Audio-visual speech perception in adult readers with dyslexia: an fMRI study.
Developmental dyslexia is a specific deficit in reading and spelling that often persists into adulthood. In the present study, we used slow event-related fMRI and independent component analysis to identify brain networks involved in perception of audio-visual speech in a group of adult readers with dyslexia (RD) and a group of fluent readers (FR). Participants saw a video of a female speaker saying a disyllabic word. In the congruent condition, audio and video input were identical whereas in the incongruent condition, the two inputs differed. Participants had to respond to occasionally occurring animal names. The independent components analysis (ICA) identified several components that were differently modulated in FR and RD. Two of these components including fusiform gyrus and occipital gyrus showed less activation in RD compared to FR possibly indicating a deficit to extract face information that is needed to integrate auditory and visual information in natural speech perception. A further component centered on the superior temporal sulcus (STS) also exhibited less activation in RD compared to FR. This finding is corroborated in the univariate analysis that shows less activation in STS for RD compared to FR. These findings suggest a general impairment in recruitment of audiovisual processing areas in dyslexia during the perception of natural speech.


Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease.
Epithelial to mesenchymal transition (EMT) converts epithelial cells to mobile and developmentally plastic mesenchymal cells. All cells in the heart arise from one or more EMTs. Endocardial and epicardial EMTs produce most of the noncardiomyocyte lineages of the mature heart. Endocardial EMT generates valve progenitor cells and is necessary for formation of the cardiac valves and for complete cardiac septation. Epicardial EMT is required for myocardial growth and coronary vessel formation, and it generates cardiac fibroblasts, vascular smooth muscle cells, a subset of coronary endothelial cells, and possibly a subset of cardiomyocytes. Emerging studies suggest that these developmental mechanisms are redeployed in adult heart valve disease, in cardiac fibrosis, and in myocardial responses to ischemic injury. Redirection and amplification of disease-related EMTs offer potential new therapeutic strategies and approaches for treatment of heart disease. Here, we review the role and molecular regulation of endocardial and epicardial EMT in fetal heart development, and we summarize key literature implicating reactivation of endocardial and epicardial EMT in adult heart disease.


Brain metastasization of breast cancer.
Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted.


Trauma and bereavement: conceptual and clinical issues revolving around relationships.
The article re-examines trauma and bereavement and the category of loss considered to be traumatic bereavement. It is argued that the perspective of the relation to the deceased is an insufficiently acknowledged source of traumatic disruption following bereavement. The significance of the relational aspect in bereavement is present in the paradigm of the Two-Track Model of Bereavement (S. Rubin, 1981, 1999). The implications of this approach are examined in the case of a soldier exposed to trauma and death. The case is examined from a traditional trauma perspective stressing exposure to life threat and again from a perspective stressing the significance of the relationship to the deceased. An examination of the different intervention strategies and their outcome lends support to the importance of the relational aspects in this case of trauma and supports the use of the Two-Track Model of Bereavement. The location of trauma as basic to the experience of all bereavement for its impact on the reorganization vis a vis the representation of the loved one now deceased is considered as fundamental to the trauma of all bereavement. The additional contribution of bereavement occurring under conditions of life threat (traumatic situations) is an important feature potentially impacting the bereavement process, but it is not what makes bereavement traumatic per se. An additional source of trauma in bereavement, occurring when the previous representation or introject of the deceased is shattered, is considered for its status as an additional source of complication in the traumas of bereavement.


Pollination biology of mass flowering terrestrial utricularia species (lentibulariaceae) in the Indian Western Ghats.
The pollination biology of three mass flowering Utricularia species of the Indian Western Ghats, U. albocaerulea, U. purpurascens, and U. reticulata, was studied for the first time by extensive observation of flower visitors, pollination experiments, and nectar analyses. The ephemerality of the Utricularia habitats on lateritic plateaus, weather conditions adverse to insects, lack of observations of flower visitors to other Utricularia spp., and the predominance of at least facultative autogamy in the few Utricularia species studied so far suggested that an autogamous breeding system is the common case in the genus. In contrast, we showed that the studied populations are incapable of autonomous selfing, or that it is an event of negligible rarity, although P/O was similarily low as in autogamous species investigated by other authors. In all three species the spatial arrangement of the reproductive organs makes an insect vector necessary for pollen transfer between and within flowers. However, U. purpurascens and U. reticulata are highly self-compatible, which allows for visitor-mediated auto-selfing and geitonogamy on inflorescence and clone level. Floral nectar is present in extremely small volumes in all three species, but sugar concentrations are high. More than 50 species of bees, butterflies, moths, hawk moths, and dipterans were observed to visit the flowers, and flower morphology facilitated pollination by all observed visitors. The results are discussed in the context of the phenological characteristics of the studied species, especially the phenomenon of mass flowering, and the environmental conditions of their habitats.


Kalirin/Trio Rho guanine nucleotide exchange factors regulate a novel step in secretory granule maturation.
The molecular mechanisms involved in the maturation of secretory granules, organelles that store hormones and neuropeptides, are poorly understood. As granule content proteins are processed, the composition of granule membranes changes, yielding constitutive-like secretion of immature content proteins and producing secretagogue-responsive mature granules. Constitutive-like secretion was not previously recognized as a process subject to regulation. We show that Kalirin and Trio, homologous Rho guanine nucleotide exchange factors (GEFs), which interact with a secretory granule resident protein, modulate cargo secretion from immature granules. Some of the Kalirin and Trio isoforms expressed in neuroendocrine cells colocalize with immature granules. Overexpression of their N-terminal GEF domain (GEF1) enhances secretion from immature granules, depleting cells of secretory cargo in the absence of secretagogue. This response requires GEF1 activity and is mimicked by Kalirin/Trio substrates Rac1 and RhoG. Accordingly, selective pharmacological inhibition of endogenous GEF1 activity decreases secretagogue-independent release of hormone precursors, accumulating product peptide in mature secretory granules. Kalirin/Trio modulation of cargo secretion from immature granules provides secretory cells with an extra layer of control over the sets of peptides released. Control of this step enhances the range of physiological responses that can be elicited, whereas lack of control could have pathological consequences.


In vivo single cell detection of tumor-infiltrating lymphocytes with a clinical 1.5 Tesla MRI system.
We demonstrate the feasibility of detecting individual tumor-infiltrating cells in vivo, by means of cellular magnetic labeling and a 1.5 Tesla clinical MRI device equipped with a high-resolution surface coil. Using a recently developed high-temperature superconducting (HTS) surface coil, single cells were detected in vitro in voxels of (60 microm)(3) at magnetic loads as low as 0.2 pg of iron per cell. The same imaging protocol was used in vivo to monitor infiltration of ovalbumin-expressing tumors by transferred OVA antigen-specific cytotoxic lymphocytes with low iron load.


The Comparison of the Surgical Outcome for the Full-Thickness Macular Hole with/without Lamellar Hole-Associated Epiretinal Proliferation.
To compare the surgical outcome of pars plana vitrectomy (PPV) for full-thickness macular hole (FTMH) with and without lamellar hole-associated epiretinal proliferation (LHEP). This retrospective study included 158 eyes of 158 patients with FTMH treated with PPV. The following variables were analyzed: sex, age, preoperative best corrected visual acuity (pre-BCVA), BCVA 6 months after the surgery (6M-BCVA), the axial length of eye, the minimum diameter of FTMH, the diameter of basal side of FTMH, postoperative continuity of subfoveal ellipsoid zone (EZ) and external limiting membrane (ELM), and the preoperative presence of LHEP. Twenty-eight eyes had FTMH with LHEP and 130 without LHEP. The mean ± SD age (years) was 72.6 ± 7.9 and 68.6 ± 8.7, respectively (p = 0.02). 6M-BCVA was 0.38 ± 0.30 and 0.26 ± 0.25, respectively (p = 0.03). The diameter of basal side of FTMH (μm) was 901.5 ± 404.9 and 658.9 ± 288.1, respectively (p = 0.00027). EZ was disrupted in 24 eyes and 63 eyes, respectively (p = 0.00071). ELM was disrupted in 15 eyes and 23 eyes, respectively (p = 0.00015). The FTMH diameters and the presence of LHEP were inversely correlated with the continuity of EZ and ELM. The preoperative appearance of LHEP could be one of the prognostic factor for the treatment of FTMH.


Skin color in the development of identity: a biopsychosocial model.
The role of skin color in the development of identity has been studied by a variety of paradigms. This paper applies the biopsychosocial model to this problem, with the hope that systems hierarchies offer a way to understand how many variables have an impact on a single point. This model postulates that complex social interactions are the life setting for the individual whose development also reflects biological endowment, including the contributions of heredity and nurturance. The final personal integration of an adult understanding of skin color requires an active assertion by the individual. This model is explored through the writings of Jessie Fauset, a leading participant in the literary movement known as the Harlem Renaissance.


