Complete hemispherotomy leads to lateralized functional organization and lower level of consciousness in the isolated hemisphere.
To quantify whole-brain functional organization after complete hemispherotomy, characterizing unexplored plasticity pathways and the conscious level of the dissected hemispheres. Evaluation with multimodal magnetic resonance imaging in two pediatric patients undergoing right hemispherotomy including complete callosotomy with a perithalamic section. Regional cerebral blood flow and fMRI network connectivity assessed the functional integrity of both hemispheres after surgery. The level of consciousness was tested by means of a support vector machine classifier which compared the intrinsic organization of the dissected hemispheres with those of patients suffering from disorders of consciousness. After hemispherotomy, both patients showed typical daily functionality. We found no interhemispheric transfer of functional connectivity in either patient as predicted by the operation. The healthy left hemispheres displayed focal blood hyperperfusion in motor and limbic areas, with preserved network-level organization. Unexpectedly, the disconnected right hemispheres showed sustained network organization despite low regional cerebral blood flow. Subcortically, functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. One patient further showed unusual ipsilateral right cerebello-cortical connectivity, which was explained by the mediation of the vascular system. The healthy left hemisphere had higher probability to be classified as in a minimally conscious state compared to the isolated right hemisphere. Complete hemispherotomy leads to a lateralized whole-brain organization, with the remaining hemisphere claiming most of the brain's energetic reserves supported by subcortical structures. Our results further underline the contribution of nonneuronal vascular signals on contralateral connectivity, shedding light on the nature of network organization in the isolated tissue. The disconnected hemisphere is characterized by a level of consciousness which is necessary but insufficient for conscious processing, paving the way for more specific inquiries about its role in awareness in the absence of behavioral output.


Sites of aromatization of [3H]testosterone in forebrain of male, female and androgen receptor-deficient Tfm mice: an autoradiographic study.
The distribution of radioactivity after injection of [3H]testosterone was studied in the forebrain of adult mice by thaw-mount autoradiography. Nuclear labeling was high in neurons in the dorsal part of the medial nucleus of the amygdala and in the dorsocaudal part of the bed nucleus of the stria terminalis. Low nuclear uptake occurred in the medial preoptic nucleus, in mediobasal hypothalamic nuclei and in the ventromedial amygdala. Nuclear concentration of radioactivity was not influenced by competition with dihydrotestosterone and was present in androgen receptor deficient Tfm mice. It was totally abolished by competition with estradiol. This indicates that in the brain [3H]testosterone is converted to estrogenic metabolites which bind to estrogen receptors. Nuclear labeling after [3H]testosterone was restricted to a few of the brain nuclei, known to contain estrogen receptors indicating that aromatization occurs only in select regions. The results suggest that testosterone acts on the brain via estrogen receptors.


Roots and stems of Kadsura coccinea extract induced developmental toxicity in zebrafish embryos/larvae through apoptosis and oxidative stress.
Although the roots and stems of Kadsura coccinea (Lem.) A. C. Smith. [Schisandraceae] are herbs and traditional foods in Li nationality, its toxicity remains unclear. To study developmental toxicity of K. coccinea consumption and explain underlying mechanisms. Zebrafish were applied to assess LC50 values of hydroethanol extract (KCH) and water extract (KCW) of Kadsura coccinea. In further study, three concentrations groups of KCH (3.75, 7.5 and 15 μg/mL for embryo, 7.5, 15 and 30 μg/mL for larvae) and control group (n = 30) were administered. At specific stages of zebrafish development, spontaneous movement, hatching rate, etc., were measured. Gene expressions related to developmental toxicity were examined. The LC50 value of KCH (24 or 45 μg/mL) was lower than KCW (1447 or 2011 μg/mL) in embryos or larvae. The inhibited spontaneous movement (20%), hatching rate (20%), body length (12%) and eye area (30%) were observed after KCH treatment. Moreover, the decreased liver areas (25%) and fluorescence intensity (33%), increased ALT (37%) and AST levels (42%) were found in larvae treated with KCH (30 μg/mL). The increased ROS (89%), MDA concentrations (30%), apoptosis generation (62%) and decreased T-SOD activity (16%) were also observed. The represented genes of developmental hepatotoxicity, oxidative stress and apoptosis in zebrafish were activated after KCH (15 or 30 μg/mL) treatment. These results demonstrate that KCH has developmental toxicity on zebrafish. Our study provides a scientific basis for further research on the toxicity of Kadsura coccinea.


An improved method for rapid identification of hook effect samples in HBsAg quantitative assay.
Quantitative hepatitis B surface antigen assay is widely used for diagnosis of hepatitis B virus infection; however, specimens with high levels of the antigen can cause false-negative results (Hook effect), which needs to be resolved. The hook effect samples and non-hook effect samples were detected on the LiCA® 500 instrument using three methods, viz., 1, 2, and 3. Method 1, the currently used procedure, was performed in two steps with a total reaction time of 25 min in a final volume of 250 µL: first incubation was with two reagents for 15 min and then with one other reagent for 10 min. In Method 2, all three reagents were added in one step with a final volume of 250 µL, and the total reaction time was still 25 min. In Method 3, the improved method, all three reagents were added in one step while the final volume was only 130 µL and the total reaction time was only 1 min. Signal values of the non-hook effect samples obtained using Method 2 were significantly lower than those with Method 1, showing competitive inhibition. The hook effect samples tested with Method 2 approximated those obtained using Method 1. Method 3 took 1 min and differentiated hook effect samples successfully, similar to the results with Method 2 which took 25 min. Changing the timing of one reagent addition and incubation time in Method 3 provided a rapid and effective method for the identification of hook effect. The results were more clearly distinguishable due to the phenomenon of competitive inhibition. Method 3 can be considered an improvement on the chemiluminescence platform.


Communication and sensorimotor functioning in children with autism.
This study examined the relationship between sensorimotor functioning and communicative intent in children with autism. Ten children with autism, four verbal and six nonverbal, served as subjects. Sensorimotor functioning was assessed on object permanence, means-end, causality, vocal and gestural imitation, the construction of objects in space and schemes for relating objects. A 2-hr communication sample was also obtained and analyzed for the number and diversity of pragmatic functions expressed. Object permanence was not significantly related to either the diversity or total number of pragmatic functions. Means-end was significantly related to both of these measures, while vocal imitation was significantly related to the total number of pragmatic functions expressed. In addition, means-end was significantly correlated with performance on the vocal and gestural imitation scales.


The Human Immunodeficiency Virus (HIV) Index: Using a Patient-Reported Outcome on Engagement in HIV Care to Explain Suboptimal Retention in Care and Virologic Control.
We investigated the prospective association between a brief self-report measure of engagement in human immunodeficiency virus (HIV) care (the Index of Engagement in HIV Care; hereafter "Index") and suboptimal retention and viral suppression outcomes. The Centers for AIDS Research Network of Integrated Clinical Systems cohort study combines medical record data with patient-reported outcomes from 8 HIV clinics in the United States, which from April 2016 to March 2017 included the 10-item Index. Multivariable logistic regression was used to estimate the risk and odds ratios of mean Index scores on 2 outcomes in the subsequent year: (1) not keeping ≥75% of scheduled HIV care appointments; and (2) for those with viral suppression at Index assessment, having viral load >200 copies/mL on ≥1 measurement. We also used generalized linear mixed models (GLMMs) to estimate the risk and odds ratios of appointment nonattendance or unsuppressed viral load at any given observation. We generated receiver operating characteristic curves for the full models overlaid with the Index as a sole predictor. The mean Index score was 4.5 (standard deviation, 0.6). Higher Index scores were associated with lower relative risk of suboptimal retention (n = 2576; logistic regression adjusted risk ratio [aRR], 0.88 [95% confidence interval, .87-.88]; GLMM aRR, 0.85 [.83-.87]) and lack of sustained viral suppression (n = 2499; logistic regression aRR, 0.75 [.68-.83]; GLMM aRR, 0.74 [.68-.80]). The areas under the receiver operating characteristic curve for the full models were 0.69 (95% confidence interval, .67-.71) for suboptimal retention and 0.76 (.72-.79) for lack of sustained viral suppression. Index scores are significantly associated with suboptimal retention and viral suppression outcomes.


Early Quantification of Salivary Gland Function after Radioiodine Therapy.
Radioiodine (I-131) is used as an effective noninvasive treatment for thyroid malignancies. Salivary gland is one of the most affected nontarget organs. The present study aims to perform early quantification of salivary gland function after I-131 therapy (RIT) for thyroid cancer considering I-131 down-scatter in the Tc-99m window. A total of 20 patients (6 males and 14 females) with differentiated thyroid carcinoma were enrolled in the study. Baseline dynamic salivary scintigraphy was performed in all patients using 185-370 MBq (5-10 mCi) Tc-99m pertechnetate. Posttherapy, salivary scintigraphy was performed 10-25 days after RIT in the range of 1.85-7.4 GBq (50-200 mCi). Time-activity curves obtained from the pre- and posttherapy dynamic salivary scintigraphy were used for semi-quantitative analysis. Uptake ratio (UR), ejection fraction (EF%), and maximum accumulation (MA%) were calculated by drawing regions of interest of individual parotid and submandibular glands over a composite image, after correcting for down-scatter from I-131 in the Tc-99m window. A paired t-test was used for comparison of the parameters obtained. Significant changes were observed in UR and EF% of both parotid and submandibular glands (P < 0.05). No significant changes were found in the value of MA% of left parotid gland and both submandibular glands in the posttherapy scans in comparison to pretherapy scans (P > 0.05). However, significant difference was observed in the MA% of the right parotid gland (P = 0.025). Salivary gland function was found to deteriorate after RIT, with the parotid glands affected more than the submandibular glands.


