Palliative Hypofractionated Radiotherapy For Non-small-cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy.
To investigate the effectiveness and toxicity of radiotherapy (RT) given as 17 Gy in 2 fractions, in patients with locally advanced non-small-cell lung cancer (NSCLC) previously treated by platinum-based chemotherapy (CHT) and the impact of total tumor volume (TTV) on symptoms control. Patients with inoperable NSCLC resistant to induction platinum-based CHT, who developed symptoms during or just after radiotherapy, were treated by 17 Gy in two fractions one week apart. In 12/28 patients a minimal response (up to 20% of TTV) and in 16/28 a stable or locally progressive disease had been recorded after induction CHT. In 26/28 patients, symptoms were present during-after CHT and before RT. The prognostic significance of pre-RT TTV on symptoms control and patients survival was also examined. We report on 28 patients. Response rates for the four main symptoms were: cough 13/19 (68%), haemoptysis 9/10 (90%), pain 8/14 (57%) and dyspnoea 5/13 (38%). Hematologic and local-thoracic toxicities were minimal. The median survival from the beginning of RT, for the whole group of patients was 9 months (95% CI:3.7-14.3), while for those patients with TTV<120 cc it was 12 months, and for those with TTV 120cc, it was 5.2 months. TTV was not suggested to influence symptoms control rate. The two-fraction radiotherapy course is safe and effective in palliation of symptomatic non-small-cell lung cancer patients non-responding to induction CHT. Present data suggests that the TTV may influence survival time.


Psychometric Properties of the Turkish Versions of the Cannabis Use Problems Identification Test (CUPIT) and the Adult Cannabis Problems Questionnaire (CPQ).
Cannabis and synthetic cannabinoids are widely used illicit substances in Turkey. The Cannabis Use Problems Identification Test (CUPIT) is a brief self-report screening instrument for detection of problematic cannabis use, whereas the Cannabis Problems Questionnaire (CPQ) is a measure for cannabis treatment outcome. The aim of this study was to evaluate the psychometric properties of the CUPIT and CPQ among Turkish male outpatients with cannabis (n = 52) and synthetic cannabinoid (n = 45) use disorder. Participants were evaluated with the CUPIT, the CPQ, and the Cannabis Withdrawal Scale (CWS). Principal Component Analysis (PCA) supported two-factor construct validity for CUPIT. Cronbach's alpha was 0.84 for CUPIT-A factor, 0.83 for CUPIT-B factor, and 0.89 for CUPIT, when considered as a unidimensional scale. Cronbach's alpha was 0.82 for CPQ-A factor, 0.73 for CPQ-B factor, 0.30 for CPQ-C, and 0.87 for CPQ, when considered as a unidimensional scale. The CUPIT and the CPQ were moderately correlated with the CWS (r = 0.63 and r = 0.74, respectively), whereas the CUPIT and the CPQ were strongly correlated with each other (r = 0.76). The Turkish version of the CUPIT and the CPQ can effectively identify substance use problems and treatment outcome, respectively, among outpatients with cannabis or synthetic cannabinoid use disorder.


Is development really the best contraceptive? A 20-year trial in Comilla district, Bangladesh.
"This article examines which public programmes and which socio-economic development indicators have had an impact on contraceptive practices and fertility in a selected group of villages in Comilla district of Bangladesh. It finds that equitable, even-handed development may be a good 'contraceptive', but is not a realistic alternative to family planning effort.... This research, undertaken in 1985, replicates a similar knowledge, attitudes and practice (KAP) type study undertaken in these same villages some 20 years earlier, in 1967/68....Thus, the two studies provide a unique look at demographic behavioural characteristics when these agricultural development programmes were in an early stage and then 20 years later."


The importance of genetic research on the dominant species of human intestinal indigenous microbiota.
Comparisons of the changes in the gut microbiota and transcriptomes as a result of changes in diet have demonstrated that the regulation of the gene functions of intestinal bacteria is fundamental for the regulation of the intestinal environment. However, the functions of only about half of the genes can be predicted using nucleotide sequences obtained from the metagenomic data of the human gut microbiota. Therefore, the regulation of gut bacterial gene functions is hindered. To resolve this issue, the functions of the genes of intestinal bacteria must be identified. In our previous study, a high-throughput cultivation system was established for the dominant species of indigenous human intestinal microbiota. Using this system, we analyzed the synthesis and transport of polyamines by intestinal bacteria. Comparison of the results with those obtained by in silico analysis indicated the existence of novel polyamine synthetic enzymes and transport proteins. Next, strains with gene deletions and complementation for the polyamine synthetic system of the genus Bacteroides were analyzed. Furthermore, we co-cultured genetically engineered Escherichia coli and Enterococcus faecalis strains to demonstrate the presence of a polyamine synthetic pathway spanning multiple bacterial species. Here, we outline the trends of research using genetically engineered intestinal bacteria and the ripple effects of studies in which intestinal bacteria have been analyzed genetically. Moreover, because studies on intestinal bacteria at the gene level are indispensable for improving our understanding of their regulation, the importance of this research will continue to increase in the future.


Modified fixed nanobite tandem appliance for rapid correction of developing Class III malocclusion.
Rapid correction of developing Class III malocclusion in pediatric patients using a method with decreased reliance on patient compliance and increased patient comfort. The modified fixed nanobite tandem appliance (MFNTA) consists of three components, two fixed and one removable. The maxillary fixed appliance consists of a nickel-titanium fixed maxillary expander and a soldered buccal arm used for Class III elastic traction. The mandibular appliance consists of modified fixed nanobite and buccal headgear tubes welded to the mandibular first molar band for facebow attachment. Pre- and posttreatment records revealed significant skeletal improvement without increase in the vertical dimension and marked improvement in facial balance and esthetics. MFNTA has the potential to be an effective tool in the treatment of developing Class III malocclusion and relief of the psychologic trauma caused by an anterior crossbite.


Occasional series: lupus around the world. The Chilean experience of systemic lupus erythematosus.
The Chilean experience with SLE began more than 40 years ago. The first series was published in 1958 with 108 patients. Lupus hair was described for the first time as a symptom that highly suggested SLE at that time. Subsequent studies have dealt with different clinical aspects of the disease. The description of silent nephropathy in SLE and inspiratory muscle dysfunction as a cause of unexplained dyspnoea have been relevant contributions to the understanding of this condition. Patient survival has improved over the last decades from 13% at 5 years in 1959 up to 87% in 1994. Reasons for this improved survival are probably related to better diagnosis and management of the severely ill patients. However, in spite of this, the incidence of infections in our patients often contributes to fatal outcome. Recently, some studies have been published related to the basic pathogenic mechanisms of this disease.


Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults.
Obese individuals have elevated platelet activation and arterial stiffness, but the strength and temporality of the relationship between these factors remain unclear. We aimed to determine the effect of increased arterial stiffness on circulating platelet activity in overweight/obese young adults. This analysis included 92 participants (mean age 40 years, 60 women) in the Slow Adverse Vascular Effects of excess weight (SAVE) trial, a clinical trial examining the effects of a lifestyle intervention with or without sodium restriction on vascular health in normotensive overweight/obese young adults. Carotid-femoral (cf), brachial-ankle (ba) and femoral-ankle (fa) pulse wave velocity (PWV) served as measures of arterial stiffness and were measured at baseline and 6, 12 and 24 months follow-up. Platelet activity was measured as plasma β-thromboglobulin (β-TG) at 24 months. Higher plasma β-TG was correlated with greater exposure to elevated cfPWV (p = 0.02) and baPWV (p = 0.04) during the preceding two years. After adjustment for serum leptin, greater exposure to elevated baPWV remained significant (p = 0.03) and exposure to elevated cfPWV marginally significant (p = 0.054) in predicting greater plasma β-TG. Greater arterial stiffness, particularly central arterial stiffness, predicts greater platelet activation in overweight/obese individuals. This relationship might partly explain the association between increased arterial stiffness and incident atherothrombotic events.


IMAge/enGINE: a freely available software for rapid computation of high-dimensional quantification.
High-dimensional image data including diffusion weighted imaging, diffusion tensor imaging and dynamic imaging are important in exploring the connectivity, cellularity, pharmacokinetic and blood supply. IMAge/enGINE is software especially designed for high-dimensional medical image computing. IMAge/enGINE is implemented based on open-source and cross-platform tools such as Qt, ITK and VTK. It processes the high-dimensional image data in a slice-by-slice computation mechanism. For computational efficiency, C++ is used for implementing IMAge/enGINE and multi-thread computing is handled in the scale of voxels. The architecture of IMAge/enGINE is modularized for easier extension. IMAge/enGINE has following features: (I) IMAge/enGINE is free for research use; (II) it has an easy-to-use graphic user interface designed for clinical users without programming or engineering background; (III) its frame work is open-source and extensible. Developers can implement algorithms as modules and integrate them into IMAge/enGINE or generate their own application. The source of IMAge/enGINE is hosted at https://github.com/VusionMed/IMAge-enGINE. Multiple diffusion and perfusion models are implemented and integrated into IMAge/enGINE and its binaries can be downloaded freely at http://www.vusion.com.cn/?page_id=14971.


Detection of IGA anti-OKT3 antibodies in OKT3-treated transplant recipients.
Murine OKT3 monoclonal antibodies function as an immunosuppressant drug for organ transplant recipients. A contraindication to retreatment may develop, however, because a high proportion of OKT3-treated patients form anti-OKT3 antibodies. Previous data have shown that only antiidiotypic IgG antibodies can negate the beneficial effect of the drug. Eighty-two OKT3-treated transplanted patients were tested by ELISA for IgG, IgK and IgA anti-OKT3 antibodies and compared with 200 controls. The anti-OKT3 antibody-positive sera were screened additionally by flow cytometry for the presence of antiidiotypic activity by measuring Ortho OKT3-FITC activity on a CD3-positive cell line, Jurkat, before and after incubation with serial dilutions of patient and control sera. Forty-four of 82 patients developed antibodies to OKT3, 20 manifested IgG, 20 produced both IgG and IgA, and 4 IgA only. We never detected IgM anti-OKT3. Of the 44 anti-OKT3-positive patient sera, 25 showed antiidiotypic specificity. Two IgG/IgA anti-OKT3-positive patient sera were IgG-depleted by Protein G. Both continued to exhibit antiidiotypic IgA activity. IgA anti-OKT3 was associated with low serum OKT3 levels and lack of ability of OKT3 to lower total CD3 cell numbers to therapeutic levels. This is the first report of IgA anti-OKT3 antibody in transplant recipients. Isotype IgA anti-OKT3 was observed in 54% of the patients whose sera tested positive for anti-OM by ELISA. The IgG/ IgA anti-OKT3-positive patient sera tested continued to exhibit antiidiotypic OKT3 reactivity when depleted of IgG. We urge that OKT3-treated patients be monitored routinely for IgA anti-OKT3 antibodies to avoid the expense and potential complications of retreatment with this drug in sensitized patients.


