Isolation of Francisella tularensis and Yersinia pestis from Blood Cultures by Plasma Purification and Immunomagnetic Separation Accelerates Antibiotic Susceptibility Determination.
The early symptoms of tularemia and plague, which are caused by Francisella tularensis and Yersinia pestis infection, respectively, are common to other illnesses, resulting in a low index of suspicion among clinicians. Moreover, because these diseases can be treated only with antibiotics, rapid isolation of the bacteria and antibiotic susceptibility testing (AST) are preferable. Blood cultures of patients may serve as a source for bacteria isolation. However, due to the slow growth rates of F. tularensis and Y. pestis on solid media, isolation by plating blood culture samples on proper agar plates may require several days. Thus, improving the isolation procedure prior to antibiotic susceptibility determination is a major clinically relevant need. In this study, we developed a rapid, selective procedure for the isolation of F. tularensis and Y. pestis from blood cultures. We examined drop-plating and plasma purification followed by immunomagnetic separation (IMS) as alternative isolation methods. We determined that replacing the classical isolation method with drop-plating is advantageous with respect to time at the expense of specificity. Hence, we also examined isolation by IMS. Sub-localization of F. tularensis within blood cultures of infected mice has revealed that the majority of the bacteria are located within the extracellular fraction, in the plasma. Y. pestis also resides within the plasma. Therefore, the plasma fraction was isolated from blood cultures and subjected to an IMS procedure using polyclonal anti-F. tularensis live vaccine strain (LVS) or anti-Y. pestis antibodies conjugated to 50-nm nano-beads. The time required to reach an inoculum of sufficient bacteria for AST was shortest when using the plasma and IMSs for both bacteria, saving up to 2 days of incubation for F. tularensis and 1 day for Y. pestis. Our isolation procedure provides a proof of concept for the clinical relevance of rapid isolation for AST from F. tularensis- and Y. pestis-infected patients.


Immunogenicity of a monovalent influenza A(H1N1)pdm09 vaccine in patients with hematological malignancies.
Patients with hematological malignancies have high risk for morbidity and mortality from influenza. This study was conducted to evaluate the immunogenicity and reactogenicity of an influenza A(H1N1)pdm09 vaccine among such subjects. Fifty subjects were vaccinated twice during the 2009-2010 season. The antibody response was expressed in terms of mean fold rise (MFR) of geometric mean titer, seroresponse proportion (sR), and seroprotection proportion (sP). The first vaccination induced only a small response, and additional antibody was acquired after the second dose (MFR 2.3 and 3.9, sR 32% and 54%, and sP 30% and 48% after the first and the second vaccination, respectively). Rituximab treatment showed an especially inhibitory effect (MFR 1.3, sR 9% and sP 0%). When analyzed using logistic regression models, only rituximab was found to have an independent effect; the adjusted odds ratio for sR was 0.09 (P = 0.05). Influenza vaccination of patients with hematological malignancies resulted in adepuate response, and the second vaccination induced additional antibody. It is therefore recommended to vaccinate this group twice.


Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy.
Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.


Molecular signature associated with bone marrow micrometastasis in human breast cancer.
Metastasis is the leading cause of cancer-related death, and bone marrow (BM) is a prominent metastatic site in solid tumors. Here, we focused on the onset of metastasis, using BM as an indicator organ for micrometastatic tumor cells in breast cancer patients without overt metastases (tumor-node-metastasis stage M(0)). Expression analysis with cDNA arrays showed distinct profiles between primary tumors from BM-positive and BM-negative patients. The differentially expressed genes are involved in extracellular matrix remodeling, adhesion, cytoskeleton plasticity, and signal transduction (in particular RAS and hypoxia-inducible factor 1alpha pathway). The BM signature was mainly characterized by transcriptional repression and different from the expression signature associated with lymphatic metastasis. Thus, BM micrometastasis is a selective process with a specific molecular signature of the primary tumor.


Fibrin immobilization vestibular extension (FIVE): A case series.
The objective of the present case series is to report on the rationale, surgical technique and outcome of a protocol for peri-implant mucosal phenotype modification therapy, referred to as "fibrin immobilization vestibular extension (FIVE)". The protocol utilized entailed apical positioning and stabilization of peri-implant flap with modular screws. The screws were also used for the immobilization of solid matrix platelet-rich fibrin to fill the gap created between apically positioned flap and the crestal margin of the flap. A total of 30 patients (12 male, 18 females) with 93 implants were treated with FIVE protocol for various indications, including for vestibular extension following alveolar ridge augmentation (N = 6), preprosthetic (N = 9), postprosthetic (N = 2), and peri-implantitis (N = 13). The keratinized mucosal width preoperatively was 1.67 mm with 95% confidence interval [CI] (1.46, 1.88). Immediately following FIVE surgery, the vestibule was extended to 9.10 with 95% CI (8.44, 9.76). At 3 months, 4.9 mm (95% CI: 4.5-5.2 mm) of peri-implant keratinized mucosal width was present. The keratinized mucosal width remained relatively stable thereafter and was 4.0 mm (95% CI: 3.5-4.5 mm) at 3 years post-FIVE surgery. When overall group means across all time points were analyzed, maxilla had mean of 6.1 mm (95% CI: 5.8-6.5) versus mandible exhibited mean of 5.1 mm (95% CI: 4.6-5.6 mm). The mean of maxilla was significantly higher than that of the mandible (p < 0.0001) across all time points. Treatment of peri-implantitis with FIVE lead to significant pocket reduction and wide band of keratinized mucosa. Seven of 38 implants in 3 of 13 peri-implantitis patients were removed due to advanced peri-implantitis. The present case series provides proof-of-principle data for efficacy of FIVE for peri-implant phenotype modification therapy that generated attached keratinized mucosa in a variety of applications. This protocol provides an alternative to procedures involving harvesting of autogenous mucosal graft.


Acoustic Radiation Force Impulse Imaging in Benign and Malignant Breast Lesions.
Elastography is a promising way to assess tissue differences regarding stiffness or elasticity, which has been historically assessed manually by palpation. Combined with conventional imaging modalities, shear wave elastography can potentially evaluate the stiffness of a breast lesion and consequently help detect malignant breast tumor from benign ones. The aim of this study was to evaluate the diagnostic role of shear wave elastography in breast lesions in the Indian population. Fifty patients presenting with breast lesions were included in the study. All the patients were subjected to B-mode ultrasound and elastography using shear wave with Virtual Touch Imaging (VTITM) (Siemens Medical Solutions USA, Inc., PA, USA) and Virtual Touch Quantification (VTQTM) (Siemens Medical Solutions USA, Inc., PA, USA) and the obtained data was analyzed using an appropriate statistical test (independent samples t-test). In our study group of 50 patients, 34 were benign and 16 were malignant. VTITM showed a sensitivity of 97% and a specificity of 93% with a positive predictive value (PPV) of 97% for benign lesions. VTITM showed a sensitivity of 87.5 % and a specificity of 100% with a PPV of 100% for malignant lesions. VTQTM showed a sensitivity of 71.4% and a specificity of 100% with a PPV of 100% for benign lesions. VTQTM showed a sensitivity of 100% and a specificity of 100% with a PPV of 76.6% for malignant lesions. VTITM was more reliable as a diagnostic tool compared to VTQTM in benign lesions and both are equally reliable in identifying malignant lesions. Acoustic radiation force impulse (ARFI) plays a significant role as an adjuvant diagnostic tool to B-mode imaging for assessing breast lesions.


[Pan-European survey on the undertreatment of hypercholesterolemia in hypolipidemias(Luxembourg)].
Cepheus (Centralized Pan-European survey on the undertreatment of hypercholesterolemia) is an observational centralized study realized in 8 European countries including Luxemburg. The aim was to evaluate the percentage of patients reaching the TJETF and 2004 NCEP ATP III recommendations for LDL-cholesterol. A secondary aim was to identify by questionnaires the determinants of patients and physicians explaining this undertreatment. Data from 706 patients in Luxemburg have shown that only 40.6% of patients and only 17.5% of high risk patients (CVD and diabetes) reach the newest european target values of LDL-cholesterol (post-hoc analysis). 90% of patients had statins prescribed and 9.7% fibrates. 60% of patients had still the same medication at the same dosage at the moment of the study, after at least 3 months treatment with a mean of 6.2 years. 40% of patients said that they forget sometimes their treatment and 13% were convinced that forgetting their tablets more than once a week did not affect their cholesterol level. These disappointing results could be due partly to insufficient dosages, too less adaptation of the treatment and a bad compliance of patients.


Making Use of Plant uORFs to Control Transgene Translation in Response to Pathogen Attack.
Reducing crop loss to diseases is urgently needed to meet increasing food production challenges caused by the expanding world population and the negative impact of climate change on crop productivity. Disease-resistant crops can be created by expressing endogenous or exogenous genes of interest through transgenic technology. Nevertheless, enhanced resistance by overexpressing resistance-produced genes often results in adverse developmental affects. Upstream open reading frames (uORFs) are translational control elements located in the 5' untranslated region (UTR) of eukaryotic mRNAs and may repress the translation of downstream genes. To investigate the function of three uORFs from the 5'-UTR of ACCELERATED CELL 11 (uORFsACD11), we develop a fluorescent reporter system and find uORFsACD11 function in repressing downstream gene translation. Individual or simultaneous mutations of the three uORFsACD11 lead to repression of downstream translation efficiency at different levels. Importantly, uORFsACD11-mediated translational inhibition is impaired upon recognition of pathogen attack of plant leaves. When coupled with the PATHOGENESIS-RELATED GENE 1 (PR1) promoter, the uORFsACD11 cassettes can upregulate accumulation of Arabidopsis thaliana LECTIN RECEPTOR KINASE-VI.2 (AtLecRK-VI.2) during pathogen attack and enhance plant resistance to Phytophthora capsici. These findings indicate that the uORFsACD11 cassettes can be a useful toolkit that enables a high level of protein expression during pathogen attack, while for ensuring lower levels of protein expression at normal conditions.


