The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells.
HIV-2 is less pathogenic for humans than HIV-1 and might provide partial cross-protection from HIV-1-induced pathology. Although both viruses replicate in the T cells of infected patients, only HIV-2 replicates efficiently in dendritic cells (DCs) and activates innate immune pathways. How HIV is sensed in DC is unknown. Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, DCs sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells. This pathway might potentially be harnessed to develop effective vaccines against HIV-1.


[Histopathological and ultrastructural changes in the liver and their pathogenesis in burns of rabbits].
48 health male rabbits were randomly divided into two groups: a napalm burn group and a healthy control group. The total area of burn was 30% TBSA full-thickness burn. Blood and liver tissue specimens were taken at 2, 6, 12, 24, 48, 72 and 168 hours postburn for quantitative analysis of serum enzymes, protein and histopathological, subcellular examination of the liver. Results indicated that hepatic pathological changes were characterized by an early onset, severity in extent, wide distribution and diversified morphology. Basic pathological changes in the liver included: (1) degeneration and necrosis of the hepatic cells and their transitional changes; (2) infiltration of inflammatory cells in parenchyma and interstices; (3) proliferation and swelling of Kupffer cells with active phagocytosis and subsequent degeneration. The overall course of changes observed in the liver specimens was divided into four phases: (1) congestive and anoxia phase, (2) inflammation phase, (3) degeneration and necrosis phase, (4) repair phase. The causes and pathogenesis of the four phases were analysed and discussed. Three possibilities of their pathogenesis were suggested according to morphological features and the course of the development of focal intracytoplasmic degeneration (FCD) and lytic necrosis (FCLY).


Maternal perception of malnutrition among infants using verbal and pictorial methods in Kenya.
To compare mothers' perceptions of their own infants' nutritional status with anthropometric indicators of undernutrition. A qualitative study and cross-sectional quantitative survey. The qualitative study involved developing tools to assess mother's perception. Two methods of verbal description and a pictorial scale were developed. The quantitative survey involved measuring maternal perception and comparing it with the anthropometric measures of weight-for-age Z-score (WAZ) and mid-upper arm circumference-for-age Z-score (MUACZ). A rural community setting in Kenya. Seventy-four infants aged between 4 and 6 months, and their mothers, living in rural Kenya were enrolled. Using verbal description, the positive and negative likelihood ratios were 3.57 (95 % CI 1.44, 9.98) and 0.69 (95 % CI 0.50, 0.96) respectively for MUACZ<-2; and 4.60 (95 % CI 1.60, 13.3) and 0.67 (95 % CI 0.49, 0.92) respectively for WAZ<-2. Using the pictorial scale, the positive and negative likelihood ratios were 8.30 (95 % CI 1.91, 36.3) and 0.69 (95 % CI 0.52, 0.93) respectively for MUACZ<-2; and 4.31 (95 % CI 1.22, 15.0) and 0.78 (95 % CI 0.61, 1.00) respectively for WAZ<-2. In a rural community, mothers better identify undernutrition in their infants using a pictorial scale than verbal description. However, neither can replace formal anthropometric assessment. Objective anthropometric tools should be validated for identification of severe acute malnutrition among infants aged less than 6 months.


Human and pet-related risk factors for household evacuation failure during a natural disaster.
This study characterized risk factors for household evacuation failure. A random digit dial telephone survey was conducted of 397 households in Yuba County, California, in July 1997, 6 months after residents had been under evacuation notice due to flooding. Case households failed to evacuate, whereas control households evacuated. The cumulative incidence of household evacuation failure was 19.4%. Fewer households with children (25.8%) failed to evacuate than households without children (45.9%, p < 0.01). More households with pets (20.9%) than households without pets failed to evacuate (16.3%, p = 0.11). With multivariate logistic regression, the risk of household evacuation failure was lower in households with children (odds ratio = 0.4, 95% confidence interval: 0.2, 0.8) compared with households without children. The risk of household evacuation failure increased in pet-owning households without children (odds ratio = 1.3, 95% confidence interval: 1.1, 1.5) compared with pet-owning households with children; the more pets a household owned, the higher the risk of household evacuation failure was. Impediments to pet evacuation, including owning multiple pets, owning outdoor dogs, or not having a cat carrier, explained why many households that owned pets failed to evacuate. Predisaster planning should place a high priority on facilitating pet evacuation through predisaster education of pet owners and emergency management personnel.


Alpha-1 antitrypsin inhibits caspase-1 and protects from acute myocardial ischemia-reperfusion injury.
Alpha-1-antitrypsin (AAT) possesses anti-inflammatory and tissue-protective properties. Here, we studied the effects of exogenously administered AAT on caspase-1 activity and on the outcome of ischemia-reperfusion injury (I/R) in a mouse model of acute myocardial infarction (AMI). Adult male mice underwent 30 min of coronary artery ligation followed by reperfusion and were randomly assigned to receive clinical-grade AAT or albumin at reperfusion. Infarct size was evaluated after 1 and 7 days. Caspase-1 activity was measured in homogenates of heart tissue. Left ventricular (LV) end-diastolic diameter (EDD) and end-systolic diameter (ESD) were measured and LV fractional shortening (FS) and ejection fraction (EF) were calculated using transthoracic echocardiography. The effect of AAT on caspase-1 activity was determined in cultures of mouse HL-1 cardiomyocytes stimulated with LPS and triggered with nigericin or when HL-1 cells were exposed to simulated ischemia. AAT-treated mice had significantly smaller infarct sizes (-30% day 1 and -55% day 7) compared with mice treated with albumin. AAT treatment resulted in >90% reduction in caspase-1 activity in homogenates of hearts 24h after I/R. Seven days after AMI, AAT-treated mice exhibited a >90% smaller increase in LVEDD and LVESD and smaller reduction in LVEF. The increase in caspase-1 activity in HL-1 cells induced by LPS and nigericin or following exposure to simulated ischemia was reduced by >80% and AAT similarly reduced cell death by >50%. In conclusion, exogenous administration of clinical grade AAT reduces caspase-1 activity in the ischemic myocardium leading to preservation of viable myocardium and prevention of adverse cardiac remodeling.


Gender-based differences in water, sanitation and hygiene-related diarrheal disease and helminthic infections: a systematic review and meta-analysis.
Qualitative evidence suggests that inadequate water, sanitation and hygiene (WASH) may affect diarrheal and helminthic infection in women disproportionately. We systematically searched PubMed in June 2014 (updated 2016) and the WHO website, for relevant articles. Articles dealing with the public health relevance of helminthic and diarrheal diseases, and highlighting the role of gender in WASH were included. Where possible, we carried out a meta-analysis. In studies of individuals 5 years or older, cholera showed lower prevalence in males (OR 0.56; 95% CI 0.34-0.94), while Schistosoma mansoni (1.38; 95% CI 1.14-1.67), Schistosoma japonicum (1.52; 95% CI 1.13-2.05), hookworm (1.43; 95% CI 1.07-1.89) and all forms of infectious diarrhea (1.21; 95% CI 1.06-1.38) showed a higher prevalence in males. When studies included all participants, S. mansoni and S. japonicum showed higher prevalence with males (OR 1.40; 95% CI 1.27-1.55 and 1.84; 95% CI 1.27-2.67, respectively). Prevalence of Trichiuris and hookworm infection showed effect modification with continent. Evidence of gender differences in infection may reflect differences in gender norms, suggesting that policy changes at the regional level may help ameliorate gender related disparities in helminthic and diarrheal disease prevalence.


Sexual function and sexual satisfaction following spinal cord injury: an interpretative phenomenological analysis of partner experiences.
This study explored how partners/spouses of people with Spinal Cord Injury (SCI) experienced intimacy, sexual function, and sexual satisfaction post-SCI. Qualitative, semi-structured interviews were conducted with the partners/spouses of people with SCI living in the community in the United Kingdom. Twelve participants (7 females; 5 males) were recruited using purposive sampling. A nine-item semi-structured interview design was used. Interviews were transcribed verbatim and analysed via Interpretative Phenomenological Analysis (IPA). Three superordinate themes were demonstrated: (1) Stolen sex through unpreparedness; (2) Redefining sex; and (3) Compromised commitment. Partners struggled to come to terms with the shock of radically altered post-SCI sexual relationships, questioning how their changed sexual relationship and sexual identity conflicted with caring requirements. To minimise post-SCI relationship changes, some partners engaged in strategies to protect against, distract from and avoid sexual intimacy, whereas others were able to retain adapted pre-injury patterns of intimate behaviour. Compromised sexual function and satisfaction significantly disrupt relationship dynamics post-SCI, initiate voluntary celibacy, and limit the perceived viability of continued sexual intimacy. Specialist partner-support provisions are urgently needed, recognising that partner support needs are not restricted to the inpatient rehabilitation phase but importantly extend long past discharge into the community.


[Physico-chemical properties of borate derivatives of DOPA, dopamine, and their liposome forms].
To increase the solubility of L-3,4-dihydroxyphenylalanine (DOPA) and dopamine (DA) incorporated in liposomes, it was suggested to convert them into ammonium and 1-adamantylammonium borate complexes. The structure of these complexes was studied by 11B and 1H NMR, IR, and mass spectrometry and conductometry. The liposomic form of the complexes is characterized by a high active compound/lipid molar ratio (0.5). Catechols in the form of complex salts are retained better within the inner volume of liposomes.


