Use of red autofluorescence for monitoring prodiginine biosynthesis.
Prodigiosin-like pigments or prodiginines (PdGs) are promising drugs owing to their reported antitumor, antibiotic, and immunosuppressive activities. These natural compounds are produced by several bacteria, including Streptomyces coelicolor and Serratia marcescens as most commonly studied models. The bright red color of these tripyrrole pigments made them excellent reporter molecules for studies aimed at understanding the molecular mechanisms that control secondary metabolite production in microorganisms. However, the natural red fluorescence of PdGs has only been rarely used as a biophysical parameter for detection and assessment of PdG biosynthesis. In this work, we used S. coelicolor in order to exemplify how intrinsic red fluorescence could be utilized for rapid, low-cost, sensitive, specific and accurate semi-quantitative analyses of PdG biosynthesis. Additionally, and contrary to the colorimetric-based approach, the fluorescence-based method allows in situ spatio-temporal visualization of PdG synthesis throughout a solid culture of S. coelicolor. As PdG production is related to cell differentiation, their red autofluorescence could be exploited, by means of confocal microscopy, as a natural marker of the entrance into a crucial developmental stage in the course of the S. coelicolor life cycle.


Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia: a systematic review.
Treatment of cervical intraepithelial neoplasia (CIN) is a common minor surgical procedure to prevent uterine cervical cancer. However, news of an abnormality detected at screening for cancer might cause the woman to worry. To investigate the psychological consequences of CIN diagnosis and treatment in a systematic review. We searched PubMed using Medical Subject Headings (MeSH) terms for articles published from January 1990 to February 2013. We also examined the reference lists of retrieved articles. Quantitative studies measuring psychological outcomes in women with a histological diagnosis or treatment of CIN, and in women having an outcome other than CIN at cervical screening. We abstracted the data using a pre-specified list of study characteristics and measured outcomes. For studies not reporting statistical testing, we estimated the statistical significance of the differences between the compared groups using unpaired t tests. From 5099 retrieved abstracts, 16 studies were included. Diagnosis and treatment of CIN were associated with worse psychological outcomes than normal cytology test results, but the impact decreased over time. In several but not all studies, CIN appeared to have similar psychological consequences to abnormal smears. No study showed a difference in psychological outcomes between CIN and cervical cancer diagnosis when these were measured some years after diagnosis. The studies suggested that CIN diagnosis and treatment have a negative psychological impact. However, this conclusion should be viewed in the context of a paucity of rigorously designed studies.


Optogenetic inhibition of Gα signalling alters and regulates circuit functionality and early circuit formation.
Optogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G-protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate a new optogenetic tool that disrupt Gαq signaling through membrane recruitment of a minimal Regulator of G-protein signaling (RGS) domain. This approach, Photo-induced Modulation of Gα protein - Inhibition of Gαq (PiGM-Iq), exhibited potent and selective inhibition of Gαq signaling. We alter the behavior of C. elegans and Drosophila with outcomes consistent with GPCR-Gαq disruption. PiGM-Iq also changes axon guidance in culture dorsal root ganglia neurons in response to serotonin. PiGM-Iq activation leads to developmental deficits in zebrafish embryos and larvae resulting in altered neuronal wiring and behavior. By altering the choice of minimal RGS domain, we also show that this approach is amenable to Gαi signaling.


Bilateral isolated retrobulbar optic neuropathy in limited Wegener's granulomatosis.
Wegener's granulomatosis causes a variety of ophthalmologic disorders, some of which occasionally constitute the initial presentation of the disease. We describe a patient who presented with bilateral, isolated, consecutive, posterior optic neuropathy with light perception and no light perception vision. The patient had no other symptoms or signs of orbital disease. Investigations revealed cavitary lung lesions, positive antineutrophilic cytoplasmic antibody (ANCA) titers, subtle focal enhancement of the intracanalicular optic nerves on magnetic resonance imaging, and a confirmatory bronchial biopsy. This exceedingly rare ocular presentation of Wegener's granulomatosis may pose a diagnostic quandary.


MicroRNA-based Targeted Therapeutics in Pancreatic Cancer.
The discovery during the last decade of microRNAs (miRs, miRNA) and their role in regulating normal physiological processes as well as in the pathogenesis of human tumors has been a revolutionary development in molecular oncology. miRNAs activating or inhibiting oncogenic molecular pathways that are involved in tumorigenesis, cell progression, invasion, angiogenesis and metastasis are now considered of major impact in many cancer types. miRNA-based therapeutics that inhibit the levels of oncogenic miRNAs (oncomiRs) or elevate tumor suppressor miRs have enormous potential as molecular therapeutic targets. Thus, the development of new targeted cancer therapies based on miRNAs promise to revolutionize cancer treatment due to their increased efficacy compared to conventional chemoradiation-based therapies and hopefully to lower levels of adverse effects.


Studies on the pathogenicity of group A streptococci. II. The antiphagocytic effects of the M protein and the capsular gel.
A QUANTITATIVE STUDY OF THE COMBINED ANTIPHAGOCYTIC EFFECTS OF THE M PROTEIN AND THE HYALURONIC ACID CAPSULES OF FOUR STRAINS OF GROUP A STREPTOCOCCI REVEALED THE FOLLOWING FACTS RELATING TO THEIR INTRAPERITONEAL VIRULENCE IN MICE AND RATS: 1. The most virulent strain, S23M (matt), produced both a large hyaluronic acid capsule and a full complement of M protein, the combined effects of which rendered the organism highly resistant to surface phagocytosis. 2. The slightly less virulent strain, T14/46 (matt virulent) was somewhat more susceptible to surface phagocytosis owing to the fact that its smaller capsule was less antiphagocytic than that of the S23M organism. 3. The glossy variant of the S23 strain (S23G), which ranked third in virulence, was still more susceptible to surface phagocytosis because of its lack of detectable M substance. Its large hyaluronic acid capsule, however, was capable of protecting it against phagocytosis on glass. 4. The least virulent strain, T14 (matt avirulent), was the most susceptible of all to phagocytosis. Though it possessed both M substance and capsule, which together prevented its phagocytosis on glass, each of them was shown to be quantitatively and functionally deficient as compared to Strain S23M. The differences in phagocytability, which appear to be directly related to the pathogenicity of the organisms, could be adequately demonstrated in vitro only by phagocytic tests designed to measure surface phagocytosis in the absence of opsonins. This fact is in keeping with the observation, previously reported, that surface phagocytosis plays a critical role in the defense of the host, particularly during the earliest stages of experimental streptococcal infections. Its possible relation to suppuration during the later stages of infection is also discussed.


[Mechanisms of development and sclerosurgical treatment methods of acute surface varicothrombophlebitis].
An analysis of complex laboratory, ultrasonic investigations and following treatment of 120 patients with acute surface varicothrombophlebitis was made. The patients were divided into two groups, each being 60 people. In the first control group the treatment was conducted in one step: standard venectomy was performed at high point of inflammatory process. In the main group, the development of thrombotic process was prevented by sclerosurgical technology at the first stage. Radical treatment was carried out at the second stage after 4-6 weeks. The number of complications in near-term postoperative period decreased in 5% and in long-term in 13.3%, the quality of life increased in 13.3% in second group patients.


Levinas, justice and health care.
In this paper I argue that the metaphysical ethics of Emmanuel Levinas captures some essential moral intuitions that are central to health care. However, there is an ongoing discussion about the relevance of ethical metaphysics for normative ethics and in particular on the question of the relationship between justice and individualized care. In this paper I take part in this debate and I argue that Levinas' idea of an ethics of the Other that guides politics and justice can shed important light on issues that are central to priorities in health care. In fact, the ethics of Levinas in seeking the foundation of normativity itself, captures the ethical core and central values of health care.


Vulnerability and Well-Being Decades After Leaving Care.
One of the most important goals of out of home placements is to reduce vulnerability and to enable well-being in the long term. This article hermeneutically reconstructs biographies decades after leaving-care to understand the impact of residential care experiences on selected dimensions of care-leavers' well-being, that were discovered in the data material. For this article three analytic areas were selected from the core of the narratives of former care leavers: Social networks, parenthood and state interventions. The selected findings on long-term outcomes presented here are based on a qualitative research project funded by the Swiss National Science Foundation on life trajectories after residential care (1950-1990). The authors have conducted 37 biographical narrative interviews with former children placed in residential care between 1950 and 1990 in the Canton of Zurich, Switzerland. The analysis of these narrative interviews was structured by the inductive procedures of Grounded Theory. Its foundation is the conceptualisation and dimensionalisation of data through inductive coding within the narratives. Research question: We mainly were interested in aspects of transitions exclusively relevant from the actors' point of view. The objective of this paper is to learn for the future by taking biographical experiences and long-term outcome in account. As we know residential care facilities have changed in last decades, but structurally some key figures are still continuing. They still interrupt the life course two times: when you start to the live in the institution and when you leave. One main question is how young people manage to integrate residential experiences through their life course and where they keep on struggling until the end of their lives. From a life-course perspective, the impact of social service intention on individual life courses, behind sending the individuals to such facilities, are important to investigate. They implicate relevant information concerning current practice and impact of placing children in residential care. Social networks and experiences of parenthood show why we must frame and accompany transitions out of care.