What Does It Mean for Something to Be "Scientific"? Community Understandings of Science, Educational Attainment, and Community Representation Among a Sample of 25 CBPR Projects.
Community-based participatory research (CBPR) seeks to conduct relevant, sustainable research that is tailored to the needs of the communities with which it is engaged through equitable collaboration between community representatives and professional researchers. Like other participatory approaches to research and planning, CBPR has been criticized for the potential to engage a biased sample of community representatives and, thereby, undermine the fundamental purpose of the approach. Moreover, the varying educational levels and areas of expertise, especially regarding science literacy, among those participating in CBPR has raised concern about the ability for true collaboration to exist within CBPR projects. This article presents findings from a qualitative study of 25 CBPR research projects and explores matters of science literacy, community representation, and the nature of CBPR. Ultimately, it is suggested that those who engage in CBPR should carefully consider the potential for biased community representation and seek to purposely and mindfully avoid any partiality.


MULTINDELS-BOV: Zebu traceback method based on DNA insertion-deletion polymorphisms.
Brazil is a major producer and exporter of beef, with a herd of approximately 210 million animals. For the meat industry, a reliable animal traceback from its origin to the consumer market is paramount. Of all available identification systems, DNA is the only one that survives the slaughterhouse and reaches the dish of the consumer. DNA polymorphisms are already used for cattle traceback, but primarily for the subspecies Bos taurus taurus. However, in Brazil, another subspecies, B. taurus indicus predominates. We describe here the development of a DNA traceback method designed primarily for B. taurus indicus (Zebu), without leaving B. taurus taurus aside. We used insertion/deletion (indel) polymorphisms, which have the advantage of being simple and easily automatable, since in most cases, the variable loci are biallelic. We studied 94 indels, with a difference of two or more base pairs, in DNA pools of 60 Zebu and 60 taurine animals. A set of 22 indels with heterozygosity greater than 0.3 were selected and used to construct two multiplex PCRs. On the basis of the allelic frequency of these indels, the probability of random match was calculated to be 1.12 x 10(-8) for B. taurus indicus and 1.60 x 10(-6) for B. taurus taurus. Moreover, we estimated that an analysis would cost less than US$15.00 per animal. Thus, this system (MULTINDELS-BOV) is perfectly suited for building large genetic databases and offering viable prospects of a national system for cattle traceback DNA in Brazil.


Accelerated cholesterol synthesis in the monocytes of young myocardial infarction survivors.
The substantial role of monocytes in atherogenesis has been demonstrated recently. The feedback regulation of endogenous cholesterol synthesis in monocytes of young myocardial infarction survivors was determined and compared to that of age- and sex-matched controls. The cholesterol synthesis in monocytes of one half of patients was three times higher compared to that of controls whereas the other half showed a rate within the range of controls.


FCE 23884, substrate-dependent interaction with the dopaminergic system. II. Preclinical biochemical studies.
The effects of FCE 23884 [4-(9,10-didehydro-6-methylergolin-8 beta-yl) methyl-piperazine-2,6-dione] were examined using a variety of biochemical methods. In vitro assays showed that FCE 23884 bound to D-2, alpha-2 and 5-hydroxytryptamine1A sites with Ki values of 6.5, 4.0 and 4.0 nM, respectively. The affinity for D-1 and S-2 receptors was moderate (submicromolar range) and slight or negligible for alpha-1, cholinergic and sigma receptors. In normal rats, FCE 23884 accelerated markedly dopamine (DA) turnover in the neostriatum and nucleus accumbens as indicated by the increased ratios of dihydroxphenyl acetic acid/DA and homovanillic acid/DA. The compound enhanced DA synthesis and utilization rate. After gamma-butyrolactone treatment, a model to study DA autoreceptors function, FCE 23884 almost antagonized completely the gamma-butyrolactone reversal induced by apomorphine on l-dihydroxyphenylalanine accumulation in the two brain areas. In addition, FCE 23884 induced a rapid 20-fold increase of serum prolactin confirming its DA antagonistic profile in normal rats. In contrast with these antidopaminergic properties, FCE 23884 consistently stimulated basal adenylate cyclase activity in vitro (ED50 = 0.6 microM) and elicited a rapid increase of cyclic AMP formation in the neostriatum of normal (35%) and reserpinized (82%) rats in vivo. Furthermore in this last condition both the DA turnover and synthesis rate in the neostriatum and nucleus accumbens decreased after treatment with FCE 23884. These neurochemical data support the behavioral studies indicating that FCE 23884 possesses mixed DA antagonist and agonist properties depending on the experimental conditions, the distinguishing factor being presence or absence of DA.(ABSTRACT TRUNCATED AT 250 WORDS)


Cross-Reactive T Cell Immunity to Dengue and Zika Viruses: New Insights Into Vaccine Development.
Dengue virus (DENV) is a member of the Flavivirus family that includes Zika virus (ZIKV), West Nile virus, Japanese encephalitis virus, and yellow fever virus. As the most prevalent of the flaviviruses, DENV is responsible for tens of millions of infections each year. The clinical manifestations of infection with one of the four DENV serotypes (DENV1-4) range from no symptoms to hemorrhagic fever and shock ("severe dengue"), which is fatal in ~25,000 patients annually. Many factors contribute to the development of severe dengue, including the DENV serotype and host expression of certain HLA alleles; however, it now seems clear that pre-existing immunity to DENV-and possibly other flaviviruses-is a major precipitating factor. While primary infection with one DENV serotype elicits strong cellular and humoral immune responses that likely confer long-lived protection against the same serotype, subsequent infection with a different serotype carries an increased risk of developing severe dengue. Thus, primary DENV infection elicits cross-reactive immunity that may be protective or pathogenic, depending on the context of the subsequent infection. Many flaviviruses share high sequence homology, raising the possibility that cross-reactive immunity to one virus may contribute to protection against or pathogenesis of a second virus in a similar manner. In addition, several flaviviruses are now endemic in overlapping geographic regions, underscoring the need to gain more knowledge about the mechanisms underlying cross-reactive immunity to different DENV serotypes and flaviviruses. Here, we review our current understanding of T cell immunity to DENV, focusing on cross-reactivity with other serotypes and flaviviruses such as ZIKV, and the role of DENV-elicited CD4+ and CD8+ T cells in protection. Recent work in this area supports a beneficial role for cross-reactive T cells and provides new insights into the design of safe and efficient flavivirus/pan-flavivirus vaccines.


Separation of three chromones from Saposhnikovia divaricata using macroporous resins followed by preparative high-performance liquid chromatography.
Prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside are three major chromone derivatives of Saposhnikovia divaricata that have many pharmacological activities, such as anti-inflammatory and antitumor activities. In the present work, an effective method for the simultaneous separation of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside with high purities was established using HPD-300 resin coupled with preparative high-performance liquid chromatography. The adsorption kinetics curves of the three compounds on the HPD-300 resin were studied and found to fit well according to the pseudo-second-order equation. The adsorption isotherm results indicated that the adsorption process of the three compounds was exothermic. After a one-run treatment with the resin, the contents of prim-O-glucosylcimifugin, cimifugin, and 5-O-methylvisamminoside increased from 0.29, 0.06, and 0.37% to 13.07, 2.83, and 16.91% with recovery yields of 76.38, 78.25, and 76.73%, respectively. Finally, the purities of the three compounds were found to reach more than 95% after further separation using preparative high-performance liquid chromatography. The method developed in this study was effective and could simultaneously separate three chromones from Saposhnikovia divaricate. The experimental results also showed that the HPD-300 resin is suitable for the separation of chromone derivatives.


[Endoscopic ligation in treatment and prevention of bleeding from esophageal varices].
To demonstrate the efficacy of endoscopic ligation in treatment and prevention of bleeding from esophageal varices in patients with liver cirrhosis and portal hypertension. We performed a retrospective analysis of 338 patients with liver cirrhosis who underwent ligation for the period 2009 - May 2016. There were 209 (61.8%) men and 129 (38.2%) women. In this group 511 ligations were performed. The total number of ligated nodes was 4086. Ligation was effective in 502 (98.2%) cases. In 9 (1.8%) cases endoscopic ligation was ineffective and Blackmore tube was required. The main cause of failed procedure was pre- or intraoperative active bleeding from esophageal varices. Complications in this group can be considered 3 cases of bleeding during ligation. Endoscopic ligation is highly effective (from an economic and medical points of view) treatment and prevention of bleeding from esophageal varices in patients with liver cirrhosis.


Predictors of condom use behaviour among male street labourers in urban Vietnam using a modified Information-Motivation-Behavioral Skills (IMB) model.
HIV risk in vulnerable groups such as itinerant male street labourers is often examined via a focus on individual determinants. This study provides a test of a modified Information-Motivation-Behavioral Skills (IMB) model to predict condom use behaviour among male street workers in urban Vietnam. In a cross-sectional survey using a social mapping technique, 450 male street labourers from 13 districts of Hanoi, Vietnam were recruited and interviewed. Collected data were first examined for completeness; structural equation modelling was then employed to test the model fit. Condoms were used inconsistently by many of these men, and usage varied in relation to a number of factors. A modified IMB model had a better fit than the original IMB model in predicting condom use behaviour. This modified model accounted for 49% of the variance, versus 10% by the original version. In the modified model, the influence of psychosocial factors was moderately high, whilst the influence of HIV prevention information, motivation and perceived behavioural skills was moderately low, explaining in part the limited level of condom use behaviour. This study provides insights into social factors that should be taken into account in public health planning to promote safer sexual behaviour among Asian male street labourers.


