White matter hyperintensities affect transcranial electrical stimulation in the aging brain.
White matter hyperintensities (WMH) are estimated to occur in greater than 63% of older adults over the age of 60 years. WMH identified in the T2-weighted FLAIR images can be combined with T1-weighted images to enhance individualized current flow models of older adults by accounting for the presence of WMH and its effects on delivered tES current in the aging brain. Individualized head models were derived from T1-weighted images of 130 healthy older adults (mean = 71 years). Lesions segmented from FLAIR acquisition were added to individualized models. Current densities were computed in the brain and compared between models with and without lesions. Integrating WMH into the models resulted in an overall decrease (up to 7%) in median current densities in the brain outside lesion regions. Changes in current density and total lesion volume was positively correlated (R2 = 0.31, p < 0.0001). Incorporating WMH into individualized models may increase the accuracy of predicted tES current flow in the aging brain.


Anion-Regulated Hierarchical Self-Assembly and Chiral Induction of Metallo-Tetrahedra.
The precise control over hierarchical self-assembly of superstructures relying on the elaboration of multiple noncovalent interactions between basic building blocks is both elusive and highly desirable. We herein report a terpyridine-based metallo-cage T with a tetrahedral motif and utilized it as an efficient building block for the controlled hierarchical self-assembly of superstructures in response to different halide ions. Initially, the hierarchical superstructure of metallo-cage T adopted a hexagonal close-packed structure. By adding Cl- /Br- or I- , drastically different hierarchical superstructures with highly-tight hexagonal packing or graphite-like packing arrangements, respectively, have been achieved. These unusual halide-ion-triggered hierarchical structural changes resulted in quite distinct intermolecular channels, which provided new insights into the mechanism of three-dimensional supramolecular aggregation and crystal growth based on macromolecular construction. In addition, the chiral induction of the metallo-cage T can be realized with the addition of chiral anions, which stereoselectively generated either PPPP- or MMMM-type enantiomers.


Association of dopamine D2/3 receptor binding potential measured using PET and [11C]-(+)-PHNO with post-mortem DRD2/3 gene expression in the human brain.
Open access post-mortem transcriptome atlases such as the Allen Human Brain Atlas (AHBA) can inform us about mRNA expression of numerous proteins of interest across the whole brain, while in vivo protein binding in the human brain can be quantified by means of neuroreceptor positron emission tomography (PET). By combining both modalities, the association between regional gene expression and receptor distribution in the living brain can be approximated. Here, we compare the characteristics of D2 and D3 dopamine receptor distribution by applying the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and human gene expression data. Since [11C]-(+)-PHNO has a higher affinity for D3 compared to D2 receptors, we hypothesized that there is a stronger relationship between D2/3 non-displaceable binding potentials (BPND) and D3 mRNA expression. To investigate the relationship between D2/3 BPND and mRNA expression of DRD2 and DRD3 we performed [11C]-(+)-PHNO PET scans in 27 healthy subjects (12 females) and extracted gene expression data from the AHBA. We also calculated D2/D3 mRNA expression ratios to imitate the mixed D2/3 signal of [11C]-(+)-PHNO. In accordance with our a priori hypothesis, a strong correlation between [11C]-(+)-PHNO and DRD3 expression was found. However, there was no significant correlation with DRD2 expression. Calculated D2/D3 mRNA expression ratios also showed a positive correlation with [11C]-(+)-PHNO binding, reflecting the mixed D2/3 signal of the radioligand. Our study supports the usefulness of combining gene expression data from open access brain atlases with in vivo imaging data in order to gain more detailed knowledge on neurotransmitter signaling.


Changes in CSF blood-brain barrier parameters in ischaemic cerebral infarction.
Total CSF protein and CSF/serum albumin and alpha 2-macroglobulin ratios as indicators of a disturbed blood-brain barrier were determined in 39 cases of ischaemic cerebral infarction proved by computed tomography (CT). About 50% of the patients had a barrier disturbance, whereat the CSF serum albumin ratio was shown to be the most sensitive parameter. A disturbed blood-brain barrier was more often found in cases of large infarction, as shown by CT, and occurred most frequently in the first 2 weeks of illness. No correlation was seen between enhancement in CT and disturbance of the blood-brain barrier.


Anticomplement and antitussive activities of major compound extracted from Chimonanthus nitens Oliv. leaf.
Chimonanthus nitens Oliv. leaf (CNOL), as a traditional Chinese medicine, has been widely used for the treatment of influenza and colds over a long history. However, the mechanism of colds related to the effects of CNOL have been little studied. In this study, the anticomplement and antitussive activities of different polarity extracts of CNOL were evaluated. Ethyl acetate extract (EAE) among different extracts not only significantly decreased cough times by 21-58% (P < 0.01), but also had anticomplement effects demonstrated by the CH50 values of 0.100 mg/ml. A total of 28 constituents (10 coumarins, 13 flavonoids and five phenolics) were identified in EAE based on the ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry technique. Eight compounds in EAE were evaluated by an ammonia-induced cough model to reveal the antitussive mechanisms and classical anticomplement pathway. The results indicated that the antitussive effects of scopoletin, kaempferol-3-O-rutinoside and kaempferol may depend on central mechanisms and that flavonoids such as compounds of kaempferol-3-O-rutinoside and kaempferol have better anticomplementary activity than coumarins like compounds of scopolin, scopoletin and isofraxidin. Taken together, kaempferol-3-O-rutinoside and kaempferol could be important chemical markers in the present study that might be used to evaluate the quality and biological activity of CNOL.


CT demonstration of a 5th ventricle--a finding to KO boxers?
The reported prevalence of 5th ventricles based on air studies varies from 1-12% and ranges up to 60% as an autopsy finding. The prevalence of what is usually an incidental anomaly has not been determined by computed tomography (CT). 5th ventricles are however known to be more common in brain damaged boxers and with the introduction of compulsory CT scanning for certain boxers it is necessary to know what significance to attach to the finding of a cavum in these individuals. To ascertain the prevalence and morphology of 5th ventricles as detected by CT in the population, a thousand consecutive scans were analysed for the presence or absence of a 5th ventricle and other associated midline developmental abnormalities and correlations made with any pathology found. A 5th ventricle was present in 5.5% of the group and in most cases was less than 3 mm wide. An apparent association with other pathology was found only in patients under the age of 15. A 6th ventricle was found in 0.5% while a cavum velum interpositum was present in 9.5%. The isolated finding of a small 5th ventricle on the CT scan of a young active boxer almost certainly represents a persistent congenital anomaly of no significance.


Assessment of endoscopic response using pan-enteric capsule endoscopy in Crohn's disease; the Sensitivity to Change (STOC) study.
The potential use of pan-enteric capsule endoscopy (pan-CE) to evaluate mucosal changes during treatment has not been evaluated. We aimed to assess the ability of pan-CE to measure changes in mucosal disease activity before and after starting biologic treatment in Crohn's disease patients. In this two-center prospective study, patients with clinical and biochemical signs of active Crohn's disease underwent pan-CE before and 8 to 12 weeks after treatment initiation with infliximab, adalimumab or vedolizumab. Endoscopic disease activity was assessed using the simple endoscopic score for Crohn's disease (SES-CD) and the Crohn's disease endoscopic index of severity (CDEIS), expanded with two segments (i.e., the jejunum and pre-terminal ileum). Occurrence of endoscopic remission (i.e., absence of ulcers) and endoscopic response (i.e., 50% decrease in SES-CD and CDEIS scores compared to baseline) was assessed and the standardized effect size was calculated. Twenty-two patients (50% females) completed the study. Endoscopic remission was observed in 6 out of 22 (27%) patients and 13/22 patients (59%) showed an endoscopic response for both the SES-CD and CDEIS score. Median SES-CD and CDEIS scores decreased from 16.0 (IQR 10.0 - 24.0) to 6.0 (IQR 2.8 - 12.0, p = .001) and from 7.1 (IQR 4.6 - 11.2) to 3.0 (IQR 0.9 - 6.0, p = .001), respectively. The standardized effect size was 1.44 and 1.24 for the SES-CD and CDEIS, respectively. No adverse events related to pan-CE were reported. Pan-CE was a useful technique to assess changes in mucosal disease activity in Crohn's disease patients.


Biotransformation of myrislignan by rat liver microsomes in vitro.
Myrislignan (1), erythro-(1R,2S)-2-(4-allyl-2,6-dimethoxyphenoxyl)-1-(4-hydroxy-3-methoxyphenyl) propan-1-ol, is a major acyclic neolignan in seeds of Myristica fragrans. Studies have suggested that myrislignan may deter feeding activity, but little is known about its metabolism. We investigated the biotransformation of myrislignan by rat liver microsomes in vitro. Seven metabolites were produced by liver microsomes from rats pre-treated with sodium phenobarbital. These were identified, using spectroscopic methods, as myrislignanometins A-G (2-8), respectively.


Stimulation of HeLa cell growth by physiological concentrations of 4-hydroxynonenal.
The aim of this study was to analyze the growth response of HeLa cells over a prolonged period of time to a single exposure of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids. Furthermore, the growth modulating effect of serum factors, particularly albumin, on the growth pattern was examined. The effects of HNE on the growth rate and viability of the cells, as well as on the incorporation of labelled amino acids were monitored daily over a period of four days. Fetal calf serum not only had a growth stimulating effect but also modulated the action of HNE. In neither respect was albumin able to substitute for serum indicating that the influence of serum was not exerted via an albumin-HNE conjugate. HNE had a clear dose-dependent effect and a distinction could be made between a supraphysiological concentration (100 microM), which was primarily cytotoxic and a physiological range (below 10 microM) which showed growth modulatory effects. These effects consisted of a transient inhibition in the initial phase of the cell growth, which under optimal conditions (in presence of serum) was followed by a period of increased proliferation, compared to untreated control cultures, until confluence was attained. It is suggested that HNE is not only a toxic product of lipid peroxidation, but a physiological growth regulating factor as well.