Convergent Validation of Methods for the Identification of Psychotherapeutic Phase Transitions in Time Series of Empirical and Model Systems.
In many cases, the dynamics of psychotherapeutic change processes is characterized by sudden and critical transitions. In theoretical terms, these transitions may be "phase transitions" of self-organizing nonlinear systems. Meanwhile, a variety of methods is available to identify phase transitions even in short time series. However, it is still an open question if different methods for timeseries analysis reveal convergent results indicating the moments of critical transitions and related precursors. Seven concepts which are commonly used in nonlinear time series analysis were investigated in terms of their ability to identify changes in psychological time series: Recurrence Plots, Change Point Analysis, Dynamic Complexity, Permutation Entropy, Time Frequency Distributions, Instantaneous Frequency, and Synchronization Pattern Analysis, i.e., the dynamic inter-correlation of the system's variables. Phase transitions were simulated by shifting control parameters in the Hénon map dynamics, in a simulation model of psychotherapy processes (one by an external shift of the control parameter and one created by a simulated control parameter shift), and three sets of empirical time series generated by daily self-ratings of patients during the treatment. The applied methods showed converging results indicating the moments of dynamic transitions within an acceptable tolerance. The convergence of change points was confirmed statistically by a comparison to random surrogates. In the three simulated dynamics with known phase transitions, these could be identified, and in the empirical cases, the methods converged indicating one and the same transition (possibly the phase transitions of the cases). Moreover, changes that did not manifest in a shift of mean or variance could be detected. Changes can occur in many different ways in the psychotherapeutic process. For instance, there can be very slow and small transitions or very high and sudden ones. The results show the validity and stability of different measures indicating pattern transitions and/or early warning signals of those transitions. This has profound implications for real-time monitoring in psychotherapy, especially in cases where a transition is not obvious to the eye. Reliably identifying points of change is mandatory also for research on precursors, which in turn can help improving treatment.


Advances in Magnetic Carbon Dots: A Theranostics Platform for Fluorescence/Magnetic Resonance Bimodal Imaging and Therapy for Tumors.
Theranostics technology that combines tumor diagnosis or monitoring with therapy is an important direction for the future development of tumor treatment. It takes advantage of efficiently observing tumor tissues, monitoring tumor treatment in real time, and significantly improving the cure efficiency. Magnetic carbon dots (CDs) are of wide interest as molecular imaging probes, drug carriers, photosensitizers, and radiosensitizers in the integration of tumor fluorescence/magnetic resonance bimodal diagnosis and treatment because of their small size, good optical stability, magnetic relaxation rate, and biocompatibility. This review first analyzes and compares the synthesis methods and physicochemical properties of magnetic CDs in recent years and then concludes their mechanism in tumor fluorescence/magnetic resonance bimodal imaging and therapy in details. Subsequently, the research progress of their application in tumor theranostics are summarized. Finally, the problems and challenges of magnetic CDs for development at this stage are prospected. This review provides new ideas for their controlled synthesis and application in efficient and precise therapy for tumors.


Team building: key to executive success.
The key to executive success is management of the information overload provided by today's high technology era. Team building, through identification of behavioral styles, helps to enhance self-esteem, utilize inherent skills of individuals, and maximize decision making. The style of the team leader who shares leadership promotes communication patterns that lead to participatory management and harmony within institutions.


Pelvic bioelectrical impedance measurements to detect rectal filling.
Anorectal sensory deficits are an important cause of defecatory disorders and are also a reason for evacuatory difficulties in patients undergoing total anorectal reconstruction. A method to detect rectal filling would be beneficial in such patients. We have investigated the feasibility of detecting rectal filling in vitro and in vivo by measuring changes in pelvic impedance. In vitro, a model of the pelvis was constructed using a cylindrical plastic tank filled with an electrolyte solution (conductivity 3 mS cm(-1)). Conductive Visking tubing representing the rectum was suspended in the tank and incrementally filled with artificial faeces. An impedance meter detected changes in voltage on rectal filling when an alternating current of 2 mA was passed at eight frequencies (4.8 to 612 kHz). In vivo, changes in pelvic bioelectrical impedance upon retrograde and antegrade rectal filling with artificial faeces were evaluated in three pigs, four electrodes being implanted in the pelvis. Impedance measurements accurately detected 'rectal' volume changes in vitro (n = 10, p < 0.0001; Kruskal Wallis), but not in vivo (n = 68, p = 0.48; Kruskal Wallis). This was probably due to extreme sensitivity of the detecting device to movement, a problem that needs to be resolved before this technique could be used in man.


Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae.
The mitochondrial genome, mtDNA, is present in multiple copies in cells and encodes essential subunits of oxidative phosphorylation complexes. mtDNA levels have to change in response to metabolic demands and copy number alterations are implicated in various diseases. The mitochondrial HMG-box proteins Abf2 in yeast and TFAM in mammals are critical for mtDNA maintenance and packaging and have been linked to mtDNA copy number control. Here, we discover the previously unrecognized mitochondrial HMG-box protein Cim1 (copy number influence on mtDNA) in Saccharomyces cerevisiae, which exhibits metabolic state dependent mtDNA association. Surprisingly, in contrast to Abf2's supportive role in mtDNA maintenance, Cim1 negatively regulates mtDNA copy number. Cells lacking Cim1 display increased mtDNA levels and enhanced mitochondrial function, while Cim1 overexpression results in mtDNA loss. Intriguingly, Cim1 deletion alleviates mtDNA maintenance defects associated with loss of Abf2, while defects caused by Cim1 overexpression are mitigated by simultaneous overexpression of Abf2. Moreover, we find that the conserved LON protease Pim1 is essential to maintain low Cim1 levels, thereby preventing its accumulation and concomitant repressive effects on mtDNA. We propose a model in which the protein ratio of antagonistically acting Cim1 and Abf2 determines mtDNA copy number.


HSP90alpha gene expression may be a conserved feature of vertebrate somitogenesis.
We have previously demonstrated that the hsp90alpha and hsp90beta genes in zebrafish are expressed in dramatically different spatial and temporal patterns in early embryos. In the case of hsp90alpha, expression is spatially restricted within the somites to putative myogenic cells which also express mRNA encoding the myogenic bHLH transcription factor myoD and is downregulated along with myoD following myogenesis. In the present study, we have examined hsp90alpha gene expression in developing chicken embryos using a gene-specific probe. We show that hsp90alpha gene expression is also localized to a subset of cells within the somites of chicken embryos and that the expression pattern correlates closely to that observed for myoD. Furthermore, expression of the hsp90alpha gene is strongly upregulated throughout the embryo following heat shock in a manner similar to that observed in heat-shocked zebrafish embryos. The data suggest that the hsp90alpha gene may play an evolutionarily conserved role during somitogenesis in vertebrates in addition to providing protection to all cells of the embryo following stress.


Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice.
Doxorubicinol (dxol) is the major metabolite formed in the hearts of cancer patients being treated with the widely used chemotherapeutic agent, doxorubicin (dox). The well-documented cardiomyopathy associated with dox treatment has been studied in vitro and ex vivo providing evidence that the C-13 hydroxy metabolite, dxol, might play a key role in the development of dox-induced cardiotoxicity. In this report, we have developed transgenic mice with heart-specific expression of human carbonyl reductase (HCBR), an enzyme that metabolizes dox to dxol. Dox was rapidly converted to dxol in the hearts of the transgenic expressers, which led to advanced development of both acute and chronic cardiotoxicity. Acute cardiotoxicity was evident by a 60% increase in serum creatine kinase activity and a 5-fold increase in cardiac damage measured by electron microscopy. Myofibril degeneration was the major damage observed in acute dox toxicity. Electrocardiograph telemetry, survival data, and electron microscopy were monitored during chronic dox-induced cardiotoxicity. HCBR expressers developed cardiotoxicity 6-7 weeks before the nonexpressers. The HCBR expressers survived for 5 weeks compared with 12 weeks for the controls. Electrocardiograph profiles and necropsies showed the cause of death to be the development of cardiomyopathies leading to congestive heart failure. Levels of dxol were four times higher in the HCBR expresser hearts than in the nonexpressers. Electron microscopy data showed swelling and major structural damage of the mitochondria in the HCBR expressers. These data demonstrate that the C-13 hydroxy metabolite of dox advances the development of dox-induced cardiotoxicity in an in vivo system and suggest that heart carbonyl reductase activity may contribute to dox-induced cardiotoxicity in humans.


Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival.
Coupled cellular respiration requires that ATP and ADP be efficiently exchanged between the cytosol and the mitochondrial matrix. When growth factors are withdrawn from dependent cells, metabolism is disrupted by a defect in ATP/ADP exchange across the mitochondrial membranes. Unexpectedly, we find that this defect results from loss of outer mitochondrial membrane permeability to metabolic anions. This decrease in anion permeability correlates with the changes in conductance properties that accompany closure of the voltage-dependent anion channel (also known as mitochondrial porin). Loss of outer membrane permeability (i) results in the accumulation of stored metabolic energy within the intermembrane space in the form of creatine phosphate, (ii) is prevented by the outer mitochondrial membrane proteins Bcl-x(L) and Bcl-2, and (iii) can be reversed by growth factor readdition. If outer membrane impermeability persists, the disruption of mitochondrial homeostasis culminates in loss of outer mitochondrial membrane integrity, cytochrome c redistribution, and apoptosis. The recognition that outer membrane permeability is regulated under physiological conditions has important implications for the understanding of bioenergetics and cell survival.


Health, absence, disability, and presenteeism cost estimates of certain physical and mental health conditions affecting U.S. employers.
Evidence about the total cost of health, absence, short-term disability, and productivity losses was synthesized for 10 health conditions. Cost estimates from a large medical/absence database were combined with findings from several published productivity surveys. Ranges of condition prevalence and associated absenteeism and presenteeism (on-the-job-productivity) losses were used to estimate condition-related costs. Based on average impairment and prevalence estimates, the overall economic burden of illness was highest for hypertension ($392 per eligible employee per year), heart disease ($368), depression and other mental illnesses ($348), and arthritis ($327). Presenteeism costs were higher than medical costs in most cases, and represented 18% to 60% of all costs for the 10 conditions. Caution is advised when interpreting any particular source of data, and the need for standardization in future research is noted.