Anti-human cytomegalovirus activity of constituents from Sasa albo-marginata (Kumazasa in Japan).
Effective new anti-human cytomegalovirus (HCMV) agents and regimens need to be developed. We examined the anti-HCMV properties of crude extract (True World Extract of Bambuseae sasa [TWEBS]) and five compounds (p-coumaric acid, 3-hydroxy-4-methoxybenzaldehyde [vanillin], p-hydroxybenzaldehyde, 3-hydroxypyridine and 4',5,7-trihydroxy-3',5'-dimethoxyflavone [tricin]), isolated from Sasa albo-marginata, a bamboo known in Japan as Sasa. Among TWEBS and five compounds screened in a plaque reduction assay, four showed anti-HCMV activity in the MRC-5 human embryonic fibroblast cell line. The anti-HCMV mechanisms of the TWEBS was examined by western blot analysis using primary antibody specific for an immediate early (IE) antigen of HCMV, for a structural late antigen of HCMV and for beta-actin. Treatment of cells with > or = 0.001% of TWEBS inhibited the observable cytopathic effects of HCMV on infected cells. Western blot analysis demonstrated that TWEBS decreased the expression of IE antigen and late antigen of HCMV in the infected cells. Next, we examined the anti-HCMV properties of five compounds isolated from TWEBS. In a viral plaque reduction assay, tricin showed dose-dependent inhibitory properties with a 50% effective concentration of 0.17 microg/ml (selective index = 1,205.8). The hot water extract (TWEBS) of Sasa albo-marginata, with tricin isolated from it, has anti-HCMV activity in MRC-5 cells. TWEBS and/or tricin are a novel compound with potential anti-HCMV activity. Future studies should evaluate these findings in vivo.


Audiological findings in cleft lip and palate children attending speech camp.
To determine the audiological status in children with clef lip and palate attending at speech camp. The present study was performed in children with cleft lip and palate attending speech camp. 14 children with cleft lip and/or palate registered in the speech camp for 4 days. All subjects had undergone otoscopic examination, hearing evaluation and speech and language assessment. Only 12 children performed the complete hearing evaluation. 16 of 23 ears had very slight hearing loss and most of them were found in children with unilateral cleft lip and palate. The air conduction thresholds ranged from 16.36 to 25.91 dB across the frequencies on the right ear and 10 to 23.18 dB on the left ear. The average pure tone thresholds showed a rising slope configuration of audiogram. The minimal hearing loss probably impacted on speech and language problems. Children with cleft lip and palate need early detection and intervention of hearing impairment.


Left Atrial Appendage Closure During Coronary Bypass Surgery in Patients on Hemodialysis.
Patients with end-stage renal disease on hemodialysis (ESRD-HD) have a lifelong risk of atrial fibrillation-related stroke. We compared clinical outcomes in ESRD-HD patients undergoing coronary artery bypass grafting (CABG) with and without concomitant left atrial appendage (LAA) closure.Methods and Results: Of 2,783 consecutive patients undergoing isolated CABG between 2002 and 2020, 242 patients had ESRD-HD with sinus rhythm. The primary outcome was a composite of death and stroke. An inverse probability (IP)-weighted cohort was created based on the propensity score. The 2 IP-weighted groups had well-balanced baseline and surgical backgrounds, with an equivalent follow-up. Five-year stroke-free survival was significantly higher in patients with LAA closure (log-rank test, P=0.035). The adjusted hazard ratio of LAA closure for death and stroke was 0.43 (95% confidence interval [CI] 0.20-0.92; P=0.023). Competing risk analysis showed that LAA closure was significantly associated with a risk reduction of stroke (subhazard ratio 0.26; 95% CI 0.08-0.96; P=0.028). No significant difference was observed in adjusted risk ratios for reoperation for bleeding, new atrial fibrillation, 30-day mortality, and readmission for heart failure. Concomitant LAA closure during CABG can reduce the risk of death and stroke in ESRD-HD patients with normal sinus rhythm.


Late complications and shape changes of the endografts after gigantic thoracic aortic aneurysm repair over a 7-year follow-up.
This report details a 7 years follow up observations in a 71-year-old patient treated with custom made endograft for gigantic thoracic aortic aneurysm (TAA). Progressive changes of the thoracic aorta and aneurysm after endograft placement led to two late complications including proximal stent graft prolapse into the aneurysm and extreme kinking of the endograft and aorta 28 and 51 months after treatment, respectively. Both complications were successfully treated with new endografts placement. Percutaneous endovascular repair is a promising, minimally invasive alternative to exclude TAA. This technique allows long-term treatment of patients who are unsuitable for conventional surgical procedures.


TGF-β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes.
The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH. Here, we introduce transforming growth factor beta (TGF-β) as a novel regulator of NBCe1 transcription and functional expression. Using hippocampal slices and primary hippocampal and cortical astrocyte cultures, we investigated regulation of NBCe1 and elucidated the underlying signaling pathways by RT-PCR, immunoblotting, immunofluorescence, intracellular H(+ ) recording using the H(+ ) -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, mink lung epithelial cell (MLEC) assay, and chromatin immunoprecipitation. Activation of TGF-β signaling significantly upregulated transcript, protein, and surface expression of NBCe1. These effects were TGF-β receptor-mediated and suppressed following inhibition of JNK and Smad signaling. Moreover, 4-aminopyridine (4AP)-dependent NBCe1 regulation requires TGF-β. TGF-β increased the rate and amplitude of intracellular H+ changes upon challenging NBCe1 in wild-type astrocytes but not in cortical astrocytes from Slc4a4-deficient mice. A Smad4 binding sequence was identified in the NBCe1 promoter and Smad4 binding increased after activation of TGF-β signaling. The data show for the first time that NBCe1 is a direct target of TGF-β/Smad4 signaling. Through activation of the canonical pathway TGF-β acts directly on NBCe1 by binding of Smad4 to the NBCe1 promoter and regulating its transcription, followed by increased protein expression and transport activity.


Medical literature search practice in paediatric junior medical staff: a questionnaire survey.
With increasing medical knowledge and emphasis upon evidence-based medicine, it is essential for practitioners to have optimal literature searching skills. There are limited data regarding the use of online information retrieval (IR) systems by paediatric junior medical officers (JMO). The aims of this questionnaire-based study of a group of JMO were to assess the accessibility, frequency of use and preferences for electronic information resources, and to ascertain their perceived adequacy of training and expertise in online searching. Questionnaires were distributed to 319 JMO at two Australian children's hospitals. A total of 106 questionnaires were returned (33.2% response rate). Twenty-four-hour access to electronic medical databases was available to almost 90% of respondents at work or home. Five or less online searches per month were performed by 53.7% of respondents. Previous formal training in database searching was reported by 72.4% of respondents, but over half felt it had been inadequate. Most JMO (91.5%) acknowledged a need for further training in search skills. In spite of widespread availability of online resources, use of these resources was sub-optimal in this group of trainee doctors. Most respondents reported a need for further training in electronic searching. Continuing targeted education in electronic database searching is required to ensure that future doctors develop skills to ensure optimal use of medical literature.


Pain intensity and psychological distress show different associations with interference and lack of life control: A clinical registry-based cohort study of >40,000 chronic pain patients from SQRP.
Both chronic pain and depressive and/or anxiety symptoms are associated with negative impacts on daily living, including interference and lack of life control. However, little is known about how pain and psychological distress affect these impacts. The first aim was to assess how pain intensity, psychological distress, and social support interact with interference and lack of life control. A second aim was to investigate whether the strength of these relationships is moderated by the presence or absence of depression and/or anxiety. Patient-Reported Outcome Measures (PROMs), which are available in the Swedish Quality Registry for Pain Rehabilitation (SQRP), were retrieved for patients with chronic pain (N = 40,184). A theoretical model with the constructs/latent variables pain intensity, psychological distress, interference, lack of life control, and social support was proposed and analyzed using Partial Least Squares Structural Equation Modelling (PLS-SEM). Indicators for these constructs were identified from the PROMs of the SQRP. Two models of the total cohort, which differed with respect to the causal relationship between pain intensity and psychological distress, were investigated. The moderating effects of anxiety and/or depression were also analyzed. Relatively low correlation and explanatory power (R 2 = 0.16) were found for the pain intensity-psychological distress relationship. Pain intensity had a stronger effect on interference than on lack of life control. The reverse was found for psychological distress - i.e., psychological distress seemed to have a higher negative influence on function than on interference. The underlying assumption of the causal relationship between pain intensity and psychological distress determined how strong pain intensity and psychological distress influenced interference and lack of life control. Social support showed very similar absolute significant correlations with interference and lack of life control. Interference and lack of life control showed relatively weak associations. The psychological distress level was a moderating factor for several of the paths investigated. A clinical treatment consequence of the low correlation between pain intensity and psychological distress may be that clinically treating one may not reduce the effect of the other. The relative importance of pain intensity and psychological distress on interference and lack of life control depends on the underlying assumption concerning the pain intensity-psychological distress relationship. Interference and lack of life control showed relatively weak associations, underscoring the need to clinically assess them separately. Social support influenced both impact constructs investigated. The cohort display heterogeneity and thus presence of definite signs of anxiety and/or depression or not was a moderating factor for several of the associations (paths) investigated. The results are important both for the assessments and the design of treatments for patients with chronic pain.


A unilateral twin extrauterine pregnancy occurring in a solitary fallopian tube: therapeutic choices.
A unilateral twin tubal pregnancy occurring in a solitary fallopian tube is presented. The gynecological history was notable for a previous extrauterine pregnancy in the contralateral fallopian tube and reconstructive surgery to the ipsilateral one. Radical total salpingectomy was performed. The rationale for this management is discussed and different therapeutic alternatives presented.


