Joint protection and hand exercises for hand osteoarthritis: an economic evaluation comparing methods for the analysis of factorial trials.
Evidence regarding the cost-effectiveness of joint protection and hand exercises for the management of hand OA is not well established. The primary aim of this study is to assess the cost-effectiveness (cost-utility) of these management options. In addition, given the absence of consensus regarding the conduct of economic evaluation alongside factorial trials, we compare different analytical methodologies. A trial-based economic evaluation to assess the cost-utility of joint protection only, hand exercises only and joint protection plus hand exercises compared with leaflet and advice was undertaken over a 12 month period from a UK National Health Service perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were calculated for each trial arm. Incremental cost-effectiveness ratios (ICERs) were estimated and cost-effectiveness acceptability curves were constructed. The base case analysis used a within-the-table analysis methodology. Two further methods were explored: the at-the-margins approach and a regression-based approach with or without an interaction term. Mean costs (QALYs) were £58.46 (s.d. 0.662) for leaflet and advice, £92.12 (s.d. 0.659) for joint protection, £64.51 (s.d. 0.681) for hand exercises and £112.38 (s.d. 0.658) for joint protection plus hand exercises. In the base case, hand exercises were the cost-effective option, with an ICER of £318 per QALY gained. Hand exercises remained the most cost-effective management strategy when adopting alternative methodological approaches. This is the first trial evaluating the cost-effectiveness of occupational therapy-supported approaches to self-management for hand OA. Our findings showed that hand exercises were the most cost-effective option.


Axonal transport of a subclass of tau proteins: evidence for the regional differentiation of microtubules in neurons.
Tubulin, the major constituent of microtubules, is anterogradely transported within the axon as part of slow component a (SCa; 0.2-1.0 mm/day). This raises the possibility that the microtubule-associated proteins (MAPs) may be transported at the same rate. To examine this question, the high molecular weight and tau MAPs obtained from whole brain preparations of microtubules were compared with the proteins of SCa in guinea pig retinal ganglion cell axons by using phosphocellulose chromatography and one- and two-dimensional polyacrylamide gel electrophoresis. Only two of the tau proteins were found to be cotransported with axonal tubulin, although four tau and two high molecular weight MAPs were synthesized in the retina. This result suggests either that the retinal ganglion cell synthesizes only those two tau proteins or that it synthesizes several of the MAPs, but commits to axonal transport just two of the tau proteins. In either case, these observations are consistent with the transport of intact microtubules and demonstrate that axonal microtubules represent a distinct subset of brain microtubules. Such a distinction may be related to unique properties of the axonal cytoskeleton.


Screening metal-organic frameworks for selective noble gas adsorption in air: effect of pore size and framework topology.
The adsorption of noble gases and nitrogen by sixteen metal-organic frameworks (MOFs) was investigated using grand canonical Monte Carlo simulation. The MOFs were chosen to represent a variety of net topologies, pore dimensions, and metal centers. Three commercially available MOFs (HKUST-1, AlMIL-53, and ZIF-8) and PCN-14 were also included for comparison. Experimental adsorption isotherms, obtained from volumetric and gravimetric methods, were used to compare krypton, argon, and nitrogen uptake with the simulation results. Simulated trends in gas adsorption and predicted selectivities among the commercially available MOFs are in good agreement with experiment. In the low pressure regime, the expected trend of increasing adsorption with increasing noble gas polarizabilty is seen. For each noble gas, low pressure adsorption correlates with several MOF properties, including free volume, topology, and metal center. Additionally, a strong correlation exists between the Henry's constant and the isosteric heat of adsorption for all gases and MOFs considered. Finally, we note that the simulated and experimental gas selectivities demonstrated by this small set of MOFs show improved performance compared to similar values reported for zeolites.


Enhanced thermoelectric performance of monolayer MoSSe, bilayer MoSSe and graphene/MoSSe heterogeneous nanoribbons.
Graphene has many superlative thermal, electrical and mechanical properties. However, the thermoelectric performance of graphene is limited by its high thermal conductivity and small Seebeck coefficient. To address this problem, monolayer and bilayer MoSSe nanoribbons together with graphene/MoSSe heterostructures have been investigated in this work. The electron and phonon transport, and the thermoelectric properties of the monolayer and bilayer MoSSe nanoribbons, together with the graphene/MoSSe heterostructures, have been analyzed by first-principles methods in conjunction with non-equilibrium Green's function and the Landauer equation. The results indicate that figure of merit (ZT) values of 2.01 and 1.64 can be achieved for graphene/SeMoS stacked nanoribbons and symmetric armchair MoSSe nanoribbons respectively at 300 K, which are much higher than the ZT value of prime graphene (ZT ∼ 0.05). The maximum ZT values of these structures increase at T < 350 K, while the maximum ZT decreases at high temperatures (T > 350 K). However, the maximum ZT values of the symmetric armchair MoSSe nanoribbons show an increase with temperatures up to 550 K. From our analysis, phonon thermal conductivity and temperature are key factors determining the ZT values in MoSSe nanoribbons. The significantly enhanced ZT values make graphene/SeMoS stacking nanoribbons and symmetric armchair MoSSe nanoribbons promising candidates for application in thermoelectric devices.


Infrared differential-absorption Mueller matrix spectroscopy and neural network-based data fusion for biological aerosol standoff detection.
An active spectrophotopolarimeter sensor and support system were developed for a military/civilian defense feasibility study concerning the identification and standoff detection of biological aerosols. Plumes of warfare agent surrogates gamma-irradiated Bacillus subtilis and chicken egg white albumen (analytes), Arizona road dust (terrestrial interferent), water mist (atmospheric interferent), and talcum powders (experiment controls) were dispersed inside windowless chambers and interrogated by multiple CO(2) laser beams spanning 9.1-12.0 microm wavelengths (lambda). Molecular vibration and vibration-rotation activities by the subject analyte are fundamentally strong within this "fingerprint" middle infrared spectral region. Distinct polarization-modulations of incident irradiance and backscatter radiance of tuned beams generate the Mueller matrix (M) of subject aerosol. Strings of all 15 normalized elements {M(ij)(lambda)/M(11)(lambda)}, which completely describe physical and geometric attributes of the aerosol particles, are input fields for training hybrid Kohonen self-organizing map feed-forward artificial neural networks (ANNs). The properly trained and validated ANN model performs pattern recognition and type-classification tasks via internal mappings. A typical ANN that mathematically clusters analyte, interferent, and control aerosols with nil overlap of species is illustrated, including sensitivity analysis of performance.


The Early Antibody-Dependent Cell-Mediated Cytotoxicity Response Is Associated With Lower Viral Set Point in Individuals With Primary HIV Infection.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an immune response largely mediated by natural killer (NK) cells that can lyse target cells and combat tumors and viral infections. However, the role of ADCC in response to primary HIV infection is poorly understood. In the present study, we explored the ADCC response and evaluated its characteristics in 85 HIV-infected individuals, including 42 with primary infections. Our results showed that ADCC occurs during acute infection, and the earliest ADCC response to a single peptide was detected at 52 days. Primary HIV-infected individuals exhibiting ADCC responses had lower viral set points than those with no ADCC response, and functional analyses demonstrated that the ADCC response could significantly inhibit viral infection during primary HIV infection. HIV epitopes that provoked the ADCC response were determined and three relatively conserved epitopes (HNVWATYACVPTDPNPQE, TSVIKQACPKISFDPIPI, and VVSTQLLLNGSLAEEEII) from the surface of the three-dimensional structure of the HIV Env protein were identified. Overall, our data indicate that ADCC responses may be significant for the control of HIV from an early stage during infection. These findings merit further investigation and will facilitate improvements in vaccines or therapeutic interventions against HIV infection.


Ventricular structure and function in children with sickle cell disease using conventional and tissue Doppler echocardiography.
Conventional 2-dimensional, M-mode, and spectral Doppler echocardiographic techniques have documented abnormal ventricular function in adults with sickle cell disease (SCD), but assessments in children are conflicting. Tissue Doppler echocardiography (TDE) provides additional information about myocardial function. Two-dimensional, M-mode, tricuspid regurgitation jet velocity (TRJV) data, and tissue Doppler echocardiographically derived myocardial velocity measurements of left ventricular (LV) and right ventricular function were taken from children with SCD compared to those of similar healthy historical controls and correlated with clinical characteristics and hemoglobin levels. Compared to 55 controls, 54 children with SCD (mean age 14.2 years, range 6 to 21) had a larger left ventricle, greater LV mass, and higher LV fractional shortening; 30% had increased pulmonary artery pressure (TRJV ≥2.5 m/s). Conventional echocardiographic measurements of LV systolic function and spectral Doppler measurements of LV and right ventricular diastolic function were essentially normal, but TDE indicated that 31% of SCD children had evidence of LV diastolic dysfunction (peak early diastolic velocity of LV inflow Doppler/peak early diastolic velocity at lateral mitral valve annulus >8), a finding that correlated with lower hemoglobin levels. Although decreasing hemoglobin levels in children with SCD correlated with LV hypertrophy, LV dilation, and LV diastolic dysfunction, long-term transfusion or hydroxyurea therapy did not affect these measurements. In conclusion, 1/3 of children with SCD had tissue Doppler echocardiographic evidence of LV diastolic dysfunction, which was correlated with hemoglobin levels. Adding serial assessments of ventricular function with TDE to conventional echocardiography may detect early cardiac changes, especially in children with severe anemia.