Application of Plasmonic Gold Nanoparticle for Drug Delivery System.
Efforts in developing various colloidal nanoparticles (NPs) as theranostic probes have been promising in the biomedical field. Specifically, colloidal gold nanoparticles (GNP) have been extensively utilized as a theranostic probe for molecular imaging and drug delivery owing to their unique physiochemical properties with excellent biocompatibility. This review outlines and discusses the progress regarding gold nanoparticle synthesis methods for controlled geometry (spherical, rod, and cage), surface functionalization (covalent and non-covalent), and associated in vitro/in vivo cytotoxicity as well as some of the interesting diagnostic (imaging) and therapeutic (photo-thermal, drug delivery) applications. GNP possesses several advantages compared to other traditional theranostic agents, we firmly believe that GNP based clinical approach will gain continuous interest with increasing numbers of innovations.


A Method for 3D Reconstruction and Virtual Reality Analysis of Glial and Neuronal Cells.
Serial sectioning and subsequent high-resolution imaging of biological tissue using electron microscopy (EM) allow for the segmentation and reconstruction of high-resolution imaged stacks to reveal ultrastructural patterns that could not be resolved using 2D images. Indeed, the latter might lead to a misinterpretation of morphologies, like in the case of mitochondria; the use of 3D models is, therefore, more and more common and applied to the formulation of morphology-based functional hypotheses. To date, the use of 3D models generated from light or electron image stacks makes qualitative, visual assessments, as well as quantification, more convenient to be performed directly in 3D. As these models are often extremely complex, a virtual reality environment is also important to be set up to overcome occlusion and to take full advantage of the 3D structure. Here, a step-by-step guide from image segmentation to reconstruction and analysis is described in detail.


Functional analysis of multiple transcription factor sites in a regulatory element of human epsilon-globin gene.
The developmental control of the human epsilon-globin gene expression is mediated by transcriptional regulatory elements in the 5' flanking DNA of this gene. A previously identified negative regulatory element (-3028 to -2902 bp, termed epsilon-NRAII) was analyzed and one putative NF-kappaB site and two GATA sites locate at -3004 bp, -2975 bp and -2948 bp were characterized. Electrophoresis mobility shift assay (EMSA) showed that the putative NF-kappaB site was specifically bound by nuclear proteins of K562 cells. Data obtained from transient transfection showed that the expression of reporter gene could be upregulated about 50% or 100% respectively when epsilon-NRAII was inserted upstream of the SV40 promoter or epsilon-globin gene proximal promoter (-177 bp to +1 bp), suggesting that epsilon-NRAII might not be a classic silencer. Mutation in the putative NF-kappaB site or in the GATA site (at -2975 bp) slightly reduced the expression of reporter gene driven by SV40 promoter or epsilon-globin gene proximal promoter. However, the mutation of GATA site at -2948 bp remarkably reduced the reporter gene activity driven by SV40 promoter, but not by epsilon-globin gene proximal promoter. Further mutation analysis showed that the negative effect of mutation in GATA site at -2948 bp on SV40 promoter was not affected by the mutation of the putative NF-kappaB site, whereas it could be abolished by the mutation of GATA site at -2975 bp. Furthermore, the mutation of both GATA sites could synergistically reduce the reporter gene activity driven by epsilon-globin gene proximal promoter. Those results suggested that epsilon-NRAII might function differently on the SV40 promoter and epsilon-globin gene proximal promoter.


Complex Attention-Deficit/Hyperactivity Disorder in a Bilingual Child with Down Syndrome and Intellectual Disability.
Maria is an 8-year-old girl with Down syndrome, described by her mother as an affectionate and social child, who was referred to developmental-behavioral pediatrics by her pediatrician because of increasing aggressive behaviors and inattention.Maria was 5 pounds at birth, delivered full-term by cesarean section, and hospitalized for 1 month after delivery because of feeding issues that required a nasogastric (NG) tube. Maternal age was 24 years, pregnancy was uncomplicated, and there were no reported prenatal exposures to substances. Additional medical history includes corrective cardiac surgery at age 11 months, mild-to-moderate hearing loss in 1 ear, and myopia.At the time of Maria's presentation to developmental-behavioral pediatrics, she was in third grade and had an IEP with placement in a substantially separate multigrade classroom and inclusion for special classes such as music and art. She had multiple academic goals and accommodations for behaviors such as eloping from class, shoving, and growling at adults; communication Picture Exchange Communication System (PECS); and extended time to complete assignments. Previously, she had attended an inclusion setting with a 1:1 aide. Maria is followed annually at a specialty clinic that focuses on the health needs of children with Down syndrome. At home, Maria's parents speak primarily Spanish, while her 2 older brothers speak primarily English. Maria has been using 3-word phrases since she was 6 years old and understands some American Sign Language. She also uses a PECS book for communication.During the visit, Maria was notably fidgety, frequently interrupted the parent interview despite having toys to play with, and became aggressive-hitting, kicking, pushing, and shoving-when she did not want to comply with directives. She used mostly single words and a variety of gestures to communicate. Both the parent-completed and teacher-completed Conners-3 (Long Version) produced elevated T-scores (>70) in the domains of inattention, hyperactivity/impulsivity, defiance/aggression, peer relations, Global Index scale, DSM-5 Hyperactive/Impulsive symptom scale, and DSM-5 Conduct Disorder symptom scale. The teacher endorsed full criteria for attention-deficit/hyperactivity disorder, consistent with combined presentation, and the parent endorsed symptoms in a similar pattern. Methylphenidate (2.5 mg) was trialed but tolerated poorly when it was titrated to 5 mg. Maria's mother reported that Maria's focus was somewhat better, but she was easily brought to tears and "not herself."What would be the next steps in Maria's evaluation/treatment? Could there be reasons for her worsening behavior other than a primary attention disorder?


Factors that influence siderophoremediated iron bioavailability: catalysis of interligand iron (III) transfer from ferrioxamine B to EDTA by hydroxamic acids.
Deferriferrioxamine B (H3DFB) is a linear trihydroxamic acid siderophore with molecular formula NH2(CH2)5[N(OH)C(O)(CH2)2C(O)NH(CH2)5]2N(OH)C(O)CH3 that forms a kinetically and thermodynamically stable complex with iron(III), ferrioxamine B. Under the conditions of our study (pH = 4.30, 25 degrees C), ferrioxamine B, Fe(HDFB)+, is hexacoordinated and the terminal amine group is protonated. Addition of simple hydroxamic acids, R1C(O)N(OH)R2 (R1 = CH3, R2 = H; R1 = C6H5, R2 = H; R1 = R2 = CH3), to an aqueous solution of ferrioxamine B at pH = 4.30, 25.0 degrees C, I = 2.0, results in the formation of ternary complexes Fe(H2DFB)A+ and Fe(H3DFB)A2+, and tris complexes FeA3, where A- represents the bidendate hydroxamate anion R1C(O)N(O)R2-. The addition of a molar excess of ethylenediaminetetraacetic acid (EDTA) to an aqueous solution of ferrioxamine B at pH 4.30 results in a slow exchange of iron(III) to eventually completely form Fe(EDTA)- and H4DFB+. The addition of a hydroxamic acid, HA, catalyzes the rate of this iron exchange reaction: (formula; see text) A four parallel path mechanism is proposed for reaction (1) in which catalysis occurs via transient formation of the ternary and tris complexes Fe(H2DFB) A+, Fe(H3DFB)A2+, and FeA3. Rate and equilibrium constants for the various reaction paths to products were obtained and the influence of hydroxamic acid structure on catalytic efficiency is discussed. The importance of a low energy pathway for iron dissociation from a siderophore complex in influencing microbial iron bio-availability is discussed. The system represented by reaction (1) is proposed as a possible model for in vivo catalyzed release of iron from its siderophore complex at the cell wall or interior, where EDTA represents the intracellular storage depot or membrane-bound carrier and HA represents a low molecular weight hydroxamate-based metabolite capable of catalyzing interligand iron exchange.


Oral cancer in the Europe Against Cancer programme--an Irish report.
The dental surgeon is in a unique position to recognise and detect precancer and cancer of the mouth. The aim of this report is to describe the action taken by the Irish Dental Association in the Europe Against Cancer programme since 1990, to highlight the relevance for the dental profession and to outline the action plan for the future.


Elaborate horns in a giant rhinoceros beetle incur negligible aerodynamic costs.
Sexually selected ornaments and weapons are among nature's most extravagant morphologies. Both ornaments and weapons improve a male's reproductive success; yet, unlike ornaments that need only attract females, weapons must be robust and functional structures because they are frequently tested during male-male combat. Consequently, weapons are expected to be particularly costly to bear. Here, we tested the aerodynamic costs of horns in the giant rhinoceros beetle, Trypoxylus dichotomus. We predicted that the long, forked head horn would have three main effects on flight performance: increased body mass, an anterior shift in the centre of mass and increased body drag. We found that the horns were surprisingly lightweight, and therefore had a trivial effect on the male beetles' total mass and mass distribution. Furthermore, because beetles typically fly at slow speeds and high body angles, horns had little effect on total body drag. Together, the weight and the drag of horns increased the overall force required to fly by less than 3 per cent, even in the largest males. Because low-cost structures are expected to be highly evolutionarily labile, the fact that horns incur very minor flight costs may have permitted both the elaboration and diversification of rhinoceros beetle horns.