Quantitative evaluation of Kaiser score in diagnosing breast dynamic contrast-enhanced magnetic resonance imaging for patients with high-grade background parenchymal enhancement.
High-grade background parenchymal enhancement (BPE), including moderate and marked, poses a considerable challenge for the diagnosis of breast disease due to its tendency to increase the rate of false positives and false negatives. The purpose of our study was to explore whether the Kaiser score can be used for more accurate assessment of benign and malignant lesions in high-grade BPE compared with the Breast Imaging Reporting and Data System (BI-RADS). A retrospective review was conducted on consecutive breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans from 2 medical centers. Included were patients who underwent DCE-MRI demonstrating high-grade BPE and who had a pathology-confirmed diagnosis. Excluded were patients who had received neoadjuvant chemotherapy or who had undergone biopsy prior to MRI examination. Two physicians with more than 7 years of experience specializing in breast imaging diagnosis jointly reviewed breast magnetic resonance (MR) images. The Kaiser score was used to determine the sensitivity, specificity, and positive predictive value (PPV), and negative predictive value (NPV) of the BI-RADS from different BPE groups and different enhancement types. The performance of the Kaiser score and BI-RADS were compared according to diagnostic accuracy. A total of 126 cases of high-grade BPE from 2 medical centers were included in this study. The Kaiser score had a higher specificity and PPV than did the BI-RADS (87.5% vs. 46.3%) as well as a higher PPV (94.3% vs. 79.8%). The value of diagnostic accuracy and 95% confidence interval (CI) for the Kaiser score (accuracy 0.928; 95% CI: 0.883-0.973) was larger than that for BI-RADS (accuracy 0.810; 95% CI: 0.741-0.879). Moreover, the Kaiser score had a significantly higher value of diagnostic accuracy for both mass and non-mass enhancement, especially mass lesions (Kaiser score: accuracy 0.947, 95% CI: 0.902-0.992; BI-RADS: accuracy 0.821, 95% CI: 0.782-0.860), with a P value of 0.006. The Kaiser score is a useful diagnostic tool for the evaluation of high-grade BPE lesions, with a higher specificity, PPV, and diagnostic accuracy as compared to the BI-RADS.


A new biophysics approach using photoacoustic spectroscopy to study the DNA-ethidium bromide interaction.
We have examined the binding processes of ethidium bromide interacting with calf thymus DNA using photoacoustic spectroscopy. These binding processes are generally investigated by a combination of absorption or fluorescence spectroscopies with hydrodynamic techniques. The employment of photoacoustic spectroscopy for the DNA-ethidium bromide system identified two binding manners for the dye. The presence of two isosbestic points (522 and 498 nm) during DNA titration was evidence of these binding modes. Analysis of the photoacoustic amplitude signal data was performed using the McGhee-von Hippel excluded site model. The binding constant obtained was 3.4 x 10(8) M(bp)(-1), and the number of base pairs excluded to another dye molecule by each bound dye molecule (n) was 2. A DNA drug dissociation process was applied using sodium dodecyl sulfate to elucidate the existence of a second and weaker binding mode. The dissociation constant determined was 0.43 mM, whose inverse value was less than the previously obtained binding constant, demonstrating the existence of the weaker binding mode. The calculated binding constant was adjusted by considering the dissociation constant and its new value was 1.2 x 10(9) M(bp)(-1) and the number of excluded sites was 2.6. Using the photoacoustic technique it is also possible to obtain results regarding the dependence of the quantum yield of the dye on its binding mode. While intercalated between two adjacent base pairs the quantum yield found was 0.87 and when associated with an external site it was 0.04. These results reinforce the presence of these two binding processes and show that photoacoustic spectroscopy is more extensive than commonly applied spectroscopies.


The acquired immunodeficiency syndrome and intravenous drug abuse.
Intravenous drug abusers constitute 25 per cent of the cases of the acquired immunodeficiency syndrome (AIDS) in adults in the United States of America and 21 per cent of such cases in Europe. The potential for the rapid spread of the human immunodeficiency virus (HIV) among intravenous drug abusers exists because such drug abusers commonly share drug injection equipment. The heterosexual and perinatal spread of AIDS is also largely associated with intravenous drug abusers, and drug abusers have been identified as a major vector for the spread of the AIDS epidemic as it is associated with intravenous drug abuse. As long as intravenous drug abusers are addicted, they will continue to be at risk of contracting AIDS. Thus, the primary AIDS prevention strategy must be to help addicts to stop using drugs. It is suggested that drug abuse treatment resources should be expanded and outreach programmes developed to encourage more intravenous drug abusers to enter treatment. AIDS risk-reduction counseling must also be provided to intravenous drug abusers who continue injecting drugs, and to addicts and their sexual partners to prevent the sexual spread of HIV. Vigorous AIDS prevention initiatives must be undertaken now, using the most promising intervention strategies, while simultaneously evaluating and refining these strategies.


Liposarcomas/atypical lipomatous tumors of the oral cavity: a clinicopathologic study of 23 cases.
Liposarcomas in the oral cavity have rarely been described, with less than 50 reported cases to date and a purported predominance of the myxoid type. We reviewed our experience with 23 atypical lipomatous tumors/liposarcomas of the oral cavity. Twelve patients were men, 10 were women, and gender was not stated in one case. Age at presentation ranged from 28 to 83 years (median, 49.5 years). The most commonly affected site was the tongue and most cases presented as a slowly growing, painless mass. The clinical impression was lipoma or fibroma in the majority of cases. Tumor size ranged from 0.6 to 8.0 cm (median, 1.5 cm). Five cases were well circumscribed, 5 cases were focally infiltrative, and 13 cases had markedly infiltrative margins. Twenty-one cases were classified as atypical lipomatous tumors (of which 10 showed spindle cell features), one as dedifferentiated liposarcoma, and one as myxoid liposarcoma. Follow-up data was available in 13 of the 23 cases. Five others were lost to follow-up after a short period. Eleven patients remained free of disease without local recurrence or metastasis during the period of follow-up that ranged from 10 months to 9 years (median, 24 months). Two patients had multiple local recurrences. Our study shows that atypical lipomatous tumor is the most common type of malignant fatty tumor to arise in the oral cavity with an apparently low risk of recurrence if widely excised, although follow-up is relatively limited thus far.


Cinecoronary arteriography in young men.
Of a group of 723 men less than 40 years old who underwent cinecoronary arteriography primarily for evaluation of chest pain, 357 (49%) were found to have at least 50% narrowing of one or more coronary arteries. The youngest person was 17 years old. The distribution of lesions in the young men was similar to that found earlier in a study of persons not selected by age. The anterior descending coronary artery was most frequently affected; the right coronary artery was most often totally occluded. No total occlusions of the left main coronary artery were seen. Electrocardiographic evidence of myocardial infarction, found in 109 patients, was less common with disease of the circumflex or right coronary arteries than with disease of the anterior descending coronary artery. This observation was confirmed by examination of left ventriculograms for areas of decreased contractility. Six patients had no significant arterial narrowing. The extent of arterial involvement seemed to be related to the duration of symptoms in patients who had angina pectoris or myocardial infarctions. Clinical diagnoses correlated well with the angiographic findings, particularly in those men considered to be normal and those with typical angina pectoris. Addition of atypical features or prolonged pain decreased the degree of correlation. Only 20% of those with cholesterol levels less than 200 mg/100 ml had significant lesions, whereas 81% with levels more than 275 mg/100 ml had such findings.


Codimension-two points in annular electroconvection as a function of aspect ratio.
We rigorously derive from first principles the generic Landau amplitude equation that describes the primary bifurcation in electrically driven convection. Our model accurately represents the experimental system: a weakly conducting, submicron thick liquid crystal film suspended between concentric circular electrodes and driven by an applied voltage between its inner and outer edges. We explicitly calculate the coefficient g of the leading cubic nonlinearity and systematically study its dependence on the system's geometrical and material parameters. The radius ratio alpha quantifies the film's geometry while a dimensionless number P , similar to the Prandtl number, fixes the ratio of the fluid's electrical and viscous relaxation times. Our calculations show that for fixed alpha, g is a decreasing function of P , as P becomes smaller, and is nearly constant for P> or =1 . As P-->0, g-->infinity. We find that g is a nontrivial and discontinuous function of alpha. We show that the discontinuities occur at codimension-two points that are accessed by varying alpha.


Calcium-entry blockers in the treatment of vestibular disorders.
Based upon the results of a double-blind study carried out in a series of 120 patients suffering from vertigo and objective vestibular symptoms, we made the following observations during the treatment of vestibular disorders by means of calcium-entry blockers: Subjective symptoms regress fairly well during treatment, but no better than after betahistine-dihydrochloride (BHC) or thietylperazine therapy (TP). Objective assessment of the therapeutic action of calcium antagonists on vestibular dysfunction is based on the results of the Harmonic Acceleration test, which was carried out by using a computerized rotatory chair. The most reliable parameter with respect to the objective assessment of the experimentally induced vestibular responses (VOR) is the gain. Our test results show a progressive decrease in GAIN, indicating a depressive or inhibitory effect of the calcium antagonist flunarizine upon the VOR. If we compare these results with those obtained in the betahistidine- and thiethylperazine groups, we cannot confirm the same decline in GAIN within the latter two groups. A statistical analysis demonstrates a significant difference between the F-gain on the one hand, and the BHC gain and TP gain on the other hand.


Anaerobic and aerobic performances in elite basketball players.
THE PURPOSE OF THIS STUDY WAS TO PROPOSE A SPECIFIC LACTATE MINIMUM TEST FOR ELITE BASKETBALL PLAYERS CONSIDERING THE: Running Anaerobic Sprint Test (RAST) as a hyperlactatemia inductor, short distances (specific distance, 20 m) during progressive intensity and mathematical analysis to interpret aerobic and anaerobic variables. The basketball players were assigned to four groups: All positions (n=26), Guard (n= 7), Forward (n=11) and Center (n=8). The hyperlactatemia elevation (RAST) method consisted of 6 maximum sprints over 35 m separated by 10 s of recovery. The progressive phase of the lactate minimum test consisted of 5 stages controlled by an electronic metronome (8.0, 9.0, 10.0, 11.0 and 12.0 km/h) over a 20 m distance. The RAST variables and the lactate values were analyzed using visual and mathematical models. The intensity of the lactate minimum test, determined by a visual method, reduced in relation to polynomial fits (2nd degree) for the Small Forward positions and General groups. The Power and Fatigue Index values, determined by both methods, visual and 3rd degree polynomial, were not significantly different between the groups. In conclusion, the RAST is an excellent hyperlactatemia inductor and the progressive intensity of lactate minimum test using short distances (20 m) can be specifically used to evaluate the aerobic capacity of basketball players. In addition, no differences were observed between the visual and polynomial methods for RAST variables, but lactate minimum intensity was influenced by the method of analysis.