Influence of dexamethasone on visible 5-ALA fluorescence and quantitative protoporphyrin IX accumulation measured by fluorescence lifetime imaging in glioblastomas: is pretreatment obligatory before fluorescence-guided surgery?
Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) is nowadays widely applied for improved resection of glioblastomas (GBMs). Initially, pretreatment with dexamethasone was considered to be essential for optimal fluorescence effect. However, recent studies reported comparably high rates of visible fluorescence in GBMs despite absence of dexamethasone pretreatment. Recently, the authors proposed fluorescence lifetime imaging (FLIM) for the quantitative analysis of 5-ALA-induced protoporphyrin IX (PpIX) accumulation. The aim of this study was thus to investigate the influence of dexamethasone on visible fluorescence and quantitative PpIX accumulation. The authors prospectively analyzed the presence of visible fluorescence during surgery in a cohort of patients with GBMs. In this study, patients received dexamethasone preoperatively only if clinically indicated. One representative tumor sample was collected from each GBM, and PpIX accumulation was analyzed ex vivo by FLIM. The visible fluorescence status and mean FLIM values were correlated with preoperative intake of dexamethasone. In total, two subgroups with (n = 27) and without (n = 20) pretreatment with dexamethasone were analyzed. All patients showed visible fluorescence independent from preoperative dexamethasone intake. Furthermore, the authors did not find a statistically significant difference in the mean FLIM values between patients with and without dexamethasone pretreatment (p = 0.097). In this first study to date, the authors found no significant influence of dexamethasone pretreatment on either visible 5-ALA fluorescence during GBM surgery or PpIX accumulation based on FLIM. According to these preliminary data, the authors recommend administering dexamethasone prior to fluorescence-guided surgery of GBMs only when clinically indicated.


Enterohemorrhagic Escherichia coli trivalent recombinant vaccine containing EspA, intimin and Stx2 induces strong humoral immune response and confers protection in mice.
Enterohemorrhagic Escherichia coli (EHEC) is an important food-borne pathogen, which causes a wide spectrum of diseases ranging from hemorrhagic colitis to life-threatening hemolytic uremic syndrome (HUS). Currently, insufficient measures to prevent and treat EHEC infection make a vaccine against EHEC in great demand. EspA (E. coli secreted protein A), intimin, and Stx2 (Shiga toxin 2) are three predominant virulence factors of EHEC, and each of them has proved to be capable of inducing partial protective immunity. In this study, we constructed a trivalent recombinant protein designated EIS that is composed of EspA (E), C-terminal 300 amino acids of intimin (I) and B subunit of Stx2 (S), and tested it as vaccine using a mouse model. Our results showed that immunization of EIS induced strong humoral response to EspA, intimin and Stx2 and protected mice against the challenges with live EHEC or EHEC sonicated lysate. Moreover, it enhanced clearance of intestinally colonized bacteria. This work suggests that for EHEC vaccines using a combination of EspA, intimin and Stx2 antigens appears to be more effective than using any of these immunogens alone.


High Resolution Melting Analysis for Rapid Detection of PIK3CA Gene Mutations in Bladder Cancer: A Mutated Target for Cancer Therapy.
PIK3CA gene mutations have clinical importance and their presence is associated with therapy response. They are also considered as a molecule for targeted therapy. As regards to their importance, genetic variation within a population as well as among different populations, this study was conducted to detect common mutations of exons 9 and 20 and other probable mutations in PIK3CA gene as well as their frequencies in Iranian bladder cancer patients. Paired tumor and adjacent normal tissues samples were obtained from 50 bladder cancer patients. Mutations of PIK3CA gene were detected using High Resolution Melting (HRM) analysis which is ahighly sensitive, repeatable, rapid, and cost-effective technique. To determine the precision of the HRM analysis, Sanger sequencing analysis was used. The result showed that mutations were present in 10% (5/50) of the subjects. The majority of these cases (4/5) had the mutation(s) in exon 9, spanning over five different mutations, among which three of them were actually novel mutations. Further analysis showed that 2 cases had simultaneous mutations for exon 9. In addition to novel mutations, the PIK3CA mutation rate observed in Iranian bladder patients was not as frequent as previous reports and COSMIC. HRM can be used as a rapid and sensitive method for mutation screening. Dysregulation of PIK3CA gene in bladder cancer reveals its potentials as a mechanistic link for cancer development, which in turn suggests its special use in interventional studies for targeted therapy.


Chemical submission: results of 4-year French inquiry.
Psychoactive substances may be administered without the knowledge of a victim in order to induce incapacitation and thus facilitate criminal actions. The characteristics of the victims and the drugs used in such suspected chemical submissions (CS) were analyzed in 309 cases collected from October 2003 to December 2007 through a national survey. Out of 309 cases, 158 met all criteria of CS. The victims were mostly female (n = 89, 56%). The type of aggression was mostly sexual assault (in 79 cases 50%). Benzodiazepines and related drugs were detected in 129 victims (82%) and were mostly clonazepam, zolpidem, and bromazepam whereas flunitrazepam and gamma hydroxybutyrate, well known for their use in CS, were identified in 11 (7%) and five (3%) of the 158 victims. CS is not an anecdotal phenomenon in France. Information for health professionals and workers in forensic structures as well as education of the general population associated with preventive measures such as drug dosage form changes should contribute to improved care management of victims and decreased risk.


Analysis of the expression of heme oxygenase-1 gene in human alveolar epithelial cells exposed to cigarette smoke condensate.
Airway epithelium is exposed to inhaled exogenous sources. Injury of the alveolar epithelium by cigarette smoking is presumed to be an important process in the pathogenesis of smoking-related pulmonary diseases. Current mechanistic assays that measure the toxicity of cigarette smoke focus on carcinogenesis. However, there is a need to design assays relevant to other disease processes. Oxidative stress is implicated in the pathogenesis of many respiratory diseases including chronic obstructive pulmonary disease. Therefore, we evaluated whether in vitro studies of cigarette smoking are appropriate to examine HO-1 mRNA expression. The human lung epithelial cell line A549 was exposed to the particulate fraction of cigarette smoke (Cigarette Smoke Condensate; CSC) and examined for the induction of HO-1 mRNA. HO-1 gene expression by CSC is increased dose-dependently. In comparison of the induction of HO-1 mRNA by CSC prepared from flue-cured or Burley tobacco, CSC from flue-cured tobacco seems to tend to induce an mRNA of HO-1 higher than CSC from Burley tobacco. The adaptation of HO-1 mRNA expression assay as a biologically relevant indicator of cigarette smoke-induced stress may be exemplified in this study whereby CSC derived from cigarette smoke positively correlated with an increase in HO-1 expression and the difference of the type of tobacco can be detected.


Phosphine-Stabilized Germylidenylpnictinidenes as Synthetic Equivalents of Heavier Nitrile and Isocyanide in Cycloaddition Reactions with Alkynes.
The reactions of chlorogermylene MsFluindtBu-GeCl 1, supported by a sterically encumbered hydrindacene ligand MsFluindtBu, with NaPCO(dioxane)2.5 and NaAsCO(18-c-6) in the presence of trimethylphosphine afforded trimethylphosphine-stabilized germylidenyl-phosphinidene 2 and -arsinidene 3, respectively. Structural and computational investigations reveal that the Ge-E' bond (E' = P and As) features a multiple-bond character. 2 and 3 exhibit diverse reactivity toward trimethylsilylacetylene and 4-tetrabutylphenylacetylene. Specifically, 2 underwent cycloadditions with both alkynes affording the first six-membered aromatic phosphagermabenzen-1-ylidenes 4 and 5, respectively, through the heavier isocyanide intermediate MsFluindtBu-PGe. In contrast, 3 could serve as a synthetic equivalent of heavier isocyanides and nitriles when treated with trimethylsilylacetylene and 4-tetrabutylphenylacetylene yielding arsagermene 6 and arsolylgermylene 7, respectively. The reaction mechanisms for the cycloadditions were investigated through density functional theory calculations. The reactivity studies highlight the potential of 2 and 3 in accessing heavy main-group element-containing heterocycles.


MTA1 promotes STAT3 transcription and pulmonary metastasis in breast cancer.
Overexpression of the prometastatic chromatin modifier protein metastasis tumor antigen 1 (MTA1) in human cancer contributes to tumor aggressiveness, but the role of endogenous MTA1 in cancer has not been explored. Here, we report the effects of selective genetic depletion of MTA1 in a physiologically relevant spontaneous mouse model of breast cancer pulmonary metastasis. We found that MTA1 acts as a mandatory modifier of breast-to-lung metastasis without effects on primary tumor formation. The underlying mechanism involved MTA1-dependent stimulation of STAT3 transcription through action on the MTA1/STAT3/Pol II coactivator complex, and, in turn, on the expression and functions of STAT3 target genes including Twist1. Accordingly, we documented a positive correlation between levels of MTA1 and STAT3 in publicly available breast cancer data sets. Together, our findings reveal an essential modifying role of the physiologic level of MTA1 in supporting pulmonary metastasis of breast cancer.


Micro-organisms in Vedas.
The word krimi is used in Veda for different macroscopic & microscopic creatures. Right from bacteria, various insects like kita, patanga were nominated as krimi. Two types of krimi viz. Drishta (Visible/Macroscopic) & Adrishta (Invisible / Microscopic) were described in veda. These two categories encompases nearly all krimi (Microbes / pathogens). According to their origin & Habitat they were categorized as pranyashrayee & Anyasthanashrayee. Different sharirika, manasika & adhyatmic vyadhis were thought to be originated from these Krimis. These harmful & debilitates (Pushtinashaka) organisms were recognized by various names based on troubles/sufferings they produce. Sun & Agni (fire) were described as internal source of krimichikitsa. Today science also confirms this fact. That early morning ultraviolet light rays emanating from sun can be used for various krimijanya-vyadhis. Apart from this various treatment modalities by using various natural resources, vegetable drugs. mineral drugs, fumigation, cleansing (Marjan-prokshana) & hymns were described for krimi & diseases caused by them.