Trueness of Intaglio Surface of Milled Digital Dentures Designed from Intraoral Scans.
To asses trueness of the intaglio surface of milled dentures fabricated according to a fully digital protocol starting from intraoral scans in a clinical study by means of 3-dimensional (3D) digital analysis. Ten maxillary and 10 mandibular dentures, designed from intraoral scans and milled in-house, were studied. Intraoral scans were compared with the scans of intaglio surface of milled dentures. To this end, they were aligned, trimmed and used in a metrology software to measure their mean 3D distance, absolute mean deviation, and other parameters. Measured differences for all parameters were statistically investigated. Subgroup analysis for the maxillary and mandibular dentures was performed using independent samples t-test or, in case of non-normal distribution, by means of Mann-Whitney test. Using a mean of 24.9 ±2.8 measurement points/mm2 , a mean 3D distance of 0.0006 ±0.007 mm between intraoral scans and the scans of the intaglio surface of milled dentures was measured. The corresponding absolute mean deviation was 0.055 ±0.032 for maxillary dentures and 0.061 ±0.016 for mandibular dentures; such a difference between arches was statistically significant (p = 0.035). Milled dentures fabricated using a fully digital protocol and intraoral scans have accurate intaglio surfaces. It is reasonable to assume that they may achieve an adequate fit.


Afferent fibers in the hypoglossal nerve: a horseradish peroxidase study in the cat.
The existence of afferent fibers in the cat hypoglossal nerve was studied by transganglionic transport of horseradish peroxidase (HRP). Injections of wheat germ agglutinin-conjugated HRP (WGA-HRP) into the hypoglossal nerve resulted in some retrograde labeling of cell bodies within the superior ganglia of the ipsilateral glossopharyngeal and vagal nerves. A few labeled cell bodies were also present ipsilaterally within the inferior ganglion of the vagal nerve and the spinal ganglion of the C1 segment. Some of the labeled glossopharyngeal and vagal fibers reached the nucleus of the solitary tract by crossing the dorsal portion of the spinal trigeminal tract. Others distributed to the spinal trigeminal nucleus pars interpolaris and to the ventrolateral part of the medial cuneate nucleus by descending through the dorsal portion of the spinal trigeminal tract. In the spinal cord these descending fibers, intermingling with labeled dorsal root fibers, distributed to laminae I, IV-V and VII-VIII of the C1 and C2 segments. Additional HRP experiments revealed that the fibers in laminae VII-VIII originate mainly from dorsal root of the C1 segment.


Practical approaches for implementing forward genetic strategies in zebrafish.
The tropical fresh water minnow, Danio rerio, more commonly known as zebrafish, has emerged rapidly over the last decade as a powerful tool for developmental geneticists. External fertilization, high fecundity, a short generation time, and optical transparency of embryos during early development combined with the amenability to a variety of genetic manipulations constitute in the zebrafish the convergence of several unique advantages for a vertebrate model system. Traditional forward genetic screens, which employ the use of a chemical mutagen such as N-ethyl-N-nitrosourea to induce mutations in the male genome, have also proven to be highly successful in the zebrafish. This chapter provides experimental approaches to successfully induce pre-meiotic mutations in the male zebrafish germline and genetic strategies to recover and maintain such mutations in subsequent generations (Section 3.1). Though discussed specifically in the context of zebrafish research in this chapter, many of these genetic approaches may also be broadly applicable in other model systems. We also discuss experimental techniques to manipulate the ploidy of zebrafish embryos, which when used in combination with the standard mutagenesis protocol significantly expedite the identification of the induced mutations (Section 3.2). Additional stand-alone procedures are provided in Section 3.3, which are also required for the execution of the experiments discussed in its preceding sections.


A novel method for the production of in vivo-assembled, recombinant Escherichia coli RNA polymerase lacking the α C-terminal domain.
The biochemical characterization of the bacterial transcription cycle has been greatly facilitated by the production and characterization of targeted RNA polymerase (RNAP) mutants. Traditionally, RNAP preparations containing mutant subunits have been produced by reconstitution of denatured RNAP subunits, a process that is undesirable for biophysical and structural studies. Although schemes that afford the production of in vivo-assembled, recombinant RNAP containing amino acid substitutions, insertions, or deletions in either the monomeric β or β' subunits have been developed, there is no such system for the production of in vivo-assembled, recombinant RNAP with mutations in the homodimeric α-subunits. Here, we demonstrate a strategy to generate in vivo-assembled, recombinant RNAP preparations free of the α C-terminal domain. Furthermore, we describe a modification of this approach that would permit the purification of in vivo-assembled, recombinant RNAP containing any α-subunit variant, including those variants that are lethal. Finally, we propose that these related approaches can be extended to generate in vivo-assembled, recombinant variants of other protein complexes containing homomultimers for biochemical, biophysical, and structural analyses.


Transcriptome-wide characterization and functional analysis of Xyloglucan endo-transglycosylase/hydrolase (XTH) gene family of Salicornia europaea L. under salinity and drought stress.
Salicornia europaea is a halophyte that has a very pronounced salt tolerance. As a cell wall manipulating enzyme, xyloglucan endotransglycosylase/hydrolase (XTH) plays an important role in plant resistance to abiotic stress. However, no systematic study of the XTH gene family in S. europaea is well known. PacBio Iso-Seq transcriptome sequence data were used for bioinformatics and gene expression analysis using real-time quantitative polymerase chain reaction (RT-qPCR). Transcriptome sequencing (PacBio Iso-Seq system) generated 16,465,671 sub-reads and after quality control of Iso-Seq, 29,520 isoforms were obtained with an average length of 2112 bp. A total of 24,869 unigenes, with 98% of which were obtained using coding sequences (CDSs), and 6398 possible transcription factors (TFs) were identified. Thirty-five (35) non-redundant potential SeXTH proteins were identified in S. europaea and categorized into group I/II and group III based on their genetic relatedness. Prediction of the conserved motif revealed that the DE(I/L/F/V)DF(I)EFLG domain was conserved in the S. europaea proteins and a potential N-linked glycosylation domain N(T)V(R/L/T/I)T(S/K/R/F/P)G was also located near the catalytic residues. All SeXTH genes exhibited discrete expression patterns in different tissues, at different times, and under different stresses. For example, 27 and 15 SeXTH genes were positively expressed under salt stress in shoots and roots at 200 mM NaCl in 24 h, and 34 SeXTH genes were also positively regulated under 48 h of drought stress in shoots and roots. This indicates their function in adaptation to salt and drought stress. The present study discovered SeXTH gene family traits that are potential stress resistance regulators in S. europaea, and this provides a basis for future functional diversity research.


Early and late brain resonance findings of two siblings with Hunter syndrome.
Mucopolysaccharidosis type II (MPS II) is a lysosomal disease caused by deficiency of the enzyme iduronate-2-sulfatase (IDS), linked to the X chromosome, producing a wide spectrum of clinical manifestations. We present the case of two siblings with MPS II of different paternal origin with the same genetic mutation; the age at the time of diagnosis was 5 years of age (case 1) and 8 months of age (case 2). These brethren present different findings in brain magnetic resonance imaging (MRI) with each other, case 1 presented classic findings for age, case 2 presented multiple early findings, such as dilated perivascular spaces up to 9.5 mm, magna megacisterna, among others; without neurological manifestations. This patient's brain compromise was presented before the year of age and prior to hepatosplenomegaly, thus, MRI becomes an early diagnostic tool for MPS II.


Ernest Everett Just (1883-1941)--an early ecological developmental biologist.
Ecological developmental biology (Eco-Devo) involves the study of development in its natural environmental context as opposed to the laboratory setting. Ernest E. Just was an early 20th century African-American embryologist who devoted his career to studying the early development of marine invertebrates in the United States and abroad. Through detailed study of the fertilization process, he came to see the cell cortex as playing a central role in development, inheritance, and evolution. This paper, after presenting some of Just's scientific and philosophical contributions, argues that Just was an Eco-Devo biologist. Three lines of evidence are given. First, Just believed that intimate knowledge of the natural history of the marine animal under study--hence, the natural setting in which fertilization occurs--was essential. Second, he stressed the importance of the egg's "normality"--how well its condition in the laboratory corresponds to the natural, fertilizable state. Finally, Just was an organicist, believing that organisms are holistic systems with emergent properties that arise from their organization and complexity. Although other scientists may stand out more clearly as founding architects of Eco-Devo, E. E. Just, with his unwavering insistence on the normality and holistic integrity of the egg cell, was one of its purest adherents.


Synchronous presentation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Report of an exceptional case with review of the literature.
The occurrence of distinct synchronous hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CC) is extremely rare. Less than 50 cases have been reported in the literature. The aim of our study was to describe the clinicopathological features of this association. A 75-year-old female patient with chronic hepatitis C cirrhosis presented with three hepatic nodules affecting segments IV, VIII and V during follow-up of her disease. Only the V-segment nodule was radiologically suspicious of malignancy (classified as LI-RADS5). These nodules were resected after discussion of the case in a multidisciplinary meeting. Histological examination showed that the nodules in segments VIII and V corresponded respectively to an HCC with immunohistochemistry showing HepPar1 (+), CK7(-) and CK19(-), and to an intrahepatic CC with immunohistochemistry showing HepPar1 (-), CK7(+) and CK19(+). The excision was radical. The post-operative course was uncomplicated. After a 6-month follow-up, the patient did not develop any locoregional recurrence or metastases. Synchronous association of HCC and CC is very uncommon, and diagnosis is based on pathological and immunohistochemical examination. Infection with the HCV represents a major risk factor for simultaneous association. Synchronous presentation in HCV-infected individuals has been associated with a poorer prognosis compared with cases where only a single type of liver cancer is present. The prognosis of this association is generally poor, notably due to the aggressive behavior of CC. Surgical resection remains the first-line treatment option, when possible, but comprehensive management of these complex cases requires a multidisciplinary approach tailored to each patient's specific circumstances.


Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia.
We examined whether early response/non-response to risperidone according to the Clinical Global Impressions-improvement scale (CGI-I) at 2 weeks could predict subsequent response. This prediction was also applied to olanzapine. We then investigated whether early non-responders (ENRs) to risperidone or olanzapine who switched to the other showed significantly greater improvement, compared with those staying on the initial antipsychotic. We performed a rater-blinded, randomized controlled trial in 18 psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as CGI-I ≤ 3 following 2 weeks of treatment. The primary outcome measure was achievement of remission and ≥ 50% improvement in the Positive and Negative Syndrome Scale at 4 weeks. At 4 weeks, 53% of risperidone early responders (ERs) went into remission, whereas only 9% of ENRs staying on risperidone (n=11) did (P=0.016). Similarly, at 4 weeks, 81% of risperidone ERs achieved ≥ 50% response, whereas only 9% of ENRs staying on risperidone achieved ≥ 50% response (P < 0.0001). In contrast, 58% of olanzapine ERs (n=33) went into remission, whereas 38% of ENRs staying on olanzapine (n=8) did at 4 weeks (P=0.44). Similarly, 61% of olanzapine ERs achieved ≥ 50% response, whereas 25% of ENRs staying on olanzapine achieved ≥ 50% response (P=0.12). The negative likelihood ratio for the prediction of ≥ 50% response at 4 weeks by early response status to risperidone at 2 weeks was 0.057. In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.


New detection and separation method for amino acids by high-performance liquid chromatography.
A simple system for simultaneous fluorescence detection of primary and secondary amines has been developed. The optimum conditions for fluorescing secondary amines in the two-stage reaction technique using sodium hypochlorite and o-phthalaldehyde have been studied, and then the switching flow method (sodium hypochlorite is added only to secondary amines) and the non-switching flow method (sodium hypochlorite is added to all the amino acids) have been compared. It was concluded that the non-switching flow method ensures high efficiency and reliability. This newly-developed system was applied to the detection of amino acids and gave satisfactory results.


Identification of differentially expressed genes in papillary thyroid cancers.
Techniques designed to identify differentially expressed genes (DEGs) in tumors have become important in modern pathology. Genefishing technique using the annealing control primer (ACP) system has recently been developed to screen for DEG transcripts. We tried to identify DEGs involved in papillary thyroid cancer (PTC) by using Genefishing technique. We utilized a new differential display method, designated with Genefishing technique, to analyze DEGs in 21 cases of PTCs. Comparing the gene expression profiles between PTC and normal thyroid, we detected 17 genes that were differentially expressed in PTCs and performed cloning with sequencing in 10 genes. We confirmed the expression patterns of 2 DEGs by RT-PCR assay and identified the same results in 17 out of 21 (81%) PTCs. The 2 DEGs over-expressed in PTCs were identified as DC-STAMP and type I collagen A1. They are novel genes identified first in PTCs. We confirmed 2 DEGs in PTCs as DC-STAMP and type I collagen A1 by using Genefishing technique. Although the detailed functions of those 2 genes and their products remain to be determined, the genes will provide insights into mechanisms of carcinogenesis or tumor progression in PTCs.


nab-Paclitaxel for the treatment of advanced squamous non-small-cell lung cancer: a comprehensive update.
Despite advances in the treatment of patients with nonsquamous non-small-cell lung cancer (NSCLC), lung cancer remains a leading cause of death globally. Studies have demonstrated that survival varies according to histological subtype, and, in many cases, patients with squamous NSCLC have a poorer survival rate than those with nonsquamous NSCLC. For patients with squamous NSCLC, platinum-based doublets remain the standard first-line therapy option. This is in part because of the efficacy and safety concerns with some of the approved therapies and is secondary to the observation that many of the mutations targetable with currently approved therapies are rare in patients with squamous NSCLC. Recently, a subset analysis of a completed phase III trial demonstrated that use of nab-paclitaxel with carboplatin led to improved responses in patients with squamous NSCLC compared with solvent-based paclitaxel with carboplatin. In this review, the current experience and evolving role of nab-paclitaxel with carboplatin in the treatment of squamous NSCLC is discussed.


Myocardial digoxin uptake: dissociation between digitalis-induced inotropism and myocardial loss of potassium.
The time course of myocardial uptake of digoxin, of increase in inotropic effect and of changes in myocardial potassium content were studied following a single intravenous dose of digoxin. Nineteen dogs with intact circulation were investigated by the use of a biopsy technique which allowed samplings before and 10, 30, 60, and 90 min after administration of digoxin. The myocardial concentration of digoxin was 196 X 10(-9) mol/kg 10 min after administration of digoxin. Uptake continued at a slower rate, maximum concentration being 293 X 10(-9) mol/kg at 60 minutes. The inotropic effect increased parallel with the uptake of digoxin; 10 min after digoxin, contractility was 127% of the control value and this increased to 139% at 90 minutes. Myocardial potassium content was slightly increased 10 min after digoxin, suggesting an initial stimulation of membrane Na+-K+ ATPase. A subsequent significant fall in the myocardial potassium content probably reflects ATPase inhibition. The temporal dissociation between the early onset of the positive inotropic effect and the delayed inhibition of membrane Na+-K+ ATPase indicates that inotropism of digitalis glycosides is not mediated by the same binding site as that responsible for inhibition of Na+-K+ ATPase.


Daily variations in the occurrence of symptomatic supraventricular tachycardia as determined by ambulatory event monitoring.
The diurnal incidence of supraventricular tachycardia (SVT), including atrial fibrillation and atrial flutter, has been quantified by examining 7,891 cases of symptomatic arrhythmia in 5,869 patients assigned to ambulatory monitoring using electrocardiographic event recorders with transtelephonic reporting. The probability of occurrence of SVT was found to be high and moderately variable throughout the normally active hours of the day between 8 A.M. and 8 P.M. and to be uniformly low during the inactive hours between 1 and 5 A.M. Age-related peaks within the active phase were independently associated with the older half of the study population (9 A.M.) and with the younger half (6 P.M.). The daily incidence of SVT is primarily characterized by 2 states of activity, active and quiescent. Quiescence of SVT is associated with normal sleep and inactivity.


Lipoprotein-X: a substrate for lecithin: cholesterol acyltransferase.
The action of lecithin:cholesterol acyltransferase (LCAT) was studied on an abnormal lipoprotein (LP-X) rich in phosphatidylcholine and cholesterol from the plasma of patients with obstructive liver disease. 60 mg LP-X isolated free of other lipoproteins and subsequently labelled with 3H-cholesterol were incubated with 1 mg highly purified enzyme in the presence of albumin. After 45 h at 37 degrees C, the incubation mixture was subjected to zonal ultracentrifugation. 3H-cholesterol and 3H-cholesteryl esters were quantified in each fraction of the zonal gradient. More than 95% of the lipoproteins in this mixture banded in the density range of LP-X with no change in size distribution, but did contain 593 nmoles of newly formed cholesteryl esters. Agarose electrophoresis revealed an alpha-migrating band in addition to the original beta-band. Also on agar, the typically cathode migrating LP-X was changed to anode moving material. These studies indicate that LP-X can serve as a substrate for LCAT.


The Epidemiology of FVIII Inhibitors in Indian Haemophilia A Patients.
A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.


Demographic and Clinicopathologic Factors of Patients With Hepatocellular Carcinoma in a Safety Net Hospital.
Safety net hospitals have historically cared for a disproportionate number of patients of low socioeconomic status, racial and ethnic minorities, and patients with cancer. These innate challenges make safety net hospitals important in understanding how to improve access to cancer care in order to fit the needs of vulnerable patients and ultimately improve their outcomes. The purpose of this study is to characterize the current state and treatment of hepatocellular carcinoma (HCC) at Ben Taub Hospital, a safety net hospital in Houston, Texas. A retrospective chart review was performed to review the demographic characteristics, clinicopathologic data, treatment strategies, and outcomes of HCC patients at Ben Taub Hospital between January 2012 and December 2014. Two-hundred twenty-six men and 78 women with a mean age of 58 y underwent evaluation. Most (87%) were either uninsured or covered by Medicaid. The majority (69%) of patients presented with advanced (stage 2 or more) disease, with 58% of patients presenting with multiple lesions. Of the 40% that presented with a solitary lesion, the average size was 4.97 cm. Transarterial chemoembolization was used in 37% of patients and sorafenib was given to 26% of patients. Five patients underwent successful transplant. One hundred seventeen (38%) patients died of their disease, 25 patients are alive with no evidence of disease, and 159 patients have been lost to follow-up. Most patients with HCC presented to this safety net hospital with advanced disease; however, multiple local and systemic treatments were offered. Screening programs to detect HCC at an earlier stage are essential for successful long-term outcomes in a resource-strapped hospital with limited access to liver transplantation.


