From Co-MOF to CoNi-MOF to Ni-MOF: A Facile Synthesis of 1D Micro-/Nanomaterials.
Controlling the growth of metal-organic frameworks (MOFs) at the micro-/nanoscopic scale will result in new physical properties and novel functions into the materials without changing the chemical identities and the characteristic features of the MOFs themselves. Herein, we report a facile approach to synthesize a series of MOFs [Co-MOF, CoxNiy-MOFs (x and y represent the molar ratio of Co2+ and Ni2+ and x/y = 1:1, 1:5, 1:10, 1:15, and 1:20), and Ni-MOF] with a one-dimensional micro-/nanoscaled rod-like architecture. From Co-MOF to CoxNiy-MOFs to Ni-MOF, the diameters of the rods turn to be spindly with the increase of Ni2+ content which will facilitate the supercapacitor performances. Interestingly, Co1Ni20-MOF exhibits a highest specific capacity of 597 F g-1 at 0.5 A g-1 and excellent cycle performance (retained 93.59% after 4000 cycles) among these MOF materials owing to its micro-/nanorod structure with a smaller diameter and the synergy effect between the optimum molar ratio of Co2+ and Ni2+.


Phylogenetic analyses of nuclear, mitochondrial, and plastid multigene data sets support the placement of Mesostigma in the Streptophyta.
All extant green plants belong to 1 of 2 major lineages, commonly known as the Chlorophyta (most of the green algae) and the Streptophyta (land plants and their closest green algal relatives). The scaly green flagellate Mesostigma viride has an important place in the debate on the origin of green plants. However, there have been conflicting results from molecular systematics as to whether Mesostigma diverges before the Chlorophyta/Streptophyta split or is an early diverging flagellate member of the Streptophyta. Previous studies employed either a limited taxon sampling (plastid and mitochondrial genomes) or a small number of phylogenetically informative sites (single nuclear genes). Here, we use large data sets from the nuclear (125 proteins; 29,319 positions), mitochondrial (33 proteins; 6,622 positions), and plastid (50 proteins; 10,137 positions) genomes with an expanded taxon sampling (21, 13, and 28 species, respectively) to reevaluate the phylogenetic position of Mesostigma. Our study supports the placement of Mesostigma in the Streptophyta (as an early diverging lineage) and provides evidence that systematic biases have played a role in generating some of the previous conflicting results. Importantly, we demonstrate that using an increased taxon sampling as well as more realistic models of evolution allows increasing congruence among the nuclear, mitochondrial, and plastid data sets.


Magnetic Iron Oxide Nanowires Formed by Reactive Dewetting.
The growth and reactive dewetting of ultrathin films of iron oxides supported on Re(0001) surfaces have been imaged in situ in real time. Initial growth forms a nonmagnetic stable FeO (wüstite like) layer in a commensurate network upon which high aspect ratio nanowires of several microns in length but less than 40 nm in width can be fabricated. The nanowires are closely aligned with the substrate crystallography and imaging by X-ray magnetic circular dichroism shows that each contain a single magnetic domain. The driving force for dewetting appears to be the minimization of strain energy of the Fe3O4 crystallites and follows the Tersoff and Tromp model in which strain is minimized at constant height by extending in one epitaxially matched direction. Such wires are promising in spintronic applications and we predict that the growth will also occur on other hexagonal substrates.


IQGAP1‑siRNA inhibits proliferation and metastasis of U251 and U373 glioma cell lines.
IQ motif containing GTPase activating protein 1 (IQGAP1) is a scaffold protein, which is aberrantly expressed in several tumor types and is closely associated with the development, metastasis and prognosis of cancer. Several studies have demonstrated that IQGAP1 has broad prospects in the basic and clinical research of tumors. The present study aimed to explore the effects of IQGAP1‑small interfering (si) NA on the proliferation and metastasis of U251 and U373 glioma cell lines, which markedly expressed IQGAP1. The human glioma cell lines (U251 and U373) were transfected with siRNA and transfection efficacy was confirmed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. Cell proliferation was detected using the Cell Counting kit‑8, and cell metastasis capabilities were detected using cell adhesion, migration and invasion assays. In addition, the expression levels of several tumor‑associated genes were determined by RT‑qPCR and western blotting. The results indicated that IQGAP1 was expressed at higher levels in glioma tissues compared with in normal brain tissues. IQGAP1‑siRNA significantly inhibited cell proliferation, and cell adhesion, migration and invasion. Furthermore, the expression levels of matrix metalloproteinase (MMP)2, Snail, MMP9, fibronectin 1 and Twist were suppressed, and E‑cadherin was upregulated in response to siRNA‑IQGAP1. The present study identified the function of IQGAP1 in glioma cell biology, and indicated that it may be considered a novel target for glioma treatment.


A dominant negative Egr inhibitor blocks nerve growth factor-induced neurite outgrowth by suppressing c-Jun activation: role of an Egr/c-Jun complex.
Members of the Egr family of transcription factors are rapidly and robustly induced by neurotransmitters and neurotrophins and have been implicated in mediating enduring changes in neuronal function elicited by these stimuli. Because we have found in previous studies that a dominant negative inhibitor of Egr action, the Egr zinc finger domain (ZnEgr), blocks NGF-induced neurite outgrowth in PC12 cells, we have used this preparation to help identify the downstream targets of Egr proteins involved in plasticity. Our investigation into the mechanism of action of ZnEgr indicates that it blocks NGF-induced neurite outgrowth by suppressing activation of c-Jun, a critical step in the signaling pathway mediating this response. Although we had assumed that ZnEgr exerts its effects by binding to the Egr response element (ERE) and thereby blocking target gene regulation by Egr proteins, this classical mode of action appears to be too slow to mediate the effects of Egr proteins on c-Jun activation. In evaluating alternative ERE-independent mechanisms of Egr (and ZnEgr) action, we found that Egr1 and c-Jun coprecipitate and that ZnEgr disrupts formation of the Egr1/c-Jun complex. Furthermore, mutations of ZnEgr that greatly impair or abolish its ability to bind to the ERE do not block its ability to suppress c-Jun activation or neurite outgrowth induced by NGF. Accordingly, our studies indicate that Egr and ZnEgr proteins regulate c-Jun activation via a novel mechanism, protein-protein interaction with c-Jun, rather than via their classical mode of action, binding to the ERE.


Electronic and optical properties of strained graphene and other strained 2D materials: a review.
This review presents the state of the art in strain and ripple-induced effects on the electronic and optical properties of graphene. It starts by providing the crystallographic description of mechanical deformations, as well as the diffraction pattern for different kinds of representative deformation fields. Then, the focus turns to the unique elastic properties of graphene, and to how strain is produced. Thereafter, various theoretical approaches used to study the electronic properties of strained graphene are examined, discussing the advantages of each. These approaches provide a platform to describe exotic properties, such as a fractal spectrum related with quasicrystals, a mixed Dirac-Schrödinger behavior, emergent gravity, topological insulator states, in molecular graphene and other 2D discrete lattices. The physical consequences of strain on the optical properties are reviewed next, with a focus on the Raman spectrum. At the same time, recent advances to tune the optical conductivity of graphene by strain engineering are given, which open new paths in device applications. Finally, a brief review of strain effects in multilayered graphene and other promising 2D materials like silicene and materials based on other group-IV elements, phosphorene, dichalcogenide- and monochalcogenide-monolayers is presented, with a brief discussion of interplays among strain, thermal effects, and illumination in the latter material family.


Expression of the glucocorticoid receptor and its isoforms in relation to glucocorticoid resistance in childhood acute lymphocytic leukemia.
In vitro prednisolone resistance is a poor prognostic factor in the treatment of childhood acute lymphoblastic leukemia (ALL). In a cohort of 54 children with ALL, a lower expression of the glucocorticoid receptor (GR), but not the relative expression levels of the GR-alpha, GR-beta and GR-P isoforms, was associated with in vitro prednisolone resistance.


(R)-Desmolactone is a sex pheromone or sex attractant for the endangered valley elderberry longhorn beetle Desmocerus californicus dimorphus and several congeners (Cerambycidae: Lepturinae).
We report here that (4R,9Z)-hexadec-9-en-4-olide [(R)-desmolactone] is a sex attractant or sex pheromone for multiple species and subspecies in the cerambycid genus Desmocerus. This compound was previously identified as a female-produced sex attractant pheromone of Desmocerus californicus californicus. Headspace volatiles from female Desmocerus aureipennis aureipennis contained (R)-desmolactone, and the antennae of adult males of two species responded strongly to synthetic (R)-desmolactone in coupled gas chromatography-electroantennogram analyses. In field bioassays in California, Oregon, and British Columbia, traps baited with synthetic (R)-desmolactone captured males of several Desmocerus species and subspecies. Only male beetles were captured, indicating that this compound acts as a sex-specific attractant, rather than as a signal for aggregation. In targeted field bioassays, males of the US federally threatened subspecies Desmocerus californicus dimorphus responded to the synthetic attractant in a dose dependent manner. Our results represent the first example of a "generic" sex pheromone used by multiple species in the subfamily Lepturinae, and demonstrate that pheromone-baited traps may be a sensitive and efficient method of monitoring the threatened species Desmocerus californicus dimorphus, commonly known as the valley elderberry longhorn beetle.


7,7-Dichloro-1,6-dimethyl-2-oxa-5-thiabicyclo[4.1.0]heptane 5,5-dioxide and 6-chloro-2,3-dihydro-7-methyl-5-methylene-2H,3H,5H-1,4-dithiepine 1,1,4,4-tetraoxide.
The structures of a 2-oxa-5-thiabicyclo[4.1.0]heptane derivative, C(7)H(10)Cl(2)O(3)S, (I), and a 2H,3H,5H-1,4-dithiepine derivative, C(7)H(9)ClO(4)S(2), (II), are reported. The six-membered ring in (I) has an envelope conformation and the seven-membered ring in (II) adopts a chair conformation. There are no untoward intermolecular interactions in (I), but two Cl atoms make a short intermolecular contact across an inversion centre in (II), with a Cl.Cl distance of 3.2784 (9) A, some 0.22 A less than the sum of the van der Waals radii.