Calcium and Vitamin D in Obesity and Related Chronic Disease.
There is a pandemic of lifestyle-related diseases. In both developed and lesser developed countries of the world, an inadequacy of calcium intake and low vitamin D status is common. In this chapter, we explore a mechanistic framework that links calcium and vitamin D status to chronic conditions including obesity, systemic inflammation, endothelial dysfunction, dyslipidemia and cardiovascular disease, and type 2 diabetes mellitus. We also update the available clinical evidence, mainly from randomized controlled trials, to provide a synthesis of evidence in favor or against these hypotheses. There is consistent data to support calcium increasing whole body fat oxidation and increasing fecal fat excretion, while there is good cellular evidence for vitamin D reducing inflammation. Clinical trials support a marginal reduction in circulating lipids and some meta-analysis support an increase in insulin sensitivity following vitamin D. However, these mechanistic pathways and intermediate biomarkers of disease do not consistently transcribe into measurable health outcomes. Cementing the benefits of calcium and vitamin D for extraskeletal health needs a reexamination of the target 25(OH)D level to be achieved and the minimum duration of future trials.


Characteristics of South Korean Patients with Hereditary Transthyretin Amyloidosis.
This retrospective cross-sectional study included 18 patients from unrelated families harboring mutations of the transthyretin gene (TTR), and analyzed their characteristics and geographical distribution in South Korea. The included patients had a diagnosis of systemic amyloidosis, clinical symptoms, such as amyloid neuropathy or cardiomyopathy, and confirmation of a TTR gene mutation using genetic analysis recorded between April 1995 and November 2014. The mean age at disease onset was 49.6 years, and the mean disease duration from symptom onset to diagnosis was 3.67 years. Fifteen of the 18 patients were classified as mixed phenotype, 2 as the neurological phenotype, and only 1 patient as the cardiac phenotype. The most-common mutation pattern in South Korea was Asp38Ala, which was detected in eight patients. Thirteen patients reported their family hometowns, and five of the eight harboring the Asp38Ala mutation were from the Gyeongsang province in southeast Korea. The other eight patients exhibited a widespread geographical distribution. A particularly noteworthy finding was that the valine at position 30 (Val30Met) mutation, which was previously reported as the most-common TTR mutation worldwide and also the most common in the Japanese population, was not detected in the present South Korean patients. South Korean patients with hereditary TTR amyloidosis exhibited heterogeneous TTR genotypes and clinical phenotypes. The findings of this study suggest that the distribution of TTR amyloidosis in South Korea is due to de novo mutations and/or related to the other countries in East Asia.


USP-11 as a predictive and prognostic factor following neoadjuvant therapy in women with breast cancer.
USP-11, a member of the ubiquitin-specific protease family, has emerged as an essential regulator of double-strand break repair. Few studies have shown that silencing USP-11 led to hypersensitivity to poly(ADP-ribose) polymerase inhibition, ionizing radiation, and DNA-damaging agents. We sought to examine the predictive and prognostic relevance of USP-11 in patients treated with neoadjuvant systemic therapy (NST) for breast cancer. Fifty-six women who were treated with NST for breast cancer between 1999 and 2004 were included in the study. The Kaplan-Meier product-limit method was used to estimate disease-free survival and overall survival rates. Logistic regression models were fit to determine the associations between USP-11 status, pathological complete response (pCR), and survival. Sixteen patients (29%) had high-USP-11-expressing tumors, and 40 (71%) patients had low-USP-11-expressing tumors. No significant differences were observed in pCR rates with respect to USP-11 status. At a median follow-up of 7.4 years, 33 patients (59%) experienced a disease recurrence or death. Patients with high-USP-11-expressing tumors had a higher risk of recurrence (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.51-9.93; P = 0.005) and death (OR, 6.03; 95% CI, 2.00-18.17; P = 0.001) than those with low-USP-11-expressing tumors. Patients who did not achieve a pCR had an increased risk of recurrence (OR, 5.16; 95% CI, 1.16-23.07; P = 0.03). Our data indicate that USP-11 is not a predictor of a pCR after anthracycline-taxane-containing NST for breast cancer. Low USP-11 expression was independently correlated with better survival outcomes.


Dual-mode immunosensor based on Cu-doped Mo2C nanosheets as signal labels.
A method for detecting of Carcinoembryonic antigen(CEA) with improved accuracy is urgently needed. In this work, a dual-mode immunosensor for accurate detection of CEA was fabricated, which used a Cu-doped Mo2C co-catalyst as an enhancer. Especially, Cu-doped Mo2C presents a strong different pulse voltammetry (DPV) signal for the electron transfer between Cu2+ and Cu+, without the addition of K3[Fe(CN6)] and other electron transfer mediators, but also shows high electrocatalytic activity towards H2O2 redox reactions. So that detection sensitivity of the chronoamperometry (CA) was enhanced. Furthermore, characterized by excellent conductivity, highly ordered pore distribution and great surface area, Ti3C2 Mxenes can be effective in promoting electron transfer and loading a large number of AuNPs. In the meantime, AuNPs can also immobilize CEA-Ab1 through Au-N bonds. Based on a Cu-Mo2C-Au dual-signal indicator, Ti3C2 Mxene-Au as the matrix, the immunsosensor was developed to achieve dual-signal detection of CEA. Satisfactory detection ranges (1 fg.mL-1 to 40 ng.mL-1) were obtained with limits of detection of 0.33 fg.ml-1 (DPV) and 1.67 fg.ml-1 (CA), respectively. Therefore, the prepared electrochemical immunosensor has good application prospects for the detection of CEA.


Vitamin D status and glucose homeostasis in obese children and adolescents living in the tropics.
Pediatric obesity continues to rise and has become a major health problem worldwide. Vitamin D deficiency has been increasing among obese non-Asian children and is associated with abnormal glucose homeostasis in obese adults. However, data on the vitamin D status and its association with glucose homeostasis in obese children residing in tropical Asian countries are unavailable. To assess vitamin D status and glucose homeostasis in obese Thai children. A total of 150 obese, and 29 healthy non-obese children and adolescents were enrolled. Weight, height, body mass index (BMI) and waist circumference were obtained. All obese children underwent an oral glucose tolerance test with glucose and insulin measurements. Plasma 25-hydroxyvitamin D (25-OHD) and calciotropic blood chemistries were measured in all participants. Insulin sensitivity indices were calculated from the measured glucose and insulin levels. Approximately 25% of the obese children and adolescents had impaired glucose tolerance, impaired fasting plasma glucose (FPG) and diabetes. Seventeen out of 150 (11.3%) obese children and 3 out of 29 (10.3%) non-obese children had vitamin D deficiency, which was defined as a 25-OHD level of <50 nmol l(-1). Glucose tolerance and insulin sensitivity indices were comparable between obese children with sufficient vitamin D and those with vitamin D deficiency. There were no relationships among serum 25-OHD; weight, height, and BMI standard deviation scores; insulin sensitivity indices; FPG and insulin; and 2-h plasma glucose and insulin levels. Vitamin D deficiency is not as prevalent in obese Thai children as in obese non-Asian children from high-latitude countries. Adiposity per se is unlikely to be a determinant of vitamin D status in these obese individuals. There was no association between vitamin D deficiency and abnormal glucose homeostasis.


Knowledge and practice of COVID-19 prevention among community health workers in rural Cross River State, Nigeria: implications for disease control in Africa.
in developing countries, community health workers (CHWs) are essential, for provision of behaviour change communication towards prevention of coronavirus 2019 (COVID-19) infection at rural grassroots level. We aimed at assessing their level of knowledge and practice of preventive measures in a developing country setting. total enumeration of all CHWs in a rural local government area in southern Nigeria was carried out, using cross-sectional descriptive study design. Pretested self-administered 15-item questionnaire was used to assess knowledge of COVID-19 including basic epidemiology, virology, preventive measures and use of personal protective equipment (PPE). Practice of preventive measures was also assessed. Each correct response to knowledge question contributed one unit to the total score which was converted to percentage. Total knowledge score of 50% or greater was considered satisfactory. complete data was obtained from eighty-six (86) respondents with mean age of 36.3±8.9 years (18-54 years). Mean total knowledge score was 28.14±12.8% (6.7 to 53.3%), and 9.3% (n=8) had score of at least 50%. Correct responses to appropriate sequence of putting on and removing personal protective equipment (PPE) were 5.8% (n=5) and 8.1% (n=7), respectively. Regular practice of use of face masks, goggles, gloves, and hand hygiene was found to be 50% (n=43), 12.8% (n=11), 30.2% (n=26), and 56.4% (n=48), respectively. community health workers are grossly underprepared for provision of health education on COVID-19, due to their poor level of knowledge. Their capacity building through workshops and effective continuing education program are urgently needed.


β-Amyloid (Aβ) oligomers impair brain-derived neurotrophic factor retrograde trafficking by down-regulating ubiquitin C-terminal hydrolase, UCH-L1.
We previously found that BDNF-dependent retrograde trafficking is impaired in AD transgenic mouse neurons. Utilizing a novel microfluidic culture chamber, we demonstrate that Aβ oligomers compromise BDNF-mediated retrograde transport by impairing endosomal vesicle velocities, resulting in impaired downstream signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation. Our data suggest that a key mechanism mediating the deficit involves ubiquitin C-terminal hydrolase L1 (UCH-L1), a deubiquitinating enzyme that functions to regulate cellular ubiquitin. Aβ-induced deficits in BDNF trafficking and signaling are mimicked by LDN (an inhibitor of UCH-L1) and can be reversed by increasing cellular UCH-L1 levels, demonstrated here using a transducible TAT-UCH-L1 strategy. Finally, our data reveal that UCH-L1 mRNA levels are decreased in the hippocampi of AD brains. Taken together, our data implicate that UCH-L1 is important for regulating neurotrophin receptor sorting to signaling endosomes and supporting retrograde transport. Further, our results support the idea that in AD, Aβ may down-regulate UCH-L1 in the AD brain, which in turn impairs BDNF/TrkB-mediated retrograde signaling, compromising synaptic plasticity and neuronal survival.


Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B.
The protective role of pregnancy in autoimmune conditions, such as multiple sclerosis (MS), is potentially associated with immune regulation by sex hormones produced during pregnancy. This study was undertaken to examine the regulatory effects of estriol on the T cell functions, including transmigration and the cytokine production. The results revealed for the first time that estriol significantly inhibited T cell transmigration at a concentration range typical of pregnancy, which correlated with decreased T cell expression of matrix metalloproteinase-9. Estriol was also found to alter the cytokine profile of T cells toward Th2 phenotype by up-regulating the production of IL-10 and inhibiting TNFalpha secretion of T cells. However, the inhibitory effects of estriol on T cells were not antigen-dependent. Further characterization indicated that estriol inhibited nuclear transcription factor kappa B (NF-kappa B), which controls a variety of immune-related genes. This study provides new evidence that estriol is a potent regulator for the T cell functions potentially through its interaction with the NF-kappa B signaling pathway.


[Treatment with nebulized lidocaine in steroid-dependent asthma].
The management of glucocorticoid dependent and resistant asthma encompasses a group of problems, affecting as much control of clinical symptoms as the onset of adverse effects to prolonged use of steroids. Woman 52 years old, steroid dependent asthma fifteen years ago. She has important adverse effects in consequence of the use of systemic glucocorticoids. The employment of methotrexate attained decrease in the dosage of steroids temporarily. The worsening of the clinical situation and deterioration of secondary effects by use of steroids necessitated treatment with nebulized lidocaine. A 2% solution to initial dosage was administered three times daily. The maximal dosage needed was 80 mg three times daily. After three months of lidocaine treatment, the patient was able to reduce oral steroids eventually discontinuing these drugs, and the effects secondary to exogenous hypercortisolism disappeared. Moreover, an improvement in clinical symptoms and quality of life was observed with stability in the pulmonary function. The use of nebulized lidocaine could be useful and provide alternatives in patients with severe asthma.


Translation, adaptation, and preliminary validation of the Brazilian version of the Behavior Problems Inventory (BPI-01).
Children with atypical development often present behavior problems that impair their psychosocial adaptation. To describe the cultural adaptation to Brazilian Portuguese of the Behavior Problems Inventory (BPI-01), as well as preliminary indicators of instrument reliability and validity. The process involved translation, back-translation, and cultural adaptation of the instrument. Psychometric properties (reliability and validity) were assessed comparing scores obtained with the BPI-01, the Wechsler Intelligence Scales for Children and Adults, the Child Behavior Checklist for Ages 6-18 (CBCL/6-18), and the Autism Screening Questionnaire (ASQ). The sample comprised 60 children (30 typically developing and 30 atypically developing). The cultural adaptation process was considered adequate. Internal consistency of the BPI-01 was satisfactory, with a Cronbach's alpha of 0.65 for the self-injurious behavior scale, 0.82 for stereotyped behaviors, and 0.91 for aggressive/destructive behaviors. Considering a mean frequency of 0.5, the receiver operating characteristic (ROC) curve revealed 80% sensitivity and 3% specificity in the stereotyped behavior scale, 50 and 10% in aggressive/destructive behaviors, and 76 and 6% in self-injurious behaviors, respectively. Low-to-moderate correlations were observed between BPI-01, ASQ, and CBCL/6-18 scores. BPI-01 showed good psychometric properties, with satisfactory preliminary indicators of reliability, convergent validity, and sensitivity for the diagnosis of atypical development.


Fusobacterium necrophorum, a major provider of sinus thrombosis in acute mastoiditis: A retrospective multicentre paediatric study.
To evaluate in children the clinical severity and evolution of otogenic lateral sinus thrombosis (OLST) due to Fusobacterium necrophorum compared with other bacterial otogenic thrombosis and propose a specific management flowchart for Fusobacterium OLST. A retrospective multicentre cohort study. Four French ENT paediatric departments. A total of 260 under 18 years old admitted for acute mastoiditis were included. Initial imaging was reviewed to focus on complicated mastoiditis and 52 OLST were identified. Children were then divided into two groups according to bacteriological results: 28 in the "OLST Fusobacterium group" and 24 in the "OLST other bacteria group". There was a significant association between F necrophorum and OLST (P < .001). When compared to the OLST other bacteria group, children in the OLST Fusobacterium group were significantly younger (61 months vs 23 months, P < .01) and had a more severe clinical presentation: higher CRP (113 mg/L vs 175.7 mg/L, P = .02) and larger subperiosteal abscess (14 mm vs 21 mm, P < .01). Medical management was also more intensive in the OLST Fusobacterium group than in the OLST other bacteria group: increased number of conservative surgeries (66.7% vs 92.9%, P = .03) and longer hospital stay (13.7 days vs 19.8 days, P = .02). At the end of follow-up, the clinical course was good in both groups without any neurological sequelae. Thrombotic complications are very frequent in case of Fusobacterium mastoiditis and clinicians should be aware of the initial severity of the clinical presentation. Under appropriate management, the clinical course of Fusobacterium OLST is as good as that of other bacterial otogenic thrombosis.


Detection of low-molecular-weight polypeptides on nitrocellulose with monoclonal antibodies.
An immunoblotting method to detect low-molecular-weight peptides with monoclonal antibodies that normally fail to demonstrate immunoreactivity using conventional blotting techniques is described. Detection of neurophysin, insulin, calcitonin, vasopressin, and beta-endorphin electroblotted on nitrocellulose membranes was optimized after introducing four modifications into the conventional procedure. These include renaturing the gels after sodium dodecyl sulfate electrophoresis, electroblotting the renatured gels in basic transfer buffer, fixing and/or heating the blots, and using avidin/alkaline phosphatase conjugates for antigen/antibody detection. This technique likely enables the denatured peptides to regain their native conformation and, therefore, restores antigenicity and recognition by highly structural specific monoclonal antibodies. Although the most dramatic improvement with this technique is with monoclonal antibodies, a modest improvement in sensitivity can be obtained when immunoblots are probed with polyclonal antibodies. The high resolution of this system will be useful in probing blots of partial proteolytic digests of proteins with both monoclonal and polyclonal antibodies.


The Southwest Oncology Group experience: adjuvant therapy for stage IB and II non-seminomatous testicular cancer.
During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.


Enhanced Eye Velocity With Backup Saccades in vHIT Tests of a Menière Disease Patient: A Case Report.
Reduced eye velocity and overt or covert compensatory saccades during horizontal head impulse testing are the signs of reduced vestibular function. However, here we report the unusual case of a patient who had enhanced eye velocity during horizontal head impulses followed by a corrective saccade. We term this saccade a "backup saccade" because it acts to compensate for the gaze position error caused by the enhanced velocity (and enhanced VOR gain) and acts to return gaze directly to the fixation target as shown by eye position records. We distinguish backup saccades from overt or covert compensatory saccades or the anticompensatory quick eye movement (ACQEM) of Heuberger et al. (1) ACQEMs are anticompensatory in that they are in the same direction as head velocity and so, act to take gaze off the target and thus require later compensatory (overt) saccades to return gaze to the target. Neither of these responses were found in this patient. The patient here was diagnosed with unilateral definite Meniere's disease (MD) on the right and had enhanced VOR (gain of 1.17) for rightward head impulses followed by backup saccades. For leftwards head impulses eye velocity and VOR gain were in the normal range (VOR gain of 0.89). As further confirmation, testing with 1.84 Hz horizontal sinusoidal head movements in the visual-vestibular (VVOR) paradigm also showed these backup saccades for rightwards head turns but normal slow phase eye velocity responses without backup saccades for leftwards had turns. This evidence shows that backup saccades can be observed in some MD patients who show enhanced eye velocity responses during vHIT and that these backup saccades act to correct for gaze position error caused by the enhanced eye velocity during the head impulse and so have a compensatory effect on gaze stabilization.


A regulatory role of activated T-lymphocytes on human megakaryocytopoiesis in vitro.
Cellular interactions responsible for regulating in vitro megakaryocytopoiesis were studied using a microagar culture system which permits the simultaneous proliferation of human megakaryocytic progenitor cells (CFU-M) and T-lymphocytic colonies (CFU-TL). The proliferation of these colony types depends mainly on two factors: phytohaemagglutinin (PHA) and erythropoietin (EP). The direct addition of increasing PHA concentrations to the liquid overlayer resulted in a parallel increase of CFU-M and CFU-TL. If the T-lymphocytes were removed by an E-rosetting technique a marked diminution of CFU-M and CFU-TL numbers was observed. However, monocyte depletion resulted in a marked augmentation of CFU-M proliferation compared to unfractionated mononuclear cells. In order to confirm that the reduction of CFU-M proliferation observed after T-depletion was primarily mediated by the absence of T-lymphocytes, we have co-cultured different concentrations of previously removed autologous T-lymphocytes with a constant number of T-depleted bone marrow cells. A parallel increase of CFU-TL and CFU-M was found if 0.75 - 7.5 X 10(4) T-lymphocytes were added to the culture. In conclusion, our results indicate that activated T-lymphocytes augment proliferation of human bone marrow CFU-M and that monocytes are less important for the growth of megakaryocytic colonies.


Aminoterminal extension peptides from type I procollagen normalize excessive collagen synthesis of scleroderma fibroblasts.
Fibroblasts derived from a skin biopsy of a patient with scleroderma in the sclerotic stage were shown to have a higher rate of DNA synthesis, and to synthesize more collagen than fibroblasts from a healthy control. The addition of procollagen peptides to the culture medium of scleroderma fibroblasts almost normalized the collagen synthesis. This observation indicates that the mechanism for the regulation of collagen synthesis by feed back inhibition of prollagen peptides is functioning in this disease. It is suggested that the level of biologically active procollagen peptides is lowered.