[Drug-resistant epilepsy treated with ketogenic diet].
A 4-year old girl affected by intractable seizures was treated with ketogenic diet. The diet was calculated to provide appropriate protein intake for growth (1.4 g/kg body weight) and adequate calories (1600 kcal) derived from 4 parts fat and 1 part protein + carbohydrates. The child remained on the diet for 8 months and had a decrease in seizure frequency of 90%. No serious side effects were reported and it was possible to discontinue or decrease antiepileptic drugs. Our results confirm the efficacy of ketogenic diet in the treatment of epilepsy. Since it is known that 20 to 30% of all patients with epilepsy do not have their seizures completely controlled with established antiepileptic drugs, it would be useful to increase the application of this dietetic treatment in selected patients in Italy as it already happens in other countries.


Three-dimensional optoacoustic reconstruction using fast sparse representation.
Optoacoustic tomography based on insufficient spatial sampling of ultrasound waves leads to loss of contrast and artifacts on the reconstructed images. Compared to reconstructions based on L2-norm regularization, sparsity-based reconstructions may improve contrast and reduce image artifacts but at a high computational cost, which has so far limited their use to 2D optoacoustic tomography. Here we propose a fast, sparsity-based reconstruction algorithm for 3D optoacoustic tomography, based on gradient descent with Barzilai-Borwein line search (L1-GDBB). Using simulations and experiments, we show that the L1-GDBB offers fourfold faster reconstruction than the previously reported L1-norm regularized reconstruction based on gradient descent with backtracking line search. Moreover, the new algorithm provides higher-quality images with fewer artifacts than the L2-norm regularized reconstruction and the back-projection reconstruction.


[The vanishing testis syndrome. Considerations on a case].
The aetiopathogenesis and clinical and diagnostic features of bilateral absence of the testicles in 46XY subjects are briefly reviewed. A eunuchoid 25-yr-old patient with male sex chromatin, 46 XY genotype, plasma testosterone slightly below normal, normal urinary 17-KS unaltered by gonadotropin stimulation, and bilateral absence of the testicles is presented. Examination of the inguinal canal showed a funiculus and ductus deferens residue terminating in an adipose mass. Section of the fibrous duct showed that this mass was full of capillaries and venules. Lesion between the 14th and 16th week of pregnancy is postulated.


SURFACE DOSE ESTIMATION BY A KAP METER FOR KILOVOLTAGE X-RAY BEAMS.
This study aims to estimate the entrance surface dose (ESD) of a water phantom for kilovoltage x-ray beams using an air kerma area product meter (KAP meter) equipped in an x-ray unit. The KAP meter was calibrated in terms of the ESD determined by a plane-parallel ionization chamber based on a 60Co absorbed dose-to-water calibration coefficient, ${N}_{D,w}^{{}^{60}\mathrm{C}\mathrm{o}}$. The ESD measured using the KAP meter was verified by comparing it with that estimated by the air kerma calibration coefficient, NK, for x-ray beam qualities. The ratio of ESDs based on ${N}_{D,w}^{{}^{60}\mathrm{C}\mathrm{o}}$ and NK was 1.003 on average and independent of the beam quality. The ESD by the KAP meter was an agreement within ±1.5% with that measured using the plane-parallel chamber for 10 × 10-30 × 30 cm2 fields with a source-surface distance of 75-150 cm. It was possible to estimate the ESD directly in a water phantom for x-ray beams without correction factors compared to the existing air kerma calibration, using a KAP meter calibrated based on ${N}_{D,w}^{{}^{60}\mathrm{C}\mathrm{o}}$.


Endovascular treatment of medium and large intracranial aneurysms with large volume coils: A single-center experience.
Large volume coils are an alternative to conventional coils for the treatment of intracranial aneurysms. However, there are no published reports documenting occlusion and complication rates in medium and large intracranial aneurysms. Therefore, we present our results in this subgroup of aneurysms. A single-center, retrospective analysis of consecutive patients treated with Penumbra coils 400 in aneurysms ≥7 mm was performed. Demographics, aneurysm features, procedural details, intraoperative complications, clinical outcomes, and occlusion rates were analyzed. Thirty-three patients were included for analysis, and a total of 33 intracranial aneurysms were analyzed. Mean age was 57.6 years (SD ± 12.4) and 85% of the patients were women. Large aneurysms represented 46% of cases. Paraclinoid (55%) followed by posterior communicating (30.3%) aneurysms was the most frequently treated. Ruptured and saccular aneurysms were found in 49% and 63% of the cases, respectively. The mean aneurysmal dimensions were 14.2 mm width, 11.9 mm length, 5.4 mm neck, and 2.4 dome-to-neck ratio. A dome-neck ratio <2 was identified in 39% of cases. The mean number of coils per aneurysm was 4.8. Immediate modified Raymond-Roy Grades 1, 2, and 3A were achieved in 15%, 21%, and 64%, respectively. Twenty-six patients were evaluated at a mean follow-up period of 11 months, with an adequate occlusion of 92% and a good clinical outcome (modified Rankin score ≤2) in 96% of patients. Endovascular treatment with PC400 coils is an effective and safe option for medium and large intracranial aneurysms with high occlusion rates, few complications, and good clinical outcomes at follow-up.


DNA length polymorphism 5' to the myelin basic protein gene is associated with multiple sclerosis.
A site of DNA polymorphism linked to the myelin basic protein gene, identified as restriction fragment length polymorphism, was analyzed in a population-based study comparing patients with clinically definite multiple sclerosis (MS) and population-matched control subjects. A 0.9-kilobase (kb) genomic DNA fragment (EcoG) encompassing the first exon of the human myelin basic protein gene, located on the long arm of chromosome 18, identified ten alleles arising from a region of DNA, 1.5 kb 5' to the myelin basic protein gene first exon coding region. Produced by RsaI digests and ranging in length from 2.05 to 2.15 kb, these alleles vary in size by up to 100 base pairs due to insertion or deletion, or both, from a 1-kb length of repetitive DNA. Allele frequencies among 65 patients with MS were compared with those of 63 control subjects. Chi square for these data was significant (p less than 0.001), largely due to a preponderance in the patients with MS of alleles in the 2.14- to 2.15-kb range. Comparison of the numbers of patients with MS and control subjects bearing specific alleles showed that 45% of the patients carried at least one allele of 2.14 to 2.15 kb as opposed to 19% of control subjects (p less than 0.005). These data, while preliminary, suggest that patients with MS differ from population-matched control subjects with respect to DNA polymorphism linked to the myelin basic protein gene. Although no pathogenic relationship between this polymorphism and MS can be presupposed, this finding raises the possibility that the myelin basic protein gene or some other myelin basic protein-linked locus may be a factor in susceptibility to MS.


Circulating tumor cells measurements in hepatocellular carcinoma.
Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC) reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1) there are few markers specific to the HCC (tumor cells versus nontumor cells) and (2) they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.


Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein.
The mechanisms underlying the selective targeting of specific brain regions by different neurodegenerative diseases is one of the most intriguing mysteries in medicine. For example, it is known that Alzheimer's disease primarily affects parts of the brain that play a role in memory, whereas Parkinson's disease predominantly affects parts of the brain that are involved in body movement. However, the reasons that other brain regions remain unaffected in these diseases are unknown. A better understanding of the phenomenon of selective vulnerability is required for the development of targeted therapeutic approaches that specifically protect affected neurons, thereby altering the disease course and preventing its progression. Prion diseases are a fascinating group of neurodegenerative diseases because they exhibit a wide phenotypic spectrum caused by different sequence perturbations in a single protein. The possible ways that mutations affecting this protein can cause several distinct neurodegenerative diseases are explored in this Review to highlight the complexity underlying selective vulnerability. The premise of this article is that selective vulnerability is determined by the interaction of specific protein conformers and region-specific microenvironments harboring unique combinations of subcellular components such as metals, chaperones and protein translation machinery. Given the abundance of potential contributory factors in the neurodegenerative process, a better understanding of how these factors interact will provide invaluable insight into disease mechanisms to guide therapeutic discovery.


From Discrete 1 to 10 Towards Continuous 0 to 10: The Continuum Approach to Estimating the Distribution of Happiness in a Nation.
Happiness is often measured in surveys using responses to a single question with a limited number of response options, such as 'very happy', 'fairly happy' and 'not too happy'. There is much variety in the wording and number of response options used, which limits comparability across surveys. To solve this problem, descriptive statistics of the discrete distribution in the sample are often transformed to a common discrete secondary scale, mostly ranging from 0 to 10. In an earlier publication we proposed a method for estimating statistics of the corresponding continuous distribution in the population (Kalmijn 2010). In the present paper we extend this method to questions using numerical response scales. The application of this 'continuum approach' to results obtained using the often used 1-10 numerical scale can make these comparable to those obtained on the basis of verbal response scales.