A multi-point heart rate monitoring using a soft wearable system based on fiber optic technology.
Early diagnosis can be crucial to limit both the mortality and economic burden of cardiovascular diseases. Recent developments have focused on the continuous monitoring of cardiac activity for a prompt diagnosis. Nowadays, wearable devices are gaining broad interest for a continuous monitoring of the heart rate (HR). One of the most promising methods to estimate HR is the seismocardiography (SCG) which allows to record the thoracic vibrations with high non-invasiveness in out-of-laboratory settings. Despite significant progress on SCG, the current state-of-the-art lacks both information on standardized sensor positioning and optimization of wearables design. Here, we introduce a soft wearable system (SWS), whose novel design, based on a soft polymer matrix embedding an array of fiber Bragg gratings, provides a good adhesion to the body and enables the simultaneous recording of SCG signals from multiple measuring sites. The feasibility assessment on healthy volunteers revealed that the SWS is a suitable wearable solution for HR monitoring and its performance in HR estimation is strongly influenced by sensor positioning and improved by a multi-sensor configuration. These promising characteristics open the possibility of using the SWS in monitoring patients with cardiac pathologies in clinical (e.g., during cardiac magnetic resonance procedures) and everyday life settings.


[Corneal ulcer caused by Serratia marcescens: case report].
A case of corneal ulcer caused by Serratia marcescens is reported in a patient with history of corneal microtrauma. Biological features (pathogenicity factors, antibiotic resistance) of isolated culture were characterized. Keratitis cases caused by this agent were analyzed.


Diffuse spike-wave status of 9-year duration without behavioral change or intellectual decline.
Continuous, generalized 2.5 to 3.5-Hz spike-wave (SW) discharges were evident in an EEG performed 13 h after a first seizure associated with a viral illness, in an 8-year-old girl. On eye opening, the EEG abnormality was suppressed and replaced by delta activity and brief spike-wave paroxysms. No alteration in consciousness and seizures or behavioral abnormalities accompanied the EEG findings. Based on the EEG, she was diagnosed as having "diffuse electrical status," the rare EEG phenomenon that occurs during wakefulness without associated behavioral changes. Although the child was completely normal clinically, the EEG findings persisted during a 9-year-follow-up period. Ethosuximide (ESM) 1 gr daily resulted in temporary disappearance of the bioelectrical status. During the last 2 years without medication the EEG finding tended to be restricted to the posterior regions.


Treatment of chronic lymphocytic leukemia requires targeting of the protective lymph node environment with novel therapeutic approaches.
Chronic lymphocytic leukemia (CLL) remains associated with low complete response rates and high relapse rates. This is in part due to poor understanding of CLL biology and thus inadequate targeting of therapy. For years CLL has been proposed as bi-compartmental: the quiescent tumor in the periphery and the proliferating cells within specific microenvironments. Historically the bone marrow was considered the major tissue of the CLL microenvironment. However, many recent innovative studies have categorically shown that peripheral CLL cells are derived from the lymph nodes (LN). Proliferation here is largely driven by helper T cells via CD40-CD40L engagement. Critically, in vitro studies have shown that such engagement additionally protects LN CLLs from apoptosis. Agents inducing apoptosis in non-CD40 engaged CLL cells are frequently ineffective against those continually engaged with CD40L. This emphasizes that, in order to improve responses and prevent relapse, novel therapies must be assessed against CD40L engaged CLL cells to show effective targeting against the LN. This review discusses the evidence supporting the superior involvement of the LN in CLL, how CD40L engaged CLL studies should be conducted, and the novel therapies studied in vitro and in vivo that have been proposed to be effective in this setting.


Histone H2A.Z regulates the expression of several classes of phosphate starvation response genes but not as a transcriptional activator.
Phosphate (Pi) availability is a major constraint to plant growth. Consequently, plants have evolved complex adaptations to tolerate low Pi conditions. Numerous genes implicated in these adaptations have been identified, but their chromatin-level regulation has not been investigated. The nuclear actin-related protein ARP6 is conserved among all eukaryotes and is an essential component of the SWR1 chromatin remodeling complex, which regulates transcription via deposition of the H2A.Z histone variant into chromatin. Here, we demonstrate that ARP6 is required for proper H2A.Z deposition at a number of Pi starvation response (PSR) genes in Arabidopsis (Arabidopsis thaliana). The loss of H2A.Z at these target loci results in their derepression in arp6 mutants and correlates with the presence of multiple Pi-starvation-related phenotypes, including shortened primary roots and increases in the number and length of root hairs, as well as increased starch accumulation and phosphatase activity in shoots. Our data suggest a model for chromatin-level control of Pi starvation responses in which ARP6-dependent H2A.Z deposition modulates the transcription of a suite of PSR genes.


Toolkit for visualization of the cellular structure and organelles in Aspergillus niger.
Aspergillus niger is a filamentous fungus that is extensively used in industrial fermentations for protein expression and the production of organic acids. Inherent biosynthetic capabilities, such as the capacity to secrete these biomolecules in high amounts, make A. niger an attractive production host. Although A. niger is renowned for this ability, the knowledge of the molecular components that underlie its production capacity, intercellular trafficking processes and secretion mechanisms is far from complete. Here, we introduce a standardized set of tools, consisting of an N-terminal GFP-actin fusion and codon optimized eforRed chromoprotein. Expression of the GFP-actin construct facilitates visualization of the actin filaments of the cytoskeleton, whereas expression of the chromoprotein construct results in a clearly distinguishable red phenotype. These experimentally validated constructs constitute the first set of standardized A. niger biomarkers, which can be used to study morphology, intercellular trafficking, and secretion phenomena.


Association of Smartphone Ownership and Internet Use With Markers of Health Literacy and Access: Cross-sectional Survey Study of Perspectives From Project PLACE (Population Level Approaches to Cancer Elimination).
Telehealth is an increasingly important component of health care delivery in response to the COVID-19 pandemic. However, well-documented disparities persist in the use of digital technologies. This study aims to describe smartphone and internet use within a diverse sample, to assess the association of smartphone and internet use with markers of health literacy and health access, and to identify the mediating factors in these relationships. Surveys were distributed to a targeted sample designed to oversample historically underserved communities from April 2017 to December 2017. Multivariate logistic regression was used to estimate the association of internet and smartphone use with outcomes describing health care access and markers of health literacy for the total cohort and after stratifying by personal history of cancer. Health care access was captured using multiple variables, including the ability to obtain medical care when needed. Markers of health literacy included self-reported confidence in obtaining health information. Of the 2149 participants, 1319 (61.38%) were women, 655 (30.48%) were non-Hispanic White, and 666 (30.99%) were non-Hispanic Black. The median age was 51 years (IQR 38-65). Most respondents reported using the internet (1921/2149, 89.39%) and owning a smartphone (1800/2149, 83.76%). Compared with the respondents with smartphone or internet access, those without smartphone or internet access were more likely to report that a doctor was their most recent source of health information (344/1800, 19.11% vs 116/349, 33.2% for smartphone and 380/1921, 19.78% vs 80/228, 35.1% for internet, respectively; both P<.001). Internet use was associated with having looked for information on health topics from any source (odds ratio [OR] 3.81, 95% CI 2.53-5.75) and confidence in obtaining health information when needed (OR 1.83, 95% CI 1.00-3.34) compared with noninternet users. Smartphone owners had lower odds of being unable to obtain needed medical care (OR 0.62, 95% CI 0.40-0.95) than nonsmartphone owners. Among participants with a prior history of cancer, smartphone ownership was significantly associated with higher odds of confidence in ability to obtain needed health information (OR 5.63, 95% CI 1.05-30.23) and lower odds of inability to obtain needed medical care (OR 0.17, 95% CI 0.06-0.47), although these associations were not significant among participants without a prior history of cancer. We describe widespread use of digital technologies in a community-based cohort, although disparities persist. In this cohort, smartphone ownership was significantly associated with ability to obtain needed medical care, suggesting that the use of smartphone technology may play a role in increasing health care access. Similarly, major illnesses such as cancer have the potential to amplify health engagement. Finally, special emphasis must be placed on reaching patient populations with limited digital access, so these patients are not further disadvantaged in the new age of telehealth.


Prevalence of autism in Iceland.
This clinic-based study estimated the prevalence of autism in Iceland in two consecutive birth cohorts, subjects born in 1974-1983 and in 1984-1993. In the older cohort classification was based on the ICD-9 in 72% of cases while in the younger cohort 89% of cases were classified according to the ICD-10. Estimated prevalence rates for Infantile autism/Childhood autism were 3.8 per 10,000 in the older cohort and 8.6 per 10,000 in the younger cohort. The characteristics of the autistic groups are presented in terms of level of intelligence, male:female ratio, and age at diagnosis. For the younger cohort scores on the Autism Diagnostic Interview-Revised and the Childhood Autism Rating Scale are reported as well. Results are compared with a previous Icelandic study and recent population-based studies in other countries based on the ICD-10 classification system. Methodological issues are discussed as well as implications for future research and service delivery.


The empty sella syndrome: much ado about nothing.
The empty sella syndrome is probably the commonest cause of an incidental, radiologically enlarged pituitary fossa. Anatomically it indicates a fossa that is partially or wholly filled with cerebrospinal fluid. It is generally an innocuous condition but must be distinguished from sellar expansion due to pituitary tumour.


d-Fused [1]benzazepines with selective in vitro antitumor activity: synthesis and structure-activity relationships.
The synthesis of novel quinolino[3,2-d][1]benzazepines and pyrido[3,2-d][1]benzazepines is described. The in vitro antitumor activity of the compounds has been tested in the antitumor screening of the National Cancer Institute (NCI). Several 2,4-diarylpyrido[3, 2-d][1]benzazepin-6-ones and -thiones turned out to exhibit considerable cytotoxicity for tumor cells. For studies of SAR within these series, substituents were introduced into the aromatic rings of the parent systems. Compounds from the thiolactam series tended to show higher potency than the corresponding lactams. Prominent compounds with noteworthy activity and remarkable selectivity for renal cancer cell lines are the lactams 10c, 10g, and 10h and the corresponding thiolactams 11c, 11g, and 11h. Methylation of the azepine nitrogen leads to complete loss of activity, whereas annelation of a triazolo ring at the lactam site or transformation of the thiolactam function to a thiolactim ether results in decreased antitumor activity and selectivity. Consequently, the secondary lactam or thiolactam structure of the seven-membered ring has to be regarded as essential for selective antitumor activity.