Effect of the laryngeal tube on the no-flow-time in a simulated two rescuer basic life support setting with inexperienced users.
Intubation with a laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). LT insertion is easy; therefore, it may also be an alternative to bag-mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data from manikin studies support the influence of LT on no-flow-time (NFT) during ALS. We performed a prospective, randomized manikin study using a two-rescuer model to compare the effects of ventilation using a LT and BMV on NFT during BLS. Participants were trained in BMV and were inexperienced in the use of a LT. There was no significant difference in total NFT with the use of a LT and BMV (LT: mean 83.1 ± 37.3 s; BMV: mean 78.7 ± 24.5 s; p = 0.313), but we found significant differences in the progression of the scenario: in the BLS-scenario, the proportion of time spent performing chest compressions was higher when BMV was used compared to when a LT was used. The quality of chest compressions and the ventilation rate did not differ significantly between the two groups. The mean tidal volume and mean minute volume were significantly larger with the use of a LT compared with the use of BMV. In conclusion, in a two-rescuer BLS scenario, NFT is longer with the use of a LT (without prior training) than with the use of BMV (with prior training). The probable reasons for this result are higher tidal volumes with the use of a LT leading to longer interruptions without chest compressions.


Treatment for vestibular schwannoma: Systematic review and single arm meta-analysis.
Vestibular schwannoma is a benign tumor in the schwannoma cells of the 8th cranial nerve. It causes symptoms like tinnitus, vertigo and end up with loss of hearing so the appropriate treatment is very important. There are many treatment techniques including conservative, surgery and radiosurgery. We aimed to systematically review and single arm meta-analysis the different treatment techniques of vestibular schwannoma. A comprehensive literature search using thirteen databases including PubMed, Scopus, and Web of Science was performed. All clinical trials about treatment vestibular schwannoma were included and single arm meta-analyzed. We assessed the risk of bias using ROBIN-I's tool and scale of Council Australia's Cancer Guidelines Wiki. The protocol was registered in PROSPERO (CRD42018089784) and has been updated on 17 April 2019. A total of 35 clinical trials studies were included in the final analysis. The pooled proportion of stable hearing capability in patients receiving gamma knife radiosurgery (GKRS) was 64% (95% CI: 52%-74%). GKRS favored increased hearing capability 10% (95% CI: 7%-16%). Regarding tumor size, GKRS is the most protective method 53% (95% CI: 37%-69%). Complications occurred most commonly in single fractional linac stereotactic radiosurgery (SFSRT) 37% (95% CI: 12%-72%). Our analysis suggested gamma knife radiosurgery could be the most ideal treatment for vestibular schwannoma based on stabilizing hearing capability, increasing hearing capability, decreasing tumor size and complications.


Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells.
Thymic stromal lymphopoietin (TSLP) plays a critical role in allergic diseases such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease. Naringenin has various effects such as anti-atherogenic, anti-oxidant, and anti-inflammatory effects. However, the effect of naringenin on the production of TSLP has not been clarified. Thus, we investigated how naringenin inhibits the production of TSLP in the human mast cell line (HMC-1) cells. Naringenin inhibited the production and mRNA expression of TSLP in HMC-1 cells. The maximal inhibition rate of TSLP production by naringenin (100 μM) was 62.27 ± 10.79%. Naringenin also inhibited the nuclear factor-κB luciferase activity induced by phorbol myristate acetate plus A23187. In the activated HMC-1 cells, the activations of receptor-interacting protein (RIP)2 and caspase-1 were increased, whereas the activations of RIP2 and caspase-1 were decreased by pretreatment with naringenin. These results suggest that naringenin can be used to treat inflammatory and atopic diseases through the inhibition of TSLP.


Dynamics of microbial populations and diversity in NAPL contaminated peat soil under varying water table conditions.
Despite the risks that hydrocarbon contamination from pipeline leaks or train derailments impose on the health of peatlands in hydrocarbon production areas and transportation corridors, assessing the effect of such contaminations on the health and sustainability of peatlands has received little attention. This study investigates the impacts of hydrocarbons on peat microbial communities. Column experiments were conducted on non-aqueous phase liquid (NAPL) contaminated undisturbed peat core (0-35 cm) under static and fluctuating water table conditions. Water table fluctuations reduced residual NAPL saturation from 8.1-11.3% to 7.7-9.5%. Biodegradation of n-C8 and n-C12 along with oxidation of CH4 together produced high CO2 concentrations in the headspace. Clear patterns in dynamics in the microbial community structure were observed, with a more pronounced population growth. However, a significant loss of microbial richness was observed in contaminated columns. The result indicates that the phylum Proteobacteria benefited most from NAPL; however, their families differed between static and fluctuating water table conditions. This study established strong evidence that peat microbes and water table fluctuation can be an excellent tool for hydrocarbon removal and its control in peatlands.


Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania.
Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era. To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN. The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16-2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18-0.97). The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV.


Metabolic and pharmacodynamic tolerance to ethanol in rats.
The development of tolerance to ethanol was studied in rats fed nutritionally adequate liquid diets containing ethanol or sucrose for up to 5 weeks. Tolerance was shown to be due to both metabolic and pharmacodynamic factors. Tolerance began to develop after 3 days of ethanol intake, reached a plateau by 16 days and persisted for up to 22 days after stopping the ethanol intake. The rate of onset and decay of both components of tolerance was similar.


Indoor confinement and physical inactivity rather than the proportion of dry food are risk factors in the development of feline type 2 diabetes mellitus.
With domestication and urbanisation, cats have transformed from being hunting animals that eat protein-rich prey into more sedentary animals that eat a carbohydrate-rich diet. It was hypothesised that a high intake of dry cat food and a lack of physical activity may play a role in the development of feline type 2 diabetes mellitus. Information on dietary history and physical activity of 96 cats with diabetes mellitus and 192 matched controls was collected retrospectively, using a telephone questionnaire. Conditional logistic regression analysis was used to investigate the association between questionnaire-derived variables and the development of diabetes mellitus. The energy percentage of dry food in the diet was not significantly correlated with the development of diabetes mellitus (P=0.29), whereas both indoor confinement (P=0.002) and low physical activity (P=0.004) were. The results indicated that the proportion of dry food in a cat's diet may not be an independent risk factor for the development of type 2 diabetes mellitus, whereas physical inactivity and indoor confinement are.


[General anesthesia in rabbits for digestive surgical research. A spontaneous ventilation technic by Nembutal-diazepam combination].
General anesthesia in the rabbit in spontaneous ventilation, followed by normal awakening and prolonged survival, has been studied here in order to have a series of chronic preparations which the authors could use in their research on digestive surgery. These type of anesthesia requires less personnel, but raises certain difficulties due to the closeness of the thresholds of efficacy and toxicity, the length of the experiment and program requirements. The reliable technic exposed here permits prolonged anesthesia (up to eight hours) with normal survival of the animals. The mortality due to anesthesia was low.


Hydrothermal production and characterization of protein and amino acids from silk waste.
Non-catalytic hydrothermal decomposition of sericin and fibroin from silk waste into useful protein and amino acids was examined in a closed batch reactor at various temperatures, reaction times, and silk to water ratios to examine their effects on protein and amino acid yields. For the decomposition of sericin, the highest protein yield was found to be 0.466 mg protein/mg raw silk, obtained after 10 min hydrothermal reaction of silk waste at 1:100 silk to water ratio at 120 degrees C. The highest amino acid yield was found to be 0.203 mg amino acids/mg raw silk, obtained after 60 min of hydrothermal reaction of silk waste at 1:20 silk to water ratio at 160 degrees C. For the hydrothermal decomposition of fibroin, the highest protein yield was 0.455 mg protein/mg silk fibroin (1:100, 220 degrees C, 10 min) and that of amino acids was 0.755 mg amino acids/mg silk fibroin (1:50, 220 degrees C, 60 min). The rate of silk fibroin decomposition could be described by surface reaction kinetics. The soluble reaction products were freeze-dried to obtain sericin and fibroin particles, whose conformation and crystal structure of the particles were shown to differ from the original silk materials, particularly in the case of fibroin, in which the change from beta-sheet conformation to alpha-helix/random coil was observed.


Breast sarcoma. A case report and review of literature.
Breast sarcomas are rare with an annual incidence of 4.6 cases/1,000,000 women. They can appear as primary forms or secondary to radiation therapy or chronic lymphedema. A 41 year old woman attended our hospital after having noticed an increase in the size of her fibroadenoma. The examination revealed a 7cm retroareolar nodule. Breast sonography described a hypoechoic bilobulated lesion and MRI showed a large size polinodular image, suggesting a Phyllodes tumor. A core needle biopsy was performed with a histological result of low-grade fusiform cells sarcoma on Phyllodes tumor so we proceeded to surgical treatment with a mastectomy. After two years and a half she noticed a tough nodule over the mastectomy scar, which was resected with a histological result of fusiform cells sarcoma. Considering the diagnosis of recurrence of the disease, surgery was undertaken. Breast sarcoma is a rare but aggressive entity. Core biopsy is the procedure of choice for the diagnosis. Lymphatic spread is uncommon so nodal status in breast sarcoma is less informative. Staging study differs from other breast tumors and chest computed tomography is helpful since lungs are the predominant metastatic sites. The use of radiotherapy or chemotherapy is controversial and will depend on the risk of tumor recurrence. Surgery represents the only potentially curative therapy for breast sarcoma. Tumor size and adequate resection margin are the most important prognostic factors. Approximately 80% of recurrences appear in the first two years.


Thoracic organ transplantation and pregnancy outcomes: systematic review and meta-analysis.
Pre-conceptual comorbidities, an inherent risk of graft loss, rejection during pregnancy, and the postpartum period in women with thoracic lung transplant may predispose them to increased risk of adverse feto-maternal outcomes. The study aimed to systematically analyze and assess the risk of adverse pregnancy outcomes in women with thoracic organ transplant. MEDLINE, EMBASE, and Cochrane library were searched for publication between January 1990 and June 2020. Risk of bias was assessed using Joanna Briggs critical appraisal tool for case series. The primary outcomes included maternal mortality and pregnancy loss. The secondary outcomes were maternal complications, neonatal complications, and adverse birth outcomes. The analysis was performed using the DerSimonian-Laird random effects model. Eleven studies captured data from 275 parturient with thoracic organ transplant describing 400 pregnancies. The primary outcomes included maternal mortality {pooled incidence (95% confidence interval) 4.2 (2.5-7.1) at 1 year and 19.5 (15.3-24.5) during follow-up}. Pooled estimates yielded 10.1% (5.6-17.5) and 21.8% (10.9-38.8) risk of rejection and graft dysfunction during and after pregnancy, respectively. Although 67% (60.2-73.2) of pregnancies resulted in live birth, total pregnancy loss and neonatal death occurred in 33.5% (26.7-40.9) and 2.8% (1.4-5.6), respectively. Prematurity and low birth weight were reported in 45.1% (38.5-51.9) and 42.7% (32.8-53.2), respectively. Despite pregnancies resulting in nearly 2/3rd of live births, high incidence of pregnancy loss, prematurity and low birth weight remain a cause of concern. Focused pre-conceptual counseling to avoid unplanned pregnancy, especially in women with transplant-related organ dysfunctions and complications, is vital to improve pregnancy outcomes. CRD42020164020.