Players' perceptions of accountability factors in secondary school sports settings.
The purpose of this study was to gauge the extent to which students believed that the accountability strategies employed by their coaches had significant effects on their involvement in sports training sessions. Questionnaire data from 235 secondary school athletes were analyzed using linear structural relations to test a model of accountability hypothesized as operating in these coaching settings. The accountability strategy of active instruction was found to be a variable that significantly affected the students' valuing of their coaches as well as their task involvement. However, the rewards/consequences variable was not found to be a predictor of valuing or task involvement, suggesting that these athletes seemed more task oriented than reliant on external sanctions. The results of this study can only be generalized to team sport settings. Detailed examination needs to be made of the processes through which accountability factors operate for other contexts, including individual sports and competitive levels. Further research could also be undertaken into gender differences, especially in relation to the gender of coaches.


Evaluation of Health Equity Impact of Structural Policies: Overview of Research Methods Used in the SOPHIE Project.
This article briefly assesses the research methods that were applied in the SOPHIE project to evaluate the impact of structural policies on population health and health inequalities. The evaluation of structural policies is one of the key methodological challenges in today's public health. The experience in the SOPHIE project was that mixed methods are essential to identify, understand, and predict the health impact of structural policies. On the one hand, quantitative studies that included spatial comparisons or time trend analyses, preferably in a quasi-experimental design, showed that some structural policies were associated with improved population health and smaller health inequalities. On the other hand, qualitative studies, often inspired by realist approaches, were important to understand how these policies could have achieved the observed impact and why they would succeed in some settings but fail in others. This review ends with five recommendations for future studies that aim to evaluate, understand, and predict how health inequalities can be reduced through structural policies.


14-3-3 Proteins Are Involved in BR-Induced Ray Petal Elongation in Gerbera hybrida.
14-3-3 proteins play a major role in the regulation of primary metabolism, protein transport, ion channel activity, signal transduction and biotic/abiotic stress responses. However, their involvement in petal growth and development is largely unknown. Here, we identified and characterized the expression patterns of seven genes of the 14-3-3 family in gerbera. While none of the genes showed any tissue or developmental specificity of spatiotemporal expression, all seven predicted proteins have the nine α-helices typical of 14-3-3 proteins. Following treatment with brassinolide, an endogenous brassinosteroid, the Gh14-3-3 genes displayed various response patterns; for example, Gh14-3-3b and Gh14-3-3f reached their highest expression level at early (2 h) and late (24 h) timepoints, respectively. Further study revealed that overexpression of Gh14-3-3b or Gh14-3-3f promoted cell elongation, leading to an increase in ray petal length. By contrast, silencing of Gh14-3-3b or Gh14-3-3f inhibited petal elongation, which was eliminated partly by brassinolide. Correspondingly, the expression of petal elongation-related and brassinosteroid signaling-related genes was modified in transgenic petals. Taken together, our research suggests that Gh14-3-3b and Gh14-3-3f are positive regulators of brassinosteroid-induced ray petal elongation and thus provides novel insights into the molecular mechanism of petal growth and development.


A practice of ultra-fine tailings disposal as filling material in a gold mine.
A practice of cemented backfill technology with ultra-fine tailings in a gold mine was comprehensively presented, and a series of tests were conducted in accordance with the peculiar properties of ultra-fine tailings and the mining technology conditions. The test results show that, the tailings from Shuiyindong Gold Mine have a great grinding fineness, with the average particle diameter 22.03 μm, in which the ultra-fine particles with the diameter below 20 μm occupying 66.13%. The analysis results of chemical components of tailings indicate that the content of SiO2 is relatively low, i.e., 33.08%, but the total content of CaO, MgO and Al2O3 is relatively high i.e., 36.5%. After the settlement of 4-6 h, the tailing slurry with the initial concentration of 40% has the maximum settling concentration of 54.692%, and the corresponding maximum settling unit weight is 1.497 g/cm3. During the field application, the ultra-fine tailings and PC32.5 cement were mixed with the cement-tailings ratios of 1:3-1:8, and the slurry concentration of 50 wt% was prepared. Using the slurry pump, the prepared cemented backfill slurries flowed into the goaf, and then the strength of the cemented backfill body met the mining technique requirements in Shuiyindong Gold Mine, where the ore body has a smooth occurrence, with the average thickness of approximately 2 m and the inclination angle ranging from 5 to 10°.


Midline facial defects with ocular colobomata.
We describe 5 children with midline facial anomalies and iris colobomata reminiscent of frontonasal "dysplasia." Two patients have, in addition, abnormalities of the eyelids and one of them probably has the rare autosomal recessive condition frontofacionasal "dysplasia." The patients may have a new syndrome of midline facial defects, iris colobomata, and mental retardation.


Sequence-independent targeting of transmembrane proteins synthesized within vaccinia virus factories to nascent viral membranes.
The primary membrane of vaccinia virus, as well as those of other poxviruses, forms within a discrete cytoplasmic factory region. We recently determined the existence of an operative pathway from the endoplasmic reticulum within the virus factory to nascent viral membranes and demonstrated that a viral protein could be diverted from this pathway to Golgi membranes by the addition of COPII-binding sites (M. Husain, A. S. Weisberg, and B. Moss, Proc. Natl. Acad. Sci. USA, 103:19506-19511, 2006). Here we describe an investigation of the structural features that are required for transit of proteins to the viral membrane. Deletion of either the N-terminal domain or the C-terminal cytoplasmic tail from the conserved A9 protein did not prevent its incorporation into viral membranes, whereas deletion of the transmembrane domain resulted in its distribution throughout the cytoplasm. Nevertheless, replacement of the A9 transmembrane domain with the corresponding region of a nonpoxvirus transmembrane protein or of a vaccinia virus extracellular envelope protein allowed viral membrane targeting, indicating no requirement for a specific amino acid sequence. Remarkably, the epitope-tagged A9 transmembrane domain alone, as well as a heterologous transmembrane domain lacking a poxvirus sequence, was sufficient for viral membrane association. The data are consistent with a sequence-independent pathway in which transmembrane proteins that are synthesized within the virus factory and lack COPII or other binding sites that enable conventional endoplasmic reticulum exiting are incorporated into nascent viral membranes.


Glucose abnormalities and heart failure predict poor prognosis in the population-based Reykjavík Study.
The risk of cardiovascular disease increases progressively with increasing blood glucose from levels well below the diabetic threshold. In the Reykjavík Study the relationship between heart failure and abnormal glucose regulation was already apparent at the level of impaired glucose tolerance. The aim of this study was to determine the prognosis of participants with any glucose abnormality and heart failure and to test whether the combination of these conditions may adversely affect the subsequent prognosis. A prospective population-based study. Data from the first visit of 19 381 participants were used. Participants were divided into groups according to their glycaemic and heart failure level, and comparisons were made between the groups and disease-free participants serving as a reference group. The risk of mortality and morbidity was calculated with adjustments for main cardiovascular risk factors and ischaemic heart disease. Participants in the reference group were younger, had lower body mass indices and more seldom a history of myocardial infarction compared with diseased groups. Mortality was lowest in the reference group (P<0.0001) increasing to a maximum in participants with the combination of glucose abnormality and heart failure. Prognostically, the mortality risk associated with abnormal glucose regulation was increased but was lower than the risk of diabetes. The risk of a new myocardial infarction was highest in participants with diabetes [hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.3-2.0] or diabetes in combination with heart failure (HR 1.8; CI 1.1-2.7). Heart failure or glucose abnormalities are related to increased morbidity and mortality. The combination of glucose abnormality and heart failure did, however, not add further to the unfavourable prognosis in the presence of ischaemic heart disease.


Prospectively isolated mesenchymal stem/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation.
Mesenchymal stem/stromal cells (MSCs), which reside in the bone marrow (BM) and various other tissues, can self-renew and differentiate into mesenchymal lineages. Many groups have harvested rat MSCs (rMSCs) from rat BM (rBM) by using a flush-out procedure and have evaluated surface marker expression after long-term culture. However, MSCs gradually differentiate during expansion and exhibit altered proliferation rates, morphological features and functions in vitro. Variations in MSC isolation methods may alter the effectiveness of therapeutic applications. Here, on the basis of CD29 (Itgb1) and CD54 (Icam1) expression, we prospectively isolated a population with a high colony-forming ability and multi-lineage potential from the rBM, and we demonstrated that most of these cells expressed CD73. Successful engraftment of rMSCs was achieved by using a fluorescence-conjugated anti-CD73 antibody. In humans and mice, MSCs were also purified by CD73, thus suggesting that CD73 may serve as a universal marker for prospective isolation of MSCs. Our results may facilitate investigations of MSC properties and function.


How to help women at risk for acute stress disorder after childbirth.
For some women, childbirth is a traumatic experience that results in significant mental and emotional distress. Whether owing to birth complications, postpartum events such as hemorrhage or pre-existing risk factors such as past history of sexual abuse or rape, the emotional effects of childbirth trauma can lead to acute stress disorder (ASD). To provide the best care for women after childbirth, it's imperative that nurses be able to identify signs of ASD and intervene appropriately. There are many things nurses can do to help women in what could be the most vulnerable time of their lives.


Biological effects and bioaccumulation of pharmaceutically active compounds in crucian carp caged near the outfall of a sewage treatment plant.
Pharmaceutically active compounds (PhACs) have been universally detected in rivers, lakes and coastal waters that are affected by effluents from sewage treatment plants (STPs). In this study, the biological effects and bioaccumulation of PhACs were assessed in crucian carp (Carassius auratus) caged in an effluent-receiving river for 21 days. Compared with control fish in the laboratory and at a reference site, a significant reduction in hepatosomatic index (HSI) and increase in the biotransformation enzymes ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities were observed in the fish that was caged downstream from the STP outfall. In general, the total concentrations of PhACs detected in fish tissues were in the order as follows: liver > brain > gill > muscle > bile. The bioaccumulation factors (BAFs) for PhACs were between 195 and 2782 in the major storage tissue liver. The corresponding results for both risk quotient (RQ) and enhanced integrated biomarker response (EIBR) based on laboratory and field studies, respectively, indicated that environmental risk for adverse effects to aquatic organisms were clearly higher at the downstream of the STP outfall than at the upstream.