Predictors for Anterior Cruciate Ligament (ACL) Re-injury after Successful Primary ACL Reconstruction (ACLR).
Few authors have addressed risk factors related to an ipsilateral graft rupture and contralateral anterior cruciate ligament (ACL) injury after return to sports (RTS) following primary ACL reconstruction. Patients with ACL re-injury to either knee after successful primary ACLR were included in Group I and those with no further re-injury were included in Group II. Variables including age, gender, side, body mass index (BMI), thigh atrophy, anterior knee laxity difference between both knees measured by KT-1000 arthrometer, mean time of return to sports (RTS), graft type, type of game, mode of injury, Tegner Activity Score, hormone levels, femoral tunnel length (FTL), posterior tibial slope (PTS) and notch width index (NWI) were studied. Binary logistic regression was used to measure the relative association. A total of 128 athletes were included with 64 in each group. Mean age in Group I and II were 24.90 and 26.47 years respectively. Mean follow-up of Group I and Group II were 24.5 and 20.11 months respectively. Significant correlation was present between ACL re-injury and following risk factors; PTS of >10º, KT difference of >3.0mm, thigh atrophy of >2.50cm and time to RTS <9.50 months P value <0.05). No correlation was found with age, sex, BMI, type of game, Tegner Activity Score, mode of injury, NWI, size of graft, FTL and hormone levels. Possible risk factors include PTS of ≥ 10º, KT difference of ≥ 3.0mm at 1 year follow-up, thigh atrophy of ≥ 2.50cm at 1 year follow-up and RTS <9.5 months after primary ACLR.


Leveraging a Peer-to-Peer Approach to Mitigate Vaccine Misinformation and Improve Vaccine Communication During a Pandemic: Experiences From the Development of a Massive Open Online Course.
The COVID-19 pandemic has not only led to massive global mortality and morbidity, but it has also fueled an infodemic of false and misleading information about COVID-19 and vaccines. The spread of misinformation and disinformation on vaccine safety and efficacy has contributed to vaccine hesitancy and distrust of public health institutions and has undermined the public health response to the COVID-19 pandemic. Because communication plays a monumental role in pandemic preparedness, a promising approach to countering the COVID-19 infodemic is empowering peers to serve as trusted messengers to provide accurate information using evidence-based communication approaches. With this in mind, we developed a massive open online course (MOOC) to provide the general public with the knowledge, skills, and resources to effectively navigate potentially contentious vaccine conversations with their peers, with a specific focus on parents. Within the first year of the course launch, 29,000 people had enrolled. Learners appreciated the information related to vaccine development, communication tips and techniques, and identifying and responding to vaccine misinformation. Over 1,000 learners who completed the course participated in an online evaluation survey. To address public distrust in healthcare providers, government, and science, our survey results indicate that peer-to-peer approaches to addressing vaccine hesitancy can empower community members to educate others and promote vaccine acceptance at scale.


Magic roundabout is a new member of the roundabout receptor family that is endothelial specific and expressed at sites of active angiogenesis.
We have used bioinformatic data mining to identify a novel, endothelial-specific gene encoding a protein with homology to the axon guidance protein roundabout (ROBO1). The new gene has been called magic roundabout (ROBO4; GenBank acc. no. AF361473) and is smaller than other members of the roundabout gene family. Thus, in the extracellular region, magic roundabout has only two of the five immunoglobulin and two of the three fibronectin domains present in other roundabout genes. Expression of magic roundabout in vitro was detected in only endothelial cells and was greater in cells exposed to hypoxia. In situ hybridization and immunohistochemistry validated the bioinformatic prediction that magic roundabout expression would be endothelial specific in vivo. Magic roundabout expression in the adult was restricted exclusively to sites of active angiogenesis, notably tumor vessels. The identification of magic roundabout shows that the roundabout gene family extends beyond neuronal tissue and that roundabout/slit interactions are likely to have a role in angiogenesis.


Nocturnal subcutaneous apomorphine infusion in Parkinson's disease and restless legs syndrome.
Nocturnal disabilities leading to fragmented sleep arising from parkinsonian off period related complications are common, under-reported and are difficult to treat. In this study, we evaluate the use of nocturnal continuous subcutaneous overnight apomorphine infusion in Parkinson's disease and restless legs syndrome. Six parkinsonian patients and 2 patients with restless legs syndrome with nocturnal disabilities refractory to conventional oral therapy were assessed using a sleep diary while on standard treatment and during nocturnal apomorphine infusion. Three patients agreed to assessments during placebo infusion with normal saline. Apomorphine led to a dramatic reduction of nocturnal awakenings, nocturnal off periods, pain, dystonia and nocturia in parkinsonian patients. In patients with restless legs syndrome, apomorphine reduced nocturnal discomfort, reduced leg movements and improved pain and spasm scores significantly. Placebo infusion reproduced pain, nocturnal spasms and sleep disruption. This study suggests that overnight apomorphine infusion may be effective in overcoming refractory nocturnal disabilities in selected patients with Parkinson's disease and restless legs syndrome.


Patella pain syndromes and chondromalacia patellae.
Patellar pain must be separated from other causes of internal derangement of the knee by a careful history and precise examination followed by appropriate investigations. Once the cause of the pain is determined, malalignment or malposition of the patella must be sought. The Merchant view of the patellar femoral joint is recommended in this regard to demonstrate patellar incongruence. The malalignment syndrome may or may not show the pathologic changes described as "chondromalacia" and respond particularly well after proximal patellar realignment. In the remaining cases, pain may be caused by overuse, trauma, the odd-facet syndrome, an abnormal femoral ridge, or degenerative arthritis. This group of cases should be managed conservatively if possible because the results of surgical treatment are often disappointing. In selected cases some improvement may occur after excision of abnormal cartilage, tibial tubercle elevation, patellar replacement, or patellectomy.


Factors influencing a self-limiting HIV outbreak among ethnic Vietnamese injecting drug users in Melbourne, Australia.
Successful HIV prevention programs-such as sterile needle and syringe programs-have ensured that incidence and prevalence of HIV among people who inject drugs remains low in Australia. However, between 1999 and 2006, 20 of the 46 injecting-related HIV notifications in Melbourne (Australia's second-largest city) were ethnic Vietnamese heroin users. Through in-depth interviews we explored and documented the coping tactics and strategies of 9 ethnic Vietnamese heroin injectors. We explored their experiences of living with HIV, and in this article identify factors that appear to have contributed to limiting the spread of HIV beyond this cluster of people. The data reveal factors associated with this self-limiting outbreak, including consciously avoiding opioid withdrawal and having closed injecting networks. Early and effective engagement with participants by health care workers also appears to have played an important role in containing the transmission of HIV within this group of ethnic Vietnamese heroin injectors.


Vitamin D Deficiency Is Associated With Increased Risk of Non-alcoholic Steatohepatitis in Adults With Non-alcoholic Fatty Liver Disease: Possible Role for MAPK and NF-κB?
The objective of this study was to determine the relationship of serum vitamin D deficiency (VDD) to histologic features of non-alcoholic fatty liver disease (NAFLD), and associated demographic, clinical, laboratory, and transcriptomic data in the well-characterized Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN) cohort. Serum vitamin D 25(OH)D (VD) was quantified by liquid chromatography-tandem mass spectrometry in 190 adults (>18 years) with biopsy-proven NAFLD. Subjects were categorized according to their level of VD as either sufficient (>30 ng/ml), insufficient (≥20≤30 ng/ml), or deficient (VDD; <20 ng/ml). Multivariable logistic regression was used to investigate the association of VDD and the presence of definite NASH and individual histological features of NAFLD after adjusting for age, sex, race, body mass index, alanine aminotransferase, and diabetes status. Hepatic transcriptomic data was compared between VDD and non-VDD subjects. VDD was present in 55% of subjects and was independently associated with definitive NASH (odds ratio (OR) 3.15, 95% confidence interval (CI), 1.62-6.15, P=0.001), increased lobular inflammation (OR=1.98, 95% CI, 1.08-3.61, P=0.026), more ballooning (OR=2.38, 95% CI, 1.32-4.30, P=0.004), and the presence of fibrosis (OR=2.32, 95% CI, 1.13-4.77, P=0.022). There was a significant inverse relationship between lower levels of serum resistin and increased VD level category (P=0.013). The KRT10, SEMA3B, SNORD3C, ARSD, and IGKV4-1 genes were differentially expressed (false discovery rate <0.05) between VDD and non-VDD subjects. Gene ontology and pathway analysis suggest activation of the mitogen-activated protein kinase and nuclear factor-κB pathways in VDD NAFLD subjects. VDD is prevalent among US adult NAFLD patients and is independently associated with a definitive diagnosis of NASH and increased histological severity. Novel associations in proinflammatory pathways were identified, which suggest the mechanism for VDD in the pathogenesis of NASH and support dietary and/or lifestyle modifications to increase vitamin D levels in these patients.


[Manic episode in a patient with Beçhet's disease].
Beçhet's disease (BD) is a chronic, heterogeneous, multisystem disease that affects young males and females around the Mediterranean region, as well as from Far and Middle East. Its etiology is vague with vasculitis being its main pathological feature. International diagnostic criteria have been established and they require the presence of recurrent oral ulcerations plus two of the following: Recurrent genital ulceration, eye lesions, skin lesions and positive pathergy test. A significant number of patients with Beçhet's disease suffers from symptoms from the central nervous system (CNS), while the most common clinical symptoms are pyramidal signs, mental-behavioral changes, hemiparesis and brain stem syndrome. The existence of mental-behavioral changes seems to be one of the most common findings in patients with Neuro-Beçhet (N-BD). These changes seem to be related with memory and attention deficits, and the process of deterioration continues even in attack-free periods, suggesting a continuously active disease process in the CNS. The prevalence of anxiety, depression and general psychiatric symptoms is higher among patients with BD compared to healthy individuals. However, the association between psychiatric symptoms and BD is not clearly understood. On the other hand, syndromes like psychosis or bipolar disorder appear to be less frequent, especially in attack-free periods. We describe the case of a 52-year old woman with Beçhet's disease who developed a single manic episode 13 years after the onset of Beçhet's disease. A 52-year old woman, suffering from Beçhet's disease since the age of 39, developed manic symptoms, namely elevated mood, pressured speech, flight of ideas, distractibility and decreased need for sleep. The above symptoms developed during a period that no other symptoms of Beçhet's disease were present. Moreover there was no other manifestation from the nervous system. A brain MRI was unremarkable, while a brain SPECT study revealed severe hypoperfusion of the left prefrontal cortex. Neuropsychological examination revealed severe disturbance in attention, working memory and learning ability, while her visuaspatial ability and executive functions were well spared. Her symptoms were well controlled after treated with quetiapine 800 mg. The manic episode developed in the absence of any neurological manifestation (Neuro-Beçhet), or other symptom of Beçhet's disease, and was clearly distinguishable from euphoria, disinhibition or irritability that are common in patients with Beçhet's disease. It looks probable that CNS damage caused by the disease constitutes a biological substrate for the development of manic episodes in patients suffering from Beçhet's disease.


