The measurement of neonates.
Accurate measurements of both healthy and premature neonates are possible but rarely performed. Routine anthropometry is often not performed at all or with large measurement errors due to inadequate training of personnel or inappropriate equipment. Sick neonates are often considered unsuitable for anthropometry and growth is wrongly equated with weight gain. Gain in length may be disturbed by poor health and permanent extrauterine growth retardation and changes in body proportions induced in some survivors of neonatal intensive care. Drug treatments may have profound effects on length gain and the relationship of length to weight.


Regioselective Cyclization of (Indol-3-yl)pentyn-3-ols as an Approach to (Tetrahydro)carbazoles.
An acid-catalyzed, highly regioselective cycloisomerization as well as dehydro-cyclization of (indol-3-yl)pentyn-3-ols has been reported for the selective synthesis of tetrahydrocarbazoles and carbazoles. This process is mild and found to be very general in terms of structural diversity of substrates. Utilizing the strategy, an efficient synthetic approach for the functionalized frameworks of carbazomycins A-D has also been developed.


Patterns of Verb Impairment in Aphasia: An Analysis of Four Cases.
Aphasic patients often have difficulty producing and/or comprehending verbs. However, there has been relatively little research into what aspects of verbs are difficult for these patients. In this paper, we examine patterns of verb impairment in four aphasic patients who show different patterns of disruption. Of particular interest, one of the four patients shows preserved knowledge of semantic features of verbs and subcategorisation frames, but an inability to map this semantic information onto argument structure. This dissociation poses problems for psycholinguistic theories that would dispose of separate representations for subcategorisation frames and raises the issue of whether intact knowledge about subcategorisation frames is dependent upon intact semantic knowledge. Another patient appears to have a disruption in knowledge of the action specified by certain verbs. Such a disruption is intriguing because verb deficits have generally been assumed to result from the different grammatical role played by verbs relative to nouns. Our results suggest that not all verb deficits derive from the subcategorisation or thematic role complexity of verbs.


EU Regulation of Nanobiocides: Challenges in Implementing the Biocidal Product Regulation (BPR).
The Biocidal Products Regulation (BPR) contains several provisions for nanomaterials (NMs) and is the first regulation in the European Union to require specific testing and risk assessment for the NM form of a biocidal substance as a part of the information requirements. Ecotoxicological data are one of the pillars of the information requirements in the BPR, but there are currently no standard test guidelines for the ecotoxicity testing of NMs. The overall objective of this work was to investigate the implications of the introduction of nano-specific testing requirements in the BPR and to explore how these might be fulfilled in the case of copper oxide nanoparticles. While there is information and data available in the open literature that could be used to fulfill the BPR information requirements, most of the studies do not take the Organisation for Economic Co-operation and Development's nanospecific test guidelines into consideration. This makes it difficult for companies as well as regulators to fulfill the BPR information requirements for nanomaterials. In order to enable a nanospecific risk assessment, best practices need to be developed regarding stock suspension preparation and characterization, exposure suspensions preparation, and for conducting ecotoxicological test.


Listening to the community: Using formative research to strengthen maternity waiting homes in Zambia.
The WHO recommends maternity waiting homes (MWH) as one intervention to improve maternal and newborn health. However, persistent structural, cultural and financial barriers in their design and implementation have resulted in mixed success in both their uptake and utilization. Guidance is needed on how to design a MWH intervention that is acceptable and sustainable. Using formative research and guided by a sustainability framework for health programs, we systematically collected data from key stakeholders and potential users in order to design a MWH intervention in Zambia that could overcome multi-dimensional barriers to accessing facility delivery, be acceptable to the community and be financially and operationally sustainable. We used a concurrent triangulation study design and mixed methods. We used free listing to gather input from a total of 167 randomly sampled women who were pregnant or had a child under the age of two (n = 59), men with a child under the age of two (n = 53), and community elders (n = 55) living in the catchment areas of four rural health facilities in Zambia. We conducted 17 focus group discussions (n = 135) among a purposive sample of pregnant women (n = 33), mothers-in-law (n = 32), traditional birth attendants or community maternal health promoters (n = 38), and men with a child under two (n = 32). We administered 38 semi-structured interviews with key informants who were identified by free list respondents as having a stake in the condition and use of MWHs. Lastly, we projected fixed and variable recurrent costs for operating a MWH. Respondents most frequently mentioned distance, roads, transport, and the quality of MWHs and health facilities as the major problems facing pregnant women in their communities. They also cited inadequate advanced planning for delivery and the lack of access to delivery supplies and baby clothes as other problems. Respondents identified the main problems of MWHs specifically as over-crowding, poor infrastructure, lack of amenities, safety concerns, and cultural issues. To support operational sustainability, community members were willing to participate on oversight committees and contribute labor. The annual fixed recurrent cost per 10-bed MWH was estimated as USD543, though providing food and charcoal added another $3,000USD. Respondents identified water pumps, an agriculture shop, a shop for baby clothes and general goods, and grinding mills as needs in their communities that could potentially be linked with an MWH for financial sustainability. Findings informed the development of an intervention model for renovating existing MWH or constructing new MWH that meets community standards of safety, comfort and services offered and is aligned with government policies related to facility construction, ownership, and access to health services. The basic strategies of the new MWH model include improving community acceptability, strengthening governance and accountability, and building upon existing efforts to foster financial and operational sustainability. The proposed model addresses the problems cited by our respondents and challenges to MWHs identified by in previous studies and elicits opportunities for social enterprises that could serve the dual purpose of meeting a community need and generating revenue for the MWH.


TRUST A v X AND OTHERS: THE GHOST OF NIELSEN RETURNS?
The case of Trust A v X and Others suggests that parents can authorise significant restrictions to be imposed on their disabled children. The court held that the parents of a D, a 15-year-old boy with autism and challenging behaviour, could consent to their son's placement in a locked psychiatric ward for over 15 months, whereas if such restrictions were placed on a child of that age without such disabilities, they would 'probably amount to ill treatment'. Focussing on two main areas of concern, it is argued that this decision is questionable and provides little assistance in determining whether parents can consent to their child's admission to hospital. First, the decision seems to be influenced by a misunderstanding of the basis on which the European Court of Human Rights (ECtHR) determines if a deprivation of liberty has arisen. Secondly, the court appears to have assumed that as D's parents were acting in his best interests, they were able to authorise extensive restrictions on their son, which is not the case. Such an approach renders disabled children's rights in this area almost non-existent and far exceeds the parental powers envisaged by the ECtHR in Nielsen v Denmark (1988), which has been subject to widespread criticism for failing to uphold the rights of the child.


Subtelomere FISH in 50 children with mental retardation and minor anomalies, identified by a checklist, detects 10 rearrangements including a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33.
Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.8%, range 2-29%; 95% confidence interval (CI) 4.60-6.84%). We performed a subtelomere FISH study of 50 unrelated children ascertained by a checklist that evaluates MR or developmental delay, dysmorphism, growth defect, and abnormal pedigree and found 10 bona fide causal rearrangements (detection rate 20%, 95% CI 10-33.7%). The findings included five unbalanced familial translocations or inversions, two unbalanced de novo translocations, and two de novo deletions. Patient 5 showed multiple anomalies (large head, vision defect, omphalocele, heart defect, enlarged kidneys, moderate MR, speech defect, mild transient homocysteinemia) and a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33. The report of a subtelomeric balanced rearrangement associated with a disease phenotype is a novel one. FISH mapping using panels of overlapping BAC clones identified a number of candidate genes at or near his breakpoints, including ASPA, TRPV3, TRPV1, and CTNS at 17p13.3, and three genes of unknown function at 20q13.33. Only the homocysteinemia could be speculatively linked to one of these genes (CTNS, the gene for cystinosis). Three within the subset of 16 children (18.8%) with mild (IQ, 50-69) or unspecified degree of MR tested positive, suggesting that the checklist approach could be especially useful within this group of patients.


Intradermal Infiltration of Local Anesthetic-Rapid and Bloodless Deepithelialization of the Breast Pedicle.
Breast reduction is one of the most commonly performed plastic surgery procedures, and pedicle deepithelialization remains a time-consuming step of the operation. This is especially true when using an inferior pedicle. We present a novel technique of intradermal infiltration of the breast pedicle with local anesthetic to facilitate efficient, bloodless deepithelialization. The senior author uses a 20-ml syringe to inject 0.25% lidocaine and 1:400,000 epinephrine just beneath the epidermis of the breast pedicle to create a series of wheals. Approximately 20 ml of local anesthetic is used per pedicle. After injection of local anesthetic, the breast pedicle is deepithelialized in less than 3 minutes. The plane is bloodless, allowing improved visualization secondary to the epinephrine-induced hemostasis. The senior author has had only one case of nipple necrosis in 20 years of experience. Intradermal infiltration of local anesthetic with epinephrine hydrodissects between the epidermis and dermis and provides hemostasis to facilitate rapid deepithelialization.


Recent developments in transposon-mediated gene therapy.
The continuous improvement of gene transfer technologies has broad implications for stem cell biology, gene discovery, and gene therapy. Although viral vectors are efficient gene delivery vehicles, their safety, immunogenicity and manufacturing challenges hamper clinical progress. In contrast, non-viral gene delivery systems are less immunogenic and easier to manufacture. In this review, we explore the emerging potential of transposons in gene and cell therapy. The safety, efficiency, and biology of novel hyperactive Sleeping Beauty (SB) and piggyBac (PB) transposon systems will be highlighted for ex vivo gene therapy in clinically relevant adult stem/progenitor cells, particularly hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), myoblasts, and induced pluripotent stem (iPS) cells. Moreover, efforts toward in vivo transposon-based gene therapy will be discussed. The latest generation SB and PB transposons currently represent some of the most attractive systems for stable non-viral genetic modification of primary cells, particularly adult stem cells. This paves the way toward the use of transposons as a non-viral gene therapy approach to correct hereditary disorders including those that affect the hematopoietic system. The development of targeted integration into "safe harbor" genetic loci may further improve their safety profile.