Thermal sensitive paper as a diagnostic for intense relativistic electron beam dynamics.
Thermal sensitive paper has been used as a diagnostic for an intense relativistic electron beam propagating in a rippled magnetic field. The E(r)xB(z) rotation of the beam has been measured from the exposed pattern on the thermal paper and used to calculate the electrostatic field of the beam E(r), and the corresponding values of electron density and beam current. Exposed strips of thermal paper show longitudinal modulation of the radial electron velocity with a period corresponding to that of a rippled magnetic field; modulation of the radial electron velocity at the cyclotron frequency has also been observed.


Circulating exosomes contain protein biomarkers of metastatic non-small-cell lung cancer.
The present study aimed to investigate the overall changes in exosomal proteomes in metastatic and non-metastatic non-small-cell lung cancers (NSCLC) and healthy human serum samples, and evaluate the potential of serum exosomal biomarkers to predict NSCLC metastasis. Tandem mass tags combined with multidimensional liquid chromatography and mass spectrometry analysis were used for screening the proteomic profiles of serum samples. Quantitative proteome, significant pathway, and functional categories of patients with metastatic and non-metastatic NSCLC and healthy donors were investigated. In total, 552 proteins of the 628 protein groups identified were quantified. Bioinformatics analysis indicated that quantifiable proteins were mainly involved in multiple biological functions, metastasis-related pathways. Moreover, lipopolysaccharide-binding proteins (LBP) in the exosomes were found to be well distinguished between patients with metastatic and patients with non-metastatic NSCLC. Area under the curve (AUC) was 0.803 with a sensitivity of 83.1% and a specificity of 67% (P < .0001). Circulating LBP were also well distinguishable between metastatic and non-metastatic NSCLC, the AUC was 0.683 with a sensitivity of 79.5% and a specificity of 47.2% (P = .005). This novel study provided a reference proteome map for metastatic NSCLC. Patients with metastatic and non-metastatic NSCLC differed in exosome-related proteins in the serum. LBP might be promising and effective candidates of metastatic NSCLC.


Inhomogeneities of ventilation and the diffusing capacity to perfusion in various chronic lung diseases.
Although impairment of gas exchange caused by ventilation-perfusion (VA/Q) mismatch has been extensively analyzed, there have been no systematic studies focused on determining the distributions of diffusion properties in dose connection with those of VA/Q. We attempted to clarify the simultaneous distributions of VA/Q and diffusion capacity to perfusion (D/Q) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD). To assess pathologic determinants causing functional abnormalities, we compared VA/Q and D/Q distributions with the findings on high-resolution computed tomography. O2, CO2, and CO together with six foreign inert gases were used as indicator gases. We transformed the measured data on indicator gases in arterial blood into a continuous distribution of Q in the VA/Q-D/Q field. In IPF, active alveolitis or acinitis played a major role in producing low D/Q regions impeding gas exchange via a diffusion limitation, whereas extensive fibrosis with minimal inflammation accounted for low D/Q as well as low VA/Q regions. In COPD, no regions with low D/Q ratios were observed, but an abnormality in the VA/Q distribution with low or high VA/Q ratios was identified. Emphysematous lesions produced high VA/Q regions, whereas peripheral airway involvement yielded low VA/Q regions. These findings suggest that hypoxemia in patients with IPF is caused by inhomogeneous distributions of D/Q in combination with those of VA/Q. Hypoxemia in patients with COPD is attributable primarily to inhomogeneities in VA/Q rather than in D/Q distributions.


[The best of vascular pathology in 1999].
In vascular pathology, the discovery of the ABC1 receptor (ATP-binding-cassette transporter 1), the deficit of which is responsible for Tangier disease and familial hypoalphalipoproteinaemias, has opened the greatest perspectives with the possibility of new active treatments in the prevention of atherosclerosis. Other advances were more expected. A large British trial convincingly demonstrated that the follow-up of small abdominal aortic aneurysms is reliable. The MEDENOX trial showed the value of prophylaxis of thromboembolic disease in a medical setting and the reduced incidence of phlebographic events. The ICAI study, on the other hand, showed the difficulty of treatment of critical ischaemia of the lower limbs: alprostadil (PGE1) was ineffective with a 6 month follow-up in this pathology. Finally, low dose aspirin is at least as effective as high doses.


Bilateral malignant Brenner tumor. A light and electron microscopic study.
A case of bilateral malignant Brenner tumor of the ovary in a 43-year-old woman was studied by light- and electron microscopy. The morphologic criteria of this rare lesion are discussed and the pertinent literature reviewed.


Effect of concentration and time upon inactivation of tobramycin, gentamicin, netilmicin and amikacin by azlocillin, carbenicillin, mecillinam, mezlocillin and piperacillin.
Carbenicillin and ticarcillin have been shown to inactivate aminoglycoside antibiotics. This study evaluated the effect of time upon in vitro interaction between mixtures of four aminoglycoside antibiotics at two concentrations with azlocillin, mecillinam, mezlocillin, piperacillin and carbenicillin at three concentrations. By linear regression analysis, the inactivation of each aminoglycoside antibiotic was shown to be directly proportional to the concentration of the semisynthetic penicillin. Aminoglycoside inactivation was greater after 72 hr of incubation with the penicillins than after 24 hr of incubation. Inactivation by each semisynthetic penicillin was greater for tobramycin and gentamicin than for netilmicin and amikacin, especially at higher concentrations of the penicillins. At concentrations of 500 microgram/ml, significantly less inactivation of amikacin occurred when compared to netilmicin. There was little difference in inactivation of a specific aminoglycoside by any of the semisynthetic penicillin antibiotics. No significant change in aminoglycoside activity occurred when the aminoglycosides were stored with the semisynthetic penicillin derivatives at -70 degrees C for 30 days. Conclusions from this study are: 1) serum specimens containing aminoglycoside-penicillin combinations should be tested immediately or frozen before antibiotic assay and 2) aminoglycoside inactivation by the newer semisynthetic penicillins may be important in patients with renal failure who are receiving these antimicrobial agents.


Activation of MAP kinase family members triggered by TPA or ionomycin occurs via the protein phosphatase 4 pathway in Jurkat leukemia T cells.
Protein phosphatase 4 (PP4) is a protein phosphatase 2A (PP2A)-related, okadaic acid-sensitive, serine/threonine protein phosphatase that shares 65% amino acid identity with PP2A. Numerous studies have shown that protein phosphatase is involved in the regulation of T cell signaling and activation. In this study, we investigated the effect of overexpression of PP4 on the expression of members of the MAP kinase family in Jurkat leukemia T cells, which had previously been stimulated with UV, 12-O-tetradecanoylphorbol-13-acetate (TPA), ionomycin and okadaic acid. We found that the overexpression of PP4 expressed relatively low activity in the absence of any kind of stimulation. However, TPA, UV or ionomycin treatment strongly increased the activity of PP4. In addition, Jurkat T cells, transfected with various expression plasmids and/or stimulated with TPA, UV or ionomycin strongly induced the c-Jun N-terminal kinase (JNK) and p38, whereas the extracellular signal-regulated kinase (ERK)-1/2 kinase pathway was weekly activated. Treatment of Jurkat T cells with okadaic acid, an inhibitor of PP2, also inhibited the increase of JNK and p38 activity induced by PP4. The effect of okadaic acid on the activity of PP4 was similar to that observed in Jurkat T cells treated with a dominant negative c-Jun (dn-jun). These results indicate that the activation of JNK and p38, but not ERKs, is a target for the PP4 activity in Jurkat leukemia T cells.


Dioxin: a case study.
The need to notify individuals of a possible health risk from their past exposure to potentially hazardous agents frequently extends beyond workers to include community groups. The issues to consider in community notification are frequently similar to those that are important for worker notification but may include some that are unique. This case study traces the evolution of one company's strategy for communicating with the public about possible dioxin contamination associated with its operations. Early communications tended to emphasize the technical aspects of the issues in the fashion of scientists talking to other scientists. This was interpreted by some to be symptomatic of an arrogant and uncaring attitude. Beginning in the early 1980s, the company's management recognized the need to reach out to a variety of audiences on multiple levels, and shifted to a more comprehensive communications strategy. A similar shift is now occurring throughout the chemical manufacturing industry as top managers realize that, if they expect to continue to operate, they must become more accountable and responsive to the public.


A Nonlinear Lens on Berta Bornstein's "Frankie".
This reading of Berta Bornstein's case of "Frankie" half a century after its publication focuses on the knowing attitude that pervades her description of child analysis and child development, and this attitude is used to explain interventions that appear harsh and anti-analytic to today's reader. Using concepts from nonlinear dynamic systems theory and, particularly, network theory help to both understand what is troubling in the case description and how these problematic features came to be part of the case description. The mistaken view that development is linear leads to attempts to get development "on track" and a view that the goal of analysis is well-defined psychological maturity, as opposed to the ongoing freedom to explore the psychological world in new and creative ways. Bornstein's authoritative style was not only coercive of her young patient but also of the reader who is invited to uncritically agree with her formulations. It is suggested that the appeal of this way of writing is best understood in the broad, historical context within which the work with Frankie was undertaken.