Limited value of 111-indium platelet scintigraphy in renal transplant patients receiving cyclosporine.
Since the differential diagnosis between cyclosporine (CyA) nephrotoxicity and acute graft rejection is still a problem in clinical routine, we studied retrospectively the value of 111-indium (In) platelet scintigraphy in 53 patients immunosuppressed with CyA and prednisolone. Autologous platelets were labeled once per week. After daily gamma camera imaging, the platelet deposition in the graft was expressed as platelet-uptake ratio (PUR). The patients were monitored during the first 4-6 weeks after surgery. PUR values measured during an episode of graft dysfunction were compared to the histological diagnosis. The PUR of well-functioning and stable grafts measured 1.07 +/- 0.11 (mean +/- SD). The 111-In platelet scintigraphy failed to register acute interstitial rejection. The PUR values in episodes of chronic vascular rejection, of acute tubular necrosis due to prolonged ischemia times, of tubular CyA nephrotoxicity and of cytomegalovirus (CMV) infection did not differ from the PUR of well-functioning and stable grafts as well. The PUR was significantly increased to 1.48 +/- 0.26 because of a marked platelet deposition in the graft in episodes of acute vascular rejection. In 4 cases of microvascular CyA nephrotoxicity the same phenomenon of significantly increased PUR (1.33 +/- 0.18), could be encountered, too. Two of these 4 cases resembled the hemolytic uremic syndrome (HUS). The value of PUR measurement for diagnosis of acute vascular rejection and microvascular CyA nephrotoxicity together, was: sensitivity 0.62, specificity 0.95, predictive value of positive result 0.64, predictive value of negative result 0.94.(ABSTRACT TRUNCATED AT 250 WORDS)


Fundamentals of Hysteresis in Perovskite Solar Cells: From Structure-Property Relationship to Neoteric Breakthroughs.
Perovskite solar cells (PSC) have shown a rapid increase in efficiency than other photovoltaic technology. Despite its success in terms of efficiency, this technology is inundated with numerous challenges hindering the progress towards commercial viability. The crucial one is the anomalous hysteresis observed in the photocurrent density-voltage (J-V) response in PSC. The hysteresis phenomenon in the solar cell presents a challenge for determining the accurate power conversion efficiency of the device. A detailed investigation of the fundamental origin of hysteresis behavior in the device and its associated mechanisms is highly crucial. Though numerous theories have been proposed to explain the causes of hysteresis, its origin includes slow transient capacitive current, trapping, and de-trapping process, ion migrations, and ferroelectric polarization. The remaining issues and future research required toward the understanding of hysteresis in PSC device is also discussed.


Mechanical characterization of 3D printed multi-morphology porous Ti6Al4V scaffolds based on triply periodic minimal surface architectures.
Heterogeneous biomaterials that simultaneously mimic the topological and mechanical properties of nature bone tissues are of great interest in recent years. In this study, multi-morphology porous scaffolds based on the triply periodic minimal surfaces (TPMS) were designed and 3D printed with spatially changing pore patterns. Experiments and numerical analyses were carried out to assess the mechanical properties of the multi-morphology graded porous scaffold. As can be seen from the results, the multi-morphology structure showed a combination of relatively low elastic moduli and high yield strength. This combination allows for simultaneously minimizing the bone damage and increasing the stability of bone-implant interface. Thus the 3D printed multi-morphology porous Ti6AlV scaffold had shown significant promise for orthopedic application.


Phorbol myristate acetate and the calcium ionophore A23187 synergistically induce release of LTB4 by human neutrophils: involvement of protein kinase C activation in regulation of the 5-lipoxygenase pathway.
Phorbol myristate acetate (PMA), a tumor-promoting phorbol ester, and the calcium ionophore A23187 synergistically induced the noncytotoxic release of leukotriene B4 (LTB4) and other 5-lipoxygenase products of arachidonic acid metabolism from human neutrophils. Whereas neutrophils incubated with either A23187 (0.4 microM) or PMA (1.6 microM) alone failed to release any 5-lipoxygenase arachidonate products, neutrophils incubated with both stimuli together for 5 min at 37 degrees C released LTB4 as well as 20-COOH-LTB4, 20-OH-LTB4, 5-(S),12-(R)-6-trans-LTB4, 5-(S),12-(S)-6-trans-LTB4, and 5-hydroxyeicosatetraenoic acid, as determined by high pressure liquid chromatography. This synergistic response exhibited concentration dependence on both PMA and A23187. PMA induced 5-lipoxygenase product release at a concentration causing a half-maximal effect of approximately 5 nM in the presence of A23187 (0.4 microM). Competition binding experiments showed that PMA inhibited the specific binding of [3H]phorbol dibutyrate ([3H]PDBu) to intact neutrophils with a 50% inhibitory concentration (IC50) of approximately 8 nM. 1-oleoyl-2-acetyl-glycerol (OAG) also acted synergistically with A23187 to induce the release of 5-lipoxygenase products. 4 alpha-phorbol didecanoate (PDD), an inactive phorbol ester, did not affect the amount of lipoxygenase products released in response to A23187 or compete for specific [3H]PDBu binding. PMA and A23187 acted synergistically to increase arachidonate release from neutrophils prelabeled with [3H]arachidonic acid but did not affect the release of the cyclooxygenase product prostaglandin E2. Both PMA and OAG, but not PDD, induced the redistribution of protein kinase C activity from the cytosol to the membrane fraction of neutrophils, a characteristic of protein kinase C activation. Thus, activation of protein kinase C may play a physiologic role in releasing free arachidonate substrate from membrane phospholipids and/or in modulating 5-lipoxygenase activity in stimulated human neutrophils.


Incomplete Partition Type III: Computed Tomography Features and Cochlear Implantation Complications.
In this case report, we review a male child who presented with severe bilateral hearing loss. Preoperative high-resolution computed tomography (HRCT) evaluation facilitated the initial diagnosis of the disease, which revealed typical findings of cochlear incomplete partition type III anomaly (IP-III), surgical planning, and cochlear implant selection to avoid possible complications. The child underwent cochlear implantation, which resulted in gushing and misplacement of the electrodes into the internal auditory canal (IAC) as postoperative complications. Postoperative imaging was used to determine the position of the implant and to assess the complications. The child's postoperative X-ray revealed misplacement of the cochlear implant, the extent of which was further assessed by a HRCT scan for preplanning the revision surgery and electrode selection. Following the revision surgery, a further HRCT scan confirmed proper implantation and ruled out any further complications.


GPR56 functions together with α3β1 integrin in regulating cerebral cortical development.
Loss of function mutations in GPR56, which encodes a G protein-coupled receptor, cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Studies from BFPP postmortem brain tissue and Gpr56 knockout mice have previously showed that GPR56 deletion leads to breaches in the pial basement membrane (BM) and neuronal ectopias during cerebral cortical development. Since α3β1 integrin also plays a role in pial BM assembly and maintenance, we evaluated whether it functions together with GPR56 in regulating the same developmental process. We reveal that loss of α3 integrin enhances the cortical phenotype associated with Gpr56 deletion, and that neuronal overmigration through a breached pial BM occurs earlier in double knockout than in Gpr56 single knockout mice. These observations provide compelling evidence of the synergism of GPR56 and α3β1 integrin in regulating the development of cerebral cortex.


Emergency valve-in-valve transcatheter aortic valve replacement in a patient with degenerated bioprosthetic aortic stenosis and cardiogenic shock on veno-arterial extracorporeal membrane oxygenation.
The use of transcatheter aortic valve replacement (TAVR) as an acute treatment in severe decompensated bioprosthetic aortic valve disease is not well documented. We describe herein a unique case in which valve-in-valve (ViV) TAVR was successfully used as both an emergency salvage therapy and a bridge to definitive fourth reoperative aortic valve replacement (AVR) in a young patient with cardiogenic shock secondary to bioprosthetic aortic valve stenosis who was dependent on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). © 2017 Wiley Periodicals, Inc.


Changes of Neurotransmitters in Youth with Internet and Smartphone Addiction: A Comparison with Healthy Controls and Changes after Cognitive Behavioral Therapy.
Neurotransmitter changes in youth addicted to the Internet and smartphone were compared with normal controls and in subjects after cognitive behavioral therapy. In addition, the correlations between neurotransmitters and affective factors were investigated. Nineteen young people with Internet and smartphone addiction and 19 sex- and age-matched healthy controls (male/female ratio, 9:10; mean age, 15.47 ± 3.06 years) were included. Twelve teenagers with Internet and smartphone addiction (male/female ratio, 8:4; mean age, 14.99 ± 1.95 years) participated in 9 weeks of cognitive behavioral therapy. Meshcher-Garwood point-resolved spectroscopy was used to measure γ-aminobutyric acid and Glx levels in the anterior cingulate cortex. The γ-aminobutyric acid and Glx levels in the addicted group were compared with those in controls and after cognitive behavioral therapy. The γ-aminobutyric acid and Glx levels correlated with clinical scales of Internet and smartphone addiction, impulsiveness, depression, anxiety, insomnia, and sleep quality. Brain parenchymal and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were higher in subjects with Internet and smartphone addiction (P = .028 and .016). After therapy, brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios were decreased (P = .034 and .026). The Glx level was not statistically significant in subjects with Internet and smartphone addiction compared with controls and posttherapy status. Brain parenchymal- and gray matter volume-adjusted γ-aminobutyric acid-to-creatine ratios correlated with clinical scales of Internet and smartphone addictions, depression, and anxiety. Glx/Cr was negatively correlated with insomnia and sleep quality scales. The high γ-aminobutyric acid levels and disrupted balance of γ-aminobutyric acid-to-Glx including glutamate in the anterior cingulate cortex may contribute to understanding the pathophysiology and treatment of Internet and smartphone addiction and associated comorbidities.


[Adenovirus-induced pneumonia in two guinea pigs].
Two cases of a rare virus-induced disease of Guinea pigs are described. The animals had died because of a pneumonia. Large intranuclear viral inclusion bodies could be demonstrated in the endothelial cells of the lungs. In the second case inclusion bodies could be found additionally in macrophages of the spleen and in macrophages, hepatocytes and endothelial cells of the liver. By means of electron microscopy the virus could be specified as adenovirus.


