Surfactant-Free Colloidal Syntheses of Gold-Based Nanomaterials in Alkaline Water and Mono-alcohol Mixtures.
Gold nanoparticles (Au NPs) and gold-based nanomaterials combine unique properties relevant for medicine, imaging, optics, sensing, catalysis, and energy conversion. While the Turkevich-Frens and Brust-Schiffrin methods remain the state-of-the-art colloidal syntheses of Au NPs, there is a need for more sustainable and tractable synthetic strategies leading to new model systems. In particular, stabilizers are almost systematically used in colloidal syntheses, but they can be detrimental for fundamental and applied studies. Here, a surfactant-free synthesis of size-controlled colloidal Au NPs stable for months is achieved by the simple reduction of HAuCl4 at room temperature in alkaline solutions of low-viscosity mono-alcohols such as ethanol or methanol and water, without the need for any other additives. Palladium (Pd) and bimetallic Au x Pd y NPs, nanocomposites and multimetallic samples, are also obtained and are readily active (electro)catalysts. The multiple benefits over the state-of-the-art syntheses that this simple synthesis bears for fundamental and applied research are highlighted.


Abortion law in Europe in 1991-1992.
... This article will analyze legal developments relating to abortion that have taken place in 1991-1992 in six countries of western and eastern Europe: Poland, Hungary, Albania, Germany, Ireland, and Belgium.


Biofunctionalities of unprocessed and processed flours of Australian lupin cultivars: Antidiabetic and organ protective potential studies.
As lupin has emerged popularity as dietary protein and nutritional source, our present research was aimed to demonstrate the antidiabetic and organ-protective activities of nine cultivars of Australian sweet lupin seed flours by means of in vitro and in vivo assays accompanied by identification of their bioactive phytocompounds and exploration of underlying mechanisms of their hypoglycemic activity using in silico approach. In vitro α-amylase and α-glucosidase activities inhibition and glucose uptake assays identified Jenabillup seed flours for exhibiting the most potential antidiabetic activity amongst the nine cultivars. In vivo antidiabetic and major organ-protective activities were investigated on streptozotocin-induced hyperglycemia and organ damages in Wister rat model. Along with attenuating hyperglycemia and retreating major organ damages, the biochemical imbalance in cardiac, hepatic and renal markers were well-balanced by Jenabillup seed flours treatment. These activities of lupin seed flours were insignificantly affected by thermal processing. Moreover, in silico investigation of 106 phytochemicals identified by gas chromatography-mass spectroscopy (GC-MS) analysis of the seed flour extracts of nine cultivars revealed that more than 35% of compounds possess moderate to high binding affinity to α-amylase and α-glucosidase enzymes. These bioactive compounds act synergistically to exert potential hypoglycemic activity. Cross-docking and binding energy calculation by molecular mechanics/generalized Born volume integration (MM/GBVI) model suggest actinomycin C2 as a potential inhibitor of both α-amylase and α-glucosidase enzymes. These findings acclaim that Australian sweet lupin seed flours may be considered not only as functional food, but also for further development of effective drugs in pharmaceuticals in the treatment of diabetes mellitus and resultant organ damages.


Rototillage, disking, and subsequent irrigation: effects on soil nitrogen dynamics, microbial biomass, and carbon dioxide efflux.
Spring and summer tillage are usually followed by irrigation before planting crops in California's summer-dry Mediterranean-type climate. Tillage treatments such as rototillage or disking are known to disturb the soil structure to different extents, but little is known about how the intensity of a tillage event and subsequent irrigation affect the microbial biomass, respiration, CO2 efflux, and mineral N of agricultural soils. We carried out an experiment with a Yolo silt loam (fine-silty, mixed, superactive, nonacid, thermic Mollic Xerofluvent) with two tilled treatments (rototillage and disked and rolled) and a nontilled control. The soil was subsequently sampled throughout a 17-d period. Nine days after tillage, all treatments were lightly sprinkler-irrigated to bring the soil water potential above -10 kPa. After tillage, the soil ammonium and nitrate content increased rapidly relative to the control with highest increases in the disked soil. Mineral N remained higher in the tilled treatments after irrigation. Rototillage and disking increased the CO2 efflux of the soil within 24 h of the disturbance. The increase was higher in the disked soil, which was more than three times the CO2 efflux of the control soil at 0.25 h after tillage. This effect may be due to degassing of dissolved CO2 since microbial respiration did not increase in tilled soils. Irrigation increased the CO2 efflux of all treatments but this was most pronounced in the control soil, which had an order of magnitude increase in CO2 efflux after irrigation. An ancillary experiment carried out under similar conditions but with more frequent sampling showed that increases in CO2 efflux after irrigation were accompanied by increases in soil respiration. This study shows that different tillage implements affect CO2 efflux, nitrate accumulation, and microbial activity, and thus have different effects on soil and atmospheric environmental quality.


A new silicon drift detector for high spatial resolution STEM-XEDS: performance and applications.
A newly designed, 100 mm2, silicon drift detector has been installed on an aberration-corrected scanning transmission electron microscope equipped with an ultra-high resolution pole piece, without requiring column modifications. With its unique, windowless design, the detector's active region is in close proximity to the sample, resulting in a dramatic increase in count rate, while demonstrating an increased sensitivity to low energy X-rays and a muted tilt dependence. Numerous examples of X-ray energy dispersive spectrometry are presented on relevant materials such as Al x Ga1-x N nanowires, perovskite oxides, and polycrystalline CdTe thin films, across both varying length scales and accelerating voltages.


The regulatory environment for artificial intelligence-enabled devices in the United States.
The regulatory environment in the United States has not kept pace with the rapidly developing market for artificial intelligence (AI)-enabled devices. The number of AI-enabled devices has increased year after year. All of these devices are registered or cleared by the US Food and Drug Administration through exempt or 510(k) premarket notification pathways, and the majority are related to the radiology or cardiovascular spaces. US Food and Drug Administration guidance has not yet addressed the unique challenges of AI-enabled devices, including development, comprehensibility, and continuously learning models. The liability aspects of AI-enabled devices deployed into use by clinicians in practice have yet to be addressed. Future guidance from government regulatory sources will be necessary as the field moves forward.


A new construct of antibody-drug conjugates for treatment of B-cell non-Hodgkin's lymphomas.
The aim of this study was to develop a new class of antibody-drug conjugates (ADCs) with the potential to not only enhance treatment efficacy but also improve tolerability for patients with B-cell lymphomas. Classic ADCs consist of monoclonal antibodies (mAbs) linked to drugs or toxins. They selectively deliver toxic moieties to tumor cells. As such, they greatly improve the therapeutic index compared to traditional chemotherapeutic agents. However, the therapeutic efficacy and safety of ADCs are dependent on linker stability and payload toxicity. Limited payload number on a single antibody (drug-to-antibody ratio, or DAR) has been driving investigators to use extremely toxic agents; however, even very low off-target binding of these ADCs may kill patients. Herein we report a new design of ADCs that consists of rituximab (RTX) and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin conjugates. The latter was selectively attached to RTX via reduced disulfide bonds. Such design allows the introduction of a large payload of drug on the antibody without adding attachment sites and without compromising the antigen-targeting ability. The binding of the new conjugate, namely RTX-P-EPI, to Ramos cells (with high CD20 expression) was confirmed. The cytotoxicity of RTX-P-EPI against Raji and Ramos cells was also determined. Interestingly, two-fold inhibition of cell proliferation was observed when using RTX-P-EPI compared with their equivalent physical mixture of RTX and P-EPI. Treatment of male SCID mice bearing subcutaneous Ramos B-cell lymphoma tumors demonstrated that RTX-P-EPI possessed superior efficacy when compared to combination of RTX with chemotherapy EPI (RTX+EPI) and P-EPI (RTX+P-EPI), whereas single RTX and a non-specific conjugate IgG-P-EPI only showed marginal effect. The conjugate RTX-EPI in which EPI was directly attached to RTX demonstrated much less antitumor activity compared with RTX-P-EPI. The results suggest that this new design possesses synergistic potential of immunotherapy combined with established macromolecular therapy; moreover, a conventional chemo-agent could be utilized to generate highly effective ADCs and to achieve lower risk of off-target toxicity.