Virtual Global Transplant Laboratory Standard Operating Protocol for Donor Alloantigen-specific Interferon-gamma ELISPOT Assay.
The quantification of frequency of IFN-γ-producing T cells responding to donor alloantigen using the IFN-γ enzyme linked immunosorbent spot (ELISPOT) holds potential for pretransplant and posttransplant immunological risk stratification. The effectiveness of this assay, and the ability to compare results generated by different studies, is dependent on the utilization of a standardized operating procedure (SOP). Key factors in assay standardization include the identification of primary and secondary antibody pairs, and the reading of the ELISPOT plate with a standardized automated algorithm. Here, we describe in detail, an SOP that should provide low coefficient of variation results. For multicenter trials, it is recommended that groups perform the ELISPOT assays locally but use a centralized ELISPOT reading facility, as this has been shown to be beneficial in reducing coefficient of variation between laboratories even when the SOP is strictly adhered to.


Solid dispersions in the form of electrospun core-sheath nanofibers.
The objective of this investigation was to develop a new type of solid dispersion in the form of core-sheath nanofibers using coaxial electrospinning for poorly water-soluble drugs. Different functional ingredients can be placed in various parts of core-sheath nanofibers to improve synergistically the dissolution and permeation properties of encapsulated drugs and to enable drugs to exert their actions. Using acyclovir as a model drug, polyvinylpyrrolidone as the hydrophilic filament-forming polymer matrix, sodium dodecyl sulfate as a transmembrane enhancer, and sucralose as a sweetener, core-sheath nanofibers were successfully prepared, with the sheath part consisting of polyvinylpyrrolidone, sodium dodecyl sulfate, and sucralose, and the core part composed of polyvinylpyrrolidone and acyclovir. The core-sheath nanofibers had an average diameter of 410 ± 94 nm with a uniform structure and smooth surface. Differential scanning calorimetry and x-ray diffraction results demonstrated that acyclovir, sodium dodecyl sulfate, and sucralose were well distributed in the polyvinylpyrrolidone matrix in an amorphous state due to favoring of second-order interactions. In vitro dissolution and permeation studies showed that the core-sheath nanofiber solid dispersions could rapidly release acyclovir within one minute, with an over six-fold increased permeation rate across the sublingual mucosa compared with that of crude acyclovir particles. The study reported here provides an example of the systematic design, preparation, characterization, and application of a novel type of solid dispersion consisting of multiple components and structural characteristics.


Pharmacokinetics and Catabolism of [3H]TAK-164, a Guanylyl Cyclase C Targeted Antibody-Drug Conjugate.
TAK-164 is an antibody-drug conjugate (ADC) comprising human anti-guanylyl cyclase C (GCC) monoclonal antibody conjugated to indolinobenzodiazepine DNA alkylator IGN-P1 through a cleavable alanine-alanine dipeptide linker. TAK-164 is currently being evaluated for the treatment of gastrointestinal cancers expressing GCC. The catabolism of TAK-164 was studied using 3H-labeled ADC using GCC-expressing HEK-293 (GCC-HEK-293) cells, rat tritosomes, cathepsin B, and tumor-bearing mice. Time- and target-dependent uptake of [3H]TAK-164 was observed in GCC-HEK-293 cells with approximately 12% of radioactivity associated with DNA after 24 hours of incubation. Rat liver tritosomes and cathepsin B yielded IGN-P1 aniline, sulfonated IGN-P1 (s-IGN-P1) aniline, and a lysine conjugate of IGN-P1 (IGN-P1-Lys) aniline as catabolites. In tumor-bearing mice, [3H]TAK-164 exhibited a terminal half-life of approximately 41 and 51 hours in plasma and blood, respectively, with low plasma clearance (0.75 ml/h per kilogram). The extractable radioactivity in plasma and tumor samples revealed the presence of s-IGN-P1 aniline and IGN-P1 aniline as payload-related components. The use of a radiolabeled payload in the ADC in tumor uptake investigations provided direct and quantitative evidence for tumor uptake, DNA binding, and proof of mechanism of action of the payload. SIGNIFICANCE STATEMENT: Since payload-related species are potent cytotoxins, a thorough characterization of released products of ADCs, metabolites, and their drug interaction potential is necessary prior to clinical investigations. This study characterized in vitro and in vivo DNA binding mechanisms and released products of TAK-164. The methodologies described here will be highly useful for characterization of payload-related products of ADCs in general.


Continuous meconium monitoring during labour using an intrauterine probe.
The fetus discharges meconium (its bowel contents) into the amniotic fluid during labour in approximately 10% of pregnancies. In about 10% of cases where meconium is passed, the fetus gasps, inhaling the sticky meconium into the upper respiratory tract. After birth, the meconium blocks the air passages in the lungs, impairing gas exchange (meconium aspiration syndrome, MAS). Up to 20% of infants suffering from MAS die and recently published studies have shown a long-term effect of MAS in causing cough and wheeze. At present, meconium is only noticed at birth or occasionally when amniotic fluid leaks past the presenting part of the fetus. We have developed a system to monitor meconium continuously during labour, using a flexible intrauterine probe. The system provides a measurement of the meconium concentration of amniotic fluid during labour every 2 min, with a 60% prediction interval of +/- 10 g l-1, and a 99% prediction interval of +/- 30 g l-1 (clinically 'thick meconium' contains around 100 g l-1). The noise of the measurement is of the order of +/- 10 g l-1, and the response to changes in the meconium concentration is from 40 to 120 s, depending on its configuration. The system also provides other obstetric variables such as fetal heart rate and uterine activity measurement, obtained from a fetal monitor. Preliminary clinical results indicate that this system can measure meconium not apparent to the attending staff; the system can detect changes in the meconium concentration of amniotic fluid; the measurements are confirmed by visual observation at delivery; and changes of meconium concentration seem to correlate with known stressful stimuli. The system therefore provides a new tool from which new variables are obtained, which can greatly enhance clinical research into the pathophysiology of meconium passage and aspiration.


Maximum weight-shifts in sitting in non-ambulatory people with stroke are related to trunk control and balance: a cross-sectional study.
Impaired sitting balance is common in persons with stroke, affecting postural control in different directions. However, studies seldomly investigate sitting balance in severely affected non-ambulatory persons with stroke and precise assessment including the diagonal directions are scarce. Are measurements of maximal voluntary weight-shifts decreased in severely affected persons with stroke in comparison to healthy controls, and is there a relationship with clinical measurements of trunk control, sitting and standing balance? 14 Persons with stroke were recruited in the rehabilitation phase along with 32 healthy controls. A clinical pressure platform (RM Ingénierie, France) evaluated the weight-distribution during static sitting and measurements of maximal voluntary weight-shifts, by centre of pressure displacements in six directions. Clinical measurements included Trunk Control Test, Trunk Impairment Scale and Berg Balance Scale. The persons with stroke had a mean (SD) age of 69 (17) years, including 5 females and 9 males and were on average 57 (40) days post stroke. No patient was able to walk without manual support and median (IQR) Berg Balance Scale score was 17 (6-33) out of 56 points. Measurements showed that the centre of pressure distance was significantly smaller in all directions in persons with stroke compared to healthy controls (p < 0.05). The clinical measurements demonstrated moderate to very high correlations with centre of pressure distance in the diagonal forward, diagonal backward and lateral directions (r = 0.54 - 0.89). This study reveals that measurements of maximal voluntary weight-shifts are feasible and show clinically relevant deficits in severely affected non-ambulatory persons with stroke. Especially the lateral and diagonal directions can be of interest to investigate further as they are most strongly correlated with clinical measurements of balance. Reaching exercises in these directions could be considered a core element of rehabilitation for this group of patients.


Postoperative Management for Articular Cartilage Surgery in the Knee.
The postoperative rehabilitation team plays a crucial role in optimizing outcomes after articular cartilage surgery. A comprehensive approach to postoperative physical therapy that considers the type of surgery, location in the knee, concurrent procedures, and patient-specific factors is imperative. While postoperative rehabilitation protocols should be specific to the patient and type of surgery performed and include phased rehabilitation goals and activities, the key principles for postoperative rehabilitation apply across the spectrum of articular cartilage surgeries and patients. These key principles consist of preoperative assessments that include physical, mental, and behavioral components critical to recovery; education and counseling with respect to expectations and compliance; and careful monitoring and adjustments throughout the rehabilitation period based on consistent communication among rehabilitation, surgical, and imaging teams to ensure strict patient compliance with restrictions, activities, and timelines to optimize functional outcomes after surgery.


The impact of fluency on explicit memory tasks in amnesia.
Abstract Distinguishing implicit and explicit memory and delineating their relationship has haunted memory researchers for decades, and Voss et al. provide an impressive overview of their work examining these issues. We briefly comment on the following: (1) There is evidence indicating that implicit memory impacts cued recall, in addition to recognition; (2) Fluency can manifest as priming in implicit memory or it can be experienced as familiarity (in association with attribution processes) in recognition tasks; and (3) The impact of fluency on accuracy of "guess" responses during recognition memory in normal subjects is reminiscent of similar effects on recognition in amnesia.


On the relation between reinforcer efficacy and preference.
Most research on stimulus preference and reinforcer assessment involves a preference assessment that is followed by a reinforcer assessment. Typically, the most and least preferred stimuli are tested as reinforcers. In the current study, we first quantified the reinforcing efficacies of six food items and then assessed relative preference for each item. Relative preference ranking and reinforcer efficacies showed almost perfect concordance for 1 participant and partial concordance for the other. Discordance tended to occur with the weakest reinforcers.


Study on Creep Damage of Ni-Based Superalloy Caused by Variable Load Conditions at Elevated Temperatures.
Higher fatigue and creep resistance at high temperatures are the essential properties for materials such as those used in gas turbines for power generation and aircraft turbines. Therefore, the nickel-based superalloy CMSX-4 was developed through single-crystal casting to satisfy these requirements. In this study, the CMSX-4 creep test results reported by previous researchers were used to mathematically derive an equation to estimate the amount of creep damage occurring under variable load conditions. In addition, low-cycle fatigue tests were performed, and the effect of creep damage occurring during fatigue on material failure was described.