[Evaluation of Anti-dsDNA antibody tests: Crithidia luciliae immunofluorescence test, immunoblot, enzyme-linked immunosorbent assay, chemiluminescence immunoassay].
Anti-double stranded DNA antibody (anti-dsDNA) test is useful for the diagnosis and monitoring of systemic lupus erythematosus (SLE). Although several methods are available, none of them is completely satisfactory and differences among them have been reported. We evaluated the diagnostic performance of 6 commercial kits for anti-dsDNA detection. A total of 142 sera (SLE [N=74], other systemic rheumatic diseases [N=50], other diseases [N=18]) were tested by 6 different assay kits using different antigenic sources of DNA: Crithidia luciliae immunofluorescence test (CLIFT), salmon testes (immunoblot, IB), human (ELISA I), salmon testes with nucleosome linker (ELISA II), plasmid (ELISA III), and synthetic oligonucleotides (chemiluminescence immunoassay, CLIA). With manufacturers' cut-off values, 6 test kits showed sensitivities of 55.4-91.9%. ELISA I had a greater sensitivity than the other five assays (P<0.001). The specificities of ELISA II, ELISA III, CLIA, and CLIFT were higher than those of ELISA I and IB (P<0.05). In ROC curve analysis, 3 ELISA kits and CLIA showed AUC values of 0.845-0.893, and revealed no significant differences among them (P>0.05). With cut-off values set at 95% of specificity, ELISA II had a higher sensitivity than ELISA III (63.5% vs. 41.9%, P<0.05). IB had poor concordance rates with other assays (42.0-65.0%). Pearson correlation coefficients among 4 quantitative assays were 0.667-0.798. Six different assays showed various performances depending on the methods and cut-off values used. Except IB, the other five assays can be used for the detection of anti-dsDNA.


Imiquimod-induced psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin.
Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates. The differentiated HaCaT cells were treated with IMQ (100μM) to induce psoriatic like inflammation and its effect was investigated using a natural anti-psoriatic compound, curcumin. The proliferation of psoriatic-like cells was inhibited by curcumin at 25 and 50µM concentrations. The psoriatic-like cells decreased in number with increase in apoptotic and dead cells upon curcumin treatment. Curcumin inhibited the proliferation of IMQ-induced differentiated HaCaT cells (Psoriatic-like cells) by down-regulation of pro-inflammatory cytokines, interleukin-17, tumor necrosis factor-α, interferon-γ, and interleukin-6. Apart from this, curcumin significantly enhanced the skin-barrier function by up-regulation of involucrin (iNV) and filaggrin (FLG), the regulators of epidermal skin barrier. The IMQ-induced differentiated HaCaT in vitro model recapitulated some aspects of the psoriasis pathogenesis similar to murine model. Henceforth, we conclude that this model may be used for rapid screening of anti-psoriatic drug candidates and warrant further mechanistic studies.


Innovative hydrogels based on semi-interpenetrating p(HEMA)/PVP networks for the cleaning of water-sensitive cultural heritage artifacts.
Water-based detergent systems offer several advantages, over organic solvents, for the cleaning of cultural heritage artifacts in terms of selectivity and gentle removal of grime materials or aged varnish, which are known to alter the readability of the painting. Unfortunately, easel paintings present specific characteristics that make the usage of water-based systems invasive. The interaction of water with wood or canvas support favors mechanical stresses between the substrate and the paint layers leading to the detachment of the pictorial layer. In order to avoid painting loss and to ensure a fine control (layer by layer) of grime removal, water-based cleaning systems have been confined into innovative chemical hydrogels, specifically designed for cleaning water-sensitive cultural heritage artifacts. The synthesized hydrogels are based on semi-interpenetrating chemical poly(2-hydroxyethyl methacrylate)/poly(vinylpyrrolidone) networks with suitable hydrophilicity, water retention properties, and required mechanical strength to avoid residues after the cleaning treatment. Three different compositions were selected. Water retention and release properties have been studied by quantifying the amount of free and bound water (from differential scanning calorimetry); mesoporosity was obtained from scanning electron microscopy; microstructure from small angle X-ray scattering. To demonstrate both the efficiency and versatility of the selected hydrogels in confining and modulating the properties of cleaning systems, a representative case study is presented.


Current genomics in cardiovascular medicine.
Cardiovascular disease (CVD) is a heterogeneous, complex trait that has a major impact on human morbidity and mortality. Common genetic variation may predispose to common forms of CVD in the community, and rare genetic conditions provide unique pathogenetic insights into these diseases. With the advent of the Human Genome Project and the genomic era, new tools and methodologies have revolutionised the field of genetic research in cardiovascular medicine. In this review, we describe the rationale for the current emphasis on large-scale genomic studies, elaborate on genome wide association studies and summarise the impact of genomics on clinical cardiovascular medicine and how this may eventually lead to new therapeutics and personalised medicine.


Survey of intestinal parasites in swine farms raised in Western Nepal.
Pigs (Sus scrofa domesticus), an important domestic livestock, are generally affected by helminth and protozoan parasites. Rearing pigs in rural regions in Nepal is a common practice for subsistence farming. A cross-sectional survey was conducted to determine the occurrence of gastrointestinal parasites (GIPs) in pigs raised in Western Nepal. A total of 200 faecal samples from commercial and smallholder farms were examined by wet mounts, flotation, sedimentation and staining techniques. The results revealed that overall 86.5% of samples were found shedding oocysts or eggs of one or more GIPs. Three species of protozoa [Eimeria sp. (26%), Entamoeba coli (25.5%) and Coccidia (29%)] and nine species of helminths parasites (Ascaris suum (32.5%), Trichuris suis (30%), strongyle-type nematode (27.5%), hookworm (26%), Fasciola sp. (17.5%), Physaloptera sp. (17.5%), Strongyloides sp. (17.5%), Metastrongylus sp. (8%) and Oesophagostomum sp. (5.5%)] were identified. Female pigs were found to have higher protozoan infection than males, but such a difference was not noticed with regard to helminth parasites. Strongyles and Oesophagostomum infection were higher in commercial farms compared to smallholder farms, whereas the prevalences of E. coli and other protozoans were higher in smallholder farms. Among the contextual factors evaluated for association, weight and gender of pigs, and annual income and gender of managers/caretakers were significantly (p < 0.05) associated with the prevalence of GIPs in pigs. The overall prevalence of certain helminths such as strongyle-type nematode and A. suum was significantly (p < 0.05) associated with the weight of pigs after adjusting other contextual factors. This study detected relatively high prevalence of intestinal parasites in domestic pig facilities. Molecular epidemiological studies are essential to verify the exact zoonotic potential of parasites carried by pigs in the region. An effective periodic monitoring of GIPs of pigs needs to be carried out to minimize their further dissemination.


Dermatofibrosarcoma Protuberans (DFSP) with Fibrosarcomatous Changes in a Patient with Crohn's Disease Treated with Anti-TNF (Adalimumab).
Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade sarcoma with a reported incidence of 4.1 per million person-years. Despite its local invasiveness, it rarely metastasizes (5% of cases). Fibrosarcomatous change in DFSP is a form of tumor progression that carries an increased risk of metastases. We reported a case of 45-year-old patient treated with adalimumab lasting 7 years for Crohn's disease who developed dermatofibrosarcoma protuberans with fibromatous changes. Adalimumab therapy was stopped before surgery, and ustekinumab was introduced 6 months after.


Buccal mucosal graft urethroplasty in men-risk factors for recurrence and complications: a third referral centre experience in anterior urethroplasty using buccal mucosal graft.
Urethral stricture disease is a challenging condition to treat and several approaches including direct visual internal urethrotomy (DVIU) and anastomotic or augmentation urethroplasties based on the use of flaps and graft have been reported. The aim of this study is to determine risk factors for stricture recurrence and complications in patients having buccal mucosal graft (BMG) urethroplasty for anterior urethral stricture under a single surgeon in a third referral centre in UK. We conducted a retrospective review of a prospectively gathered database of 128 patients having various forms of BMG urethroplasty between 2001 and 2015. Success and failure in terms of stricture recurrence, patient demographics, stricture aetiology and anatomy, and the adverse outcomes of: post-micturition dribbling (PMD), erectile dysfunction (ED) >12 months and complications were recorded in order to determine risk factors for recurrent stricture and complications. The mean age of all patients was 42.8 years (range, 16-74 years). Average follow-up was 45 months (range, 3-159 months). The total re-stricture rate was 19% (24 men). PMD was reported in 16% (n=20) and ED in 12.5% (n=16). All ED was none organic and responded to oral PDE5 inhibitor treatment. Post-operative complications were reported in 16 patients (12.5%). The most frequent complications recorded were urinary fistula (n=4; 3.1%), graft contracture (n=4; 3.1%) and graft failure (n=4; 3.1%), all reported after penile urethroplasty. Univariate analysis indicated that age at surgery, stricture length, site and aetiology were all significant risk factors for stricture recurrence. On multivariate analysis penile site was the only significant independent variable for restricture. BMG urethroplasty represents a reliable therapeutic option for patient with urethral strictures with a success rate of 81% at 45 months of follow-up. Complications are more common in complex stricture of the penile urethra. On multivariate analysis penile site was the only significant independent variable for re-stricture.


Sinus histiocytosis with massive lymphadenopathy--a review of seven cases.
Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology. Histological features currently define it. Persistent painless lymphadenopathy due to expansion of sinuses infiltrated with benign histiocytes and plasma cells and emperipolesis are the characteristic features of SHML. Our study includes seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides and blocks were reviewed. IHC was performed on the main lesion, from a panel of S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane antigen. In our series we have work up available in 7 cases out of which a detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a stable disease, while one developed histiocytic sarcoma after a gap of four years.


Noncovalent Interactions in Ir-Catalyzed C-H Activation: L-Shaped Ligand for Para-Selective Borylation of Aromatic Esters.
An efficient strategy for the para-selective borylation of aromatic esters is described. For achieving high para-selectivity, a new catalytic system has been developed modifying the core structure of the bipyridine. It has been proposed that the L-shaped ligand is essential to recognize the functionality of the oxygen atom of the ester carbonyl group via noncovalent interaction, which provides an unprecedented controlling factor for para-selective C-H activation/borylation.


