence of IHPOD following TAVR was 10.5% (95% CI: 9.2-11.9%, I2=95.82%, P<0.001). Incidence based on CAM was 15.6% (95% CI: 10.5-20.7%, I2=95.36%, P<0.001). The incidence of IHPOD after TF-TAVR was 9.3% (95% CI: 7.6-11.0%, I2=94.52%, P<0.001), and after non-TF TAVI was 25.3% (95% CI: 15.4-35.1%, I2=92.45%, P<0.001). The incidence of stroke was 3.7% (95% CI: 2.9-4.5%, I2=89.76%, P<0.001). Meta-regression analyses between mean age (P=0.146), logistic EuroSCORE (P=0.099), or percentage of participants treated using the TF approach (P=0.276) were nonsignificant while stroke (P=0.010) was significant. When considering these variables, the residual heterogeneity remained high indicating that other variables influence the heterogeneity. IHPOD following TAVR was observed in 10.5% of individuals and in 15.6% using CAM. Its incidence was found to be three times higher after non-TF TAVR (25.3%) compared to TF TAVR (9.3%). Stroke showed an incidence of 3.7% after TAVR and was found to be significantly associated with the risk of developing delirium following TAVR. Further studies are needed to evaluate possible causes and risk factors responsible for delirium and to assess the role of anesthesia and cerebral embolic protection in preventing delirium after TAVR.


Legionella species colonization of water distribution systems, pools and air conditioning systems in cruise ships and ferries.
Legionnaires' disease continues to be a public health concern in passenger ships. This study was scheduled in order to investigate Legionella spp. colonization of water distribution systems (WDS), recreational pools, and air-conditioning systems on board ferries and cruise ships in an attempt to identify risk factors for Legionella spp. colonization associated with ship water systems and water characteristics. Water systems of 21 ferries and 10 cruise ships including WDS, air conditioning systems and pools were investigated for the presence of Legionella spp. The 133 samples collected from the 10 cruise ships WDS, air conditioning systems and pools were negative for Legionella spp. Of the 21 ferries WDS examined, 14 (66.7%) were legionellae-positive. A total of 276 samples were collected from WDS and air conditioning systems. Legionella spp. was isolated from 37.8% of the hot water samples and 17.5% of the cold water samples. Of the total 96 positive isolates, 87 (90.6%) were L. pneumophila. Legionella spp. colonization was positively associated with ship age. The temperature of the hot water samples was negatively associated with colonization of L. pneumophila serogroup (sg) 1 and that of L. pneumophila sg 2 to 14. Increases in pH >/=7.8 and total plate count > or =400 CFU/L, correlated positively with the counts of L. pneumophila sg 2 to 14 and Legionella spp. respectively. Free chlorine of > or =0.2 mg/L inhibited colonization of Legionella spp. WDS of ferries can be heavily colonized by Legionella spp. and may present a risk of Legionnaires' disease for passengers and crew members. Guidelines and advising of Legionnaires' disease prevention regarding ferries are needed, in particular for operators and crew members.


Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease.
Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death. Treatment is possible via supplement of biotin and/or thiamine, with early treatment resulting in significant lifelong improvements. Here we report two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5' UTR and minimal promoter region. This deletion is the smallest promoter deletion reported to date, further defining the minimal promoter region of SLC19A3 Unfortunately, one of the siblings died prior to diagnosis, but the other is showing significant improvement after commencement of therapy. This case demonstrates the power of whole-genome sequencing for the identification of structural variants and subsequent diagnosis of rare neurodevelopmental disorders.