Reduction in the number and associated costs of unindicated dual-phase head CT examinations after a quality improvement initiative.
During this study, we instituted a phased quality improvement initiative designed to educate referring clinicians and departmental radiologists about the recommendations of the American College of Radiology (ACR) Appropriateness Criteria for dual-phase (without and with contrast material) head CT examinations. The primary aims of the study were to evaluate whether the quality improvement initiative was associated with an improvement in ACR Appropriateness Criteria appropriateness ratings and a reduction in the number of unindicated dual-phase head CT examinations performed. A secondary aim was to assess the impact of the quality improvement initiative on health care costs. This study included-with the exception of the examinations performed during a 3-month training period-all single- and dual-phase head CT examinations performed of adult patients at a tertiary care medical center from January 2009 through October 2011. Both inpatients and outpatient examinations were included. There were no exclusion criteria. Implementation of the initiative enhanced patient safety and reduced health care costs by achieving a significant reduction (p = 0.006) in the number of unindicated dual-phase head CT examinations performed from a median number of 40 per month to 17 per month. Although there are potential benefits for dual-phase head CT examinations, the medical and economic risks should be measured against these potential benefits. Incorporating the ACR Appropriateness Criteria applies evidence-based medicine to this algorithm. In this outcomes-driven study, the number of unindicated dual-phase head CT examinations was reduced and imaging efficacy improved primarily through physician education and monitoring.


Phytochemistry, Pharmacology and Traditional Uses of Plants from the Genus Trachelospermum L.
This paper is intended to review advances in the botanical, phytochemical, traditional uses and pharmacological studies of the genus Trachelospermum. Until now, 138 chemical constituents have been isolated and characterized from these plants, particularly from T. asiaticum and T. jasminoides. Among these compounds, lignans, triterpenoids, and flavonoids are the major bioactive constituents. Studies have shown that plants from the genus Trachelospermum exhibit an extensive range of pharmacological properties both in vivo and in vitro, including anti-inflammatory, analgesic, antitumor, antiviral and antibacterial activities. In Traditional Chinese Medicine (TCM) culture, drugs that include T. jasminoides stems have been used to cure rheumatism, gonarthritis, backache and pharyngitis, although there are few reports concerning the clinical use and toxicity of these plants. Further attention should be paid to gathering information about their toxicology data, quality-control measures, and the clinical value of the active compounds from genus Trachelospermum.


Cabergoline plasma concentration is increased during concomitant treatment with itraconazole.
We report on 2 patients with idiopathic Parkinson's disease who experienced marked improvement in symptoms following the addition of itraconazole to current cabergoline treatment. Plasma levels of cabergoline were analyzed in one of the patients and increased to approximately 300% during treatment with itraconazole, which paralleled major clinical improvement.


A simpler solution to the old problem of frozen leads.
Pacemaker generator replacement is usually a straightforward and simple procedure. However, it is occasionally complicated by entrapment of the lead in the header. Solutions to this problem have been described previously. We describe a simpler and safer technique to solve this old problem.


Iron-induced metallothionein in chick liver: a rapid, route-dependent effect independent of zinc status.
The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status.


[Combined thymoma (AB + B)--pathological diagnosis and clinical significance].
To discuss the pathological and biological characteristic and the clinic-pathological relevance of combined thymoma (AB + B). According to the WHO Histological Typing of Thymic Tumors, the clinical features and pathological characteristics of AB + B thymomas were analyzed in a series of 141 thymic epithelial tumors (TET) collected in Shanghai Chest Hospital and analyzed statistically with clinical therapy and follow-up data. Seven cases of type A (5.0%), 48 cases of type AB (34.0%), 14 cases of combined thymoma (AB + B) (9.9%), 9 cases of type B1 (6.4%), 22 cases of type B2 (15.6%), 21 cases of type B3 (14.9%) and 20 cases of type C (14.2%) were classified. The overall postoperative survival data showed highly significant differences amongst the histological subtypes. Combined thymoma (AB + B) showed distinctive histopathological characteristics, their prognostic properties were between A, AB and B1-B3, the differences between them being highly significant (log rank: chi(2) = 48.18, P < 0.001). Seventy-three patients (51.8%) were in stage I, 16 (11.3%) were in stage II, 44 (31.2%) were in stage III, and 8 (5.7%) were in stage IV. The association between histological subtype and invasive stage was significant (chi(2) = 71.3, P < 0.001). Combined thymoma (AB + B) was grouped to grade II thymoma. Thymoma grading has a positive relationship with therapy and prognosis (log rank: chi(2) = 57.49, P < 0.001). It is proposed that combined thymoma (AB + B) may be named as the borderline thymoma. It has a distinctive histopathological definition and criteria and may be grouped as a subtype of thymoma. Its pathological and biological properties are between benign and malignant thymomas, and have significant differences.


Mental health of individuals who are deaf during COVID-19: Depression, anxiety, aggression, and fear.
This study aims to assess depression and anxiety levels among individuals, who are deaf during the lockdown throughout the first wave of the pandemic United Arab Emirates. The sample of the study consisted of 36 (n = 36) individuals aged 20.3 ± 1.2 years, who were deaf from birth. The respondents were divided into two groups; (1) those who were living with their parents (n = 20), (2) those who were independently living on their own (n = 16). Results of the study indicated that from May to October, there was decrease in the number of normal mental health cases among those living with parents (p ≤ 0.05). The results of the study show that in the time of the pandemic, deaf people constitute a vulnerable portion of the population. The correlation between living alone and stress levels was 0.78. The correlation between living with parents and stress levels was -0.85.


A Drosophila Mitochondrial Complex I Deficiency Phenotype Array.
Mitochondrial diseases are a group of rare life-threatening diseases often caused by defects in the oxidative phosphorylation system. No effective treatment is available for these disorders. Therapeutic development is hampered by the high heterogeneity in genetic, biochemical, and clinical spectra of mitochondrial diseases and by limited preclinical resources to screen and identify effective treatment candidates. Alternative models of the pathology are essential to better understand mitochondrial diseases and to accelerate the development of new therapeutics. The fruit fly Drosophila melanogaster is a cost- and time-efficient model that can recapitulate a wide range of phenotypes observed in patients suffering from mitochondrial disorders. We targeted three important subunits of complex I of the mitochondrial oxidative phosphorylation system with the flexible UAS-Gal4 system and RNA interference (RNAi): NDUFS4 (ND-18), NDUFS7 (ND-20), and NDUFV1 (ND-51). Using two ubiquitous driver lines at two temperatures, we established a collection of phenotypes relevant to complex I deficiencies. Our data offer models and phenotypes with different levels of severity that can be used for future therapeutic screenings. These include qualitative phenotypes that are amenable to high-throughput drug screening and quantitative phenotypes that require more resources but are likely to have increased potential and sensitivity to show modulation by drug treatment.


Heat resistant chocolate development for subtropical and tropical climates: a review.
Heat resistant chocolate (HRC) which can retain the desired texture and mouthfeel in tropical and subtropical climatic conditions has become a major research area in the chocolate industry. Liking of the chocolate products keeps on changing with the geographical conditions of the world due to the availability of ingredients from local resources and consumer's taste preferences. The geographical changes also bring about the change in climatic conditions and as such no chocolates have been formulated to withstand the hot tropical or sub-tropical temperature conditions. Textural issues and various storage related problems faced due to meltability of chocolate in different countries has opened up a broad research field of sustainable HRC manufacturing. Over the years, there are broadly three different approaches (fat modification, sugar structure modification and innovative process approach) to develop the HRC and all these scientific approaches have given different scientific insights about improving the heat resistance characteristics and textural stability of chocolate. There is a lack or coordinated fundamental and applied research related to cocoa butter polymorphism, and thermal-textural issues during product development/storage. This review paper is an attempt to describe the different scientific approaches for developing HRC and how they affect the physical/sensory chocolate attributes.


Influenza-associated bacterial pathogens in patients with 2009 influenza A (H1N1) infection: impact of community-associated methicillin-resistant Staphylococcus aureus in Queensland, Australia.
Secondary bacterial pneumonia due to community onset methicillin-resistant Staphylococcus aureus (MRSA) has become a highly publicised cause of influenza-associated death. There is a risk that case reports of fatal outcomes with post-influenza MRSA pneumonia may unduly influence antibiotic prescribing. The aim of this study was to demonstrate the incidence of community-onset MRSA pneumonia in 2009 H1N1 influenza patients. The microbiology records of patients positive for influenza A (H1N1) in 2009 were reviewed for positive blood or respiratory tract cultures and urinary pneumococcal antigen results within a Queensland database. Patients with such positive results within 48 h of hospital admission and a positive H1N1 influenza result in the prior 6 weeks were included. In 2009, 4491 laboratory-confirmed pandemic influenza A (H1N1) infections were detected. Fifty patients (1.1% of the H1N1 cohort) who were hospitalised with H1N1 and who had a bacterial respiratory tract pathogen were identified. Streptococcus pneumoniae (16 patients; 32%), Staphylococcus aureus (13 patients; 26%) and Haemophilus influenzae (9 patients; 18%) were the most commonly cultured organisms. Of the cohort of 4491 patients, MRSA was detected in only two patients, both of whom were admitted to intensive care units and survived after prolonged admissions. Influenza-associated community-onset MRSA pneumonia was infrequently identified in the 2009 H1N1 season in Queensland, despite community-onset MRSA skin and soft tissue infections being very common. Although post-influenza MRSA pneumonia is of great concern, its influence on empiric-prescribing guidelines should take into account its incidence relative to other secondary bacterial pathogens.