Metastatic melanoma with spontaneous regression, psoriasis and HLA-Cw6: case report and a hypothesis to explore.
Spontaneous regressions of metastatic melanoma are rare, but several cases have been described in the literature. Although the mechanism of the phenomenon is not well understood, it is postulated that an activation of the immune system is behind it. Here we report the case of a patient with metastatic melanoma that, without any treatment, regressed spontaneously. The patient presented psoriasis (a disease of the skin related with autoimmunity) linked with HLA-Cw6. We review the literature and hypothesize with the possible relationship between psoriasis, HLA-Cw6 and the spontaneous regression.


Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication.
The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were implanted into the mammary fat pad of nude mice. Subsequent immunolocalization studies on xenograph sections revealed only cytoplasmic stores of Cx43 and no detectable gap junctions. Moreover, DNA array and Western blot analysis demonstrated that overexpression of Cx43 or Cx26 in MDA-MB-231 cells down-regulated fibroblast growth factor receptor-3. Surprisingly, these results suggest that Cx43 and Cx26 induce their tumor-suppressing properties by a mechanism that is independent of significant gap junctional intercellular communication and possibly through the down-regulation of key genes involved in tumor growth. Moreover, our studies show that retroviruses are effective vehicles for delivering connexins to human breast tumor cells, facilitating potential gene therapy applications.


Clinical factors associated with positive capsule endoscopy findings in patients with obscure gastrointestinal bleeding: a single-center study.
Capsule endoscopy (CE) is a useful tool for patients with obscure gastrointestinal bleeding (OGIB), but positive finding rate differs among trials, which may be attributable to the difference in patients' background. To evaluate the predictive factors associated with positive findings on CE. Consecutive patients with OGIB who underwent CE between March 2004 and May 2015 at a single university hospital were enrolled. Patients' clinical factors and CE data were reviewed retrospectively, and we evaluated the relationship between clinical factors and positive findings by univariate and multivariate logistic regression analyses. Five hundred and seventy-eight patients were included in the analysis. Positive CE findings were obtained in 284 patients (49.1%). In multivariate analysis, low hemoglobin level (odds ratio (OR), 1.142 per 1 g/dL decrease; p < .001), Charlson comorbidity index (CCI) score (OR, 1.170 per 1 point increase; p = .002), and non-steroidal anti-inflammatory drug (NSAID) use (OR, 1.640; p = .044) were associated with an increased prevalence of positive findings. As for components of CCI, malignant tumor (OR, 1.839; p = .017) was associated with the positive findings. OGIB patient with a low-hemoglobin level, complex and severe comorbidities, and NSAID use should receive CE.


Liquid-Liquid Phase Separation in Oligomeric Peptide Solutions.
Oligomeric peptides exist widely in living organisms and play a role in a broad range of biological functions. We report the first observation of liquid-liquid phase separation (LLPS) in peptide solutions, in particular, solutions of peptides consisting of noncovalent oligomers. We determined the binary phase boundary of the oligomeric peptide solution and compared the result to the well-established phase diagram of globular proteins. We also provide simple theoretical interpretations of the similarities and differences between the phase diagrams of peptides and proteins. Finally, by tuning inter-oligomer interactions using a crowding agent, we demonstrated that LLPS is a universal phenomenon that can be observed under different solution conditions for a variety of peptides.


Remooring: A Qualitative Focus Group Exploration of How Educators Maintain Identity in a Sea of Competing Demands.
Longitudinal faculty development programs (LFDPs) are communities of practice (CoPs) that support development of participants' educator identity (EID). This study explored how program graduates negotiated their newly formed EIDs among competing identities and demands in academic medicine. In this multicenter, cross-sectional, qualitative study, graduates of two LFDP cohorts (one and five years post graduation) were invited in 2015 to participate in a one-hour, cohort-specific focus group. The focus group included questions about views of themselves as educators, experiences of transition out of the LFDP, and sustainability of their EID following program participation. Researchers analyzed transcripts using Wenger's CoP and Tajfel's social identity theories to guide interpretation of findings. Thirty-seven graduates, 17 from one year and 20 from five years post graduation, participated in eight focus groups. They described developing a new EID in their LFDP CoPs. Three major themes emerged: context, agency, and identity. A push-pull relationship among these themes influenced faculty members' EID trajectory over time. Graduates described feeling unmoored from their LFDP community after graduation and relied on individual agency to remoor their new identities to supports in the larger institutional context. LFDP graduation represented a transition point. Graduates found it challenging to lose supports from their time-limited CoP and remoor their EIDs to workplace supports. Remooring required individual agency and external support and affirmation. Faculty development programs must be designed with transition periods and sustainability in mind to ensure that participants and institutions can benefit from their transformative effects over time.


G-6-PD deficiency in the Pootai and the So communities in northeast Thailand.
The distribution of G-6-PD deficiency amongst two ethnic groups the Pootai and the So in northeast Thailand were studied. The prevalence of G-6-PD deficiency amongst the Pootai males was 9.7% while that amongst the So males was only 2.3%.


[Performance analysis of methods that predict transmembrane regions].
The increasing protein sequences from the genome project require the oretical methods to predict transmembrane regions. Evaluation of these prediction methods will not only help biologists to select appropriate methods, but also provide bioinformatian guidance to develop new methods. In this work, the latest membrane protein topology database was used as the test set and selected soluble proteins was used as control. The analyses of performance of published online prediction methods are presented. Results show that HMMTOP (2.0) has the best performance among current methods.


Abcb1a but not Abcg2 played a predominant role in limiting the brain distribution of Huperzine A in mice.
Huperzine A has been used for improving symptoms of Alzheimer's disease. Its cholinergic side effect is thought to be an exaggerated pharmacological outcome linked to its high brain or CNS concentrations. Although Huperzine A is brain penetrable, its interaction with efflux transporters (ABCB1 and ABCG2) has not been fully investigated. The aim of the present study was to characterize roles of ABCB1 and ABCG2 in the transmembrane transport of Huperzine A and identify a rate limiting step in its brain distribution. Data obtained from stably transfected MDCK II cells showed that Huperzine A is a substrate of ABCB1 but not ABCG2. ABCB1 inhibitors significantly inhibited ABCB1 mediated efflux of Huperzine A. In Abcb1a-/- mice, the brain to plasma concentration ratio of Huperzine A was significantly increased as compared to the wild type mice, while there were no obvious differences between the wild type and Abcg2-/- mice. Taken together, the present study demonstrated that ABCB1 but not ABCG2 played a predominant role in the efflux of Huperzine A across BBB. The current finding is clinically relevant as changes in ABCB1 activity in the presence of ABCB1 inhibitors or genetic polymorphism may affect efficacy and safety of Huperzine A.


[Amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea (author's transl)].
The amniotic alpha 1-foetoprotein of the 17th week of pregnancies with amenorrhea was tested by electroimmunodiffusion and radioimmunology. The results show a very good correlation between both methods. We can see from this study the possibility for any laboratory to test alpha 1-foetoprotein in amniotic fluid of patients with high risk pregnancies, as the beginning of pregnancy when amniotic punction is necessary without using radioimmunology.


Neuroplasticity in the adaptation to prosthodontic treatment.
To investigate cerebral cortical changes by using functional magnetic resonance imaging (fMRI) after denture renewal and to test how these relate to prosthodontic treatment adaptability as measured by chewing efficiency and maximum bite force. Ten complete denture wearers (five women and five men, mean age ± standard deviation: 70.3 ± 9.1 years) participated in the study. Each had their complete dentures renewed and underwent an fMRI examination with three functional tasks (lip pursing; jaw tapping; jaw clenching) as well as a color-mixing test for chewing efficiency and unilateral maximum bite force measurements. Recordings were performed with the old dentures (T0) and with the new dentures on insertion (T1) and at 1 week (T2) and 3 months postinsertion (T3). At T1, denture stability and retention (S/T) were assessed by two independent operators. Wilcoxon signed rank tests and Spearman's rho correlation were carried out for data analysis. The right and the left precentral gyrus (PRCG) and postcentral gyrus (POCG) were identified with significant activation across all three functional tasks. A statistically significant increase in the level of activity between T0 and T2 (POCG: P = .022; PRCG: P = .017) was found during jaw clenching tasks. Both regions of interest (PRCG, POCG) appeared to correlate with S/T of the new dentures while the subject performed a lip-pursing task (PRCG: r = 0.689, P = .027; POCG: r = 0.665, P = .036). The chewing efficiency and maximum bite force increased significantly during the adaptation to replacement dentures (chewing efficiency: T1-T2 P = .032, T2-T3 P = .012; maximum bite force right side: T2-T3 P = .047). Changes in brain activity occurred in the adaptation to replacement dentures and appeared to regain preinsertion activity levels during motor tasks involving the dental occlusion after 3 months postinsertion.


Total thyroidectomy for benign thyroid disease.
The use of total thyroidectomy in thyroid cancer treatment is not unanimous, and it is even more controversial when this procedure is advocated for benign diseases. On the other hand, the complication risk may have an increase up to 20 times in repeat operations for recurrence. The objective of the study was to evaluate the use of total thyroidectomy in benign diseases, multinodular goiter, and Graves disease to justify the authors' preference. Retrospective study of use of total thyroidectomy in benign diseases. Retrospective study of 1789 patients who underwent thyroidectomies from June 1990 to December 2000. Indication, extension of thyroidectomy, cancer incidence, and complications were analyzed. Total thyroidectomy was performed in 81.19% of 456 patients with nontoxic multinodular goiter, 93.93% of 33 with toxic multinodular goiter, 93.93% of 66 with recurrent multinodular goiter, and 49.18% of 122 with Graves disease. Thyroid cancer was found in 16.62%, 9.09%, 3.03% and 5.73% of patients, respectively. Transitory and permanent hypoparathyroidism, hematoma requiring surgical intervention, and transitory and permanent recurrent laryngeal nerve injury occurred in 12.27%, 1.61%, 0.26%, 1.88%, and 0.35% of the patients undergoing total thyroidectomy, respectively. Permanent complications of total thyroidectomy for nontoxic multinodular goiter and Graves disease were similar to nontotal thyroidectomy. Use of total thyroidectomy for nontoxic multinodular goiter increased from 53.33% of the patient to 81.19%, on average, with a concomitant increase of cancer diagnosis from 11.11% to 16,62%. The authors performed total thyroidectomy for all patients with Graves disease. Total thyroidectomy is the treatment of choice for multinodular goiter and thyroiditis, when there is bilateral gland involvement posterior to middle thyroid veins, and for Graves disease because it decreases the likelihood of future repeat operations for recurrent disease and thus the associated risks, when performed safely.