Pregnancy-Associated Deaths in Rural, Nonrural, and Metropolitan Areas of Georgia.
To characterize pregnancy-associated deaths and examine the relationship between area of residence and pregnancy-associated deaths and pregnancy-related mortality ratios in Georgia from 2010 to 2012. The cohort of pregnancy-associated deaths was reviewed and categorized as pregnancy-related or resulting from other medical conditions not related to pregnancy, suicide, drug toxicity, homicide, or motor vehicle accident. Georgia Online Analytical Statistical Information System data were used to calculate pregnancy-related mortality ratio by rural, nonrural, and metropolitan Atlanta area and by race. Causes of death and pregnancy-related mortality ratio were compared by area of residence and race using χ tests; a P value <.05 was considered significant. There were 262 pregnancy-associated deaths; 40.1% (n=105) were pregnancy-related. The 2010-2012 pregnancy-related mortality ratio was 26.5 per 100,000 live births and the pregnancy-related mortality ratio did not differ statistically among rural (27.1), nonrural (24.4), and metropolitan Atlanta (27.7) areas (P=.845). Most pregnancy-related deaths were the result of hemorrhage and cardiovascular factors. In aggregate, the pregnancy-related mortality ratio for black women was 49.5 compared with 14.3 for white women (P<.001). The gap in pregnancy-related mortality ratio between black and white women was highest for metropolitan Atlanta (51.6 compared with 12.4, P<.001), less in nonrural areas (50.3 compared with 12.0, P<.001), and comparable in rural areas (39.4 compared with 22.4, P=.281). Although the pregnancy-related mortality ratio was similar for rural, nonrural, and metropolitan Atlanta areas, it was significantly higher for black compared with white women living outside of rural areas.


Oligomer Formation of Amyloid-β(29-42) from Its Monomers Using the Hamiltonian Replica-Permutation Molecular Dynamics Simulation.
Oligomers of amyloid-β peptides (Aβ) are formed during the early stage of the amyloidogenesis process and exhibit neurotoxicity. The oligomer formation process of Aβ and even that of Aβ fragments are still poorly understood, though understanding of these processes is essential for remedying Alzheimer's disease. In order to better understand the oligomerization process of the C-terminal Aβ fragment Aβ(29-42) at the atomic level, we performed the Hamiltonian replica-permutation molecular dynamics simulation with Aβ(29-42) molecules using the explicit water solvent model. We observed that oligomers increased in size through the sequential addition of monomers to the oligomer, rather than through the assembly of small oligomers. Moreover, solvent effects played an important role in this oligomerization process.


Serum lactate dehydrogenase and survival following cancer diagnosis.
There is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear. A total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis. At the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31-1.56) and 1.46 (1.32-1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death. Our findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.


Multi-dimensional liquid chromatography in proteomics--a review.
Proteomics is the large-scale study of proteins, particularly their expression, structures and functions. This still-emerging combination of technologies aims to describe and characterize all expressed proteins in a biological system. Because of upper limits on mass detection of mass spectrometers, proteins are usually digested into peptides and the peptides are then separated, identified and quantified from this complex enzymatic digest. The problem in digesting proteins first and then analyzing the peptide cleavage fragments by mass spectrometry is that huge numbers of peptides are generated that overwhelm direct mass spectral analyses. The objective in the liquid chromatography approach to proteomics is to fractionate peptide mixtures to enable and maximize identification and quantification of the component peptides by mass spectrometry. This review will focus on existing multidimensional liquid chromatographic (MDLC) platforms developed for proteomics and their application in combination with other techniques such as stable isotope labeling. We also provide some perspectives on likely future developments.


The effect of image content on detail preservation and file size reduction in lossy compression.
To demonstrate the effect of image content on image detail preservation and file size reduction. The first set, containing 16 in vitro images with variable projection geometry, exposure time, bone level and number of teeth, was compressed with three compression modes: JPEG quality factor (JPQF), JPEG2000 quality factor (J2QF) and JPEG2000 compression ratio (J2CR). Image detail degradation was evaluated by local mean square error (MSE) on a standardized region of interest (ROI), containing bone. The second set, containing 105 clinical bitewings, was compressed with the same compression modes at 3 quality factors/compression ratios and local MSEs were calculated on two ROIs, containing bone and crown. For the first image set, nearly constant MSE was found for the JPQF and J2QF compression modes, while file size depended on projection geometry, exposure time, bone level and the number of teeth. In contrast, file size reduction was nearly constant for the J2CR compression mode, while MSE depended on the abovementioned factors. Similarly, for the second image set, nearly constant MSE and variation of file size reduction were found for JPQF and J2QF but not for the J2CR compression mode. All of these results were consistent for all three quality factors/compression ratios. Constant image detail preservation, crucial for diagnostic accuracy in radiology, can only be assured in QF compression mode in which the file size of the compressed image depends on the original image content. CR compression mode assures constant file size reduction, but image detail preservation depends on image content.


Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model.
Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. Staphylococcus aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be upregulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (P=0.22, Fisher's exact test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.


Lethal Epistaxis.
Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified.


Epithelial responses and Candida albicans pathogenicity are enhanced in the presence of oral streptococci.
Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.


The free parascapular flap.
The parascapular flap is a new, reliable and thin flap with a constant anatomy of the vascular pedicle. The flap can be taken with the lateral border of the scapula or used in combination with the latissimus dorsi muscle. Primary closure of the donor site can be achieved with a flap size up to 30 X 15 cm. The various applications of the parascapular flap are discussed and the results of four patients are presented.


Factors associated with prospective long-term treatment adherence among individuals with bipolar disorder.
Clinical characteristics, adverse effects of medication, and treatment attitudes have been associated with adherence in bipolar populations in cross-sectional studies. The aim of this secondary analysis from a larger study was to identify the association between baseline variables and average treatment adherence over a subsequent three-year period. Veterans with bipolar disorder were evaluated on self-reported adherence status at baseline and every six months over a three-year period. The sample was dichotomized into two clinically relevant categories: those who were primarily adherent and those who were primarily nonadherent. Demographic and clinical variables were examined for the two groups of patients in relation to their average adherence over the three-year period. The study recruited a sample of 306 persons with severe bipolar disorder. The sample was predominantly male (278 men, or 91%), with a mean+/-SD age of 46.6+/-10.1 years. A total of 240 individuals (78%) were largely adherent to treatment, and 37 individuals (12%) were largely nonadherent to treatment. Nonadherent individuals were less likely to be on intensive somatotherapy regimens (p=.001); experienced more barriers to care, including lack of telephone access (p<.05) and life obligations and commitments (p<.05); and had more prior suicide attempts (p=.003). Nonadherent individuals with bipolar disorder received less intensive pharmacologic treatments, had more suicide attempts, and experienced more barriers to care than adherent individuals. Nonadherence may have system as well as patient components. Consideration of nonadherence as a function of both patient factors and system factors will enhance our ability to understand nonadherence and intervene more effectively.


Europa's differentiated internal structure: inferences from two Galileo encounters.
Doppler data generated with the Galileo spacecraft's radio carrier wave during two Europa encounters on 19 December 1996 (E4) and 20 February 1997 (E6) were used to measure Europa's external gravitational field. The measurements indicate that Europa has a predominantly water ice-liquid outer shell about 100 to 200 kilometers thick and a deep interior with a density in excess of about 4000 kilograms per cubic meter. The deep interior could be a mixture of metal and rock or it could consist of a metal core with a radius about 40 percent of Europa's radius surrounded by a rock mantle with a density of 3000 to 3500 kilograms per cubic meter. The metallic core is favored if Europa has a magnetic field.


Evaluation of inorganic particles of composite resins with nanofiller content.
The purposes of this study were evaluate by energy dispersed X-ray (EDS) and scanning electron microscopy (SEM) the inorganic particles of three nanofilled composite resins, comparing particles sizes, shape and composition, and the filler weight content by thermogravimetric analyzes (TGA). Three composite resins classified as nanofilled were selected to this study: Esthet-X; Grandio; Filtek Supreme XT. The shade was standardized (A2) for enamel (E) or dentin (D). Ten samples with 20 mg (±10 mg) of each composite resin were submitted to thermogravimetric analyzes (TGA) in order to record the filler weight content (wt%). The amount of inorganic phase ranged from 75.75 to 87 wt%, to Esthet-X (D) and Grandio (D), respectively. The filler composition was analyzed by energy dispersed X-ray (EDS), and the size and shape were evaluated by scanning electron microscopy (SEM). The filler average size (µm) obtained by SEM were: Esthet-X (E) 1.16; Esthet-X (D) 1.39; Filtek Supreme XT (E) 0.6 (nanocluster); Filtek Supreme XT (D) 1.14 (nanocluster); Grandio (E) 2.05 and Grandio (D) 3.1. Silica (SiO2), Ba and Al were observed through EDS. The shape of Esthet-X and Grandio fillers showed similar characteristics with high quantity of irregular inorganic particles and heterogeneous filler. However, Filtek Supreme XT showed spherical and regular particles with homogeneous distribution and sizes. Based in the analysis of nanofilled composites inorganic phase, inconsistencies of weight content, composition, shape and size can be stated between the literature and manufacturer's instructions.