Leptin Is an Important Endocrine Player That Directly Activates Gonadotropic Cells in Teleost Fish, Chub Mackerel.
Leptin, secreted by adipocytes, directly influences the onset of puberty in mammals. Our previous study showed that leptin stimulation could promote the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from pituitary cells in primary culture and ovarian development in chub mackerel. This study aimed to elucidate the detailed mechanism of leptin-induced effects on gonadotropin hormone-producing cells. We produced recombinant leptin using silkworm pupae and investigated the effects of leptin on FSH and LH secretion and gene expression in the primary culture of pituitary cells from chub mackerel. The presence or absence of co-expression of lepr mRNA, FSH and LH b-subunit mRNA in gonadotropic cells was examined by double-labeled in situ hybridization. The addition of leptin significantly increased the secretion and gene expression of FSH and LH from male and female pituitary cells in primary culture. In contrast, gonadotropin-releasing hormone 1 affected neither FSH secretion in cells from females nor fshb and lhb expression in cells from males and females. The expression of lepr was observed in FSH- and LH-producing cells of both males and females. The results indicate that leptin directly regulates gonadotropin synthesis and secretion and plays an important role in the induction of puberty in teleost fish.


Synthesis and characterization of nanosized Cu/ZnO catalyst by polyol method.
Nanosized catalysts composed of metallic copper supported on zinc oxide have been synthesized by the polyol process. Average crystallite size of copper was between 10 and 45 nm. Cu/ZnO catalyst particles were characterized by various techniques, such as X-ray Powder Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED), and dynamic light scattering analysis (DLS).


[Basic aspects of the nursing care for the patients with South American Pemphigus Foliaceus].
The author analysis the problems of the South American Pemphigus Foliaceus, its epidemiology, diagnosis, treatment and prophilaxie. She presents the main needs of the patients with that disease and the basic aspects of the nursing care.


Original mechanisms of antipsychotic action by the indole alkaloid alstonine (Picralima nitida).
Alstonine is the major component of plant based remedies that traditional psychiatrists use in Nigeria. Alstonine is an indole alkaloid that has an antipsychotic experimental profile comparable with that of clozapine and is compatible with the alleged effects in mental patients. Representing a desirable innovation in the pharmacodynamics of antipsychotic medications, the evidence indicates that alstonine does not bind to D2 dopamine receptors (D2R) and differentially regulates dopamine in the cortical and limbic areas. The purpose of this study was to further investigate the effects of alstonine on D2R binding in specific brain regions using quantitative autoradiography (QAR) and its effects on dopamine (DA) uptake in mouse striatal synaptosomes. The effects of alstonine on D2R binding were determined in the nucleus accumbens and caudate-putamen using QAR in mice treated with alstonine doses that have antipsychotic effects. The effects of alstonine [3H]DA uptake were assessed in synaptosomes prepared from striatal tissue obtained from mice treated acutely or for 7 days with alstonine. Alstonine did not change the D2R binding densities in the studied regions. DA uptake was increased after acute (but not after 7 days) treatment with alstonine. Consistent with the alstonine behavioral profile, these results indicate that alstonine indirectly modulates DA receptors, specifically by modulating DA uptake. This unique mechanism for DA transmission modulation contributes to the antipsychotic-like effects of alstonine and is compatible with its behavioral profile in mice and alleged effects in patients. These results may represent an innovation in the antipsychotic development field.


DREME: motif discovery in transcription factor ChIP-seq data.
Transcription factor (TF) ChIP-seq datasets have particular characteristics that provide unique challenges and opportunities for motif discovery. Most existing motif discovery algorithms do not scale well to such large datasets, or fail to report many motifs associated with cofactors of the ChIP-ed TF. We present DREME, a motif discovery algorithm specifically designed to find the short, core DNA-binding motifs of eukaryotic TFs, and optimized to analyze very large ChIP-seq datasets in minutes. Using DREME, we discover the binding motifs of the the ChIP-ed TF and many cofactors in mouse ES cell (mESC), mouse erythrocyte and human cell line ChIP-seq datasets. For example, in mESC ChIP-seq data for the TF Esrrb, we discover the binding motifs for eight cofactor TFs important in the maintenance of pluripotency. Several other commonly used algorithms find at most two cofactor motifs in this same dataset. DREME can also perform discriminative motif discovery, and we use this feature to provide evidence that Sox2 and Oct4 do not bind in mES cells as an obligate heterodimer. DREME is much faster than many commonly used algorithms, scales linearly in dataset size, finds multiple, non-redundant motifs and reports a reliable measure of statistical significance for each motif found. DREME is available as part of the MEME Suite of motif-based sequence analysis tools (http://meme.nbcr.net).


Effectively identifying eQTLs from multiple tissues by combining mixed model and meta-analytic approaches.
Gene expression data, in conjunction with information on genetic variants, have enabled studies to identify expression quantitative trait loci (eQTLs) or polymorphic locations in the genome that are associated with expression levels. Moreover, recent technological developments and cost decreases have further enabled studies to collect expression data in multiple tissues. One advantage of multiple tissue datasets is that studies can combine results from different tissues to identify eQTLs more accurately than examining each tissue separately. The idea of aggregating results of multiple tissues is closely related to the idea of meta-analysis which aggregates results of multiple genome-wide association studies to improve the power to detect associations. In principle, meta-analysis methods can be used to combine results from multiple tissues. However, eQTLs may have effects in only a single tissue, in all tissues, or in a subset of tissues with possibly different effect sizes. This heterogeneity in terms of effects across multiple tissues presents a key challenge to detect eQTLs. In this paper, we develop a framework that leverages two popular meta-analysis methods that address effect size heterogeneity to detect eQTLs across multiple tissues. We show by using simulations and multiple tissue data from mouse that our approach detects many eQTLs undetected by traditional eQTL methods. Additionally, our method provides an interpretation framework that accurately predicts whether an eQTL has an effect in a particular tissue.


Proapoptotic function of deubiquitinase DUSP31 in Drosophila.
Drosophila have been used to identify new components in apoptosis regulation. The Drosophila protein Dark forms an octameric apoptosome complex that induces the initiator caspase Dronc to trigger the caspase cell death pathway and, therefore, plays an important role in controlling apoptosis. Caspases and Dark are constantly expressed in cells, but their activity is blocked by DIAP1 E3 ligase-mediated ubiquitination and subsequent inactivation or proteasomal degradation. One of the regulatory mechanisms that stabilize proapoptotic factors is the removal of ubiquitin chains by deubiquitinases. In this study performed a modified genetic screen for deubiquitinases (dsRNA lines) to identify those involved in stabilizing proapoptotic components. Loss-of-function alleles of deubiquitinase DUSP31 were identified as suppressors of the Dronc overexpression phenotype. DUSP31 deficiency also suppresses apoptosis induced by the RHG protein, Grim. Genetic analysis revealed for the first time that DUSP31 deficiency sufficiently suppresses the Dark phenotype, indicating its involvement in the control of Dark/Dronc apoptosome function in invertebrate apoptosis.


Wound healing effects of collagen-laminin dermal matrix impregnated with resveratrol loaded hyaluronic acid-DPPC microparticles in diabetic rats.
An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery.


Surgical treatment of bony ankylosis in a child using a composite cartilage-bone iliac crest graft.
A previously unreported approach to the treatment of temporomandibular ankylosis in the child is reported. The procedure involves using the iliac crest and fixing it to the zygomatic portion of the temporal bone, with the cartilagenous portion facing the stump of the mandibular ramus. The procedure is easier to accomplish than a costochondral graft, does not require maxillomandibular fixation, and offers the possibility of appositional growth. In our case, opening has been maintained and growth sustained in a five-year-old child for 18 months without physiotherapy.


Differences between genotyping and phenotyping methods for assessing apolipoprotein(a) size polymorphisms.
The aim of the present study was to analyze, on a double-blind basis, the relationships between the apolipoprotein(a) (apo(a)) gene and protein size polymorphisms in healthy volunteers (n = 99) and patients with premature myocardial infarction (n = 91). Apo(a) genotypes were determined by pulse-field electrophoresis and phenotypes were separated by sodium dodecyl sulfate-agarose gel electrophoresis. Results showed that phenotyping overestimated apo(a) size with respect to genotyping (mean (SD) = 3.7 (3.4) kringle units; p < 0.001) in subjects with a double-band genotype, although both measurements were highly correlated (r = 0.83; p < 0.001). We also observed that the protein band in subjects with a single-band phenotype was related more closely to the smallest allele than to the largest allele band. The correlation of plasma lipoprotein(a) (Lp(a)) concentration was stronger with the phenotype than with the genotype. We hypothesize that post-translational modifications in the apo(a) molecule may be the most plausible explanation for the discrepancies observed. In conclusion, the present study highlights the dissimilarities between phenotyping and genotyping methods for the measurement of apo(a) size and suggests that laboratories should carefully consider these relationships and the transfer of results between such methodologies.