Diastolic wave initiating ventricular tachyarrhythmias and suppressible by lignocaine and isoprenaline.
A patient is described with ventricular tachycardia and premature beats (VPB) probably initiated by a diastolic wave, which--like the VPBs--could be eliminated by lignocaine and isoprenaline.


Knockdown of TNFAIP1 prevents di-(2-ethylhexyl) phthalate-induced neurotoxicity by activating CREB pathway.
Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer. It has neurotoxicity and exposure to it causes impairment of neurodevelopment, behavior and cognition. However, the molecular mechanisms responsible for the DEHP-induced neurotoxicity are not yet clearly defined. Tumor necrosis factor-induced protein 1 (TNFAIP1) was first discovered in umbilical vein endothelial cells and was further found to be important in the progress of Alzheimer's disease. Herein we explore the mechanism of TNFAIP1 in DEHP-induced neurotoxicity with the involvement of cyclic AMP response elements binding protein (CREB) signaling pathway in a mouse neuroblastoma cell line (N2a cells). We found that exposure to DEHP induced apoptosis and downregulated the expression of brain-derived neurotrophic factor (BDNF), synaptic proteins PSD 95 and synapsin-1 while upregulated the expression of TNFAIP1 and decreased the levels of phosphorylated Akt, CaMK Ⅳ, catalytic subunits of PKA and CREB in CREB signaling pathway. Knockdown of TNFAIP1 using TNFAIP1 small interfering RNA (siRNA) expression vector prevented DEHP from inhibiting CREB pathway, thus reduced apoptosis and restored expression of BDNF, PSD 95 and synapsin-1. Our data indicate that downregulation of TNFAIP1 prevents DEHP-induced neurotoxicity via activating CREB pathway. Therefore, TNFAIP1 is a potential target for relieving the DEHP-induced neurotoxicity and related neurological disorders.


Non-precocial grey-faced petrel chicks (Pterodroma macroptera gouldi) show no age-related variation in corticosterone responses to capture and handling.
Development patterns in birds range from precocial species, which hatch chicks largely capable of independent existence, to altricial species, chicks of which are highly dependent on their parents for extended periods. Previous work indicates precocial chicks have a robust corticosterone response from hatching whereas non-precocial and altricial chicks have a small response that increases through development. Grey-faced petrels are characteristic of most burrowing procellariiform seabirds with non-precocial chicks that are unable to locomote and are dependent on adults for food, although chicks have well developed downy plumage and can thermoregulate at or soon after hatching. Initial plasma corticosterone concentrations and corticosterone responses to handling were measured during development in semi-precocial grey-faced petrel (Pterodroma macroptera gouldi) chicks to determine whether they showed a precocial or altricial corticosterone response pattern. Chicks were sampled at six intervals through development from shortly after hatching until close to fledging. Mean corticosterone responses to handling after 30 min were high (115.9+/-10.7 ng/ml) from 2 to 4d after hatching and remained high throughout development (70-110 ng/ml). Contrary to expectations for non-precocial chicks, this pattern of corticosterone responses to handling indicates that grey-faced petrel chicks are able to perceive and respond to potential stressors from hatching, a response previously only demonstrated for precocial birds.


Extractable iron in experimental hematomas.
The extractable iron and total iron were determined in experimental, subcutaneous hematomas (5 ml blood) of rats after different periods of vital time. The extractable iron was determined from homogenate extract obtained after 24-h incubation with concentrated HCl diluted 1:3 and protein precipitation. For the determination of total iron, the specimens were wet-ashed. The same iron determinations were also made for the corresponding control specimens of the subcutaneous tissue. Extractable iron started to rise over the control values in 2-day-old hematomas, being about 5 times higher after 3 days, about 15 times higher after 7 days, and about 20 times higher after 14 days. The ratio of extractable iron and total iron expressed as percentages was about 1% in 1-h and in 1-day-old hematomas, about 20% in 3-day-old hematomas, about 50% in 7-day-old hematomas, and about 65% in 14-day-old or older hematomas. The effect of autolysis for 3 days at room temperature was studied on 1-h-old hematomas. Extractable iron values were slightly higher in the autolyzed specimens, but the difference was statistically insignificant as compared to specimens taken immediately after death.


Detection of feline immunodeficiency proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction.
Feline immunodeficiency virus (FIV) proviral DNA was detected by the polymerase chain reaction method (PCR). PCR products were detected by gel electrophoresis and ethidium bromide staining. The P-10, P-15 and P-24 regions of the gag gene of FIV were chosen as the target sequences for amplification, and three primer pairs were prepared. The PCR products subjected to amplification with each primer pair were found to possess sites of digestion by a restriction enzyme, as hypothesized. They did not react with feline leukemia virus (FeLV)-infected or feline syncytium-forming virus (FeSFV)-infected cell-derived DNA, and specifically amplified FIV-infected cell-derived DNA. FIV proviral DNA was detected by the PCR method with either primer pair (one-step amplification: single PCR) in DNA derived from peripheral blood lymphocytes (PBL) from 7 of 12 FIV antibody-positive cats. When PCR products in each of the 12 cats were subjected to a second amplification using the same primer pair (two-step amplification: double PCR), FIV proviral DNA was detected in all of the cats. When PBL samples collected from three cats that were negative and three that were positive in the single PCR were cultured for a few weeks in the presence of interleukin 2, FIV proviral DNA was detected in all six cats by the single PCR method. The results suggest that either the use of cultured PBL as the sample or the performance of the double PCR method enables simple and specific detection of FIV proviral DNA in PBL.


Efficacy and safety of embolization in iatrogenic traumatic uterine vascular malformations.
To retrospectively evaluate the efficacy of embolotherapy in patients with iatrogenic traumatic uterine arteriovenous malformations (AVMs). A retrospective review of all patients who underwent uterine arterial embolization in Peking Union Medical College Hospital between January 2000 and December 2010 was performed. Forty-two patients were diagnosed with a uterine vascular malformation. All patients had obstetric manipulations before. Serial beta-human chorionic gonadotropin (β-HCG) levels were measured to exclude gestational trophoblastic neoplasia. All patients underwent transcatheter embolization of bilateral uterine arteries. The complications, control of haemorrhage, and outcome of subsequent pregnancies were assessed. A total of 49 embolization procedures were performed in 42 patients. Seven patients required repeated embolizations for recurrence of bleeding. The technical success rate of embolization was 100%. Bleeding was controlled in 35 of 42 patients (83%) after the first embolization procedures, and bleeding was controlled in another two patients who underwent repeat embolization at a median follow-up of 29 months (range 3 months to 5 years). The overall clinical success rate was 88% (37/42). Thirteen patients subsequently became pregnant and eight of 13 patients had uneventful intrauterine pregnancies carried to term. Seven patients had post-embolization syndrome and no other complication occurred. Percutaneous embolotherapy is a safe and effective treatment for traumatic AVMs. Future pregnancy is still possible after embolization.


Intermittent cyclic mechanical compression promotes endplate chondrocytes degeneration by disturbing Nrf2/PINK1 signaling pathway-dependent mitophagy.
An abnormal mechanical load is a pivotal inducer of endplate cartilage degeneration, which subsequently promotes intervertebral disc degeneration. Our previous study indicated that intermittent cyclic mechanical compression (ICMC) promotes endplate chondrocyte degeneration, but the mechanism underlying this effect is unclear. In this study, we investigated PTEN-induced kinase 1(PINK1) dependent mitophagy during ICMC-induced endplate chondrocyte degeneration. Furthermore, we determined whether NF-E2-related factor 2 (Nrf2) activation correlated with PINK1-dependent mitophagy regulation and increased oxidation resistance of endplate chondrocytes under ICMC application. First, we generated a mechanical compression-induced endplate chondrocyte degeneration model in vitro and in vivo. ICMC was found to promote endplate chondrocyte extracellular matrix degradation. PINK1-mediated mitophagy was suppressed in the ICMC-stimulated endplate chondrocytes, while increased mitochondrial reactive oxygen species generation suggested that mitophagy is involved in the protective effect of mechanical strain on endplate chondrocytes. Moreover, Nrf2 expression, interaction with Kelch-like ECH-associated protein (Keap1), and nuclear translocation were inhibited by ICMC. Nrf2 overexpression inhibited reactive oxygen species production and reversed ICMC-induced endplate chondrocyte degeneration. Transfection with PINK1 shRNA abolished this effect and partially blocked Nrf2-induced mitophagy. Our findings suggested that ICMC could inhibit the Nrf2/PINK1 signaling pathway to reduce the mitophagy levels which significantly promote oxidative stress and thereby endplate chondrocyte degeneration. Therapeutic regulation of the Nrf2/PINK1 signaling pathway may be an efficient anabolic strategy for inhibiting this process.