Applications of genomic tools to colorectal cancer therapeutics.
Clinically and histopathologically similar colorectal cancers exhibit considerable variability in their responses to chemotherapeutics. The advent of genomic technologies has enabled the unbiased determination of changes in DNA and RNA, alterations that may be responsible for, or predictive of the variability in response to chemotherapy. This review highlights several advances made in applying genomic tools toward colorectal cancer therapeutics. Progress has been made using gene expression profiling to identify which colorectal cancer patients would benefit most from adjuvant chemotherapy. In addition, advances have been made in colorectal cancer pharmacogenomics by identifying gene expression patterns associated with sensitivity to specific chemotherapeutic agents. Lastly, the use of genome-wide mutation screening of individual tumor samples to identify the profiles of mutated genes is explored. Future research toward integrating genomic information with clinical and histopathological data is expected to lead to improved therapeutic management of colorectal cancer.


Popliteal Retrograde Approach is Effective and Safe for Superficial Femoral Artery Chronic Total Occlusion.
Endovascular treatment (EVT) using a popliteal approach is effective for superficial femoral artery (SFA) chronic total occlusion (CTO); however, its effectiveness, safety, and consequent complications are unclear. We studied 324 consecutive EVTs (in 187 patients) performed at three centers between April 2008 and March 2013, and selected all EVTs that included SFA CTO regions. A total of 91 EVTs (in 65 patients) were included and divided into two groups; "with popliteal approach" (WPA) and "without popliteal approach" (WOPA). Despite higher rates of hypertension (WPA, 88.9% vs. WOPA, 69.1%; p = 0.04) and CTO length >200 mm (55.6% vs. 28.3%, respectively; p <0.01), the primary success rate was better in the WPA group (97.2% vs. 78.2%, respectively; p <0.01); however, both total complication rate and major complication rate were not significantly different. We compared popliteal puncture using a sheath and using a microcatheter alone. There were no significant differences between sheath and microcatheter use in terms of primary success rates (95.5% vs. 100%, respectively; p = 0.61) and puncture site complications (22.7% vs. 14.2%, respectively; p = 0.53). A popliteal approach improved the primary success rate of EVT for SFA CTO.


A 3D model of a human epiblast reveals BMP4-driven symmetry breaking.
Breaking the anterior-posterior symmetry in mammals occurs at gastrulation. Much of the signalling network underlying this process has been elucidated in the mouse; however, there is no direct molecular evidence of events driving axis formation in humans. Here, we use human embryonic stem cells to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression are similar to a day 10 human epiblast. A defined dose of BMP4 spontaneously breaks axial symmetry, and induces markers of the primitive streak and epithelial-to-mesenchymal transition. We show that WNT signalling and its inhibitor DKK1 play key roles in this process downstream of BMP4. Our work demonstrates that a model human epiblast can break axial symmetry despite the absence of asymmetry in the initial signal and of extra-embryonic tissues or maternal cues. Our three-dimensional model is an assay for the molecular events underlying human axial symmetry breaking.


Inherited disorders of glycoprotein synthesis: cell biological insights.
Disorders of glycoprotein synthesis have been described only recently, and few have been studied extensively at both the clinical and biochemical level. The identification and characterization of these rare diseases are important, not only for the patients and their families, but because they offer enormous insight into biological processes. For example, the targeting of acid hydrolases to lysosomes by mannose-6-phosphate was discovered as a direct result of the elucidation of the defect in I-cell disease. The notion of carbohydrates as targeting agents continues to have ramifications today, with the success of macrophage-targeted enzyme replacement therapy for Gaucher disease. Likewise, confirmation of the in vivo role of fucose-containing glycans and selectins in neutrophil function came from studies using specimens from patients with leucocyte adhesion deficiency type II due to reduced availability of GDP-fucose. Identification of the in vivo ligands of selectins also has implications for anti-inflammatory therapies. Macular corneal dystrophy and spondyloepiphyseal dysplasia tarda offer an opportunity to investigate the number of different sulfotransferases in cells, their substrates, and their tissue expression. The Ehlers-Danlos progeroid variant offers insight into the function and regulation of the proteoglycan decorin, and suggests that several of the enzymes involved in proteoglycan synthesis may function as a multienzyme complex. The common occurrence of hypergonadotropic hypogonadism in patients with galactosemia or carbohydrate-deficient glycoprotein protein syndrome, due to defective N-linked glycosylation, suggests that ovarian function is particularly dependent on proper glycan-synthesis. A host of other concepts await discovery as a fuller contingent of human disorders of glycan synthesis achieves recognition.


Correlates of help-seeking behavior among at-risk adolescents.
This study compared demographic, academic, and clinical characteristics of adolescents at risk for mental health problems who either did or did not request help during a voluntary mental health screening. High school students completed a self-report to identify risk of mental health problems (n=364). Students at risk were administered a clinical interview. Among those at risk, we compared those who requested help (n=61) to those who did not (n=22). The group who did not request help had a larger proportion of Caucasian students, higher grades, fewer days absent, and fewer detentions than their counterparts. In addition, those who did not request help were significantly more likely to report suicidal ideation in the preceding 3 months (63.6% vs. 27.9%, p< .001). Relying on adolescents' requests for help alone would likely not identify many of those with suicidal ideation. Two-stage voluntary mental health screenings increase the detection of these adolescents at risk.


Treatment decision-making capacity in hospitalized patients with schizophrenia.
In contemporary medical ethics and clinical practice the autonomy of patients and their right to accept or refuse an offered treatment is acknowledged and respected. Prerequisite for the right of a patient to consent to any medical act is the capacity to make valid decisions regarding his/ her treatment. The objective of our study was to assess -for the first time in our country- treatment decision-making capacity of hospitalized patients with schizophrenia; to explore any possible association with demographic and clinical variables; and to compare treatment decision-making capacity of patients with schizophrenia with medical patients' capacity. The sample of patients comprised of 21 patients with schizophrenia who were hospitalized in the psychiatric ward of the General Hospital of Arta, north-west Greece. Those patients' capacity was compared with treatment decision-making capacity of 78 patients hospitalized in the internal medicine ward of the same hospital. All patients' capacity was assessed within 72 hours of admission with the use of the Greek version of the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), a valid and reliable tool for capacity assessment. The performance of patients with schizophrenia on the MacCAT-T was significantly worse than medical patients' performance, suggesting that patients with schizophrenia, as a group had poorer decision-making capacity compared to medical patients. Both negative symptomatology (anergia) and positive symptoms (hostility and suspiciousness), as measured with the use of the Brief Psychiatric Rating Scale (BPRS) were associated with poor performance on the MacCAT-T. Although medical patients as a group scored better in the MacCAT-T, there were several cases that lacked decision-making capacity. In conclusion, patients with schizophrenia had higher incapacity rates than medical patients during the first days of hospitalization. Lack of treatment decision-making capacity is not necessarily the rule for patients with schizophrenia, and capacity is not present in all medical patients. The ability of patients to consent to treatment should be re-assessed during hospitalization, and when restored, informed consent should be obtained by clinicians.


The calcium-stimulated incorporation of ethanolamine and serine into the phospholipids of the housefly Musca domestica.
1. The calcium-stimulated incorporation of [2-(14)C]ethanolamine and l-[3-(14)C]-serine into the phospholipids of homogenates of the fat bodies from larval houseflies (Musca domestica) was studied. 2. Ethanolamine and serine acted as competitive inhibitors with one another. N-Methylethanolamine was not distinguished from ethanolamine by the system. Tris buffer was also a competitor with these compounds, and a number of other amino alcohols were inhibitory, probably competitively. 3. The incorporation of [(32)P]phosphorylethanolamine into phospholipids was observed in suspensions of whole fat bodies. This incorporation was stimulated by magnesium. 4. During the incubation of the homogenates, a calcium-stimulated breakdown of phospholipids by a phospholipase A occurred. 5. These results are compared with results published for similar mammalian systems, and their possible physiological significance is discussed.


[Clinical aspects of pulmonary tuberculosis].
The low incidence of pulmonary tuberculosis has led to a decrease of doctors expertise in this field. This review deals with clinical aspects of the disease. This article does not refer to the problem of simultaneous infection with tuberculosis and HIV. Pathogenesis, symptoms and diagnosis are discussed. A classification of intrathoracal manifestations of the disease with respect to clinical, radiologic and pathogenetic criteria is raised. To facilitate dealing with a certain case, a couple of questions are formulated and pragmatic answers are given. Risk-groups are specially emphasized to attract attention to the possibility of specific disease.