Cesium adsorption on clay minerals: an EXAFS spectroscopic investigation.
Cesium adsorption on the clay minerals vermiculite and montmorillonite is described as a function of surface coverage using extended X-ray adsorption fine structure spectroscopy (EXAFS). Cesium (Cs) possessed a variable coordination environment consisting of Cs-O distances between 3.2 and 4.3 A; however, disorder typical of the Cs coordination environments prevented the resolution of all oxygen shells. On the basis of the influence of Cs loading and exchangeability on this structural arrangement, we could recognize both inner-sphere and outer-sphere adsorption complexes. The shorter Cs-O bond distance belongs to outer-sphere complexes typical of hydrated ions. In inner-sphere complexes, partially or fully dehydrated Cs coordinates directly to siloxane groups of the clay minerals forming longer Cs-O bonds. The inner-sphere adsorption complexes may have occurred within the interlayer or at frayed edge sites and were less extractable than the outer-sphere complexed Cs. Both coordination number ratios and linear combination fitting of EXAFS spectra were useful in estimating the fractions of inner-sphere and outer-sphere adsorption complexes. Our results show that X-ray absorption spectroscopy (XAS), and particularly EXAFS, is a valuable technique for exploring the type of Cs binding in environmental samples.


Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.


Real-time observation of nucleation and growth of Au on CdSe quantum dot templates.
Semiconductor quantum dot (QD) arrays can be useful for optical devices such as lasers, solar cells and light-emitting diodes. As the size distribution influences the band-gap, it is worthwhile to investigate QDs prepared using different solvents because each of them could influence the overall morphology differently, depending on the ligand network around individual QDs. Here, we follow the nucleation and growth of gold (Au) on CdSe QD arrays to investigate the influence of surface ligands and thereby realized interparticle distance between QDs on Au growth behaviour. We particularly emphasize on the monolayer stage as the Au decoration on individual QDs is expected at this stage. Therefore, we sputter-deposit Au on each QD array to investigate the morphological evolution in real-time using time-resolved grazing-incidence small-angle X-ray scattering (GISAXS). The growth kinetics - independent of the template - signifies that the observed template-mediated nucleation is limited only to the very first few monolayers. Delicate changes in the Au growth morphology are seen in the immediate steps following the initial replicated decoration of the QD arrays. This is followed by a subsequent clustering and finally a complete Au coverage of the QD arrays.


A 40-Month Follow-Up of Ebola Virus Disease Survivors in Guinea (PostEbogui) Reveals Long-Term Detection of Ebola Viral Ribonucleic Acid in Semen and Breast Milk.
With the increasing frequency and impact of Ebola virus disease (EVD) outbreaks illustrated by recent epidemics, a good understanding of the extent of viral persistance or ribonucleic acid (RNA) detection in body fluids from survivors is urgently needed. Ebola viral RNA shedding was studied with molecular assays in semen (n = 1368), urine (n = 1875), cervicovaginal fluid (n = 549), saliva (n = 900), breast milk (n = 168), and feces (n = 558) from EVD survivors in Guinea (PostEbogui cohort, n = 802) at a regular base period until 40 months after inclusion. Twenty-seven of 277 (9.8%) male survivors tested positive for Ebola RNA in at least 1 semen sample. The probability of remaining positive for Ebola RNA in semen was estimated at 93.02% and 60.12% after 3 and 6 months. Viral RNA in semen was more frequent in patients with eye pain (P = .036), joint pain (P = .047), and higher antibody levels to Ebola virus antigens (nucleoprotein [P = .001], glycoprotein [P = .05], and viral protein-40 [P = .05]). Ebola RNA was only rarely detected in the following body fluids from EVD survivors: saliva (1 of 454), urine (2 of 593), breast milk (2 of 168), cervicovaginal secretions (0 of 273), and feces (0 of 330). Ribonucleic acid was detected in breast milk 1 month after delivery but 500 days after discharge of Ebola treatment unit (ETU) in 1 woman who became pregnant 7 months after discharge from the ETU. The frequency and potential long-term presence of viral RNA in semen confirmed that systematic prevention measures in male survivors are required. Our observation in breast milk suggests that our knowledge on viral reservoir in immune-privileged sites and its impact are still incomplete.


How ethylene works in the reproductive organs of higher plants: a signaling update from the third millennium.
Ethylene (ET) is a notable signaling molecule in higher plants. In the year 1993 the ET receptor gene, ETR1, was identified; this ETR1 receptor protein being the first plant hormone receptor to be isolated. It is striking that there are six ET receptors in tomato instead of five in Arabidopsis, the two best-known signaling-model systems. Even though over the last few years great progress has been made in elucidating the genes and proteins involved in ET signaling, the complete pathway remains to be established. The present review examines the most representative successive advances that have taken place in this millennium in terms of the signaling pathway of ET, as well as the implications of the signaling in the reproductive organs of plants (i.e., flowers, fruits, seeds and pollen grains). A detailed comparative study is made on the advances in knowledge in the last decade, showing how the characterization of ET signaling provides clues for understanding how higher plants regulate their ET sensitivity. Also, it is indicated that ET signaling is at present sparking interest within phytohormonal molecular physiology and biology, and it is explained why several socio-economic aspects (flowering and fruit ripening) are undoubtedly involved in ET physiology.


Antimicrobial Properties of Graphene Oxide Nanosheets: Why Size Matters.
Graphene oxide (GO) is a promising material for the development of antimicrobial surfaces due to its contact-based antimicrobial activity. However, the relationship between GO physicochemical properties and its antimicrobial activity has yet to be elucidated. In this study, we investigated the size-dependency of GO antimicrobial activity using the Gram-negative bacteria Escherichia coli. GO suspensions of average sheet area ranging from 0.01 to 0.65 μm(2) were produced and their antimicrobial activity evaluated in cell suspensions or as a model GO surface coating. The antimicrobial activity of GO surface coatings increased 4-fold when GO sheet area decreased from 0.65 to 0.01 μm(2). The higher antimicrobial effect of smaller GO sheets is attributed to oxidative mechanisms associated with the higher defect density of smaller sheets. In contrast, in suspension assays, GO interacted with bacteria in a cell entrapment mechanism; in this case, the antimicrobial effect of GO increased with increasing sheet area, with apparent complete inactivation observed for the 0.65 μm(2) sheets after a 3 h exposure. However, cell inactivation by GO entrapment was reversible and all initially viable cells could be recovered when separated from GO sheets by sonication. These findings provide useful guidelines for future development of graphene-based antimicrobial surface coatings, where smaller sheet sizes can increase the antimicrobial activity of the material. Our study further emphasizes the importance of an accurate assessment of the antimicrobial effect of nanomaterials when used for antimicrobial surface design.


Behavior change intervention research in healthcare settings: a review of recent reports with emphasis on external validity.
Information to judge both the internal and external validity of health behavior research conducted in healthcare settings is vital to translate research findings to practice. This paper reviews the extent to which this research has reported on elements of internal and external validity, with emphasis on the extent to which research has been conducted in representative settings with representative populations. A comprehensive review was conducted of controlled interventions for dietary change, physical activity, or smoking cessation conducted in healthcare settings and published in 12 leading health behavior journals between 1996 and 2000. Using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, the characteristics and results of these studies were summarized to document the extent to which intervention reach, adoption, implementation, and maintenance were reported and what has been learned about each of these dimensions. A total of 36 studies qualified for review. Participation rates among eligible patients were reported in 69% of studies and were generally quite high; in contrast, only 30% of studies reported on participation rates among either healthcare settings or providers. Implementation data were reported in 77% of the studies and these rates were generally high, with the caveat that intervention was often delivered by paid research staff. Long-term maintenance results were reported very consistently at the individual level, but program continuation was almost never reported at the setting level. We conclude that a much stronger emphasis needs to be placed on the representativeness of providers and settings that are studied. Examples of how this can be done and recommendations for future research are provided.


Runx transcription factors: lineage-specific regulators of neuronal precursor cell proliferation and post-mitotic neuron subtype development.
Runt-related (RUNX) genes encode evolutionarily conserved transcription factors that play essential roles during development and adult tissue homeostasis. RUNX proteins regulate the transition from proliferation to differentiation in a variety of cell lineages. Moreover, they control the diversification of distinct cellular phenotypes in numerous tissues. Alterations of RUNX functions are associated with several cancers and other human pathologies, underscoring the vital roles of these transcription factors in adult organs. Insights into the functions and regulations of mammalian RUNX proteins have been provided mostly by studies of RUNX involvement in mechanisms of hematopoietic and skeletal development and disease. A growing number of recent investigations are revealing new functions for RUNX family members during the development of the mammalian nervous system. This review will discuss recent progress in the study of RUNX protein involvement in mammalian neural development, with emphasis on the differentiation of olfactory, sensory, and motor neuron lineages.


Rhadinoviral interferon regulatory factor homologues.
Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV8) is a gammaherpesvirus and the etiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman disease. The KSHV genome contains genes for a unique group of proteins with homology to cellular interferon regulatory factors, termed viral interferon regulatory factors (vIRFs). This review will give an overview over the oncogenic, antiapoptotic and immunomodulatory characteristics of KSHV and related vIRFs.


[Non-caloric compounds with fat-like functional properties (pseudofats)].
The review deals with the synthesis, characterization, physicochemical and physiological properties with respect to nutrition of acaloric fat-like compounds (pseudofats) with special regard to fatty acid esters of sucrose, glycerol ethers and glycerol dicarbonic acid esters. Furthermore an outlook is given of other classes of compounds that are potentially suited to substitute fat as for instance polycarbonic acid-, polyglycerol-, and polyglycol derivatives.