Intraocular lens power calculation after refractive surgery.
To analyze the results of phacoemulsification cataract surgery in eyes that had had refractive surgery and to compare the predictability of various methods of intraocular lens (IOL) power calculation. Instituto de la Visión, Buenos Aires, Argentina. The study involved 7 cases that had phacoemulsification after radial keratotomy or laser in situ keratomileusis. The spherical equivalent (SE) and visual acuity were evaluated preoperatively and postoperatively to assess the changes before cataract development. The IOL power calculated with conventional keratometry (CK), adjusted keratometry, the clinical history method (CHM), corneal topography (CT), and the contact lens method (CLM) was compared with the final refractive and keratometric results measured with the BackCalcs (Holladay(R) IOL Consultant Program, Holladay Consulting, Inc.) to assess the accuracy and predictability of each method. The mean SE was -4.82 diopters (D) +/- 5.13 (SD) before phacoemulsification and +0.19 +/- 1.01 D after phacoemulsification, and the mean best corrected visual acuity was 0.39 +/- 0.07 (20/50) and 0.80 +/- 0.06 (20/25), respectively. Post-phacoemulsification refraction in cases with previous refractive surgery appeared to be predictable when the appropriate calculation method was applied. When all the data were available, the CHM provided the best results. Adjusted keratometry and CT seemed to be more accurate than CK and the CLM.


Gender differences in changes in and stability of conduct problems from early adolescence to early adulthood.
The present paper examines whether there are gender differences in changes in the aggregate level and individual stability of conduct problems from early adolescence to early adulthood. We analysed self-reported data collected as part of a longitudinal general population study of Norwegian adolescents (n = 1,234). The analyses showed that involvement in conduct problems for both genders peaked in mid-adolescence. The extent to which this peak reflected changes in the number of participants or differences in the frequency of problems among the participants varied according to gender. In most cases, the individual stability of involvement in conduct problems was similar for girls and boys. However, in the long term, relative involvement was more stable for boys than for girls. Moreover, the proportion of boys who showed a high level of involvement both during adolescence and early adulthood was greater than for girls.


The effect of glycerol on properties of chitosan/poly(vinyl alcohol) films with AlCl3·6H2O aqueous solution as the solvent for chitosan.
The AlCl3·6H2O aqueous solution was used to dissolve chitosan (CS) and the CS/poly(vinyl alcohol) (PVA) blend films were prepared at the absence of acetic acid. AlCl3·6H2O was retained in CS/PVA film and glycerol was added to form the complex plasticizer with AlCl3·6H2O. The effect of glycerol on the water sorption, crystalline, thermal and mechanical properties of AlCl3·6H2O doped CS/PVA film was studied by atomic force microscopy, X-ray diffraction, thermal gravity analysis and tensile testing, respectively. The experimental results showed that glycerol had a significant positive effect on the properties of AlCl3·6H2O doped CS/PVA films. With the synergism effect of AlCl3·6H2O and glycerol, the prepared CS/PVA films showed excellent mechanical properties. With the addition of 30wt% glycerol, the AlCl3·6H2O doped CS/PVA films behave the tensile strength of 39MPa and elongation at break of 120%, respectively.


Global reorganization of deep-sea circulation and carbon storage after the last ice age.
Using new and published marine fossil radiocarbon (14C/C) measurements, a tracer uniquely sensitive to circulation and air-sea gas exchange, we establish several benchmarks for Atlantic, Southern, and Pacific deep-sea circulation and ventilation since the last ice age. We find the most 14C-depleted water in glacial Pacific bottom depths, rather than the mid-depths as they are today, which is best explained by a slowdown in glacial deep-sea overturning in addition to a "flipped" glacial Pacific overturning configuration. These observations cannot be produced by changes in air-sea gas exchange alone, and they underscore the major role for changes in the overturning circulation for glacial deep-sea carbon storage in the vast Pacific abyss and the concomitant drawdown of atmospheric CO2.


A competitive enzyme-linked immunosorbent assay for quantification of tetrastatin in body fluids and tumor extracts.
Basement membrane collagens or derived fragments are measured in biological fluids such as blood and urine of patients and appear to be useful for diagnosis, prognostication, or treatment monitoring as proposed for endostatin, a fragment of collagen XVIII, or tumstatin, a fragment of collagen IV. Tetrastatin, the NC1 alpha 4 collagen IV domain, was previously reported to inhibit tumor growth and angiogenesis. The aim of this study was to develop and validate a method to measure tetrastatin concentrations in human fluids. We developed a competitive enzyme-linked immunosorbent assay (ELISA). It allowed measuring tetrastatin levels in human serum, bronchial aspiration and bronchoalveolar lavage fluids, and lung tissue extracts. The tetrastatin level was significantly higher in tumor tissues than in healthy lung tissues. Tetrastatin competitive ELISA could be useful to quantify tetrastatin in tissues and biological fluids for the diagnosis or prognostication of diseases in which basement membrane metabolism may be altered, especially tumor progression.


New species and new distributional records of the hygropetric water scavenger beetle genus Oocyclus Sharp (Coleoptera, Hydrophilidae) from the Brazilian Shield.
Nine new species of the water scavenger beetle genus Oocyclus Sharp, 1882 are described from the Brazilian Shield: O. ecolab sp. n., O. espinhacu sp. n., O. giganteus sp. n., O. humboldti sp. n., O. lacia sp. n., O. ovalis sp. n., O. sulcatus sp. n., O. thrixdiastematus sp. n., and O. thysanus sp. n. New locality records are provided for four species previously known from Brazil: O. rotundus Clarkson Short, 2012, O. pilosus Jordo, Clarkon Ferreira-Jr, 2018, O. xanthus Clarkson Short, 2012 and O. yubai Clarkson Short, 2012. All species are associated with rock-face seepages such as wet rocks, waterfalls, and seepages. An updated key to the Brazilian species of Oocyclus is provided.


Chronic subdural haematoma and arachnoid cyst in autosomal dominant polycystic kidney disease (ADPKD).
We present the unusual association between chronic subdural haematoma (CSDH), intracranial arachnoid cyst and autosomal dominant polycystic kidney disease (ADPKD) in a 27-year-old man. CSDH is a documented complication of intracranial arachnoid cyst, the incidence of which is increased in patients with ADPKD. Awareness of this association may lead to earlier diagnosis of ADPKD and treatment of its systemic complications, including renal insufficiency, systemic hypertension and previously unsuspected intracranial saccular aneurysm. Surgery for CSDH associated with intracranial arachnoid cyst may be complicated by over-drainage of cerebrospinal fluid due to communication between the cyst and the cisternal subarachnoid space, as illustrated in the present case, and the development of epidural haemorrhage.


Phospholipase A and lysophospholipase activity of the epidermis.
Phospholipase A and lysophospholipase activities have been demonstrated in cow snout epidermis. The phospholipase A activity was dependent on Ca2+ ions and the pH for optimum activity was between 6-1 and 7-4.


Therapeutic modalities and novel approaches in regenerative medicine for COVID-19.
The recent coronavirus disease 2019 outbreak around the world has had an enormous impact on the global health burden, threatening the lives of many individuals, and has had severe socio-economic consequences. Many pharmaceutical and biotechnology companies have commenced intensive research on different therapeutic strategies, from repurposed antiviral drugs to vaccines and monoclonal antibodies to prevent the spread of the disease and treat infected patients. Among the various strategies, advanced therapeutic approaches including cell- and gene-editing-based therapeutics are also being investigated, and initial results in in-vitro and early phase I studies have been promising. However, further assessments are required. This article reviews the underlying mechanisms for the pathogenesis of severe acute respiratory syndrome coronavirus-2, and discusses available therapeutic candidates and advanced modalities that are being evaluated in in-vitro/in-vivo models and are of note in clinical trials.


Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with clozapine solid oral 100-mg tablets after multiple doses in patients with schizophrenia.
This study compared the bioequivalence of FazaClo (clozapine orally disintegrating tablets) 100 mg to Clozaril (clozapine standard oral tablets) 100 mg after multiple doses in patients with schizophrenia. This was a randomized, open-label, multiple-dose study in which patients with schizophrenia received FazaClo or Clozaril 100 mg twice daily for 5 days before crossing over to the alternate therapy. Blood samples were obtained at regular intervals during and after the completion of treatment, and standard pharmacokinetic parameters were calculated. Safety and patient satisfaction with FazaClo were also assessed. Thirty-six patients were enrolled, of whom 33 completed the study and 30 were included in the steady-state analyses. All pharmacokinetic parameters for clozapine and desmethylclozapine (the major metabolite of clozapine) were similar between FazaClo and Clozaril in both the completer and steady-state populations. Geometric mean values for steady-state maximum and minimum concentrations and area under the plasma concentration-time curve for FazaClo were all within 95-105% of those for Clozarilwell within the range considered by the US FDA as acceptable for bioequivalence (80-125%). Patients also expressed a high level of satisfaction with the FazaClo orally disintegrating tablet formulation. FazaClo produced pharmacokinetic profiles almost identical to those of Clozaril. This should provide clinicians with reassurance that patients who receive FazaClo will achieve plasma drug concentrations similar to those produced by the same daily dose of Clozaril, and that no cross-titration is necessary when switching from one of these clozapine formulations to the other.


Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer.
In 50-60 per cent of patients who undergo hepatic resection for metastasis of colorectal cancer the first site of tumour recurrence is extrahepatic, indicating the presence of more extensive disease at the time of resection. The aim of this study was to evaluate whether the presence of disseminated tumour cells in blood and bone marrow could predict extrahepatic tumour recurrence. Cytokeratin 20 (CK20) reverse transcriptase-polymerase chain reaction was used to study the presence of tumour cells in preoperative peripheral blood and bone marrow samples from 41 patients with liver metastasis scheduled for surgical resection. CK20 expression was detected in six of 41 peripheral blood samples and in eight of 32 bone marrow samples. There was no correlation between CK20-positive samples and subsequent extrahepatic recurrence. Positive blood samples did, however, correlate with high serum carcinoembryonic antigen level and large tumour volume. None of the 14 patients previously treated with chemotherapy had CK20-positive samples, whereas six of 27 blood and eight of 20 bone marrow samples were positive in the chemotherapy-naive group. Although the number of patients in this study is limited, the presence of disseminated tumour cells did not predict subsequent extrahepatic recurrence. The results strongly suggest that the presence of circulating tumour cells in peripheral blood may reflect transient shedding of tumour cells related to large tumour volume.


The MTT Assay: A Method for Error Minimization and Interpretation in Measuring Cytotoxicity and Estimating Cell Viability.
The MTT assay is extensively used, most often to infer a measure of cytotoxicity of treatments to cells. As with any assay though, there are a number of limitations. The method described here is designed with consideration of how the MTT assay fundamentally works to account for, or at least identify, confounding factors in measurements. It also provides a decision-making framework to best interpret and complement the MTT assay to apply it as either a measure of metabolic activity or cell viability.