Comprehensive analysis of lncRNA-mediated ceRNA network in papillary thyroid cancer.
Papillary thyroid cancer (PTC) is one type of thyroid cancer. Although it has a good prognosis, the recurrence and metastasis rates remain high. The microarray dataset GSE66783 was downloaded from the Gene Expression Omnibus (GEO). With the R package, the differentially expressed genes (DEGs) and lncRNAs between normal adjacent tissues and cancer tissues of PTC were identified. The miRNAs that were targeted by DElncRNAs and the mRNAs that were targeted by miRNAs were discovered through miRcode and through miRTarBase, TargetScan, and miRDB, respectively. Furthermore, the ceRNA network was constructed. GO and KEGG enrichment analyses were performed on the DEGs. The PPI network of the DEGs was obtained from the STRING database, and the top 5 hub genes that had a tight correlation with the disease were obtained by using Cytoscape. Finally, the study used the Kaplan-Meier method to analyze PTC patient survival time, and the Human Protein Atlas database was used to retrieve the expression of the hub genes in normal and PTC patient tissues. Five hub genes showed significant differences in expression in the PPI network, and 12 lncRNA-miRNA-mRNA pathways might participate in the potential pathophysiological process of PTC. The study indicated that these ceRNAs might contribute to future therapies for PTC.


The efficacy of tranexamic acid using oral administration in total knee arthroplasty: a systematic review and meta-analysis.
Total knee arthroplasty (TKA) is gradually regarded as an effective choice for end-stage osteoarthritis or rheumatic arthritis. In the past, the management of tranexamic acid (TXA) using intravenous injection or topical application has been extensively researched. However, several studies have reported that oral TXA has an effect on blood loss. Therefore, a meta-analysis should be performed to determine whether oral TXA helps to prevent blood loss. Randomized controlled trials or retrospective cohort studies about relevant studies were searched in PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Six studies that compared oral TXA to non-TXA were included in our meta-analysis. Meta-analyses (PRISMA) guidelines, the Cochrane Handbook, and the Jadad scale were used to evaluate the included studies and the results to ensure that the meta-analysis was viable. In accordance with inclusion and exclusion, six studies with 2553 patients (oral TXA = 1386, without TXA = 1167) were eligible and accepted into this meta-analysis. Pooled data indicated that the oral TXA group was effective compared to the without TXA group in terms of hemoglobin (Hb) drop (P < 0.05), blood loss at 24 h (P < 0.05), total blood loss (P < 0.05), and the transfusion rate (P < 0.05). No significant differences were found in the length of hospital stay (P = 0.96) and complications (P = 0.39). Compared to the non-TXA group, the oral TXA group showed effects of blood sparing. Considering the cost and effectiveness, oral TXA is useful for TKA.


[Doppler sonography after extra-intracranial anastomosis operations].
Extra-intracranial anastomosis are thought to improve the regional cerebral blood flow in patients with a stenosis or occlusion of the carotid system and prevent the later occurrence of ischemic cerebral diseases. Doppler-sonography has been used for a follow up of the effectiveness of the surgical procedure. We believe that minor hemodynamic improvements after surgery cannot be detected by Doppler-sonography. However this method is very useful in demonstrating the patency of the anastomosis.


Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease.
Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins.


[Surgical treatment of postburn deformities of the back of the hand].
The authors sum up their experience with the surgical treatment of postburn deformations of the dorsal surface of the hand in 50 patients. They describe the technique of radical dissection of all the scars of the dorsal surface of the hand and fingers and plasty of the interdigital commissures by palmar trapezoid whole thickness grafts. Wounds after excision of the scars were closed by nonperforated grafts of 0.3-0.4 mm thick splitted skin. Long-term results were followed up in 21 patients. All of them showed good functional and cosmetic results.


[Contribution of molecular biology to the diagnosis of monogenic hereditary nephropathies].
Schematically, gene identification can be achieved by functional cloning, based on preexisting knowledge about the basic biochemical defect, positional cloning, initiated by the mapping of the responsible gene to its correct location on a chromosome, or by a combination of these two approaches called "candidate gene" approach. Genes of numerous monogenic hereditary renal disorders have been identified during the last few years by one of these approaches, particularly, the PKD1 and PKD2 genes involved in autosomal dominant polycystic kidney disease, as well as the genes encoding different type IV collagen alpha chains, responsible for Alport syndrome. This allows novel insights in the understanding of the pathogenesis of hereditary renal diseases and has opened new areas of genetic diagnosis.


Activation of Xenopus eggs by RGD-containing peptides accompanied by intracellular Ca2+ release.
To investigate the mechanism of egg activation in Xenopus, unfertilized eggs were treated with various oligopeptides related to the RGD sequence-containing peptides. When dejellied eggs were treated with RGDS at concentrations higher than 250 microM, the eggs produced a positive-going activation potential concomitant with intracellular Ca2- release. The eggs underwent cortical granule breakdown, cortical contraction, and resumption of meiosis. The activation by RGDS was independent of the voltage of egg membranes. GRGD, GRGDTP, and RGPFPI caused activation in some eggs, but RGES, RFDS, GPRP amide, and GPA did not. Denuded eggs were activated by Sepharose beads bound to RGDS, indicating an interaction of the RGD sequence with receptor molecules on the egg plasma membrane. The activation by RGDS did not occur under a Ca(2+)- and Mg(2+)-free condition, but occurred in a Ca(2+)-free solution containing Mg2+, concomitant with an intracellular Ca2+ release. These results indicate that a receptor of the RGD sequence on egg plasma membrane causes egg activation through an intracellular signal transduction system. A sperm agonist including the RGD sequence may play an important role in egg activation through the egg membrane receptor during the normal fertilization process.


Where are the limits of the centrosome?
The centrosome is a key component of the cell is involved in the processes of cell division, cell motility, intracellular transport, organization of the microtubules (MT) network and the production of cilia and flagella. The peculiarity of this organelle is that its boundaries are not clearly defined, the centrioles at the center of the centrosome are surrounded by electron dense pericentriolar material, the size and protein composition of this centrosome component experiences significant transformation during the cell cycle. It has been shown in this study that within the centrosome different proteins occupy different areas corresponding to: MT nucleation region (defined as gamma-tubulin-stained area), regulatory region (defined as kinase pEg2-stained area) and motor proteins region (kinesin-like motor XlEg5-stained area). The boundary of pEg2 is near 1.3 times greater while XlEg5 is 3.0 times greater than that of gamma-tubulin. Thus, the size of the centrosome, determined according to the structural electron microscopy (EM) analysis (about 1 µm) corresponds to the regulatory proteins area, but the actual functional centrosome size defined at the motor proteins region, is more than twice the size.


Consumption of Low-Calorie Sweetened Beverages Compared to Water Is Associated with Reduced Intake of Carbohydrates and Sugar, with No Adverse Relationships to Glycemic Responses: Results from the 2001-2012 National Health and Nutrition Examination Surveys.
Although the 2015 Dietary Guidelines Advisory Committee concluded that there was moderate evidence that substituting sugar-containing sweeteners with low-calorie sweeteners (LCS) reduces calorie intake and weight, dietary recommendations encourage substituting only water for sugar-sweetened beverages during weight management. This cross-sectional study evaluated the relation of water and no- and low-calorie sweetened beverage (LCSB) intake with nutrient intakes and prediabetes criteria using data from the National Health and Nutrition Examination Survey (NHANES) 2001-2012 in 25,817 adults that were free of diabetes. Although linear trends were observed with both beverages, higher LCSB intake was associated with significantly lower consumption of carbohydrates (-9.1 g/day vs. -1.4 g/day), total sugars (-10.9 g/day vs. -2.2 g/day), and added sugars (-2.0 tsp eq vs. -0.8 tsp eq) than those associated with higher water intake. Higher intake of both beverages was significantly associated with lower insulin levels (p < 0.01); however, higher intake of LCSB was also associated with lower hemoglobin A1c (HbA1c) and lower homeostatic model assessment of insulin resistance (HOMA-IR) (p < 0.01). We observed lower odds ratios for elevated HbA1c (adjusted odds ratio [OR] 0.79, 95% CI 0.64-0.98), HOMA-IR (0.68, 0.53-0.87), and insulin levels (0.63, 0.49-0.80) in LCSB among the higher (2+ servings) intake group compared to the lowest (<1 serving) intake group. Contrary to conventional wisdom, LCSB consumption was associated with equal, if not better, dietary intake and glycemic response than water consumption. Although observational in nature, these results contribute to the growing body of evidence from human studies suggesting that in addition to water, LCSBs can also be sensible choices for reducing sugars and carbohydrate intake, with no adverse associations to measures of glycemic response.


Target-Responsive Smart Nanomaterials via a Au-S Binding Encapsulation Strategy for Electrochemical/Colorimetric Dual-Mode Paper-Based Analytical Devices.
Target-responsive nanomaterials attract growing interest in the application of drug delivery, bioimaging, and sensing due to the responsive releasing of guest molecules by the smart molecule gate. However, it remains a challenge to develop smart nanomaterials with simple assembly and low nonspecific leakage starting from encapsulation strategies, especially in the sensing field. Herein, Au nanoclusters (Au NCs) were first grown on porous carbon derived from ZIF-8 (PCZIF) to be employed as nanocarriers. By employing the Au NCs as linkers and aptamer (Apta) double-strand hybrids (target Apta and SH-complementary DNA) as capping units, we reported the novel target-responsive nanomaterials of Apta/Au NCs-PCZIF/hemin through Au-S binding encapsulation for sensing assays. The Au-S binding encapsulation strategy simplified the packaging procedure and reduced non-target responsive leakage. As a proof, ochratoxin A (OTA) as a model target participates in the double-strand hybrid competitive displacement reaction and triggered Apta conformation switches from a coil to a G-quadruplex structure accompanied by the dissociation of the gatekeeper. Simultaneously, the released hemin can initiate a self-assembly to form G-quadruplex/hemin DNAzyme. Interestingly, owing to DNAzyme providing electron transfer mediators and peroxidase-like activity, we proposed an electrochemical/colorimetric dual-mode paper-based analytical device (PAD) that provided self-verification to enhance reliability and accuracy, benefiting from independent signal conversion and transmission mechanism. As a consequence, the proposed dual-mode PAD could achieve sensitive electrochemical detection and visual prediction of OTA in the range of 1 pg/mL to 500 ng/mL and 50 pg/mL to 500 ng/mL, respectively. The electrochemical detection limit for OTA was as low as 0.347 pg/mL (S/N = 3). We believe that this work provides point-of-care testing (POCT) tools for a broad spectrum of applications.