Sample size calculations for comparative studies of medical tests for detecting presence of disease.
Technologic advances give rise to new tests for detecting disease in many fields, including cancer and sexually transmitted disease. Before a new disease screening test is approved for public use, its accuracy should be shown to be better than or at least not inferior to an existing test. Standards do not yet exist for designing and analysing studies to address this issue. Established principles for the design of therapeutic studies can be adapted for studies of screening tests. In particular, drawing upon methods for superiority and non-inferiority studies of therapeutic agents, we propose that confidence intervals for the relative accuracy of dichotomous tests drive the design of comparative studies of disease screening tests. We derive sample size formulae for a variety of designs, including studies where patients undergo several tests and studies where patients receive only one of the tests under evaluation. Both cohort and case-control study designs are considered. Modifications to the confidence intervals and sample size formulae are discussed to accommodate studies where, because of the invasive nature of definitive testing, true disease status can only be obtained for subjects who are positive on one or more of the screening tests. The methods proposed are applied to a study comparing a modified pap test to the conventional pap for cervical cancer screening. The impact of error in the gold standard reference test on the design and evaluation of comparative screening test studies is also discussed.


Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines.
The presence of thyroid autoantibodies is relatively high in women of childbearing age. There is evidence that positive thyroperoxidase antibody even in euthyroid women may increase the risk of spontaneous and recurrent pregnancy loss and preterm delivery. However, the evidence is not enough to justify recommendation on the screening of pregnant women for thyroid autoantibodies or LT4 supplementation for reducing maternal or fetal complications. In this paper we reviewed the related evidence and compared the new guidelines of the American Thyroid Association and Endocrine Society with respect to the screening and management of positive thyroperoxidase antibody in euthyroid pregnant women. As there was no major contradiction or disagreement between the two guidelines, either one of two guidelines may be used by clinicians for the appropriate management of thyroid autoimmunity during pregnancy.


The Effect of Supportive-Training Intervention on the Burnout ofMothers with Disabled Child: A Randomized Clinical Trial.
Introduction: Mothers with a disabled child experience excessive stress, fatigue, frustration, and depression. Failure of mothers to effectively deal with these symptoms can lead to chronic fatigue and, in the long run, burnout. The objective of the present study was to determine the effect of supportive-training intervention on the burnout of mothers with disabled children. Methods: In this randomized controlled trial, 70 mothers with disabled children studying in special schools were selected in one of the urban areas of Iran. They were divided into two groups of intervention and control, using Minimization Random Method. In the intervention group, mothers participated in supportive-training sessions once a week for a period of 6 weeks. The control group did not receive any special interventions. The data collection tool was a demographic data form and Shirom-Melamed Burnout Questionnaire (SMBQ). Burnout was evaluated as primary outcome at the beginning of the study and one month after the end of the intervention. The data were analyzed by SPSS software version 18. Results: Based on the results, there was no significant difference between the mean score of burnout in the intervention and control groups before the intervention. However, after the intervention, the mean score of burnout in the intervention group was significantly lower than that of the control group. Conclusion: Considering the positive effect of supportive-training intervention on the burnout of mothers of disabled children, this intervention is recommended by nurses and other health care providers in special schools, health centers, and supportive institutions.


Widespread CRISPR repeat-like RNA regulatory elements in CRISPR-Cas systems.
CRISPR- cas loci typically contain CRISPR arrays with unique spacers separating direct repeats. Spacers along with portions of adjacent repeats are transcribed and processed into CRISPR(cr) RNAs that target complementary sequences (protospacers) in mobile genetic elements, resulting in cleavage of the target DNA or RNA. Additional, standalone repeats in some CRISPR- cas loci produce distinct cr-like RNAs implicated in regulatory or other functions. We developed a computational pipeline to systematically predict crRNA-like elements by scanning for standalone repeat sequences that are conserved in closely related CRISPR- cas loci. Numerous crRNA-like elements were detected in diverse CRISPR-Cas systems, mostly, of type I, but also subtype V-A. Standalone repeats often form mini-arrays containing two repeat-like sequence separated by a spacer that is partially complementary to promoter regions of cas genes, in particular cas8 , or cargo genes located within CRISPR-Cas loci, such as toxins-antitoxins. We show experimentally that a mini-array from a type I-F1 CRISPR-Cas system functions as a regulatory guide. We also identified mini-arrays in bacteriophages that could abrogate CRISPR immunity by inhibiting effector expression. Thus, recruitment of CRISPR effectors for regulatory functions via spacers with partial complementarity to the target is a common feature of diverse CRISPR-Cas systems.


DNA barcoding species inventory of Microgastrinae wasps (Hymenoptera, Braconidae) from a Mexican tropical dry forest.
The cosmopolitan Microgastrinae is probably the most diverse braconid subfamily of parasitoid wasps, yet its species diversity is far from being known. As part of a global initiative for DNA barcoding Microgastrinae species, here we show the results of a study that assessed the species richness of this subfamily in a Mexican tropical dry forest located in the Chamela region, near the Pacific coast of Jalisco. Barcoding sequences of a total of 551 microgastrine specimens were generated, corresponding to 238 haplotypes. Performance of two species delineation approaches, a 2% corrected pairwise distance criterion and the general mixed Yule-coalescent (GMYC) method, yielded 100 and 112 putative species, respectively, which belong to 13 genera. The species delimited by the above two approaches were mostly congruent with our morphospecies identification. Ten molecular operational taxonomic units (MOTUs) were split into twenty-two species by the GMYC approach. We found morphological differences between the GMYC species corresponding to three of these MOTUs. Thus, a total of 103 microgastrine species were confirmed for the region of study. Thirty-three species were only represented by males, and therefore, their generic assignment is only tentatively proposed. Fornicia, Dolichogenoidea, Distatrix, Glyptapanteles and Pholetesor represent new generic records for the Mexican territory. A new record for the country is also provided for the Diolcogaster-basimacula species group. Based on a comparison of nearly 20 000 barcoding sequences released for Microgastrinae from 75 countries, only five microgastrine species from Chamela were found to occur in other countries, four in Costa Rica and one in Canada and the United States.


Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration.
To define the relationship, if any, between insulin-mediated glucose disposal and serum uric acid. Cross-sectional study of healthy volunteers. General Clinical Research Center, Stanford (Calif) University Medical Center. Thirty-six presumably healthy individuals, nondiabetic, without a history of gout. Obesity (overall and regional), plasma glucose and insulin responses to a 75-g oral glucose load, fasting uric acid concentrations, plasma triglyceride and high-density lipoprotein-cholesterol concentrations, systolic and diastolic blood pressure, insulin-mediated glucose disposal, and urinary uric acid clearance. Magnitude of insulin resistance and serum uric acid concentration were significantly related (r = .69; P less than .001), and the relationship persisted when differences in age, sex, overall obesity, and abdominal obesity were taken into account (r = .57; P less than .001). Insulin resistance was also inversely related to urinary uric acid clearance (r = -.49; P less than .002), and, in addition, urinary uric acid clearance was inversely related to serum uric acid concentration (r = -.61; P less than .001). Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney.


Morphogenesis of the developing mammary gland: stage-dependent impact of adipocytes.
Mammary gland development is critically dependent on the interactions between the stromal and the epithelial compartments within the gland. These events are under the control of a complex interplay of circulating and locally acting hormones and growth factors. To analyze the temporal and quantitative contributions of stromal adipocytes, we took advantage of the FAT-ATTAC mice (apoptosis through triggered activation of caspase-8), a model of inducible and reversible loss of adipocytes. This loss can be achieved through the induced dimerization of a caspase-8 fusion protein. In the context of female mice, we can achieve ablation of mammary adipocytes relatively selectively without affecting other fat pads. Under these conditions, we find that adipocytes are essential for the formation of the extended network of ducts in the mammary gland during puberty. Beyond their role in development, adipocytes are also essential to maintain the normal alveolar structures that develop during adulthood. Loss of adipose tissue initiated 2 weeks after birth triggers fewer duct branching points and fewer terminal end buds (TEBs) and also triggers changes in proliferation and apoptosis in the epithelium associated with the TEBs. The reduced developmental pace that adipocyte-ablated glands undergo is reversible, as the emergence of new local adipocytes, upon cessation of treatment, enables the ductal epithelium to resume growth. Conversely, loss of local adipocytes initiated at 7 weeks of age resulted in excessive lobulation, indicating that adipocytes are critically involved in maintaining proper architecture and functionality of the mammary epithelium. Collectively, using a unique model of inducible and reversible loss of adipocytes, our observations suggest that adipocytes are required for proper development during puberty and for the maintenance of the ductal architecture in the adult mammary gland.


Histo-blood group gene polymorphisms as potential genetic modifiers of the development of coronary artery lesions in patients with Kawasaki disease.
Abnormal immunological responses to certain microbial agents may play a crucial role in the pathogenesis of Kawasaki disease (KD). The association studies between histo-blood group genes (Lewis and ABO blood types) and various types of infectious diseases or vasculopathy have been carried out based on the fact that glycosylated antigens could directly mediate microbial infections. We attempted to clarify the role of blood type antigens in the development of KD and coronary artery lesions in KD patients. The subjects included 164 KD patients enrolled from 1998 to 2003 (1st group), 232 patients from 2004 to 2009 (2nd group), and 223 healthy children and 118 patients with growth hormone deficiency as controls. The genotyping of the FUT2 and FUT3 genes, and ABO genotypes, was determined with the TaqMan SNP assay and allele-specific polymerase chain reaction. No significant differences were observed in the genotypes and allele frequencies of the FUT2 and FUT3 genes between the groups. The frequency of the BB blood genotype was significantly higher in KD patients with coronary artery lesions in the 1st and 2nd groups than in the controls (17% and 14% vs. 5%, P = 0.0020). This is the first report to investigate the roles of ABO and Lewis blood types in the development of KD, and in the formation of coronary artery lesions in KD patients. These data suggest that the ABO blood type may play a role in the development of coronary artery lesions in KD patients.