Mitotic ER exit site dynamics: insights into blockade of secretion from the ER during mitosis.
How ER exit sites disassemble during mitosis is not well understood. Transport ANd Golgi Organization 1 (TANGO1, also known as MIA3), a cargo receptor originally identified for collagens, acts as a hub for ER exit site disassembly under the control of Casein Kinase 1 (CK1)-mediated phosphorylation and Protein Phosphatase 1 (PP1)-mediated dephosphorylation. Impaired dephosphorylation during mitosis induces ER exit site disassembly.


International air travel attitude and travel planning lead times across 45 countries in response to the COVID-19 pandemic.
This paper explores global differences in travel risk perception based on i) attitudes towards travel abroad, and ii) the time required to plan travel. Baseline data from 2019 is compared with data from 2020, the first year of the COVID-19 pandemic. A methodology based on Big Data is developed through the Skyscanner metasearch engine, working with 20,756 million flight searches and 1979 million flight picks worldwide. We conduct an exploratory analysis by region, followed by a cluster analysis of 45 countries. We argue that the findings respond to uncertainty avoidance, with clear differences between Europe, America and Asia-Pacific. This knowledge has marketing implications for tourist destinations in terms of what marketing messages to convey and the best time to introduce marketing campaigns for each country or group of countries, so that the opportunity for reactivation of tourism is maximised.


Community-based participatory research with Latino community members: horizonte Latino.
As the demographic makeup of the United States undergoes rapid transformation, the importance of studying ethnic and cultural variations between and within population subgroups becomes increasingly clear. Researchers must challenge themselves to move beyond simply matching their methodology to the research question at hand and seek out methods that are compatible with the culture, language, traditions, and particular life circumstances of the cultural group under study. Community-based participatory research is collaborative and includes community members as participants in the research process, which ensures the cultural and community specificity of the research. This article demonstrates how experiential learning of community members as research participants provided culturally grounded insights used in grant writing. The experiences and involvement of the community researchers shaped the research questions and provided the major conceptual basis in response to a National Institutes of Health Request for Applications.


Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components and Binding Proteins.
Fetal blood and plasma volume and binding components are critical parameters in a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of their changes during fetal development has not been reported. The objective of this work was to collate and analyze physiological information on fetal blood and plasma volume and binding component data during development and to provide a mathematical description of these parameters that can be integrated within a fetal physiologically based pharmacokinetic model. A comprehensive literature search was conducted on fetal blood and plasma volume and binding component parameters and their changes during growth from apparently healthy fetuses from uncomplicated pregnancies. Collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing their growth trends with fetal age and weight. Data were available from 14 studies for blood, ten studies for hematocrit, 12 studies for albumin, and four studies for alpha-1-acid glycoprotein, while plasma and red blood cell volumes were described based on blood and hematocrit data. Fetal physiologically based pharmacokinetic parameters, including blood, plasma and red blood cell volumes, hematocrit, serum albumin, and acid glycoprotein were quantified as a function of fetal age and weight. Variability around the mean parameters at different fetal ages was also investigated. The growth of each of these parameters was different (with respect to direction and monotonicity). Despite the limitations identified in the availability of some values, the collected data presented in this article provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications include predicting xenobiotic exposure and risk assessment in the fetus following maternally administered drugs or unintended exposure to environmental toxicants.


Integrating practice guidelines with financial incentives.
Practice guidelines, in whatever form, hold significant implications for the delivery and the financing of health care. Hence, great care must be taken in developing them. They must be scientifically sound and thus defensible. They must incorporate clinical perspectives and consider patients' preferences. They must cover appropriate as well as inappropriate services. They must foster creation and adoption of a rational payment system. What guidelines, in their best form, can do is enable physicians, faced with an overwhelming array of often conflicting information, to reduce some of the uncertainty they must cope with and to practice the most clinically effective medicine. For physicians to do so requires valid information from a credible source, most often in conjunction with appropriate financial incentives.


Perpetuation of immunological memory: role of serum antibodies and accessory cells.
A self-sustaining mechanism for perpetuation of immunological memory is proposed which requires the involvement of idiotypic-anti-idiotypic antibody immune-complexes, antigen-presenting cells and follicular dendritic cells, but not long-lived memory cells or persisting antigens.


Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor.
The selectively outbred alcohol-non-tolerant (ANT) rat line is highly susceptible to impairment of postural reflexes by benzodiazepine agonists such as diazepam. ANT cerebella are generally devoid of diazepam-insensitive high-affinity binding of the benzodiazepine [3H]Ro15-4513, whereas in non-selected strains such binding marks a granule-cell-specific GABAA (gamma-aminobutyric acid) receptor containing the alpha 6 subunit. A critical determinant for diazepam insensitivity of this 'wild-type' cerebellar GABAA receptor is an arginine residue in alpha 6 position 100, where other alpha subunits carry a histidine. Here we report that the alpha 6 gene of ANT rats is expressed at wild-type levels but carries a point mutation generating an arginine-to-glutamine substitution at position 100. In consequence, alpha 6(Q100)beta 2 gamma 2 receptors show diazepam-mediated potentiation of GABA-activated currents and diazepam-sensitive binding of [3H]Ro15-4513. Our results suggest that cerebellar motor control may be a distinct behavioural correlate of the alpha 6-subunit-containing GABAA receptor subtype.


Scaffold hopping identifies 6,8-disubstituted purines as novel anaplastic lymphoma kinase inhibitors.
Rearrangements of anaplastic lymphoma kinase (ALK) are associated with several cancer diseases. Due to resistance development against existing ALK-inhibitors, new, structurally unrelated inhibitors are required. By a scaffold hopping strategy, 6,8-disubstituted purines were designed as analogues of similar ALK-inhibiting thieno[3,2-d]pyrimidines. While the new title compounds indeed inhibited ALK and several ALK mutants in submicromolar concentrations, they retained poor water solubility.


A first step quantification by correlation techniques of the variability in some time intervals measured on the Politecnico/Ca' Granda VCG Database On Young Normal Subjects.
The unevident variability during a 30-min period on intervals measured once every cardiac cycle was investigated by correlation techniques implemented on a digital computer, on normal healthy subjects from the "Politecnico/Ca' Granda VCG Database On Young Normal Subjects". Our most important conclusions are as follows: Generally each time series, related to the many interval values measured, shows that its variability is different from that of the R-R intervals. In particular Bazzett's formula, which provides the widely used "corrected QT interval", has to be amended.


Nuchal cord management and nurse-midwifery practice.
Nuchal cord, or cord around the neck of an infant at birth, is a common finding that has implications for labor, management at birth, and subsequent neonatal status. A nuchal cord occurs in 20% to 30% of births. All obstetric providers need to learn management techniques to handle the birth of an infant with a nuchal cord. Management of a nuchal cord can vary from clamping the cord immediately after the birth of the head and before the shoulders to not clamping at all, depending on the provider's learned practices. Evidence for specific management techniques is lacking. Cutting the umbilical cord before birth is an intervention that has been associated with hypovolemia, anemia, shock, hypoxic-ischemic encephalopathy, and cerebral palsy. This article proposes use of the somersault maneuver followed by delayed cord clamping for management of nuchal cord at birth and presents a new rationale based on the available current evidence.


Osteoclasts in bone modeling, as revealed by in vivo imaging, are essential for organogenesis in fish.
Bone modeling is the central system controlling the formation of bone including bone growth and shape in early development, in which bone is continuously resorbed by osteoclasts and formed by osteoblasts. However, this system has not been well documented, because it is difficult to trace osteoclasts and osteoblasts in vivo during development. Here we showed the important role of osteoclasts in organogenesis by establishing osteoclast-specific transgenic medaka lines and by using a zebrafish osteoclast-deficient line. Using in vivo imaging of osteoclasts in the transgenic medaka carrying an enhanced GFP (EGFP) or DsRed reporter gene driven by the medaka TRAP (Tartrate-Resistant Acid Phosphatase) or Cathepsin K promoter, respectively, we examined the maturation and migration of osteoclasts. Our results showed that mononuclear or multinucleated osteoclasts in the vertebral body were specifically localized at the inside of the neural and hemal arches, but not at the vertebral centrum. Furthermore, transmission electron microscopic (TEM) analyses revealed that osteoclasts were flat-shaped multinucleated cells, suggesting that osteoclasts initially differentiate from TRAP-positive mononuclear cells residing around bone. The zebrafish panther mutant lacks a functional c-fms (receptor for macrophage colony-stimulating factor) gene crucial for osteoclast proliferation and differentiation and thus has a low number of osteoclasts. Analysis of this mutant revealed deformities in both its neural and hemal arches, which resulted in abnormal development of the neural tube and blood vessels located inside these arches. Our results provide the first demonstration that bone resorption during bone modeling is essential for proper development of neural and vascular systems associated with fish vertebrae.


(R)-2-Cyano-N-(1-phenyl-eth-yl)acetamide.
In the title compound, C11H12N2O, the dihedral angle between the acetamide group and the benzene ring is 68.7 (1)°. In the crystal, N-H⋯O and weak C-H⋯O hydrogen bonds link the mol-ecules into chains along the a-axis direction.


A dimethoxynaphthalene derivative (RS-43179 gel) compared with 0.025% fluocinolone acetonide gel in the treatment of psoriasis.
Thirty patients were entered into a double-blind trial comparing a dimethoxynaphthalene derivative (RS-43179 gel) and fluocinolone acetonide (Synalar gel) in the treatment of psoriasis. The two preparations were applied three times daily for 4 weeks, and the patients were assessed at weeks 1, 2, 3, 4, 7 and 9. No significant differences between the two preparations could be detected. By the end of the 4-week treatment period, the number of patients showing a 'Good, Excellent or Clear' therapeutic response was 25 out of 28 after RS-43179 treatment and 26 out of 28 after Synalar treatment. Four patients experienced irritation on the side treated with RS-43179. In two of these patients the reaction was severe and the treatment was discontinued, but in the other two patients, the local irritation was only moderate. No other adverse reactions were seen.