Effectiveness and safety of ferric carboxymaltose treatment in children and adolescents with inflammatory bowel disease and other gastrointestinal diseases.
The treatment of iron deficiency anemia in children with inflammatory bowel disease is a particular challenge and often insufficient. Absorption of orally given iron may be impaired by intestinal inflammation and treatment with oral iron may aggravate intestinal inflammation. This retrospective study is the first to describe the use of intravenous ferric carboxymaltose (FCM) in the pediatric setting. All subjects who had received at least one dose of FCM intravenously in the observation period were included in this analysis with data collected for up to 3 months post last FCM dose. In total, 72 children between 0 and 18 years with underlying gastrointestinal disorders had been treated for concomitant iron deficiency anemia. The majority of patients had Crohn's disease (40.3%) or ulcerative colitis (30.5%). The total number of FCM administrations was 147, the mean number per patient was 2.0 and the mean cumulative dose 821 mg iron (median single dose: 500 mg; max. 1000 mg). Post administration of FCM, correction of iron deficiency anemia was observed with improved mean hemoglobin levels from 9.5 g/dL at baseline to 11.9 g/dL within 5-12 weeks. Decreases in white cell count, platelets and C-reactive protein were observed post FCM, potentially suggesting reduced inflammation with iron repletion. Three subjects reported mild adverse drug reactions related to FCM; two of these were considered to be potentially related to long duration of administration and to high volume of saline solution for dilution. As such, the method of administration was amended to have a maximum infusion time of 60 minutes and dilution with less than or equal to 100 mL saline solution. Overall FCM was well tolerated in this pediatric population and appeared to be effective in correcting iron deficiency anemia. We cannot exclude that the correction of iron deficiency anaemia is in some part due to the treatment of the underlying disease and not related to the iron supplementation only.


Well-being of Canadian Veterans during the COVID-19 pandemic: cross-sectional results from the COVID-19 Veteran well-being study.
The impacts of the COVID-19 pandemic have disproportionally affected different population groups. Veterans are more likely to have pre-existing mental health conditions compared to the general Canadian population, experience compounded stressors resulting from disruptions to familial, social, and occupational domains, and were faced with changes in health-care delivery (e.g. telehealth). The objectives of this study are to assess (a) the mental health impact of COVID-19 and related life changes on the well-being of Veterans and (b) perceptions of and satisfaction with changes in health-care treatments and delivery during the pandemic. A total of 1136 Canadian Veterans participated in an online survey. Participants completed questions pertaining to their mental health and well-being, lifestyle changes, and concerns relating to the COVID-19 pandemic, as well as experiences and satisfaction with health-care treatments during the pandemic. Results showed that 55.9% of respondents reported worse mental health functioning compared to before the pandemic. The frequency of probable posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, alcohol use disorder, and suicidal ideation were 34.2%, 35.3%, 26.8%, 13.0%, and 22.0%, respectively. Between 38.6% and 53.1% of respondents attributed their symptoms as either directly related to or exacerbated by the pandemic. Approximately 18% of respondents reported using telehealth for mental health services during the pandemic, and among those, 72.8% indicated a choice to use telehealth even after the pandemic. This study found that Veterans experienced worsening mental health as a result of the COVID-19 pandemic. The use of telehealth services was widely endorsed by mental health treatment-seeking Veterans who transitioned to virtual care during the pandemic. Our findings have important clinical and programmeadministrator implications, emphasizing the need to reach out to support veterans, especially those with pre-existing mental health conditions and to enhance and maintain virtual care even post-pandemic.


Ethacrynic acid increases facility of outflow in the human eye in vitro.
Anterior segments of human donor eyes were perfused with culture medium at a perfusion pressure of 15 mm Hg in a 5% carbon dioxide environment at 37 degrees C. After determination of a baseline facility of outflow, the perfusion chamber contents were exchanged with either drug vehicle or ethacrynic acid, at concentrations ranging from 0.01 to 0.25 mmol/L, after which postdrug facility was measured in the continuous presence of drug vehicle or ethacrynic acid. Ethacrynic acid increased facility of outflow from 28% to 105% at ethacrynic acid concentrations of 0.01 to 0.25 mmol/L, respectively. No morphologic correlate of the facility increase was observed with 0.01-mmol/L ethacrynic acid, nor were there any signs of cellular toxic effects. At 0.1 mmol/L, separations between trabecular meshwork cells and breaks between inner-wall cells were observed. At 0.25 mmol/L, focal areas of cell swelling and necrosis were noted. This study demonstrated that ethacrynic acid increases outflow facility in the aged human eye at concentrations that produce no apparent toxic effects. Therefore, ethacrynic acid may potentially prove useful in the treatment of glaucoma.


miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF.
Asthma is a disease characterized by goblet cell differentiation, mucus hypersecretion, airway inflammation, and airway hyperresponsiveness. miR-125b was downregulated as normal human bronchial epithelial cells differentiation to pseudostratified epithelium. However, its role in asthma remains unknown especially in regulating goblet cell differentiation. miR-125b expression in the sputum of 50 asthmatic children and 50 age- and sex-matched healthy controls were assessed by quantitative RT-PCR (qRT-PCR). Meanwhile, expressions of miR-125b and SAM pointed domain-containing ETS transcription factor (SPDEF) in normal human tracheal epithelial (HTEpC) and A549 cells stimulated with lipopolysaccharide (LPS) for 2h were detected by qRT-PCR and western blot. Furthermore, the predicted miR-125b target was determined in silico and confirmed with dual-luciferase reporter assay. Additionally, intranasal delivery of miR-125b mimic in mice was performed to study its effects on house dust mite-induced allergic airway inflammation mouse models. We found that miR-125b expression was decreased in the sputum of the asthmatic patients especially in eosinophilic asthma. After stimulation with LPS, miR-125b expression was downregulated, accompanied by the upregulation of SPDEF in HTEpC and A549 cells. Moreover, SPDEF is a target of miR-125b, which regulates SPDEF at the posttranscriptional level. Additionally, intranasal delivery of miR-125b decreased SPDEF protein levels, goblet cell differentiation, mucus hypersecretion, and altered relevant gene expressions. Taken together, these results suggest that miR-125b inhibits SPDEF expression modulating goblet cell differentiation and mucus secretion in asthma.


Global gene expression response of a population exposed to benzene: a pilot study exploring the use of RNA-sequencing technology.
The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA-sequencing (RNA-seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (≥5 ppm) in air and 10 matched unexposed control workers, from a large study (n = 125) in which gene expression was previously measured by microarray. RNA-seq is more sensitive and has a wider dynamic range for the quantification of gene expression. Further, it has the ability to detect novel transcripts and alternative splice variants. The main conclusions from our analysis of the 20 workers by RNA-seq are as follows: The Pearson correlation between the two technical replicates for the RNA-seq experiments was 0.98 and the correlation between RNA-seq and microarray signals for the 20 subjects was around 0.6. 60% of the transcripts with detected reads from the RNA-seq experiments did not have corresponding probes on the microarrays. Fifty-three percent of the transcripts detected by RNA-seq and 99% of those with probes on the microarray were protein-coding. There was a significant overlap (P < 0.05) in transcripts declared differentially expressed due to benzene exposure using the two technologies. About 20% of the transcripts declared differentially expressed using the RNA-seq data were non-coding transcripts. Six transcripts were determined (false-discovery rate < 0.05) to be alternatively spliced as a result of benzene exposure. Overall, this pilot study shows that RNA-seq can complement the information obtained by microarray in the analysis of changes in transcript expression from chemical exposures.


Replication of dendrimer monolayer as nanopores in titania ultrathin film.
An ultrathin titania film with molecular-sized cavities was synthesized by treating a ca. 8 nm thick (TiO2)3(dendrimer)(TiO2)2 sandwich film with activated oxygen gas.


Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells.
The actin cytoskeletal regulator Wiskott Aldrich syndrome protein (WASp) has been implicated in maintenance of the autophagy-inflammasome axis in innate murine immune cells. Here, we show that WASp deficiency is associated with impaired rapamycin-induced autophagosome formation and trafficking to lysosomes in primary human monocyte-derived macrophages (MDMs). WASp reconstitution in vitro and in WAS patients following clinical gene therapy restores autophagic flux and is dependent on the actin-related protein complex ARP2/3. Induction of mitochondrial damage with CCCP, as a model of selective autophagy, also reveals a novel ARP2/3-dependent role for WASp in formation of sequestrating actin cages and maintenance of mitochondrial network integrity. Furthermore, mitochondrial respiration is suppressed in WAS patient MDMs and unable to achieve normal maximal activity when stressed, indicating profound intrinsic metabolic dysfunction. Taken together, we provide evidence of new and important roles of human WASp in autophagic processes and immunometabolic regulation, which may mechanistically contribute to the complex WAS immunophenotype.


Affinity labelling in situ of the bL12 protein on E. coli 70S ribosomes by means of a tRNA dialdehyde derivative.
In this report, we have used periodate-oxidized tRNA (tRNAox) as an affinity laleling reagent to demonstrate that: (i) the bL12 protein contacts the CCA-arm of P-site bound tRNA on the Escherichia coli 70S ribosomes; (ii) the stoichiometry of labelling is one molecule of tRNAox bound to one polypeptide chain of endogenous bL12; (iii) cross-linking in situ of bL12 with tRNAox on the ribosomes provokes the loss of activity; (iv) intact tRNA protects bL12 in the 70S ribosomes against cross-linking with tRNAox; (v) both tRNAox and pyridoxal 5'-phosphate (PLP) compete for the same or for proximal cross-linking site(s) on bL12 inside the ribosome; (vi) the stoichiometry of cross-linking of PLP to the recombinant E. coli bL12 protein is one molecule of PLP covalently bound per polypeptide chain; (vii) the amino acid residue of recombinant bL12 cross-linked with PLP is Lys-65; (viii) Lys-65 of E. coli bL12 corresponds to Lys-53 of eL42 which was previously shown to cross-link with P-site bound tRNAox on human 80S ribosomes in situ; (ix) finally, E. coli bL12 and human eL42 proteins display significant primary structure similarities, which argues for evolutionary conservation of these two proteins located at the tRNA-CCA binding site on eubacterial and eukaryal ribosomes.