Theoretical limitations of quantification for noncompetitive sandwich immunoassays.
Immunoassays exploit the highly selective interaction between antibodies and antigens to provide a vital method for biomolecule detection at low concentrations. Developers and practitioners of immunoassays have long known that non-specific binding often restricts immunoassay limits of quantification (LOQs). Aside from non-specific binding, most efforts by analytical chemists to reduce the LOQ for these techniques have focused on improving the signal amplification methods and minimizing the limitations of the detection system. However, with detection technology now capable of sensing single-fluorescence molecules, this approach is unlikely to lead to dramatic improvements in the future. Here, fundamental interactions based on the law of mass action are analytically connected to signal generation, replacing the four- and five-parameter fittings commercially used to approximate sigmoidal immunoassay curves and allowing quantitative consideration of non-specific binding and statistical limitations in order to understand the ultimate detection capabilities of immunoassays. The restrictions imposed on limits of quantification by instrumental noise, non-specific binding, and counting statistics are discussed based on equilibrium relations for a sandwich immunoassay. Understanding the maximal capabilities of immunoassays for each of these regimes can greatly assist in the development and evaluation of immunoassay platforms. While many studies suggest that single molecule detection is possible through immunoassay techniques, here, it is demonstrated that the fundamental limit of quantification (precision of 10 % or better) for an immunoassay is approximately 131 molecules and this limit is based on fundamental and unavoidable statistical limitations.


Identification of CD68+lin- peripheral blood cells with dendritic precursor characteristics.
Expression of CD68 (macrosialin) in the absence of surface and lysosomal lineage marker molecules is a characteristic feature of T zone-associated plasmacytoid monocytes, which were recently shown to represent precursors of dendritic cells (DC). We demonstrate here a minor population of strongly CD68-positive (CD68bright) blood cells that lack all analyzed myeloid surface (CD14-, CD33-, CD13-, CD11b-, CD11c-) and lysosomal (myeloperoxidase, MPO- and lysozyme, LZ-) marker molecules (0.4 +/- 2% of the total mononuclear cells). These CD68bright, lineage marker-negative (lin-) cells can be induced to proliferate in the presence of IL-3. They do not acquire myeloid features even upon stimulation with granulocyte-macrophage CSF plus IL-1, IL-3, and IL-6. Instead, these cells develop typical DC characteristics upon culture. Furthermore, these CD68brightlin- DC precursors acquire mature DC characteristics (CD86+, CD83+, CD54bright) upon stimulation with CD40 ligand plus IL-3. A second subset of DC precursor-like blood cells was found to weakly express CD68 (0.3 +/- 0.2% of the total mononuclear cells) and to coexpress several myeloid lineage associated molecules (LZ+, CD11c+, CD33+, CD13+). Cells of this second subset resemble both previously described myeloid-related peripheral blood DC and germinal center DC. Analysis of peripheral blood leukocytes for CD68 thus revealed the existence of two cell subsets that phenotypically resemble lymphoid tissue-associated DC. The unique phenotype CD68brightlin- is highly reminiscent of T zone-associated plasmacytoid monocytes. CD68brightlin- blood leukocytes also functionally resemble plasmacytoid monocytes. The lack of all analyzed myeloid features by CD68brightlin- blood leukocytes suggests that these cells arise from a novel nonmyeloid human DC differentiation pathway.


cPPB-aE is discovered from photosynthetic benthic dinoflagellates.
Although chlorophyll degradation pathways in higher plants have been well studied, little is known about the mechanisms of chlorophyll degradation in microalgae. In this article, we report the occurrence of a chlorophyll a derivative that has never been discovered in photosynthetic organisms. This chlorophyll derivative emits no fluorescence and has a peculiar absorbance peak at 425, 451, 625, and 685 nm. From these features, it was identified as 13(2) ,17(3) -cyclopheophorbide a enol (cPPB-aE), reported as a degradation product of chlorophyll a derived from prey algal cells in heterotrophic protists. We discovered cPPB-aE in six benthic photosynthetic dinoflagellates that are phylogenetically separated into four clades based on SSU rDNA molecular phylogeny. This is the first report of this chlorophyll derivative in photosynthetic organisms and we suggest that the derivative is used to quench excess light energy.


Organ donations from deceased persons in the Saudi Arabian population.
We aimed to determine the factors that influence organ donation consent and refusal in Saudi Arabia and see if they are different from those reported elsewhere. By determining these, we hope to introduce strategies to enhance donor consent by families of deceased persons. We examined next-of-kin records of Saudi brain dead persons who had been approached for consent for donation during 1998. These same next of kin were approached in 2004 and asked to fill out a questionnaire examining demographics, awareness, and emotions regarding their decision to donate a family member's organ(s). In addition, data related to the deceased persons also were recorded. During 1998, 41 Saudi next of kin had been approached for permission to obtain organs from their deceased relatives. Of these, 16 consented and 25 did not. We obtained responses from all the consenters (group 1) and from 16 of the nonconsenters (group 2). The consenters were more educated; had positive feelings about donation and still do; and had keener knowledge regarding organ donation, religious standpoints about donation, and the results of transplantation. The results demonstrate that consent for donation depends on prior knowledge and awareness of the various aspects of organ donation. Public education methods used to encourage organ donation need review. We found no differences in economic status or age between consenters and nonconsenters. The relationship between the deceased person and the next of kin does not appear to play a role in determining consent or refusal. On the other hand, consent was less likely when death was caused by a motor vehicle accident than it when other factors led to death.


Cascaded collective decay in regular arrays of cold trapped atoms.
Energy and lifetime of collective optical excitations in regular arrays of atoms and molecules are significantly influenced by dipole-dipole interaction. While the dynamics of closely positioned atoms can be approximated well by the Dicke superradiance model, the situation of finite regular configurations is hard to access analytically. Most treatments use an exciton based description limited to the lowest excitation manifold. We present a general approach studying the complete decay cascade of a finite regular array of atoms from the fully inverted to the ground state. We explicitly calculate all energy shifts and decay rates for two generic cases of a three-atom linear chain and an equilateral triangle. In numerical calculations we show that despite fairly weak dipole-dipole interactions, collective vacuum coupling allows for superradiant emission as well as subradiant states in larger arrays through multi-particle interference. This induces extra dephasing and modified decay as important limitations for Ramsey experiments in lattice atomic clock setups as well as for the gain and frequency stability of superradiant lasers.


Chlorpyrifos-methyl solubilisation by humic acids used as bio-surfactants extracted from lignocelluloses and kitchen wastes.
Chlorpyrifos-methyl (CLP-m) is a widely used organophosphate insecticide that can accumulate in soil and become toxic to humans. CLP-m can be removed from soil by its solubilisation using synthetic surfactants. However, synthetic surfactants can accumulate in soil causing contamination phenomena themselves. Bio-surfactants can be used as an alternative to synthetic ones, reducing costs and environmental issues. In this work, humic acid (HA) extracted from raw biomasses, i.e. lignocelluloses (HAL) and lignocelluloses plus kitchen food waste (HALF), corresponding composts (C) (HALC and HALFC) and leonardite (HAc), were tested in comparison with commercial surfactants, i.e. SDS, Tween 20 and DHAB, to solubilize CLP-m. Results obtained indicated that only biomass-derived HA, composted biomass-derived HA, and SDS solubilized CLP-m: SDS = 0.006; HAL = 0.007; HALC = 0.009 g; HALF = 0.025; HALFC = 0.024) (g CLP-m g(-1) surfactant). Lignocelluloses HAs (HAL, HALF) solubilized CLP-m just as well as SDS while lignocellulosic plus kitchen food waste HA (HALF, HALFC) showed a three times higher CLP-m solubilisation capability. This difference was attributed to the higher concentration of alkyl-Carbon that creates strong links with CLP-m in the hydrophobic micelle-core of the surfactants.


Psychometric properties of the Short Inventory of Problems (SIP) with adjudicated DUI intervention participants.
We used responses of two large samples of court-ordered participants from a statewide alcohol/driving safety program to investigate factor structure, score reliability, and criterion-related validity of the Short Inventory of Problems (SIP). Exploratory and confirmatory factor analyses, using both item-level and subscore-level data, support a one-factor structure for the SIP. Internal consistency score reliability estimates were consistent across samples and high enough to warrant use for making decisions about individuals. Item response theory model calibration of the scale, using a two-parameter logistic model, yielded consistent estimates of location and discrimination (slope) across samples. Estimated scale scores correlated moderately with an independent indicator of alcohol problems and poorly with an indicator of risky driving behavior, lending evidence of convergent and discriminant validity. We judge the SIP as adequately described by a single factor, that the joint person-item scale is coherent, and scores behave consistently across samples. (PsycINFO Database Record


Enhanced Activity of Au/NiO Nanohybrids for the Reductive Amination of Benzyl Alcohol.
Gold nanoparticles were prepared by sol immobilization (AuSI) or deposition precipitation (AuDP), then deposited on NiO and commercial TiO₂ (P25). The Au/NiO catalysts showed higher activity and yield to the secondary amine, compared to Au/TiO₂ catalysts, when tested for the reductive amination of benzyl alcohol with isopropylamine. We attribute this result to a synergistic effect between Au and NiO. Moreover, as a result of the protective effect of the polyvinyl alcohol used in the sol immobilization synthesis, the gold nanoparticles on NiO demonstrate an increased resistance to structural changes during the reaction. This effect results in enhanced catalytic efficiency in terms of activity, and better stability against deactivation.


Diary of a daughter.
This is a personal account of my struggle as a young medical student after my mother was diagnosed with an incurable illness; she subsequently passed away. Through this story, I share my experience with the medical profession from the perspective of the daughter of a terminally ill mother.