Measurements of brain activity complexity for varying mental loads.
Using functional magnetic resonance imaging, we investigate the variation in dynamical complexity of human brain activity for different mental loads. Our experiments measured the activity of ten subjects under three experimental conditions: a rest condition, a periodic task of finger opposition, and a task of finger opposition alternated with mathematical serial calculation. We used the correlation dimension to gauge the spatiotemporal complexity of brain activity. The experiments show a direct relationship between this complexity and the difficulty of the task. A natural interpretation is that higher levels of mental load recruit a larger number of independent neural processes that contribute to complex brain dynamics. These results suggest the possibility that the relative change in correlation dimension can be a useful global measure of brain dynamics, e.g., in determining the levels of mental activity, even if little is known about the underlying neurological processes.


Unusual morphologic features of endometrial stromal tumors: a report of 2 cases.
Endometrial stromal tumors with typical morphology usually do not pose diagnostic problems. However, the finding of unusual morphologic features may be misleading in the final interpretation of these tumors. Herein, we described two endometrial stromal sarcomas discovered in hysterectomy specimens of women 31 and 75 years of age. Features typical of endometrial stromal neoplasia were present in both cases. Additionally, in 1 case, extensive fatty metaplasia as well as smooth and skeletal muscle metaplasia were found; and in the second case, focal bizarre nuclei, smooth muscle differentiation, and fibrous change were present. The differential diagnosis in the first case included cellular intravenous leiomyomatosis/lipoleiomyomatosis with skeletal muscle differentiation; and in the second case, a cellular smooth muscle tumor with bizarre nuclei was considered.


High incidence of vaginal mesh extrusion using the intravaginal slingplasty sling.
The intravaginal slingplasty (IVS) is a tension-free vaginal tape variant that uses a multi-filament polypropylene tape to support the mid urethra for the treatment of female stress urinary incontinence. Numerous cases of defective vaginal wound healing have been described in the international urogynecological literature. We describe our experience of vaginal mesh extrusion using the IVS sling. A total of 35 patients underwent suburethral sling procedures for anatomical stress urinary incontinence using the IVS system from November 2002 to September 2003. A retrospective chart review was performed to retrieve data on safety and efficacy, complications and outcomes using this product. Six patients (17%) to date have presented with defective vaginal healing manifested by extrusion of the sling material. Mean time to presenting symptoms was 9 months (range 2 to 15). All patients required surgical removal of the sling material. No urethral erosions were noted. Our experience suggests that the IVS sling system, which uses a multi-filament polypropylene suburethral mesh, incurs an unacceptably high rate of defective vaginal wound healing and mesh extrusion.


[Glandulo-cystic polyps of the stomach. Apropos of 12 cases and review of the literature].
We report 12 cases of cystic glandular fundic polyps detected in 7 women and 5 men. As in the 238 similar previously reported cases these lesions were always located in the fundic gastric mucosae and did not involve the muscularis mucosae. They were discovered by endoscopy in patients with minor abdominal discomfort. They were less than 5 mm in diameter and were more often multiple and sessile; only a few of them were pedunculate. They consisted of mucosal cysts lined with cuboidal, parietal or chief cells and surrounded with a normal lamina propria. If in 213 cases, these polyps were not associated with polyposis coli in 37 cases they occurred with a Gardner's syndrome or a familial adenomatosis coli. These benign lesions are without malignant potential. Careful gastroscopic follow up with biopsy is recommended for all patients with multiple gastric polyps. The etio-pathogenesis of these polyps is still unknown. Their relationship to familial polyposis coli or to Gardner's syndrome is obscure.


The Role of miRNAs in Angiogenesis, Invasion and Metabolism and Their Therapeutic Implications in Gliomas.
MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules that function in gene silencing by post-transcriptional regulation of gene expression. The dysregulation of miRNA plays a pivotal role in cancer tumorigenesis, including the development and progression of gliomas. Their small size, stability and ability to target multiple oncogenes have simultaneously distinguished miRNAs as attractive candidates for biomarkers and novel therapeutic targets for glioma patients. In this review, we summarize the most frequently cited miRNAs known to contribute to gliomagenesis and progression by regulating the defining hallmarks of gliomas, including angiogenesis, invasion, and cell metabolism. We also discuss their promising potential as prognostic and predictive biomarkers and novel therapeutic targets, in addition to the challenges that must be overcome before their translation from bench to bedside.


Evaluation of differentially expressed immune-related genes in intestine of Pelodiscus sinensis after intragastric challenge with lipopolysaccharide based on transcriptome analysis.
Pelodiscus sinensis is the most common turtle species that has been raised in East and Southeast Asia. However, there are still limited studies about the immune defense mechanisms in its small intestine until now. In the present research, histological analysis and transcriptome analysis was performed on the small intestine of P. sinensis after intragastric challenge with LPS to explore its mechanisms of immune responses to pathogens. The result showed the number of intraepithelial lymphocytes (IELs) and goblet cells (GCs) in its intestine increased significantly at 48 h post-challenge with LPS by intragastrical route, indicating clearly the intestinal immune response was induced. Compared with the control, a total of 748 differentially expressed genes (DEGs) were identified, including 361 up-regulated genes and 387 down-regulated genes. Based on the Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG), 48 immune-related DEGs were identified, which were classified into 82 GO terms and 14 pathways. Finally, 18 DEGs, which were randomly selected, were confirmed by quantitative real-time PCR (qRT-PCR). Our results provide valuable information for further analysis of the immune defense mechanisms against pathogens in the small intestine of P. sinensis.


Sex differences in treatment quality of self-managed oral anticoagulant therapy: 6,900 patient-years of follow-up.
Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists has demonstrated efficacy in randomized, controlled trials. However, the effectiveness and efficacy of PSM in clinical practice and whether outcomes are different for females and males has been sparsely investigated.The objective is to evaluate the sex-dependent effectiveness of PSM of oral anticoagulant therapy in everyday clinical practice. All patients performing PSM affiliated to Aarhus University Hospital and Aalborg University Hospital, Denmark in the period 1996-2012 were included in a case-series study. The effectiveness was estimated using the following parameters: stroke, systemic embolism, major bleeding, intracranial bleeding, gastrointestinal bleeding, death and time spent in the therapeutic international normalized ratio (INR) target range. Prospectively registered patient data were obtained from two databases in the two hospitals. Cross-linkage between the databases and national registries provided detailed information on the incidence of death, bleeding and thromboembolism on an individual level. A total of 2068 patients were included, representing 6,900 patient-years in total. Males achieved a significantly better therapeutic INR control than females; females spent 71.1% of the time within therapeutic INR target range, whereas males spent 76.4% (p<0.0001). Importantly, death, bleeding and thromboembolism were not significantly different between females and males. Among patients treated with self-managed oral anticoagulant therapy, males achieve a higher effectiveness than females in terms of time spent in therapeutic INR range, but the incidence of major complications is low and similar in both sexes.


Different secretory IgA antibody responses after immunization with inactivated and live poliovirus vaccines.
The influence on secretory IgA antibody levels in milk and saliva of vaccination with oral, live poliovirus vaccine ( OPV ) and inactivated poliovirus vaccine (IPV) was studied. IPV, especially the antigen-rich Dutch vaccine, more often induced increases in antibody titers in milk (50%) than did OPV (26%) (P less than .01). OPV more often decreased the antibody levels in milk (40%) than did IPV (10%) (P less than .01). It was striking that mainly high prevaccination titers were decreased. The increases of IgA antibody in saliva were less striking. IPV caused increases as often in milk as in saliva, whereas OPV more often induced increases in IgA antibody in saliva, but there was a poor correlation between the changes in antibody titers in milk and those in saliva.


[Automatic segmentation of three dimension medical image series].
We propose an improved version of regional competition algorithm in this paper, and apply it to the automatic segmentation of medical image series, particularly in the segmentation and recognition of brain tumor. The traditional regional competition is enhanced by combining the attractive aspects of fuzzy segmentation, and thus it provides an efficient approach to segment the fuzzy and heterogeneous medical images. In order to perform regional competition on medical image series, we utilize the segmentation result of a slice to initiate the next segmented slice, while the first slice is initialized using regional growing algorithm. Moreover, we develop an algorithm to recognize the tumors automatically, taking into account its characters. Experimental results show that our algorithm performs well on the segmentation of magnetic resonance imaging (MRI) image series with high speed and precision.


Social Data: An Underutilized Metric for Determining Participation in COVID-19 Vaccinations.
Many measures have been taken since late 2019 to combat the coronavirus disease (COVID-19) pandemic. National, state, and local governments employed precautions, including mask mandates, stay-at-home orders, and social distancing policies, to alleviate the burden on healthcare workers and slow the spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) virus until an efficacious vaccine was made widely available. By early spring of 2021, three effective and well-tolerated SARS-CoV-2 vaccines emerged and underwent broad distribution. Throughout the course of the COVID-19 vaccination campaign, several key logistical and psychological issues surfaced. Of these, access to vaccines and vaccination hesitancy are cited as two substantial hindrances towards vaccination. Noting the demand for the SARS-CoV-2 vaccine and its highly sensitive storage requirements, accurate dose allocation is critical for vaccinating the population quickly and successfully. Here, we propose the use of social data as a tool to predict vaccination participation by correlating Google searches with state-level daily vaccination. We identified a temporal and regionally-ubiquitous Google search syntax that broadly captures daily vaccination trends. By correlating trends in the search syntax with daily vaccination rates, we were able to quantify the correlation and identify optimal lag periods between Google searches and daily vaccination. This work highlights the importance of analyzing social data as a metric to effectively arrange vaccination roll-outs, identify voluntary vaccination participation, and identify inflection points in vaccination participation. In addition, social data assessments can help direct dose allocation, identify geographic areas that may seek, but lack, access to the vaccines, and actively prepare for fluctuations in vaccination demands.


Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells.
IL-10 is a pleiotropic cytokine with multifaceted functions in establishing immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1 cells produce marginal levels of IL-10 compared with their Th2 counterparts. In this study, we investigated the epigenetic mechanisms of Il-10 gene expression in Th1 cells. Bioinformatics EMBOSS CpG plot analysis and bisulfite pyrosequencing revealed three CpG DNA methylation sites in the Il-10 gene locus. Progressive DNA methylation at all of the CpG regions of interest (ROIs) established a repressive program of Il-10 gene expression in Th1 cells. Interestingly, Th1 cells treated with IL-12 and IL-27 cytokines, thereby mimicking a chronic inflammatory condition in vivo, displayed a significant increase in IL-10 production that was accompanied by selective DNA demethylation at ROI 3 located in intron 3. IL-10-producing T cells isolated from lymphocytic choriomeningitis virus-infected mice also showed enhanced DNA demethylation at ROI 3. Binding of STAT1 and STAT3 to demethylated ROI 3 enhanced IL-10 expression in an IL-12/IL-27-dependent manner. Accordingly, CD4+ T cells isolated from STAT1- or STAT3-knockout mice were significantly defective in IL-10 production. Our data suggest that, although stably maintained DNA methylation at the promoter may repress IL-10 expression in Th1 cells, locus-specific reversible DNA demethylation may serve as a threshold platform to control transient Il-10 gene expression.


Advancing the quality of environmental microplastic research.
Investigations into the environmental fate and effects of microplastics have been gaining momentum. Small, insoluble polymeric particles are implicated by scientists in a wide variety of studies that are used to suggest a potential for widespread impacts in freshwater and marine pelagic and sediment environments. An exponential growth in scientific publications and an increase in regulatory attention have occurred. However, despite these efforts, the environmental hazard of these particles is still unknown. To evaluate the hazard of microplastics within a risk assessment context, we need a way to evaluate the quality of experimental studies. We performed a thorough review of the quality and focus of environmental microplastic research, to understand the methodologies employed and how this may assist or distract from the ability of environmental risk assessors to evaluate microplastics. We provide guidance to improve the reliability and relevance of ecotoxicological studies for regulatory and broader environmental assessments. Nine areas of needed improvement are identified and discussed. Important data gaps and experimental limitations are highlighted. Environ Toxicol Chem 2017;36:1697-1703. © 2017 SETAC.


Comparative luciferase assay for establishing reliable in vitro screening system of juvenile hormone agonists.
The cultured cell-based in vitro assay using the stringency of ligand-receptor interactions is typically useful for screening certain hormone agonists from among a very large number of molecules. However, ligands are frequently altered or modified through evolution; indeed, even in the same receptor orthologs, different ligand sensitivity profiles are considered to arise among species and/or taxa. Such ligand transition has been observed in juvenile hormone (JH), one of the most important endocrine factors in arthropods. To understand the molecular basis of ligand selectivity alteration in hormone receptors, we compared the amino acid sequences and ligand selectivity of the JH receptor, Methoprene-tolerant (Met), among three insects (Drosophila melanogaster, Aedes aegypti and Tribolium castaneum) and one crustacean (Daphnia pulex). Compared with D. pulex, we found that the receptors of the three insects showed a higher sensitivity to JH III, which is the major innate JH ligand in insects. Furthermore, point mutation analysis in Met sequences revealed a candidate amino acid residue that is important for increasing JH sensitivity in insects. Amino acid mutations in Met may have affected changes in ligand selectivity intermittently over the course of the evolution of the JH-signaling pathway. These findings are useful to improve the existing (developing) cultured cell-based assay system and may shed light on the relationship between functional diversification in hormonal signaling and the molecular evolution of hormone receptors. Copyright © 2017 John Wiley & Sons, Ltd.


Effect of Preconception Care Intervention on Maternal Nutritional Status and Birth Outcome in a Low-Resource Setting: Proposal for a Nonrandomized Controlled Trial.
The provision of preconception care approaches such as maternal assessments and education on healthy lifestyle (including physical activity, nutrition, and dietary supplements such as folic acid), general and sexual health, avoidance of high-risk behavior, and immunizations has been shown to identify and reduce the risk of adverse birth outcomes through appropriate management and preventive measures. The goal of the study is to determine the effect of an integrated preconception care intervention on delivery outcomes, which is a novel challenge for lowering unfavorable birth outcomes in India's low-resource setting. The main objectives are to investigate the relationship of birth outcomes to both maternal and paternal preconception health and determine the effect of preconception care intervention on improvement of maternal nutritional status and reduction of the risk of adverse birth outcomes such as prematurity, low birth weight, and maternal and neonatal complications. A nonrandomized controlled trial design will be used for comparing 2 groups: preconception care with a standard maternal health care (MHC) program and an integrated MHC program (without preconception care). Two rural field areas of Khordha district, Odisha, will be selected for conducting the study. The study will enroll 782 married women between the ages of 18 and 35 years with their spouses, with 391 women in each group. The couples will receive preconception care based on their health circumstances, and they will be followed up at 3-month intervals before pregnancy. Following pregnancy, they will be followed up for 8 prenatal monitoring and care visits as well as 6 weeks after delivery as part of the standard MCH program. The preconception care intervention package includes couples counseling, contraceptive education and distribution, sex education, lifestyle modification, and nutritional supplementation of iron and folic acid, along with multivitamins if needed. The proposal was approved by the institutional ethical committee for conducting the study in June 2020 (Ref No: T/EMF/Nursing/20/6). Participants were enrolled in phase 1 in April 2021, phase 2 of offering preconception services will begin in August 2021, and study outcomes will be measured from 2023 to 2024. Through preconception care and counseling, the eligible couples will recognize, embrace, and implement the actions to improve their preconception health. Finally, it is expected that maternal and paternal health will have a significant impact on enhancing maternal nutritional status and birth outcomes. Clinical Trials Registry-India CTRI/2021/04/032836; http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=48239&EncHid=&userName=CTRI/2021/04/032836. PRR1-10.2196/28148.


Suppressive effect of morphine on single-unit activity of cells in Rexed lamina VII.
Using an extracellular microelectrode recording technique, the effects of intravenously administered morphine sulfate upon the single-unit activities of cells in Rexed lamina VII of the lumbar spinal cord were studied in cats following decerebration and spinal cord transection at L1. These neurons responded principally to high-threshold mechanical and thermal stimuli applied to a receptive field in the ipsilateral hind limbs. Morphine sulfate, 0.25, 0.5, and 1.0 mg/kg, caused dose-related suppression of the spontaneous activities of these neurons. The firing rates at maximum suppression, observed 5-10 min after administration of morphine, were 63.9 +/- 9.2 (mean +/- 1 SE), 43.0 +/- 5.4, and 26.5 +/- 6.0 per cent of the control values, respectively. Since these cells have been shown by others to be associated with the spinothalamic and spinoreticular pathways, the results suggest that the analgesic state may result from the action of morphine on the cells of origin of these major ascending pathways in the spinal cord.


Relativistic attosecond electron bunches from laser-illuminated droplets.
The generation of relativistic attosecond electron bunches is observed in three-dimensional, relativistic particle-in-cell simulations of the interaction of intense laser light with droplets. The electron bunches are emitted under certain angles which depend on the ratios of droplet radius to wavelength and plasma frequency to laser frequency. The mechanism behind the multi-MeV attosecond electron bunch generation is investigated using Mie theory. It is shown that the angular distribution and the high electron energies are due to a parameter-sensitive, time-dependent local field enhancement at the droplet surface.


Simultaneous removal of NOx and SO2 from simulated marine ship flue gas in a novel wet scrubbing system based on divided diaphragm seawater electrolysis technology: efficiency optimization and economic assessment.
This work constructed a divided diaphragm seawater electrolysis system with two tandem packed towers for the synergistic removal of NOx and SO2. The first tower was mainly used to oxidize NO and SO2 by AC (active chlorine), and the second tower was used to further absorb NOx. The factors affecting on NO removal, including ACC (active chlorine concentration), pH value, initial NO concentration and temperature in the oxidation tower were investigated. Moreover, the effect of different inlet gas concentrations and current values were explored. The results showed that with the increase of ACC, the NO and NOx removal efficiency increased rapidly, but when the ACC was higher than 500 mg/L [Cl2], the removal efficiency did not increase further in the oxidation tower. Low pH values in the oxidation tower were favorable for NO removal. NO removal efficiency reached a maximum at 40 °C. Higher NO and SO2 concentrations were favorable for NO removal. The decline of pH in the anode cell was not conducive to the storage of AC in the continuous electrolysis removal process. NOx and SO2 were almost completely removed after being scrubbed in the oxidation and absorption towers. The relationship between current and removal efficiency of NO and SO2 in the oxidation tower was also analyzed. Finally, the removal mechanism and the application prospects were discussed.


Evaluation of Daptomycin-Induced Cellular Membrane Injury in Skeletal Muscle.
Daptomycin, a cyclic lipopeptide antibiotic, has bactericidal activity against Gram-positive organisms and is especially effective against methicillin-resistant Staphylococcus aureus. Although daptomycin causes unique adverse drug reactions such as elevation of creatine phosphokinase or rhabdomyolysis, the detailed mechanisms underlying these adverse drug reactions in skeletal muscle are unclear. This study aimed to elucidate whether daptomycin causes direct skeletal muscle cell toxicity and investigate the relationship between daptomycin exposure and musculoskeletal toxicity. First, we evaluated the relationship between daptomycin exposure and skeletal muscle toxicity. Of the 38 patients who received daptomycin intravenously, an elevation in creatine phosphokinase levels was observed in five. The median plasma trough concentration of daptomycin in patients with elevated creatine phosphokinase levels was significantly higher than that in patients whose creatine phosphokinase levels were within the normal range, suggesting that increased exposure to daptomycin is related to elevation in creatine phosphokinase levels. In an in vitro study using human rhabdomyosarcoma cells, daptomycin reduced cell viability and increased membrane damage. These effects were more marked under hypoxic conditions. A necroptotic pathway seemed to be involved because phosphorylated mixed lineage kinase domain-like protein expression was enhanced following daptomycin exposure, which was significantly enhanced under hypoxic conditions. These findings indicate that daptomycin elicits cytotoxic effects against skeletal muscle cells via the necroptotic pathway, and the extent of toxicity is enhanced under hypoxic conditions.