Factors Influencing Depression among Elderly Patients in Geriatric Hospitals.
[Purpose] The purpose of this study was to investigate the prevalence of depression among elderly patients and identify the factors influencing depression in a geriatric hospital in Korea. [Subjects] A self-report questionnaire was administered to the patients in community geriatric hospitals. Participants were 195 elderly patients. [Methods] The instruments utilized in this study were the Geriatric Depression Scale Short Form Korea (GDSSF-K), an activity of daily living scale, a self-esteem scale, a social support scale, and a life satisfaction scale. Data were collected from April 20 to June 20, 2011. Data were analyzed using descriptive statistics, Pearson correlations, and multiple logistic regression analysis using SPSS 15.0 and Stata 11.0. [Results] The average GDSSF-K score of the participants was 8.94, indicating a moderate level of depression. About 78.4% of the elderly patients in this study were classified as predisposed toward depression. Significant predictors for depression included the patients' perceived health status and life satisfaction. [Conclusion] The results indicate that elderly patients face a high risk of developing depression and that efforts should be made to address it wherever possible. Regular depression screening will be beneficial for early detection of depression in patients at community geriatric hospitals.


The multifaceted role of autophagy in cancer and the microenvironment.
Autophagy is a crucial recycling process that is increasingly being recognized as an important factor in cancer initiation, cancer (stem) cell maintenance as well as the development of resistance to cancer therapy in both solid and hematological malignancies. Furthermore, it is being recognized that autophagy also plays a crucial and sometimes opposing role in the complex cancer microenvironment. For instance, autophagy in stromal cells such as fibroblasts contributes to tumorigenesis by generating and supplying nutrients to cancerous cells. Reversely, autophagy in immune cells appears to contribute to tumor-localized immune responses and among others regulates antigen presentation to and by immune cells. Autophagy also directly regulates T and natural killer cell activity and is required for mounting T-cell memory responses. Thus, within the tumor microenvironment autophagy has a multifaceted role that, depending on the context, may help drive tumorigenesis or may help to support anticancer immune responses. This multifaceted role should be taken into account when designing autophagy-based cancer therapeutics. In this review, we provide an overview of the diverse facets of autophagy in cancer cells and nonmalignant cells in the cancer microenvironment. Second, we will attempt to integrate and provide a unified view of how these various aspects can be therapeutically exploited for cancer therapy.


Mechanical Ventilation Strategy Guided by Transpulmonary Pressure in Severe Acute Respiratory Distress Syndrome Treated With Venovenous Extracorporeal Membrane Oxygenation.
Previous studies have suggested that adjusting ventilator settings based on transpulmonary pressure measurements may minimize ventilator-induced lung injury, but this has never been investigated in patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation. We aimed to evaluate whether a transpulmonary pressure-guided ventilation strategy would increase the proportion of patients successfully weaned from venovenous extracorporeal membrane oxygenation support in patients with severe acute respiratory distress syndrome. Single-center, prospective, randomized controlled trial. Sixteen-bed, respiratory ICU at a tertiary academic medical center. Severe acute respiratory distress syndrome patients receiving venovenous extracorporeal membrane oxygenation. One-hundred four patients were randomized to transpulmonary pressure-guided ventilation group (n = 52) or lung rest strategy group (n = 52) groups. Two patients had cardiac arrest during establishment of venovenous extracorporeal membrane oxygenation in the lung rest group did not receive the assigned intervention. Thus, 102 patients were included in the analysis. The proportion of patients successfully weaned from venovenous extracorporeal membrane oxygenation in the transpulmonary pressure-guided group was significantly higher than that in the lung rest group (71.2% vs 48.0%; p = 0.017). Compared with the lung rest group, driving pressure, tidal volumes, and mechanical power were significantly lower, and positive end-expiratory pressure was significantly higher, in the transpulmonary pressure-guided group during venovenous extracorporeal membrane oxygenation support. In the transpulmonary pressure-guided group, levels of interleukin-1β, interleukin-6, and interleukin-8 were significantly lower, and interleukin-10 was significantly higher, than those of the lung rest group over time. Lung density was significantly lower in the transpulmonary pressure-guided group after venovenous extracorporeal membrane oxygenation support than in the lung rest group. A transpulmonary pressure-guided ventilation strategy could increase the proportion of patients with severe acute respiratory distress syndrome successfully weaned from venovenous extracorporeal membrane oxygenation.