Use of tetramethylammonium hydroxide to determine the total fatty acid composition of microorganisms.
A destructive chromatographic method of identifying microorganisms is described. The method is based on hydrolysis of the biomass of the microorganisms in the presence of tetramethylammonium hydroxide, followed by introduction of the hydrolyzate into the heated injector of a gas chromatograph. The main products in this case are methyl esters of fatty acids, the composition of which is used as a diagnostic criterion. Chromatograms of the residues after chloroform-methanol extraction and the dynamics of the change in total fatty acids in the process of growth can also be used for identification. The dynamics of total fatty acids was studied in E. coli strain K-12, and destructive chromatograms for bacteria and yeasts are cited.


Neural Conversion and Patterning of Human Pluripotent Stem Cells: A Developmental Perspective.
Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.


Species delimitation based on diagnosis and monophyly, and its importance for advancing mammalian taxonomy.
A recently proposed taxonomic classification of extant ungulates sparked a series of publications that criticize the Phylogenetic Species Concept (PSC) claiming it to be a particularly poor species concept. These opinions reiteratively stated that (1) the two fundamental elements of the "PSC", i.e., monophyly and diagnosability, do not offer objective criteria as to where the line between species should be drawn; and (2) that extirpation of populations can lead to artificial diagnosability and spurious recognitions of species. This sudden eruption of criticism against the PSC is misleading. Problems attributed to the PSC are common to most approaches and concepts that modern systematists employ to establish species boundaries. The controversial taxonomic propositions that sparked criticism against the PSC are indeed highly problematic, not because of the species concept upon which they are based, but because no evidence (whatsoever) has become public to support a substantial portion of the proposed classification. We herein discuss these topics using examples from mammals. Numerous areas of biological research rest upon taxonomic accuracy (including conservation biology and biomedical research); hence, it is necessary to clarify what are (and what are not) the real sources of taxonomic inaccuracy.


[The effect of nitroglycerin on the external respiration function and central hemodynamics in patients with tuberculosis of the lungs].
To estimate the effect of nitroglycerin (NTG) on the external respiration function and central hemodynamics, 124 patients with various forms of pulmonary tuberculosis and chronic nonspecific diseases of the lungs were examined. The indices of the external respiration function, central hemodynamics, pulmonary artery systolic pressure (PASP), general pulmonary resistance (GPR) and blood gaseous composition were determined before and after NTG sublingual use in a dose of 1 mg. It was noted that improvement of bronchial patency after the use of NTG was not significant and subsequently its indication as an agent arresting bronchospasm is not expedient. A statistically significant decrease in PASP and the indices of central hemodynamics, as well as a decrease in GPR might be considered as a basis for the use of nitrates in prophylaxis and treatment of chronic pulmonary heart in patients with pulmonary tuberculosis.


Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes.
Ramón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory plexuses that wrap Purkinje cell somata and terminate as pinceaux at the initial segment of axons. Here, we demonstrate that HCN1, Kv1.1, PSD95 and GAD67 unexpectedly mark patterns of basket cell pinceaux that map onto Purkinje cell functional zones. Using cell-specific genetic tracing with an Ascl1CreERT2 mouse conditional allele, we reveal that basket cell zones comprise different sizes of pinceaux. We tested whether Purkinje cells instruct the assembly of inhibitory projections into zones, as they do for excitatory afferents. Genetically silencing Purkinje cell neurotransmission blocks the formation of sharp Purkinje cell zones and disrupts excitatory axon patterning. The distribution of pinceaux into size-specific zones is eliminated without Purkinje cell GABAergic output. Our data uncover the cellular and molecular diversity of a foundational synapse that revolutionized neuroscience.


Language Skills Influence Transition Planning in Adolescents With Fragile X Syndrome.
Individuals with fragile X syndrome (FXS) and their parents have a range of experiences navigating the crucial transition period between adolescence and adulthood. Semistructured interviews of 47 mothers of adolescents with FXS (mean child age = 15.89 years) were analyzed to identify mothers' changing expectations during the adolescent period and parent goals related to work and postsecondary education. Mothers' work and education goals were explored in relation to child factors such as language skills and autism characteristics. Lower language skills were associated with lower likelihood of reporting vocational goals. Results suggest that adolescents with FXS with lower language ability are less likely to have vocational plans for adulthood during this critical period and may need greater transition planning assistance.


Novel Technique of Vaginoplasty Developing Normal Vagina, Role of Stemness Markers and Translational Genes.
To study development of neo-vagina by metaplastic conversion of peritoneum, To identify translational Stemness markers using NANOG/OCT4/SOX2 from serial neo-vaginal mRNA, cDNA and to study role of WNT and HOXA genes in patients undergoing vaginoplasty. 75 MRKH Syndrome women underwent laparoscopic peritoneal vaginoplasty (LPV). Two patients underwent serial neo-vaginal biopsies on day 0, 7-9, 12-14, 21 and 33. Fifteen MRKHS and twelve controls were subjected for neo-vaginal biopsy to detect genes upregulation. Remaining patients were evaluated anatomically and functionally. The translational stemness markers NANOG, OCT4 and SOX2 responsible for neo-vaginal formation were identified. Their appearance, concentration at different stages of conversion were demonstrated. The neo-vagina has shown up-regulation of these translational stemness markers. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. In the subjects stemness markers (NANOG, OCT4 and SOX2) appeared from day 9 to 14 of the neo-vaginal biopsies and after achieving the peak declined later. Genetic analysis showed low values in HOXA 9,10,11,13 and up-regulation of WNT 4A,5A,7 genes in neo-vagina. Study shows peritoneal metaplastic conversion to normal vagina, identified the translational stemness markers and genes responsible. The neo-vagina has shown up-regulation of these genes. The study demonstrates expression of the specific genes (WNT4, WNT5A and WNT7A) and their role in formation of the neo-vagina. Furthering this research, activating these genes may lead to treatment of developmental defects of Mullerian duct, obviating the need of transplant.


Thermally activated delayed fluorescence materials towards the breakthrough of organoelectronics.
The design and characterization of thermally activated delayed fluorescence (TADF) materials for optoelectronic applications represents an active area of recent research in organoelectronics. Noble metal-free TADF molecules offer unique optical and electronic properties arising from the efficient transition and interconversion between the lowest singlet (S1 ) and triplet (T1 ) excited states. Their ability to harvest triplet excitons for fluorescence through facilitated reverse intersystem crossing (T1 →S1 ) could directly impact their properties and performances, which is attractive for a wide variety of low-cost optoelectronic devices. TADF-based organic light-emitting diodes, oxygen, and temperature sensors show significantly upgraded device performances that are comparable to the ones of traditional rare-metal complexes. Here we present an overview of the quick development in TADF mechanisms, materials, and applications. Fundamental principles on design strategies of TADF materials and the common relationship between the molecular structures and optoelectronic properties for diverse research topics and a survey of recent progress in the development of TADF materials, with a particular emphasis on their different types of metal-organic complexes, D-A molecules, and fullerenes, are highlighted. The success in the breakthrough of the theoretical and technical challenges that arise in developing high-performance TADF materials may pave the way to shape the future of organoelectronics.


Matrix-assisted laser desorption ionization time of flight mass spectrometry and diagnostic testing for prosthetic joint infection in the clinical microbiology laboratory.
Identification of pathogen(s) associated with prosthetic joint infection (PJI) is critical for patient management. Historically, many laboratories have not routinely identified organisms such as coagulase-negative staphylococci to the species level. The advent of matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) has enhanced clinical laboratory capacity for accurate species-level identification. The aim of this study was to describe the species-level identification of microorganisms isolated from periprosthetic tissue and fluid specimens using MALDI-TOF MS alongside other rapid identification tests in a clinical microbiology laboratory. Results of rapid identification of bacteria isolated from periprosthetic joint fluid and/or tissue specimens were correlated with clinical findings at Mayo Clinic, Rochester, Minnesota, between May 2012 and May 2013. There were 178 PJI and 82 aseptic failure (AF) cases analyzed, yielding 770 organisms (median, 3/subject; range, 1-19/subject). MALDI-TOF MS was employed for the identification of 455 organisms (59%) in 197 subjects (123 PJIs and 74 AFs), with 89% identified to the species level using this technique. Gram-positive bacteria accounted for 68% and 93% of isolates in PJI and AF, respectively. However, the profile of species associated with infection compared to specimen contamination differed. Staphylococcus aureus and Staphylococcus caprae were always associated with infection, Staphylococcus epidermidis and Staphylococcus lugdunensis were equally likely to be a pathogen or a contaminant, whereas the other coagulase-negative staphylococci were more frequently contaminants. Most streptococcal and Corynebacterium isolates were pathogens. The likelihood that an organism was a pathogen or contaminant differed with the prosthetic joint location, particularly in the case of Propionibacterium acnes. MALDI-TOF MS is a valuable tool for the identification of bacteria isolated from patients with prosthetic joints, providing species-level identification that may inform culture interpretation of pathogens versus contaminants.


Is Europe putting theory into practice? A qualitative study of the level of self-management support in chronic care management approaches.
Self-management support is a key component of effective chronic care management, yet in practice appears to be the least implemented and most challenging. This study explores whether and how self-management support is integrated into chronic care approaches in 13 European countries. In addition, it investigates the level of and barriers to implementation of support strategies in health care practice. We conducted a review among the 13 participating countries, based on a common data template informed by the Chronic Care Model. Key informants presented a sample of representative chronic care approaches and related self-management support strategies. The cross-country review was complemented by a Dutch case study of health professionals' views on the implementation of self-management support in practice. Self-management support for chronically ill patients remains relatively underdeveloped in Europe. Similarities between countries exist mostly in involved providers (nurses) and settings (primary care). Differences prevail in mode and format of support, and materials used. Support activities focus primarily on patients' medical and behavioral management, and less on emotional management. According to Dutch providers, self-management support is not (yet) an integral part of daily practice; implementation is hampered by barriers related to, among others, funding, IT and medical culture. Although collaborative care for chronic conditions is becoming more important in European health systems, adequate self-management support for patients with chronic disease is far from accomplished in most countries. There is a need for better understanding of how we can encourage both patients and health care providers to engage in productive interactions in daily chronic care practice, which can improve health and social outcomes.