Tubulinosema sp. microsporidian myositis in immunosuppressed patient.
The Phylum Microsporidia comprises >1,200 species, only 15 of which are known to infect humans, including the genera Trachipleistophora, Pleistophora, and Brachiola. We report an infection by Tubulinosema sp. in an immunosuppressed patient.


Analytical interference in the therapeutic drug monitoring of methotrexate.
High-dose of methotrexate chemotherapy is used in the treatment of some tumors. It presents several side effects that required therapeutic drug monitoring, which is commonly performed on 24, 48 and 72h after the beginning of the methotrexate infusion. Treatment of overexposure to methotrexate is based on injection of carboxypeptidase G2, which specifically degrades methotrexate into inactive metabolite: DAMPA. FPIA immunoassay on TDx automated analyzer (Abbott™) was used for therapeutic drug monitoring of methotrexate. This immunoassay presented a significant cross-reactivity between methotrexate and DAMPA, which widely overestimate the residual concentration compared to the gold standard HPLC/MS. TDx automated analyzer was substituted by a new immunoassay on Architect automated analyzer (Abbott™). However, this immunoassay has the same cross-reactivity, which needs to be careful when monitoring methotrexate after an injection of carboxypeptidase G2. In order to determine the most suitable assay for the therapeutic drug monitoring of methotrexate, the knowledge of injection of carboxypeptidase G2 remains essential.


Highly Efficient Oxygen Reduction Electrocatalyst Derived from a New Three-Dimensional PolyPorphyrin.
Metal-encapsulated nitrogen-doping porous carbonaceous materials (NDPCs) prepared from metalloporphyrin-based covalent organic frameworks (MP-COFs) have become very promising candidates for highly effective oxygen reduction electrocatalysts. To enhance the ORR performance and durability of these NDPCs in novel energy conversion and storage devices, we develop a new type of metal-encapsulated NDPCs (HBY-COF-900) composed of FeN4 active sites by introduction of metalloporphyrin into porous COFs. Comparable to the benchmark 20% Pt/C, HBY-COF-900 in acidic solutions exhibits higher oxygen reduction electrocatalytic activity, long-term durability, and good CO tolerance. These properties can be attributed to a synergistic effect of FeN4 active sites, high graphitization, and porous structure. This work opens an avenue for the development of metal-encapsulated NDPCs from three-dimensional polyporphyrin prepared by one-step polymerization.


Lacrimal gland ductal cyst abscess.
To describe a case of lacrimal gland ductal cyst complicated by secondary infection. Case report. A 51-year-old woman presented acutely with an enlarging, painful mass in the superotemporal fornix. Clinical examination, echography, and surgical evaluation revealed a lacrimal gland ductal cyst with abscess formation. The lacrimal gland cyst was treated with oral antibiotics in combination with incision, drainage, and marsupialization. Lacrimal gland ductal cysts are rare but must be considered in the differential diagnosis of lacrimal gland and upper eyelid mass lesions. Typically, lacrimal gland ductal cysts develop after chronic inflammation, infection, or trauma. We describe a patient who presented acutely with a lacrimal gland ductal cyst associated with a rare complication of abscess formation.


Identification and Analysis of Differentially Expressed Genes in Human Saphenous Vein Endothelial Cells Overexpressing Domain-Containing mTOR-Interacting Protein (DEPTOR) by RNA-Seq.
BACKGROUND Autologous saphenous vein is the most common choice for coronary artery bypass grafting. This study was conducted to identify and characterize differentially expressed genes (DEGs) induced by overexpressing DEPTOR in human saphenous vein endothelial cells (hsVECs) that might play roles in restenosis. MATERIAL AND METHODS hsVECs isolated from the saphenous veins were transfected with DEPTOR overexpression vector and analyzed for mTOR expression. RNA was prepared from the cells and sequenced using high-throughput sequencing technology (RNA-Seq). The DEGs were analyzed based on enrichment scores in GO terms and KEGG pathways. RESULTS The cells had typical hsVEC morphology and characteristics based on the HE staining and immunohistochemical and immunofluorescence assays. The expression of mTOR increased, and 102 genes were upregulated, and 409 genes were downregulated after DEPTOR overexpression. KEGG analysis showed that the DEGs were mainly enriched in 20 signal pathways, such as Focal adhesion and ECM-receptor interaction pathways. The DEGs were enriched in GO terms such as integrin binding and glycosaminoglycan binding. For cellular components, GO analysis revealed that the DEGs were enriched in main axon, plasma membrane part, cell junction, and proteinaceous extracellular matrix. DEGs included many cytokines, such as bone morphogenetic protein-7, interleukin-8, interleukin-1ß, and inhibin, which have important effects on vascular growth and inflammation. CONCLUSIONS The overexpression of DEPTOR in hsVECs results in DEGs that are involved in cell proliferation and differentiation, intercellular junction, and extracellular matrix receptor. These findings may provide valuable molecular information for improving venous permeability through manipulation of DEPTOR and related mTOR pathways.


Determinants of drug metabolism in early neonatal life.
Clinical pharmacology intends to predict drug-specific effects and side effects based on pharmacokinetics (i.e. absorption, distribution, metabolism and elimination) and pharmacodynamics (i.e. dose/effect relationship). Developmental pharmacology focuses on the maturational aspects of these phenomena during perinatal life and later stages of infancy. In general, phenotypic variation in drug metabolism is based on constitutional, environmental and genetic factors but in early neonatal life, it mainly reflects ontogeny. Although the major site of drug metabolism is the liver, the gastro-intestinal tract, blood cells and other organs like kidneys or lungs might also be involved in drug metabolism. Important alterations in hepatic drug metabolism occur in early neonatal life. These alterations are of relevance when age-dependent aspects of pharmacokinetics, -dynamics or toxicology are considered. Age dependent maturation of various phase I and II processes will be illustrated based on recently reported observations on the in vivo disposition of various analgesics (paracetamol, tramadol) in human neonates and young infants. However, age only in part explains the interindividual variability observed. Therefore, concerted efforts should be developed to simultaneously assess the impact of age, environmental factors, co-morbidity and polymorphisms in this specific population. The implementation of multivariable models like non-linear mixed effects (NONMEM) models hereby provide us with the tools to disentangle the impact of various co-variables in this specific population.


Effect of Phosphatase Activity of the Control of Virulence Sensor (CovS) on Clindamycin-Mediated Streptolysin O Production in Group A Streptococcus.
Severe manifestations of group A Streptococcus (GAS) infections are associated with massive tissue destruction and high mortality. Clindamycin (CLI), a bacterial protein synthesis inhibitor, is recommended for treating patients with severe invasive GAS infection. Nonetheless, the subinhibitory concentration of CLI induces the production of GAS virulent exoproteins, such as streptolysin O (SLO) and NADase, which would enhance bacterial virulence and invasiveness. A better understanding of the molecular mechanism of how CLI triggers GAS virulence factor expression will be critical to develop appropriate therapeutic approaches. The present study shows that CLI activates SLO and NADase expressions in the emm1-type CLI-susceptible wild-type strain but not in covS or control of virulence sensor (CovS) phosphatase-inactivated mutants. Supplementation with Mg2+, which is a CovS phosphatase inhibitor, inhibits the CLI-mediated SLO upregulation in a dose-dependent manner in CLI-susceptible and CLI-resistant strains. These results not only reveal that the phosphorylation of response regulator CovR is essential for responding to CLI stimuli, but also suggest that inhibiting the phosphatase activity of CovS could be a potential strategy for the treatment of invasive GAS infection with CLI.


A comparative study of different enzyme immunosorbent assays for human tumor necrosis factor-alpha.
Enzyme immunosorbent assays (ELISA) for human tumor necrosis factor-alpha (TNF-alpha) are available from many companies. Although this cytokine is meanwhile well established in scientific work its detection in human blood still leads often to conflicting results. We studied the analytical performance of three different commercial ELISA (Amersham, Immunotech and Medgenix Diagnostics) in plasma samples of 30 human immunodeficiency virus (HIV) infected individuals. All kits showed significantly different mean concentrations of TNF-alpha in the study population (p < 0.05). Kit A: 30.9 pg/ml +/- 46.6 vs. kit B: 46.9 pg/ml +/- 24.8 vs kit C: 11.8 pg/ml +/- 11.6. Results of assays A and B (r = 0.34) as well as A and C (r = 0.31) were not significantly correlated. A good statistical relation between values was only found for assay B and assay C (r = 0.80. p < 0.001). Three plasma samples were spiked with TNF-alpha standard of the corresponding kit to a final concentration of 200 pg/ml. The detection results of these samples were compared with the variation conceded by the manufacturer. Assay A detected two samples above the corresponding coefficient of intra-assay variation (recovery: 81.8% and 89.2%). All three values obtained with assay B were markedly out of its variation range (recovery: 88.7%, 84.6% and 89.0%) while assay C showed again two results above the intra-assay variation (recovery: 92.1% and 89.6%). In our observations we found relevant differences between commercial ELISA kits of different manufacturers, which made interpretation of TNF-alpha in human plasma samples difficult. Additionally, it should be taken into consideration that plasma specimen may contain cytokine-binding proteins or autoantibodies which are capable of blocking epitopes of TNF-alpha. This may lead to the loss of the necessary immunoreactivity which prevents detection antibodies from recognizing these molecules.


Formation of an RNA polymerase II preinitiation complex on an RNA promoter derived from the hepatitis delta virus RNA genome.
Although RNA polymerases (RNAPs) are able to use RNA as template, it is unknown how they recognize RNA promoters. In this study, we used an RNA fragment derived from the hepatitis delta virus (HDV) genome as a model to investigate the recognition of RNA promoters by RNAP II. Inhibition of the transcription reaction using an antibody specific to the largest subunit of RNAP II and the direct binding of purified RNAP II to the RNA promoter confirmed the involvement of RNAP II in the reaction. RNA affinity chromatography established that an active RNAP II preinitiation complex forms on the RNA promoter and indicated that this complex contains the core RNAP II subunit and the general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH and TFIIS. Binding assays demonstrated the direct binding of the TATA-binding protein and suggested that this protein is required to nucleate the RNAP II complex on the RNA promoter. Our findings provide a better understanding of the events leading to RNA promoter recognition by RNAP II.