Comprehensive Analysis of HHLA2 as a Prognostic Biomarker and Its Association With Immune Infiltrates in Hepatocellular Carcinoma.
Inhibitory immune checkpoint proteins promote tumor immune escape and are associated with inferior patient outcome. However, the biological functions and regulatory roles of one of its members, HHLA2, in the tumor immune microenvironment have not been explored. RandomForest analyses (371 cases), qRT-PCR (15 cases), and immunohistochemical staining (189 cases) were used to validate the prognostic value of HHLA2 in hepatocellular carcinoma (HCC) patients. Bioinformatic analyses were further performed to explore the biological functions and potential signaling pathways affected by HHLA2. Moreover, ESTIMATE, single sample gene set enrichment analysis, CIBERSORT, TIMER, and other deconvolution methods were used to analyze the composition and infiltration level of immune cells. Multiplex immunofluorescence assays were employed to validate the fractions of suppressive immune cells, and HHLA2-related molecular alterations were investigated. Finally, the clinical response to chemotherapy and immune checkpoint blockade was predicted by TIDE, Submap, and several other in silico analyses. RandomForest analysis revealed that HHLA2 was the most important inhibitory immune checkpoint associated with HCC patient prognosis (relative importance = 1). Our HCC cohorts further revealed that high HHLA2 expression was an independent prognostic biomarker of shorter overall survival (P<0.01) and time to recurrence (P<0.001) for HCC patients. Bioinformatics experiments revealed that HHLA2 may accelerate the cell cycle of cancer cells. Additionally, we found that high expression of HHLA2 was associated with immune infiltrates, including some immunosuppressive cells, cytokines, chemokines, and corresponding receptors, resulting in an immunosuppressive environment. Notably, HHLA2 expression was positively correlated with the infiltration of exhausted CD8+ T cells, which was validated by immunofluorescence. Genomic alteration analyses revealed that promoter hypermethylation of HHLA2 may be associated with its low expression. More importantly, patients with high HHLA2 expression may be more sensitive to chemotherapy and have better responses to immunotherapy. High expression of HHLA2 is an independent prognostic biomarker for HCC patients. It can activate the cell cycle and foster an immunosuppressive tumor microenvironment by enriching exhausted CD8+ T cells. Promoter hypermethylation might lead to low expression of HHLA2 in HCC. Thus, targeting HHLA2 may be a practical therapeutic strategy for HCC patients in the future.


Clinical implementation of brass mesh bolus for chest wall postmastectomy radiotherapy and film dosimetry for surface dose estimates.
This study presents the dosimetric data taken with radiochromic EBT3 film with brass mesh bolus using solid water and semi-breast phantoms, and its clinical implementation to analyze the surface dose estimates to the chest wall in postmastectomy radiotherapy (PMRT) patients. Water-equivalent thickness of brass bolus was estimated with solid water phantom under 6 megavoltage photon beam. Following measurements with film were taken with no bolus, 1, 2, and 3 layers of brass bolus: (a) surface doses on solid water phantom with normal incidence and on curved surface of a locally fabricated cylindrical semi-breast phantom for tangential field irradiation, (b) depth doses (in solid phantom), and (c) surface dose measurements around the scar area in six patients undergoing PMRT with prescribed dose of 50 Gy in 25 fractions. Water-equivalent thickness (per layer) of brass bolus 2.09 ± 0.13 mm was calculated. Surface dose measured by film under the bolus with solid water phantom increased from 25.2% ±0.9% without bolus to 62.5% ± 3.1%, 80.1% ± 1.5%, and 104.4% ± 1.7% with 1, 2, and 3 layers of bolus, respectively. Corresponding observations with semi-breast phantom were 32.6% ± 5.3% without bolus to 96.7% ± 9.1%, 107.3% ± 9.0%, and 110.2% ± 8.7%, respectively. A film measurement shows that the dose at depths of 3, 5, and 10 cm is nearly same with or without brass bolus and the percentage difference is <1.5% at these depths. Mean surface doses from 6 patients treated with brass bolus ranged from 79.5% to 84.9%. The bolus application was discontinued between 18th and 23rd fractions on the development of Grade 2 skin toxicity for different patients. The total skin dose to chest wall for a patient was 3699 cGy from overall treatment with and without bolus. Brass mesh bolus does not significantly change dose at depths, and the surface dose is increased. This may be used as a substitute for tissue-equivalent bolus to improve surface conformity in PMRT.


A comparison of transcriptomic profiles in endometrium during window of implantation between women with unexplained recurrent implantation failure and recurrent miscarriage.
The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not in the other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq). In total 20 patients (9 RIF and 11 RM) were recruited. In addition 4 fertile subjects were included as reference. Endometrium samples were precisely timed on the 7th day after luteal hormone surge (LH + 7). All the 24 endometrium samples were extracted for total RNA. The transcriptome was determined by RNA-Seq in the first 14 RNA samples (5 RIF, 6 RM and 3 fertile). Differentially expressed genes between RM and RIF were validated by quantitative real-time PCR (qPCR) in all 24 RNA samples (9 RIF, 11 RM and 4 fertile). Transcriptomic profiles of RM and RIF, but not control samples, were separated from each other by principle component analysis (PCA) and support vector machine (SVM). Complementary and coagulation cascades pathway was significantly up-regulated in RIF while down-regulated in RM. Differentially expressed genes C3, C4, C4BP, DAF, DF and SERPING1 in complement and coagulation cascade pathway between RM and RIF were further validated by qPCR. This study compared endometrial transcriptome among patients with RIF and RM in the window of implantation; it identified differential molecular pathways in endometrium between RIF and RM, which potentially affect the implantation process.


Impact of baby behaviour on caregiver's infant feeding decisions during the first 6 months of life: A systematic review.
Caregivers are often concerned about baby behaviours. Without adequate counselling, parental response can lead to altering infant feeding and jeopardizing breastfeeding. We conducted a systematic review to assess the evidence about the influence of baby behaviours perceived as problematic (crying, sleep waking and posseting) on infant feeding decisions during the first 6 months of life (self-reported milk insufficiency, breastfeeding duration and introduction of formula). The review focused on quantitative studies published in English, Portuguese or Spanish without date restriction. The search was designed with the support of a medical librarian and conducted in seven databases. Data were managed in Covidence and risk of bias was assessed through the Johanna Briggs Institute critical appraisal checklists. Synthesis of the literature was guided by a conceptual model of the impact of baby behaviours on caregivers feeding practices. We retrieved and reviewed 4312 titles/abstracts and selected 22 for review; 10 were purely descriptive and 12 were cross-sectional, prospective and quasi-experimental studies. Although studies from diverse regions were included in the review, more than half were from high-income countries. All studies reported that baby behaviours affect feeding decisions, the most common baby behaviours studied were crying and fussiness, and the studies suggested relationships with lactation problems and reports of milk insufficiency, maternal breastfeeding confidence, breastfeeding duration and discontinuation, and introduction of formula. There are many factors that lead to perceiving baby behaviours as problematic and there is a need to provide anticipatory guidance to parents and caregivers, starting in pregnancy and counselling through well-trained health providers.


Phylogeographic analysis of Pseudogymnoascus destructans partitivirus-pa explains the spread dynamics of white-nose syndrome in North America.
Understanding the dynamics of white-nose syndrome spread in time and space is an important component for the disease epidemiology and control. We reported earlier that a novel partitivirus, Pseudogymnoascus destructans partitivirus-pa, had infected the North American isolates of Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome in bats. We showed that the diversity of the viral coat protein sequences is correlated to their geographical origin. Here we hypothesize that the geographical adaptation of the virus could be used as a proxy to characterize the spread of white-nose syndrome. We used over 100 virus isolates from diverse locations in North America and applied the phylogeographic analysis tool BEAST to characterize the spread of the disease. The strict clock phylogeographic analysis under the coalescent model in BEAST showed a patchy spread pattern of white-nose syndrome driven from a few source locations including Connecticut, New York, West Virginia, and Kentucky. The source states had significant support in the maximum clade credibility tree and Bayesian stochastic search variable selection analysis. Although the geographic origin of the virus is not definite, it is likely the virus infected the fungus prior to the spread of white-nose syndrome in North America. We also inferred from the BEAST analysis that the recent long-distance spread of the fungus to Washington had its root in Kentucky, likely from the Mammoth cave area and most probably mediated by a human. The time to the most recent common ancestor of the virus is estimated somewhere between the late 1990s to early 2000s. We found the mean substitution rate of 2 X 10-3 substitutions per site per year for the virus which is higher than expected given the persistent lifestyle of the virus, and the stamping-machine mode of replication. Our approach of using the virus as a proxy to understand the spread of white-nose syndrome could be an important tool for the study and management of other infectious diseases.


Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But Not to Empathy.
Responding to pro-social cues plays an important adaptive role in humans. Our aims were (i) to create a catalog of bonding and matched-control pictures to compare the emotional reports of valence and arousal with the International Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the valence and arousal of bonding and matched-control pictures; (iii) to investigate if empathy and loneliness traits exert a specific influence on emotional reports for the bonding pictures. To provide a finer tool for social interaction studies, the present work defined two new sets of pictures consisting of "interacting dyads" (Bonding: N = 70) and matched controls "non-interacting dyads" (Controls: N = 70). The dyads could be either a child and an adult, or two children. Participants (N = 283, 182 women) were divided in 10 groups for the experimental sessions. The task was to rate the hedonic valence and emotional arousal of bonding and controls; and of pleasant, neutral, and unpleasant pictures from the IAPS. Effects of social-related traits, empathy and loneliness, on affective ratings were tested. Participants rated bonding pictures as more pleasant and arousing than control ones. Ratings did not differentiate bonding from IAPS pleasant pictures. Control pictures showed lower ratings than pleasant but higher ratings than neutral IAPS pictures. Women rated bonding and control pictures as more positive than men. There was no sex difference for arousal ratings. High empathic participants rated bonding and control pictures higher than low empathic participants. Also, they rated pleasant IAPS pictures more positive and arousing; and unpleasant pictures more negative and arousing than the less empathic ones. Loneliness trait, on the other hand, affected very specifically the ratings of bonding pictures; lonelier participants rated them less pleasant and less arousing than less lonely. Loneliness trait did not modulate ratings of other categories. In conclusion, high empathy seems related to emotional strength in general, while high loneliness seems to weaken the engagement in social interaction cues.


Factors associated with the achievement of mucosal healing in Crohn's disease: the benefit of endoscopic monitoring in treating to target.
Mucosal healing (MH), the proposed treat to target in Crohn's disease (CD), is associated with improved disease outcomes. There are still scant data on factors associated with achieving MH in clinical practice. We evaluated the probability of achieving MH and identified factors predictive of subsequent MH in patients with CD. This was a retrospective, observational cohort study. A total of 272 patients with CD with serial endoscopy assessment and subsequent therapeutic management were reviewed. The primary outcome was MH. The cumulative incidence of MH and endoscopic improvement was estimated using the Kaplan-Meier method. Factors independently associated with MH were identified using the Cox proportional hazards model. Of the 272 patients, 126 (46.32%) achieved MH after a median follow-up period of 33 months (interquartile range: 27-38 months). Factors independently associated with MH by multivariate analysis were time between endoscopic procedures within 26 weeks (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.05-3.39), adjustment of medical therapy when MH was not achieved (HR: 2.07; 95% CI: 1.26-2.33), prior enteric fistula (HR: 0.22; 95% CI: 0.06-0.91), perianal disease at CD diagnosis (HR: 0.58; 95% CI: 0.35-0.95), and C-reactive protein normalization within 12 weeks (HR: 3.23; 95% CI: 1.82-5.88). Similar factors have also been identified for endoscopic improvement. Performing serial endoscopic procedures at a 26-week interval and subsequent adjustment in medical treatment are helpful in achieving MH. Endoscopic monitoring plays an important role in the treating to target of CD.


The cognitive-behavioral system of leadership: cognitive antecedents of active and passive leadership behaviors.
In the present paper, we propose a cognitive-behavioral understanding of active and passive leadership. Building on core evaluations theory, we offer a model that explains the emergence of leaders' active and passive behaviors, thereby predicting stable, inter-individual, as well as variable, intra-individual differences in both types of leadership behavior. We explain leaders' stable behavioral tendencies by their fundamental beliefs about themselves, others, and the world (core evaluations), while their variable, momentary behaviors are explained by the leaders' momentary appraisals of themselves, others, and the world (specific evaluations). By introducing interactions between the situation the leader enters, the leader's beliefs, appraisals, and behavior, we propose a comprehensive system of cognitive mechanisms that underlie active and passive leadership behavior.


Toxicology and the immune system: a perspective.
The relationship of immunology to toxicology has not always been an easy one, and the product of this association, immunotoxicology, has not infrequently been viewed with a certain scepticism by some of those who consider themselves 'classical' toxicologists. A recent meeting of the British Toxicology Society ('Toxicology and the Immune System', New College Oxford, March 21-22, 1991) provided an opportunity for some remedial work toward a wider appreciation of the issues which exercise immunotoxicologists, and the ways in which they are being addressed. It is not the purpose of this short article to provide a comprehensive account of the scientific presentations, but rather to give a perspective, necessarily a personal one, of immunotoxicology in the context of the meeting.


Postnatal differentiation of Leydig cells in the rabbit testis.
After the gradual disappearance of fetal Leydig cells in the first week after birth, the interstitial tissue of the rabbit testis is composed principally of undifferentiated mesenchymal cells between one and five weeks of age. Also present during this time are scattered partially differentiated cells with oval-shaped nuclei, prominent nucleoli and abundant cytoplasm. These cells exhibit some of the cytoplasmic features of steroid-secreting cells, but extensive development of smooth endoplasmic reticulum and the grouped perivascular arrangement of characteristic of fully differentiated Leydig cells are not present. The latter features appear at five weeks of age, indicating the formation of mature Leydig cells at that time. By seven weeks, the bulk of the interstitial tissue consists of Leydig cell aggregates, typical of the appearance in adult testis. Since spermatogonial mitoses first appear at seven to eight weeks of age, the findings indicate that Leydig cell differentiation precedes the onset of spermatogenesis.


Stenotic Bicuspid and Tricuspid Aortic Valves - Micro-Computed Tomography and Biological Indices of Calcification.
Valve calcification is well estimated by ex-vivo micro-computed tomography (micro-CT). The objective of this study was to investigate the associations between micro-CT findings and biological indices of calcification in aortic stenosis (AS), as well as differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).Methods and Results:Aortic valves and plasma were obtained from patients undergoing valve surgery. Valves were dissected and underwent micro-CT, genetic analyses, and calcium content assessment. Plasma levels of calcification markers were measured. Forty-two patients with isolated severe AS, including 22 with BAV, were studied. BAV patients had a lower median CT value (140.0 [130.0-152.0] vs. 157.0 [147.0-176.0], P=0.002) and high-density calcification (HDC) fraction (9.3 [5.7-23.3] % vs. 21.3 [14.3-31.2] %, P=0.01), as compared with TAV. Calcification fraction (CF) correlated with AS severity (measured as maximal transvalvular pressure gradient [r=0.34, P=0.03], maximal flow velocity [r=0.38, P=0.02], and indexed aortic valve area [r=-0.37, P=0.02]). For TAV patients only, mRNA expression of integrin-binding sialoprotein correlated with CF (r=0.45, P=0.048), and the receptor activator of the nuclear factor κ-B ligand transcript correlated with HDC corrugation (r=0.54, P=0.01). TAV patients with AS present more mineralized calcifications in micro-CT than BAV subjects. The relative volume of calcifications increases with the AS severity. In TAV patients, upregulated expression of genes involved in osteoblastogenesis in AS correlates with leaflet mineralization in micro-CT.


Cholangioscopy-guided lithotripsy for difficult bile duct stone clearance in a single session of ERCP: results from a large multinational registry demonstrate high success rates.
Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. RESULTS : 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % - 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 - 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % - 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.


Redox reactions of hemoglobin: mechanisms of toxicity and control.
In the last several years, significant work has been done studying hemoglobin (Hb) oxidative reactions and clearance mechanisms using both in vitro and in vivo model systems. One active research area involves the study of molecular chaperones and other proteins that are thought to mitigate the toxicity of acellular Hb. For example, the plasma protein haptoglobin (Hp) and the pre-erythroid protein alpha-hemoglobin-stabilizing protein (AHSP) bind to acellular Hb and alpha-subunits of Hb, respectively, to reduce these adverse effects. Moreover, there has been significant work studying hemopexin and alpha-1 microglobulin, both of which are thought to be involved with hemin degradation. These studies have coincided with the timely publication of the first crystal structure of the Hb-Hp complex. In constructing this Forum, we have invited a number of researchers in the area of Hb and myoglobin (Mb) redox biochemistry, as well as those who have contributed fundamentally to our knowledge of Hp function. Our goal has been to update this critically important research area, because we believe that it will ultimately impact the practice of transfusion medicine in a number of important ways.


External validity, generalisability, applicability and directness: a brief primer.
External validity is a construct that attempts to answer the question of whether we can use the results of a study in patients other than those enrolled in the study. External validity consists of two unique underlying concepts, generalisability and applicability. When the concern is about extending the results from a sample to the population from which the sample was drawn, the problem is one of generalisability. When the concern is about using inferences drawn from study participants in the care of specific patients belonging to any population, the problem is one of applicability. Clinicians, guideline developers and policymakers do not struggle with generalisability, but often struggle with applicability. When applicability is deemed to be low for a certain population, certainty in the supporting evidence becomes low due to indirectness.


Exposure to Parasitic Protists and Helminths Changes the Intestinal Community Structure of Bacterial Communities in a Cohort of Mother-Child Binomials from a Semirural Setting in Mexico.
An estimated 3.5 billion people are colonized by intestinal parasites worldwide. Intestinal parasitic eukaryotes interact not only with the host but also with the intestinal microbiota. In this work, we studied the relationship between the presence of multiple enteric parasites and the community structures of gut bacteria and eukaryotes in an asymptomatic mother-child cohort from a semirural community in Mexico. Fecal samples were collected from 46 mothers and their respective children, with ages ranging from 2 to 20 months. Mothers and infants were found to be multiparasitized by Blastocystis hominis, Entamoeba dispar, Endolimax nana, Chilomastix mesnili, Iodamoeba butshlii, Entamoeba coli, Hymenolepis nana, and Ascaris lumbricoides. Sequencing of bacterial 16S rRNA and eukaryotic 18S rRNA genes showed a significant effect of parasite exposure on bacterial beta-diversity, which explained between 5.2% and 15.0% of the variation of the bacterial community structure in the cohort. Additionally, exposure to parasites was associated with significant changes in the relative abundances of multiple bacterial taxa, characterized by an increase in Clostridiales and decreases in Actinobacteria and Bacteroidales. Parasite exposure was not associated with changes in intestinal eukaryote relative abundances. However, we found several significant positive correlations between intestinal bacteria and eukaryotes, including Oscillospira with Entamoeba coli and Prevotella stercorea with Entamoeba hartmanni, as well as the co-occurrence of the fungus Candida with Bacteroides and Actinomyces, Bifidobacterium, and Prevotella copri and the fungus Pichia with Oscillospira. The parasitic exposure-associated changes in the bacterial community structure suggest effects on microbial metabolic routes, host nutrient uptake abilities, and intestinal immunity regulation in host-parasite interactions. IMPORTANCE The impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in infants and mothers with multiple parasitic infections. In this work, we studied the relationship between protist and helminth parasite colonization and the intestinal microbiota structure in an asymptomatic population of mother-child binomials from a semirural community in Mexico. We found that the presence of parasitic eukaryotes correlated with changes in the bacterial gut community structure in the intestinal microbiota in an age-dependent way. Parasitic infection was associated with an increase in the relative abundance of the class Clostridia and decreases of Actinobacteria and Bacteroidia. Parasitic infection was not associated with changes in the eukaryote community structure. However, we observed strong positive correlations between bacterial and other eukaryote taxa, identifying novel relationships between prokaryotes and fungi reflecting interkingdom interactions within the human intestine.