Hypolipidemic effect of glycosaminoglycans from the sea cucumber Metriatyla scabra in rats fed a cholesterol-supplemented diet.
The purpose of this study was to determine the hypolipidemic effects of the glycosaminoglycans (GAGs) extracted from a sea cucumber, Metriatyla scabra. Using DEAE column chromatography, two major peaks containing GAGs were obtained: peak 1 (P-1) contained mainly GAGs (as hexuronic acid and hexosamine), whereas P-2 contained mostly free glycan (as fucose) with little hexuronic acid or hexosamine. Therefore, we used only the P-1 fraction (with molecular weights in the range 200-500 kDa) for evaluation of hypolipidemic effects. The lyophilized GAGs were administered orally to male Wistar rats at 5, 10, 20, and 50 mg/kg body weight for six consecutive weeks, during which the rats were fed ad libitum a basal laboratory diet with or without 1% cholesterol. The results show that the 1% cholesterol diet significantly increased plasma total cholesterol, LDL-cholesterol, and atherogenic index. Cholesterol supplementation also significantly increased hepatic TG, cholesterol, phospholipid, and liver weight. When rats fed the 1% cholesterol diet were supplemented orally with the sea cucumber GAGs, plasma levels of total cholesterol, LDL-cholesterol, and atherogenic index were significantly decreased, while HDL-cholesterol was significantly increased, although these effects of the GAGs were only dose-dependent at doses lower than 20 mg/kg b.w. Similarly, the GAGs significantly prevented the increase (p < 0.05) in hepatic contents of triglyceride, cholesterol, and phospholipid. Thus, the present study demonstrates that the sea cucumber GAGs have the potential of being used for reducing the risk of atherosclerosis and hyperlipoproteinemia.


Coupling of Ag Nanoparticle with Inverse Opal Photonic Crystals as a Novel Strategy for Upconversion Emission Enhancement of NaYF4: Yb(3+), Er(3+) Nanoparticles.
Rare-earth-ion-doped upconversion (UC) nanoparticles have generated considerable interest because of their potential application in solar cells, biological labeling, therapeutics, and imaging. However, the applications of UC nanoparticles were still limited because of their low emission efficiency. Photonic crystals and noble metal nanoparticles are applied extensively to enhance the UC emission of rare earth ions. In the present work, a novel substrate consisting of inverse opal photonic crystals and Ag nanoparticles was prepared by the template-assisted method, which was used to enhance the UC emission of NaYF4: Yb(3+), Er(3+) nanoparticles. The red or green UC emissions of NaYF4: Yb(3+), Er(3+) nanoparticles were selectively enhanced on the inverse opal substrates because of the Bragg reflection of the photonic band gap. Additionally, the UC emission enhancement of NaYF4: Yb(3+), Er(3+) nanoparticles induced by the coupling of metal nanoparticle plasmons and photonic crystal effects was realized on the Ag nanoparticles included in the inverse opal substrate. The present results demonstrated that coupling of Ag nanoparticle with inverse opal photonic crystals provides a useful strategy to enhance UC emission of rare-earth-ion-doped nanoparticles.


What do we measure when we measure cell-associated HIV RNA.
Cell-associated (CA) HIV RNA has received much attention in recent years as a surrogate measure of the efficiency of HIV latency reversion and because it may provide an estimate of the viral reservoir size. This review provides an update on some recent insights in the biology and clinical utility of this biomarker. We discuss a number of important considerations to be taken into account when interpreting CA HIV RNA measurements, as well as different methods to measure this biomarker.


Characterization of DESI-FTICR mass spectrometry - from ECD to accurate mass tissue analysis.
Implementation of desorption electrospray ionization (DESI) technique on a 9.4 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer is described. Desorption electrospray technique is capable of the direct investigation of natural samples without any need for sample preparation or chromatographic separation. Since the DESI mass spectra of natural samples are very complex owing to the lack of preseparation or cleanup, the ideal mass spectrometric analyzer for these applications is a high-resolution instrument such as FTICR mass spectrometer. DESI was implemented by constructing an electronically controlled source framework comprising six linear moving stages and one rotating stage. A three-dimensional linear stage was used to accommodate samples, while another 3D linear stage equipped with rotating stage was used as a spray mount. A modified electrosonic sprayer was used as a primary electrospray device. DESI-FTICR setup was characterized with regard to geometrical, electrical and flow conditions using deposited peptide samples in range of 1-100 pmol gross deposited amount on glass and polymer surfaces. Optimized conditions enabled the routine acquisition of DESI-MS spectra on the instrument at 130 000 resolution in the broadband mode and with comparable sensitivity to data reported in the literature. Since the main significance of DESI-FTICR MS is the combination of intact tissue analysis, the capabilities of the technique were demonstrated by analyzing murine liver samples. Presence of lysophospholipids in the liver tissue was tentatively associated with the lipid metabolism taking place in liver. DESI-FTICR is also a promising technique in the field of peptide analysis due to capability of top-down sequencing using electron capture dissociation. As a proof-of-principle experiment, a small synthetic polypeptide containing 36 amino acids was ionized using DESI and was sequenced in the FTICR by means of ECD (electron capture dissociation) fragmentation. Spectra gave almost full sequence information in agreement with the known amino acid sequence of the species.


Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung.
Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial Pco2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O2 difference, arterial Po2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-alpha was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable.


A Polytomous Scoring Approach to Handle Not-Reached Items in Low-Stakes Assessments.
In low-stakes assessments, some students may not reach the end of the test and leave some items unanswered due to various reasons (e.g., lack of test-taking motivation, poor time management, and test speededness). Not-reached items are often treated as incorrect or not-administered in the scoring process. However, when the proportion of not-reached items is high, these traditional approaches may yield biased scores and thereby threatening the validity of test results. In this study, we propose a polytomous scoring approach for handling not-reached items and compare its performance with those of the traditional scoring approaches. Real data from a low-stakes math assessment administered to second and third graders were used. The assessment consisted of 40 short-answer items focusing on addition and subtraction. The students were instructed to answer as many items as possible within 5 minutes. Using the traditional scoring approaches, students' responses for not-reached items were treated as either not-administered or incorrect in the scoring process. With the proposed scoring approach, students' nonmissing responses were scored polytomously based on how accurately and rapidly they responded to the items to reduce the impact of not-reached items on ability estimation. The traditional and polytomous scoring approaches were compared based on several evaluation criteria, such as model fit indices, test information function, and bias. The results indicated that the polytomous scoring approaches outperformed the traditional approaches. The complete case simulation corroborated our empirical findings that the scoring approach in which nonmissing items were scored polytomously and not-reached items were considered not-administered performed the best. Implications of the polytomous scoring approach for low-stakes assessments were discussed.


Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat.
This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type-2 diabetes in rat. Diabetes was induced by streptozotocin injection to neonatal rats which were breastfed for 4 weeks, then fed 6 weeks with normal food or food supplemented with 2% vitamin E and 4% vitamin C. Some diabetic rats were treated with gliclazide for 6 weeks. Endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside (SNP) were recorded in thoracic aortic rings. Plasma insulin, HbA(1c) and antioxidant vitamins (A, C and E); plasma and aortic malondialdehyde (MDA) levels were determined. Induction of diabetes resulted in decreased body weight and increased blood glucose, plasma insulin and HbA(1c) levels compared to controls. Acetylcholine relaxation was impaired in diabetic aorta, while SNP relaxation remained unchanged. Aortic MDA level was significantly higher, while plasma vitamin levels were lower in diabetic rats. Diminished acetylcholine response, enhanced aortic MDA level and decreased plasma vitamin levels were all restored after gliclazide and/or vitamin therapy. However, vitamin supplementation in control rats significantly impaired acetylcholine relaxations and increased aortic MDA levels. Apparently, a selective endothelial dysfunction accompanies the imbalance in oxidant/antioxidant status in the type-2 diabetes model of rat and gliclazide and/or vitamin supplementation improves the impairment in diabetic vasculature. However, vitamin supplementation triggers oxidative stress in normal aortic tissue, thereby, leads to endothelial dysfunction; indicating that nutritional extra-supplementation of antioxidant vitamins isn't advisable for normal subjects, although it's beneficial in disease status.