Three Airway Management Techniques for Airway Decontamination in Massive Emesis: A Manikin Study.
Emesis occurs during airway management and results in pulmonary aspiration at rates of 0.01% - 0.11% in fasted patients undergoing general anesthesia and 0% - 22% in non-fasted emergency department patients. Suction-assisted laryngoscopy and airway decontamination (SALAD) involves maneuvering a suction catheter into the hypopharynx, while performing laryngoscopy and endotracheal intubation. Intentional esophageal intubation (IEI) involves blindly intubating the esophagus to control emesis before endotracheal intubation. Both are previously described techniques for endotracheal intubation in the setting of massive emesis. This study compares the SALAD and IEI techniques with the traditional approach of ad hoc, rigid suction catheter airway decontamination and endotracheal intubation in the setting of massive simulated emesis. Senior anesthesiology and emergency medicine (EM) residents were randomized into three trial arms: the traditional, IEI, or SALAD. Each resident watched an instructional video on the assigned technique, performed the technique on a manikin, and completed the trial simulation with the SALAD simulation manikin. The primary trial outcome was aspirate volume collected in the manikin's lower airway. Secondary outcomes included successful intubation, intubation attempts, and time to successful intubation. We also collected pre- and post-simulation demographics and confidence questionnaire data. Thirty-one residents (21 anesthesiology and 10 EM residents) were randomized. Baseline group characteristics were similar. The mean aspirate volumes collected in the lower airway (standard deviation [SD]) in the traditional, IEI, and SALAD arms were 72 (45) milliliters per liter (mL), 100 (45) mL, and 83 (42) mL, respectively (p = 0.392). Intubation success was 100% in all groups. Times (SD) to successful intubation in the traditional, IEI, and SALAD groups were 1.69 (1.31) minutes, 1.74 (1.09) minutes, and 1.74 (0.93) minutes, respectively (p = 0.805). Overall, residents reported increased confidence (1.0 [0.0-1.0]; P = 0.002) and skill (1.0 [0.0-1.0]; P < 0.001) in airway management after completion of the study. The intubation techniques provided similar performance results in our study, suggesting any one of the three can be employed in the setting of massive emesis; although this conclusion deserves further study. Residents reported increased confidence and skill in airway management following the experience, suggesting use of the manikin provides a learning impact.


Multilayer and MATR3-dependent regulation of mRNAs maintains pluripotency in human induced pluripotent stem cells.
Matrin3 (MATR3) is a nuclear RNA/DNA-binding protein that plays pleiotropic roles in gene expression regulation by directly stabilizing target RNAs and supporting the activity of transcription factors by modulating chromatin architecture. MATR3 is involved in the differentiation of neural cells, and, here, we elucidate its critical functions in regulating pluripotent circuits in human induced pluripotent stem cells (hiPSCs). MATR3 downregulation affects hiPSCs' differentiation potential by altering key pluripotency regulators' expression levels, including OCT4, NANOG, and LIN28A by pleiotropic mechanisms. MATR3 binds to the OCT4 and YTHDF1 promoters favoring their expression. YTHDF1, in turn, binds the m6A-modified OCT4 mRNA. Furthermore, MATR3 is recruited on ribosomes and controls pluripotency regulating the translation of specific transcripts, including NANOG and LIN28A, by direct binding and favoring their stabilization. These results show that MATR3 orchestrates the pluripotency circuitry by regulating the transcription, translational efficiency, and epitranscriptome of specific transcripts.


Fasting enhances extinction retention and prevents the return of fear in humans.
Fear is prone to return following extinction that is the basis of exposure therapy for fear-related disorders. Manipulations that enhance the extinction process can be beneficial for treatment. Animal studies have shown that fasting or caloric restriction can enhance extinction and inhibit the return of fear. The present study examined the effects of fasting on fear acquisition, extinction, and the return of fear in humans. One hundred and twenty-five male participants were randomized into a fasting group and food group and exposed to a Pavlovian fear conditioning paradigm. Changes in plasma cortisol and ghrelin levels were examined using enzyme-linked immunosorbent assays. One-night fasting had no effect on fear acquisition but enhanced fear extinction retention and prevented the return of fear, and this effect persisted for at least 6 months. This procedure was also effective for remote fear memory. Plasma ghrelin levels were elevated after fasting and had a negative relationship with the fear response in spontaneous recovery test. However, overnight fasting did not affect cortisol levels. These findings indicate that fasting enhances extinction retention and prevents the return of fear, without influencing fear memory formation. We propose that this novel procedure may open new avenues for promoting extinction-based therapies for fear-related disorders.


Experimental evaluation of the sustainability of dwarf bamboo (Pseudosasa usawai) sprout-harvesting practices in Yangminshan National Park, Taiwan.
Sustainable harvest of natural products that meets the needs of local people has been viewed by many as an important means for sustaining conservation projects. Although plants often respond to tissue damage through compensatory growth, it may not secure long-term sustainability of the populations because many plants enhance individual well-being at the expense of propagation. Sustainability may further be threatened by infrequent, large-scale events, especially ill-documented ones. We studied the impacts of sprout harvesting on sprout growth in a dwarf bamboo (Pseudosasa usawai) population that has seemingly recovered from an infrequent, large-scale masting event. Experimental results suggest that although a single sprout harvest did not significantly alter the subsequent abundance and structure of sprouts, culm damage that accompanied sprout harvesting resulted in shorter, thinner, and fewer sprouts. Weaker recovery was found in windward, continually harvested, and more severely damaged sites. These findings suggest that sprout growth of damaged dwarf bamboos is likely non-compensatory, but is instead supported through physiological integration whose strength is determined by the well-being of the supplying ramets. Healthy culms closer to the damage also provided more resources than those farther away. Sustainable harvesting of sprouts could benefit from organized community efforts to limit the magnitude of culm damage, provide adequate spacing between harvested sites, and ensure sufficient time interval between harvests. Vegetation boundaries relatively resilient to infrequent, large-scale events are likely maintained by climatic factors and may be sensitive to climate change. Continual monitoring is, therefore, integral to the sustainability of harvesting projects.


Measurement of precipitin reactions in the millimicrogram protein-nitrogen range.
Exploitation of newer instrumentation and a dye-binding method for protein measurement made possible reduction in volume down to 1/1000 that commonly used, with no greater error. The procedure was tested at two levels, 1- and 10-microl volumes, with human gamma globulin and rabbit antiserum. Of the dyes tested, bromsulfalein proved best for the protein estimation.


PfMDR1 Transport Rates Assessed in Intact Isolated Plasmodium falciparum Digestive Vacuoles Reflect Functional Drug Resistance Relationship with pfmdr1 Mutations.
Drug resistance often emerges from mutations in solute transporters. Single amino acid exchanges may alter functionality of transporters with 'de novo' ability to transport drugs away from their site of action. The PfMDR1 transporter (or P-glycoprotein 1) is located in the membrane of the digestive vacuole (DV), functions as an ATP-dependent pump, and transports substrates into the DV. In this study, four strains of Plasmodium falciparum, carrying various pfmdr1 gene mutations, were analysed for their transport characteristics of Fluo-4 in isolated DVs of parasites. To obtain quantitative estimates for PfMDR1 DV surface expression, PfMDR1 protein amounts on each strain's DV membrane were evaluated by quantitative ELISA. Fluo-4, acting as a substrate for PfMDR1, was applied in DV uptake assays ('reverse Ca2+ imaging'). Viable DVs were isolated from trophozoite stages with preserved PfMDR1 activity. This newly developed assay enabled us to measure the number of Fluo-4 molecules actively transported into isolated DVs per PfMDR1 molecule. The drug-resistant strain Dd2 presented the highest transport rates, followed by K1 and the drug-sensitive strain 3D7, compatible with their copy numbers. With this assay, an evaluation of the probability of resistance formation for newly developed drugs can be implemented in early stages of drug development.


Genome-wide association: a promising start to a long race.
A recent study by Cheung et al. demonstrates how to identify expression quantitative trait loci (eQTLs) underlying gene expression phenotypes through a combination of genome-wide linkage analysis and subsequent fine mapping or by genome-wide association (GWA) analysis. This study emphasizes the complexity of human traits, highlighting the challenges faced by investigators--in particular, insufficient linkage disequilibrium between the trait and marker variant, genetic heterogeneity and correcting for multiple testing will all adversely impact the power to detect loci by association. These issues must be considered carefully if the GWA approach is to succeed in mapping complex phenotypes.


Weight Loss During Neoadjuvant Therapy Is Associated With Poor Response Among the Patients With Gastrointestinal Cancer: A Propensity Score Matching Analysis.
The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients. From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared. A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable. BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.


Utilization of patterned bioprinting for heterogeneous and physiologically representative reconstructed epidermal skin models.
Organotypic skin tissue models have decades of use for basic research applications, the treatment of burns, and for efficacy/safety evaluation studies. The complex and heterogeneous nature of native human skin however creates difficulties for the construction of physiologically comparable organotypic models. Within the present study, we utilized bioprinting technology for the controlled deposition of separate keratinocyte subpopulations to create a reconstructed epidermis with two distinct halves in a single insert, each comprised of a different keratinocyte sub-population, in order to better model heterogonous skin and reduce inter-sample variability. As an initial proof-of-concept, we created a patterned epidermal skin model using GPF positive and negative keratinocyte subpopulations, both printed into 2 halves of a reconstructed skin insert, demonstrating the feasibility of this approach. We then demonstrated the physiological relevance of this bioprinting technique by generating a heterogeneous model comprised of dual keratinocyte population with either normal or low filaggrin expression. The resultant model exhibited a well-organized epidermal structure with each half possessing the phenotypic characteristics of its constituent cells, indicative of a successful and stable tissue reconstruction. This patterned skin model aims to mimic the edge of lesions as seen in atopic dermatitis or ichthyosis vulgaris, while the use of two populations within a single insert allows for paired statistics in evaluation studies, likely increasing study statistical power and reducing the number of models required per study. This is the first report of human patterned epidermal model using a predefined bioprinted designs, and demonstrates the relevance of bioprinting to faithfully reproduce human skin microanatomy.