[A novel model for visualization of tumor cell-induced angiogenesis in vivo].
The bladder transitional cell carcinoma cell line, BTT739 from the T739 mouse, was transfected with a plasmid that encoded an enhanced green fluorescence protein (GFP) and the cells stably expressing GFP were selected and subcloned. 1 x 10(3)-1 x 10(4) GFP-labeled BTT739 cells were injected under the skin of ear of T739 mice. On day 2-5 post injection, the most interesting manifestations observed were the chemotaxis-like movement of the tumor cells toward the pre-existing host vasculature, host vessel dilation and tortuosity and increased extravasation. On day 10 or later, the sprout from pre-existing host vasculature was observed. Once angiogenesis was triggered on, the tumor cells grew more rapidly and exhibited a specific growth pattern where tumor cells always associated with or surrounded the vessels. The newly formed microvessels always showed heavy extravasation. Immunohistochemistry staining revealed strong VEGF and VEGFR2 (Flk-1) expression in tumor cells. Angiography using Rhodamin-labeled dextran showed neovascularization with unprecedented clarity. However, the tumor mass, even bigger than 2 mm and being neovascularized, shrunk and then disappear in 3-5 days and left only delicated host vessels and recovered extravasation. The evidence from this observation indicated that angiogenesis induced by tumor cells after implantation into the host begins at very early stage. The micrometastases foci could not form or survive without vigorous and continuous angiogenesis. Furthermore, there was active VEGF paracrine and autocrine expression in tumor and high level VEGF secretion by tumor cells plays an important role in initiating angiogenesis and supporting micrometastases.


PuMA: A papillomavirus genome annotation tool.
High-throughput sequencing technologies provide unprecedented power to identify novel viruses from a wide variety of (environmental) samples. The field of 'viral metagenomics' has dramatically expanded our understanding of viral diversity. Viral metagenomic approaches imply that many novel viruses will not be described by researchers who are experts on (the genomic organization of) that virus family. We have developed the papillomavirus annotation tool (PuMA) to provide researchers with a convenient and reproducible method to annotate and report novel papillomaviruses. PuMA currently correctly annotates 99% of the papillomavirus genes when benchmarked against the 655 reference genomes in the papillomavirus episteme. Compared to another viral annotation pipeline, PuMA annotates more viral features while being more accurate. To demonstrate its general applicability, we also developed a preliminary version of PuMA that can annotate polyomaviruses. PuMA is available on GitHub (https://github.com/KVD-lab/puma) and through the iMicrobe online environment (https://www.imicrobe.us/#/apps/puma).


Racemization in cataractous lens from diabetic and aging individuals: analysis of Asp 58 residue in αA-crystallin.
Cataract is the leading cause of visual impairment globally. Racemization of lens proteins may contribute to cataract formation in aging individuals. As a special type of age-related cataract (ARC), diabetic cataract (DC) is characterized by the early onset of cortical opacification and finally developed into a mixed type of cortical and nuclear opacification. We compared racemization of Asp 58 residue, a hotspot position in αA-crystallin, from the cortex and nucleus of diabetic and age-matched senile cataractous lenses, by identifying L-Asp/L-isoAsp/D-Asp/D-isoAsp by mass spectrometry. Compared to nondiabetic cataractous lenses, DC lenses showed a significantly increased cortex/nucleus ratio of D-Asp 58, which originated primarily from an increased percentage of D-Asp 58 in the lens cortex of DC. Moreover, patients diagnosed with diabetes for over 10 years showed a lower cortex/nucleus ratio of D-isoAsp 58 in the lens compared with those who had a shorter duration of diabetes, which originated mainly from an increased percentage of D-isoAsp 58 in the lens nucleus of DC with increasing time of hyperglycemia. Further analysis confirmed decreased protein solubility in diabetic cataractous lenses. The different racemization pattern in DC may be distinguished from ARC and influence its phenotype over the protracted duration of diabetes.


C23, an oligopeptide derived from cold-inducible RNA-binding protein, suppresses inflammation and reduces lung injury in neonatal sepsis.
Neonatal sepsis remains a leading cause of infant mortality. Cold-inducible RNA binding protein (CIRP) is an inflammatory mediator that induces TNF-α production in macrophages. C23 is a CIRP-derived peptide that blocks CIRP from binding its receptor. We therefore hypothesized that treatment with C23 reduces systemic inflammation and protects the lungs in neonatal sepsis. Sepsis was induced in C56BL/6 mouse pups (5-7 days) by intraperitoneal injection of adult cecal slurry (0.525 mg/g body weight, LD100). One hour later pups received retroorbital injection of C23 (8 mg/kg) or vehicle (normal saline). Ten hours after sepsis induction, blood and tissues were collected for analysis. C23 treatment resulted in a 58% and 69% reduction in serum levels of proinflammatory cytokines IL-6 and IL-1β, respectively, and a 40% and 45% reduction of AST and LDH, as compared to vehicle-treated septic pups. In the lungs, C23 treatment reduced expression of cytokines IL-6 and IL-1β by 78% and 74%. In addition, the mRNA level of neutrophil chemoattractants KC and MIP-2 was reduced by 84% and 74%, respectively. These results corresponded to a reduction in histologic lung injury score. Vehicle-treated pups scored 0.49 ± 0.19, while C23 treatment reduced scores to 0.29 ± 0.12 (p < 0.05; Max = 1). Apoptosis in the lungs, measured by TUNEL assay, was also decreased by 53% with C23 treatment (p < 0.05). Inhibition of CIRP with C23 treatment is protective in septic neonatal mice as demonstrated by reduced inflammatory markers systemically and in the lung. Therefore, C23 has promising therapeutic potential in treatment of neonatal sepsis. Level I.


Effects of 17α-trenbolone and melengestrol acetate on Xenopus laevis growth, development, and survival.
The synthetic growth-promoting hormones trenbolone and melengestrol acetate have been detected in the environment near beef cattle feedlots and are reportedly transported via wind-borne particulate matter. Therefore, movement of synthetic hormones from beef cattle feedlots to water bodies via particulate matter is possible. Our objective was to evaluate potential effects of 17α-trenbolone (17α-TB), melengestrol acetate (MGA), and combinations of both on growth, development, and survival of Xenopus laevis larvae. On post-hatch day 2 (stage 33/34), X. laevis larvae were exposed to three nominal concentrations of 17α-TB (10, 100, and 500 ng/L), MGA (1, 10, and 100 ng/L), a combination of both (1/10, 10/100, and 100/500 ng/L MGA/17α-TB), frog embryo teratogenesis assay-Xenopus medium, or a solvent control. Significant increases in all X. laevis growth metrics were observed among larvae in the 1 ng/L MGA + 10 ng/L 17α-TB and 10 ng/L MGA + 100 ng/L 17α-TB treatments. Stage of development was increased among larvae in the 1 ng/L MGA + 10 ng/L 17α-TB treatment group and significantly decreased among those in the 500 ng/L 17α-TB treatment. Total body mass and snout-vent length of X. laevis larvae were significantly reduced in the 100 ng/L MGA and 100 ng/L MGA + 500 ng/L 17α-TB treatment groups. Larvae exposed to 500 ng/L 17α-TB had decreased total body mass, snout-vent length, and total length. In general, growth measurements decreased with increasing concentration of MGA, 17α-TB, or a combination of both. Survival among all treatments was not significantly different from controls. Amphibians exposed to MGA and 17α-TB in the environment may experience alterations in growth and development.


[Interprofessional assistance in the rehabilitation of communication skills of laryngectomized patients].
The purpose of this study was to bring basic information about the work of a multiprofessional group involved with the laryngectomees rehabilitation and vocal rehabilitation. Those patients take part in the GARPO-Laryngectomees. The authors describe the different possibilities of vocal rehabilitation for the patients and the framework of the activities and steps of the process. They emphasize the laryngectomees characteristics, the surgical results, and the meaning of being a laryngectomee, as the basis to direct the nurses and the speech therapeutists assistance.


Bacterial symbionts in the hepatopancreas of isopods: diversity and environmental transmission.
The midgut glands (hepatopancreas) of terrestrial isopods contain bacterial symbionts. We analysed the phylogenetic diversity of hepatopancreatic bacteria in isopod species from various suborders colonizing marine, semiterrestrial, terrestrial and freshwater habitats. Hepatopancreatic bacteria were absent in the marine isopod Idotea balthica (Valvifera). The symbiotic bacteria present in the midgut glands of the freshwater isopod Asellus aquaticus (Asellota) were closely related to members of the proteobacterial genera Rhodobacter, Burkholderia, Aeromonas or Rickettsiella, but differed markedly between populations. By contrast, species of the suborder Oniscidea were consistently colonized by the same phylotypes of hepatopancreatic bacteria. While symbionts in the semiterrestrial isopod Ligia oceanica (Oniscidea) were close relatives of Pseudomonas sp. (Gammaproteobacteria), individuals of the terrestrial isopod Oniscus asellus (Oniscidea) harboured either 'Candidatus Hepatoplasma crinochetorum' (Mollicutes) or 'Candidatus Hepatincola porcellionum' (Rickettsiales), previously described as symbionts of another terrestrial isopod, Porcellio scaber. These two uncultivated bacterial taxa were consistently present in each population of six and three different species of terrestrial isopods, respectively, collected in different geographical locations. However, infection rates of individuals within a population ranged between 10% and 100%, rendering vertical transmission unlikely. Rather, feeding experiments suggest that 'Candidatus Hepatoplasma crinochetorum' is environmentally transmitted to the progeny.