How Natural are Conceptual Anaphors?
This paper reports three experiments on the interpretation of "conceptual" anaphors. These are anaphors that do not have an explicit linguistic antecedent, but one constructed from context. For instance, if one says "I need a knife. Where do you keep them?", them means something like "the knives that I presume you have in your house". In the first experiment, subjects rated sentences containing conceptual anaphors, of three different types, to be as natural as ones with a "linguistically correct" antecedent (e.g. "I need an iron. Where do you keep it?"), and as more natural than ones with neither a plausible conceptual antecedent nor a plausible linguistic one. In a second (self-paced) experiment, subjects judged whether the second sentence in such pairs was a sensible continuation from the first, and the time to make these judgements was measured. We found that acceptability judgements were high, and judgement times low, in just those sentences that were rated as more natural in the first experiment. These first two experiments showed that conceptual anaphors are quite easily understood. However, they did not show that such anaphors are processed without difficulty. In the third experiment, we therefore compared conceptual anaphors ("plate … them") with matched plural anaphors whose antecedents were explicit ("some plates … them"). The results were different for different types of anaphor: in one case (pronouns that referred to collective sets), the conceptual version followed by a plural pronoun was easier than the explicit plural version. For the other two types (references to generics and to implied multiple items), the explicit plurals were understood more rapidly than their conceptual counterparts.


Pheromone-based monitoring of Pseudococcus maritimus (Hemiptera: Pseudococcidae) populations in concord grape vineyards.
The grape mealybug, Pseudococcus maritimus (Ehrhorn), is the dominant mealybug in Washington's Concord grape vineyards (Vitis labrusca L.). It is a direct pest of fruit clusters and a vector of grapevine leafroll-associated viruses. Using traps baited with the sex pheromone of Ps. maritimus, we determined the optimal trap density for monitoring Ps. maritimus, with the goal of providing a more rapid monitoring method for Ps. maritimus than visual surveys. Varying densities of pheromone-baited traps (one, four, and eight traps per 12.14 ha) were deployed in Concord vineyards to monitor Ps. maritimus seasonal phenology in 2010 and 2011. In both years, flights of adult males were detected in early May and captures peaked twice per season in mid-June and mid-August, indicating two generations each year. Trap data were analyzed using Taylor's Power Law, Iwao's patchiness regression, and the K parameter of the negative binomial model to determine optimal sample size. The formula using the K parameter provided the lowest required sample size, showing that four to eight traps per 12.14 ha were needed to provide 30% sampling precision efficiency throughout the entire season. Fewer traps were needed during flight peaks when trap capture numbers were great. Only one pheromone-baited trap per 12.14 ha was sufficient to provide Ps. maritimus flight phenology data to make informed management decisions. Species-specific pheromone-baited traps deployed for Planococcus ficus (Signoret), Pseudococcus longispinus (Targioni Tozzetti), and Pseudococcus viburni (Signoret) did not detect any of these species in the vineyards sampled.


Handedness, Hinduism and sculpture: searching for evidence of lateralisation.
The majority of people throughout the world show extreme preference for the right hand. We studied lateral bias depicted in ancient Indian sculptures dating between the 7th and 9th centuries ad. A total of 288 sculptures were selected from various excavation sites/museums and the frequencies were computed on 13 different criteria in order to see the preferential bias for hand depicted in sculptures of male and female figures. The findings are discussed in the light of Hindu mythology and rituals.


Sudden infant death syndrome, sleep, and seizures.
benign febrile seizures seen in 7% of infants before 6 months play a role in the terminal pathway in a subset of sudden infant death syndrome victims. Supporting evidence: (1) lack of 5-hydroxitryptamine, one consistent finding in sudden infant death syndrome that Kinney et al coined a developmental serotonopathy, is consistent with risk for seizures. (2) Non-rapid eye movement sleep increasing during the age of highest risk for sudden infant death syndrome facilitates some seizures (seizure gate). (3) Sudden unexpected death in epilepsy is associated with severe hypoxemia and hypercapnia during postictal generalized electroencephalographic (EEG) suppression. In toddlers, sudden unexplained deaths are associated with hippocampal abnormalities and some seizures. (4) The sudden nature of both deaths warrants an exploration of similarities in the terminal pathway. Moreover, sudden infant death syndrome, febrile seizures, sudden unexplained death in childhood, and sudden unexpected death in epilepsy share some of the following risk factors: prone sleeping, infections, hyperthermia, preterm birth, male gender, maternal smoking, and mutations in genes that regulate sodium channels. State-of-the-art molecular studies can be exploited to test this hypothesis.


Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: Shared neuronal mechanisms?
Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based also on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent pre-clinical experimental data in rodents, we provide a coherent and unifying neuropathological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.


Olanzapine-induced DNA methylation in the hippocampus and cerebellum in genes mapped to human 22q11 and implicated in schizophrenia.
Although there is indirect evidence that the effects of antipsychotic drugs may involve modulation of dopamine transmission, their mechanism of action is poorly understood. We hypothesized that antipsychotic drugs mediate their effects by epigenetic modulation. Here, we tested the effect of an antipsychotic, olanzapine, on the DNA methylation status of genes following chronic treatment using rat-specific methylation arrays. Forty-eight hours after the last dose of olanzapine/vehicle, rats were habituated to an open-field activity-monitoring chamber for 30 min to verify whether stress-induced locomotor activity was reduced in olanzapine-treated rats. To test this hypothesis, we examined the effect of olanzapine, a commonly used atypical antipsychotic drug, on the DNA methylation status of 49 genes mapped to human 22q11 and implicated in schizophrenia. Genomic DNA isolated from the cerebellum, hippocampus, and liver of olanzapine-treated (n=2) and control (n=2) rats were analyzed using rat-specific methylation arrays. Significantly reduced locomotor activity of olanzapine-treated rats confirmed the therapeutic efficacy of the drug administered. The effects of olanzapine have been shown through significantly increased (P<0.01) DNA methylation of genes affecting several networks mainly (i) neurological disease, inflammatory disease, and inflammatory response and (ii) cancer, cell death and survival, tumor morphology. Also, proline degradation and L-DOPA degradation were affected by olanzapine-induced DNA methylation. Further, from a set of genes in the 22q11.2 microdeletions that has been implicated previously in psychosis, 29 genes showed increased methylation following olanzapine treatment. The results showed that considerable number of genes (34/49) mapped to human 22q11 and implicated in schizophrenia were affected by olanzapine-induced DNA methylation. The results suggest that DNA methylation may play a role in the therapeutic efficacy of olanzapine.


Numerical Optimization and Map-Based Manipulation With a Quadrupole Electromagnetic Actuated System.
Electromagnetic actuation is a new technique for non-invasive manipulation, which provides wireless and controllable power source for magnetic micro-/nano-particles. This technique shows great potential in the field of precise mechanics, environment protection, and biomedical engineering. In this paper, a new quadrupole electromagnetic actuated system was constructed, which was composed of four electromagnetic coils, each coil being actuated by an independent DC power supplier. The magnetic field distribution in the workspace was obtained through finite element modeling and numerical simulation via COMSOL software, as well as the effect of the current flow through the coil in the field distribution. Moreover, parameters of the electromagnetic system were optimized through parametric modeling analysis. A magnetic field map was constructed for rapidly solving the desired driving current from the required magnetic flux density. Experiments were conducted to manipulate a micro-particle along the desired circular path. The proposed work provides theoretical references and numerical fundamentals for the control of magnetic particle in future.


Strain improvement of industrially important microorganisms based on resistance to toxic metabolites and abiotic stress.
Improvement of the biosynthetic capabilities of industrially relevant microbes to produce desired metabolites in higher quantities is one of the important topics of modern biotechnology. In this article, different strategies of improvement of mutated microbial strains are briefly described. This is followed by the first comprehensive review of the literature on obtaining high yielding microorganisms, that is, mutants exhibiting resistance to antimetabolites, nutritional repression, and abiotic stresses as well as tolerance to solvents and toxic substrates or products. Furthermore, the efficiency of the microbial metabolites produced by improved microbial strains, advantages, and limitations, as well as future prospects for strategies of strain development are discussed.