Improved Genetic Map Identified Major QTLs for Drought Tolerance- and Iron Deficiency Tolerance-Related Traits in Groundnut.
A deep understanding of the genetic control of drought tolerance and iron deficiency tolerance is essential to hasten the process of developing improved varieties with higher tolerance through genomics-assisted breeding. In this context, an improved genetic map with 1205 loci was developed spanning 2598.3 cM with an average 2.2 cM distance between loci in the recombinant inbred line (TAG 24 × ICGV 86031) population using high-density 58K single nucleotide polymorphism (SNP) "Axiom_Arachis" array. Quantitative trait locus (QTL) analysis was performed using extensive phenotyping data generated for 20 drought tolerance- and two iron deficiency tolerance-related traits from eight seasons (2004-2015) at two locations in India, one in Niger, and one in Senegal. The genome-wide QTL discovery analysis identified 19 major main-effect QTLs with 10.0-33.9% phenotypic variation explained (PVE) for drought tolerance- and iron deficiency tolerance- related traits. Major main-effect QTLs were detected for haulm weight (20.1% PVE), SCMR (soil plant analytical development (SPAD) chlorophyll meter reading, 22.4% PVE), and visual chlorosis rate (33.9% PVE). Several important candidate genes encoding glycosyl hydrolases; malate dehydrogenases; microtubule-associated proteins; and transcription factors such as MADS-box, basic helix-loop-helix (bHLH), NAM, ATAF, and CUC (NAC), and myeloblastosis (MYB) were identified underlying these QTL regions. The putative function of these genes indicated their possible involvement in plant growth, development of seed and pod, and photosynthesis under drought or iron deficiency conditions in groundnut. These genomic regions and candidate genes, after validation, may be useful to develop molecular markers for deploying genomics-assisted breeding for enhancing groundnut yield under drought stress and iron-deficient soil conditions.


The Floral Repressor GmFLC-like Is Involved in Regulating Flowering Time Mediated by Low Temperature in Soybean.
Soybean is an important crop that is grown worldwide. Flowering time is a critical agricultural trait determining successful reproduction and yields. For plants, light and temperature are important environmental factors that regulate flowering time. Soybean is a typical short-day (SD) plant, and many studies have elucidated the fine-scale mechanisms of how soybean responds to photoperiod. Low temperature can delay the flowering time of soybean, but little is known about the detailed mechanism of how temperature affects soybean flowering. In this study, we isolated GmFLC-like from soybean, which belongs to the FLOWERING LOCUS C clade of the MADS-box family and is intensely expressed in soybean leaves. Heterologous expression of GmFLC-like results in a delayed-flowering phenotype in Arabidopsis. Additional experiments revealed that GmFLC-like is involved in long-term low temperature-triggered late flowering by inhibiting FT gene expression. In addition, yeast one-hybrid, dual-luciferase reporter assay, and electrophoretic mobility shift assay revealed that the GmFLC-like protein could directly repress the expression of FT2a by physically interacting with its promoter region. Taken together, our results revealed that GmFLC-like functions as a floral repressor involved in flowering time during treatments with various low temperature durations. As the only the FLC gene in soybean, GmFLC-like was meaningfully retained in the soybean genome over the course of evolution, and this gene may play an important role in delaying flowering time and providing protective mechanisms against sporadic and extremely low temperatures.


6-Gingerol Ameliorates Behavioral Changes and Atherosclerotic Lesions in ApoE-/- Mice Exposed to Chronic Mild Stress.
Chronic mild stress (CMS) has been demonstrated to contribute to atherosclerosis. 6-gingerol (6-Gin), a phenolic component of ginger (Zingiber officinale), has been shown to exert numerous pharmacological properties, such as anti-inflammatory and cardioprotective effects. Here we investigated the role of CMS in the development of atherosclerosis in high-fat diet (HFD)-fed ApoE-/- mice and evaluated the potential therapeutic effects of 6-Gin. Mice were exposed to CMS for 20 weeks, at week 5, they were fed with a high-fat diet (HFD), then received 6-Gin (20 mg/kg/day, intragastrically) treatment. Antiatherosclerotic simvastatin (Sim) and antidepressant lorazepam (Lor) were used for positive drugs. The behavioral and atherosclerotic changes, plasma lipid profiles as well as inflammatory cytokine levels were measured. Our results showed that CMS-exposed mice exhibited reduced body weight gain, sucrose preference and locomotor activity, which are representative of some of the core symptoms of depression. Furthermore, CMS challenge aggravated atherosclerotic lesions, as indicated by increased plaque formation, elevation of plasma total cholesterol, triglyceride, low-density lipoprotein cholesterin, and proinflammatory cytokines including TNF-α, IL-1β, and IL-6. In addition, the expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), acetyl-CoA carboxylase (ACC), hHMG-CoA reductase (HMGCR), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP)-1 and SREBP-2 in the liver tissues were altered after CMS exposure. 6-Gin not only improved the behavioral changes, but also alleviated atherosclerotic lesions, and reversed the expression levels of lipid profiles and inflammatory cytokines in stressed mice. Moreover, the antiatherosclerotic effects of 6-Gin is mediated in part by the AMPK signaling pathway, which is closely associated with cholesterol synthesis and lipid accumulation. Together, these results suggest that 6-Gin attenuates arteriosclerosis in ApoE-/- mice exposed to CMS and HFD, and it may be a potential therapeutic agent for the treatment of atherosclerosis.


[Myocardial ischemia in general medicine and the revolution of coronary stents].
Since Gruentizg's first percutaneous transluminal ballon angioplasty in 1977 in Zurich, percuta. neous coronary intervention evolved significantly in order to overcome the numerous associated complications of each technique. Bare-metal stents (BMS) made their initial appearance followed by three generations of drug-eluting stents (DES). The use of bioabsorbable vascular scaffold stents (BVS) has become more frequent creating a temporary scaffold allowing healing of the endothelium within 2 years. In this article, we discuss the nomenclature of the main intravascular complications linked to percuta. neous coronary intervention such as stent thrombosis (ST), Instent restenosis (ISR), neoatherosclerosis, and stents evolution to overcome these complications. We will finally mention the new technologies of intracoronary imaging such as OCT (Optical Coherence Tomography) having an increasing vital role in percutaneous coronary intervention,


Nutrients for the aging eye.
The incidence of age-related eye diseases is expected to rise with the aging of the population. Oxidation and inflammation are implicated in the etiology of these diseases. There is evidence that dietary antioxidants and anti-inflammatories may provide benefit in decreasing the risk of age-related eye disease. Nutrients of interest are vitamins C and E, β-carotene, zinc, lutein, zeaxanthin, and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. While a recent survey finds that among the baby boomers (45-65 years old), vision is the most important of the five senses, well over half of those surveyed were not aware of the important nutrients that play a key role in eye health. This is evident from a national survey that finds that intake of these key nutrients from dietary sources is below the recommendations or guidelines. Therefore, it is important to educate this population and to create an awareness of the nutrients and foods of particular interest in the prevention of age-related eye disease.


Lower osteopontin plasma levels are associated with superior outcomes in advanced non-small-cell lung cancer patients receiving platinum-based chemotherapy: SWOG Study S0003.
S0003 was a phase III trial of carboplatin/paclitaxel with or without the hypoxic cytotoxin tirapazamine in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). We investigated the relationship between clinical outcomes and plasma levels of the hypoxia-associated protein osteopontin (OPN) in patients on this protocol. Baseline plasma was obtained from 172 patients. In 56 patients, sequential plasma was obtained after one or two cycles. Concentrations of OPN, as well as plasminogen activator inhibitor-1 (PAI-1) and vascular endothelial growth factor (VEGF), were measured using enzyme-linked immunosorbent assay. Tumor expression of OPN was assessed by immunohistochemistry in 61 matched archival specimens. Patients with lower OPN levels (below the median) had a significantly superior overall survival compared with patients with higher levels, regardless of treatment arm (hazard ratio [HR] = 0.60, P = .002). A similar correlation was observed for progression-free survival (HR = 0.69, P = .02). When examined as a continuous variable, OPN maintained its significant association with both progression-free (HR = 1.05, P = .01) and overall survival (HR = 1.09, P < .0001). Patients with lower plasma OPN levels were significantly more likely to have tumor response (P = .03). No differences were observed between treatment arms. Tumor OPN levels did not correlate with patient outcomes or with plasma levels. No associations were observed between patient outcomes and VEGF or PAI-1 levels; however, plasma concentrations of these markers were significantly interrelated (P < .0001) and significantly decreased after treatment (P = .0002 and P = .03, respectively). Pretreatment plasma levels of OPN are significantly associated with patient response, progression-free survival, and overall survival in chemotherapy-treated patients with advanced NSCLC.


Clinical and prognostic features of erionite-induced malignant mesothelioma.
This review analytically examines the published data for erionite-related malignant pleural mesothelioma (E-MPM) and any data to support a genetically predisposed mechanism to erionite fiber carcinogenesis. Adult patients of age ≥18 years with erionite-related pleural diseases and genetically predisposed mechanisms to erionite carcinogenesis were included, while exclusion criteria included asbestos- or tremolite-related pleural diseases. The search was limited to human studies though not limited to a specific timeframe. A total of 33 studies (31042 patients) including 22 retrospective studies, 6 prospective studies, and 5 case reports were reviewed. E-MPM developed in some subjects with high exposures to erionite, though not all. Chest CT was more reliable in detecting various pleural changes in E-MPM than chest X-ray, and pleural effusion was the most common finding in E-MPM cases, by both tests. Bronchoalveolar lavage remains a reliable and relatively less invasive technique. Chemotherapy with cisplatin and mitomycin can be administered either alone or following surgery. Erionite has been the culprit of numerous malignant mesothelioma cases in Europe and even in North America. Erionite has a higher degree of carcinogenicity with possible genetic transmission of erionite susceptibility in an autosomal dominant fashion. Therapeutic management for E-MPM remains very limited, and cure of the disease is extremely rare.