Vanishing Confinement Regime in Terahertz HgTe Nanocrystals Studied under Extreme Conditions of Temperature and Pressure.
While HgTe nanocrystals (NCs) in the mid-infrared region have reached a high level of maturity, their far-infrared counterparts remain far less studied, raising the need for an in-depth investigation of the material before efficient device integration can be considered. Here, we explore the effect of temperature and pressure on the structural, spectroscopic, and transport properties of HgTe NCs displaying an intraband absorption at 10 THz. The temperature leads to a very weak modulation of the spectrum as opposed to what was observed for strongly confined HgTe NCs. HgTe NC films present ambipolar conduction with a clear prevalence of electron conduction as confirmed by transistor and thermoelectric measurements. Under the application of pressure, the material undergoes phase transitions from the zinc blende to cinnabar phase and later to the rock salt phase which we reveal using joint X-ray diffraction and infrared spectroscopy measurements. We discuss how the pressure existence domain of each phase is affected by the particle size.


[Technology of magnetic resonance tomography].
Analyzes specific features in technology of magnetic resonance tomography. Presents technical characteristics of magnetic resonance tomographers with various magnetic field size and compares their basic characteristics.


Aqueous synthesis of sulfonate-functionalized 1,2,4-triazole ligands and their 2D Cd2+ coordination networks: crystal structure and photoluminescent properties.
We have developed a water-based synthesis for the preparation of 4-substituted 1,2,4-triazole ligands with highly polar functional groups. This general synthetic approach has allowed us to prepare two sulfonate functionalized 4-substituted 1,2,4-triazole anions ( L1(-)= 4-(1,2,4-triazol-4-yl)benzenesulfonate; L2(-)= 4-(1,2,4-triazol-4-yl)ethanesulfonate). Reaction of these ligands with cadmium(II) salts leads to the formation of two novel two-dimensional coordination networks of formula [Cd(L)Cl]n (1, L1; and 2, L2), which were structurally characterized by X-ray diffraction. In both compounds, the cadmium ions are bridged by chloride ions and the triazole ligands in a bis-bidentate coordination mode using the N1, N2 atoms from the triazole and two oxygen atoms from the -SO3 group. The photoluminescence studies indicate that the ligand photoemission is retained in these networks.


Correlation of activation of Ca2+/calmodulin-dependent protein kinase II with catecholamine secretion and tyrosine hydroxylase activation in cultured bovine adrenal medullary cells.
We have investigated the activation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in cultured bovine adrenal medullary cells. The activation was assayed as an increase in the Ca(2+)-independent (autonomous) activity of CaM kinase II, using the synthetic substrate Syntide-2. Incubation of cells with acetylcholine increased the Ca(2+)-independent activity in a time (20 sec to 5.0 min)- and concentration (10-300 microM)-dependent manner. These curves were closely correlated with those of catecholamine secretion and tyrosine hydroxylase activation. Removal of extracellular Ca2+ completely abolished the stimulatory effects of acetylcholine on the Ca(2+)-independent activity, as well as on catecholamine secretion and activation of tyrosine hydroxylase. Nicotine but not muscarine increased the Ca(2+)-independent activity as potently as did acetylcholine, and hexamethonium but not atropine completely blocked the acetylcholine-induced increase. In 32P-labeled cells, acetylcholine stimulated the phosphorylation of a 50-kDa protein that was immunoprecipitated with an anti-brain CaM kinase II antibody. These results suggest that acetylcholine stimulates CaM kinase II activity through nicotinic acetylcholine receptor-mediated influx of Ca2+ and that the activation of CaM kinase II is closely related to catecholamine secretion and tyrosine hydroxylase activation in cultured adrenal medullary cells.


Diagnostic accuracy of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid with a point-of-care cardiac troponin assay.
Point-of-care (POC) cardiac troponin (cTn) assays have a rapid turnaround time but are generally less sensitive than laboratory-based assays. Previous research found that the Abbott i-Stat cardiac troponin I (cTnI) assay has good diagnostic accuracy when used with the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid and serial sampling over 3 hours. Accuracy of other assays may differ. We therefore evaluated the diagnostic accuracy of a different POC cTnI assay with serial sampling over 3 hours, both with T-MACS and when used alone. In a prospective diagnostic accuracy study at eight EDs in England (July 2015-October 2017), we collected clinical data from consenting adults with suspected ACS at the time of assessment in the ED. Blood samples were drawn on arrival and 3 hours later for POC cTnI (Cardio 3 Triage, Alere). The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI), based on reference standard serial laboratory-based cTn testing. We calculated test characteristics for POC cTnI using the limit of detection (LoD, 0.01 µg/L) and the T-MACS decision aid. Of 347 participants, 59 (14.9%) had AMI. With serial POC cTnI testing over 3 hours, POC cTnI at the LoD cut-off ruled out AMI in 193 (55.6%) patients with 98.1% sensitivity (95% CI 89.9% to 100.0%) and 99.5% negative predictive value (NPV, 95% CI 96.5% to 99.9%). T-MACS ruled out AMI in 117 (33.7%) patients with 98.1% sensitivity (95% CI 89.9% to 100%) and 99.2% NPV (95% CI 94.3% to 99.9%). T-MACS ruled in AMI with 97.9% specificity (95% CI 95.8% to 99.5%) and 83.7% positive predictive value (95% CI 70.6% to 91.7%). With serial sampling over 3 hours, the Alere Cardio 3 Triage cTnI assay has relatively high NPV for AMI using either the LoD cut-off alone or the T-MACS decision aid. However, wide CIs around the measures of diagnostic accuracy mean that further prospective testing of this strategy is required before clinical implementation. UKCRN 18000.


Illustrative cases for monitoring by quantitative analysis of BRAF/NRAS ctDNA mutations in liquid biopsies of metastatic melanoma patients who gained clinical benefits from anti-PD1 antibody therapy.
Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma. The cases described exemplify four distinct clinical benefit patterns: rapid and durable complete response (CR), early progression, followed by CR, CR followed by early progression after interrupting treatment and long-term disease stabilization. These representative cases suggest that comprehensive BRAF/NRAS ctDNA monitoring during anti-PD1 therapy is informative and can be of added value for the monitoring of melanoma patients gaining clinical benefit on anti-PD1 treatment. An important advantage of our approach is that using the cartridge system on the Idylla platform for mutation analysis, the results become available the same day 2 h after plasma collection. Therefore, in the future, the ctDNA level can be an element in the clinical management of the patients.


The influence of initial selection age, relative age effect and country long-term performance on the re-selection process in European basketball youth national teams.
The aims of the study were to: (a) analyse the re-selection patterns in European youth basketball national teams, and (b) investigate how the chance of re-selection is influenced by the initial selection age and relative age of the players, as well as the long-term performance of the country at the youth level. The sample consisted of 8362 basketball players (5038 men, 3324 women) born 1988-1997 who have participated in at least one U16, U18 or U20 European youth basketball championship between 2004 and 2017. The results from the survival analysis showed that around 75% of male and 80% of female players participating in a championship were re-selected the following year. Also, initial selection age, relative age effect, and the country long-term performance influenced the re-selection rates, with relationships being different between men and women. To conclude, the results of the present study show that the re-selection process by which players progress in European youth national basketball teams is complex and influenced by several different factors.


Clinic staff attitudes towards the use of mHealth technology to conduct perinatal depression screenings: a qualitative study.
The use of mHealth technology is an innovative approach for screening low-income mothers for depression. Past studies show that the use of technology removes barriers such as literacy issues, language challenges, concerns about privacy and lack of transportation and can also increase reliability. However, little is known about staff attitudes and perceptions towards using mHealth technology for screening low-income women for depression in clinics. Four focus groups were conducted with staff members in a supplemental nutrition program for women, infants and children located in a public health clinic. A semi-structured focus group interview guide was used to examine staff perceptions related to depression screening with tablet technology. All interviews were audio recorded and transcribed verbatim. Thematic analysis was used to analyse all focus group data. Three major benefits and two major barriers were found. The benefits of using technology for perinatal depression screenings were reduction of literacy and language barriers, reduction of redundancy and errors and increased privacy for clients. The barriers were increased network issues and responsibility for technology, which included fear of the devices being lost, stolen or broken. Before implementing mHealth tablet technology for depression screening in a public health clinic, it is important to address the concerns of staff members to make the transition more effective. This study provides timely information on staff-perceived benefits and barriers when implementing mHealth technology in a public health setting.


Technology Use and Sleep Quality in Preadolescence and Adolescence.
The purpose of this study was to analyze differences between preadolescents and adolescents on the use of technology and to test the contribution of using Internet and mobile phone, and circadian preference on sleep quality. We recruited a sample of 850 (364 males) preadolescents and adolescents. Self-report questionnaires about sleep schedule, sleep wake behavior problems, circadian preferences, and the use of technology (e.g., Internet and mobile phone) were administered. Students were asked to fill out the School Sleep Habits Survey, a self-report questionnaire on the use of technology, the Mobile Phone Involvement Questionnaire (MPIQ), and the Shorter Promis Questionnaire (SPQ). Adolescents reported more sleep problems, a tendency toward eveningness, and an increase of Internet and phone activities, as well as social network activities, while preadolescents were more involved in gaming console and television viewing. The regression analysis performed separately in the two age groups showed that sleep quality was affected by the circadian preference (eveningness) in both groups. Adolescents' bad sleep quality was consistently associated with the mobile phone use and number of devices in the bedroom, while in preadolescents, with Internet use and turning-off time. The evening circadian preference, mobile phone and Internet use, numbers of other activities after 21:00, late turning off time, and number of devices in the bedroom have different negative influence on sleep quality in preadolescents and adolescents.