Cross-Cultural Adaptation and Validation of the Hong Kong-Chinese Version of Vocal Fatigue Index (VFI(HK)).
This study aimed to cross-culturally adapt and validate the Hong Kong-Chinese version of the Vocal fatigue index (VFI(HK)). The original English version of the Vocal fatigue index (VFI) was translated and adapted to the VFI(HK). A total of 206 subjects (87 in the Fatigue group and 119 in the Control group) completed the VFI(HK) and validity, reliability and receiver operating characteristic (ROC) were analysed. The VFI(HK) exhibited satisfactory psychometric properties. It showed good content validity (scale-level content validity indices ≥ 0.842) and excellent internal consistency (Part 1: α = 0.945, Part 2: α = 0.914, Part 3: α = 0.951). Parts 1 and 2 of the questionnaire showed good construct validity (Part 1: t(204) = 5.743, P < 0.001; Part 2: t(204) = 5.049, P < 0.001). Test-retest reliability ranged from acceptable (Part 3: Ρ = 0.702) to good (Part 1: Ρ = 0.885, Part 2: Ρ = 0.827). ROC curves showed acceptable and close-to-acceptable intrinsic accuracies for Parts 1 (Aera under curve (AUC) = 0.712) and 2 (AUC = 0.694) respectively. Cutoff scores of 25 and 10 are suggested for Parts 1 and 2 respectively. The VFI(HK) is a valid and sensitive assessment tool. It may be adopted to identify individuals with vocal fatigue in the Hong Kong-Chinese population.


Novel humidity sensors based on nanomodified Portland cement.
Commonly used humidity sensors are based on metal oxides, polymers or carbon. Their sensing accuracy often deteriorates with time, especially when exposed to higher temperatures or very high humidity. An alternative solution based on the utilization of Portland cement-based mortars containing in-situ grown carbon nanofibers (CNFs) was evaluated in this study. The relationship between the electrical resistivity, CNF content and humidity were determined. The highest sensitivity was observed for samples containing 10 wt.% of the nanomodified cement which corresponded to 0.27 wt.% of CNFs. The highest calculated sensitivity was approximately 0.01024 per 1% change in relative humidity (RH). The measured electrical resistivity is a linear function of the RH in the humidity range between 11 and 97%. The percolation threshold value was estimated to be at around 7 wt.% of the nanomodified cement, corresponding to ~ 0.19 wt.% of CNFs.


Antibody status to influenza A/Singapore/1/57(H2N2) in Finland during a period of outbreaks caused by H3N2 and H1N1 subtype viruses.
The incidence of haemagglutination inhibition (HI) antibody (titre greater than or equal to 12) to influenza A/Singapore/1/57(H2N2) in sera collected from a Finnish population in the summer of 1981 was 58%. Subjects born after 1968 were essentially seronegative, and a comparable low HI antibody status was also recorded among the elderly, the lowest being in people born during the period 1901-10. A small increase in antibody titre to the H2N2 virus was observed in the different age groups after infections with the H3N2, but not the H1N1, subtype influenza A viruses. The heterotypic response, which could be due to HI or NA antibodies, was restricted almost exclusively to subjects already exhibiting this antibody in acute phase sera. Moreover, the anamnestic boosting was not as strong as that described in earlier studies from samples collected at the beginning of the present era of H3N2 viruses. At population level, the HI antibody status to H2N2 was about the same at the beginning and end of the follow-up period which covered eight epidemic seasons. The results are discussed with respect to the doctrine of 'original antigenic sin' and to the threat of re-emergence of the H2N2 viruses.


Permanent cardiac pacing in patients on chronic renal dialysis.
We reviewed the need for permanent pacemaker implantation in patients with chronic renal failure who were undergoing dialysis. During a 10-year span, there were seven patients undergoing dialysis in whom a permanent pacemaker was indicated; this was an incidence of 0.68%. During that same period, the general patient population of this hospital had an incidence of permanent pacemaker implantation of about 0.29%. The need for hemodialysis in the same hospital population was 0.51%. Of the seven patients, four had universal pacemakers. Cardiac function was evaluated via radionuclide angiography. Three of the four patients showed improvement with dual-chambered pacing over ventricular pacing. Permanent pacemaker implantation was often needed after initiation of dialysis from 6 to 51 months with a mean of 21 months. During the follow-up period, three patients died from 7 months to 6 years after the institution of permanent pacing; their deaths were secondary to renal disease.


Impaired Peroxisomal Fitness in Obese Mice, a Vicious Cycle Exacerbating Adipocyte Dysfunction via Oxidative Stress.
Aims: Peroxisome is a critical organelle for fatty acid oxidation (FAO) and metabolism of reactive oxygen species (ROS). Increased oxidative stress in adipose tissue contributes to the development of insulin resistance and metabolic syndrome in obesity. This study aimed to investigate the role of peroxisomal fitness in maintaining adipocyte function, which has been under-rated in the obesity research area. Results: Reduced peroxisomal gene expressions in white adipose tissue (WAT) of obese mice suggested a close correlation between peroxisomes and obesity. Peroxisomal biogenesis factor 5 siRNA increased cellular ROS and inflammatory mediators in 3T3-L1 adipocytes. On the contrary, hydrogen peroxide or tumor necrosis factor-α treatment significantly decreased biogenesis- and function-related peroxisomal proteins, suggesting a positive feedback loop of ROS/inflammation and peroxisomal dysfunction. Correspondingly, catalase (a major peroxisomal antioxidant)-knockout mice fed with high-fat diet (HFD) exhibited suppressed peroxisomal proteins along with increased oxidative stress and accelerated obesity. In response to fenofibrate (a peroxisomal proliferator) treatment, WAT of HFD-fed wild-type mice showed not only increases in peroxisomal biogenesis and FAO but also attenuated features of adipocyte dysfunction and obesity. However, these results were not observed in peroxisome proliferator-activated receptor-alpha null obese mice. Innovation: Impaired peroxisomal fitness enhanced oxidative stress and inflammation in adipocytes, which exacerbates obesity. Conclusion: Adipose tissue peroxisomal homeostasis plays an important role in attenuating the features of obesity, and it can be a potential therapeutic target of obesity.


Detection of restenosis with dobutamine stress test after coronary angioplasty.
Dobutamine ECG tests were serially performed before, at 15 days, and at 2 and 6 months after successful coronary angioplasty in 58 patients. The dose of dobutamine was progressively increased from 5 micrograms/kg/min to a maximum of 40 micrograms/kg/min every 5 minutes, with ECG and blood pressure control. Coronary angiography was performed at the end of the study. At 15 days after coronary angioplasty, the dobutamine test was of little value for the diagnosis or prediction of restenosis. At the end of the study, both the presence of angina and the results of the dobutamine test were related to coronary angiography, and their accuracy was calculated for the detection of mild (> or = 50%) and severe (> or = 70%) restenosis or new coronary lesions. The accuracy of angina was 68% for the detection of mild lesions and 70% for that of severe lesions, whereas the accuracy of the dobutamine test was 78% for mild lesions and 80% for severe lesions. It is concluded that the dobutamine stress test is a simple and useful method for the detection of restenosis when it is performed at 2 and 6 months after coronary angioplasty. However, it cannot distinguish between restenosis or new coronary lesions.


A new fractional orthogonal basis and its application in nonlinear delay fractional optimal control problems.
This paper aims to devise a novel fractional orthogonal basis to solve a certain class of nonlinear fractional optimal control problems with delay whose system dynamics is governed by a nonlinear fractional differential equation of the Caputo type. The foundation of the new framework is based on a hybrid of block-pulse and fractional-order Legendre functions. A new integral operator associated with the proposed orthogonal basis is constructed by using the Riemann-Liouville integral operator. This operator enables one to immensely reduce the complexity of computations related to the Riemann-Liouville integral operator. Some significant theoretical results concerning the new fractional basis are provided. Several problems are tested for the validation and verification of our numerical findings. It is demonstrated that the new fractional basis produces an exact solution for a specific class of nonlinear delay fractional optimal control problems. Generally, the developed fractional basis is a promising mathematical tool for investigating fractional-order systems.


[The role of specific IgE antibodies in the immune adherence of normal macrophages to schistosomes of Schistosoma mansoni].
Specific IgE antibodies from immune rat serum were demonstrated to mediate the immune adherence of normal rat macrophages to Schistosome mansoni schistosomules, which was followed by a cytototoc action. Hence, a new positive role of IgE antibodies in protective immunity is argued.


Molybdenum-Catalyzed Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds.
The transition-metal-catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo-catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench-stable 1,2-dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram-scale syntheses, late-stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo-oxo complexes.