Successful Non-Transplant Treatment of Double Hit Richter Transformation with Long-Term Remission.
Richter transformation (RT) is defined as the transformation of chronic lymphocytic leukemia (CLL) to a high-grade B cell lymphoma. It usually carries a dismal prognosis and represents an unmet need for novel therapeutic interventions. We report a case of an 80-year-old male who developed double-hit (DH) RT with translocations of MYC and BCL6 after 5 years of watchful waiting for standard-risk CLL. He was treated with induction therapy consisting of 4 cycles of anthracycline-based chemoimmunotherapy (CIT) and 2 cycles of platinum-based CIT with intrathecal methotrexate for CNS prophylaxis followed by continuous maintenance therapy with ibrutinib. He achieved complete remission after the induction therapy. At the time of writing, four and a half years after the diagnosis with DH-RT, he remains in complete remission without evidence of RT or CLL. The novel therapeutic approach used in successful treatment of this patient should be further explored.


Flow-injection chemiluminescence determination of acetylsalicylic acid based on its enhancing effect on the lucigenin–hydrogen peroxide system.
A sensitive flow-injection chemiluminescence method for the determination of acetylsalicylic acid is described. It is based on the enhanced chemiluminescent emission of the alkaline lucigenin–H2O2 system by acetylsalicylic acid. The difference in chemiluminescent intensity of alkaline lucigenin–H2O2 in the presence of acetylsalicylic acid from that in the absence of acetylsalicylic acid was linear at acetylsalicylic acid concentrations in the range of 0.0029–47.37 μg/mL, with detection and quantification limits of 0.0011 and 0.0029 μg/mL, respectively. The correlation coefficient of the working curve was 0.9983. The relative standard deviation (n = 10) for 25 μg/mL acetylsalicylic acid is 1.95%. All experimental parameters were optimized. The method was successfully applied to the determination of acetylsalicylic acid in pharmaceutical preparations. The recovery results obtained by the method were satisfactory.


Identification of an alternative CTLA-4 ligand costimulatory for T cell activation.
Stimulation of T cell proliferation generally requires two signals: The first signal is provided by the T cell receptor binding to antigen, and the second signal or costimulus is provided by a different receptor-ligand interaction. In mouse and human, the CD28-B7 interaction has been identified as a source of costimulatory signals. We have identified a cell surface molecule (GL1) that is distinct from B7 and abundantly expressed on activated B cells. On activated B cells GL1, rather than B7, is the predominant ligand for the T cell-activation molecule CTLA-4. GL1 provides a critical signal for T cell-dependent responses in vitro and in vivo.


Local adaptation and ecological differentiation under selection, migration, and drift in Arabidopsis lyrata.
How the balance between selection, migration, and drift influences the evolution of local adaptation has been under intense theoretical scrutiny. Yet, empirical studies that relate estimates of local adaptation to quantification of gene flow and effective population sizes have been rare. Here, we conducted a reciprocal transplant trial, a common garden trial, and a whole-genome-based demography analysis to examine these effects among Arabidopsis lyrata populations from two altitudinal gradients in Norway. Demography simulations indicated that populations within the two gradients are connected by gene flow (0.1 < 4Ne m < 11) and have small effective population sizes (Ne < 6000), suggesting that both migration and drift can counteract local selection. However, the three-year field experiments showed evidence of local adaptation at the level of hierarchical multiyear fitness, attesting to the strength of differential selection. In the lowland habitat, local superiority was associated with greater fecundity, while viability accounted for fitness differences in the alpine habitat. We also demonstrate that flowering time differentiation has contributed to adaptive divergence between these locally adapted populations. Our results show that despite the estimated potential of gene flow and drift to hinder differentiation, selection among these A. lyrata populations has resulted in local adaptation.


Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults.
Past studies have shown that measures of attentional control and semantic memory are sensitive markers of Alzheimer's disease (AD). The effects of established biomarkers of AD (cerebrospinal fluid tau and amyloid-beta42, positron emission tomography Pittsburgh compound-B, and apolipoprotein E [APOE] genotype) on concurrent cognitive performance in cognitively normal individuals have been mixed. The present study examined the utility of combining attentional control with semantic retrieval as a sensitive correlate of AD biomarkers and used mediation analyses to examine possible mechanisms by which the biomarkers influence cognition. Three hundred sixty-three participants completed a category verification task (CVT), and 113 of them concurrently underwent biomarker assessments. On each trial, participants viewed a category (e.g., "unit of time") and verified whether a subsequent target item was an exemplar of the category ("hour") or not ("clock"). Importantly, the nonmembers of the category were associatively related to the category (e.g., "clock" is not "a unit of time," but is highly related), and demanded attentional control to reject. Accuracy to the foil items was the strongest discriminator between healthy aging and very mild symptomatic AD. Cerebrospinal fluid biomarkers had independent yet synergistic influence on CVT performance in cognitively healthy older adults. Furthermore, the influence of the biomarkers and APOE genotype was mediated primarily through increased levels of PIB. The combined influence of attentional control with semantic retrieval is a marker of symptomatic AD and a sensitive correlate of established biomarkers for AD risk in cognitively healthy participants. The biomarkers influenced cognition primarily through increased levels of amyloid in the brain.


Familial risk ratios for high and low physical fitness levels in the Canadian population.
To estimate the familial risk of being physically fit or unfit in Canada. The sample consisted of 11,680 participants from 4144 nuclear families of the 1981 Canada Fitness Survey. Indicators of physical fitness included estimated physical working capacity at a heart rate of 150 beats x min(-1) derived from a step test (PWC150), hand grip strength, sit-ups, and trunk flexibility. Probands were defined as reference individuals who were physically fit (95th, 85th, and 75th percentiles) or physically unfit (25th, 15th, and 5th percentiles) for each fitness indicator, respectively. Standardized risk ratios, adjusted for age and sex (SRR), for spouses and first-degree relatives of probands exceeding the 95th percentile are 1.63 and 1.81 for PWC150, 2.38 and 3.16 for grip strength, 2.63 and 3.98 for sit-ups, and 2.59 and 3.56 for trunk flexibility, respectively, whereas the SRR for spouses and first-degree relatives of probands below the 5th percentile are 1.54 and 1.34 for PWC150, 1.83 and 1.85 for grip strength, 1.13 and 1.53 for sit-ups, and 1.42 and 1.84 for trunk flexibility, respectively. The familial risks tend to be greatest at the extremes (95th and 5th percentiles) and the risks for first-degree relatives of physically fit probands are generally greater than those for spouses for grip strength, sit-ups and trunk flexibility, whereas those for PWC150 show no clear pattern. There is significant familial risk for being physically fit or unfit in the Canadian population. The pattern of SRR suggests that the familial risk for indicators of strength and flexibility may be due, in part, to genetic factors, whereas the shared family environment is largely contributing to the familial risk for PWC150.


Identification and tissue-specific expression of a NADH-dependent activity of dihydropyrimidine dehydrogenase in man.
Homogenates of human liver and human fibroblasts were able to convert thymine into dihydrothymine in the presence of NADH whereas almost no NADH-dependent activity could be detected in human lymphocytes. The different tissue distribution of the NADH-dependent activity suggests that different types of human dihydropyrimidine dehydrogenase exist. Both types of human liver dihydropyrimidine dehydrogenase showed a comparable affinity towards thymine, NADH and NADPH. Only a ten-fold lower Vmax value was observed for the NADH-dependent enzyme. During partial purification of the NADPH-dependent enzyme, on a 2', 5' - ADP Sepharose 4B column, the NADH-dependent activity was completely lost. Neither type of activity was retained on a 5' - AMP Sepharose 4B column.


The Influence of Glycated Hemoglobin on the Cross Susceptibility Between Type 1 Diabetes Mellitus and Periodontal Disease.
Periodontal disease is a major complication of type 1 diabetes mellitus (T1DM). The aim of the present study is to investigate the relationship between glycated hemoglobin and circulating levels of interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand 5 (CXCL5) in non-smoking patients suffering from T1DM, with and without periodontitis. In addition, to determine the effect of advanced glycation end products (AGE) in the presence and absence of Porphyromonas gingivalis lipopolysaccharide (LPS) on IL-6, IL-8, and CXCL5 expression by THP-1 monocytes and OKF6/TERT-2 cells. There were 104 participants in the study: 19 healthy volunteers, 23 patients with periodontitis, 28 patients with T1DM, and 34 patients with T1DM and periodontitis. Levels of blood glucose/glycated hemoglobin (International Federation of Clinical Chemistry [IFCC]) were determined by high-performance liquid chromatography. Levels of IL-6, IL-8, and CXCL5 in plasma were determined by enzyme-linked immunosorbent assay (ELISA). In vitro stimulation of OKF6/TERT-2 cells and THP-1 monocytes was performed with combinations of AGE and P. gingivalis LPS. Changes in expression of IL-6, IL-8, and CXCL5 were monitored by ELISA and real-time polymerase chain reaction. Patients with diabetes and periodontitis had higher plasma levels of IL-8 than patients with periodontitis alone. Plasma levels of IL-8 correlated significantly with IFCC units, clinical probing depth, and attachment loss. AGE and LPS, alone or in combination, stimulated IL-6, IL-8, and CXCL5 expression in both OKF6/TERT-2 cells and THP-1 monocytes. Elevated plasma levels of IL-8 potentially contribute to the cross-susceptibility between periodontitis and T1DM. P. gingivalis LPS and AGE in combination caused significantly greater expression of IL-6, IL-8, and CXCL5 from THP-1 monocytes and OKF6/TERT-2 cells than LPS alone.