The associations between fatigue, apathy, and depression in Parkinson's disease.
Fatigue and apathy are two of the most common and most disabling non-motor symptoms of Parkinson's disease (PD). They have a high coincidence and can often be confused; moreover, their relationship is not fully understood. The aim of our study was to describe the coincidence of apathy with different fatigue domains in the presence/absence of depression and to separately describe the associations of different aspects of primary and secondary fatigue with apathy and other clinical and disease-related factors. A total of 151 non-demented patients with PD were examined using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Multidimensional Fatigue Inventory (MFI), Beck Depression Inventory-II, and Epworth Sleepiness Scale. The prevalence and severity of fatigue and apathy were significantly higher in depressed PD patients. However, our results show that depression, fatigue, and apathy can be clearly distinguished in PD. Apathy was associated with the MFI's-reduced motivation domain in both depressed and non-depressed patients. However, apathy was associated with mental fatigue aspects only in non-depressed patients, and it was not related to the physical aspects of fatigue in any of the studied groups. Although the pathophysiology of fatigue and apathy in PD is clearly multifactorial, in a proportion of PD patients, these symptoms are associated with depression, dopaminergic depletion in the mesocorticolimbic structures, and disruption of the prefrontal cortex-basal ganglia axis. Therefore, in some PD patients, adequate management of depression and optimal dopaminergic medication may improve both fatigue and apathy.


Anti-Helicobacter pylori and thrombin inhibitory components from Chinese dragon's blood, Dracaena cochinchinensis.
Chemical studies on the constituents of Dracaena cochinchinensis led to the discovery of eight new flavonoid derivatives ( 1- 8) along with 14 known compounds ( 9- 22). The identification and structural elucidation of these isolates were based on spectral analyses. All isolates were tested for antibacterial activities against Helicobacter pylori (ATCC43504) and thrombin inhibitory effects. As a result, new flavonoid derivatives 6 and 7 and (2 S)-4',7-dihydroxy-8-methylflavan ( 11) were found to be most efficacious against H. pylori (ATCC43504) with MIC values of 29.5, 29.5, and 31.3 microM, respectively, and the seven new flavonoid derivatives ( 1- 7) and one known biflavonoid ( 9) were observed to exhibit moderate thrombin inhibitory activity.


[A legal perspective on trends in eHealth].
eHealth aims to support and enhance citizens' health and healthcare in general using information technology. Medical confidentiality and protection of personal data play an important role in most eHealth applications. In July 2014, the Dutch Lower House adopted a bill that imposes conditions on electronic provision of patient data. When using social media, healthcare professionals would be prudent to observe the guidelines of the professional group. A European quality mark is required for medical apps that fall under the European Medical Devices Directive, but that does not dispel doubts about the reliability of medical apps.


Serial study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B.
To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibitory factor assay) and humoral (RIA) immunity to LSP (a macromolecular, liver-derived lipoprotein complex) and hepatic lectin (HL), the liver-specific receptor for desialylated glycoproteins, which appears to be a major target antigen for autoreactions in autoimmune chronic active hepatitis. Anti-LSP and anti-HL autoantibodies were found, at some stage during acute HBV infection, in 4/5 subjects, whereas cellular immunity to the same antigens was detected in only two patients. Sustained production of anti-HL antibodies was noted only in patients showing cellular immunity to this antigen and was apparently secondary to liver damage, whereas anti-LSP antibodies were first detected at the onset of liver injury when there was no evidence of T-cell immunity to the same antigenic complex. One explanation for this apparent dichotomy between cellular and humoral responses to LSP is that a helper T-cell response to the major envelope component of HBV, HBsAg, which precedes by 10-20 days the development of anti-LSP antibodies, promotes a humoral reaction to autoantigens contained in the LSP preparation, coexpressed with HBsAg, on the surface of infected hepatocytes.


Generalized pruritus in dysmetabolic hyperferritinemia treated by phlebotomy.
This paper describes a case of pruritus caused by dysmetabolic hyperferritinemia treated by multiple phlebotomies. A 63-year-old man was followed for generalized pruritus, which was resistant to the usual treatments. He presented with metabolic syndrome. Physical examination showed only excoriations and lichenification on the skin. The serum ferritin was high at 1043 ng/ml, with transferrin saturation at 67%. The other biological investigations and genetic tests for hemochromatosis were negative. In spite of the dietary measures, the ferritin level was still high (853 ng/ml). Magnetic resonance imaging confirmed hepatic iron overload.The association of hyperferritinemia, hepatic iron overload, and metabolic syndrome led to the diagnosis of dysmetabolic hyperferritinemia. Phlebotomies are an unusual treatment, but because the pruritus and hyperferritinemia were still present, phlebotomy was initiated. After 19 months, the patient reported improvement of his pruritus and normalization of ferritin levels.


[Persistent primitive trigeminal artery associated to aneurysm of the posterior communicating artery: a case report].
We report the case of a patient that presented with an intense headache caused by a subarachnoid hemorrhage. Magnetic resonance angiography demonstrated the existence of an aneurysm of the left posterior communicating artery, as well as of a persistent primitive trigeminal artery.


Antibody to Ebola virus in guinea pigs: Tandala, Zaire.
A case-control study was conducted to investigate the findings of antibody to Ebola virus in the serum of a guinea pig from Tandala, Zaire. Case households, defined by the possession of one or more guinea pigs, were compared to neighboring households without guinea pigs. Seven (5.1%) of 138 samples of human sera and 36 (26%) of 138 samples of guinea pig sera had antibody to Ebola virus. There was no clustering of seropositivity among humans or guinea pigs within households, nor was there any association between the ownership of guinea pigs and seropositivity among household members. These data suggest sporadic subclinical infection of guinea pigs and humans without a dominant role for person-to-person or guinea pig-to-guinea pig transmission.


Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane.
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells. In addition, the relevant molecular mechanism was explored by immunoprecipitation. The increase in Fluoromyelin Green staining and proteolipid protein expression was not significant in the corpus callosum of CathD-/- mice at the age of P11, P14 and P24. Proteolipid protein expression was weak at each time point and was mostly accumulated around the nucleus. The number of oligodendrocyte lineage cells (olig2+) and mature oligodendrocytes (CC1+) significantly decreased between P14 and P24. In the oligodendrocyte precursor cell culture of CathD-/- mice, the morphology of myelin basic protein-positive mature oligodendrocytes was simple while oligodendrocyte precursor cells showed delayed differentiation into mature oligodendrocytes. Moreover, more proteolipid protein gathered in late endosomes/lysosomes (LEs/Ls) and fewer reached the plasma membrane. Immunohistochemistry and immunoelectron microscopy analysis showed that CathD, proteolipid protein and VAMP7 could bind with each other, whereas VAMP7 and proteolipid protein colocalized with CathD in late endosome/lysosome. The findings of this paper suggest that CathD may have an important role in the myelination of CNS, presumably by altering the trafficking of proteolipid protein.


Age does not affect airway pH and ammonia as determined by exhaled breath measurements.
Measurement of airway pH has been used as a diagnostic and monitoring tool in a variety of pulmonary diseases in adults. These diseases occur across a wide age range. Few investigations have addressed the effects of aging on airway pH and ammonia. The aim of this study was to determine whether exhaled breath condensate (EBC) measurements of pH and ammonia differ in older and younger populations of normal subjects. Twenty-three normal younger individuals (median age-24 years) and 25 normal older participants (median age-72 years) were investigated by measuring EBC for pH and ammonia using recommended methodologies. EBC ammonia and pH values were not significantly different between younger and older individuals. Thus, we conclude that EBC ammonia and pH do not appear to be affected by age.


Evaluation of the marrow culture on the macrophage layer covering intraperitoneally implanted membrane as an assay for hemopoietic progenitor cells.
When cellulose acetate membranes are implanted into abdominal cavity of mice they turn into a foreign body overgrown with macrophages. Such macrophage layer has been shown by other authors to be able to support the growth of hemopoietic colonies formed by intraperitoneally injected hemopoietic cells. This study confirms and extends this observation by showing that both granulopoietic and erythropoietic colonies may be observed. The number of colonies grown is in linear correlation with that of injected hemopoietic cells. The frequency of erythropoietic colonies was greatly enhanced by blood letting of the host mice. Colony forming cells were most numerous in the bone marrow then in the spleen and peripheral blood and hardly in the thymus. Prior irradiation of the host mice was essential for obtaining colony growth and the optimal dose was determined to be 6.0 Gy. This technique opens the way to studies into hemopoietic progenitor cells for laboratories having no sophisticated tissue culture equipment and where necessary reagents are easily available.


Humidity-conditioned gravimetric method to measure the water content of hydrogel contact lens materials.
A method to determine the humidity-conditioned gravimetric water content of hydrogel contact lens materials has been developed, in which errors due to blotting have been eliminated by conditioning the lens in a series of relative humidity (RH) environments before measuring the water content gravimetrically, and then extrapolating the water content to 100% RH. This method has been used to determine the water contents of representative materials from each of the four FDA lens groups, which were compared with their labeled values, as well as with values obtained from refractive index measurements. The deviation of the water content of soft contact lenses as measured by refractive index from that obtained gravimetrically increased as the water content decreased. The humidity-conditioned gravimetric method to determine water content of hydrophilic contact lenses is being proposed as an International Organization for Standardization (ISO) standard, as an improvement over the gravimetric and refractive index methods.


Ab initio, density functional theory, and continuum solvation model prediction of the product ratio in the S(N)2 reaction of NO2(-) with CH3CH2Cl and CH3CH2Br in DMSO solution.
The reaction pathways for the interaction of the nitrite ion with ethyl chloride and ethyl bromide in DMSO solution were investigated at the ab initio level of theory, and the solvent effect was included through the polarizable continuum model. The performance of BLYP, GLYP, XLYP, OLYP, PBE0, B3PW91, B3LYP, and X3LYP density functionals has been tested. For the ethyl bromide case, our best ab initio calculations at the CCSD(T)/aug-cc-pVTZ level predicts product ratio of 73% and 27% for nitroethane and ethyl nitrite, respectively, which can be compared with the experimental values of 67% and 33%. This translates to an error in the relative DeltaG* of only 0.17 kcal mol(-1). No functional is accurate (deviation <0.5 kcal mol(-1)) for predicting relative DeltaG*. The hybrid X3LYP functional presents the best performance with deviation 0.82 kcal mol(-1). The present problem should be included in the test set used for the evaluation of new functionals.