Elucidating the transdiagnostic dimensional structure of trauma-related psychopathology: Findings from VA cooperative study 504 - risperidone treatment for military service related chronic post traumatic stress disorder.
Three of the most common trauma-related mental disorders-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD)-are highly comorbid and share common transdiagnostic symptom dimensions of threat (i.e., fear) and loss (i.e., dysphoria) symptomatology. However, empirical evaluation of the dimensional structure of component aspects of these disorders is lacking. Using structured clinical interview data from U.S. military veterans with chronic military-related PTSD, we evaluated the transdiagnostic dimensional structure of PTSD, MDD, and GAD symptoms. We then examined the relationship between the best-fitting transdiagnostic model of these symptoms, and measures of physical and mental functioning, and life satisfaction and well-being. Exploratory factor analysis revealed that a 3-factor transdiagnostic model comprised of loss (i.e., dysphoria), threat (i.e., anxious arousal, re-experiencing, and avoidance symptoms), and somatic anxiety (i.e., physiological manifestations of anxiety) symptoms provided the best representation of trauma-related PTSD, MDD, and GAD symptoms. Somatic anxiety symptoms were independently associated with physical functioning, while loss symptoms were independently associated with mental functioning and life satisfaction and well-being. Evaluation of study aims in a relatively homogeneous sample of veterans with chronic, military-related PTSD. Results of this study suggest that a 3-factor transdiagnostic model best characterizes the dimensional structure of PTSD, MDD, and GAD symptoms in military veterans with chronic military-related PTSD. This model evidenced external validity in demonstrating differential associations with measures of physical and mental functioning, and life satisfaction and well-being. Results provide support for emerging contemporary models of psychopathology, which emphasize transdiagnostic and dimensional conceptualizations of mental disorders. Such models may have utility in understanding the functional status of trauma survivors.


Different methods of pain relief for IVF and ICSI oocyte retrieval - A Dutch survey.
Which analgesia methods are used during oocyte retrieval in the Netherlands? In April 2017, an online survey containing questions on the analgesia protocol used for IVF/ICSI oocyte retrieval was sent to all clinics in the Netherlands that perform oocyte retrievals. The response rate was 97%. We uncovered the large variety of medication protocols used for pain relief during oocyte retrieval in the Netherlands. Based on the main component of the given analgesia, we distinguished the three most frequently used analgesia protocols: intravenously (i.v.) administered opioids, intramuscularly (i.m) administered opioids, and non-sedative oral analgesics. Aside from analgesia, 61% provided anxiolysis with a benzodiazepine. Nearly half of the clinics registered pain scores. The vital functions were monitored at all clinics administering opioids i.v., but at none of the clinics administering opioids i.m. A wide variety of analgesia protocols are used. The three most frequently used are i.v. administered opioids, i.m. administered opioids, and non-sedative oral analgesics. The variety of analgesia protocols is not desirable in the context of good clinical practice, and considering the risks of combining opioids and benzodiazepines. Monitoring of vital functions was only performed after administration of i.v. medication. A comparison of the pain scores could be a first step in finding the optimal method of analgesia, thereby forming the basis of guidelines for analgesia during oocyte retrieval.


Phylogeny of the cricket subfamily Eneopterinae (Orthoptera, Grylloidea, Eneopteridae) based on four molecular loci and morphology.
The phylogenetic relationships of 39 species of Eneopterinae crickets are reconstructed using four molecular markers (16S rRNA, 12S rRNA, cytochrome b, 18S rRNA) and a large morphological data set. Phylogenetic analysis via direct optimisation of DNA sequence data using parsimony as optimality criterion is done for six combinations of weighting parameter sets in a sensitivity analysis. The results are discussed in a twofold purpose: first, in term of significance of the molecular markers for phylogeny reconstruction in Ensifera, as our study represents the first molecular phylogeny performed for this insect suborder at this level of diversity; second, in term of corroboration of a previous phylogeny of Eneopterinae, built on morphological data alone. The four molecular markers all convey phylogenetic signal, although variously distributed on the tree. The monophyly of the subfamily, that of three over five tribes, and of 10 over 13 genera, are recovered. Finally, previous hypotheses on the evolution of acoustic devices and signals in the Eneopterinae clade are briefly tested, and supported, by our new data set.


Agroecology and Health: Lessons from Indigenous Populations.
The article aims to systematize and disseminate the main contributions of indigenous ancestral wisdom in the agroecological production of food, especially in Latin America. For this purpose, it is necessary to ask whether such knowledge can be accepted by academia research groups and international forums as a valid alternative that could contribute to overcome the world's nutritional problems. Although no new findings are being made, the validity of ancestral knowledge and agroecology is recognized by scientific research, and by international forums organized by agencies of the United Nations. These recommend that governments should implement them in their policies of development, and in the allocation of funds to support these initiatives. Agroecology and ancestral knowledge are being adopted by a growing number of organizations, indigenous peoples and social groups in various parts of the world, as development alternatives that respond to local needs and worldviews. Its productive potential is progressively being recognized at an international level as a model that contributes to improve the condition of people regarding nutritional food.


Biodiversity effects on resource use efficiency and community turnover of plankton in Lake Nansihu, China.
The relationship between biodiversity and ecosystem functioning is a central issue in ecology, especially in aquatic ecosystems due to the ecophysiological characteristics of plankton. Recently, ecologists have obtained conflicting conclusions while analyzing the influence of species diversity on plankton resource use efficiency (RUE) and community turnover. In this study, both phytoplankton and zooplankton communities were investigated seasonally from 2011 to 2013 in Lake Nansihu, a meso-eutrophic and recovering lake in China. The effects of phytoplankton diversity on RUE of phytoplankton (RUEPP), zooplankton (RUEZP), and community turnover were analyzed. Results showed that both phytoplankton species richness and evenness were positively correlated with RUEPP. RUEZP had a negative relationship with phytoplankton species richness, but a weak unimodal relationship with phytoplankton evenness. Cyanobacteria community had the opposite influence on RUEPP and RUEZP. Thus, cyanobacteria dominance will benefit RUEPP in eutrophic lakes, but the growth and reproduction of zooplankton are greatly limited. The strong negative relationship between total phosphorus and RUEZP confirmed these results. Phytoplankton community turnover tended to decrease with increasing phytoplankton evenness, which was consistent with most previous studies. The correlation coefficient between phytoplankton species richness and community turnover was negative, but not significant (p > 0.05). Therefore, phytoplankton community turnover was more sensitive to the variation of evenness than species richness. These results will be helpful in understanding the effects of species diversity on ecosystem functioning in aquatic ecosystems.


Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy.
Sepiapterin reductase deficiency (SRD) is an under-recognized levodopa-responsive disorder. We describe clinical, biochemical, and molecular findings in a cohort of patients with this treatable condition. We aim to improve awareness of the phenotype and available diagnostic and therapeutic strategies to reduce delayed diagnosis or misdiagnosis, optimize management, and improve understanding of pathophysiologic mechanisms. Forty-three individuals with SRD were identified from 23 international medical centers. The phenotype and treatment response were assessed by chart review using a detailed standardized instrument and by literature review for cases for which records were unavailable. In most cases, motor and language delays, axial hypotonia, dystonia, weakness, oculogyric crises, and diurnal fluctuation of symptoms with sleep benefit become evident in infancy or childhood. Average age of onset is 7 months, with delay to diagnosis of 9.1 years. Misdiagnoses of cerebral palsy (CP) are common. Most patients benefit dramatically from levodopa/carbidopa, often with further improvement with the addition of 5-hydroxytryptophan. Cerebrospinal fluid findings are distinctive. Diagnosis is confirmed by mutation analysis and/or enzyme activity measurement in cultured fibroblasts. Common, clinical findings of SRD, aside from oculogyric crises and diurnal fluctuation, are nonspecific and mimic CP with hypotonia or dystonia. Patients usually improve dramatically with treatment. Consequently, we recommend consideration of SRD not only in patients with levodopa-responsive motor disorders, but also in patients with developmental delays with axial hypotonia, and patients with unexplained or atypical presumed CP. Biochemical investigation of cerebrospinal fluid is the preferred method of initial investigation. Early diagnosis and treatment are recommended to prevent ongoing brain dysfunction.


Effect of thyroliberin on the concentration of adenosine 3':5'-phosphate and on the activity of adenosine 3':5'-phosphate-dependent protein kinase in prolactin-producing cells in culture.
1. The effects of thyroliberin were studied in cultured rat pituitary-tumour cells that synthesize and secrete prolactin (the GH4C1 cell strain). 2. Prolactin and cyclic AMP were measured by radioimmunological methods, and a cyclic AMP-dependent protein kinase was characterized by using histone as substrate. 3. Prolactin release was studied after 5-60min of treatment, and synthesis after 48h of treatment with thyroliberin. One-half maximum stimulation of release and synthesis were observed at 0.25 and at 4nM respectively. 4. Cyclic AMP was temporarily increased in cell suspensions after treatment with thyroliberin, and one-half maximum stimulation was observed at 25nM. 5. Dibutyryl cyclic AMP increased prolactin release and synthesis, one-half maximum effects being obtained at 20 micronM. 6. A cyclic AMP-dependent protein kinase, which was one-half maximally stimulated at 30 nM-cyclic AMP, was demonstrated. 7. An increase in the activity ratio (-cyclic AMP/+cyclic AMP) of the cyclic AMP-dependent protein kinase was observed after treatment with thyroliberin. Total protein kinase activity in the presence of cyclic AMP was unaltered. The time-course of enzyme activation was similar to that of cyclic AMP formation and corresponded to the time when prolactin release was first observed. 8. It is concluded that thyroliberin induces cyclic AMP formation, resulting in the activation of a cyclic AMP-dependent protein kinase.


Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis.
Previously, studies have shown increased risks of second primary malignancies (SPM) after Hodgkin lymphoma and non-Hodgkin lymphoma. Nevertheless, investigation quantifying risks of SPM in patients with diffuse large B-cell lymphoma (DLBCL) remains scarce. We used the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub to analyze the risks of SPM in patients with DLBCL. The standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence intervals (CIs) were calculated. Among patients with DLBCL as a primary malignancy, 3751 patients had second cancer episodes identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P < 0.05). There was a significantly higher risk of tumors/malignancies in the following sites of patients with DLBCL compared with the general population: Oral cavity and pharynx, hepatobiliary system, head and neck, thorax, bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently in patients with DLBCL than in the general population. Risk for a subsequent colon/rectum/anus cancer, bone and joint malignancy, and melanoma were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies was not significantly increased in those without a radiation record. Notably, for patients under 45 years of age, the risk for SPM was higher than their counterparts in other age groups. Our results offer insight into the occurrence of SPM among patients with DLBCL, suggesting awareness of the increased risk of subsequent malignancies is crucial for DLBCL survivors as well as for their physicians.