Construction and analysis of a recombinant cyanobacterium expressing a chromosomally inserted gene for an ethylene-forming enzyme at the psbAI locus.
The coding sequence of a gene for a Pseudomonas syringae ethylene-forming enzyme was inserted at the psbAI locus in a cyanobacterium, Synechococcus elongatus PCC 7942 via rps12-mediated gene replacement. The recombinant strain photoautotrophically produced ethylene at 451 nl ml(-1) h(-1) OD730(-1), but showed a depressed specific growth rate as well as a yellow-green phenotype indicating a severe metabolic stress. The rate of ethylene production in the recombinant culture decreased as a result of competition with faster growing ethylene-non-forming mutants that carried short nucleotide insertions within the coding sequence of the gene for the ethylene-forming enzyme.


[Progress in research of relationship between heavy metal exposure and cardiovascular disease].
Heavy metal is one of pollutants existed widely in the environment, its relationship with cardiovascular disease has attracted more and more attention. In this review, the concentrations of heavy metals, including lead, cadium and asenic, in the body from several national surveillance networks and the epidemiological studies on the effects of the exposure of three heavy metals on cardiovascular system were summarized. It is suggested to strengthen nationwide surveillance for body concentrations of heavy metals in general population in order to provide baseline data for quantitative evaluation of the risk of heavy metal exposure on cardiovascular disease.


[Differentiation and function of monocyte/macrophage lineage cells and osteoblasts].
Macrophages, osteoclasts and dendritic cells are derived from hematopoietic stem cells through monocyte/macrophage lineage common precursor cells. Macrophages are induced in the presence of M-CSF alone whereas osteoclasts are induced by M-CSF and RANKL. The cooperation of transcription factors, c-Fos and NFATc1 is essential for osteoclast differentiation. GM-CSF is an inducer of dendritic cells, and in contrast to osteoclast differentiation, M-CSF and c-Fos are inhibitors of dendritic cell differentiation. On the other hand, mesenchymal stem cells(MSCs) give rise to osteoblasts. In embryonic stage, MSCs in perichondrium are marked by ALCAM. Recently, osteoblasts are reported to provide 'Niche' for hematopoietic stem cells in bone marrow. Here we review the differentiation and functions of monocyte/macrophage lineage cells and osteoblasts.


Dopaminergic modulation of some central actions of angiotensin II in vivo.
Studies were performed in 12 conscious sheep of both sexes to determine if a brain dopaminergic pathway is involved in modulating the central actions of angiotensin II (Ang II) in regulating body temperature and plasma renin activity (PRA). Previous data showed that intracerebroventricular (ICV) infusion of Ang II significantly decreased PRA and body temperature. In contrast, converting enzyme inhibitor SQ 20881 (SQ) or dopamine (DA) significantly increased PRA and body temperature of sheep. In the present study, ICV infusion of the DA antagonist metoclopramide (MCP) (20 micrograms/min) significantly decreased PRA to 68 +/- 5% of the basal level. When sheep were pretreated with ICV MCP (20 micrograms/min) for 2 hr and then infused ICV with MCP (20 micrograms/min) plus DA (20 micrograms/min), Ang II (25 ng/min), or SQ (1 microgram/min), the PRA and temperature responses to DA, Ang II, or SQ were all abolished or attenuated significantly. The converse did not hold. Sheep pretreated with SQ (1 microgram/min) still showed a significant increase in body temperature (0.43 +/- 0.05 degree C) when infused with DA (20 micrograms/min). These results support the hypothesis that a central DA pathway is involved in the modulation of the actions of centrally administered Ang II on temperature and PRA.


Effects of Caloric Intake on Learning and Memory Function in Juvenile C57BL/6J Mice.
Dietary composition may influence neuronal function as well as processes underlying synaptic plasticity. In this study, we aimed to determine the effect of high and low caloric diets on a mouse model of learning and memory and to explore mechanisms underlying this process. Mice were divided into three different dietary groups: normal control (n = 12), high-caloric (HC) diet (n = 12), and low-caloric (LC) diet (n = 12). After 6 months, mice were evaluated on the Morris water maze to assess spatial memory ability. We found that HC diet impaired learning and memory function relative to both control and LC diet. The levels of SIRT1 as well as its downstream effectors p53, p16, and peroxisome proliferator-activated receptor γ (PPARγ) were decreased in brain tissues obtained from HC mice. LC upregulated SIRT1 but downregulated p53, p16, and PPARγ. The expressions of PI3K and Akt were not altered after HC or LC diet treatment, but both LC and HC elevated the levels of phosphorylated-cAMP response element-binding protein (p-CREB) and IGF-1 in hippocampal CA1 region. Therefore, HC diet-induced dysfunction in learning and memory may be prevented by caloric restriction via regulation of the SIRT1-p53 or IGF-1 signaling pathways and phosphorylation of CREB.


Role of infarct location and pre-existing depression on cardiac baroreceptor sensitivity in subacute ischemic stroke.
Reduced cardiac baroreceptor sensitivity (BRS) after acute stroke is associated with worse outcome. The underlying mechanisms of reduced BRS are unclear. We evaluated cross correlation BRS (xBRS) in 184 patients with suspected acute ischemic stroke within 72 h of symptom onset. Among these patients, 22 had a transient ischemic attack (TIA) and 27 had a stroke mimic. Sixty-four age- and sex-matched ambulant control subjects without stroke were included. Compared with controls, xBRS was significantly lower in patients with ischemic stroke, TIA, and stroke mimics (4.6, 4.7, and 4.4, respectively, vs 6.6, p < 0.01). There was no difference in xBRS between right and left hemispheric infarctions (4.3 vs 4.9, p = 0.144), right and left insular infarctions (4.5 vs 5.3, p = 0.286), and insular infarction vs non-insular infarctions (4.7 vs 4.5, p = 0.996). Stroke patients with pre-existing depression/use of antidepressant medication had lower xBRS values than stroke patients with normal mental health (2.9 vs 4.8, p < 0.05). Control patients with depression also had lower xBRS compared to controls without depression (3.4 vs 5.9, p < 0.01). Our results suggest that decreased xBRS in the subacute phase after stroke is not associated with infarct localization. We found preliminary evidence for an association between pre-existing depression and use of antidepressant medication, and decreased BRS.


Increasing interest in rural mental health work: the impact of a short term program to orientate allied health and nursing students to employment and career opportunities in a rural setting.
Ongoing workforce shortages affect the provision of mental health services to rural and remote communities. This article examines the immediate impact of a novel recruitment strategy that aims to increase the number of mental health professionals commencing their careers in a rural area of Australia. This study utilised a sequential confirmatory mixed methods design which included both online pre- and post-program surveys and semi-structured individual interviews. Statistical analyses compared participants' pre- and post-program survey interest in rural work/career, mental health work/career and rural mental health work/career. Content analysis was undertaken to explore interview transcripts for data that confirmed, contradicted or added depth to the quantitative findings. Comparison of pre- and post-program surveys indicated a significant increase in participants' interest in rural work/career and rural mental health work/career. The qualitative findings provided depth to and supported the change in interest toward working in a rural environment. Despite qualitative evidence that the program has increased participants' knowledge and understanding of the mental health sector as a whole, overt support for the changes in interest toward mental health work was not evident. The study provides evidence that a short-term program can change allied health and nursing students' interest in rural mental health work. The findings have important implications for the recruitment of mental health practitioners to underserved rural areas.


Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA Infections.
Blocking the biosynthesis process of staphyloxanthin has emerged as a promising antivirulence strategy. Our previous research revealed that diapophytoene desaturase was an attractive and druggable target against infections caused by pigmented Staphylococcus aureus. Benzocycloalkane-derived compounds were effective inhibitors of diapophytoene desaturase but limited by high hERG (human Ether-a-go-go Related Gene) inhibition activity. Here, we identified a new type of benzo-hepta-containing cycloalkane derivative as diapophytoene desaturase inhibitors. Among the fifty-eight analogues, 48 (hERG inhibition activity, half maximal inhibitory concentration, IC50, of 16.1 μM) and 51 (hERG inhibition activity, IC50 > 40 μM) were distinguished for effectively inhibiting the pigment production of Staphylococcus aureus Newman and three methicillin-resistant Staphylococcus aureus strains, and the four strains were highly sensitize to hydrogen peroxide killing without a bactericidal growth effect. In an in vivo assay, 48 and 51 displayed a comparable effect with linezolid and vancomycin in livers and hearts in mice against Staphylococcus aureus Newman and a more considerable effect against Mu50 and NRS271 with normal administration.


Peginterferon-alpha-2a (40kD) and ribavirin in patients with chronic hepatitis C: a phase II open-label study.
Addition of a 40kD polyethylene glycol moiety to interferon-alpha-2a [peginterferon-alpha-2a (40kD)] improves pharmacokinetic properties over those of standard interferon. We conducted a phase II study to assess the safety and initial efficacy of peginterferon-alpha-2a (40kD) plus ribavirin combination therapy in patients with chronic hepatitis C (CHC). Twenty patients received open-label 180 microg peginterferon-alpha-2a (40kD) subcutaneously once weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or > or =75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus (HCV) genotype 1 and a virological response at week 24 received study drugs for an additional 24 weeks. A sustained virological response, defined as undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy, was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1 and 4/4 genotype non-1). Adverse events were similar to those reported with unmodified interferon plus ribavirin combination therapy. Anaemia led to ribavirin dose reduction in five patients. Neutropenia led to dose reduction in three patients treated with peginterferon-alpha-2a (40kD). The addition of ribavirin to a once-weekly peginterferon-alpha-2a (40kD) regimen should be investigated in larger clinical trials.