The utility of heart-type free fatty-acid binding-protein (HFABP) levels for differentiating acute ischemic stroke from stroke mimics.
Heart-type fatty acid-binding protein (HFABP) is found in the myocardium, brain, and some organs and is rapidly released from damaged cells into the circulation in case of ischemia. We aimed to determine the diagnostic utility of HFABP levels in patients suggesting acute ischemic stroke (AIS). This study was a prospective, single-center, observational diagnostic accuracy study with a nested cohort design. The estimated sample size was 126 patients, with a 1:1 case and control ratio. We included all consecutive patients with a lateralizing symptom (motor or sensory) or finding suggesting AIS (139 patients) who presented to ED within 24 h of their symptom onset and collected plasma at admission to the ED. After further evaluations, 111 patients (79.8%) were diagnosed with AIS and 28 with other neurological diseases (stroke-mimics). In our study, the median HFABP levels of the cases and controls were 2.6 μg/ml and 2.2 μg/ml, respectively, without any statistically significant difference (p = 0.120). The diagnostic accuracy of HFABP for AIS was also insignificant at 0.60 (95% CI 0.51-0.68; p = 0.119). Plasma HFABP level is not a marker that can differentiate AIS from other neurological pathologies in patients presenting to the ED, with findings suggesting AIS.


Calcium oxalate crystals in fetal bovine serum: implications for cell culture, phagocytosis and biomineralization studies in vitro.
Cell culture methods and models are key investigative tools for cell and molecular biology studies. Fetal bovine serum (FBS) is commonly used as an additive during cell culture since its constituents promote cell survival, proliferation and differentiation. Here we report that commercially available FBS from different major suppliers consistently contain precipitated, calcium oxalate crystals-either in the monohydrate (COM) or dihydrate (COD) form. Mineral structure and phase identification of the crystals were determined by X-ray diffraction, chemical composition by energy-dispersive X-ray microanalysis, and imaging and measurement of crystal growth steps by atomic force microscopy-all identified and confirmed crystallographic parameters for COM and COD. Proteins binding to the crystals were identified by immunoblotting, revealing the presence of osteopontin and fetuin-A (alpha(2)HS-glycoprotein)--known regulators of crystal growth found in serum. Macrophage cell cultures exposed to calcium oxalate crystals showed internalization of the crystals by phagocytosis in a process that induced disruption of cell-cell adhesion, release of reactive oxygen species and membrane damage, events that may be linked to the release of inflammatory cytokines by these cells into the culture media. In conclusion, calcium oxalate crystals found in commercially available FBS are toxic to cells, and their presence may confound results from in vitro studies where, amongst others, phagocytosis, biomineralization, renal cell and molecular biology, and drug and biomaterial testing are being examined.


How to prevent burnout in cardiologists? A review of the current evidence, gaps, and future directions.
Burnout is rising in all physicians, and cardiologists are not an exemption. Cardiology is a very popular specialty among medical students as it is associated with outstanding training standards and high prestige and income. In this review, we critically summarize the evidence on consequences, causes, and evidence-based interventions for burnout with a view toward recommending the best strategies for promoting wellness in cardiologists. Only a handful of studies have examined burnout specifically in cardiologists. Evidence therefore was mainly extrapolated by larger studies in all physicians and other physician specialties. Burnout in cardiologists has serious negative personal and professional consequences and is associated with suboptimal healthcare outcomes for patients. Burnout in cardiologists is primarily driven by professional and healthcare system demands and inefficiencies such as excessive workload and role complexity, training and certification demands, inefficient compensation models and lack of resources, computerization, and loss of autonomy. Moreover, loss of connectedness with patients, difficulties in balancing work and personal life and overvaluing compulsiveness and perfectionism in medical practice further increase the risk for burnout. Burnout among cardiologists may be best mitigated by organizational strategies complemented by individual stress reduction and reflection techniques under the resilience-based approach. Large-scale strategies are needed to mitigate burnout and promote physician wellness as a shared responsibility of healthcare systems and individuals and be committed in creating a new culture in medicine.


Severe obstructive sleep apnoea, aortic dissection and aortopulmonary fistula in a 56-year-old patient with syncope.
We present a case of a 56-year-old patient with obstructive sleep apnoea (OSA) presenting with acute decompensated heart failure and signs of cardiogenic shock. Echocardiography and CT imaging led to the diagnosis of acute type A aortic dissection (AD) complicated by aortopulmonary fistula (APF). The patient underwent successful surgical repair with complicated postoperative course including pulseless electrical activity arrest. This case highlights the underappreciated role of untreated OSA as a risk factor for AD. Furthermore, it presents an opportunity to review APFs as a rare complication of AD. We discuss the available evidence linking OSA and AD, review currently reported cases of APF, briefly outline the haemodynamics of this acute left-to-right shunt and discuss management of this rare but deadly complication.


Simultaneous sequence transfer into two independent locations of a reporter vector using MultiSite Gateway technology.
The bacteriophage lambda recombination system is increasingly used for recombinant DNA applications that involve the frequent transfer of sequences into and between shuttle and reporter vectors. This approach bypasses the need for restriction endonucleases or ligases and, as such, is easily scalable and automated. However this system has not yet been tested for the ability to support the simultaneous introduction of donor fragments into two separate target sites of a single reporter plasmid. This attribute would greatly facilitate studies of cis-regulatory elements that only function in specific combinations, such as a class of regulatory elements known as chromatin insulators. With the goal of facilitating a screen for chromatin insulators, we sought to determine whether the commercially available MultiSite Gateway Technology recombination system could be used to simultaneously insert candidate insulator elements into two separate locations of a functional reporter plasmid. We show that this application is both highly efficient and specific, generating the desired recombination products nearly three quarters of the time without disrupting the specificity of the reporter system. As such, these studies establish a novel application of the MultiSite Gateway Technology for the generation of recombinant reporter plasmids where the constituent elements function in a combinatorial fashion.


[Assessment of the Quantel Medical 20-Mhz Ultrasound Cinescan in intraocular measurements].
Evaluation of the Quantel Medical 20-MHz Ultrasound Cinescan using a closed transducer in intraocular measurements and its reproducibility. We measured sulcus-to-sulcus distance of 40 control eyes using the20-MHz Cinescan. Then we compared the sonography to the Oculus Pentacam based on the Scheimpflug principle in the measurements of anterior chamber depth, cornea-to-implant distance, and implant-to-crystallin lens distance in patients who underwent phakic implantation (56 eyes). With this technique, the sulcus-to-sulcus distance can be measured with a reproducibility of 86%-88% (p<0.05). The authors show that the corneal diameter is not correlated with the sulcus measurement (R=24%, p<0.05). Several techniques are used to quantify anterior segment biometry. Some of these methods, such as White-to-White, are too empirical and others, such as the Scheimpflug camera - for example the EAS-1000 (Nidek) - or high-frequency ultrasound - Ultrasound BioMicroscopy UBM P45 (Paradigm) - are too expensive. The 20-MHz Cinescan has good reproducibility and provides easier access to anterior segment biometry. The 20-MHz Cinescan appears to be an accessible technique that may become a useful tool in the refractive surgery of the phakic intraocular lens.


High Dose Intravitreal Bevacizumab for Refractory Pigment Epithelial Detachment in Age-related Macular Degeneration.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is the first choice of treatment for age-related macular degeneration. However, quite a few eyes treated using conventional dose anti-VEGF (CDAV) have persistent pigment epithelial detachment (PED) on optical coherence tomography. This study investigated the efficacy and safety of high dose anti-VEGF (HDAV) for refractory PED. In this retrospective study, 31 eyes of neovascular age-related macular degeneration patients with persistent PED findings despite six or more intravitreal injections of CDAV (bevacizumab 1.25 mg or ranibizumab 2.5 mg) were analyzed. Changes in visual outcome, central foveal thickness, and PED height were compared before and after HDAV (bevacizumab 5.0 mg) for these refractory PED cases. The mean age of patients was 67.7 years. The number of CDAV injections was 12.1. The number of HDAV injections was 3.39. Best-corrected visual acuity in logarithm of the minimum angle of resolution before and after HDAV was 0.49 and 0.41 (p < 0.001), respectively. Central foveal thickness before and after HDAV was 330.06 and 311.10 µm (p = 0.125), respectively. PED height before and after HDAV was 230.28 and 204.07 µm (p = 0.014), respectively. There were no serious adverse reactions in all the eyes. Increasing the dose of bevacizumab in refractory PED may be a possible treatment option.


An analysis of tacrolimus-related complications in the first 30 days after liver transplantation.
Orthotopic liver transplantation has improved survival in patients with end-stage liver disease; however, therapeutic strategies that achieve ideal immunosuppression and avoid early complications are lacking. To correlate the dose and level of Tacrolimus with early complications, e.g., rejection, infection and renal impairment, after liver transplantation. From November 2011 to May 2013, 44 adult liver transplant recipients were studied in this retrospective comparative study. The most frequent indication for liver transplantation was hepatitis C cirrhosis (47.7%), with a higher prevalence observed in male patients (68.18%). The ages of the subjects ranged from 19-71 and the median age was 55.5 years. The mean length of the hospital stay was 16.1±9.32 days and the mean Model for End-stage Liver Disease score was 26.18±4.28. There were five cases of acute cellular rejection (11.37%) and 16 cases of infection (36.37%). The blood samples that were collected and analyzed over time showed a significant correlation between the Tacrolimus blood level and the deterioration of glomerular filtration rate and serum creatinine (p<0.05). Patients with infections had a higher serum level of Tacrolimus (p = 0.012). The dose and presence of rejection were significantly different (p = 0.048) and the mean glomerular filtration rate was impaired in patients who underwent rejection compared with patients who did not undergo rejection (p = 0.0084). Blood Tacrolimus levels greater than 10 ng/ml were correlated with impaired renal function. Doses greater than 0.15 mg/kg/day were associated with the prevention of acute cellular rejection but predisposed patients to infectious disease.