Controlled silicon surface functionalization by alkene hydrosilylation.
Immobilization of indene ligands onto two types of hydrogen-terminated surfaces, oxide-free Si [H/Si(111)] and oxidized Si [H/SiO2/Si], has been investigated by infrared absorption spectroscopy. The activity of a common catalyst (H2PtCl6) is shown to depend critically on the nature of the solvent. For instance, 2-propanol preferentially reacts with the surface, preventing any ligand attachment. Chlorobenzene is more stable, allowing some ligand attachment, but the H2PtCl6 catalyst also fosters silicon oxidation. In contrast, UV irradiation on oxide-free surfaces promotes a cleaner and more efficient reaction, leading to ligand attachment without substrate oxidation. The complete inactivity of H-terminated surfaces with a thin oxide layer [H/SiO2/Si] suggests that the UV-induced immobilization is mediated solely by the excitation of electron-hole pairs (excitons) in the substrate and is not the result of direct Si-H bond breaking.


Detection of Anaplasma antibodies in wildlife and domestic species in wildlife-livestock interface areas of Kenya by major surface protein 5 competitive inhibition enzyme-linked immunosorbent assay.
The seroprevalence of Anaplasma antibodies in wildlife (eland, blue wildebeest, kongoni, impala, Thomson's gazelle, Grant's gazelle, giraffe and plains zebra) and domestic animal (cattle, sheep and goat) populations was studied in wildlife/livestock interface areas of Kenya. Serum samples were analyzed by competitive inhibition enzyme-linked immunosorbent assay (CI-ELISA), using a recombinant antigen (MSP-5) from Anaplasma marginale surface membrane. A monoclonal antibody, FC-16, was used as the primary antibody, while anti-mouse conjugated to horseradish peroxidase was used as the secondary antibody. The results indicate a high seroprevalence in both wildlife and livestock populations, in contrast to earlier reports from Kenya, which indicated a low seroprevalence. The differences are attributed to the accurate analytical method used (CI-ELISA), as compared with agglutination techniques, clinical signs and microscopy employed by the earlier workers.


Gene transduction in human monocyte-derived dendritic cells using lentiviral vectors.
Monocyte-derived dendritic cells (MDDCs) are widely used in the field of human immunology. Although a variety of gene delivery procedures have been used in MDDC, it has remained difficult to achieve robust gene transductions. In this chapter, we describe a procedure for high efficiency gene transduction in human MDDCs using lentiviral vectors. Gene transduction based on HIV-1-derived lentiviral vectors is restricted at the level of reverse transcription by the cellular protein SAMHD1 in MDDCs. Co-transduction of the MDDCs with helper particles derived from SIVmac that contain the viral protein Vpx removes this restriction, leading to a drastic increase in the rate of gene transduction. This procedure leads to nontoxic, efficient and stable transduction in MDDCs. It can be applied to any HIV-1-derived lentiviral vector, including shRNA lentiviral vectors for RNAi. Transduced MDDCs are not activated by the transduction and can be activated normally by TLR ligands.


[Nuclear magnetic resonance (NMR) spectroscopy and its application to biomedical research].
The principles of nuclear magnetic resonance (NMR) spectroscopy were explained and its application to biomedical research discussed. With 31P-NMR, it is feasible to conduct a continuous, non-invasive measurement of the contents of myocardial high-energy phosphate compounds and the intracellular pH (determined by monitoring the pH dependent shift of the inorganic phosphate peak relative to that of creatine phosphate), and to correlate them with the mechanical function. The determination of the free magnesium concentration is also possible on a similar principle to that for pH determination (the shift of MgATP peaks relative to ATP is utilized in this case). It is estimated to be 0.3 mM and was found not to be changed during ischemia. Several examples of studies including our own conducted to delineate the ischemic derangements of the myocardial energy metabolism and the effects of various interventions thereupon were illustrated. Finally a brief mention was made of the saturation transfer technique. This is the only method with which one can study the kinetics of the enzyme reactions under in vivo conditions. The application of the method for analysis of the creatine kinase reaction and the ATP synthesis was demonstrated.


Development of myringosclerosis during acute otitis media caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae: a clinical otomicroscopical study using the rat model.
The present study was performed in order to study development of myringosclerosis during acute otitis media caused by different bacteria in myringotomized and non-myringotomized ears. A rat model of acute otitis media caused by Streptococcus pneumoniae type 3 and non-typeable Haemophilus influenzae was used. A sample consisted of 42 animals. Four days following middle ear inoculation, a myringotomy was performed in 10 animals from the Streptococcus pneumoniae group and 6 from the non-typeable Haemophilus influenzae group. Another group of 24 animals was inoculated only. On day 4, 7, 14 and 28 after inoculation the status of the drum was inspected under the otomicroscope for vascular reaction, effusion, perforation, myringosclerosis and scarring. On day 4 after inoculation all infected ears had typical signs of acute otitis media. Tympanic membranes healed with scar formation in most cases of myringotomized Streptococcus pneumoniae type 3 infection and deposition of sclerotic plaques was observed by day 14. Otomicroscopically visible myringosclerosis was not found after non-typeable Haemophilus influenzae induced acute otitis media neither in myringotomized nor in non-myringotomized animals. We conclude that Streptococcus pneumoniae type 3 provokes a severe clinical course of acute otitis media that healed with scarring and myringosclerosis formation in the tympanic membrane. Clinically visible myringosclerosis develops after middle ear infection caused by Streptococcus pneumoniae type 3, but not in cases caused by non-typeable Haemophilus influenzae.


Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator.
Silibinin is a natural plant polyphenol with high antioxidant and anticancer properties, which causes broad-spectrum efficacy against cancer, including cell cycle arrest and apoptosis in most cancer cell types. Silibinin, by modulating the apoptosis, cell cycle progression and autophagic pathways in various cellular and molecular routs might be used to design more effective anticancer strategies. Silibinin also regulates aberrant miRNAs expression linked to many aspects of cell biology in cancer. Maybe the most interesting aspect of silibinin is its ability to trigger multiple cellular signaling pathways to induce a particular biologic effect in various cell types. This review discusses investigations supporting the ability of silibinin to be as a natural modulator of involved cellular biological events in cancer progression. In this review, we introduce the salient features of silibinin therapy to optimize clinical outcomes for oncology patients. The goal of the treatments is to make it possible to eliminate the tumor with the minimum side effects and cure the patient in the early stage cancer. Therefore, plant extracts such as silibinin can be included in the treatments.


Complex Relationship between Obesity and the Fat Mass and Obesity Locus.
In the 21st century, obesity has become a serious problem because of increasing obese patients and numerous metabolic complications. The primary reasons for this situation are environmental and genetic factors. In 2007, FTO (fat mass and obesity associated) was the first gene identified through a genome-wide association study (GWAS) associated with obesity in humans. Subsequently, a cluster of single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene was discovered to be associated with BMI and body composition. Various studies have explored the mechanistic basis behind this association. Thus, emerging evidence showed that FTO plays a key role regulating adipose tissue development and functions in body size and composition. Recent prevalent research topic concentrated in the three neighboring genes of FTO: RPGRIP1L, IRX3 and IRX5, as having a functional link between obesity-associated common variants within FTO and the observed human phenotypes. The purpose of this review is to present a comprehensive picture of the impact of FTO on obesity susceptibility and to illuminate these new studies of FTO function in adipose tissue.


Routes of viral spread in the von Szily model of herpes simplex virus retinopathy.
Intraocular inoculation of herpes simplex virus type 1 (HSV-1) in one eye of rabbits results in encephalitis and contralateral necrotizing viral retinopathy. The effects of viral inoculation site and optic nerve (ON) transection on the spread of virus to the brain and contralateral eye in this model were investigated. A surgical technique was developed for transection of the retrobulbar optic nerve posterior to the entrance of the central retinal vessels. HSV-1 was inoculated into the AC or vitreous of one eye in normal rabbits and in rabbits with one ON transected, either ipsilateral or contralateral to the side of inoculation. Animals were followed clinically for signs of disease. Encephalitis and contralateral retinopathy (CR) occurred following both AC and vitreous inoculation of virus, although CR developed later in AC-inoculated rabbits. Ipsilateral retinopathy (IR) developed in 83% of vitreous-inoculated rabbits, but in only 5% of AC-inoculated animals. IR developed 8 days after the onset of CR in the AC-inoculated group. ON transection on the side of virus inoculation prevented development of CR only in vitreous-inoculated rabbits. ON transection on the side opposite virus inoculation prevented CR regardless of the site of inoculation. These findings suggest that HSV-1 can leave the inoculated eye by multiple routes depending on the site of virus inoculation, but that virus reaches the retina of the contralateral eye via the optic nerve.


Calculating the free energy of transfer of small solutes into a model lipid membrane: Comparison between metadynamics and umbrella sampling.
We compare the performance of two well-established computational algorithms for the calculation of free-energy landscapes of biomolecular systems, umbrella sampling and metadynamics. We look at benchmark systems composed of polyethylene and polypropylene oligomers interacting with lipid (phosphatidylcholine) membranes, aiming at the calculation of the oligomer water-membrane free energy of transfer. We model our test systems at two different levels of description, united-atom and coarse-grained. We provide optimized parameters for the two methods at both resolutions. We devote special attention to the analysis of statistical errors in the two different methods and propose a general procedure for the error estimation in metadynamics simulations. Metadynamics and umbrella sampling yield the same estimates for the water-membrane free energy profile, but metadynamics can be more efficient, providing lower statistical uncertainties within the same simulation time.