An online questionnaire survey on preferred timing for the diagnosis and management of thyroid carcinoma in general population in Korea.
An optimal timing for diagnosis and management of papillary thyroid microcarcinoma (PTMC) has become the subject for much controversy. The aim of the present study is to analyze people's preference in Korea for timing of diagnosis and management of PTMC using an online questionnaire. The questionnaire consists of 3 questions about preference for the diagnosis and management of PTMC and 3 additional questions about respondents' personal information. An online survey was conducted from March 3 to June 3 in 2015 using Google Survey (http://goo.gl/forms/b81yEjqNUA). A total 2,308 persons (1,246 males, 1,053 females) answered the questionnaire. Respondents' ages varied widely from teenagers to 70-year-olds. If there was a suspicious thyroid nodule from PTMC measuring less than 1 cm in diameter, 95.7% of respondents want to know a cytological diagnosis for it. If a thyroid nodule turned out to be a PTMC, 59.5% of respondents wanted it removed immediately. For surgical management of PTMC, 53.0% of respondents were worried more about recurrences than complications. In subgroup analyses, respondents younger than 40 years old more often want immediate surgery than others: 66.7% vs. 32.7% (P < 0.05). Respondents who underwent thyroid cancer surgery (n = 91) were worried more about recurrences than others: 69.2% vs. 52.4% (P < 0.05). Almost all respondents in the present study wanted diagnosis of suspicious thyroid nodules immediately. However, there were opposing opinions about the preferred timing for surgical treatment and surgical extents. A patient's right to know their disease status and decision on treatments should be emphasized all the more.


Plasma asymmetric dimethylarginine and its association with some of cardiovascular disease risk factors in chronic kidney disease.
Chronic kidney disease (CKD) usually has increase of asymmetric dimethylarginine (ADMA) levels. ADMA is a cardiovascular disease (CVD) risk factor and its elevation associated with other CVD risk factors at CKD leads to increasing risk of death. In this article, we aimed to identify levels and elevation proportion of plasma ADMA in CKD as well as association between ADMA with CVD risk factors. This cross-sectional study was performed at Hue Central Hospital from 2012-2016 on 176 CKD and 64 control subjects. ADMA levels were measured by using the enzyme linked immunosorbent assay (ELISA) method. Mean ADMA level was markedly higher (p<0.001) in all patients combined (0.73±0.24μmol/L) than in control subjects (0.47±0.13μmol/L). Mean ADMA levels in advanced kidney disease were higher than control subjects. ADMA levels correlated inversely and relatively strictly to estimated glomerular filtration rate (eGFR) (r = -0.689; p<0.001), haemoglobin (r = -0.525; p<0.001) and haematocrit (r = - 0.491; p<0.001); correlated favourably and relatively strictly to serum creatinine (r = 0.569; p<0.001) and serum urea (r = 0.642; p<0.001). ADMA elevation was predicted simultaneously by eGFR<60 mL/min/1.73m2 (p<0.001), anaemia (p=0.002), body mass index (BMI) (p=0.011) and high sensitivity C-reactive protein (hs-CRP) (p=0.041). Cutoff of ≥0.68μmol/L, ADMA levels predict reduction of eGFR<60 mL/min/1.73m2, sensitivity of 86.9 %, specificity of 82.6%, area under ROC 92.4% (95%CI: 88.6-96.1%).


[Use of the plastic "Terphane" for the maintenance and the study of cell cultures].
Terphane plastic used as substrate for tissue culture, facilitates both cytochemcial, biochemical and ulstratructural studies of cells in situ. Particularly pliable, thin and resistant, the sheet of Terphane plastic is held tense by a system of two plaques of Petri dish type. This apparatus is perfectly waterproof, sterilisable and may be used indefinitely. Growth, morphology, ultrastructure and enzyme activities of primary or subcultures of rat and human liver maintained on terphane plastic are comparable with those of cells cultivated on Falcon polystyrene. Furthermore, terphane offers several advantages over the Melinex plastic: its thinness, resistance and plasticity render easy all manipulations.


An introduction to the special issue on psychotherapy termination.
This introduction to the special issue on psychotherapy termination begins by noting the almost complete lack of research and clinical discussion on this topic in the literature. It is with a desire to effect some sort of change to this current state of affairs that Psychotherapy invited manuscripts for this special issue. Specifically, the editors sought contributions on both the clinical practice and research aspects of the psychotherapy termination process from a variety of different theoretical orientations, perspectives, and methodologies. This special issue will include two sections, clinical practice and research, each serving to help better define the nature and extent of this important, but often ignored aspect of psychotherapy. (PsycINFO Database Record


Pulmonary function improves after expandable metal stent placement for benign airway obstruction.
To determine whether expandable metal stent placement for benign airway lesions improves pulmonary function. Case series. University medical center. Nine patients who underwent balloon-mediated expandable metal stent deployment for airway obstruction due to benign etiologies. All nine patients had expandable stents deployed for benign airway lesions using fiberoptic bronchoscopy and fluoroscopic guidance. Pulmonary function improved after stent placement. The mean FVC increased by 388 mL (95% confidence interval [CI], 30 to 740 mL), the mean peak expiratory flow (PEF) increased by 1,288 mL (95% CI, 730 to 1,840 mL), the mean FEV1 increased by 550 mL (95% CI, 240 to 860 mL), and the mean forced expiratory flow between 25% and 50% of vital capacity (FEF25-75%) increased by 600 mL (95% CI, 110 to 1,090 mL). Corresponding relative measurements included increases in FVC (12%), PEF (95%), FEV1 (38%), and FEF25-75% (87%). The complete characterization of a benign airway obstruction generally required a multimodal approach. Expandable metal stent placement appears to be an effective therapy for benign airway obstruction.


Histological and immunohistochemical study of the eyelid basal cell carcinomas.
The eyelids represent a frequent site for numerous malignant tumors, which generally present subtle symptoms or can imitate benignant tumors. Our study was carried on 80 patients, 48 males and 32 females aged between 48 and 92 years. The patients were hospitalized in the Ophthalmology Clinic of the Emergency County Hospital of Craiova, Romania. The study was conducted over five years, between 2010 and 2014. Our study included 80 basal cell carcinomas of the eyelids, of which 48 (60%) were nodular basal cell carcinomas, 15 (18.75%) were adenoid basal cell carcinomas, 10 (12.5%) were cystic and seven (8.75%) were morpheaform basal cell carcinoma. Our study showed a moderate expression of bcl-2 marker in the nodular type of basal cell carcinoma and a high expression in the other histopathological types, thus inducing an increased malignancy comparing to the nodular type. E-cadherin was absent in nodular, cystic and adenoid basal cell carcinomas and had a moderate expression in morpheaform basal cell carcinoma. Morpheaform and adenoid types presented 20% expression of Ki67 of the malignant cells nuclei, while the cystic type presented Ki67 expression in less than 10% of the malignant cells nuclei. Due to high morbidity and increasing incidence, basal cell carcinoma of the eyelid represents an important health issue nowadays.


Topological Crystalline Insulator Pb1-x Snx Se Nanowires with {100} Facets.
Surface states properties of topological crystalline insulator Pb1-x Snx Se are strongly dependent on crystallographic plane orientation. Rectangular prismatic Pbx Sn1-x Se nanowires and nanoplates are grown with distinct {100} surfaces on mica sheets. Substrate surface chemical properties are found to be the critical factors that affect the vapor deposition process and final shapes of Pb1-x Snx Se nanostructures.


What is dystonia?
1. Dystonia affects 20,000 people in Britain; it presents in almost any part of the body, and can become a chronic progressive disease. Dystonia can have an hereditary route, or an environmental cause. 2. Most dystonias are incurable but their symptoms can be treated. 3. Dystonias are often mistakenly thought to have psychological rather than pathological origin.


Yield degradation due to laser drive asymmetry in D3He backlit proton radiography experiments at OMEGA.
Mono-energetic proton radiography is a vital diagnostic for numerous high-energy-density-physics, inertial-confinement-fusion, and laboratory-astrophysics experiments at OMEGA. With a large number of campaigns executing hundreds of shots, general trends in D3He backlighter performance are statistically observed. Each experimental configuration uses a different number of beams and drive symmetry, causing the backlighter to perform differently. Here, we analyze the impact of these variables on the overall performance of the D3He backlighter for proton-radiography studies. This study finds that increasing laser drive asymmetry can degrade the performance of the D3He backlighter. The results of this study can be used to help experimental designs that use proton radiography.


Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in mice.
Peroxisome proliferator-activated receptor (PPAR)gamma is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPARgamma display lipodystrophy and extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) in PPARgamma developed normal amounts of adipose tissue and were insulin sensitive. This finding raised important doubts about the interspecies translatability of PPARgamma-related findings, bringing into question the relevance of other PPARgamma murine models. Here, we demonstrate that when expressed on a hyperphagic ob/ob background, the P465L PPARgamma mutant grossly exacerbates the insulin resistance and metabolic disturbances associated with leptin deficiency, yet reduces whole-body adiposity and adipocyte size. In mouse, coexistence of the P465L PPARgamma mutation and the leptin-deficient state creates a mismatch between insufficient adipose tissue expandability and excessive energy availability, unmasking the deleterious effects of PPARgamma mutations on carbohydrate metabolism and replicating the characteristic clinical symptoms observed in human patients with dominant-negative PPARgamma mutations. Thus, adipose tissue expandability is identified as an important factor for the development of insulin resistance in the context of positive energy balance.


Magnetostatic detection using magnetoresistive sensors with vertical motion flux modulation.
Recently, the flux modulation has been presented to deal with the 1/f noise of magnetoresistive (MR) sensors. However, the efficiency of most flux modulation schemes with simple micro- electromechanical-system (MEMS) actuators is not satisfying yet. In this paper, the vertical motion flux modulation (VMFM) is proposed to improve the modulation efficiency. In VMFM, the soft magnetic film driven by a MEMS actuator vibrates vertically above the MR sensors with a pair of flux concentrators. Consequently, the detected magnetostatic field is modulated to the higher frequency where the 1/f noise is much lower. A VMFM prototype based on AA002 (multi-layered giant magnetoresistive sensors) was fabricated and its flux modulation efficiency can reach 18.7%, which exceeds most achieved efficiency with other schemes. Also, the magnetostatic detection ability is improved to 530 pT/√Hz.