Effects of supervised structured aerobic exercise training program on high and low density lipoprotein in patients with type II diabetes mellitus.
Hyperlipidemia and dyslipidemia are very common conditions among patients with Type-2 diabetes mellitus (T2DM) and associated with increased risk of coronary heart diseases. Physical activity and exercises along with medical management and dietary plan are common strategies to use for the management of deranged lipid profile in patients with T2DM. We aimed to determine the effects of supervised structured aerobic exercise training (SSAET) program on high and low density lipoprotein in patients with T2DM. This randomized control trial study was conducted at Riphah Rehabilitation Research Centre (RRRC), Pakistan Railway General Hospital (PRGH) Rawalpindi from 1st January 2015 to 30th March 2016. The inclusion criteria was Type-2 diabetes patients of both gender aged between 40 to 70 years. Patients with severe complications like coronary artery diseases (CAD), and other serious complications like diabetic foot, and severe knee and hip osteoarthritis (OA) were excluded from the study. A total of 195 patients diagnosed with T2DM were screened out and 102 were selected for the study as per the inclusion criteria. All participants were randomly assigned into two groups, experimental 'A' (n=51) and control 'B' (n=51). Patients in group A were treated with SSAET program of 25 weeks at 3 days a week in addition to routine medical management, while patients in Group-B were on their routine medications and dietary plan. Serum LDL, and HDL were tested at baseline and after 25 weeks. The data was analysed through SPSS 20. Mean and standard deviation of LDL in group A (n=51) was 118.56±19.17 (pre) and 102.64±13.33 (post), while the mean and standard deviation for Group-B (n=51) was 116.50±18.45 (Pre) and 109.88±17.13 (post). Both groups showed improvement but, Group-A treated with SSAET along with RMM showed significantly higher (P Value ≤ 0.05) improvement as compared with group B treated with RMM alone. Mean and standard deviation of HDL in Group-A was 42.70±8.06 (pre) and 47.47±7.16 (post), while the mean and standard deviation of group B is 43.37±8.15 (Pre) and 44.41±7.91 (post). Both groups showed improvement but Group-A treated with SSAET program along with RMM showed significantly higher (P Value ≤ 0.05) improvement than group B treated with RMM alone. SSAET program along with RMM is more effective strategy for the management of deranged lipid profile in patients with T2DM.


SHaploseek is a sequencing-only, high-resolution method for comprehensive preimplantation genetic testing.
Recent advances in genomic technologies expand the scope and efficiency of preimplantation genetic testing (PGT). We previously developed Haploseek, a clinically-validated, variant-agnostic comprehensive PGT solution. Haploseek is based on microarray genotyping of the embryo's parents and relatives, combined with low-pass sequencing of the embryos. Here, to increase throughput and versatility, we aimed to develop a sequencing-only implementation of Haploseek. Accordingly, we developed SHaploseek, a universal PGT method to determine genome-wide haplotypes of each embryo based on low-pass (≤ 5x) sequencing of the parents and relative(s) along with ultra-low-pass (0.2-0.4x) sequencing of the embryos. We used SHaploseek to analyze five single lymphoblast cells and 31 embryos. We validated the genome-wide haplotype predictions against either bulk DNA, Haploseek, or, at focal genomic sites, PCR-based PGT results. SHaploseek achieved > 99% concordance with bulk DNA in two families from which single cells were derived from grown-up children. In embryos from 12 PGT families, all of SHaploseek's focal site haplotype predictions were concordant with clinical PCR-based PGT results. Genome-wide, there was > 99% median concordance between Haploseek and SHaploseek's haplotype predictions. Concordance remained high at all assayed sequencing depths ≥ 2x, as well as with only 1ng of parental DNA input. In subtelomeric regions, significantly more haplotype predictions were high-confidence in SHaploseek compared to Haploseek. In summary, SHaploseek constitutes a single-platform, accurate, and cost-effective comprehensive PGT solution.


Fully integrated low-noise readout circuit with automatic offset cancellation loop for capacitive microsensors.
Capacitive sensing schemes are widely used for various microsensors; however, such microsensors suffer from severe parasitic capacitance problems. This paper presents a fully integrated low-noise readout circuit with automatic offset cancellation loop (AOCL) for capacitive microsensors. The output offsets of the capacitive sensing chain due to the parasitic capacitances and process variations are automatically removed using AOCL. The AOCL generates electrically equivalent offset capacitance and enables charge-domain fine calibration using a 10-bit R-2R digital-to-analog converter, charge-transfer switches, and a charge-storing capacitor. The AOCL cancels the unwanted offset by binary-search algorithm based on 10-bit successive approximation register (SAR) logic. The chip is implemented using 0.18 μm complementary metal-oxide-semiconductor (CMOS) process with an active area of 1.76 mm². The power consumption is 220 μW with 3.3 V supply. The input parasitic capacitances within the range of -250 fF to 250 fF can be cancelled out automatically, and the required calibration time is lower than 10 ms.


Computational and NMR Spectroscopic Evidence for Stereochemistry-Dependent Conformations of 2,2,6,6-Tetramethylpiperidinyl-Masked 1,2-Diols.
2,2,6,6-Tetramethylpiperidinyl-masked 1,2-diols exhibited stereochemistry-dependent hydroxyl proton chemical shifts: ca. 7 ppm for the syn diastereomer and ca. 2 ppm for the anti diastereomer. A computational search for low energy geometries revealed that the syn isomer favors a six-membered ring hydrogen bond to nitrogen and the anti isomer favors a five-membered ring hydrogen bond to oxygen. The computed low energy conformations were found to have a large difference in hydroxyl proton shielding that was reflected in the experimental chemical shift difference. This chemical shift difference was observed in a broad range of solvents, and thus may be useful as a stereochemical probe. The stereochemistry-dependent conformation and chemical shift signature appeared to be due to a syn pentane interaction between the gem-dimethyl groups on the 2,2,6,6-tetramethylpiperidinyl moiety.


Na+-induced structural change of a soil bacterium, S34, and Ca2+ requirement for preserving its original structure.
A drastic change in the outer membrane structure of a salt-sensitive soil bacterium, S34, related to the genus Deinococcus was induced by 0.2 to 0.4% (wt/vol) NaCl. The change was relieved by 6 mM CaCl2 and induced by 1 mM EGTA. The results indicate the strong dependence of the organism on calcium.


Aging, exercise, training, and the immune system.
Human immune function undergoes adverse changes with aging, including development of a relative immune deficiency and an immune dysregulated state. The T cells show the largest age-related differences in distribution and function. The antibody production capacity of B cells also shows an age-related decline. Acute bouts of exercise modulate many immune parameters as seen in peripheral blood. With regard to NK cell activity, a single bout of moderate exercise seems to be well tolerated by the elderly, and the resting NK cell activity of elderly subjects seems to increase with training. Cross-sectional comparisons of immune status imply that habitual physical activity may enhance NK cell activity and check certain aspects of the age-related decline in T cell function. Future studies are required to clarify whether such long-term exercise and resulting improvements of immune function give rise to any beneficial effects on infections, malignancies, and autoimmune disorders.


[Historical study of moth repellent, "Fujisawa Camphor" (6) - manufacturing and selling of "Fujisawa Camphor" during World War II.].
During World War II, the amount of camphor production did not decrease, since it was used for munitions. At that time, camphor was not use for moth repellents, are not a life supporting necessity. The factory that took charge of camphor production was busy producing medicine for military use. Due to the war, an abnormal situation in the factory arose when the procurement department requested supplementation because of reinforcement of a lack of materials. Additionally, in the home, the use of moth repellent for clothing was not a concern. Of importance where was ensuring sufficient food to survive. The supply of "Fujisawa Camphor" for home use started in the post-war days, 1947.


Malignant catatonia: role of right unilateral electroconvulsive therapy.
Malignant catatonia is defined as a life-threatening febrile neuropsychiatric disorder, characterized by psychosis with autonomic instability, hyperactivity, mutism, and stuperous exhaustion. Although historically nearly always fatal, there has been a recent decline in mortality, secondary to earlier diagnoses and appropriate treatment implementation. This includes administration of standing benzodiazepines, and without timely response to this pharmacological intervention, electroconvulsive therapy is the next appropriate treatment. We present a case of a young woman with malignant catatonia who was successfully treated with right-unilateral electroconvulsive therapy.


Comparison of gene expression in hepatocellular carcinoma, liver development, and liver regeneration.
Proliferation of liver cells can be observed in hepatocarcinogenesis, at different stages of liver development, and during liver regeneration after an injury. Does it imply that they share similar molecular mechanisms? Here, the transcriptional profiles of hepatocellular carcinoma (HCC), liver development, and liver regeneration were systematically compared as a preliminary attempt to answer this question. From the comparison, we found that advanced HCC mimics early development in terms of deprived normal liver functions and activated cellular proliferation, but advanced HCC and early development differ in expressions of cancer-related genes and their transcriptional controls. HCC and liver regeneration demonstrate different expression patterns as a whole, but regeneration is similar to dysplasia (pre-stage of HCC) in terms of their proximity to the normal state. In summary, of these three important processes, the carcinogenic progress carries the highest variance in expression; HCC pre-stage shares some resemblance with liver regeneration; and advanced HCC stage displays similarity with early development.


Overview of prostate-specific membrane antigen.
Efforts to evaluate and discover diagnostic and therapeutic markers for prostate cancer continue. One of these, prostate-specific membrane antigen (PSMA), a transmembrane protein expressed in all types of prostatic tissue, remains a useful diagnostic and possibly therapeutic target. The radio-immunoconjugate form of the anti-PSMA monoclonal antibody 7E11 is used in the commercially available and US Food and Drug Administration-approved diagnostic tool, the ProstaScint(R) (Cytogen Corporation, Princeton, NJ) scan. Recent studies have demonstrated other possible useful roles for PSMA as a target, not only in prostate cancer, but in other malignancies.


[Clinical-chemical diagnosis of poisoning].
There is a disparity between the number of reported cases of poisoning and the number of chemical analyses performed for the identification and quantitative determination of a particular poison. The aim of the workshop conference was to clarify the extent to which different clinics possess or require the necessary facilities for the investigation of poisons. The following summary of 16 lectures and accompanying discussion puts into perspective the present state of clinical toxicological analysis. Guide lines for the further development of clinical-toxicological analysis are formulated in the final discussion, where a plan is proposed for the incorporation of toxicological analysis into clinical chemistry.


Immunohistochemical localization of glutathione peroxidase in ocular tissue.
In this study enzyme glutathione peroxidase was localized in ocular tissue of Lewis rats using the peroxidase antiperoxidase immunohistochemical technique. Antisera to glutathione peroxidase was raised in a rabbit. Immunoreactive glutathione peroxidase was found to be distributed predominantly in the corneal epithelium and endothelium, choroid, inner segment of photoreceptors and retinal pigmented epithelium. Its presence in these sites suggests an adaptation to oxidative stress where this antioxidant enzyme along with other antioxidant systems serves to prevent damage.