Fluorescence "turn-on" chemosensor for the selective detection of zinc ion based on Schiff-base derivative.
N,N'-phenylenebis(salicylideaminato) (L) has been used to detect trace amounts of zinc ion in acetonitrile-water solution by fluorescence spectroscopy. The fluorescent probe undergoes fluorescent emission intensity enhancement upon binding to zinc ions in MeCN/H(2)O (1:1, v/v) solution. The fluorescence enhancement of L is attributed to the 1:1 complex formation between L and Zn(II), which has been utilized as the basis for selective detection of Zn(II). The linear response range for Zn(II) covers a concentration range of 1.6x10(-7) to 1.0x10(-5)mol/L, and the detection limit is 1.5x10(-7)mol/L. The fluorescent probe exhibits high selectivity over other common metal ions, and the proposed fluorescent sensor was applied to determine zinc in water samples and waste water.


The distribution of physical activity in an after-school friendship network.
To examine whether a child's friendship network in an afterschool program influences his/her physical activity. Three waves of data were collected from school-aged children participating in aftercare (n = 81; mean [SD] age, 7.96 [1.74] years; 40% African American, 39% white, and 19% Latino) a name generator survey was used to map each child's social network, and accelerometers were used to measure physical activity. We applied stochastic actor-based modeling for social networks and behavior. Children did not form or dissolve friendships based on physical activity levels, but existing friendships heavily influenced children's level of physical activity. The strongest influence on the amount of time children spent in moderate-to-vigorous activity in the afterschool hours was the activity level of their immediate friends. Children consistently made adjustments to their activity levels of 10% or more to emulate the activity levels of their peers (odds ratio [OR] = 6.89, P < .01). Age (OR = 0.92, P < .10) and obesity status (OR = 0.66, P < .10) had marginally significant and relatively small direct effects on the activity. Gender had no direct effect on activity. These results suggest that friendship ties play a critical role in setting physical activity patterns in children as young as 5 to 12 years. Children's activity levels can be increased, decreased, or stabilized depending on the activity level of their immediate social network during a 12-week afterschool program. Network-based interventions hold the potential to produce clinically significant changes to children's physical activity.


Advance misoprostol distribution for preventing and treating postpartum haemorrhage.
Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious. To assess the effectiveness and safety of a strategy of advance misoprostol distribution for PPH prevention and treatment in non-facility births. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 October 2011). We did not apply any language restrictions. Randomised or quasi-randomised controlled trials of advance misoprostol distribution to lay health workers or pregnant women compared with usual care for PPH prevention or treatment in non-facility births. We excluded studies without any form of random design. Two review authors independently assessed trial eligibility for inclusion. The search strategies identified three studies. None of the studies met the inclusion criteria. There is no evidence from randomised or quasi-randomised trials on the benefits or risks of a strategy of advance misoprostol distribution for PPH prevention or treatment in non-facility births. In view of the increasing interest to scale up this strategy, there is an urgent need for large and well-designed randomised trials to evaluate its comparative benefits and risks.


Spatially resolved scattering polarimeter.
We demonstrate a compact, spatially resolved polarimeter based on a coherent optical fiber bundle coupled with a thin layer of scattering centers. The use of scattering for polarization encoding allows the polarimeter to work across broad angular and spectral domains. Optical fiber bundles provide high spatial resolution of the incident field. Because neighboring elements of the bundle interact with the incident field differently, only a single interaction of the fiber bundle with the unknown field is needed to perform the measurement. Experimental results are shown to demonstrate the capability to perform imaging polarimetry.


Psychological coping in depressed outpatients: association with cortisol response to the combined dexamethasone/CRH test.
Depression is associated with dysfunctional coping styles and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. Studies have shown that maladaptive coping strategies relate to abnormal HPA axis function; however, such a relationship has been under-studied in patients with depression. We aimed to examine whether dysfunctional coping styles in depression would be associated with abnormal cortisol reactivity. Seventy-four outpatients with major depressive disorder and 133 age- and sex-matched healthy individuals were recruited. Coping was assessed by the Ways of Coping Checklist. Psychological distress was assessed by the Hopkins Symptom Checklist. Cortisol reactivity was measured by the combined dexamethasone/corticotropin-releasing hormone test. Compared to healthy individuals, depressed patients demonstrated significantly less use of problem-solving, positive reappraisal and social support coping styles and more use of self-blame and wishful thinking styles. Such a pattern of coping styles was significantly associated with patients' greater distress. Partial correlation analysis in patients, controlling for age and sex, revealed a significant correlation between more use of escape-avoidance coping and lower levels of reactive cortisol measures. A stepwise multiple regression analysis predicting cortisol reactivity from age, sex, distress, symptom severity and coping styles revealed that escape-avoidance coping was a significant predictor. The neuroendocrine challenge test was administered only once, based on a simple test protocol. More use of escape-avoidance coping in depressed patients was associated with less cortisol reactivity. Our findings shed light on the heterogeneity of depression in terms of low and high levels of avoidance associated with exaggerated and blunted HPA axis reactivity, respectively.


Self-configuration and self-optimization process in heterogeneous wireless networks.
Self-organization in Wireless Mesh Networks (WMN) is an emergent research area, which is becoming important due to the increasing number of nodes in a network. Consequently, the manual configuration of nodes is either impossible or highly costly. So it is desirable for the nodes to be able to configure themselves. In this paper, we propose an alternative architecture for self-organization of WMN based on Optimized Link State Routing Protocol (OLSR) and the ad hoc on demand distance vector (AODV) routing protocols as well as using the technology of software agents. We argue that the proposed self-optimization and self-configuration modules increase the throughput of network, reduces delay transmission and network load, decreases the traffic of HELLO messages according to network's scalability. By simulation analysis, we conclude that the self-optimization and self-configuration mechanisms can significantly improve the performance of OLSR and AODV protocols in comparison to the baseline protocols analyzed.


Reclassification of Bifidobacterium stercoris Kim et al. 2010 as a later heterotypic synonym of Bifidobacterium adolescentis.
The taxonomic position of Bifidobacterium stercoris Eg1(T) ( = JCM 15918(T)) based on comparative 16S rRNA gene and hsp60 sequence analyses was found to be controversial, as the strain showed high similarity to the type strain of Bifidobacterium adolescentis, CCUG 18363(T). Therefore, the relationship between the two species was investigated by a taxonomic study that included, in addition to re-evaluation of the 16S rRNA gene sequence, determination of DNA-DNA binding and multilocus sequence analysis (MLSA) of housekeeping genes encoding the DNA-directed RNA polymerase B subunit (rpoC), putative xylulose-5-phosphate/fructose-6-phosphate phosphoketolase (xfp), elongation factor EF-G (fusA), 50S ribosomal protein L2 (rplB) and DNA gyrase B subunit (gyrB). Comparative 16S rRNA gene sequence analysis showed relatively high similarity (98.9 %) between B. stercoris KCTC 5756(T) and B. adolescentis ATCC 15703(T). MLSA revealed close relatedness between B. stercoris KCTC 5756(T) and B. adolescentis CCUG 18363(T), with 99.3-100 % similarity between the rpoC, xfp, fusA, rplB and gyrB gene sequences. In addition, relatively high dnaJ1 gene sequence similarity of 97.7 % was found between the strains. Similar phenotypes and a high DNA-DNA binding value (78.9 %) confirmed that B. stercoris and B. adolescentis are synonymous. Based on these results, it is proposed that the species Bifidobacterium stercoris Kim et al. 2010 should be reclassified as a later heterotypic synonym of Bifidobacterium adolescentis Reuter 1963 (Approved Lists 1980).


[Allergic contact eczema due to 'tea tree' oil].
In four patients, three women aged 45, 29 and 52 years and a man aged 45 years, allergic contact dermatitis due to 'tea tree' oil was diagnosed. The case of the man was published before. 'Tea tree' oils are essential oils distilled from the leaves of myrtaceous trees and shrubs occurring in Australia and South-East Asia. The 'tea tree' oil available in the Netherlands is distilled from the Melaleuca alternifolia and mainly contains eucalyptol. Eucalyptol is probably the most important allergen.


Genome-Wide Identification, Cloning and Functional Analysis of the Zinc/Iron-Regulated Transporter-Like Protein (ZIP) Gene Family in Trifoliate Orange (Poncirus trifoliata L. Raf.).
Zinc (Zn) and iron (Fe) deficiency are widespread among citrus plants, but the molecular mechanisms regarding uptake and transport of these two essential metal ions in citrus are still unclear. In the present study, 12 members of the Zn/Fe-regulated transporter (ZRT/IRT)-related protein (ZIP) gene family were identified and isolated from a widely used citrus rootstock, trifoliate orange (Poncirus trifoliata L. Raf.), and the genes were correspondingly named as PtZIPs according to the sequence and functional similarity to Arabidopsis thaliana ZIPs. The 12 PtZIP genes were predicted to encode proteins of 334-419 amino acids, harboring 6-9 putative transmembrane (TM) domains. All of the PtZIP proteins contained the highly conserved ZIP signature sequences in TM-IV, and nine of them showed a variable region rich in histidine residues between TM-III and TM-IV. Phylogenetic analysis subdivided the PtZIPs into four groups, similar as found for the ZIP family of A. thaliana, with clustered PtZIPs sharing a similar gene structure. Expression analysis showed that the PtZIP genes were very differently induced in roots and leaves under conditions of Zn, Fe and Mn deficiency. Yeast complementation tests indicated that PtIRT1, PtZIP1, PtZIP2, PtZIP3, and PtZIP12 were able to complement the zrt1zrt2 mutant, which was deficient in Zn uptake; PtIRT1 and PtZIP7 were able to complement the fet3fet4 mutant, which was deficient in Fe uptake, and PtIRT1 was able to complement the smf1 mutant, which was deficient in Mn uptake, suggesting their respective functions in Zn, Fe, and Mn transport. The present study broadens our understanding of metal ion uptake and transport and functional divergence of the various PtZIP genes in citrus plants.