Prediction of air trapping or pulmonary hyperinflation by forced spirometry in COPD patients: results from COSYCONET.
Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated via spirometry. We used data from visits 1-5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2-5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933). Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1-4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV1) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV1 % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV1 % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively. The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available.


The Relationship Between Nature and Immigrants' Integration, Wellbeing and Physical Activity: A Scoping Review.
Exposure to nature has been suggested to promote immigrants' health and facilitate adaptation. This review summarizes previous research focusing on the relationship between nature and immigrants' integration, wellbeing and physical activity. A search strategy was developed and adapted to seven databases. After removing duplicates, 4861 records were screened, 81 met inclusion criteria. Community gardens and urban parks were the most studied environments. In these settings, embodied experiences (the interactive processes of sensing and cognition) can foster new memories that facilitate adaptation and attachment to new natural environments. Social interaction and reconnecting with pre-migration experiences through specific use patterns can promote cultural continuation, sense of belonging and wellbeing. Other health benefits such as physical activity, disease management and improved nutrition were less frequently studied. Barriers to participation and recommendations for research and practice were also identified. Use of stronger study designs and greater inclusion of immigrant groups in research, design and evaluation of nature-based initiatives is needed.


Differential activation of ornithine decarboxylase and tyrosine kinase in the rectal mucosa of patients with hyperplastic and adenomatous polyps.
Hyperplastic polyps are considered to be benign colonic lesions with almost no potential for malignant transformation. Recent reports have shown an increased association of hyperplastic polyps with adenomatous polyps and have advocated a full colonoscopy in patients who harbor hyperplastic polyps. Hyperproliferative mucosa is known to be associated with adenomatous polyps, but its relationship to hyperplastic polyps is unknown. In the present pilot study, it is determined whether a change in mucosal proliferative patterns is observed in patients who harbor only hyperplastic polyps or a history of hyperplastic polyps relative to those who harbor both hyperplastic polyps and adenomatous polyps by measuring ornithine decarboxylase and tyrosine kinase activity in macroscopically normal rectal mucosa. Fifteen patients had either adenomatous polyps proximally or harbored adenomatous polyps and hyperplastic polyps. Seven patients had hyperplastic polyps and 15 patients had a prior history of hyperplastic polyps with no polyps found during the current examination. The ornithine decarboxylase activity of the rectal mucosa with proximal adenomatous polyps or both polyp types was significantly higher than that of hyperplastic polyps, the history of hyperplastic polyps, or controls, and values for hyperplastic polyps and the history of hyperplastic polyps were similar to controls. On the other hand, tyrosine kinase activity in the rectal mucosa of patients with both or either polyp type was elevated without any significant difference between hyperplastic and adenomatous polyps. Thus, it is concluded that although increased ornithine decarboxylase activity in rectal mucosa suggests the presence of adenomatous polyps or a combination of adenomatous with hyperplastic polyps, increased tyrosine kinase activity suggests the presence of any type of polyp.


Lipoprotein lipase secretion from isolated rat fat cells of different size.
Lipoprotein lipase(LPL) release from isolated small fat cells from young rats and large fat cells from older, fatter rats was compared during in vitro incubation at 30 degrees C. Although large fat cells had nearly three times higher cellular LPL activity, they secreted similar amounts of LPL activity into the incubation medium under both basal conditions (Krebs Ringer bicarbonate buffer containing 4% albumin and 6mM glucose) and after stimulation of LPL release by 5% human serum, or serum plus 1 U/ml heparin. These data suggest that previous observations of an altered tissue distribution of LPL in adipose tissue containing large fat cells can be at least in part explained by an alteration at the level of LPL secretion.


Suppression of the TRIF-dependent signaling pathway of TLRs by epoxomicin.
Toll-like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88- and the TRIF-dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide α',β'-epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF-kB and IRF3 induced by TLR agonists, decreased the expression of interferon-inducible protein-10, and inhibited the activation of NF-kB and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88- and TRIF-dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.


Perceptual learning as a potential treatment for amblyopia: a mini-review.
Amblyopia is a developmental abnormality that results from physiological alterations in the visual cortex and impairs form vision. It is a consequence of abnormal binocular visual experience during the "sensitive period" early in life. While amblyopia can often be reversed when treated early, conventional treatment is generally not undertaken in older children and adults. A number of studies over the last twelve years or so suggest that Perceptual Learning (PL) may provide an important new method for treating amblyopia. The aim of this mini-review is to provide a critical review and "meta-analysis" of perceptual learning in adults and children with amblyopia, with a view to extracting principles that might make PL more effective and efficient. Specifically we evaluate: 1). What factors influence the outcome of perceptual learning? 2). Specificity and generalization - two sides of the coin. 3). Do the improvements last? 4). How does PL improve visual function? 5). Should PL be part of the treatment armamentarium? A review of the extant studies makes it clear that practicing a visual task results in a long-lasting improvement in performance in an amblyopic eye. The improvement is generally strongest for the trained eye, task, stimulus and orientation, but appears to have a broader spatial frequency bandwidth than in normal vision. Importantly, practicing on a variety of different tasks and stimuli seems to transfer to improved visual acuity. Perceptual learning operates via a reduction of internal neural noise and/or through more efficient use of the stimulus information by retuning the weighting of the information. The success of PL raises the question of whether it should become a standard part of the armamentarium for the clinical treatment of amblyopia, and suggests several important principles for effective perceptual learning in amblyopia.


Dietary Supplementation with Saccharomyces cerevisiae, Clostridium butyricum and Their Combination Ameliorate Rumen Fermentation and Growth Performance of Heat-Stressed Goats.
This study aimed to evaluate the effects of Saccharomyces cerevisiae, and their combination on rumen fermentation and growth performance of heat-stressed goats. Twelve heat-stressed goats (20.21 ± 2.30 kg) were divided equally into four groups: control group (CG, fed the basal diet, Saccharomyces cerevisiae supplemented group (SC, 0.60% Saccharomyces cerevisiae added to the basal diet), Clostridium butyricum supplemented group (CB, 0.05% Clostridium butyricum added to the basal diet), and their combination supplemented group (COM 0.60% Saccharomyces cerevisiae and 0.05% Clostridium butyricum added to the basal diet) and were assigned to a 4 × 3 incomplete Latin square design. The rumen fluid and feces were collected for fermentation parameters and feed digestibility analysis, and animal growth performance was also assessed during all the experiment periods. The results showed that rumen pH, rumen cellulolytic enzymes (avicelase, CMCaes, cellobiase, and xylanase) activities, and the concentrations of rumen total volatile fatty acid (TVFA), acetic acid, and propionic acid were significantly increased with Saccharomyces cerevisiae, Clostridium butyricum, and their combination supplementation (p < 0.05). Besides, the dry matter intake (DMI), average daily gain (ADG), and the digestibility of dry matter (DM), neutral detergent fiber (NDF), and acidic detergent fiber (ADF) were significantly increased (p < 0.05) with supplemented these probiotics. However, the ammonia nitrogen (NH3-N) concentration only significantly increased in CB and A/P ratio (acetic acid to propionic acid ratio) only significantly increased in SC and CB. These results indicated that the supplementation with these probiotics could ameliorate rumen fermentation and growth performance of heat-stressed goats.


Appearance of cytolytic antibodies in sheep lymph following immunisation with tumour cells. Identification of antibody subclasses.
Sheep were immunised with mouse P815 tumour cell suspensions and at intervals afterwards lymph was collected draining from the stimulated lymph nodes. The lymph samples were fractionated by column chromatography into IgM, IgG1 and IgG2 antibody fractions; these were then assayed for cytolytic functions on 51Cr labelled target P815 cells. Complement dependent antibodies were assayed using sheep complement; activity was first detected in the IgM fraction 3-4 days after immunisation and in the IgG1 fraction at 5-6 days. No CDA activity was found in fractions of the IgG2 antibody subclass at any time. Leucocyte dependent antibodies were detected only in the IgG fraction, and they appeared simultaneously in both IgG1 and IgG2 subclasses 5-6 days after immunisation.


[Systematic research on an etiology in apparently primary deep venous thrombosis. Apropos of 59 cases].
Primary deep vein thrombosis was confirmed by phlebography in 59 cases between Jan. 1981 and Jan. 1984 in the department of Cardiovascular Surgery of the Academic Hospital of the V.U.B. Brussels. Investigations conducted in all patients included blood and urine analyses, chest radiography, electrocardiogram, gynecologic or urologic examinations and abdominal and pelvic ultrasound imaging. Findings demonstrated one or more risk factors in 92% of cases, the principal ones being obesity, a history of thromboemboli and, in women, the use of oral contraceptives. Nine patients had cancer and 4 of these received combined surgery-chemotherapy. All cases of so-called primary deep vein thrombosis should be investigated routinely for risk factors, because of the need and possibilities for treatment in some of them, particularly since procedures are non-invasive, of low cost, and easily performed during initial heparin therapy.


Long-term semantic transfer: an overlapping-operations account.
Semantic priming is usually a short-lived effect. However, it is also usually investigated using undemanding tasks, such as naming or lexical decision. We instead required subjects to perform category verification. We observed semantically mediated transfer occurring at an average lag of 90 intervening trials. We also observed that this priming was specific to the stimulus properties made salient in prime and probe displays and the particular task demanded in those displays. We interpret the results within an overlapping-operations framework, based on the work of Kolers (e.g., 1976).