A novel label-free multi-throughput optical biosensor based on localized surface plasmon resonance.
A novel and sensitive multi-throughput localized surface plasmon resonance (MLSPR) biosensor was developed for the first time. Various gold nanorods with different aspect ratios were used to fabricate the optical sensor. Five kinds of gold nanorods with different aspect ratios were chosen to construct five throughputs of MLSPR. Various LSPR peaks imply that different acceptor-ligand pairs can be detected simultaneously in the wavelength range from 530 to 940nm. The biosensor immobilized on glass slides was applied to label-free detection between acceptor and ligand. The MLSPR-based optical biosensor can be used to detect three antigen-antibody pairs simultaneously. The biosensor proposed herein is easy to fabricate, and its operation procedure is convenient as labeling procedure is unnecessary.


New findings in the genetics of major psychoses.
Schizophrenia and bipolar disorder have a largely unknown pathophysiology and etiology, but they are highly heritable. Although linkage and association studies have identified a series of chromosomal regions likely to contain susceptibility genes, progress in identifying causative genes has been largely disappointing. However, rapid technological advances are beginning to lead to new insights. Systematic genome-wide association and follow-up studies have reported genome-wide significant association findings of common variants for schizophrenia and bipolar disorder. The risk conferred by individual variants is small, and some variants confer a risk for both disorders. In addition, recent studies have identified rare, large structural variants (copy number variants) that confer a greater risk for schizophrenia. This review summarizes recent developments in genetic research into schizophrenia and bipolar disorder, and discusses possible future directions in this field.


Efficacy of ultrasonic mass survey for abdominal cancer.
From August 1983 through March 1995, 204,099 people received ultrasonic mass survey of the abdomen for the first time. Among these examinees, 631 (0.31%) malignant neoplasm cases, such as 201 hepatocellular carcinoma (HCC), 81 gallbladder (GB) cancer, 57 pancreatic cancer, and 169 renal cell carcinoma (RCC), were detected. Three hundred seventy six out of 590 cases (64%), excluding chronic leukemia cases and metastatic liver cancer cases, were surgically resected. The resection rate of HCC, GB cancer, pancreatic cancer, and RCC were 25%, 88%, 49%, and 99%, respectively. The cumulative survival rate of the 376 resected cases was 79.5% at 10 years. The cumulative survival rates of resected cases of HCC, GB cancer, pancreatic cancer and cumulative survival rates of resected cases of HCC, GB cancer, pancreatic cancer and RCC were 34% at ten years, 83% at 10 years, 49% at 7 years, and 99% at 10 years, respectively. Ultrasonic mass survey is dramatically useful for early detection of various kinds of abdominal cancers, especially RCC and GB cancer. From now on, many earlier abdominal cancers will be found by establishing and promoting ultrasonic mass survey systems.


Mouse very-low-density-lipoprotein receptor (VLDLR) cDNA cloning, tissue-specific expression and evolutionary relationship with the low-density-lipoprotein receptor.
The very-low-density-lipoprotein receptor (VLDLR) is a recently described lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor (LDLR). This receptor has been suggested to be important for the metabolism of apoprotein-E-containing triacylglycerol-rich lipoproteins, such as very-low-density-lipoprotein (VLDL), beta-migrating VLDL and intermediate-density lipoprotein. cDNA clones that code for the VLDLR were isolated from a mouse heart cDNA library. The deduced amino acid sequence predicts a mature protein of 846 amino acids preceded by a 27-residue signal peptide. Three mRNA species for the VLDLR with sizes of 3.9, 4.5 and 7.9 kilobases were present in high concentration in heart and muscle, which utilize triacylglycerols as an energy source. VLDLR mRNA is also detected in decreasing amounts in kidney, brain, ovary, testis, lung and adipose tissue. It is essentially absent in liver and small intestine. The amino acid sequence of the VLDLR is highly conserved among rabbit, human and mouse. VLDLR contains five structural domains very similar to those in LDLR, except that the ligand-binding domain in VLDLR has an eightfold repeat instead of a sevenfold repeat in LDLR. Sequence conservation among animal species is much higher for the VLDLR than the LDLR. Sequences of the VLDLR from three vertebrate species and the LDLR from five vertebrate species were aligned and a phylogenetic tree was reconstructed. Although both receptors contain five domains and share amino acid sequence similarity, our computations showed that they diverged before the divergence between mammals and amphibians. In addition, sequence comparison of both receptor sequences suggests that the rabbit is evolutionarily closer to man than to the mouse. These results are consistent with the hypothesis that the VLDLR and the LDLR have evolved from a common ancestral gene to play distinct roles in lipoprotein metabolism and that the metabolic handling of triacylglycerol by the body via the VLDLR is a highly conserved mechanism.


In Vivo Mechanisms of Intestinal Drug Absorption from Aprepitant Nanoformulations.
Over recent decades there has been an increase in the proportion of BCS class II and IV drug candidates in industrial drug development. To overcome the biopharmaceutical challenges associated with the less favorable properties of solubility and/or intestinal permeation of these substances, the development of formulations containing nanosuspensions of the drugs has been suggested. The intestinal absorption of aprepitant from two nanosuspensions (20 μM and 200 μM total concentrations) in phosphate buffer, one nanosuspension (200 μM) in fasted-state simulated intestinal fluid (FaSSIF), and one solution (20 μM) in FaSSIF was investigated in the rat single-pass intestinal perfusion model. The disappearance flux from the lumen (Jdisapp) was faster for formulations containing a total concentration of aprepitant of 200 μM than for those containing 20 μM, but was unaffected by the presence of vesicles. The flux into the systemic circulation (Japp) and, subsequently, the effective diffusion constant (Deff) were calculated using the plasma concentrations. Japp was, like Jdisapp, faster for the formulations containing higher total concentrations of aprepitant, but was also faster for those containing vesicles (ratios of 2 and 1.5). This suggests that aprepitant is retained in the lumen when presented as nanoparticles in the absence of vesicles. In conclusion, increased numbers of nanoparticles and the presence of vesicles increased the rate of transport and availability of aprepitant in plasma. This effect can be attributed to an increased rate of mass transport through the aqueous boundary layer (ABL) adjacent to the gut wall.


[Formation and accumulation of myelin bodies and other membrane structures in the arterial wall in man in atherosclerosis].
Unaltered areas and fibrolipid plaques of various human arteries were examined electronmicroscopically. Myelin bodies were found to be produced by smooth-muscle cells of the intima and media of unaltered parts of the arterial wall. The formation of myelin bodies by smooth-muscle cells significantly increases in the fibrolipid plaques. Myelin bodies are frequently located in the cytoplasm matrix of altered smooth-muscle cells, in the areas of myofilament lysis. They are also found within mytochondria and in the cystern lumina of the granular cytoplasmatic reticulum. The accumulation of membranous structures in the fibrolipid plaques results from myelin-body production by smooth-muscle cells and vacuoles and vesicules of a varying size.


Spontaneous resolution of subdural hematoma. MRI findings.
A 33-year-old man suffered a traumatic subdural hematoma with complete spontaneous resolution, as demonstrated by computed tomography scanning and magnetic resonance imaging. After resolution, there was obliteration of the subarachnoid space on the affected side, giving rise to relative dilation of the subarachnoid space over the uninvolved convexity. A resolved subdural hematoma should be considered in the differential diagnosis of such an asymmetry.


Asprosin, visfatin and subfatin as new biomarkers of obesity and metabolic syndrome.
Metabolic syndrome (MetS) and obesity are important public health problems associated with adipose tissue mass. Asprosin, visfatin, and subfatin are new members of which fate in MetS and obesity has not been fully revealed yet. Thus, this study was to investigate the association between asprosin, visfatin, subfatin, and biochemical values, demographic data, and body composition measurement values in MetS patients with and without obesity. Blood samples were taken from a total of 90 people, including 31 MetS patients with obesity, 29 MetS patients without obesity, and 30 healthy (control). Asprosin, visfatin, and subfatin were studied by the ELISA method. There was a negative correlation between asprosin and Body Mass Index (BMI) in the MetS + Obese group. The correlations between asprosin and urea and fasting insulin (FI) levels in the MetS group were positive and statistically significant (p < 0.05). While there was a statistically significant negative correlation (p < 0.05) between visfatin and BMI in the MetS + Obese group, the correlation with waist circumference in the MetS + Obese and MetS groups was statistically significant and negative (p < 0.05). There was a statistically significant negative relationship (p < 0.05) between aspartate aminotransferase value and visfatin. The results between visfatin values and asprosin and subfatin in all groups were significant (p < 0.05). There is a direct relationship between circulating amounts of asprosin, visfatin, and subfatin hormones and age, weight, height, diastolic blood pressure, high-density lipoprotein-cholesterol, aspartate aminotransferase, alanine transaminase, and creatinine. Therefore, asprosin, visfatin, and subfatin hormones are the new biomarkers of metabolic turbulence.