[Vertebroplasty in the treatment of spinal diseases].
The results of surgical treatment by vertebroplasty are analyzed in 28 patients with different spinal diseases. A procedure for percutaneous vertebroplasty with polymethyl methacarylate is presented. This miniinvasive method has been shown to be highly effective in treating vertebral hemangiomas, osteoporotic compression fractures, and vertebral metastases and in strengthening the anterior vertebral column as compared with anterior spondylosis in open surgical operations.


Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis.
The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both upper and lower motor neuron loss, as well as altered proteomic and metabolomic signatures in the CSF. The role of the BCSFB and the CP in ALS is unknown. Here we describe a transcriptomic and ultrastructural analysis of BCSFB and CP alterations in human postmortem tissues from ALS and non-neurologic disease controls. ALS-CP exhibited widespread disruptions in tight junctional components of the CP epithelial layer and vascular integrity. In addition, we detected loss of pericytes around ALS blood vessels, accompanied by activation of platelet aggregation markers vWF and Fibrinogen, reminiscent of vascular injury. To investigate the immune component of ALS-CP, we conducted a comprehensive analysis of cytokines and chemokine panels in CP lysates and found a significant down-regulation of M-CSF and V-CAM1 in ALS, as well as up-regulation of VEGF-A protein. This phenotype was accompanied by an infiltration of MERTK positive macrophages into the parenchyma of the ALS-CP when compared to controls. Taken together, we demonstrate widespread structural and functional disruptions of the BCSFB in human ALS increasing our understanding of the disease pathology and identifying potential new targets for ALS therapeutic development.


Selenium nanoparticles inhibit Staphylococcus aureus growth.
Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 μg/mL. The percentage of live bacteria also decreased in the presence of selenium nanoparticles. Therefore, this study suggests that selenium nanoparticles may be used to effectively prevent and treat S. aureus infections and thus should be further studied for such applications.


Early Retinal Microvasculopathy in Prediabetic Patients and Correlated Factors.
We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.


Major thermogenic defect associated with insulin resistance in brown adipose tissue of obese diabetic SHR/N-cp rats.
The effects of norepinephrine and insulin on thermogenesis were investigated in adipocytes isolated from brown adipose tissue (BAT) of obese non-diabetic LA/N-cp rats (obese LA), obese diabetic SHR/N-cp rats (obese SHR), and their corresponding lean controls. The maximal calorigenic response (Vmax) and the sensitivity [50% effective concentration (EC50)] to norepinephrine (1 microM) were markedly reduced in brown adipocytes from obese SHR rats compared with their lean controls (3- to 4-fold decrease in the Vmax and 50% increase in the EC50 value). In the same cells, there was a similar decrease in the respiratory response to dibutyryl adenosine 3',5'-cyclic monophosphate, indicating the presence of a major postreceptor defect. Remarkably, total BAT cytochrome oxidase activity (an index of cellular mitochondrial content) was also diminished three to four times in obese SHR rats, suggesting that a reduced BAT mitochondrial content is responsible for the decreased thermogenesis. Ultrastructural studies revealed that the cytoplasm of brown adipocytes from obese SHR rats contained a large lipid droplet, numerous tiny droplets, and few atypical mitochondria with loosely packed cristae. Adipocytes from obese SHR rats were also characterized by a significant resistance to the antithermogenic effect of insulin but not to that of the nonmetabolizable adenosine analogue N6-phenylisopropyl adenosine. In contrast, all the above biochemical parameters were normal in obese LA rats. These results demonstrate that the marked insulin resistance in BAT of obese SHR rats is associated with a decreased responsiveness and sensitivity to norepinephrine, indicating the presence of receptor and postreceptor defects. It is suggested that insulin resistance and/or diabetes in SHR/N-cp rats lead to a decreased mitochondriogenesis in BAT, which results in a reduced thermogenic capacity, thereby contributing to the development of obesity.


A detailed analysis of partial molecular volumes in DPPC/cholesterol binary bilayers.
We examined the volumetric behavior of the dipalmitoylphosphatidylcholine (DPPC)/cholesterol binary bilayer system with high accuracy and more cholesterol concentrations to reveal the detailed molecular states in the liquid-disordered (Ld) phase, the liquid-ordered (Lo) phase and the gel phase. We measured the average specific volume of the binary bilayer at several temperatures by the neutral flotation method and calculated the average volume per molecule to estimate the partial molecular volumes of DPPC and cholesterol in each phase. As a result, we found that the region with intermediate cholesterol concentrations showed a more complicated behavior than expected from simple coexistence of Ld and Lo domains. We also measured fluorescence decay of trans-parinaric acid (tPA) added into the binary bilayer with more cholesterol concentrations to get further insight into the cholesterol-induced formation of the Lo phase. On the basis of these results we discuss the molecular interaction between DPPC and cholesterol molecule in the Lo phase and the manner of Ld/Lo phase coexistence.


Early versus delayed shoulder motion following axillary dissection: a randomized prospective study.
The role and timing of physical therapy following axillary dissection for melanoma, or in conjunction with modified radical mastectomy has not been extensively studied. A prospective randomized clinical trial was carried out over an 18-month period in the Surgery Branch, National Cancer Institute (NCI) and Department of Rehabilitation Medicine, Clinical Center, in which patients were assigned to receive one of two postoperative physical therapy regimens. Patients were assigned to receive graduated increases in allowed range of motion (ROM), either beginning on postoperative day 1 (early) or day 7 (delayed). All patients were advanced to full pain-free ROM when the suction catheters were removed. A total of 36 patients with 40 axillary dissections (19 for melanoma, 21 for breast cancer) were included in this study. Patients randomized to receive early motion had more total wound drainage (805 +/- 516 cc vs. 420 +/- 301 cc, p < 0.01), more days of drainage (10.3 +/- 5.3 vs. 6.2 +/- 2.7, p < 0.01), and later postoperative day of discharge (12.8 +/- 5.1 days vs. 9.2 +/- 4.0 days, p < 0.02) than did patients who started motion on day 7. Wound complications including infection and small areas of skin breakdown occurred more frequently in the early group (seven patients vs. one patient, p < 0.02). No significant differences in the per cent of patients achieving functional ROM could be identified between these two groups at one, three or six months after operation. Transient serratus anterior palsy (12 patients) and latissimus dorsi palsy (2 patients) occurred in approximately 30% of all patients, regardless of group (breast vs. melanoma, early vs. delayed), but returned to normal in all patients. The early institution of flexion and abduction exercises following axillary dissection thus appears to have a deleterious effect on wound healing and drainage. Adequate functional ROM is attained in all patients with a minimum of complications when active motion exercises are delayed for up to 7 days after axillary dissection.


Evaluation and transplantation of corneas from pseudophakic donor eyes.
To evaluate the quality of corneal donor tissue from pseudophakic eyes for transplantation. Only capsular-supported posterior chamber pseudophakia was studied. Forty-five pairs of donor eyes were assessed and evaluated by standard Minnesota Lions Eye Bank (MLEB) protocol. Thirty-three pairs were unilaterally pseudophakic with the unoperated phakic eye used as a control eye. Twelve donors were bilaterally pseudophakic. All corneas were rated for corneal clarity, epithelial defects, stromal edema, Descemet's membrane folding, endothelial cell density (ECD), and cell damage by slit-lamp examination and specular microscopy. If the corneas were not transplanted, the endothelium was vital stained with trypan blue and counterstained with alizarin red S for quantitation, localization, and visualization of cell morphology and damage. Sixty-eight of the 90 corneas in this study did not meet transplantation criteria. A significant difference in ECD (>22%) and in overall corneal rating was found in seven (21%) of 33 pairs of unilateral pseudophakic donors. Fourteen corneal transplants were performed using corneas from the donors in this study. Nine corneas from pseudophakic donor eyes were transplanted, resulting in one primary graft failure reported. Corneas from pseudophakic donor eyes may need more extensive evaluation for endothelial viability than is currently required by eye bank standards.


The Role of Pea (Pisum sativum) Seeds in Transmission of Entero-Aggregative Escherichia coli to Growing Plants.
Crop plants can become contaminated with human pathogenic bacteria in agro-production systems. Some of the transmission routes of human pathogens to growing plants are well explored such as water, manure and soil, whereas others are less explored such as seeds. Fenugreek seeds contaminated with the entero-hemorrhagic Escherichia coli O104:H4 were suspected to be the principle vectors for transmission of the pathogen to sprouts at the food-borne disease outbreak in Hamburg and surrounding area in 2011. In this study we raised the questions of whether cells of the entero-aggregative E. coli O104:H4 strain 55989 is capable of colonizing developing plants from seeds and if it would be possible that, via plant internalization, these cells can reach the developing embryonic tissue of the next generation of seeds. To address these questions, we followed the fate of strain 55989 and of two other E. coli strains from artificially contaminated seeds to growing plants, and from developing flower tissue to mature seeds upon proximate introductions to the plant reproductive organs. Escherichia coli strains differing in origin, adherence properties to epithelial cells, and virulence profile were used in our experimentation to relate eventual differences in seed and plant colonization to typical E. coli properties. Experiments were conducted under realistic growth circumstances in greenhouse and open field settings. Entero-aggregative E. coli strain 55989 and the two other E. coli strains were able to colonize the root compartment of pea plants from inoculated seeds. In roots and rhizosphere soil, the strains could persist until the senescent stage of plant growth, when seeds had ripened. Colonization of the above-soil parts was only temporary at the start of plant growth for all three E. coli strains and, therefore, the conclusion was drawn that translocation of E. coli cells via the vascular tissue of the stems to developing pea seeds seems unlikely under circumstances realistic for agricultural practices. Proximate introductions of cells of E. coli strains to developing flowers also did not result in internal seed contamination, indicating that internal seed contamination with E. coli is an unlikely event. The fact that all three E. coli strains showed stronger preference for the root-soil zones of growing pea plants than for the above soil plant compartments, in spite of their differences in clinical behaviour and origin, indicate that E. coli in general will colonize root compartments of crop plants in production systems.