Effect of age on the human high affinity interleukin 2 receptor of phytohaemagglutinin stimulated peripheral blood lymphocytes.
High affinity interleukin 2 receptors (HA-IL-2R) on mitogen- or antigen-stimulated T cells have been shown to efficiently bind interleukin 2 (IL-2) and to transduce the activation signal(s) that facilitate proliferation. This study was initiated to determine whether the impaired proliferative response of T cells from elderly individuals can be attributed to the defective expression of HA-IL-2R. While cells from both young and old individuals had statistically insignificant differences in the number of HA-IL-2R per membrane IL-2R-positive cell and these receptors displayed similar binding affinities with 125I-IL-2, there were consistently fewer cells and fewer cells expressing HA-IL-2R in the cell cultures from elderly individuals. The magnitude of the age-associated impairment in cell proliferation was decreased, but remained present, when Percoll fractionated lymphoblasts, as compared to peripheral blood lymphocytes (PBL), were cultured in the presence of exogenous interleukin 2 (IL-2). The results demonstrate that a significantly larger percentage of lymphocytes from elderly individuals do not respond to mitogenic stimulation and, probably due to stimulus stress, die in culture. As a consequence there are fewer functionally competent cells expressing the HA-IL-2R in cultures from elderly individuals, which in turn contributes to the age-related defect in the lymphocyte proliferative response.


Psychiatric-Mental Health Nurses' Exposure to Clients With Problematic Internet Experiences: A Mixed-Methods Pilot Study.
The current study explored the type and number of problematic Internet experiences (PIE) encountered by psychiatric-mental health nurses (PMHN) in clinical practice and analyzed PMHNs' clinical cases of clients with PIE. A mixed-methods quantitative survey with a qualitative component measured the types and number of PIE cases via a descriptive survey and derived themes using narrative inquiry methodology from written case descriptions. A sample of 16 PMHNs provided quantitative data and nine participants summarized clinical cases. PMHNs reported 92 adult and 33 child cases of PIE. Six themes were derived from the narrative data: (a) searching for pornography; (b) developing online romantic relationships; (c) online gaming is ruining my life; (d) spending excessive time on the Internet; (e) coming to terms with online sexual behaviors and addiction; and (f) cyberbullying. Implications for PMHN practice include the need for further assessment and intervention as PIE increase in the future.


Geographically weighted temporally correlated logistic regression model.
Detecting the temporally and spatially varying correlations is important to understand the biological and disease systems. Here we proposed a geographically weighted temporally correlated logistic regression (GWTCLR) model to identify such dynamic correlation of predictors on binomial outcome data, by incorporating spatial and temporal information for joint inference. The local likelihood method is adopted to estimate the spatial relationship, while the smoothing method is employed to estimate the temporal variation. We present the construction and implementation of GWTCLR and the study of the asymptotic properties of the proposed estimator. Simulation studies were conducted to evaluate the robustness of the proposed model. GWTCLR was applied on real epidemiologic data to study the climatic determinants of human seasonal influenza epidemics. Our method obtained results largely consistent with previous studies but also revealed certain spatial and temporal varying patterns that were unobservable by previous models and methods.


Differences in epidemiologic risk factors for colorectal adenomas and serrated polyps by lesion severity and anatomical site.
Using a case-control design, we evaluated differences in risk factors for colorectal polyps according to histological type, anatomical site, and severity. Participants were enrollees in the Group Health Cooperative aged 20-79 years who underwent colonoscopy in Seattle, Washington, between 1998 and 2007 and comprised 628 adenoma cases, 594 serrated polyp cases, 247 cases with both types of polyps, and 1,037 polyp-free controls. Participants completed a structured interview, and polyps were evaluated via standardized pathology review. We used multivariable polytomous logistic regression to compare case groups with controls and with the other case groups. Factors for which the strength of the association varied significantly between adenomas and serrated polyps were sex (P < 0.001), use of estrogen-only postmenopausal hormone therapy (P = 0.01), and smoking status (P < 0.001). For lesion severity, prior endoscopy (P < 0.001) and age (P = 0.05) had significantly stronger associations with advanced adenomas than with nonadvanced adenomas; and higher education was positively correlated with sessile serrated polyps but not with other serrated polyps (P = 0.02). Statistically significant, site-specific associations were observed for current cigarette smoking (P = 0.05 among adenomas and P < 0.001 among serrated polyps), postmenopausal estrogen-only therapy (P = 0.01 among adenomas), and obesity (P = 0.01 among serrated polyps). These findings further illustrate the epidemiologic heterogeneity of colorectal neoplasia and may help elucidate carcinogenic mechanisms for distinct pathways.


A new leafhopper genus and two new species of the tribe Scaphytopiini (Hemiptera: Cicadellidae: Deltocephalinae) from China.
New leafhopper taxa in the deltocephaline tribe Scaphytopiini Oman are described: Xenovarta lui sp. n., and a new genus and species Aparaphysis lushuiiensis, gen. n., sp. n. from China. Detailed morphological descriptions and illustrations of the new genus and species are given. A checklist to genera of Scaphytopiini is provided.


Enhanced production of tumour necrosis factor alpha (TNF-alpha) by its precursor on the cell surface of primed THP-1 cells.
To clarify the biological significance of tumour necrosis factor alpha (TNF-alpha) precursor, we analysed its expression at the primed and triggered stages using human monocyte-like cell line THP-1. To prime them, THP-1 cells were treated with either recombinant human interferon gamma (rIFN-gamma) or recombinant human tumour necrosis factor alpha (rTNF-alpha). At the primed stage, transient accumulation of TNF-alpha, mRNA and a small amount of 26-KDa TNF-alpha precursor was observed, and the precursor molecule was located on the cell surface. Following treatment of the primed cells with bacterial lipopolysaccharide (LPS), augmentation of transcription of TNF-alpha mRNA and production of a larger amount of TNF-alpha precursor were observed followed by secretion of a larger amount of mature TNF-alpha (17-KDa) than secreted by the unprimed cells (triggered stage). This suggests that with priming THP-1 cells might be changed to a stage where they are ready for production of a larger amount of TNF-alpha at the triggered stage. When either primed or unprimed THP-1 cells were pretreated with anti-TNF-alpha antibody, augmentation of TNF-alpha production by primed THP-1 cells was specifically suppressed, suggesting that TNF-alpha precursor itself may play an important role in the enhancement of TNF-alpha production by the primed macrophages after treatment with LPS.


A new measuring and identification approach for time-varying bioimpedance using multisine electrical impedance spectroscopy.
The bioimpedance measurement/identification of time-varying biological systems Z(ω, t) by means of electrical impedance spectroscopy (EIS) is still a challenge today. This paper presents a novel measurement and identification approach, the so-called parametric-in-time approach, valid for time-varying (bio-)impedance systems with a (quasi) periodic character. The technique is based on multisine EIS. Contrary to the widely used nonparametric-in-time strategy, the (bio-)impedance Z(ω, t) is assumed to be time-variant during the measurement interval. Therefore, time-varying spectral analysis tools are required. This new parametric-in-time measuring/identification technique has experimentally been validated through three independent sets of in situ measurements of in vivo myocardial impedance. We show that the time-varying myocardial impedance Z(ω, t) is dominantly periodically time varying (PTV), denoted as ZPTV(ω, t). From the temporal analysis of ZPTV(ω, t), we demonstrate that it is possible to decompose ZPTV(ω, t) into a(n) (in)finite sum of fundamental (bio-)impedance spectra, the so-called harmonic impedance spectra (HIS) Zk(ω)s with [Formula: see text]. This is similar to the well-known Fourier series of a periodic signal, but now understood at the level of a periodic system's frequency response. The HIS Zk(ω)s for [Formula: see text] actually summarize in the bi-frequency (ω, k) domain all the temporal in-cycle information about the periodic changes of Z(ω, t). For the particular case k = 0 (i.e. on the ω-axis), Z0(ω) reflects the mean in-cycle behavior of the time-varying bioimpedance. Finally, the HIS Zk(ω)s are directly identified from noisy current and voltage myocardium measurements at the multisine measurement frequencies (i.e. nonparametric-in-frequency).


Aldosterone-sensitive repression of ENaCalpha transcription by a histone H3 lysine-79 methyltransferase.
Aldosterone is a major regulator of epithelial Na(+) absorption. One of its principal targets is the epithelial Na(+) channel alpha-subunit (ENaCalpha), principally expressed in the kidney collecting duct, lung, and colon. Models of aldosterone-mediated trans-activation of the ENaCalpha gene have focused primarily on interactions of liganded nuclear receptors with the ENaCalpha gene promoter. Herein, we demonstrate that the murine histone H3 lysine-79 methyltransferase, murine disruptor of telomeric silencing alternative splice variant "a" (mDot1a), is a novel component in the aldosterone signaling network controlling transcription of the ENaCalpha gene. Aldosterone downregulated mDot1a mRNA levels in murine inner medullary collecting ducts cells, which was associated with histone H3 K79 hypomethylation in bulk histones and at specific sites in the ENaCalpha 5'-flanking region, and trans-activation of ENaCalpha. Knockdown of mDot1a by RNA interference increased activity of a stably integrated ENaCalpha promoter-luciferase construct and expression of endogenous ENaCalpha mRNA. Conversely, overexpression of EGFP-tagged mDot1a resulted in hypermethylation of histone H3 K79 at the endogenous ENaCalpha promoter, repression of endogenous ENaCalpha mRNA expression, and decreased activity of the ENaCalpha promoter-luciferase construct. mDot1a-mediated histone H3 K79 hypermethylation and repression of ENaCalpha promoter activity was abolished by mDot1a mutations that eliminate its methyltransferase activity. Collectively, our data identify mDot1a as a novel aldosterone-regulated histone modification enzyme, and, through binding the ENaCalpha promoter and hypermethylating histone H3 K79 associated with the ENaCalpha promoter, a negative regulator of ENaCalpha transcription.