Vitis vinifera peel and seed gold nanoparticles exhibit chemopreventive potential, antioxidant activity and induce apoptosis through mutant p53, Bcl-2 and pan cytokeratin down-regulation in experimental animals.
Several studies suggest surface modifications of gold nanoparticles (AuNPs) by capping agents or surface coatings could play an important role in biological systems, and site directed delivery. The present study was carried out to assess the antioxidant and apoptotic activities of the Vitis vinifera peel and seed gold nanoparticles in experimentally induced cancer in Swiss albino mice. 12-dimethylbenz [a] anthracene (DMBA) (single application) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (thrice a week) were applied on the dorsal area of the skin to induce skin papillomagenesis in Swiss albino mice for 16 weeks. Gold nanoparticles were synthesized using Vitis vinifera peel and seed aqueous extracts and characterized by Transmission electron microscopic (TEM) analyses. On topical application, peel and seed gold nanoparticles demonstrated chemopreventive potential by significantly (p<0.05) reducing the cumulative number of tumors while increasing the antioxidant enzyme activities in the gold nanoparticles treated mice. The down-regulated expression of mutant p53, Bcl-2 and the levels of pan-cytokeratins might have facilitated the process of apoptosis in the chemical carcinogenesis process. The results were supported by the histopathological evaluation which exhibited mild dysplasia and acanthosis in the skin tissues of Vitis vinifera peel and seed AuNPs treated mice. Based on the present study, the chemopreventive action of Vitis vinifera peel and seed AuNPs is probably due to its ability to stimulate the antioxidant enzymes within the cells and suppressed abnormal skin cell proliferation that occurred during DMBA-induced skin papillomagenesis.


Ipsilateral femoral neck and shaft fractures: complications and their treatment.
An ipsilateral femoral neck fracture occurs in approximately 6% to 9% of all femoral shaft fractures. Despite this relatively common presentation, decision-making often is difficult. Furthermore, the risk for complications is greater in the treatment of this combination injury pattern than for single-level fractures. A retrospective review of the authors' large trauma database revealed 13 patients who had healing complications develop after their index surgical procedure. Six of the eight (75%) femoral neck nonunions occurring in these 13 patients developed after the use of a second generation, reconstruction-type intramedullary nail. Factors contributing to nonunion of the femoral shaft were the presence of an open fracture, use of an unreamed, small diameter intramedullary nail, and prolonged delay to weightbearing. The femoral neck nonunions healed after either valgus intertrochanteric osteotomy (seven patients) or compression hip screw fixation (one patient). The femoral shaft nonunion proved more difficult than expected to treat with some patients with femoral shaft nonunions requiring more than one operative procedure to achieve union. Lag screw fixation of the femoral neck fracture and reamed intramedullary nailing for shaft fracture stabilization were associated with the fewest complications. Therefore, this approach is recommended as the treatment of choice.


Mechanistic Study of Glucose Photoreforming over TiO2-Based Catalysts for H2 Production.
Glucose is a key intermediate in cellulose photoreforming for H2 production. This work presents a mechanistic investigation of glucose photoreforming over TiO2 and Pt/m-TiO2 catalysts. Analysis of the intermediates formed in the process confirmed the α-scission mechanism of glucose oxidation forming arabinose (Cn-1 sugar) and formic acid in the initial oxidation step. The selectivity to sugar products and formic acid differed over Pt/TiO2 and TiO2, with Pt/TiO2 showing the lower selectivity to formic acid due to enhanced adsorption/conversion of formic acid over Pt/TiO2. In situ ATR-IR spectroscopy of glucose photoreforming showed the presence of molecular formic acid and formate on the surface of both catalysts at low glucose conversions, suggesting that formic acid oxidation could dominate surface reactions in glucose photoreforming. Further in situ ATR-IR of formic acid photoreforming showed Pt-TiO2 interfacial sites to be key for formic acid oxidation as TiO2 was unable to convert adsorbed formic acid/formate. Isotopic studies of the photoreforming of formic acid in D2O (with different concentrations) showed that the source of the protons (to form H2 at Pt sites) was determined by the relative surface coverage of adsorbed water and formic acid.


[Laparoscopic partial nephrectomy for renal leiomyoma: a case report].
A 60-year-old man visited our hospital with a complaint of right renal incidentaloma which was pointed out on abdominal ultrasonography for a medical check-up. Abdominal computed tomography showed a renal tumor in the right kidney, which was a slightly high-dense relative to the renal parenchyma and was enhanced in the arterial phase. The tumor had grown gradually from 1.4 to 1.7 cm in diameter. After the observation for 4 years, he underwent pure laparoscopic non-ischemic partial nephrectomy using a microwave tissue coagulator. Histological examination of the specimen revealed a leiomyoma of the kidney. This is the 5th case of successful laparoscopic partial nephrectomy for renal leiomyoma in Japan within the retrieved references.


The failure of theories of personhood.
The belief persists in philosophy, religion, science, and popular culture that some special cognitive property of persons like self-consciousness confers a unique moral standing. However, no set of cognitive properties confers moral standing, and metaphysical personhood is not sufficient for either moral personhood or moral standing. Cognitive theories all fail to capture the depth of commitments embedded in using the language of "person." It is more assumed than demonstrated in these theories that nonhuman animals lack a relevant form of self-consciousness or its functional equivalent. Although nonhuman animals are not plausible candidates for moral personhood, humans too fail to qualify as moral persons if they lack one or more of the conditions of moral personhood. If moral personhood were the sole basis of moral rights, then these humans would lack rights -- and precisely for the reasons that nonhuman animals would.


Should a school honor a student's DNR order? An educator responds: a school's interest in denying the request.
My goal in this commentary is to try to construct a picture of the interests of school officials in considering the request of S.A. and her family. It is not clear from the case presentation whether one or more administrators were responsible for the decision not to honor S.A.'s request; I will call the decision maker "ADMIN," who may be regarded as an individual or a corporate body. I will try to make sense of ADMIN's decision by exploring some plausible lines of argument for it that seem worthy of consideration, even though I may not accept any or all of them....


Oxygen saturation targets for children with respiratory distress: a systematic review.
In children with respiratory distress, supplemental oxygen is indicated at peripheral oxygen saturation (SpO2) thresholds of 90-94%. However, these thresholds are poorly studied. We conducted a systematic review to summarise the existing evidence for SpO2 thresholds in children with respiratory distress. Electronic databases and registries were searched for original articles published from 1 January 2010 to 7 January 2022 comparing two or more SpO2 thresholds in children with respiratory distress. Primary outcomes were safety, including mortality, neurocognitive outcomes and readmissions, and effectiveness, including admission rate and length of hospital stay. Methodological appraisal was performed using the Cochrane Risk of Bias 2 (RoB-2) or Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) tools. Results were narratively synthesised. We retrieved 3384 results; seven studies were included. Lower thresholds ranged from 80% to 92% and were compared with higher thresholds ranging from 92% to 94%. Studies were highly heterogeneous in setting, design, population and outcomes. Risk of bias varied from low to high. Lower SpO2 thresholds had equivalent mortality, neurocognitive outcomes and readmissions or re-attendance to healthcare to higher thresholds. Lower SpO2 thresholds showed a significant decrease in admission rates by up to 40% and shortened hospitalisation duration by 10-18 h. The current SpO2 thresholds of 90-94% in children with respiratory distress may be too high, which could lead to unnecessary hospitalisations and prolonged hospitalisation duration. SpO2 thresholds as low as 88% are potentially safe in children with respiratory distress and may reduce hospitalisation rates and length of stay. However, high-quality evidence is needed to support this.