A randomized factorial trial of internet-delivered cognitive behavioural therapy: An 8-week program with or without extended support and booster lesson.
While internet-delivered cognitive behavioural therapy (ICBT) is effective, some patients suggest extended support post-treatment could improve care. In this randomized factorial trial, we examined the benefits of an 8-week therapist-assisted ICBT program offered with or without an optional 4-week extension of support (Factor 1) and with or without an optional booster lesson (Factor 2). Patients screened for ICBT for depression and/or anxiety were randomly assigned to the conditions (N = 434) and we examined the use of the extension and booster, differences between those who did or did not use extension or booster, and the impact of the extension or booster on outcomes, engagement, and satisfaction at 26-weeks post-enrollment. Therapists recorded time and observations with offering support during the extension and booster. In the extension group, 54.4% (n = 56) requested the extension, while in the booster group 50.9% (n = 56) accessed the booster, and in the combined group, 41.6% (n = 47) requested the extension and 51.3% (n = 58) accessed the booster. Those who requested the extension were older, and more likely to report medication and mental health service use and severe mental health-related disability at pre-treatment; they also reported putting less effort into ICBT and finding skills more difficult. The booster was more often used among those with lower symptom severity, and those who put more effort into and had more positive experiences with ICBT. As expected, those assigned to extension sent more messages to their therapist, and those assigned to booster logged in more often. Therapists also took more time to deliver ICBT with an extension (>18 min) or booster (>13 min) compared to the 8-week program, and perceived extension and booster as beneficial for some, but not all patients. Treatment satisfaction was high across conditions, and effect sizes were large from pre-treatment to 26-week follow-up on most measures. No significant group differences were found in this study. Lack of group differences, however, could reflect low use of the extension and booster. Results provide helpful information about the demand for extensions and boosters, and provide directions for future research.


Effects of postnatal stimulation on the passive avoidance behaviour of young rats.
We examined the effects of stimulation on either postnatal days 1-7 or 21-27 on passive avoidance reaction (PAR) of young rats. Animals received tactile or visual stimulation for 10 min each day, and were trained on postnatal day 28 in a step-through apparatus using a footshock of 0.75 mA for 2 s. Retention was tested on five consecutive days beginning on day 29. Memory retention was measured for each rat 24, 48, 72, 96 and 120 h after the acquisition trial. Step-through latencies to enter the dark compartment, time spent in the illuminated compartment and number of crossings of the light beam were recorded up to 200 s. Rats that received tactile or visual stimulation during the 4th postnatal week displayed significantly lower PAR latencies, a shorter stay in the illuminated compartment and a higher number of crossings of the light beam compared to rats treated during the 1st postnatal week. The untreated control group showed a rapid decline of PAR latencies. All experimental groups remained in the illuminated compartment longer and showed PAR latencies well above those of the control group. The differences became more pronounced when visual stimulation in the first postnatal week was used. The number of crossings of the light beam was significantly reduced by the treatment, with the exception of the experimental group stimulated visually in the 4th week. The behavioural changes induced by tactile or visual stimulation have a long-lasting effect in coping with a stressful task.


The effect of Delphinium denudatum (Jadwar) on fatigue: A randomized double blind placebo-controlled clinical trial.
Fatigue is a common problem in modern-day life. The aim of this study was to evaluate the effect of Delphinium denudatum (Jadwar) on fatigue. This study was a randomized double-blind placebo-controlled clinical trial between healthy normal university students. In each group, participants were given one capsule of either WEACURE® (containing 500 mg of Jadwar root powder) or placebo for 15 consecutive days. Multidimensional Fatigue Inventory (MFI) questionnaire was used before and after the intervention to evaluate different aspects of fatigue. A total number of 64 participants completed the study. Data analysis showed decrease in the scores of all five domains of fatigue in Jadwar group (13.31 ± 3.05-7.75 ± 2.66, 12.31 ± 3.55-7.63 ± 2.62, 12.22 ± 4.26-6.97 ± 2.06, 11.56 ± 4.21 to 7.28 ± 2.37, 12.91 ± 3.09-7.34 ± 2.13 in general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue domains, respectively) which was statistically significant (P value<0.0001). This situation was significantly superior to the placebo group. Prescribed dosage of WEACURE® capsule was well tolerated. As a complementary tonic agent, Jadwar have a potential to reduce fatigue in normal population. However, objective evaluation of its anti-fatigue effect should be further evaluated.


Long-term dietary supplementation with a yang-invigorating Chinese herbal formula increases lifespan and mitigates age-associated declines in mitochondrial antioxidant status and functional ability of various tissues in male and female C57BL/6J mice.
To investigate whether Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula, could affect survival of aging animals, male and female C57BL/6J mice were given a VI-28-supplemented diet (0.05 and 0.5%, wt/wt) starting at 36 weeks of age, until death. VI-28 dietary supplementation at 0.05% significantly increased median lifespans of both male and female mice as compared to controls. Survival enhancement was associated with protection against age-associated impairments in mitochondrial antioxidant status and functional ability in various tissues. In conclusion, VI-28 could retard the aging process in mice, probably by mitigating age-associated declines in mitochondrial antioxidant status and functional ability in tissues.


Studies on Mapping Plant Genes That Confer Tolerance to Abiotic Stresses.
Climate change is affecting the Earth's environment through temperature fluctuation, rainfall patterns, wind, and radiation [...].


We sought to evaluate ginger's cardiovascular and metabolic effects (Zingiberofficinale) add-on therapy in type 2 diabetes patients over six weeks. We performed a single-arm clinical trial. In well-to-moderately controlled Type 2 diabetic patients with unchanged treatment for at least three months, the intervention consisted of 6-week add-on oral supplementation of powdered ginger extracts in capsules at a dose of 399 mg three times per day. Transthoracic Doppler echocardiography, ambulatory blood pressure monitoring (ABPM), glycatedhaemoglobin (HbA1c), lipid profile, kidney and liver function analysis were performed at initial and final visits, with a follow-up visit on day 21. Adherence to treatment, palatability and safety were also assessed. Overall, 21 participants (16 females) were included in the analysis. We found a non-significant decrease of E' wave from 0.05[0.04-0.09] to 0.06[0.05-0.7]cm/s, A-wave from 0.8[0.6-0.8] to 0.7[0.6-0.8] cm/s, and E-wave from 0.6[0.5-0.7] to 0.5[0.425-0.6]cm/s. There was a significant reduction of HbA1c from 49.7[47.0-57.4] to 44.3[38.8-53.0] mmol/mol and triglycerides from 1.6[1.4-1.9] to 1.2[0.9-1.8] mmol/l. A 5% decrease or more was observed for diurnal DBP, diurnal MAP and 24-hour DBP. Zingiberofficinale used as add-on therapy tend to improve diastolic function, blood pressure and lipid profile of type 2 diabetes patients. Further studies are needed to define the dosage and duration of this supplementary treatment accurately. NCT04222738.


Visualization and Quantification of Neutrophil Extracellular Traps.
Neutrophils are innate immune cells that play important roles in many physiological and pathological processes, including immune defense and cancer metastasis. In addition to the release of proinflammatory cytokines, chemokines, and cytoplasmic granules containing digestive proteins, in recent years, neutrophils have been observed to release neutrophil extracellular traps (NETs) that consist of extracellular DNA associated with antimicrobial proteins, such as histones and myeloperoxidase. These NETs are increasingly being recognized as an important mechanism of neutrophil host defense and function. This chapter will summarize the current literature on the known processes of NET formation and describe in detail an immunofluorescence approach that can be employed to visualize and quantify NETs in vitro.


Fluorescence-detection size-exclusion chromatography utilizing nanobody technology for expression screening of membrane proteins.
GFP fusion-based fluorescence-detection size-exclusion chromatography (FSEC) has been widely employed for membrane protein expression screening. However, fused GFP itself may occasionally affect the expression and/or stability of the targeted membrane protein, leading to both false-positive and false-negative results in expression screening. Furthermore, GFP fusion technology is not well suited for some membrane proteins, depending on their membrane topology. Here, we developed an FSEC assay utilizing nanobody (Nb) technology, named FSEC-Nb, in which targeted membrane proteins are fused to a small peptide tag and recombinantly expressed. The whole-cell extracts are solubilized, mixed with anti-peptide Nb fused to GFP for FSEC analysis. FSEC-Nb enables the evaluation of the expression, monodispersity and thermostability of membrane proteins without the need for purification but does not require direct GFP fusion to targeted proteins. Our results show FSEC-Nb as a powerful tool for expression screening of membrane proteins for structural and functional studies.


Clinical neurophysiology of aging brain: from normal aging to neurodegeneration.
Physiological brain aging is characterized by a loss of synaptic contacts and neuronal apoptosis that provokes age-dependent decline of sensory processing, motor performance, and cognitive function. Neural redundancy and plastic remodelling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. However, age is the main risk factor for neurodegenerative disorders such as Alzheimer's disease (AD) that impact on cognition. Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including electroencephalography (EEG), event-related potential (ERP), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) can accurately index normal and abnormal brain aging to facilitate non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing and coherence of rhythmic oscillations at various frequencies. The present review provides a perspective of these issues by assaying different neurophysiological methods and integrating the results with functional brain imaging findings. It is concluded that discrimination between physiological and pathological brain aging clearly emerges at the group level, with applications at the individual level also suggested. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost and non-invasive evaluation of at-risk populations. Practical implications of the methods are emphasized.