Sleep apnoea.
Sleep apnoea is the popular term for obstructive sleep apnoea-hypopnoea syndrome (OSAHS). OSAHS is abnormal breathing during sleep that causes recurrent arousals, sleep fragmentation, excessive daytime sleepiness, and nocturnal hypoxaemia. Apnoea may be "central", in which there is cessation of inspiratory effort, or "obstructive", in which inspiratory efforts continue but are ineffective because of upper airway obstruction. OSAHS affects up to 4% of men and 2% of women in the USA, with obesity being a major determinant. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatment for severe obstructive sleep apnoea-hypopnoea syndrome? What are the effects of treatment for non-severe obstructive sleep apnoea-hypopnoea syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: nasal continuous positive airway pressure (CPAP); measures aimed at improving compliance with CPAP; oral appliances; and weight loss.


Longitudinal relationships among posturography and gait measures in multiple sclerosis.
Gait and balance dysfunction frequently occurs early in the multiple sclerosis (MS) disease course. Hence, we sought to determine the longitudinal relationships among quantitative measures of gait and balance in individuals with MS. Fifty-seven ambulatory individuals with MS (28 relapsing-remitting, 29 progressive) were evaluated using posturography, quantitative sensorimotor and gait measures, and overall MS disability with the Expanded Disability Status Scale at each session. Our cohort's age was 45.8 ± 10.4 years (mean ± SD), follow-up time 32.8 ± 15.4 months, median Expanded Disability Status Scale score 3.5, and 56% were women. Poorer performance on balance measures was related to slower walking velocity. Two posturography measures, the anterior-posterior sway and sway during static eyes open, feet apart conditions, were significant contributors to walk velocity over time (approximate R(2) = 0.95), such that poorer performance on the posturography measures was related to slower walking velocity. Similarly, the anterior-posterior sway and sway during static eyes closed, feet together conditions were also significant contributors to the Timed 25-Foot Walk performance over time (approximate R(2) = 0.83). This longitudinal cohort study establishes a strong relationship between clinical gait measures and posturography. The data show that increases in static posturography and reductions in dynamic posturography are associated with a decline in walk velocity and Timed 25-Foot Walk performance over time. Furthermore, longitudinal balance measures predict future walking performance. Quantitative walking and balance measures are important additions to clinical testing to explore longitudinal change and understand fall risk in this progressive disease population.


[Is detection and treatment of familial hypercholesterolemia indicated in children?].
Familial hypercholesterolaemia (FH) is a congenital metabolic disorder predisposing to severe atherosclerosis resulting in coronary heart disease sometimes even at early adult age. Children with FH lack the stigmata at physical examination and measuring the cholesterol level does not always enable the clinician to make the diagnosis. In about 70% of the cases, the diagnosis of FH in childhood can be made by means of molecular-biological examination, by demonstrating the underlying defect of the LDL cholesterol receptor gene. In the remaining cases, the combination of the positive family history for cardiovascular diseases and increased total cholesterol and LDL cholesterol levels should suggest the diagnosis of FH. Pharmaceutical agents inhibiting the cholesterol synthesis have been researched very little in children and are not registered in the Netherlands. Nevertheless, drug treatment of children with FH is advisable because of the better possibilities to make a definite diagnosis and the early occurrence of coronary heart disease. If this treatment were indicated before patients reach adult age, the question arises whether screening for FH of children in families in which this disorder prevails, should not be promoted more strongly.


Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice.
Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2.


Homelessness and mental health in Ghana: everyday experiences of Accra's migrant squatters.
This article discusses everyday experiences of transient homelessness in Ghana's capital, Accra. Episodic interviews with individuals living in squatter settlements in the wealthy East Legon suburb explored: (1) roots of homelessness; (2) everyday experiences and coping strategies; (3) relationship between experiences and (mental) health; (4) needs and interventions. Three intersecting forms of insecurity framed participants' everyday experience: financial, legal and psychosocial. Physical and psychological stresses were common; physical illnesses rare. Coping strategies facilitated adaptation but not transformation of everyday circumstances. We explore possibilities for intervention and discuss relevance of this study to the health psychology and African literatures on homelessness.


Soldier peer mentoring care and support: bringing psychological awareness to the front.
Since the Persian Gulf War of 1990-1991, the operational tempo for soldiers has steadily increased, whereas the numbers of soldiers available to fulfill these missions has decreased. As a result, soldiers and their families are experiencing increased levels of stress that continue to manifest in ways that can often be destructive for the soldiers, their families, and the Army community. Current mitigation and identification support systems such as the Chain of Command, noncommissioned officer leadership, chaplains, and family support systems have all provided critical services, but may not be expected to optimally perform necessary early risk management assessment. Behavioral health care as a self-referral system is often still perceived as career ending, shameful, or even culturally unacceptable. Our allies have also experienced similar family, operational, and combat concerns. In 1996, at the direction of their Commandant General, the British Royal Marines developed and instituted a peer-driven risk management and support system that has experienced a high degree of success and acceptance among its forces-enough so that the Royal Navy is now in the process of implementing a similar program. The Soldier Peer Mentoring and Support program, as part of the proposed deployment Cycle Support Program, is a model for peer group assessment based on the British Royal Marines psychological risk management and support system. This article presents and describes this project, which has been considered for use within the U.S. Army, as a potential augmenter of existing behavioral health support assets as a culturally acceptable, company-level support program in deployment and home stations.


The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion.
The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. Over-diagnosis and over-treatment are common. To develop a pre-test clinical scoring model for HIT based on broad expert opinion that may be useful in guiding clinical decisions regarding therapy. A pre-test model, the HIT Expert Probability (HEP) Score, was constructed based on the opinions of 26 HIT experts. Fifty patients referred to a reference laboratory for HIT testing comprised the validation cohort. Two hematology trainees scored each patient using the HEP Score and a previously published clinical scoring system (4 T's). A panel of three independent experts adjudicated the 50 patients and rendered a diagnosis of HIT likely or unlikely. All subjects underwent HIT laboratory testing with a polyspecific HIT ELISA and serotonin release assay (SRA). The HEP Score exhibited significantly greater interobserver agreement [intraclass correlation coefficient: 0.88 (95% CI 0.80-0.93) vs. 0.71 (0.54-0.83)], correlation with the results of HIT laboratory testing and concordance with the diagnosis of the expert panel (area under receiver-operating curve: 0.91 vs. 0.74, P = 0.017) than the 4 T's. The model was 100% sensitive and 60% specific for determining the presence of HIT as defined by the expert panel and would have allowed for a 41% reduction in the number of patients receiving a direct thrombin inhibitor (DTI). The HEP Score is the first pre-test clinical scoring model for HIT based on broad expert opinion, exhibited favorable operating characteristics and may permit clinicians to confidently reduce use of alternative anticoagulants. Prospective multicenter validation is warranted.


Acoustics Apps: Interactive simulations for digital teaching and learning of acoustics.
This paper presents the Acoustics Apps, an e-learning platform that offers an interactive and playful environment for teaching and learning the principles of acoustics and vibration. The Acoustics Apps address the increasing demand for digitized teaching methods, which might be suitable for home schooling or as a complement to physical experiments by adding interactive simulation. The apps combine learning by experimenting, observing, and exploring using state-of-the-art scientific methods and numerical simulations. The ability to visualize and control acoustic phenomena facilitates understanding of the relevant physical principles. The apps are designed to be used intuitively and can be tailored to suit the existing knowledge of the user. As such, a wide range of users can benefit from this learning aid. It has been developed to allow barrier-free access to modern educational tools, requiring only a device with a browser and Internet access. The necessary computing power is provided by an external server using the COMSOL ServerTM technology. The Acoustics Apps are freely available for academic and teaching purposes at apps.vib.mw.tum.de.


Coral recovery at Aldabra Atoll, Seychelles: five years after the 1998 bleaching event.
Changes in reef benthos were assessed at Aldabra Atoll following the mass coral bleaching event of 1998. Video transects were used to survey the benthos and analysed using the Australian Institute of Marine Science five-dot method. Comparison of coral cover data collected by the Cambridge Southern Seychelles Atoll Research Programme with data collected during this study revealed that mortality of coral at Aldabra following the bleaching event was approximately 66% at 10 m depth and 38% at 20 m depth. Five years on, there are signs of hard coral recovery at some locations, but in spite of several years of high coral recruitment (7-9 recruits per m2 at 10 m depth, 4-6 recruits per m2 at 20 m depth, where recruits are defined as any colony under 5 cm maximum diameter), recovery of hard coral has not occurred at a significant level. There has been a considerable increase in soft coral cover at some locations, which was dominated by the genus Rhytisma. Macro algal cover did not increase following the bleaching event, although, as would be expected, dead corals have been colonized by coralline algae. There have been no further events leading to large-scale coral mortality at Aldabra since 1998.


Mutations in the voltage-dependent anion channel of the mitochondrial outer membrane cause a dominant nonlethal growth impairment.
Point mutations at K234 and K236 in the yeast voltage-dependent anion channel 1 (VDAC1) of the mitochondrial outer membrane have been shown to markedly impair the membrane insertion of this protein (Smith et al., 1995; Angeles et al., 1998). Mutants of this type were expressed in vivo in a strain of yeast with a disruption in the VDAC1 gene. Expression of the various VDAC1 forms was under the control of a Gall promoter. Wild-type VDAC1 expression fully complemented the slow growth phenotype caused by the disruption. VDAC1 mutants in which K234 and K236 were replaced by arginine, glutamate, or glutamine caused a more severe negative effect on growth. This effect appeared to be dominant since the mutant VDAC1 forms suppressed growth in a yeast strain that retained its VDAC1 gene. This apparent dominant negative effect on growth did not seem to be specific for any stage of the cell cycle. However, the growth defect was not lethal as the affected cells still could accumulate the vital stain, FUN1. Expression of a mutant in which K234 had been replaced by glutamate had more serious negative growth effects than did a similar mutation at K236. Expression of delta71-116 VDAC1 complemented the VDAC1 disruption; however, expression of the same deletion mutant in which the lysines corresponding to K234 and K236 were mutated to glutamate severely impaired growth. These results have shown that a deficiency of lysine at positions 234 and 236 in VDAC I causes a nonlethal growth defect that is more severe than deletion of 45 amino acids from VDACI or disruption of the VDAC1 gene. They also indicate that there is a hierarchy in the importance of these lysines with mutations at K234 being the more serious.