Characterization of site-specific N-glycosylation signatures of isolated uromodulin from human urine.
Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.


Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of ursolic acid.
This study aims to characterize the glucuronidation kinetics of ursolic acid (UA) in human liver microsomes (HLMs) and intestinal microsomes (HIMs) and identify the main UDP-glucuronosyltransferases (UGTs) involved. In our present study, only one type of UA glucuronide was observed after incubation with HLMs and HIMs respectively and was identified as a UA hydroxyl O-glucuronide. The glucuronidation of UA can be shown in HLMs and HIMs with Km values of 3.29 ± 0.16 and 3.74 ± 0.22 μM and Vmax values of 0.33 ± 0.03 and 0.42 ± 0.03 nmol/min/(mg protein). Among the 12 recombinant UGT enzymes investigated, UGT1A3 and UGT1A4 were identified as the major enzymes catalyzing the glucuronidation of UA [Km values of 2.58 ± 0.12 and 4.66 ± 0.60 μM, Vmax values of 0.72 ± 0.01 and 1.00 ± 0.06 nmol/min/(mg protein)]. The chemical inhibition study showed that the IC50 for hecogenin inhibition of UA glucuronidation was 51.79 ± 4.32 μM in HLMs. And chenodeoxycholic acid inhibited UA glucuronidation in HLMs with an IC50 of 28.26 ± 2.91 μM. In addition, UA glucuronidation in a panel of eight HLM was significantly correlated with telmisartan glucuronidation (r(2) = 0.7660, p < 0.01) and trifluoperazine glucuronidation (r(2) = 0.5866, p < 0.01) respectively. These findings collectively indicate that UGT1A3 and UGT1A4 were the main enzymes responsible for the glucuronidation of UA in human.


A macrocycle-assisted nanoparticlization process for bulk Ag2S.
We report herein a new nanoparticlization process for the bulk-to-nano transformation of Ag2S by incorporating both top-down and bottom-up approaches. Bulk Ag2S was dissolved in solution with the assistance of a macrocyclic ligand, hexamethylazacalix[6]pyridine (Py[6]), to produce polynuclear silver sulfide cluster aggregates. All Ag-S cluster aggregates obtained in three crystalline complexes were protected by Py[6] macrocycles. Removing the protective Py[6] macrocycles by protonation led to the generation of unconventional Ag-S nanoparticles with a large energy gap. Theoretical calculations by a hybrid DFT method demonstrated that the silver sulfide clusters with high Ag/S ratio exhibited more localized HOMO-LUMO orbitals, which consequently enlarged their band gap energies. These experimental and theoretical studies broaden our understanding of the fabrication of nanomaterials by virtue of the advantages of both bottom-up and top-down methods and meanwhile provide a viable means of adjusting the band gap of binary nanomaterials independent of their size.


Following in the footsteps of Hippocrates-interrelation between the incidence of odontogenic abscess and meteorological parameters.
Although many physicians in daily practice assume a connection between odontogenic infections and meteorological parameters, this has not yet been scientifically proven. Therefore, the aim of the present study was to evaluate the incidence of odontogenic abscess (OA) in relation to outdoor temperature and atmospheric pressure. An analysis of patients with an odontogenic abscess who presented at the emergency department within a period of 24 months was performed. Only patients who had not received surgical or antibiotic treatment prior to presentation and who lived in Berlin/Brandenburg were included. The OA incidence was correlated with the mean/maximum outdoor temperature and atmospheric pressure starting from 14 days before presentation. The statistical analysis was carried out using Poisson regression models with OA incidence as dependent and meteorological parameters as independent variables. A total of 535 patients (mean age 39.4 years; range 1 to 95 years) with 538 cases were included. Of these, 227 were hospitalized. The most frequent diagnosis was a canine fossa abscess. A significant association between mean (p = 0.0153) and maximum temperature (p = 0.008) on the day of the presentation and abscess incidence was observed. Furthermore, a significant correlation between OA incidence and maximum temperature 2 days before presentation was found (p = 0.034). The deviation of the mean temperature on the day of the presentation from the monthly mean temperature had a significant influence (p = 0.021) on the incidence of OA. In contrast to temperature, atmospheric pressure had no significant influence on the incidence of OA. This study supports a relationship between the incidence of odontogenic abscess and outdoor temperature, but not atmospheric pressure. A significantly higher frequency of patients with an OA presented at our emergency department on days with (comparably) low and high outdoor temperatures. Furthermore, a significant correlation between incidence and maximum temperature 2 days before presentation was found. The treatment of odontogenic infections has become a significant economic burden to public health care facilities. The results of this study may help to adapt the numbers of doctors/dentists on duty in relation to different weather conditions. In any case, it is an impetus to think outside the box.


Volatile organic compounds in asthma diagnosis: a systematic review and meta-analysis.
We aimed to assess the value and classification rate of exhaled volatile organic compounds (VOCs) in asthma diagnosis. A PRISMA-oriented systematic search for published studies regarding exhaled VOCs in asthma diagnosis was conducted based on predefined criteria. Studies presenting sensitivity and specificity values for the test were included in the meta-analysis. Pooled diagnosis odds ratios (DOR), area under the curve (AUC) and positive and negative likelihood ratios (LR) for exhaled VOC profiles were calculated; and publication bias, threshold effect and heterogeneity were estimated. Eighteen studies were selected for the qualitative analysis and six met the criteria for inclusion in the quantitative analysis. Mean (95% CI) pooled DOR, positive and negative LR were 49.3 (15.9-153.3), 5.86 (3.07-11.21) and 0.16 (0.10-0.26), respectively. The AUC value was 0.94. Only three of the 18 reviewed studies performed an external validation of the model using a different data set. The results from the revised studies suggest that exhaled VOCs are promising biomarkers for asthma diagnosis and that several compounds, mainly alkanes, may be significantly associated with asthma inflammation. However, there are still various constraints associated with standardization and externally validated studies are needed to introduce exhaled VOC profiling in a clinical scenario.


Hyperbaric oxygen therapy for sudden sensorineural hearing loss: a prospective trial of patients failing steroid and antiviral treatment.
To investigate the safety and efficacy of hyperbaric oxygen therapy (HBOT) in adult patients with sudden sensorineural hearing loss (SSNHL) who fail standard of care steroid and antiviral therapy. Prospective cohort study. An urban tertiary referral center. Nine adult patients presenting with SSNHL from December 2002 through February 2004. Patients with acute onset SSNHL of greater than 30 dB in three contiguous frequencies who failed to show audiometric improvement after 2 weeks of systemic steroids and antivirals were enrolled. Study patients received HBOT at 2.0 atmospheric pressure for 90 minutes while breathing 100% oxygen under a clear plastic hood in the chamber. Treatments were administered daily for 10 days over a 2-week period. Pre-and postHBOT mean hearing gains measured in decibels for pure-tone audiometry at 0.5, 1, 2, 3, and 4 KHz for bone and additional 8 KHz for air; pure-tone averages for air and bone; speech reception thresholds; and speech discrimination levels. Patient-reported subjective recovery rates (completely, substantially, partially, not improved) were also recorded. Overall, two patients had a dramatic improvement, and one patient had a dramatic improvement in his speech discrimination without improvement in other audiometric measures. Six patients had no demonstrable hearing gains. Two patients had complications of serous otitis media requiring myringotomy and pressure equalizing tube placement. No other complications were observed. Secondary HBOT after failure of systemic steroid and antiviral therapy may be associated with hearing gains in some patients with SSNHL.


Distributing questionnaires about smoking to patients: impact on general practitioners' recording of smoking advice.
Little is known about the impact of questionnaire-based data collection methods on the consulting behaviour of general practitioners (family physicians) who participate in research. Here data collected during a research project which involved questionnaires on smoking being distributed to patients before and after appointments with general practitioners (GPs) is analyzed to investigate the impact of this data collection method on doctors' documenting of smoking advice in medical records. Researchers distributed questionnaires on smoking behaviour to 6775 patients who attended consultations during surgery sessions with 32 GPs based in Leicestershire, UK. We obtained the medical records for patients who had attended these surgery sessions and also for a comparator group, during which no researcher had been present. We compared the documenting of advice against smoking in patient's medical records for consultations within GPs' surgery sessions where questionnaires had been distributed with those which occurred when no questionnaires had been given out. We obtained records for 77.9% (5276/6775) of all adult patients who attended GPs' surgery sessions, with 51.9% (2739) being from sessions during which researchers distributed questionnaires. Discussion of smoking was recorded in 8.0% (220/2739) of medical records when questionnaires were distributed versus 4.6% (116/2537) where these were not. After controlling for relevant potential confounders including patients' age, gender, the odds ratio for recording of information in the presence of questionnaire distribution (versus none) was 1.78 (95% CI, 1.36 to 2.34). Distributing questionnaires about smoking to patients before and after they consult with doctors significantly increases GPs' recording of discussions about smoking medical records. This has implications for the design of some types of research into addictive behaviours and further research into how data collection methods may affect patients' and doctors' behaviours is warranted.