Quality assessment of routine brain imaging at 0.55 T: initial experience in a clinical workflow.
The purpose of this study was to assess the quality of clinical brain imaging in healthy subjects and patients on an FDA-approved commercial 0.55 T MRI scanner, and to provide information about the feasibility of using this scanner in a clinical workflow. In this IRB-approved study, brain examinations on the scanner were prospectively performed in 10 healthy subjects (February-April 2022) and retrospectively derived from 44 patients (February-July 2022). Images collected using the following pulse sequences were available for assessment: axial DWI (diffusion-weighted imaging), apparent diffusion coefficient maps, 2D axial fluid-attenuated inversion recovery images, axial susceptibility-weighted images (both magnitude and phase), sagittal T1 -weighted (T1w) Sampling Perfection with Application Optimized Contrast images, sagittal T1w MPRAGE (magnetization prepared rapid gradient echo) with contrast enhancement, axial T1w turbo spin echo (TSE) with and without contrast enhancement, and axial T2 -weighted TSE. Two readers retrospectively and independently evaluated image quality and specific anatomical features in a blinded fashion on a four-point Likert scale, with a score of 1 being unacceptable and 4 being excellent, and determined the ability to answer the clinical question in patients. For each category of image sequences, the mean, standard deviation, and percentage of unacceptable quality images (<2) were calculated. Acceptable (rating ≥ 2) image quality was achieved at 0.55 T in all sequences for patients and 85% of the sequences for healthy subjects. Radiologists were able to answer the clinical question in all patients scanned. In total, 50% of the sequences used in patients and about 60% of the sequences used in healthy subjects exhibited good (rating ≥ 3) image quality. Based on these findings, we conclude that diagnostic quality clinical brain images can be successfully collected on this commercial 0.55 T scanner, indicating that the routine brain imaging protocol may be deployed on this system in the clinical workflow.


When Not to Go SOLO? Contraindications Based on Implant Experience.
Because of the design and specific implantation technique of the stentless Freedom SOLO bioprosthesis, patient selection is crucial. The aim of the study was to discuss the contraindications to this prosthesis based on the authors' implant experience. Between April 2005 and February 2015, one surgeon at the authors' center performed 292 aortic valve replacements using a bioprosthesis, with the initial intention of implanting a SOLO valve in every patient. A search was conducted for all of these patients and data collected on whether a SOLO valve was used, or not. A SOLO valve was implanted in 238 patients (82%), and a stented bioprosthesis in 54 (18%). The predominant reasons not to implant a SOLO valve were asymmetric commissures (26%) and a large aortic annulus (24%). Only one patient had structural valve deterioration, and none of the patients had to undergo reoperation because of aortic valve insufficiency or paravalvular leakage. Asymmetric commissures, large aortic annulus (>27 mm), calcified aortic sinuses, dilated sinotubular junction, aberrant location of coronary ostia and whenever the stent of a stented bioprosthesis is useful, were contraindications to implant a SOLO valve. When these contraindications were taken into account, a very good durability could be achieved with the SOLO valve during mid-term follow up.


False detection of Plasmodium falciparum sporozoites in Anopheles marshallii group mosquitoes.
A study was conducted to determine the role of members of the Anopheles funestus group in malaria transmission in the Mpumalanga Province, in the northeastern region of South Africa. Female anopheline mosquitoes were collected between January 1996 and November 1997 by means of human landing catches and tested for salivary gland Plasmodium falciparum infections by means of the enzyme-linked immunosorbent assay (ELISA) method with PF2A10 antibodies. Infection rates from April and May 1997 collections were 3.73% and 19.4%, respectively. None of the nonimmune collectors became infected with malaria. The ELISA-positive mosquitoes were tested with a polymerase chain reaction (PCR) malaria detection assay based on sequence variation present in the small subunit ribosomal RNA gene. Only 1.09% of ELISA-positive mosquitoes were PCR-positive for malaria. Initially, all mosquitoes were assumed to belong to the An. funestus group but subsequent molecular taxonomy showed this assumption to be false. The use of a single-strand conformation polymorphism (SSCP) assay revealed only 1 member of the An. funestus group, An. rivulorum. All other specimens produced banding patterns not seen before. Those samples were identified morphologically as An. demeilloni and An. marshallii s.l. These 2 species are not recognized malaria vectors and thus it is possible that the ELISA results are misleading.


Siblings' voices: A prospective investigation of experiences with a dying child.
Sibling relationships reflect a unique childhood bond, thus the impact on a sibling when a child is seriously ill or dying is profound. We conducted a prospective, longitudinal, qualitative study over 2 years using interpretive descriptive methodology to understand siblings' perspectives when a brother or sister was dying at home or in hospital. The insights from the 10 siblings revealed complex experiences, both personal and with the ill child, their families, and peers. These experiences were paradoxically sources of strain and of support, revealing the importance of validation and normalization in assisting siblings to successfully navigate the experience.


Primary structure of peptides and ion channels. Role of amino acid side chains in voltage gating of melittin channels.
Melittin produces a voltage-dependent increase in the conductance of planar lipid bilayers. The conductance increases when the side of the membrane to which melittin has been added (cis-side) is made positive. This paper reports observations on the effect of modifying two positively charged amino acid residues within the NH2-terminal region of the molecule: lysine at position 7 (K7), and the NH2-terminal glycine (G1). We have synthesized melittin analogues in which K7 is replaced by asparagine (K7-N), G1 is blocked by a formyl group (G1-f), and in which both modifications of the parent compound were introduced (G1-f, K7-N). The time required to reach peak conductance during a constant voltage pulse was shorter in membranes exposed to the analogues than in membranes modified by melittin. The apparent number of monomers producing a conducting unit for [K7-N]-melittin and [G1-f]-melittin, eight, was found to be greater than the one for [G1-f], K7-N]-melittin and for melittin itself, four. The apparent gating charge per monomer was less for the analogues, 0.5-0.3 than for melittin, one. Essentially similar results were obtained with melittin analogues in which the charge on K7 or G1 or both was blocked by an uncharged N-linked spin label. These results show that the positive charges in the NH2-terminal region of melittin play a major but not exclusive role in the voltage gating of melittin channels in bilayers.


Seungmagalgeun-Tang, a Traditional Herbal Formula, Alleviates Skin Inflammation and Depression-Like Behavior in Atopic Dermatitis Mice under Sleep Deprivation Conditions.
Atopic dermatitis (AD) is a common inflammatory skin disease, which can be worsened under sleep deprivation (SD) conditions. This study investigated the efficacy and the mechanism of action of the traditional herbal formula Seungmagalgeun-tang (SMGGT) on the inflammation and behavioral changes in a mouse model of AD exposed to SD. SMGGT decreased levels of IgE, TNF-α, IL-4, IL-13, and mast cell infiltration and reduced the expression of CD3 in the mouse skin. SMGGT also reversed the SD-induced increase in corticosterone and decrease in melatonin level. Furthermore, SMGGT reduced the immobility time in the tail suspension test significantly. HaCaT cells and HMC-1 cells were used to investigate the effects of SMGGT on cell signaling pathways. In TNF-α/IFN-γ (TI) treated HaCaT cells, SMGGT reduced production of TARC/CCL17 and MDC/CCL22 and suppressed the p38 MAPK, STAT1, and NF-κB pathways. In substance P (SP)/CRH-stimulated HMC-1 cells, SMGGT decreased VEGF production and inhibited ERK phosphorylation. Network pharmacology and molecular docking analysis revealed that puerarin and paeoniflorin might contribute to the effects of SMGGT by targeting several AD-related molecules and pathways. Puerarin and paeoniflorin exerted anti-inflammatory effects by decreasing production of MDC/CCL22 and IL-6 in TI-treated HaCaT cells and VEGF production in SP/CRH-stimulated HMC-1 cells. This study suggests that SMGGT with puerarin and paeoniflorin as main bioactive components alleviates skin inflammation and depression-like behavior in a sleep-deprived mouse model of AD.


Regulation of arsenite toxicity in lettuce by pyrite and glutamic acid and the related mechanism.
Compared with the effect of a single substance on arsenic plant toxicity, the effect of coexisting pyrite and natural organic matter can better reflect actual environmental conditions. In this study, the interaction between pyrite and glutamic acid in arsenite solution was explored, the influence of pyrite and glutamic acid on arsenite plant toxicity was evaluated, and the metabolic regulation mechanism of pyrite and glutamic acid on the arsenite phytotoxic effect was clarified by metabolomics analysis. Combined pyrite and glutamic acid treatment fixed more arsenic by forming chemical bonds such as AsS, AsO, and As-O-OH in culture solution and reduced inorganic arsenic levels in plants. Compared with glutamic acid alone and pyrite alone, the combined treatment reduced the inorganic arsenic concentration in plants by 4.7 % and 40.0 %, respectively. The combined treatment limited plant ROS accumulation and maintained the leaf chlorophyll content by increasing SOD synthesis. Compared with the effect of As(III) alone, the chlorophyll content increased by 15.1-21.0 % on average under the combined treatment. The combined treatment promoted the absorption of Ca, Cu, Fe, Mo and Zn in lettuce, enhanced plant adaptation to As(III) and significantly improved plant nutritional quality. Compared with glutamic acid alone, the combined treatment increased the VC, fiber and protein contents by 128.9 %, 202.8 % and 36.7 %, respectively. Metabolomics analysis indicated that in the combined treatment group, the upregulation of tyrosine, pyruvate and N metabolism increased the plant chlorophyll content. The upregulation of S metabolism increases VC synthesis in plants and inhibits ROS accumulation, thus maintaining normal plant growth and development. The upregulation of glutathione and glycine metabolism enhances plant stress resistance. This study will provide a new way to scientifically and rationally evaluate the ecological risk of arsenic and regulate its toxicity.