Comparative genomics and phylogenomics of Campylobacter unveil potential novel species and provide insights into niche segregation.
Campylobacter is a bacterial genus associated with community outbreaks and gastrointestinal symptoms. Studies on Campylobacter generally focus on specific pathogenic species such as C. coli and C. jejuni. Currently, there are thousands of publicly available Campylobacter genomes, allowing a more complete assessment of the genus diversity. In this work, we report a network-based analysis of all available Campylobacter genomes to explore the genus structure and diversity, revealing potentially new species and elucidating genus features. We also hypothesize that the previously established Clade III of C. coli is in fact a novel species (referred here as Campylobacter spp12). Finally, we found a negative correlation between pangenome fluidity and saturation coefficient, with potential implications to the lifestyles of distinct Campylobacter species. Since pangenome analysis depends on the number of available genomes, this correlation could help estimate pangenome metrics of Campylobacter species with less sequenced genomes, helping understand their lifestyle and niche adaptation. Together, our results indicate that the Campylobacter genus should be re-evaluated, with particular attention to the interplay between genome structure and niche segregation.


Evaluating the organizational structure and specificity of network topology within the face processing system.
There is increasing appreciation that network-level interactions among regions produce components of face processing previously ascribed to individual regions. Our goals were to use an exhaustive data-driven approach to derive and quantify the topology of directed functional connections within a priori defined nodes of the face processing network and evaluate whether the topology is category-specific. Young adults were scanned with fMRI as they viewed movies of faces, objects, and scenes. We employed GIMME to model effective connectivity among core and extended face processing regions, which allowed us to evaluate all possible directional connections, under each viewing condition (face, object, place). During face processing, we observed directional connections from the right posterior superior temporal sulcus to both the right occipital face area and right fusiform face area (FFA), which does not reflect the topology reported in prior studies. We observed connectivity between core and extended regions during face processing, but this limited to a feed-forward connection from the FFA to the amygdala. Finally, the topology of connections was unique to face processing. These findings suggest that the pattern of directed functional connections within the face processing network, particularly in the right core regions, may not be as hierarchical and feed-forward as described previously. Our findings support the notion that topologies of network connections are specialized, emergent, and dynamically responsive to task demands.


Three-year outcome of children exposed prenatally to drugs.
To evaluate the 3-year behavioral and developmental outcome of children prenatally exposed to maternal substances of abuse. Ninety-three children exposed prenatally to cocaine and other drugs taken by the mother during pregnancy (Group 1), 24 polydrug/noncocaine exposed children (Group 2), and 25 nonexposed children (Group 3) were evaluated at 3 years of age as part of a longitudinal prospective study of the impact of intrauterine substance exposure on long-term outcome. The Stanford-Binet Intelligence Scale: Fourth Edition(SBIS) was administered by examiners blinded to the exposure background of the children, and a pediatrician performed a complete medical evaluation on all the children. The children's primary caregiver completed the Achenbach Child Behavior Checklist. Stepwise multiple regression procedures were used to determine the factors that best predicted 3-year growth, intelligence, and behavior. Groups 1 and 2 differed from Group 3 on head circumference. Group 1 scored lower than Group 3 on SBIS Verbal Reasoning. Group 2 scored Slower than Group 3 on SBIS Abstract/Visual Reasoning. Cocaine exposure predicted poor verbal reasoning. Marijuana exposure predicted poor abstract/visual reasoning. Examiner rating predicted intellectual outcome and caregiver ratings. Caregivers rated exposed children as more aggressive than nonexposed. Contrary to information in the popular media, not all substance-exposed children suffer the same poor prognosis. In fact, generalizations about the fate of drug-exposed children must await additional research into the outcome of the broader population of drug-exposed children, examining the roles of maternal and environmental factors across a variety of geographic locations and socioeconomic levels.


Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.
Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.


Single-cell transcriptional analysis of taste sensory neuron pair in Caenorhabditis elegans.
The nervous system is composed of a wide variety of neurons. A description of the transcriptional profiles of each neuron would yield enormous information about the molecular mechanisms that define morphological or functional characteristics. Here we show that RNA isolation from single neurons is feasible by using an optimized mRNA tagging method. This method extracts transcripts in the target cells by co-immunoprecipitation of the complexes of RNA and epitope-tagged poly(A) binding protein expressed specifically in the cells. With this method and genome-wide microarray, we compared the transcriptional profiles of two functionally different neurons in the main C. elegans gustatory neuron class ASE. Eight of the 13 known subtype-specific genes were successfully detected. Additionally, we identified nine novel genes including a receptor guanylyl cyclase, secreted proteins, a TRPC channel and uncharacterized genes conserved among nematodes, suggesting the two neurons are substantially different than previously thought. The expression of these novel genes was controlled by the previously known regulatory network for subtype differentiation. We also describe unique motif organization within individual gene groups classified by the expression patterns in ASE. Our study paves the way to the complete catalog of the expression profiles of individual C. elegans neurons.


A role for insulin-like growth factor in the regulation of IL-6-responsive human myeloma cell line growth.
Insulin-like growth factors (IGF-I, IGF-II) have long been recognized as important mitogens in many types of malignancies. Because the role of IGFs in growth control of myeloma cells has not been extensively examined, we have used a panel of IL-6-responsive myeloma cell lines to address this issue. Initial studies demonstrated that IGF-I and IGF-II significantly enhanced DNA synthesis by each of the four cell lines, even when assayed in the absence of IL-6. The specificity of the IGF response was confirmed using an IGF-I receptor Ab, and additional studies demonstrated that IGF responsiveness did not result from induction of autocrine IL-6 expression. When IL-6 responsiveness was assayed, three of four cell lines synthesized DNA in response to IL-6 alone; however, the magnitude of responsiveness was greatly enhanced by addition of IGFs. Similar results were obtained when proliferation and cell cycle progression were analyzed. By contrast, the KP-6 cell line was responsive to IL-6 only when IGF was present. Finally, we analyzed the effects of IGF-I on normal B lymphocytes. IGF, however, did not stimulate B cell DNA synthesis, suggesting that IGF responsiveness may represent a key difference between normal and malignant B cells. In summary, these studies suggest that IGFs may play an important role in multiple myeloma by virtue of their ability to directly stimulate tumor cell growth as well as modulate the magnitude of IL-6-driven growth.


Long-Term Evaluation of Mandibular Growth in Children With FGFR2 Mutations.
Understanding mandibular growth in children with fibroblast growth factor receptor 2 (FGFR2) mutations is important for planning the degree of midface advancement, and for determining the best treatment for obstructive sleep apnea. Yet, relatively little is known about growth of the unoperated mandible in affected children. The purpose of this study was to evaluate mandibular growth through skeletal maturity in Apert, Crouzon, and Pfeiffer syndromes. A retrospective chart review was performed. Long-term, unoperated mandibular growth was assessed using multiple anthropologic measurements including: mandibular width, height, depth, and the cranial base width (approximating bicondylar width). Measurements were compared over 3 age intervals: 6 to 7 years, 10 years, and at skeletal maturity (15 years+). Out of 327 treated patients with FGFR2 mutations, 21 were found to have complete mandibular measurements through skeletal maturity (11 Apert, 7 Crouzon, and 3 Pfeiffer). Initial measurements revealed that mandibular height and bigonial breadth were slightly larger than normal, but sagittal depth and cranial base width were deficient. Early growth was slightly accelerated along the vertical and sagittal axes, stable across the bigonial distance, and marked deficient at the cranial base. At skeletal maturity, vertical height and bigonial width remained above average, but mandibular depth (forward sagittal growth) and cranial base width, remained deficient. Mandibular growth in children with FGFR2 mutations is not normal with impairments found in forward sagittal growth and skull base widening. Knowledge of these deficiencies has significant implications for both planning the degree of midfacial advancements, as well as treating obstructive sleep apnea.


Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: implications for human diabetes.
In insulin-deprived alloxan-induced diabetic dogs with severe hyperglycemia and marked hyperglucagonemia, glucagon was not suppressed by intravenous infusion of glucose at a progressively increasing rate up to 24 mg/kg of body weight per min. However, when the hyperglycemia was corrected by phloridzin, a blocker of renal tubular glucose reabsorption, the hyperglucagonemia was readily suppressed by as little as 2 mg of glucose per kg/min. Direct perfusion of phloridzin into the isolated pancreas of nondiabetic dogs had no effect on the in vitro glucagon response to increments in glucose. However, in pancreata isolated from dogs whose glucose levels had been lowered by phloridzin pretreatment, in vitro glucagon suppression in response to glucose increments was more than twice that of controls. This enhancing effect of phloridzin treatment was completely abolished by giving an intravenous infusion of glucose for the 5 hr prior to surgery for isolation of the pancreas. It is concluded that (i) alpha cells have a glucose-sensing system that is independent of insulin and beta cells, and (ii) this system is reversibly attenuated by hyperglycemia. Thus, hyperglycemia, a metabolic consequence of islet cell dysfunction, may be a self-exacerbating inducer of further islet cell dysfunction, a possibility with implications for human diabetes.