Layered boron nitride as a release layer for mechanical transfer of GaN-based devices.
Nitride semiconductors are the materials of choice for a variety of device applications, notably optoelectronics and high-frequency/high-power electronics. One important practical goal is to realize such devices on large, flexible and affordable substrates, on which direct growth of nitride semiconductors of sufficient quality is problematic. Several techniques--such as laser lift-off--have been investigated to enable the transfer of nitride devices from one substrate to another, but existing methods still have some important disadvantages. Here we demonstrate that hexagonal boron nitride (h-BN) can form a release layer that enables the mechanical transfer of gallium nitride (GaN)-based device structures onto foreign substrates. The h-BN layer serves two purposes: it acts as a buffer layer for the growth of high-quality GaN-based semiconductors, and provides a shear plane that makes it straightforward to release the resulting devices. We illustrate the potential versatility of this approach by using h-BN-buffered sapphire substrates to grow an AlGaN/GaN heterostructure with electron mobility of 1,100 cm(2) V(-1) s(-1), an InGaN/GaN multiple-quantum-well structure, and a multiple-quantum-well light-emitting diode. These device structures, ranging in area from five millimetres square to two centimetres square, are then mechanically released from the sapphire substrates and successfully transferred onto other substrates.


A systematic review of non-pharmacological interventions for BPSD in nursing home residents with dementia: from a perspective of ergonomics.
Non-pharmacological interventions for Behavioral and Psychological Symptoms of Dementia (BPSD) have been developed; however, a systematic review on the effectiveness of this type of intervention from a perspective of ergonomics is lacking. According to ergonomics, the capabilities of Persons with Dementia (PwD) should be considered in the interventions for the outcomes to be reliable. We aimed to systematically review the non-pharmacological interventions for BPSD in nursing home residents with an additional assessment criterion based on ergonomics, specifically, capability consideration. The electronic databases MEDLINE, EMBASE, and PsycINFO were searched for non-pharmacological interventions treating BPSD in nursing homes. The interventions were categorized according to the capabilities of PwD required to participate. Study quality was assessed by National Health and Medical Research Council (NHMRC) evidence hierarchy and the capability consideration. Sixty-four clinical trials met the inclusion criteria; 41 trials reported a significant reduction in at least one BPSD symptom; 20 trials reported no significant reduction in BPSD symptoms; three trials reported adverse effects after the intervention. Interventions were categorized into sensory-, cognition-, and movement-oriented. Capabilities of PwD were not considered in 28 trials, especially for sensory capabilities. The majority of the clinical trials reported a significant reduction in BPSD. The quality of evidence for nonpharmacological interventions in these trials is low due to the lack of capability consideration, data inhomogeneity, and inadequate study design and reporting. Future studies should focus on improving the quality of evidence by including capability consideration and examining if a relationship between capability consideration and effectiveness of non-pharmacological interventions exists.


THE RHEOLOGY OF THE BLOOD. III.
The authors have confirmed the fact that blood serum and plasma behave rheologically like a true viscous liquid. It is true for whole blood only to a first approximation, but with this reservation they have studied the available data and extended the equation of Bingham and Durham to cover protein solutions of various concentrations and at various temperatures as well as mixtures of proteins and corpuscles present in whole blood. If Phi is the fluidity of whole blood, Phi(1) is the fluidity of water and DeltaPhi = Phi - Phi(1), then DeltaPhi = beta(1)b(1) + beta(2)b(2) + beta(3)b(3) + ... where beta(1), beta(2), beta(3), etc., are constants for the fluidity lowering of the salts, albumin, globulin, fibrinogen, and the corpuscles, etc., present in the whole blood. The conclusions from the data referred to are intended to buttress this simple equation (6).


Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype.
Breast cancer has recently been linked to cadmium exposure. Although not uniformly supported, it is hypothesized that cadmium acts as a metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the effects of chronic exposure to cadmium on the normal human breast epithelial cell line MCF-10A, which is ER-negative but can convert to ER-positive during malignant transformation. Cells were continuously exposed to low-level cadmium (2.5 μM) and checked in vitro and by xenograft study for signs of malignant transformation. Transformant cells were molecularly characterized by protein and transcript analysis of key genes in breast cancer. Over 40 weeks of cadmium exposure, cells showed increasing secretion of matrix metalloproteinase-9, loss of contact inhibition, increased colony formation, and increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated cells into mice produced invasive, metastatic anaplastic carcinoma with myoepithelial components. These cadmium-transformed breast epithelial (CTBE) cells displayed characteristics of basal-like breast carcinoma, including ER-alpha negativity and HER2 (human epidermal growth factor receptor 2) negativity, reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell markers, were prominently overexpressed in CTBE cell mounds, indicative of persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc and k-ras overexpression, typical in aggressive breast cancers. CTBE cell xenograft tumors were also ER-alpha negative. Cadmium malignantly transforms normal human breast epithelial cells-through a mechanism not requiring ER-alpha-into a basal-like cancer phenotype. Direct cadmium induction of a malignant phenotype in human breast epithelial cells strongly fortifies a potential role in breast cancer.


Comparing the power of family-based association tests for sequence data with applications in the GAW18 simulated data.
We apply a family-based extension of the sequence kernel association test (SKAT) to 93 trios extracted from the 20 pedigrees in the Genetic Analysis Workshop 18 simulated data. Each extracted trio includes a unique set of parents to ensure conditionally independent trios are sampled. We compare the empirical type I error and power between the family-based SKAT and the burden test under varying percentages of causal single-nucleotide polymorphisms included in the analysis. Our investigation using simulated data suggests that, under the setting used for Genetic Analysis Workshop 18 data, both the family-based SKAT and the burden test have limited power, and that there is no substantial impact of percentage of signal on the power of either test. The low power is partially a result of the small sample size. However, we find that both the family-based SKAT and the burden test are more powerful when we use only rare variants, rather than common variants, to test the association.


Untargeted metabolomics analysis reveals the metabolic disturbances and exacerbation of oxidative stress in recurrent spontaneous abortion.
Recurrent spontaneous abortion (RSA) is characterized by the occurrence of two or more consecutive spontaneous abortions, with a rising prevalence among pregnant women and significant implications for their physical and mental well-being. The multifaceted etiology of RSA has posed challenges in unraveling the molecular mechanisms underlying that underlie its pathogenesis. Oxidative stress and immune response have been identified as pivotal factors in the development of its condition. Eleven serum samples from healthy pregnant women and 17 from RSA were subjected to liquid chromatography/mass spectrometry (LC-MS) analysis. Multivariate statistical analysis was employed to excavate system-level characterization of the serum metabolome. The measurement of seven oxidative stress products, namely superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), glutathione (GPx), glutathione peroxidase (GSH), oxidized glutathione (GSSG), heme oxygenase (HO-1), was carried out using ELISA. Through the monitoring of metabolic and lipid alternations during RSA events, we have identified 816 biomarkers that were implicated in various metabolic pathways, including glutathione metabolism, phosphonate and phosphinate metabolism, nucleotide metabolism, sphingolipid metabolism, lysine degradation and purine metabolism, etc. These pathways have been found to be closely associated with the progression of the disease. Our finding indicated that the levels of MDA and HO-1 were elevated in the RSA group compared to the control group, whereas SOD, CAT and GPx exhibited a contrary pattern. However, no slight difference was observed in GSH and GSSG levels between the RSA group and the control group. The manifestation of RSA elicited discernible temporal alternations in the serum metabolome and biochemical markers linked to the metabolic pathways of oxidative stress and immune response. Our investigation furnished a more comprehensive analytical framework encompassing metabolites and enzymes associated with oxidative stress. This inquiry furnished a more nuanced comprehension of the pathogenesis of RSA and established the ground work for prognostication and prophylaxis.


Panic attack symptom dimensions and their relationship to illness characteristics in panic disorder.
Subtyping panic disorder by predominant symptom constellations, such as cognitive or respiratory, has been done for some time, but criteria have varied considerably between studies. We sought to identify statistically symptom dimensions from intensity ratings of 13 DSM-IV panic symptoms in 343 panic patients interviewed with the Anxiety Disorders Interview Schedule for DSM-IV Lifetime Version. We then explored the relation of symptom dimensions to selected illness characteristics. Ratings were submitted to exploratory maximum likelihood factor analysis with a Promax rotation. A three-factor solution was found to account best for the variance. Symptoms loading highest on the first factor were palpitations, shortness of breath, choking, chest pain, and numbness, which define a cardio-respiratory type (with fear of dying). Symptoms loading highest on the second factor were sweating, trembling, nausea, chills/hot flashes, and dizziness, which defines a mixed somatic subtype. Symptoms loading highest on the third factor were feeling of unreality, fear of going crazy, and fear of losing control, which defines a cognitive subtype. Subscales based on these factors showed moderate intercorrelations. In a series of hierarchical multiple regression analyses, the cardio-respiratory subscale was a strong predictor of panic severity, frequency of panic attacks, and agoraphobic avoidance, while the cognitive subscale mostly predicted worry due to panic. In addition, patients with comorbid asthma had higher scores on the cardio-respiratory subscale. We conclude that partly independent panic symptom dimensions can be identified that have different implications for severity and control of panic disorder.