α-Helices propagating from stable nucleators exhibit unconventional thermal folding.
Although the effect of thermal perturbations on protein structure has long been modeled in helical peptides, several details, such as the relation between the thermal stabilities of the propagating and nucleating segments of helices, remain elusive. We had earlier reported on the helix-nucleating propensities of covalent H-bond surrogate-constrained α-turns. Here, we analyze the thermal stabilities of helices that propagate along peptides appended to these α-helix nucleators using their NMR and far-UV CD spectra. Unconventional thermal folding of these helix models reveals that the helical fold in propagating backbones resists thermal perturbations as long as their nucleating template is intact. The threshold temperature of such resistance is also influenced by the extent of similarity between the natures of helical folds in the nucleating and propagating segments. Correlations between helicities and rigidities of helix-nucleating and helix-propagating segments reveal subtle interdependence, which explains cooperativity and residual helix formation during protein folding.


Vaccinia virus proteins on the plasma membranes of infected cells. II. Expression of viral antigens and killing of infected cells by vaccinia virus-specific cytotoxic T cells.
Evidence is presented that virion-derived antigens as well as viral antigens expressed on cell surfaces after infection, may participate in the formation of "target-antigen complexes" (TACs) which render vaccinia virus-infected cells susceptible to recognition and killing by syngeneic, vaccinia virus-specific cytotoxic T cells (VV-CTLs). By employing L cells infected with trypsin-treated and untreated virions, evidence was obtained that proteins with molecular weights of 32K and 37K may be among the virion-derived antigens which participate in TAC formation. Following virus infection, a sequential expression of virus-specified antigens on the plasma membrane of infected cells could be detected. At 1 hr p.i., polypeptides with molecular weights of 48K-50K and 36K-37K were present on infected cell surfaces; by 2 hr p.i., polypeptides with molecular weights of 48K-50K, 42K-44K, 36K-37K, 29K-30K, and 16K-17K were detected on plasma membranes. As measured by in vitro, 51Cr-release assays, vaccinia virus-infected L cells were completely susceptible to lysis by VV-CTLs (greater than or equal to 50% measured specific lysis) when (a) "early" but not late viral functions were expressed as measured with virus-infected cells which had been treated with hydroxyurea (5 X 10(-3) M) to block DNA replication or (b) when active protein synthesis was allowed to proceed for 90 min postadsorption and the infected cells were then treated with cycloheximide (100 micrograms/ml) to block further protein synthesis. Under these experimental conditions, polypeptides with molecular weights of 58K, 48K-50K, 42K, 36K-37K, 34K, 32K-33K, 27K-29K, and 16K-17K were expressed on the plasma membranes of vaccinia virus-infected cells but not uninfected cells. Whether each of the virion-derived and (or) virus-encoded polypeptides can associate with Class I, major histocompatibility antigens on the surfaces of virus-infected cells to form a primary or cross-reacting TAC recognized by VV-CTLs remains to be investigated.


Effect of a combined education and eHealth programme on the control of oral anticoagulation patients (PORTALS study): a parallel cohort design in Dutch primary care.
To analyse the effect on therapeutic control and self-management skills of the implementation of self-management programmes, including eHealth by e-learning versus group training. Primary Care Thrombosis Service Center. Of the 247 oral anticoagulation therapy (OAT) patients, 63 started self-management by e-learning, 74 self-management by group training and 110 received usual care. Parallel cohort design with two randomised self-management groups (e-learning and group training) and a group receiving usual care. The effect of implementation of self-management on time in therapeutic range (TTR) was analysed with multilevel linear regression modelling. Usage of a supporting eHealth platform and the impact on self-efficacy (Generalised Self-Efficacy Scale (GSES)) and education level were analysed with linear regression analysis. After intervention, TTR was measured in three time periods of 6 months. (1) TTR, severe complications,(2) usage of an eHealth platform,(3) GSES, education level. Analysis showed no significant differences in TTR between the three time periods (p=0.520), the three groups (p=0.460) or the groups over time (p=0.263). Comparison of e-learning and group training showed no significant differences in TTR between the time periods (p=0.614), the groups (p=0.460) or the groups over time (p=0.263). No association was found between GSES and TTR (p=0.717) or education level and TTR (p=0.107). No significant difference was found between the self-management groups in usage of the platform (0-6 months p=0.571; 6-12 months p=0.866; 12-18 months p=0.260). The percentage of complications was low in all groups (3.2%; 1.4%; 0%). No differences were found between OAT patients trained by e-learning or by a group course regarding therapeutic control (TTR) and usage of a supporting eHealth platform. The TTR was similar in self-management and regular care patients. With adequate e-learning or group training, self-management seems safe and reliable for a selected proportion of motivated vitamin K antagonist patients. NTR3947.


Measuring the hidden burden of violence: use of explicit and proxy codes in Minnesota injury hospitalizations, 2004-2014.
Commonly-used violence surveillance systems are biased towards certain populations due to overreporting or over-scrutinized. Hospital discharge data may offer a more representative view of violence, through use of proxy codes, i.e. diagnosis of injuries correlated with violence. The goals of this paper are to compare the trends in violence in Minnesota, and associations of county-level demographic characteristics with violence rates, measured through explicitly diagnosed violence and proxy codes. It is an exploration of how certain sub-populations are overrepresented in traditional surveillance systems. Using Minnesota hospital discharge data linked with census data from 2004 to 2014, this study examined the distribution and time trends of explicit, proxy, and combined (proxy and explicit) codes for child abuse, intimate partner violence (IPV), and elder abuse. The associations between county-level risk factors (e.g., poverty) and county violence rates were estimated using negative binomial regression models with generalized estimation equations to account for clustering over time. The main finding was that the patterns of county-level violence differed depending on whether one used explicit or proxy codes. In particular, explicit codes suggested that child abuse and IPV trends were flat or decreased slightly from 2004 to 2014, while proxy codes suggested the opposite. Elder abuse increased during this timeframe for both explicit and proxy codes, but more dramatically when using proxy codes. In regard to the associations between county level characteristics and each violence subtype, previously identified county-level risk factors were more strongly related to explicitly-identified violence than to proxy-identified violence. Given the larger number of proxy-identified cases as compared with explicit-identified violence cases, the trends and associations of combined codes align more closely with proxy codes, especially for elder abuse and IPV. Violence surveillance utilizing hospital discharge data, and particularly proxy codes, may add important information that traditional surveillance misses. Most importantly, explicit and proxy codes indicate different associations with county sociodemographic characteristics. Future research should examine hospital discharge data for violence identification to validate proxy codes that can be utilized to help to identify the hidden burden of violence.


CB-Fake: A multimodal deep learning framework for automatic fake news detection using capsule neural network and BERT.
The progressive growth of today's digital world has made news spread exponentially faster on social media platforms like Twitter, Facebook, and Weibo. Unverified news is often disseminated in the form of multimedia content like text, picture, audio, or video. The dissemination of such false news deceives the public and leads to protests and creates troubles for the public and the government. Hence, it is essential to verify the authenticity of the news at an early stage before sharing it with the public. Earlier fake news detection (FND) approaches combined textual and visual features, but the semantic correlations between words were not addressed and many informative visual features were lost. To address this issue, an automated fake news detection system is proposed, which fuses textual and visual features to create a multimodal feature vector with high information content. The proposed work incorporates the bidirectional encoder representations from transformers (BERT) model to extract the textual features, which preserves the semantic relationships between words. Unlike the convolutional neural network (CNN), the proposed capsule neural network (CapsNet) model captures the most informative visual features from an image. These features are combined to obtain a richer data representation that helps to determine whether the news is fake or real. We investigated the performance of our model against different baselines using two publicly accessible datasets, Politifact and Gossipcop. Our proposed model achieves significantly better classification accuracy of 93% and 92% for the Politifact and Gossipcop datasets, respectively, compared to 84.6% and 85.6% for the SpotFake+ model.


Automated identification of diabetic type 2 subjects with and without neuropathy using wavelet transform on pedobarograph.
Diabetes is a disorder of metabolism-the way our bodies use digested food for growth and energy. The most common form of diabetes is Type 2 diabetes. Abnormal plantar pressures are considered to play a major role in the pathologies of neuropathic ulcers in the diabetic foot. The purpose of this study was to examine the plantar pressure distribution in normal, diabetic Type 2 with and without neuropathy subjects. Foot scans were obtained using the F-scan (Tekscan USA) pressure measurement system. Various discrete wavelet coefficients were evaluated from the foot images. These extracted parameters were extracted using the discrete wavelet transform (DWT) and presented to the Gaussian mixture model (GMM) and a four-layer feed forward neural network for classification. We demonstrated a sensitivity of 100% and a specificity of more than 85% for the classifiers.


[Food consumption and nutritional adequacy in Brazilian children: a systematic review].
To perform a review of studies of food consumption and nutritional adaptation in Brazilian infants pointing the main findings and limitations of these studies. The articles were selected from Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (Latin-American and Caribbean Literature in Health Sciences), Scientific Electronic Library Online (SciELO) and Science Direct in Portuguese and in English. The descriptors were: "food consumption", "nutritional requirements", "infant nutrition" and "child". The articles selected were read by two evaluators that decided upon their inclusion. The following were excluded: studies about children with pathologies; studies that approached only food practices or those adaptation of the food groups or the food offert; and studies that did not utilize the Dietary Reference Intakes (DRI). Were selected 16 studies published between 2003 and 2013. In the evaluation of the energy consumption, four studies presented energetic consumption above the individual necessities. The prevalence of micronutrients inadequacy ranged from 0.4% to 65% for iron, from 20% to 59.5% for vitamin A, from 20% to 99.4% for zinc, from 12.6% to 48.9% for calcium and from 9.6% 96.6% for vitamin C. The food consumption of Brazilian infants is characterized by high frequencies of inadequacy of micronutrients consumption, mainly iron, vitamin A and zinc. These inadequacies do not exist only as deficiencies, but also as excesses, as noted for energetic consumption.