Digoxin disposition in elderly humans with hypochlorhydria.
Digoxin (D3) metabolism is partially mediated by the gastrointestinal tract via acid hydrolysis of digitoxose sugar moieties and bacterial reduction of the lactone. The hypothesis that hypochlorhydria influences digoxin disposition was tested in six normochlorhydric (NC) and four hypochlorhydric (HC) subjects. D3 tablets were administered daily for 19 to 28 days, and quantitative urine and fecal samples were collected over the last 3 days (steady state). Samples were analyzed for D3 and its extractable metabolites by fluorescence-derivatization HPLC. Excretion of D3 in urine increased from 37% of the dose in NC to 46% in HC, whereas excretion of D3 in feces decreased from 29 to 14%. These changes were statistically significant (P < .05) and consistent with decreased hydrolysis of D3 by stomach acid and increased intestinal metabolism in HC. In each subject, D3 was added to anaerobic cultures of both feces and jejunal fluid. Digoxin was reduced in all but two of the fecal incubates, and was not reduced in any jejunal fluid incubates. Because dihydrodigoxin (DHD3) was found in only two hypochlorhydric subjects, in vitro measures of bacterial reduction of D3 were not predictive of in vivo excretion of reduced metabolites. Sugar-hydrolyzed, reduced metabolites were not found in any subjects. It is concluded that D3 disposition is altered by hypochlorhydria, and that an understanding of the metabolic mechanisms requires further study.


Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.
Bone mineral density (BMD) decreases postrenal transplantation. Evidence demonstrating the effects of bisphosphonates on BMD and fracture risk beyond 1-year posttransplant is sparse in existing literature, but remains essential to enhance clinical outcomes in this population. Our study aimed to systematically review and meta-analyze the current literature on the use of any bisphosphonate in the adult renal transplant population beyond the first year of renal transplant to determine its effect on BMD and fracture incidence. We conducted a systematic review and meta-analysis of primary research literature that included full-text, English-language, original randomized clinical trials (RCTs) and observational studies. Patient data were primarily captured in an outpatient setting across various studies. Our population of interest was patients older than 18 years who received deceased/living donor kidney transplantation and any bisphosphonate with a follow-up greater than 12 months posttransplantation. The primary outcome was change in BMD from baseline. Secondary outcomes were the incidence of fractures and effects of other confounders on bone health. We included RCTs and observational studies that satisfied our inclusion criteria. Each study was analyzed for risk of bias and data were extrapolated to analyze for overall statistical significance accounting for heterogeneity of studies. Sixteen studies (N = 1762) were analyzed. The follow-up ranged from 12 to 98 months. There was a nonsignificant improvement in BMD with bisphosphonate treatment persisting into the second and third years posttransplant at the lumbar spine. The calculated standardized mean BMD difference was -0.29 (-0.75 to 0.17), P = .22. Only 5 studies reported a total of 43 new fractures. Prednisone (P < .01), low body weight (P < .001), low body mass index (P < .01), and male gender (P < .05) correlated with reduced lumbar and femoral BMD. Limitations of this review include the use of BMD as a surrogate outcome, the bias of the included studies, and the incomplete reporting data in numerous analyzed studies. We demonstrate no statistically significant benefit of bisphosphonate treatment on BMD beyond the first year postrenal transplantation. Despite heterogeneity of treatment, a differential nonsignificant improvement in lumbar spine BMD was consistent and may be clinically relevant. PROSPERO CRD42019125593.


One-Pot Synthesis of Block Copolymers by a Combination of Living Cationic and Controlled Radical Polymerization.
The reversible addition-fragmentation chain-transfer (RAFT) process represents a sophisticated polymerization technique for the preparation of tailored and well-defined polymers from acrylates, acrylamides, and (meth)acrylates. The direct switching from other methods, such as cationic polymerizations, without the need for tedious functionalization and purification steps remains challenging. Within this study, it is demonstrated that poly(2-oxazoline) (P(Ox)) macro chain-transfer agents (macro-CTAs) can be prepared through the quenching of the cationic ring-opening polymerization with a carbonotrithioate salt. The end-functionalization of the P(Ox)s is observed to be almost quantitative and the macro-CTAs could be directly used for RAFT polymerization without further purification. This one-pot procedure could be extended to a variety of (multi)block copolymers consisting of different 2-oxazolines and acrylates with good-to-excellent control. Kinetic studies revealed the controlled polymerization of block copolymers, which are further accessible for α- and ω-end-functionalization. The simplicity and versatility of the approach promise a straightforward access to block copolymers from cationic and controlled radical polymerizations.


Sobriety Treatment and Recovery Teams: Implementation Fidelity and Related Outcomes.
Although integrated programs between child welfare and substance abuse treatment are recommended for families with co-occurring child maltreatment and substance use disorders, implementing integrated service delivery strategies with fidelity is a challenging process. This study of the first five years of the Sobriety Treatment and Recovery Team (START) program examines implementation fidelity using a model proposed by Carroll et al. (2007). The study describes the process of strengthening moderators of implementation fidelity, trends in adherence to START service delivery standards, and trends in parent and child outcomes. Qualitative and quantitative measures were used to prospectively study three START sites serving 341 families with 550 parents and 717 children. To achieve implementation fidelity to service delivery standards required a pre-service year and two full years of operation, persistent leadership, and facilitative actions that challenged the existing paradigm. Over four years of service delivery, the time from the child protective services report to completion of five drug treatment sessions was reduced by an average of 75 days. This trend was associated with an increase in parent retention, parental sobriety, and parent retention of child custody. Conclusions/Importance: Understanding the implementation processes necessary to establish complex integrated programs may support realistic allocation of resources. Although implementation fidelity is a moderator of program outcome, complex inter-agency interventions may benefit from innovative measures of fidelity that promote improvement without extensive cost and data collection burden. The implementation framework applied in this study was useful in examining implementation processes, fidelity, and related outcomes.


Immunochemical investigations on Bacteroides fragilis antigenic structure.
Bacteroides fragilis strain 62/73 was studied. We demonstrated that formation of capsules is not a constant feature of cells of this strain. After chemical treatment we obtained six serologically active substances. The studied strain releases serologically active substances into the culture medium. We also found that endotoxin is the bacterial fraction according to which the strain may be classified to the appropriate serotype.


Checking behavior in rhesus monkeys is related to anxiety and frontal activity.
When facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed "Check-or-Go" task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas.


Neutrophils in secondary lymphoid organs.
Neutrophils are traditionally considered short-lived, circulating innate immune cells that are rapidly recruited to sites of inflammation in response to infectious and inflammatory stimuli. Neutrophils efficiently internalize, kill or entrap pathogens, but their effector molecules may cause collateral tissue damage. More recently, it has been appreciated that neutrophils can also influence adaptive immunity. Lymph nodes (LNs) are immune cell-rich secondary lymphoid organs that provide an ideal platform for cellular interaction and the integration of immunological information collected from local tissues. A variety of peripheral stimuli promote neutrophil migration to draining LNs via blood or lymphatics, utilizing differing molecular cues depending on the site of entry. Within LNs, neutrophils interact with other innate and adaptive cells. Crosstalk with subcapsular sinus macrophages contributes to the control of pathogen spread beyond the LN. Neutrophils can influence antigen presentation indirectly by interacting with DCs or directly by expressing major histocompatibility complex (MHC) and costimulatory molecules for antigen presentation. Interactions between neutrophils and adaptive lymphocytes can alter B-cell antibody responses. Studies have shown conflicting results on whether neutrophils exert stimulatory or inhibitory effects on other LN immune cells, with stimulus-specific and temporal differences in the outcome of these interactions. Furthermore, neutrophils have also been shown to traffick to LNs in homeostasis, with a potential role in immune surveillance, antigen capture and in shaping early adaptive responses in LNs. Understanding the mechanisms underpinning the effects of neutrophils on LN immune cells and adaptive immunity could facilitate the development of neutrophil-targeted therapies in inflammatory diseases.


Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation.
Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.


[Our experience with rare primary localizations of hydatidosis. Analysis of etiopathogenetic aspects].
The authors relate their experience on seventeen cases of unusual localizations of Echinococcus cyst operated in the last fifteen years. They present a critical analysis of the different pathogenetic theories trying to explain the peripheral localization of the larva. It is made examination of the factors which would consent the passing through of the hepatic and pulmonary filter, the mechanisms that could avoid such filters and the hypothesis referring to the possibility of direct setting up. They dwell quickly on the peculiar pathogenetic aspects of the various observed localizations.


Ascomycete communities in the rhizosphere of field-grown wheat are not affected by introductions of genetically modified Pseudomonas putida WCS358r.
A long-term field experiment (1999-2002) was conducted to monitor effects on the indigenous microflora of Pseudomonas putida WCS358r and two transgenic derivatives constitutively producing phenazine-1-carboxylic acid (PCA) or 2,4-diacetylphloroglucinol (DAPG). The strains were introduced as seed coating on wheat into the same field plots each year. Rhizosphere populations of ascomycetes were analysed using denaturing gradient gel electrophoresis (DGGE). To evaluate the significance of changes caused by the genetically modified microorganisms (GMMs), they were compared with effects caused by a crop rotation from wheat to potato. In the first year, only the combination of both GMMs caused a significant shift in the ascomycete community. After the repeated introductions this effect was no longer evident. However, cropping potato significantly affected the ascomycete community. This effect persisted into the next year when wheat was grown. Clone libraries were constructed from samples taken in 1999 and 2000, and sequence analysis indicated ascomycetes of common genera to be present. Most species occurred in low frequencies, distributed almost evenly in all treatments. However, in 1999 Microdochium occurred in relatively high frequencies, whereas in the following year no Microdochium species were detected. On the other hand, Fusarium-like organisms were low in 1999, and increased in 2000. Both the DGGE and the sequence analysis revealed that repeated introduction of P. putida WCS358r had no major effects on the ascomycete community in the wheat rhizosphere, but demonstrated a persistent difference between the rhizospheres of potato and wheat.