Orientation-resolving pulsed electron dipolar high-field EPR spectroscopy on disordered solids: I. Structure of spin-correlated radical pairs in bacterial photosynthetic reaction centers.
Distance and relative orientation of functional groups within protein domains and their changes during chemical reactions determine the efficiency of biological processes. In this work on disordered solid-state electron-transfer proteins, it is demonstrated that the combination of pulsed high-field EPR spectroscopy at the W band (95 GHz, 3.4 T) with its extensions to PELDOR (pulsed electron-electron double resonance) and RIDME (relaxation-induced dipolar modulation enhancement) offers a powerful tool for obtaining not only information on the electronic structure of the redox partners but also on the three-dimensional structure of radical-pair systems with large interspin distances (up to about 5 nm). Strategies are discussed both in terms of data collection and data analysis to extract unique solutions for the full radical-pair structure with only a minimum of additional independent structural information. By this novel approach, the three-dimensional structure of laser-flash-induced transient radical pairs P(865)(*+)Q(A)(*-) in frozen-solution reaction centers (RCs) from the photosynthetic bacterium Rhodobacter (Rb.) sphaeroides is solved. The measured positions and relative orientations of the weakly coupled ion radicals P(865)(*+) and Q(A)(*-) are compared with those of the precursor cofactors P865 and QA known from X-ray crystallography. A small but significant reorientation of the reduced ubiquinone QA is revealed and interpreted as being due to the photosynthetic electron transfer. In contrast to the large conformational change of Q(B)(*-) upon light illumination of the RCs, the small light-induced reorientation of Q(A)(*-) had escaped previous attempts to detect structural changes of photosynthetic cofactors upon charge separation. Although small, they still may be of functional importance for optimizing the electronic coupling of the redox partners in bacterial photosynthesis both for the charge-separation and charge-recombination processes.


Vertical canal function in normal subjects and patients with benign paroxysmal positional vertigo.
To assess the dynamics of the vertical semicircular canal (VSCC)-ocular reflex in normal subjects and then to compare their gain in VSCC-ocular reflex with that of patients with benign paroxysmal positional vertigo (BPPV). Subjects were sinusoidally rotated around the earth-vertical axis with their head tilted 60 degrees backward and turned 45 degrees to the right or left side from the sagittal plane at frequencies of 0.1, 0.3, 0.5, 0.7 and 1.0 Hz with a maximum angular velocity of 50 degrees/s. Head rotation to the right side on the right anterior semicircular canal (SCC)-left posterior SCC plane or to the left side on the left anterior SCC-right posterior SCC plane stimulated the pair of VSCCs. Eye movements were recorded on a video imaging system with an infrared charge-coupled device camera, using our new technique for analyzing the rotation vector of eye movements in three dimensions. The mean gains in left posterior SCC-ocular reflex in normal subjects ranged from 0.44 at 0.1 Hz to 0.79 at 1.0 Hz, while the mean gains in right anterior SCC-ocular reflex ranged from 0.45 at 0.1 Hz to 0.73 at 1.0 Hz. The mean gains in right posterior SCC-ocular reflex in normal subjects ranged from 0.53 at 0.1 Hz to 0.89 at 1.0 Hz, while the mean gains in left anterior SCC-ocular reflex ranged from 0.53 at 0.1 Hz to 0.88 at 1.0 Hz. Thus, the gains in VSCC-ocular reflex did not differ among the four VSCCs in normal subjects. Similarly, vestibulo-ocular reflex (VOR) gains of the four VSCCs in patients with right- or left-sided BPPV were almost the same at all frequencies compared to those of normal subjects. In patients with BPPV, gains in VOR in the four VSCCs were not changed in comparison with those of normal subjects. It is suggested that the mass of free-floating otoconial debris associated with canalolithiasis was too small compared to that of the endolymph to change the canal dynamics.


The value of lymphoscintigraphy, lymphangiography and computer tomography scanning in the preoperative assessment of lymph nodes involved by pelvic malignant conditions.
In a preoperative study to identify accurately metastases to the lymph nodes within the pelvis and retroperitoneum, the three imaging techniques of pelvic interstitial lymphoscintigraphy, bipedal lymphangiography and computer tomography (CT) scanning were compared in 69 patients with carcinoma of the cervix uteri or rectum. Results were correlated with histologic node examination in all patients and each technique was assessed for sensitivity, specificity and over-all accuracy. Lymphoscintigraphy is too unreliable for routine use in the diagnosis or staging of pelvic malignant conditions. Lymphangiography detects involved lateral pelvic and para-aortic nodes but is unable to visualize the internal iliac or other medial pelvic nodes. CT scanning is only accurate if metastatic nodes are enlarged but may reveal other pathways of spread which will alter the surgical approach.


Development of the IRIS-AR strategy: an intervention to improve rates of accrual and retention for the VTE-PRO randomized controlled trial.
The Venous Thromboembolism Prophylaxis (VTE-PRO) randomized trial is a pilot study evaluating the impact of extended-duration prophylaxis on venous thromboembolic events in patients undergoing lung cancer resection. Enrolled VTE-PRO participants self-inject either low-molecular weight heparin or a saline placebo for 30 days postoperatively. Study outcomes include feasibility, incidence of venous thromboembolism, and venous thromboembolism-related morbidity and mortality. Initial analyses demonstrated low rates of accrual and retention for the VTE-PRO pilot. Therefore, the purpose of the current study was to develop a knowledge translation intervention to improve VTE-PRO pilot trial accrual and retention. Eligible participants were surveyed to identify the barriers to VTE-PRO participation. The Theoretical Domains Framework was used to categorize these barriers. Barriers were mapped to the capabilities, opportunities, and behavior (COM-B) behavioral change wheel to identify potential interventions to support trial accrual and retention. The resulting knowledge translation intervention was titled Inform, Remind, Involve and Support to improve Accrual and Retention (IRIS-AR). Key informant interviews with patients were held to refine and confirm the validity of identified barriers and perceived acceptability of the proposed IRIS-AR intervention. Institutional Review Board approval was granted for this study. The resulting intervention included: information booklets and counseling sessions to identify unique participant challenges to trial participation (Inform); daily reminders to administer injections (Remind); involvement of family/caregivers in study processes (Involve); and leverage of an existing home-care nursing program to provide injection support when needed (Support). Twenty-six key informant participants were interviewed. The most common barriers to trial participation included lack of social support and fear of needle injection. Participants generally supported use of information booklets, involvement of family/caregivers, and support by a home-care nursing program; however, not all supported the use of daily reminders. Developed using theory and integrated knowledge translation, the IRIS-AR presents a patient-centered intervention that leverages existing programs to promote trial engagement. The proposed strategy can likely be adapted to improve compliance with other patient-directed interventions. ClinicalTrials.gov, NCT02334007 . Registered on 8 January 2015.


Artesunate enhances radiosensitivity of esophageal cancer cells by inhibiting the repair of DNA damage.
Radiotherapy plays an important therapeutic role in esophageal cancer (EC). However, acquired radioresistance impairs the efficacy of radiotherapy, often leading to treatment failure. Therefore, it is important to develop novel radiosensitizers to enhance the clinical treatment of EC. The purpose of this study was to investigate the role of artesunate (ART) on radiosensitivity of human EC cell line TE-1. We found that ART inhibited the proliferation of EC cells and enhanced the radiosensitivity of TE-1 cells (SER = 1.24). In vivo tumor growth of xenografts was inhibited markedly by irradiation (IR) combined with ART, with a tumor inhibition rate of 53.76% in IR + ART group vs. 41.13% in IR-alone group. Pretreatment with ART significantly prompted cell apoptosis and reversed the IR-induced G2/M arrest. ART treatment could aggravate DNA damage of EC cells and prolong the formation of γ-H2AX foci induced by IR. ART up-regulated P21 and down-regulated the expression of cyclin D1, RAD51, RAD54, Ku70 and Ku86 protein of irradiated TE-1 cells. These findings support that ART induce radiosensitivity of TE-1 cells in vitro and in vivo, and may prove to be a promising radiosensitizer for EC treatment.


Surgery of foot drop in leprosy by tibialis posterior transfer.
In the surgery of foot drop the common method of correction is by transfer of tibialis posterior muscle, either to the joint capsule in the middle of the foot (Selvapandian's method) or a double transfer to the toe extensor tendons (Srinivason's method). A retrospective study was done to compare the results of surgery done by those two methods at the Sacred Heart Leprosy Centre, Kumbakonam with a follow-up ranging from one to nine years where 78 feet had tibialis posterior transfer by Srinivasan's method and 20 by Selvapandian-Brand method. Restoration of the normal heel-toe gait was the criteria taken to evaluate the results. Good results were obtained by either method in nearly 70% of cases. The post operative findings and the causes of failure are analysed in detail. The pre and post-operative physiotherapy methods which mainly contribute a successful result are described and stressed.


[Interlevel relations in neural memory: extrasynaptic reception of mediators, potentiation, and spontaneous activity].
The firing of "spontaneous" spikes is regarded as a result of mediator propagation to extrasynaptic receptors. Receptor-receptor interaction unites them in dimer and dimer clusters, which accept three conformational states under agonist action. There are two cooperative and potential dependent transitions between the states, where cluster accumulates or releases energy. The released energy can trigger a mechanism of endogenous (spontaneous) neuron firing in potentiation condition. These accumulating and triggering properties are absent in third (passive) conformational state, where gating charges immobilization reduces conformational mobility. The features of ionotropic, metabotropic and combined mediator action are discussed for different level of slow potential. Conformational effect depends on conformity of pattern space-temporal structure to geometric and functional features of metabotropic mediator sources in cluster environment. Each cluster appears to be adjusted for recognizing a certain vast set of afferent patterns. Number, structure and dimensionality of the recognized patterns are given by: 1) threshold of conformational transition, 2) allocation of synaptic and extrasynaptic mediator ejecting points in gap-hole environment of the receptive cluster 3) combinatorial connections of presynaptic cells with inhibit and excite synapses and 4) signal delays in presynaptic ways and neuropil. Numerous receptive clusters of soma-dendrite membrane are capable to write down information, to keep and accumulate it and to recover. Engram stored as passive/active conformational receptive cluster states is recovered in inversion by "spontaneous" neuronal activity. The original information may be recovered by reading via inhibit synapses.