Effects of vitamin E on chronic hepatitis C genotype 3: a randomized, double-blind, placebo-controlled study.
Hepatitis C virus (HCV) infection is associated with chronic inflammation and oxidative damage, with hepatic steatosis being common in genotype 3 cases. Vitamin E, a potent antioxidant protective against oxidative stress-induced liver damage in vitro and in vivo, has beneficial effects on alanine aminotransferase (ALT) and histological outcomes in patients with non-alcoholic steatohepatitis. To assess the effect of vitamin E on ALT status in patients with HCV genotype 3. This randomized, placebo-controlled, double-blind trial was conducted in a single tertiary-care hospital (Rajavithi Hospital, Bangkok) between 2010 and 2011. We included patients with HCV genotype 3 infection, unable to receive or tolerate, or did not respond to standard therapy. Responders were defined as patients exhibiting a decrease in serum ALT of at least 5% below the baseline value after 12 weeks of treatment. Thirty-seven eligible patients were randomly assigned either to receive vitamin E 400 IU twice daily (n = 19) or placebo (n = 18; 1 dropped outearly) for 12 weeks. In all, 11 of 19 patients in the vitamin E group (57.8%) and 5 of 17 patients in the placebo group (29.4%) were ALT responders. Among responders, serum ALT levels were greatly decreased in the vitamin E group (reducing from 122.6±80.1 IU/L to 68.4±25.3 IU/L, p = 0.016), when compared with the placebo group (reducing from 89.2±40.6 IU/L to 73.6±30.6 IU/L, p > 0.05). Vitamin E treatment was well-tolerated with no serious adverse events in the present study. Vitamin E treatment decreased serum ALT levels in patients with HCV genotype 3. Because of its good safety profile, vitamin E may be a worthwhile supportive therapy for patients with HCV particularly for those who were unable to achieve viral eradication by standard therapy.


Size-Dependent Catalytic Activity of PVA-Stabilized Palladium Nanoparticles in p-Nitrophenol Reduction: Using a Thermoresponsive Nanoreactor.
Palladium nanoparticles (Pd NPs) of various average global diameters (2.1-7.1 nm) encapsulated with hydrophilic polymer polyvinyl alcohol (PVA) have been synthesized and used as catalysts for sodium borohydride assisted reduction of p-nitrophenol to p-aminophenol. The synthesized catalysts exhibit excellent and typical size-dependent catalytic activity in the green protocol. UV-visible absorption spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were employed to characterize the prepared Pd NPs. The kinetics of this reaction was easily monitored by a UV-visible absorption spectrophotometer. The mechanism of the reaction is explained by the Langmuir-Hinshelwood model. The catalytic performance increases with decreasing size of the synthesized nanoparticles. The apparent rate constants (k app × 103/s-1) of the catalytic reduction in the presence of Pd NPs of average diameters of 2.1, 3.35, 6.2, and 7.1 nm are determined as 8.57, 7.67, 6.16, and 5.04, respectively, at 298 K by using 2.91 mol % palladium nanocatalyst in each case. Moreover, the estimated activation energy of 22.2 kJ mol-1 obtained for Pd NPs with the smallest average diameter of 2.1 nm is very low as reported in the literature for the reduction. The influences of catalyst dose and concentration of p-nitrophenol on catalytic reduction are fully investigated. The catalyst with the largest diameter shows a temperature-sensitive property that might be due to the presence of a very low amount of rapped PVA used as stabilizer during the fabrication process. Thus, the synthetic protocol provides a unique fabrication process of a catalytically active thermoresponsive nanoreactor consisting of Pd NPs encapsulated into a PVA stabilizing agent.


Car accident leading to "traumatic" macular hole formation proven by optical coherence tomography.
We present the case of a car accident where the cause-consequence of the subsequent visual loss in one eye of the victim was proven by optical coherence tomography (OCT). A 66-year-old woman was hit by a car from her right side and complained of immediate visual loss after the accident in her right eye. The patient was referred to our outpatient clinic 2.5 months after the car accident in order to elucidate the cause-consequence of the visual loss and the car accident. Following routine ophthalmologic examination OCT was performed in both eyes. Fundus biomicroscopy revealed a full thickness macular hole in the affected eye which was proven by OCT, while OCT showed an arrested stage of macular hole development in the unaffected left eye. Pars plana vitrectomy was performed resulting in closure of the hole. The arrested stage of macular hole formation seen by OCT in the fellow eye lead us to the conclusion that the accident could have been the trigger in the pathologic changes of the retina in the affected eye. The authors review the current literature related to head injury and macular hole formation.


Modified Technique of Cultured Epithelial Cells Transplantation on Facial Segmental Vitiligo.
Cultured epithelial cells transplantation is a known surgical technique for vitiligo. To evaluate the factors influencing efficacy and safety of cultured epithelial cells transplantation in 9-month follow-up. Demographic, clinical, and repigmentation outcomes were reviewed for patients with facial segmental vitiligo who had undergone cultured epithelial cells transplantation from November 2013 to July 2015 at the clinic of the Department of Dermatology, Huashan Hospital, China. Twenty-eight patients who had undergone cultured epithelial cells transplantation were included. A satisfactory result (>50% repigmentation) was achieved in 79% patients with facial segmental vitiligo in 9 months. The treatment effect was significantly different in 6th month (P = 0.032), 9th month (P = 0.006) compared with 3rd month. Disease stability did significantly affect repigmentation outcome in 9th month (Z = 2.113, P = 0.035). No significant difference was observed between single segmental type versus mixed type (Z = 1.081, P = 0.280). Adverse effects were nearly absent. Cultured epithelial cells transplantation is a relatively safe and effective therapy for facial segmental stable vitiligo patients.


Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis.
Autoimmune pancreatitis is a rare condition which can mimic pancreatic carcinoma. We report the cases of 10 patients with autoimmune pancreatitis investigated in two different centers using contrast-enhanced endosonography. In these patients, contrast-enhanced endosonography showed a unique vascularization pattern which makes it easy to discriminate between autoimmune pancreatitis and lesions caused by pancreatic cancer. Lesions caused by autoimmune pancreatitis and the surrounding pancreas typically showed hypervascularization, whereas lesions caused by pancreatic cancer were hypovascularized. This was true for all patients with the exception of one who showed a normal vascularization pattern in comparison with normal patients and no signs of hypovascularization. Final diagnosis was achieved either by transcutaneous biopsy or a combination of endoscopic fine-needle aspiration with IgG4 immunostaining of the sample. All patients were followed up over a period of at least 12 months to rule out pancreatic carcinoma.


Intracytoplasmic retention of type VII collagen and dominant dystrophic epidermolysis bullosa: reversal of defect following cessation of or marked improvement in disease activity.
It has been recently shown that the presence of perinuclear "stellate bodies" within the epidermis in patients with a form of dominant dystrophic epidermolysis bullosa named "transient bullous dermolysis of the newborn" corresponds to collections of type VII collagen. To determine the temporal relationship of this unique immunohistochemical defect with course of clinical disease activity, we have longitudinally studied the expression of two epitopes of type VII collagen (LH 7:2; L3d) in nine patients in four such kindreds by immunofluorescence and immunoelectron microscopic technique. In every infant so studied at the time of active blistering, type VII collagen was detectable primarily within basilar and, to a lesser extent, suprabasilar keratinocytes. In contrast, type VII collagen was detectable solely in linear array along the dermoepidermal junction in skin from each patient following complete cessation or at least marked diminution of visible clinical disease activity. These findings support the hypothesis that the temporary mechanical fragility and blistering of the skin in infants with this rare subset of dominant dystrophic epidermolysis bullosa reflect the presence of reduced amounts of type VII collagen along the dermoepidermal junction, and that this diminution may be the result of either a delay in transport and integration of type VII collagen from basilar keratinocytes into the skin basement membrane or excessive phagocytosis of type VII collagen.


The Protective Effect of Breastfeeding and Ingesting Human Breast Milk on Subsequent Risk of Endometriosis in Mother and Child: A Systematic Review and Meta-Analysis.
Background: Endometriosis is a chronic and debilitating disease characterized by ectopic, endometrium-like tissue outside the uterine cavity. Objective: The current meta-analysis was conducted to evaluate the effect of breastfeeding and ingesting human breast milk on the subsequent risk of endometriosis. Materials and Methods: The English and Persian databases were systematically searched in accordance with the Mesh browser keywords and free-text words until March 12, 2022. The Newcastle-Ottawa was used to evaluate the quality of the included studies. Publication bias was assessed using Begg's and Egger's tests, and funnel plot. The heterogeneity of studies was evaluated using I2 statistics. Results of the random-effects meta-analysis were presented using odds ratios (ORs) and 95% confidence intervals (CIs). Results: In total, 18 articles with 10,994 subjects were included in the meta-analysis. Overall, the pool estimates show that breastfeeding (OR = 0.79, 95% CI: 0.71-0.88, I2 = 89%) and ingesting human breast milk (OR = 0.67, 95% CI: 0.50-0.83, I2 = 84.5%) have significantly a protective effect on the risk of endometriosis. Conclusion: Our findings confirm an inverse association between endometriosis risk and ingesting human breast milk, and breastfeeding. Therefore, the importance of breastfeeding for both mother and child should be considered by policymakers and health care providers.


Changes in regional cerebral blood volume in frontal cortex during mental work with and without caffeine intake: functional monitoring using near-infrared spectroscopy.
Near-infrared spectroscopy (NIRS) was used to measure frontal regional cerebral blood volume (rCBV) in a person whose brain was under the influence of pharmacological agents while the person was performing a complex task. Fourteen healthy participants were administered Uchida-Kraepelin psychodiagnostic (UKP) tests before and after caffeine intake, and the concentration of caffeine in the urine was measured. The average number of answers and the average number of correct answers given by the participants improved significantly following caffeine intake. During the UKP testing, changes in the rCBV in the inferior frontal cortex were continuously measured using NIRS. The volume during the rest periods decreased as a result of caffeine-induced constriction of the cerebral arteriola. The volume increased during the mental work, but the degree of the increase was the same before and after caffeine intake. Although the performance of the mental work improved following caffeine intake, the improvement was not reflected in the rCBV in the inferior frontal cerebral cortex. These results suggest that caffeine helps to protect the brain from excessive hyperemia in addition to activating the neurons in the prefrontal cortex.