Frequency of self-monitoring and its effect on metabolic control in patients with type 2 diabetes.
The aim of the study was to investigate the frequency of self-monitoring of blood glucose in patients with type 2 diabetes and to determine its effect on metabolic control measured as glycosylated hemoglobin level. The study involved 218 patients with type 2 diabetes (68.8% of females and 31.19% of males) who reported to the Outpatient Department for Diabetes at the Institute of Agricultural Medicine in Lublin. All patients were asked to complete a questionnaire form containing questions concerning, among other things, demographic data, course of diabetes, method of treatment, ability to adjust insulin doses and frequency of self-monitoring of blood glucose level. The levels of glycosylated emoglobin were obtained based on medical records. The analysis of the data showed that 59.22% of patients tested their blood glucose levels at home > or = 1/day, 21.36% of them tested their blood glucose > or = 1/week, whereas 8.74% of patients tested glucose < or = 1/week. 10.68% of patients stated that they never racticed SMBG. Statistical differences were observed in the level of education. Among the group of patients who exercised self-monitoring the most dominant were those with secondary school or university level of education (60.66%), while among patients who did not maintain self-monitoring the greatest number had only elementary or vocational education (72.73) (p = 0.01). The greatest number of patients who most often maintained self-monitoring were office workers (52.46%), whereas among those who did not exercise self-monitoring, those employed in agriculture dominated (45.45%) (p < 0.01). Urban inhabitants exercised self-monitoring more frequently than urban inhabitants (p < 0.01). The frequency of self-monitoring did not affect glycemia control. Urban inhabitants with secondary school or university education level and those who perform office work are more keen on frequent home monitoring of glycemia. In patients with type 2 diabetes the intensity of self-monitoring does not exert any effect on diabetes control evaluated by means of glycosylated hemoglobin level.


T-Bet Expression Mediated by the mTOR Pathway Influences CD4+ T Cell Count in Mice With Lethal Candida Sepsis.
The sustained high morbidity and mortality of Candida sepsis are mainly caused by compromise of host immunity. Clinically, it is often manifested as a significant decrease in CD4+ T cell count, although the mechanism is unclear. We established a lethal mice Candida sepsis model and used Murine Sepsis Score to group mice with different disease severity to establish the influence of T-bet expression on CD4+ T cell count in Candida sepsis. We found that CD4+ T cell count decreased in Candida-infected compared to uninfected mice, and the degree of decrease increased with aggravation of sepsis. Expression of T-bet similarly decreased with worsening of sepsis, but it was significantly enhanced in candidiasis in comparison of naïve state. To clarify its possible mechanism, we measured the activity of mammalian target of rapamycin (mTOR), which is a key regulator of T-bet expression. The mTOR pathway was activated after infection and its activity increased with progression of sepsis. We used mice with T-cell-specific knockout of mTOR or tuberous sclerosis complex (TSC)1 to further inhibit or strengthen the mTOR signaling pathway. We found that mTOR deletion mice had a higher CD4+ T cell count by regulating T-bet expression, and the result in TSC1 deletion mice was reversed. These results demonstrate that T-bet expression mediated by the mTOR pathway influences the CD4+ T cell count in mice with Candida sepsis.


Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population.
Chronic hepatitis B virus (HBV) carriers with high-titer viremia (>10(5) virions/ml) are at increased risk for hepatocellular carcinoma (HCC). The aim of this study was to determine the relationship between clearance of high-titer viremia and subsequent risk of HCC. The study population was a prospective cohort of 114 adults from Haimen City, China, all HBV DNA(+) at study entry and followed for 797.8 person-years in total. During follow-up, 54 (47.4%) subjects spontaneously cleared high-titer viremia at least once. Of these, 27 were considered to have undergone stable seroconversion, 16 were considered unstable (12 reversions to HBV DNA positivity and 4 multiple clearances), and 11 did not have sufficient follow-up to determine stability. Of the 114 persons, 26 (22.8%) died during follow-up, 21 (18.4%) from HCC. Using Cox proportional hazards models, the RR of HCC death associated with seroconversion was 2.8 (95% CI = 1.1-7.4), controlling for age, sex, family HCC history, history of acute hepatitis, alcohol use and cigarette smoking. In conclusion, fluctuations of high-titer viremia may indicate increased hepatocellular damage and at least short-term increases in HCC risk. Long-term longitudinal studies are needed to clarify this relationship and its potential usefulness as a prognostic marker in chronic HBV infection.


Lengthening in Congenital Femoral Deficiency: A Comparison of Circular External Fixation and a Motorized Intramedullary Nail.
Circular external fixation for limb-lengthening is associated with frequent and numerous complications. Intramedullary lengthening devices represent a potential advance in limb-lengthening. The purpose of this study was to compare the outcomes of femoral lengthening in pediatric patients treated by either circular external fixation or a motorized intramedullary nail. All patients with a diagnosis of congenital femoral deficiency who had undergone femoral lengthening with either circular external fixation or a motorized intramedullary nail were identified. The motorized intramedullary nail (FITBONE) was used with approval of the U.S. Food and Drug Administration on an individual compassionate-use basis. Fourteen skeletally mature patients underwent fourteen femoral lengthening sessions using circular external fixation, and thirteen patients underwent fifteen lengthening sessions using the motorized nail. The amount lengthened was similar, with a mean of 4.8 cm (range, 1.0 to 7.4 cm) in the circular fixation group and 4.4 cm (range, 1.5 to 7.0 cm) in the motorized nail group. Complications occurred in all lengthening sessions in all fourteen patients managed with the circular external fixation and in 73% of fifteen lengthening sessions in the thirteen patients managed with the motorized nail. The circular external fixation group averaged 2.36 complications per lengthening session compared with 1.2 per session in the motorized nail group. Twenty-nine percent of the circular fixation group failed to achieve a lengthening goal of at least 4 cm compared with 27% of the motorized nail group who failed to reach the goal. Eight patients had undergone eleven femoral lengthening sessions with circular external fixation prior to undergoing ten lengthening sessions by motorized nail. These patients had a comparable rate of complications with both types of lengthening, but the total number of complications averaged 2.6 per lengthening session with circular external fixation compared with 1.6 per lengthening session with the motorized nail. A decreased number of complications was noted with use of a motorized intramedullary nail compared with circular external fixation in pediatric patients undergoing femoral lengthening for congenital femoral deficiency. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Pharmacologic management of diabetes mellitus.
Recently, the number of agents to treat type 2 diabetes has increased markedly. In the past, the only agents practitioners had available to treat patients with type 2 diabetes mellitus were insulin and sulfonylureas. Today, three additional classes of agents with a total of six new drugs are available: acarbose, migital, repaglinide, metformin hydrochloride, troglitazone, and rosiglitazone. In the not-too-distant future, several other agents will be available for treating patients with diabetes. These new agents will allow physicians to control their diabetic patients' blood sugar levels without the need for insulin injections. This article reviews the new agents and provides practical suggestions regarding their use as monotherapy or in combination therapy.


Adult safeguarding managers' understandings of self-neglect and hoarding.
Self-neglect and hoarding are behaviours that are hard to define, measure and address. They are more prevalent among older people because of bio-psycho-social factors, which may be exacerbated by advancing age. This paper aims to further understandings of self-neglect and hoarding in England's Care Act 2014 context, drawing on a study involving qualitative interviews with local authority adult safeguarding managers who play an important role in determining interventions with individuals who self-neglect and/or hoard. Online interviews were conducted with adult safeguarding leads and managers from 31 English local authorities in 2021. Interview data were subject to thematic analysis. This paper explores the commonalities and differences in adult safeguarding managers' understandings of the causes and consequences of self-neglect and/or hoarding among older people, which are likely to have tangible impacts on service provision in their local authority, and influencing of wider changes to policies and procedures. Most participants understood these phenomena as caused by a range of bio-psycho-social factors, including chronic physical conditions, bereavement, isolation. A minority took a more clinical or psycho-medical perspective, focusing on mental ill-health, or referred to the social construction of norms of cleanliness and tidiness. Whatever their understanding, by the time such behaviours are brought to the attention of safeguarding professionals a crisis response may be all that is offered. The implications of the findings are that other agencies should be encouraged to provide more early help to older people at risk of self-neglect and/or of developing harmful hoarding behaviours, and that sustained engagement with those affected may help to understand some of the causes of these behaviours to enable effective support or practice interventions.


A high-performance polydimethylsiloxane electrospun membrane for cell culture in lab-on-a-chip.
Thin porous membranes are important components in a microfluidic device, serving as separators, filters, and scaffolds for cell culture. However, the fabrication and the integration of these membranes possess many challenges, which restrict their widespread applications. This paper reports a facile technique to fabricate robust membrane-embedded microfluidic devices. We integrated an electrospun membrane into a polydimethylsiloxane (PDMS) device using the simple plasma-activated bonding technique. To increase the flexibility of the membrane and to address the leakage problem, the electrospun membrane was fabricated with the highest weight ratio of PDMS to polymethylmethacrylate (i.e., 6:1 w/w). The membrane-integrated microfluidic device could withstand a flow rate of up to 50 μl/min. As a proof of concept, we demonstrated that such a compartmentalized microfluidic platform could be successfully used for cell culture with the capability of providing a more realistic in vivo-like condition. Human lung cancer epithelial cells (A549) were seeded on the membrane from the top microchannel, while the continuous flow of the culture medium through the bottom microchannel provided a shear-free cell culture condition. The tortuous micro-/nanofibers of the membrane immobilized the cells within the hydrophobic micropores and with no need of extracellular matrix for cell adhesion and cell growth. The hydrophobic surface conditions of the membrane were suitable for anchorage-independent cell types. To further extend the application of the device, we qualitatively showed that rinsing the membrane with ethanol prior to cell seeding could temporarily render the membrane hydrophilic and the platform could also be used for anchorage-dependent cells. Due to the three-dimensional (3D) topography of the membranes, three different configurations were observed, including individual single cells, monolayer cells, and 3D cell clusters. This cost-effective and robust compartmentalized microfluidic device may open up new avenues in translational medicine and pharmacodynamics research.