Patient- and lesion-tailored algorithm of endovascular treatment for arterial occlusive disease of extracranial arteries supplying the brain: safety of the treatment at 30-day follow-up.
Although surgical endarterectomy remains the treatment of choice for carotid artery stenosis, stenting plays an important role as an alternative treatment modality, especially in high-risk patients. The actual safety profile associated with stenting procedures is probably better than that reported by randomized controlled trials. To assess the safety of stent implantations in extracranial arteries supplying the brain, and also to identify risk factors associated with this procedure. This was a post hoc analysis, with 30-day follow-up. We analyzed the results of treatment of 372 patients who underwent 408 procedures, 197 such procedures in asymptomatic, and 211 in symptomatic individuals. Stenting procedures were performed using a technique and armamentarium which were tailored to the type and anatomy of lesions. There were 6 (1.5%) strokes, including 2 (0.5%) major strokes, 1 ipsi- and 1 contralateral, and 4 (1.0%) minor strokes. In asymptomatic patients there was 1 (0.3%) minor stroke. Transient ischemic attacks occurred in 5 (1.2%) patients. There were 2 (0.5%) non-STEMI myocardial infarctions and 2 (0.5%) non-stroke related fatalities. Risk factors of these adverse events were diabetes mellitus, lesions localized in a tortuous segment of the artery, embolic material in the filter and bilateral stenoses of carotid arteries. Additional risk factors in asymptomatic patients were renal impairment and advanced coronary artery disease; and in symptomatic patients, grade 3 arterial hypertension, dislipidemia, cigarette smoking and lesions requiring predilatation. Stenting procedures of extracranial arteries supplying the brain, which are tailored to the type and anatomy of lesions, seem to be relatively safe.


Enhanced erythrocytic lipid peroxides level in rabbits after repeated parental administration of iron.
An experiment was conducted in rabbits to evaluate the possible involvement of oxidative stress in iron-overload animals. Ten adult female New Zealand white rabbits were divided into 2 equal groups with 5 animals each. Group II animals received intramuscular iron dextran injections (120 mg/kg body wt/day) on alternate day for 14 days (8 injections), while Group I animals did not receive any iron supplementation to serve as negative controls. The blood samples were collected by cardiac puncture before the start of iron dosing and thereafter, at weekly intervals for 28 days. The samples were processed to measure blood iron concentration, packed cell volume, erythrocytic lipid peroxide (LPO) level, superoxide dismutase (SOD) and catalase (CAT) activities. The blood iron concentration showed a rising trend following repeated iron administration, and the mean level recorded on day 14 was significantly higher than respective day 0 value. LPO level remained significantly higher from day 14 onwards till the end of the observation period of 14 more days after cessation of iron adminstration. Erythrocytic superoxide dismutase activities showed a transient significant rise on day 7, and thereafter, showed a declining trend, but remained statistically comparable to respective day 0 or corresponding value of the control animals.


Health inequalities. On a roll.
The New Opportunities Fund is now five years old and has distributed 750 m Pounds, generally to address health inequalities. Healthy living centres have been a high-profile NOP beneficiary and are now being evaluated. Morecambe Bay suffers from a diverse range of inequality issues and has responded with a series of initiatives.


Resident memory T cells in the skin mediate durable immunity to melanoma.
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ). CD103 expression on CD8 T cells was required for the establishment of TRM cells in the skin but was dispensable for vitiligo development. CD103+ CD8 TRM cells were critical for protection against melanoma rechallenge. This work establishes that CD103-dependent TRM cells play a key role in perpetuating antitumor immunity.


Intraluminal rotatory device: a hypothesized new approach for the treatment of type B aortic dissections.
Acute dissection is the most common and frequently fatal catastrophic event to effect the aorta. Current treatments are unsatisfactory, particularly for Type B dissections where the mortality is excessive (approaching 33%) yet the late complication rate is high. It is hypothesized that an alternative approach would be to introduce an intraluminal freely rotating device via the femoral artery to lie adjacent to the site of the initial intimal tear. As a result it is predicted that the local shear stress would become zero, effectively arresting the dissection process. At the same time, the centrifugal force developed by the device would oppose the layers of the dissection, increasing the likelihood of false lumen obliteration. Such an approach may result in less short-term mortality and a lower long-term complication rate than current treatments.


The Impact of Resilience on Employment Among Post-9/11 Veterans With and Without Military Sexual Trauma Exposure.
Successful employment is a functional outcome of high importance for veterans after military discharge. There is a significant rising concern regarding exposure to military sexual trauma (MST) and related mental health outcomes that can impair functional outcomes, such as employment. Although resilience training is a key component of preparing for military service, to date the impact of resilience on employment outcomes for veterans with exposure to MST has yet to be examined. We sought to examine the relationship between resilience and employment in a national sample of post-9/11 veterans with and without MST exposure. A national survey was conducted between October 2021 and January 2022 to respond to the 2021 National Defense Authorization Act mandate to identify factors affecting post-9/11 women veteran's unemployment. Of veterans, 1,185 completed the survey. Of these, 565 (47.6%) were post-9/11 veterans. The survey collected data on demographics and employment; MST, adult sexual trauma (AST, outside of military), and childhood sexual trauma (CST) exposure; resilience (Response to Stressful Experiences Scale); Post Traumatic Stress Disorder (PTSD) Checklist (PCL-5); and depression (Patient Health Questionnaire-2). Multivariable logistic regression models identified gender-specific associations of resilience with employment among those exposed and not exposed to MST, adjusting for AST, CST, PTSD, and depression. Significance was set at P < .05. Of 322 women and 243 men post-9/11 veterans, 86.5% were employed. MST exposure (MST[+]) was reported by 31.4% (n = 101) of women and 16.9% (n = 41) of men. MST(+) women veterans were more likely to report CST (35.6% vs. 14.5%; P < .001), AST (68.3% vs. 17.2%; P < .001), and both CST and AST (19.8% vs. 7.2%; P < .001) than MST(-) women. MST(+) men were more likely to report AST (65.9% vs. 7.9%; P < .001), and both CST and AST (14.6% vs. 1.0%; P < .001) than MST(-) men. Levels of self-reported resilience were similar for MST(+) women and men and their MST(-) counterparts (women: 11.1 vs. 11.0; men: 11.5 vs. 12.0). For MST(+) women, each unit increase in resilience was associated with a 36% increase in odds of employment (OR: 1.36, 95% CI, 1.08-1.71); resilience was not associated with increased odds of employment among MST(-) women. Among MST(+) men veterans, each unit increase in resilience was associated with an 83% increase in odds of employment (aOR: 1.83, 95% CI, 1.13-2.98), and like women veterans, resilience was not associated with employment among MST(-) men. Among MST(+) women and men post-9/11 veterans, higher resilience was associated with increased odds of employment, whereas resilience was not associated with employment in MST(-) veterans. These findings suggest that resiliency during and after military service is a key component for potentially improving long-term outcomes. Improving resilience using evidence-based approaches among post-9/11 veterans exposed to MST may be an important avenue for increasing successful functional outcomes such as employment. Moreover, MST(+) women and men veterans may benefit from trauma-informed care as a substantial proportion of these individuals also report exposure to CST, AST, PTSD, and depression.


Fighting Fire or Fighting War: Examining the Framing Effects of COVID-19 Metaphors.
Metaphorical language describing the COVID-19 pandemic as a war has been pervasive in public discourse (e.g. "the pandemic is a war," "the virus is an enemy," and "the vaccine is a weapon"). This study employs an online survey experiment (N = 551 U.S. adults) to examine the impact of war metaphors compared to non-metaphorical literal frames and fire metaphors (e.g. "the pandemic is a wildfire"). War metaphors exhibited little advantage over literal frames across a variety of desirable outcomes (i.e. the adoption of pro-health behaviors against COVID-19, perceived solidarity and collective responsibility to curb the pandemic, and intentions to discuss and share the health news with others). However, this study revealed some benefits of war metaphors over fire metaphors. Compared with fire metaphors, health news featuring war metaphors increased both positive emotions and perceived threats of COVID-19, which in turn promoted pro-health behaviors against COVID-19 and perceived solidarity to cope with the public health crisis. Moreover, positive emotions in response to war metaphors also indirectly encouraged the retransmission of science-based COVID-19 health news. This study thus showcased the benefits and limitations of war metaphors and revealed the mediating roles of perceived threats and positive emotions in explaining war metaphorical framing effects. Implications of using war and fire metaphors for communicating about public health crises are also discussed.


Transesterification in Microreactors-Overstepping Obstacles and Shifting Towards Biodiesel Production on a Microscale.
Biodiesel, which was earlier used only as an alternative fuel, is now an indispensable component of commercial diesel. Conventional production processes are unable to cope with the increasing demand for biodiesel, and therefore more and more work is being done to intensify the existing processes. The intensification of the biodiesel production process, taking into account the environmental and economic factors, is based on increasing productivity. One way to achieve that is by reducing the volume of production units. The application of the enzymatic reaction path, while reducing the volume of process equipment to the micro-level, has significantly magnified the productivity of the biodiesel production process, which is primarily due to better mass transfer in microsystems. Additional breakthrough is the use of deep eutectic solvents (DES) instead of buffers for enzyme stabilization. In this study, a lipase from Thermomyces lanuginosus (TlL) (both commercial and produced by solid-state fermentation) was used as a catalyst for biodiesel production. Edible and waste sunflower oil, as well as methanol, were used as substrates. The reaction mediums were buffer and DES. The transesterification reaction was carried out in a batch reactor and the emphasis was made on different microreactor configurations. The highest yield of 32% for residence time of only τ = 30 min was obtained in the microreactor system with an emulsion of waste oil and a commercial enzyme suspended in a buffer. This indicates that enzymatic transesterification could be a valuable reaction path for dealing with waste oils. Furthermore, biodiesel synthesis in DES showed somewhat lower yields, but by increasing the water content in the system, the reaction could prove much better results. In the end, the effects of reaction conditions on the volumetric productivity of the process were analyzed.


Use of immunohistochemically demonstrated c-erb B-2 oncoprotein expression as a prognostic factor in transitional cell carcinoma of the urinary bladder.
Formalin-fixed, paraffin-embedded specimens from 91 primary transitional cell cancers (TCC) of the urinary bladder were stained with a monoclonal antibody to c-erb B-2 oncoprotein. Twelve percent (11/91) of the TCC stained for c-erb b-2 oncoprotein, and in 4% (4/91) of cases, the expression was graded as moderate or heavy. The expression of c-erb B-2 was significantly (p = 0.072) related to the WHO grade, whereas no significant difference in its expression was found between (a) the superficial and invasive TCC and (b) between the papillary and nonpapillary TCC. One of the tumours had a verified metastasis at the time of diagnosis and it exhibited heavy expression of c-erb B-2. The expression of c-erb B-2 was significantly related to the number of nucleolar organiser regions/TCC nucleus (p = 0.003). Aneuploid TCC were more frequently associated with moderate or heavy expression of c-erb B-2 than the diploid ones. Recurrence and progression of TCC could not be significantly related to expression of c-erb B-2 oncoprotein. In survival analysis, moderate and heavy expression of c-erb B-2 were related to poor prognosis (p = 0.032) during a mean follow-up time of 14 years. In conclusion, moderate and heavy expression of c-erb B-2 oncoprotein in TCC seems to be related to more aggressive behaviour whereas low expression of this oncoprotein had no predictive value. No evidence was obtained, however, that the expression of c-erb B-2 concoprotein alone would determine the biological behaviour of TCC.