Words matter: implications of semantics and imagery in framing animal-welfare issues.
As criticisms of contemporary farm-animal production escalate, scholars have begun to scrutinize the imagery and linguistic techniques used to frame animal issues and their implications. Pro-animal rights groups typically present animal use as unnecessary, oppressive, and exploitive and adopt themes of compassion and protection to engage the public. In contrast, anti-animal rights groups represent animal use as necessary for human benefit and often situate animal and human interests as being incompatible. Overly simplistic, polarized representations of animal issues therefore emerge. Several analyses, however, have indicated that the discourse on farm-animal production fails to either make a compelling ethical argument for animal agriculture or address the ethical concerns raised by animal-rights activists. Proponents of animal agriculture are argued to consistently misrepresent animal production practices and portray animals as inanimate objects, reflecting lack of genuine concern for animal suffering or welfare. Thus far, the veterinary community has escaped this level of scrutiny. However, veterinarians are often viewed as being connected to animal agriculture. As veterinarians strive to assume leadership in animal welfare, it is useful for the profession to recognize that, as is the case for members of the animal sciences and industries, some aspects of its discourse may contradict its professed values and beliefs about animal care and welfare. Analysis of this discourse affords the opportunity to more effectively engage with the public on animal-welfare issues and to develop a compelling narrative of the role of animals in an increasingly urban society.


Directly observed 15N NMR spectra of uniformly enriched proteins.
The proteins cytochrome c2, cytochrome c', and ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum were enriched in 15N by growth of the organism on 15NH4Cl. The proteins were purified to homogeneity and studied by 15N NMR. Longitudinal and transverse relaxation times as well as the nuclear Overhauser effects were determined for various groups of the proteins which vary in molecular weight from 13,000 to 114,000. The values of these parameters for the amide resonances or for groups thought to be rigid were consistent with the molecular weights of the proteins. Relaxation times of the amino-terminal alpha-amino groups and the side chain nitrogen atoms of arginine and lysine were consistent with much more rapid motion. Nitrogen atoms having bound protons were generally found to be decoupled from the protons by chemical exchange. Demonstrable 1H-15N coupling was taken as an indication that exchange was hindered, either by hydrogen bonding interactions or by inaccessibility of the group to solvent. Histidine side chain nitrogen atoms, which experience a large chemical shift upon protonation/deprotonation, were often found to be broadened beyond detectability by chemical exchange and tautomerization. Strategies for improving sensitivity and for obtaining specific peak assignments are also discussed.


The role of orthographic and phonological processing during reading Chinese sentences: Evidence from eye movements.
The role of phonological and orthographic processing and their time course during lexical processing and sentence reading remain controversial. By adopting a misspelled-characters disruption paradigm and eye-tracking technique, we manipulated the writing for the first characters of two-character target words to investigate the relative role of orthographic and phonological processing on word recognition in Chinese reading. There are four conditions: (a) correct character, (b) misspelled character with a stroke missing, (c) misspelled homographic character, and (d) misspelled homophonic character. The results showed that homophonic errors caused more disruptions than other conditions in the early (first-pass reading times) and later (total reading time) stages of lexical processing during Chinese reading. Homographic errors and omitted stroke errors lead to equal disruptions at the early stage of word recognition, but homographic errors cause more disruptions at the later stage. These results suggest that orthography plays a dominant role in word recognition during Chinese reading, whereas phonology plays a weaker and more limited role. The direct access and dual-rote hypothesis may well explain the mechanism of lexical processing in Chinese reading.


Incidence of sleep disturbances in patients with familial Mediterranean fever and the relation of sleep quality with disease activity.
To evaluate the sleep quality and the relation of sleep quality with depression, anxiety, fatigue and disease activity in adult patients with familial Mediterranean fever (FMF). One hundred and seventy-four FMF patients and 84 age-sex matched healthy individuals were included in this study. The Pittsburgh Sleep Quality Index (PSQI), Multidimensional Assessment of Fatigue (MAF) and the Hospital Anxiety and Depression Index (HADS) were used to assess sleep quality, fatigue, depression and anxiety, respectively. FMF patients had significantly higher depression, anxiety, fatigue and PSQI scores than healthy controls. As the severity of the disease increased, scores of total PSQI and its domains increased. Patients with total PSQI score higher than 5 had statistically significantly higher erythrocyte sedimentation rates (ESR), serum C-reactive protein and serum amyloid levels during attacks, more attack numbers in last 3 months and worse fatigue, depression scores. Total PSQI score was positively correlated with inflammatory markers during attacks, attack numbers in the last 3 months and fatigue score. Logistic regression models identified disease duration, ESR during attacks, fatigue, attack numbers in the last 3 months as predictors of poor sleep quality. Poor sleep quality is common in adult FMF patients. Anxiety, depression and fatigue are more frequent in FMF patients than healthy individuals. Poor sleep quality is associated with inflammatory marker levels during attacks, fatigue and attack numbers in the last 3 months.


Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence.
Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13 months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95% CI, 1.11-2.31; P = .01) and had improved 5-year survival (hazard ratio, 0.66; 95% CI, 0.49-0.90; P < .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival.


Hydrophobization Engineering of the Air-Cathode Catalyst for Improved Oxygen Diffusion towards Efficient Zinc-Air Batteries.
Poor oxygen diffusion at multiphase interfaces in an air cathode suppresses the energy densities of zinc-air batteries (ZABs). Developing effective strategies to tackle the issue is of great significance for overcoming the performance bottleneck. Herein, inspired by the bionics of diving flies, a polytetrafluoroethylene layer was coated on the surfaces of Co3 O4 nanosheets (NSs) grown on carbon cloth (CC) to create a hydrophobic surface to enable the formation of more three-phase reaction interfaces and promoted oxygen diffusion, rendering the hydrophobic-Co3 O4 NSs/CC electrode a higher limiting current density (214 mA cm-2 at 0.3 V) than that (10 mA cm-2 ) of untreated-Co3 O4 NSs/CC electrode. Consequently, the assembled ZAB employing hydrophobic-Co3 O4 NSs/CC cathode acquired a higher power density (171 mW cm-2 ) than that (102 mW cm-2 ) utilizing untreated-Co3 O4 NSs/CC cathode, proving the enhanced interfacial reaction kinetics on air cathode benefiting from the hydrophobization engineering.


Complex formation of myrosinase isoenzymes in oilseed rape seeds are dependent on the presence of myrosinase-binding proteins.
The enzyme myrosinase (EC 220.127.116.11) degrades the secondary compounds glucosinolates upon wounding and serves as a defense to generalist pests in Capparales. Certain myrosinases are present in complexes together with other proteins such as myrosinase-binding proteins (MBP) in extracts of oilseed rape (Brassica napus) seeds. Immunhistochemical analysis of wild-type seeds showed that MBPs were present in most cells but not in the myrosin cells, indicating that the complex formation observed in extracts is initiated upon tissue disruption. To study the role of MBP in complex formation and defense, oilseed rape antisense plants lacking the seed MBPs were produced. Western blotting and immunohistochemical staining confirmed depletion of MBP in the transgenic seeds. The exclusive expression of myrosinase in idioblasts (myrosin cells) of the seed was not affected by the down-regulation of MBP. Using size-exclusion chromatography, we have shown that myrosinases with subunit molecular masses of 62 to 70 kD were present as free dimers from the antisense seed extract, whereas in the wild type, they formed complexes. In accordance with this, MBPs are necessary for myrosinase complex formation of the 62- to 70-kD myrosinases. The product formed from sinalbin hydrolysis by myrosinase was the same whether MBP was present or not. The performance of a common beetle generalist (Tenebrio molitor) fed with seeds, herbivory by flea beetles (Phyllotreta undulata) on cotyledons, or growth rate of the Brassica fungal pathogens Alternaria brassicae or Lepthosphaeria maculans in the presence of seed extracts were not affected by the down-regulation of MBP, leaving the physiological function of this protein family open.


Severe spontaneous pneumomediastinum, pneumothorax and subcutaneous emphysema precipitated by pepper spray-induced acute laryngitis: a case report.
We report a patient with severe spontaneous pneumomediastinum (SPM), pneumothorax and widespread subcutaneous emphysema with acute epiglottitis after inhaling pepper spray. The effects of pepper spray, which is a lachrymatory agent, on the respiratory system have not been reported. Upper airway obstruction is not a well-described cause of SPM, with which subcutaneous emphysema and pneumothorax might coexist; thus, mechanical ventilation might be detrimental.


Intrinsic dimensionality of human behavioral activity data.
Patterns of spatial behavior dictate how we use our infrastructure, encounter other people, or are exposed to services and opportunities. Understanding these patterns through the analysis of data commonly available through commodity smartphones has become an important arena for innovation in both academia and industry. The resulting datasets can quickly become massive, indicating the need for concise understanding of the scope of the data collected. Some data is obviously correlated (for example GPS location and which WiFi routers are seen). Codifying the extent of these correlations could identify potential new models, provide guidance on the amount of data to collect, and even provide actionable features. However, identifying correlations, or even the extent of correlation, is difficult because the form of the correlation must be specified. Fractal-based intrinsic dimensionality directly calculates the minimum number of dimensions required to represent a dataset. We provide an intrinsic dimensionality analysis of four smartphone datasets over seven input dimensions, and empirically demonstrate an intrinsic dimension of approximately two.