Concentrations in bird feathers reflect regional contamination with organic pollutants.
Feathers have recently been shown to be potentially useful non-destructive biomonitoring tools for organic pollutants. However, the suitability of feathers to monitor regional variations in contamination has not been investigated until now. Here concentrations of organic pollutants were compared in feathers of common magpies (Pica pica) between urban and rural areas in Flanders, Belgium. The results showed that concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE) were significantly higher in the rural areas (rural: 12-140 ng/g feather, urban: 1.1-7.2 ng/g feather), while polychlorinated biphenyls (PCBs) were significantly more available in an urban environment (sum PCBs--rural: 2.9-22 ng/g feather, urban: 41-240 ng/g feather). This pattern agrees with previous studies using other tissues than feathers as a biomonitoring tool. In addition, differences in PCBs and PBDEs profiles were found with lower halogenated congeners being more prominent in the urban areas in comparison to the rural areas. In summary, feathers seem to reflect regional variations in contamination, which strengthens their usefulness as a non-destructive biomonitor for organic pollutants.


Genomic characterization of IMP and VIM carbapenemase-encoding transferable plasmids of Enterobacteriaceae.
IMP and VIM carbapenemases, in association with class 1 integrons, have spread globally among multiple Enterobacteriaceae species. We characterized IMP- and VIM-encoding transferable plasmids of clinical Enterobacteriaceae collected from two global surveillance programmes. We performed conjugation and transformation experiments for 38 IMP and 89 VIM producers. Plasmids, obtained from transconjugants or transformants, were sequenced with Illumina next-generation sequencing and analysed for replicon types and antimicrobial resistance genes. A total of 41 transconjugants (blaIMP, n = 22; blaVIM, n = 19) and 10 transformants (blaIMP, n = 1; blaVIM, n = 9) were obtained. Broad-host-range IncL/M, IncC and IncN plasmids were associated with blaIMP and blaVIM, contained various integrons and showed inter-species and international distribution. Narrow-host-range IncFII(K) plasmids were limited to Klebsiella pneumoniae with blaIMP-26 from the Philippines, while IncR and IncHI1B-IncFIB(Mar) plasmids were restricted to K. pneumoniae with blaVIM from Greece and Spain. IncA-like hybrid plasmids were detected in Enterobacter xiangfangensis from Italy and K. pneumoniae from Spain. Transferable plasmids were major contributors of antimicrobial resistance genes among Enterobacteriaceae with blaIMP and blaVIM. This is the first report, to the best of our knowledge, describing blaIMP on IncFII(K) plasmids and blaVIM on IncL/M, IncN2, IncHI1B-IncFIB(Mar) and IncX3-IncC-like plasmids and showed that broad-host-range and narrow-host-range plasmids have contributed to the global spread of blaIMP and blaVIM among different species. This study highlights the importance of molecular analysis of plasmids in providing insight into horizontal spread of these carbapenemases.


Frequency and Phenotype of RFC1 Repeat Expansions in Bilateral Vestibulopathy.
Bilateral vestibulopathy (BVP) is a chronic debilitating neurologic disorder with no monogenic cause established so far despite familiar presentations. We hypothesized that replication factor complex subunit 1 (RFC1) repeat expansions might present a recurrent monogenic cause of BVP. The study involved RFC1 screening and in-depth neurologic, vestibulo-oculomotor, and disease evolution phenotyping of 168 consecutive patients with idiopathic at least "probable BVP" from a tertiary referral center for balance disorders, with127 of them meeting current diagnostic criteria of BVP (Bárány Society Classification). Biallelic AAGGG repeat expansions in RFC1 were identified in 10/127 patients (8%) with BVP and 1/41 with probable BVP. Heterozygous expansions in 10/127 patients were enriched compared with those in reference populations. RFC1-related BVP manifested at a median age of 60 years (range 34-72 years) and co-occurred predominantly with mild polyneuropathy (10/11). Additional cerebellar involvement (7/11) was subtle and limited to oculomotor signs in early stages, below recognition of classic cerebellar ataxia, neuropathy, and vestibular areflexia syndrome. Clear dysarthria, appendicular ataxia, or cerebellar atrophy developed 6-8 years after onset. Dysarthria, absent patellar reflexes, and downbeat nystagmus best discriminated RFC1-positive BVP from RFC1-negative BVP, but neither sensory symptoms nor fine motor problems. Video head impulse gains of patients with RFC1-positive BVP were lower relative to those of patients with RFC1-negative BVP and decreased until 10 years disease duration, indicating a potential progression and outcome marker for RFC1-disease. This study identifies RFC1 as the first-and frequent-monogenic cause of BVP. It characterizes RFC1-related BVP as part of the multisystemic evolution of RFC1 spectrum disease, with implications for designing natural history studies and future treatment trials. This study provides Class II evidence that RFC1 repeat expansions cause BVP.


Constituents from Polygonum cuspidatum.
Two lignan sulfates, a stilbene derivative and a phenol sulfate, together with 10 known compounds, were isolated from an aqueous extract of the root of Polygonum cuspidatum. The new compounds were elucidated based on chemical evidence and spectroscopic techniques including two-dimensional NMR methods. They exhibited no inhibition of lipid peroxidation and no cytotoxic and DNA cleavage activities.


[Standardized radiation treatment method for carcinoma of the uterine cervix].
Due to a world-wide information exchange on cancer therapy, a standardized treatment method for cancer is desirable. Radiation therapy for carcinoma of the uterine cervix is usually in combination with external and intracavitary irradiation. A basic treatment regiment for carcinoma of the uterine cervix with external and intracavitary irradiation was established by the major Japanese institutions. The consensus include: size and shape of irradiation field, dose, the reference from which to calculate the point A dose the external orifice of cervix is point A dose is regarded as the minor dose between right and left point As', categorized treatment methods with RALS according to cancer stage, the post operative irradiation method. This standardized treatment method will be applied for data analysis at each institution and will promote the further development of radiation therapy.


Economic Impact of Donating a Kidney on Living Donors: A Korean Cohort Study.
Although existing studies have reported adverse health outcomes after kidney donation, its socioeconomic impact on living donors requires further study. A retrospective observational cohort study including a matched comparison group. 1,285 living kidney donors from 7 tertiary hospitals between 2003 and 2016, and a matched comparison group consisting of the same number of health screening examinees with similar baseline clinical characteristics and socioeconomic status. All participants were receiving Korean national health insurance. Kidney donation as reflected in the Korean National Health Insurance System (NHIS) database. Changes in household economic status estimated by Korean national health insurance fees and changes in employment status reflected in the NHIS database. The outcomes of the donor group and matched control group were compared annually using multivariable logistic regression analyses adjusted for clinical and demographic characteristics. The median ages of the donors and matched controls were 45 and 46 years, respectively; 44.6% of both groups were male. Compared to the comparison group, living donors were at higher risk of being unemployed or losing employment during the first 2 years after donation (eg, first-year loss of employment: odds ratio (OR), 2.27 [95% CI, 1.55-3.33]); however, this association did not persist. Donors also had a significantly lower odds of improvement in economic status (OR, 0.57 [95% CI, 0.47-0.71]) and a higher odds of deterioration in financial status (OR, 1.54 [95% CI, 1.23-1.93]) in the first year after transplantation and subsequently. Unmeasured differences between donors and matched controls creating residual selection bias and confounding. Living kidney donors may suffer loss of employment and poor economic status after their voluntary donation. The socioeconomic impact on these donors should be considered in conjunction with the potential long-term adverse health outcomes after donation.


Hybrid dispersion laser scanner.
Laser scanning technology is one of the most integral parts of today's scientific research, manufacturing, defense, and biomedicine. In many applications, high-speed scanning capability is essential for scanning a large area in a short time and multi-dimensional sensing of moving objects and dynamical processes with fine temporal resolution. Unfortunately, conventional laser scanners are often too slow, resulting in limited precision and utility. Here we present a new type of laser scanner that offers ∼1,000 times higher scan rates than conventional state-of-the-art scanners. This method employs spatial dispersion of temporally stretched broadband optical pulses onto the target, enabling inertia-free laser scans at unprecedented scan rates of nearly 100 MHz at 800 nm. To show our scanner's broad utility, we use it to demonstrate unique and previously difficult-to-achieve capabilities in imaging, surface vibrometry, and flow cytometry at a record 2D raster scan rate of more than 100 kHz with 27,000 resolvable points.


Persistent symptomatic parvovirus B19 infection with severe thrombocytopenia transmitted by red blood cell transfusion containing low parvovirus B19 DNA levels.
Transfusion-mediated human parvovirus B19 (PVB19) infection is rare but often causes severe hematologic disorders. In Japan, routine blood donor screening for PVB19 antigen (detection sensitivity, 106.4 IU/mL) using a chemiluminescent enzyme immunoassay (CLEIA) was introduced in 2008. However, there is no consensus on the minimal infectious dose of PVB19 permissible for red blood cells (RBCs). A 64-year-old man, who had received hemodialysis for diabetic nephropathy for 5 years, underwent an RBC transfusion for anemia caused by hemorrhagic enterocolitis. He developed persistent high fever and progressive thrombocytopenia. He was diagnosed with PVB19 infection when a marrow examination showed giant erythroblasts, and his serum was positive for PVB19 DNA. His serum was negative for PVB19 immunoglobulin (Ig)M and IgG before transfusion, but positive for both after transfusion. This PVB19 infection was deemed to be transmitted by the RBC transfusion because low levels of PVB19 DNA (1.10 × 104 IU/mL) were detected in one of the blood donors. A DNA homology test of PVB19 showed complete genomic identity between the virus in the donor and our patient. We report a patient who developed persistent PVB19 infection from an RBC transfusion containing low levels of PVB19. This is the second case of transfusion-mediated PVB19 infection since the introduction of CLEIA in 2008. Transmission may occur in immunocompromised patients lacking PVB19-neutralizing antibodies. The report of further such cases will allow the establishment of minimal threshold values and more effective screening tests for PBV19 transmission through RBC products.