Memory performance in Holocaust survivors with posttraumatic stress disorder.
The authors evaluated memory performance in Holocaust survivors and its association with posttraumatic stress disorder (PTSD) and age. Memory performance was measured in Holocaust survivors with PTSD (N=31) and without PTSD (N=16) and healthy Jewish adults not exposed to the Holocaust (N=35). Explicit and implicit memory were measured by paired-associate recall and word stem completion, respectively. The groups did not differ by age or gender, but the survivors with PTSD had significantly fewer years of education and had lower estimated IQs than the survivors without PTSD and the nonexposed group. There was a significant overall group effect for paired-associate recall but not word stem completion. The survivors with PTSD recalled fewer semantically unrelated words than did the survivors without PTSD and the nonexposed group and fewer semantically related words than the nonexposed group. Of the survivors with PTSD, 36% performed at a level indicative of frank cognitive impairment. Older age was significantly associated with poorer paired-associate recall in the survivors with PTSD but not in the other two groups. Markedly poorer explicit but not implicit memory was found in Holocaust survivors with PTSD, which may be a consequence of or a risk factor for chronic PTSD. Accelerated memory decline is one of several explanations for the significantly greater association of older age with poorer explicit memory in survivors with PTSD, which, if present, could increase the cognitive burden of this illness with aging.


Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly.
Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0.02], and the rs3810950 and rs8178990 ancestral GC haplotype was also associated with better cross-sectional cognitive composite score (P = 0.04, regression coefficient 0.59, 95% CI 0.03 to 1.16). Growth curve model analyses applied to up to 10 years of follow-up data showed that the rs3810950 A allele was associated with a lower cognitive composite score and Mini Mental State Examination at the lowest age (73 years of age), and was lower in the whole interval 73-82 although the absolute difference became smaller with age. Stratification by the presence of the APOE ε4 allele showed that rs3810950 AG/non-APOE ε4 carriers and rs3810950 AA/APOE ε4 carriers were associated with a lower cognitive composite score in younger elderly 73-83 years of age, similar to previous reports of association with AD.


STATSLAB: An open-source EEG toolbox for computing single-subject effects using robust statistics.
Research on robust statistics during the past half century provides concrete evidence that classical hypothesis tests that rely on the sample mean and variance are problematic. Even seemingly minor departures from normality are now known to create major problems in terms of increased error rates and decreased power. Fortunately, numerous robust estimation techniques have been developed that circumvent the need for strict assumptions of normality and equal variances, leading to increased power and accuracy when testing hypotheses. Two robust methods that have been shown to have practical value across a wide range of applied situations are the trimmed mean and percentile bootstrap test. To facilitate the uptake of robust methods into the behavioural sciences, especially when dealing with trial-based data such as EEG, we introduce STATSLAB: An open-source EEG toolbox for computing single-subject effects using robust statistics. With the STATSLAB toolbox users can apply the percentile bootstrap test, with trimmed means, to a variety of neural signals including voltages, global field amplitude, and spectral features for both scalp channels and independent components. The toolbox offers a range of analytical strategies and is packaged with a fully functional graphical user interface that includes documentation.


Mouse models for human familial adenomatous polyposis.
Colorectal cancer (CRC) is the second most frequent type of cancer in the Western hemisphere. In the United States alone, it is estimated that 150 000 new cases are detected every year and more than 65 000 patients die from complications associated with this cancer. Identification of genes implicated in the initiation and progression of colorectal cancer in humans has prompted the generation of mouse models for this cancer. We will provide a brief overview of these mouse models for CRC and what they have contributed to our understanding of the events involved in the initiation and progression of this cancer.


Real-time PCR systems targeting giant viruses of amoebae and their virophages.
Giant viruses that infect amoebae, including mimiviruses and marseilleviruses, were first described in 2003. Virophages were subsequently described that infect mimiviruses. Culture isolation with Acanthamoeba spp. and metagenomic studies have shown that these giant viruses are common inhabitants of our biosphere and have enabled the recent detection of these viruses in human samples. However, the genomes of these viruses display substantial genetic diversity, making it a challenge to examine their presence in environmental and clinical samples using conventional and real-time PCR. We designed and evaluated the performance of PCR systems capable of detecting all currently isolated mimiviruses, marseilleviruses and virophages to assess their prevalence in various samples. Our real-time PCR assays accurately detected all or most of the members of the currently delineated lineages of giant viruses infecting acanthamoebae as well as the mimivirus virophages, and enabled accurate classification of the mimiviruses of amoebae in lineages A, B or C. We were able to detect four new mimiviruses directly from environmental samples and correctly classified these viruses within mimivirus lineage C. This was subsequently confirmed by culture on amoebae followed by partial Sanger sequencing. PCR systems such as those implemented here may contribute to an improved understanding of the prevalence of mimiviruses, their virophages and marseilleviruses in humans.


Protocol for accurate assessment of ABPI in patients with leg ulcers.
Ankle brachial pressure index (ABPI) calculations are performed by nurses in the assessment of patients with leg ulceration. The measurement of pressure in one arm alone can result in inaccuracy which may be clinically significant. Two vascular nurse technologists performed ABPI measurements on 250 patients with 487 lower limbs. Community nurses replicated the study on 71 patients, assessing 123 lower limbs. The study shows that 22% of patients in the vascular laboratory and 20% in the community had a difference in brachial pressures of > or = 15 mmHg, indicating the presence of arch vessel or upper limb arterial disease. Furthermore, 6% of patients in the laboratory and 2% in the community demonstrated that the difference in brachial pressures affected the ABPI calculation around the value of 0.8, thus potentially influencing their clinical management. ABPI measurements should be performed, taking both brachial pressures for optimum results.


Modeling and Predicting the Stress Relaxation of Composites with Short and Randomly Oriented Fibers.
The addition of short fibers has been experimentally observed to slow the stress relaxation of viscoelastic polymers, producing a change in the relaxation time constant. Our recent study attributed this effect of fibers on stress relaxation behavior to the interfacial shear stress transfer at the fiber-matrix interface. This model explained the effect of fiber addition on stress relaxation without the need to postulate structural changes at the interface. In our previous study, we developed an analytical model for the effect of fully aligned short fibers, and the model predictions were successfully compared to finite element simulations. However, in most industrial applications of short-fiber composites, fibers are not aligned, and hence it is necessary to examine the time dependence of viscoelastic polymers containing randomly oriented short fibers. In this study, we propose an analytical model to predict the stress relaxation behavior of short-fiber composites where the fibers are randomly oriented. The model predictions were compared to results obtained from Monte Carlo finite element simulations, and good agreement between the two was observed. The analytical model provides an excellent tool to accurately predict the stress relaxation behavior of randomly oriented short-fiber composites.


Primary Vaginal Malignant Melanoma: A Case Report and Review of Literature.
Primary vaginal malignant melanoma is an extremely rare and aggressive tumor with very few reported cases worldwide. It often occurs in post-menopausal women, with a mean age of 57 years. The most common presenting symptom is vaginal bleeding. Other less common presenting symptoms are vaginal discharge, vaginal mass, and pain. Vaginal melanomas are often diagnosed at an advanced stage, and despite the aggressive treatment approach, the prognosis is poor. We present to you a case of a 56-year-old post-menopausal woman who presented with intermittent vaginal bleeding and passage of dark clots. She was found to have symptomatic anemia requiring blood transfusions. Further workup revealed a mass in the upper vagina on imaging studies, and the patient eventually underwent a biopsy, which confirmed the diagnosis of malignant melanoma of the vagina on pathological examination.


Task analysis of a christian-integrated psychotherapy framework.
This study aimed to gain a deeper understanding of spiritual change processes by conducting an empirical investigation of clinically meaningful events occurring within the context of a Christian-Integrated Psychotherapy Framework. The discovery phase of task analysis was used to build a rational-empirical model that explicated how clients developed stronger attachments to their God images. A rational model was specified, and five cases were selected for further analysis from a pool of 27 client-participants and 423 video-recorded psychotherapy sessions. Clinical observations and the coding of in-session measures were used to select resolved and unresolved cases, which were then contrasted to create a 10-step rational-empirical model. In this model, clients initially presented with intense feelings of shame, guilt, or helplessness but concluded with heightened levels of love and joy. Clients who reached this resolution all underwent an experience whereby their God images became dynamic, alive, intimate, and authentic. Results are discussed, and implications for the existence of an in vivo God image and corrective emotional spiritual experiences are introduced. Specifically, corrective emotional spiritual experiences appear to have influenced clients to transition from being insecurely attached to more securely attached to their in vivo God images. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Determinants of increased frequency of depressive and anxiety symptoms in exercise professionals during the COVID-19 pandemic.
The coronavirus disease (COVID-19) pandemic has affected workers in different health services including exercise professionals (EP). The urgent need to adapt in-person to online activities might have led to increased frequency of anxiety and depressive symptoms. We aimed to identify the determinants of aggravated depressive and anxiety symptoms in EP in southern Brazil during social distancing from the COVID-19. A cross-sectional study was conducted with EP who worked at fitness centers, sports clubs, private schools, or at a public exercise program offered by the municipal council. We used an online-based, self-administered, adapted version of the Hospital Anxiety and Depression scale to compare symptoms of depression and anxiety pre- and during social distancing. Participants (n = 201) had a mean age of 32.7±8.0 years, with more than half being male, white, and having an university degree. We observed that 81%and 71%of respondents reported higher frequency in anxiety and depression symptoms, respectively, during social distancing than in the period before it. Physical education teachers, women, non-white professionals, and those with chronic disease were more likely to worsen anxiety symptoms. Women had higher odds to increased frequency in depressive symptoms. Physical activity and previous experience with internet-based tools for working activities reduced the risk of increased depressive symptoms. Sex, ethnicity, chronic diseases, educational level, physical activity, and experience with online tools were determinants for increased frequency of depression and anxiety symptoms in EP.