A deficiency in cathelicidin reduces lung tumor growth in NNK/NTHi-induced A/J mice.
Cathelicidin is an antimicrobial peptide that plays an essential role in cell proliferation, angiogenesis, and also has been indicated in tumor promotion. However, it is unclear how cathelicidin causes tumor growth, and the pathogenic mechanisms based on gain or loss of function have not been proposed. Here, a cathelicidin related antimicrobial peptide (CRAMP) knockout mouse was generated using an A/J background (A/J-CRAMP-/- mice), and lung carcinoma growth was induced using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Non-typeable Haemophilus influenzae (NTHi). Compared with A/J mice, A/J-CRAMP-/- mice were found to have a lower tumor burden and longer survival times, with a significant reduction in both PCNA and Ki-67 positive cells. However, there was no difference between the number of apoptotic lung-cancer cells between the A/J and A/J-CRAMP-/- mice. This indicated cathelicidin might be a tumor growth factor for lung cancer, which was associated for proliferation of tumor cells. In the future, this animal model will be useful to study the distinct role of cathelicidin in induced-lung cancer development.


Socio-economic life course and obesity among adults in Florianopolis, southern Brazil.
To estimate the association between socio-economic life course and body mass index (BMI), waist circumference (WC) and general and abdominal obesity in adults. A cross-sectional analysis of a population-based cohort study of 1,222 adults (aged 22-63) from Florianopolis, southern Brazil. The socio-economic life course was analysed using the educational level of participants and their parents. Height, weight and WC were measured by specially trained staff. Linear and logistic regressions were used with adjustment for confounding factors, and data were stratified according to sex. Mean BMI and WC were about 2kg/m2 (95% CI: -3.3 to -0.7) and 6cm (95% CI: -9.7 to -2.9) lower in women with a high socio-economic position, while the association was reversed in men with a high socio-economic position, with WC being about 4cm higher (95% CI: 0.1 to 7.5). In addition, women who had always been in a high socio-economic position were less likely to have abdominal obesity (OR: 0.38; 95% CI: 0.20 to 0.76) while no such association was found in men. Socio-economic life course influences BMI, WC and obesity, with differences between males and females, thereby indicating that public policies that contemplate a socio-economic life course approach can be effective for controlling obesity.


Overexpression of MicroRNA-216a Suppresses Proliferation, Migration, and Invasion of Glioma Cells by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5.
Increasing studies have suggested that microRNAs (miRNAs) are involved in the development of gliomas. MicroRNA-216a has been reported to be a tumor-associated miRNA in many types of cancer, either as an oncogene or as a tumor suppressor. However, little is known about the function of miR-216a in gliomas. The present study was designed to explore the potential role of miR-216a in gliomas. We found that miR-216a was significantly decreased in glioma tissues and cell lines. Overexpression of miR-216a significantly suppressed the proliferation, migration, and invasion of glioma cells. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was identified as a target gene of miR-216a in glioma cells by bioinformatics analysis, dual-luciferase reporter assay, real-time quantitative polymerase chain reaction, and Western blot analysis. Moreover, miR-216a overexpression inhibited the Wnt/β-catenin signaling pathway. The restoration of LGR5 expression markedly reversed the antitumor effect of miR-216a in glioma cells. Taken together, these findings suggest a tumor suppressor role for miR-216a in gliomas, which inhibits glioma cell proliferation, migration, and invasion by targeting LGR5. Our study suggests that miR-216a may serve as a potential therapeutic target for future glioma treatment.


KB-68A7.1 Inhibits Hepatocellular Carcinoma Development Through Binding to NSD1 and Suppressing Wnt/β-Catenin Signalling.
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies with extremely poor prognosis. Therefore, revealing the critical molecules involved in HCC progression and prognosis is urgently needed. In this study, through combining public dataset and our cohort, we found a novel prognosis-related long non-coding RNA KB-68A7.1 in HCC. KB-68A7.1 was lowly expressed in HCC, whose low expression was associated with large tumour size, aggressive clinical characteristic, and poor survival. Gain- and loss-of-function assays demonstrated that KB-68A7.1 restricted HCC cellular proliferation, induced HCC cellular apoptosis, and suppressed HCC cellular migration and invasion in vitro. Xenograft assays demonstrated that KB-68A7.1 suppressed HCC tumour growth and metastasis in vivo. These functional assays suggested KB-68A7.1 as a tumour suppressor in HCC. Histone methyltransferase nuclear receptor binding SET domain-containing protein 1 (NSD1) was found to bind to KB-68A7.1. KB-68A7.1 was mainly distributed in the cytoplasm. The binding of KB-68A7.1 to NSD1 sequestrated NSD1 in the cytoplasm, leading to the reduction in nuclear NSD1 level. Through decreasing nuclear NSD1 level, KB-68A7.1 reduced di-methylation of histone H3 at lysine 36 (H3K36me2) and increased tri-methylation of histone H3 at lysine 27 (H3K27me3) at the promoter of WNT10B, a target of NSD1. Thus, KB-68A7.1 repressed WNT10B transcription. The expression of WNT10B was negatively correlated with that of KB-68A7.1 in HCC tissues. Through repressing WNT10B, KB-68A7.1 further repressed Wnt/β-catenin signalling. Functional rescue assays showed that overexpression of WNT10B reversed the tumour-suppressive roles of KB-68A7.1, whereas the oncogenic roles of KB-68A7.1 depletion were abolished by Wnt/β-catenin signalling inhibitor. Overall, this study identified KB-68A7.1 as a lowly expressed and prognosis-related lncRNA in HCC, which suppressed HCC progression through binding to NSD1 and repressing Wnt/β-catenin signalling.


Cost-effectiveness and satisfaction following arthroscopic rotator cuff repair: does age matter?.
The aim of this study was to investigate the influence of age on the cost-effectiveness of arthroscopic rotator cuff repair. A total of 112 patients were prospectively monitored for two years after arthroscopic rotator cuff repair using the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), the Oxford Shoulder Score (OSS), and the EuroQol five-dimension questionnaire (EQ-5D). Complications and use of healthcare resources were recorded. The incremental cost-effectiveness ratio (ICER) was used to express the cost per quality-adjusted life-year (QALY). Propensity score-matching was used to compare those aged below and above 65 years of age. Satisfaction was determined using the Net Promoter Score (NPS). Linear regression was used to identify variables that influenced the outcome at two years postoperatively. A total of 92 patients (82.1%) completed the follow-up. Their mean age was 59.5 years (sd 9.7, 41 to 78). There were significant improvements in the mean DASH (preoperative 47.6 vs one-year 15.3; p < 0.001) and OSS scores (26.5 vs 40.5; p < 0.001). Functional improvements were maintained with no significant change between one and two years postoperatively. The mean preoperative EQ-5D was 0.54 increasing to 0.81 at one year (p < 0.001) and maintained at 0.86, two years postoperatively. There was no significant difference between those aged below or above 65 years of age with regards to postoperative shoulder function or EQ-5D gains. Smoking was the only characteristic that significantly adversely influenced the EQ-5D at two years postoperatively (p = 0.005). A total of 87 were promoters and five were passive, giving a mean NPS of 95 (87/92). The total mean cost per patient was £3646.94 and the mean EQ-5D difference at one year was 0.2691, giving a mean ICER of £13 552.36/QALY. At two years, this decreased further to £5694.78/QALY. This was comparable for those aged below or above 65 years of age (£5209.91 vs £5525.67). Smokers had an ICER that was four times more expensive. Arthroscopic rotator cuff repair results in excellent patient satisfaction and cost-effectiveness, regardless of age. Cite this article: Bone Joint J 2019;101-B:860-866.


Imaging viral infection: studies on Nicotiana benthamiana plants infected with the pepper mild mottle tobamovirus.
We have studied by kinetic Chl-fluorescence imaging (Chl-FI) Nicotiana benthamiana plants infected with the Italian strain of the pepper mild mottle tobamovirus (PMMoV-I). We have mapped leaf photosynthesis at different points of the fluorescence induction curve as well as at different post-infection times. Images of different fluorescence parameters were obtained to investigate which one could discriminate control from infected leaves in the absence of symptoms. The non-photochemical quenching (NPQ) of excess energy in photosystem II (PSII) seems to be the most adequate chlorophyll fluorescence parameter to assess the effect of tobamoviral infection on the chloroplast. Non-symptomatic mature leaves from inoculated plants displayed a very characteristic time-varying NPQ pattern. In addition, a correlation between NPQ amplification and virus localization by tissue-print was found, suggesting that an increase in the local NPQ values is associated with the areas invaded by the pathogen. Changes in chloroplast ultrastructure in non-symptomatic leaf areas showing different NPQ levels were also investigated. A gradient of ultrastructural modifications was observed among the different areas.


Tuning the electrical performance of Ge nanowire MOSFETs by focused ion beam implantation.
In this work, we demonstrate an approach to tune the electrical behavior of our Ω-gated germanium-nanowire (Ge-NW) MOSFETs by focused ion beam (FIB) implantation. For the MOSFETs, 35 nm thick Ge-NWs are covered by atomic layer deposition (ALD) of a high-κ gate dielectric. With the Ω-shaped metal gate acting as implantation mask, highly doped source/drain (S/D) contacts are formed in a self-aligned process by FIB implantation. Notably, without any dopant activation by annealing, the devices exhibit more than three orders of magnitude higher I(ON) currents, an improved I(ON)/I(OFF) ratio, a higher mobility and a reduced subthreshold slope of 140 mV/decade compared to identical Ge-NW MOSFETs without FIB implantation.