Influence of host cells on the infectivity and neutralizability echovirus type 4 (Pesascek).
The heterogeneity of echovirus type 4 (strain Pesascek) is documented. This strain had a higher EOP on RD cells than on GMK-AH1 or primary green monkey kidney cells. It was more effectively neutralized in tests on RD cells than on GMK-AH1 cells. The latter phenomenon was analyzed on materials of Pesascek virus after banding in density gradients. A minor fraction was found that resisted neutralization as tested on either RD or GMK-AH1 cells. Another fraction containing the main peak of infectivity was rendered almost harmless to RD cells by neutralizing antibody, while still infecting GMK-AH1 cells. Filtration diminished the non-neutralizable fraction of virus, as did treatment of virus with disrupted membranes. The validity of the theory which holds aggregation of virus responsible for the non-neutralizable fractions, as well as the role played by different host cells for neutralizability, are discussed.


Squeezing the funding you need from today's capital sources.
Healthcare providers need to understand traditional and nontraditional financing options and other potential strategies for accessing capital. Common financing options include bonds, commercial lending, acquisition financing, and financing through the Department of Housing and Urban Development's Section 232 program. Alternative strategies for accessing capital include joint ventures, equity, sale of assets, fund-raising, capital leases, internal capital, public grants, and grants from foundations.


Papillary thyroid cancer: dual-energy spectral CT quantitative parameters for preoperative diagnosis of metastasis to the cervical lymph nodes.
To evaluate the use of dual-energy spectral computed tomographic (CT) quantitative parameters compared with the use of conventional CT imaging features for preoperative diagnosis of metastasis to the cervical lymph nodes in patients with papillary thyroid cancer. This study was approved by the ethics committee and all patients provided written informed consent. Analyses of quantitative gemstone spectral imaging data and qualitative conventional CT imaging features were independently performed by different groups of radiologists. Excised lymph nodes were located and labeled during surgery according to location on preoperative CT images and were evaluated histopathologically. Single and combined parameters were fitted to simple and multiple logistic regression models, respectively, by means of the generalized estimating equations method. Sensitivity and specificity analyses were performed by using receiver operating characteristic curves and were compared with data from the qualitative analysis. The slope of the spectral Hounsfield unit curve ( λHU slope of the spectral Hounsfield unit curve ), normalized iodine concentration, and normalized effective atomic number measured during both arterial and venous phases were significantly higher in metastatic than in benign lymph nodes. The best single parameter for detection of metastatic lymph nodes was venous phase λHU, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 62.0%, 91.1%, 80.6%, 79.7%, and 81.0%, respectively. The best combination of parameters was venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration, with values of 73.0%, 88.4%, 82.9%, 78.0%, and 85.3%, respectively. Compared with qualitative analysis, the venous phase λHU slope of the spectral Hounsfield unit curve showed higher specificity (91.1% vs 83.0%, P < .001) and similar sensitivity (62.0% vs 61.9%, P > .99), and the combined venous phase λHU slope of the spectral Hounsfield unit curve and arterial phase normalized iodine concentration showed higher sensitivity (73.0% vs 61.9%, P < .001) and specificity (88.4% vs 83.0%, P < .001). Quantitative assessment with gemstone spectral imaging quantitative parameters showed higher accuracy than qualitative assessment of conventional CT imaging features for preoperative diagnosis of metastatic cervical lymph nodes in patients with papillary thyroid cancer.


Control of unidirectional transport of single-file water molecules through carbon nanotubes in an electric field.
The transport of water molecules through nanopores is not only crucial to biological activities but also useful for designing novel nanofluidic devices. Despite considerable effort and progress that has been made, a controllable and unidirectional water flow is still difficult to achieve and the underlying mechanism is far from being understood. In this paper, using molecular dynamics simulations, we systematically investigate the effects of an external electric field on the transport of single-file water molecules through a carbon nanotube (CNT). We find that the orientation of water molecules inside the CNT can be well-tuned by the electric field and is strongly coupled to the water flux. This orientation-induced water flux is energetically due to the asymmetrical water-water interaction along the CNT axis. The wavelike water density profiles are disturbed under strong field strengths. The frequency of flipping for the water dipoles will decrease as the field strength is increased, and the flipping events vanish completely for the relatively large field strengths. Most importantly, a critical field strength E(c) related to the water flux is found. The water flux is increased as E is increased for E ≤ E(c), while it is almost unchanged for E > E(c). Thus, the electric field offers a level of governing for unidirectional water flow, which may have some biological applications and provides a route for designing efficient nanopumps.


Hospital physician payment mechanisms in Austria: do they provide gateways to institutional corruption?
Institutional corruption in the health care sector has gained considerable attention during recent years, as it acknowledges the fact that service providers who are acting in accordance with the institutional and environmental settings can nevertheless undermine a health care system's purposes as a result of the (financial) conflicts of interest to which the service providers are exposed. The present analysis aims to contribute to the examination of institutional corruption in the health sector by analyzing whether the current payment mechanism of separately remunerating salaried hospital physicians for treating supplementary insured patients in public hospitals, in combination with the public hospital physician's possibility of taking up dual practice as a self-employed physician with a private practice and/or as an attending physician in private hospitals, has the potential to undermine the primary purposes of the Austrian public health care system. Based on the analysis of the institutional design of the Austrian public hospital sector, legal provisions and directives have been identified, which have the potential to promote conduct on the part of the public hospital physician that systematically undermines the achievement of the Austrian public health system's primary purposes.


[Preventive treatment to avoid recurrence of stroke and TIA is effective].
Healthy living with physical activity, healthy eating habits, no smoking, and no alcohol overuse have an important role in primary and secondary stroke prevention. Further secondary prevention depends on type and cause of stroke or TIA. After intracerebral bleeding, ischemic stroke or TIA, preventive pharmacological therapies include antihypertensive drugs. After ischemic stroke or TIA, treatment with antithrombotics (oral anticoagulants or antiplatelets) and statins is recommended. In stroke due to unusual causes, the pharmacological preventive treatment described above may need modification. For symptomatic carotid stenosis, carotid surgery is recommended, preferably within the first 14 days after onset. A surgical preventive treatment is closure of patent foramen ovale in patients aged 18-60 years with ischemic stroke of unknown cause.


Transducin activation by the bovine opsin apoprotein.
The interaction of the bovine opsin apoprotein with transducin in rod outer segment membranes was investigated using a guanyl nucleotide exchange assay. In exhaustive binding experiments, opsin activates transducin, with half-maximal exchange activity occurring at 0.8 mol of opsin/mol of transducin. The opsin activity was light-insensitive, hydroxylamine-resistant, unaffected by stoichiometric concentrations of retinaloxime, and more heat-labile than rhodopsin. The t1/2 of transducin activation in the presence of excess opsin was 8.5 min, compared with 0.7 min for metarhodopsin (II). The second-order rate constants were determined to be 0.012 pmol of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S) bound per min/nM opsin and 0.35 pmol of GTP gamma S bound per min/nM metarhodopsin (II). Opsin was able to activate more than one transducin, although there appeared to be a turnover-dependent inactivation of the apoprotein. Opsin showed a broad pH range (5.8-7.4) for optimal activity, with no activity in buffers of pH > 9, whereas metarhodopsin (II) exhibited activity at pH > 9. Regulation of opsin activity by stoichiometric amounts of retinal was observed, with inhibition by 11-cis-retinal and stimulation by all-trans-retinal. A model for opsin activity is proposed.


Inhibition of compensatory renal growth by the N-terminus of a sheep-derived peptide.
The N-terminal sequence of a novel sheep-derived peptide with growth inhibitory activity has been obtained. The N-terminal fragment was chemically synthesised and designated EPL001. The kidney was chosen as the first mammalian system in which to study EPL001 since kidney growth can be accurately quantified following a surgical reduction in renal mass. Cell proliferation was measured in mouse collecting duct kidney (MCDK) cells stimulated with insulin-like growth factor I (IGF-I). Compensatory renal growth (CRG) was induced in Wistar rats and either EPL001 or an EPL001 antibody delivered by continuous renal tissue infusion. Mouse monoclonal antibodies to EPL001 were generated for immunoneutralisation, rabbit polyclonal antibodies were generated for immunohistochemistry. EPL001 had no apparent effect on IGF-I stimulated cell proliferation in MCDK cells in vitro, yet provoked a dose-dependent inhibition of CRG in vivo. An EPL001 antibody potentiated CRG, in the absence of exogenous EPL001, consistent with an inhibitory role in kidney growth for an endogenous peptide containing the EPL001 sequence. Tubular staining for epitopes to the EPL001 sequence was detected in normal human kidney sections and enhanced in renal cell carcinoma. Results support the presence of growth inhibitory activity in the N-terminus of a sheep-derived peptide with evidence for both its presence and endogenous activity in the kidney. Attempts to further characterise its structure and activity are ongoing.


A Systematic Review of Motivational Interviewing to Address Substance Use with Justice-Involved Adults.
Motivational Interviewing (MI) is widely used in substance abuse treatment, possibly due to the short sessions and the treatment's cost-effectiveness. Previous research has established the efficacy of MI among a broad range of populations and outcomes. However, there is a lack of a review of the knowledge about if MI works with justice-involved individuals who have substance use issues. Purpose: This review aimed to examine the extent of the literature on MI as a treatment to decrease rates of substance use for justice-involved individuals. Methods: The databases utilized for the review include Academic Search Complete (EBSCO), PsycINFO, and ProQuest. The dates for the literature inclusion were from 2008 to March 2020. The literature search was initiated in February and was completed in March 2020. Results: Five RCT studies were identified. Studies were conducted using populations during incarceration in prison, prior to release from jail, through probation, and those with DWI charges. However, all of the populations included were actively being monitored for substance use. All five studies found no difference between groups at the latest point in the study, which for most included the follow-up measure. Consideration for potential moderators such as severity and type of substance use, and length of treatment and follow up data are discussed. Conclusion: The results of the review indicated that more standardized and rigorous research is needed for exploring MI with individuals involved with the justice system with the focus of decreasing substance use.