Comparison of acute phase protein and hemodynamic variables in dogs undergoing video-assisted thoracoscopic vs. open pneumonectomy.
It has been demonstrated that video-assisted thoracoscopic surgery (VATS) is feasible and safe in humans and animal models. The aim of the present study was to compare the surgical outcome using VATS with that of the standard transthoracic approach for pneumonectomy in dogs, to determine the acute-phase reaction in VATS pneumonectomy, and to analyze the difference between VATS and the standard transthoracic approach. A total of 14 dogs were divided into two groups (n=7); one group underwent VATS and the other group underwent a transthoracic pneumonectomy. Pre-, intra- and post-operative physiologic parameters were monitored, in addition to the blood cell count and serum acute-phase protein (APP) concentrations. The APP and hemodynamic changes between the two approaches were analyzed. Mean surgical time in the VATS group (176.7 min) was significantly longer compared with the open group (132.4 min). All APP concentrations were significantly increased at day 1 postoperation and gradually decreased to preoperative concentrations. The serum concentration of C-reactive protein on day 3 and the white blood cell count on day 1 were significantly higher following surgery in the open group compared with the VATS group (P<0.05). No differences were observed in the physiological parameters between the two groups. Although VATS took longer, animals experienced smaller incision and less stress. Therefore, the VATS approach was satisfactory for total pneumonectomy.


Omphalocele and epigastric heteropagus: implications and treatment.
In heteropagus twins, the parasitic twin is incompletely formed which is attached to the autosite. We report a case of epigastric heteropagus twins with omphalocele. The parasite had two lower limbs, a rudimentary upper limb, genitalia with developed phallus and scrotum but absent testis. An omphalocele was present just below the attachment of the parasitic twin. A single kidney with ureter and a bladder filled with urine seen during exploration. The parasite bowel was attached to a sleeve of liver tissue from the autosite within the omphalocele sac and this connection was also the main source of its blood supply. Less than 20 cases of omphalocele with EH have been reported previously. The thin sac with underlying adherent bowel led us to go ahead with surgery in the neonatal period for both, excision of epigastric heteropagus and omphalocele repair. The rectus sheath around the omphalocele sac helped in the final wound closure.


Swallowing function and upper airway sensation in obstructive sleep apnea.
The objective of this study was to determine whether impaired upper airway (UA) mucosal sensation contributes to altered swallowing function in obstructive sleep apnea (OSA). We determined UA two-point discrimination threshold (2PDT) and vibratory sensation threshold (VST) in 15 men with untreated OSA and 9 nonapneic controls (CL). We then assessed swallowing responses to oropharyngeal fluid boluses delivered via a catheter. The threshold volume required to provoke swallowing and the mean latency to swallowing were determined, as was the phase of the respiratory cycle in which swallowing occurred [expressed as percentage of control cycle duration (%CCD)] and the extent of prolongation of the respiratory cycle after swallowing [inspiratory suppression time (IST)]. 2PDT and VST were significantly impaired in OSA patients compared with CL subjects. 2PDT was positively correlated with swallowing latency and threshold volume in CL subjects, but not in OSA patients. Threshold volume did not differ between the groups [median value = 0.1 ml (95% confidence interval = 0.1-0.2) for OSA and 0.15 ml (95% confidence interval = 0.1-0.16) for CL], whereas swallowing latency was shorter for OSA patients [3.3 (SD 0.7) vs. 3.9 (SD 0.8) s, P = 0.04]. %CCD and IST were similar for OSA patients and CL subjects. However, among OSA patients there was a significant inverse relation between VST and IST. These findings suggest that oropharyngeal sensory impairment in OSA is associated with an attenuation of inhibitory modulating inputs to reflex and central control of UA swallowing function.


Effects of age and alcohol abuse on pattern reversal visual evoked potentials.
The Pattern Reversal Visual Evoked Potential (PRVEP) was recorded in normal subjects and alcoholics. The recordings were made from the patients during withdrawal and repeated after three weeks of detoxification. It was found that the N76 latency was longer in the alcoholic patient in the withdrawal phase than in the normal subjects. The latency returned to normal range after detoxification in younger alcoholic patients but did not in the older alcoholics. The age-related increase in the N76 latency in the alcoholic patients was similar to that in normal subjects but more exaggerated. For alcoholics, the age-related change in the N76 latency reached significance, but was only a trend in normal subjects. The P100 latency demonstrated significant age-related change, but far less modification related to the alcoholism than the N76 latency. It is unclear at present whether the failure of the latency to return to normal in older patients after detoxification is related to longer periods of excessive drinking, or to a particular vulnerability of the older patients to continued use of alcohol.


An Interactive Module to Teach Common Biostatistical Tests to Learners in the Health Professions.
Biostatistics are ubiquitous in medicine, providing quantitative insights into trials and experiments that shape the healthcare field. Despite training in evidence-based medicine, medical students and residents struggle to master biostatistical concepts and apply biostatistics to appraise research. There are limited resources available for students to quickly and cost-effectively learn biostatistical tests. From this problem, a two-part biostatistical educational module was created using Rise Articulate 360® software, an interactive module platform. The study aimed to assess the effectiveness of an educational biostatistics module's ability to improve learners' knowledge and application of commonly used biostatistical tests, as well as their confidence in biostatistics. Each part of the module contained five biostatistical test tutorials. Each biostatistical test was explained, as well as how the test was typically applied in healthcare. Knowledge acquisition, test application, and confidence regarding biostatistical tests were assessed using a pretest and a posttest. The module was completed by 33 first- and second-year medical students. Knowledge acquisition improved from a mean of 2.41 to 3.53 (P <= 0.001). Participants expressed that the biostatistical educational module was easy to use and improved both their confidence and knowledge of specific biostatistical tests. Most students found that the biostatistical educational module applied to their future work. In summary, our module was successful in exposing learners in the health professions to commonly used biostatistical tests and tests' applications to the medical literature and their future research. Biostatistics is a pillar of medical research and education, and students' mastery of the concept will prove to be of longitudinal valuable, whether they pursue careers as clinicians and/or researchers.


Complex Müllerian malformation: report of a case with a hypoplastic non-cavitated uterus and two rudimentary horns.
Various classifications have been used for congenital anomalies of the Müllerian system. We report a case of a previously unknown anomaly of the uterus, and propose its possible embryological causes. The patient presented with primary amenorrhoea and infertility, and during laparoscopy three distinct uterine horns were observed. The tubes were connected to the two most lateral horns, each juxtaposed to a normal ovary. The middle horn had a seemingly normal attachment to the right uterosacral ligament, whereas its attachment to the left uterosacral ligament appeared attenuated and less normal. Furthermore, the right horn was immediately attached to the middle horn, whereas the left horn was, like its ipsilateral uterosacral ligament, attached to the middle horn by a more attenuated, stretched fibrous bridge. Only the middle horn, with its uterosacral ligaments, had an attached, although obstructed, cervix. Ultrasonographic examination revealed no endometrium echogeneity in any of these uterine bulbs. No etiologic factors were noted in the patient's history; her mother denied known ingestion of estrogens or other drugs while carrying her daughter. The pathogenesis of this anomaly cannot be clearly defined, but may involve sequential embryological errors of duplication of the Müllerian tracts, failure of fusion of each set of the Müllerian tracts with expected failed canalization of each tract and, finally, agenesis of the medial horn of the left duplicated tracts.


Secretory proteins are delivered to the septin-organized penetration interface during root infection by Verticillium dahliae.
Successful infection of the host requires secretion of effector proteins to evade or suppress plant immunity. Secretion of effectors in root-infecting fungal pathogens, however, remains unexplored. We previously reported that Verticillium dahliae, a root-infecting phytopathogenic fungus, develops a penetration peg from a hyphopodium to infect cotton roots. In this study, we report that a septin ring, requiring VdSep5, partitions the hyphopodium and the invasive hypha and form the specialized fungus-host interface. The mutant strain, VdΔnoxb, in which NADPH oxidase B (VdNoxB) is deleted, impaired formation of the septin ring at the hyphal neck, indicating that NADPH oxidases regulate septin ring organization. Using GFP tagging and live cell imaging, we observed that several signal peptide containing secreted proteins showed ring signal accumulation/secretion at the penetration interface surrounding the hyphal neck. Targeted mutation for VdSep5 reduced the delivery rate of secretory proteins to the penetration interface. Blocking the secretory pathway by disrupting the vesicular trafficking factors, VdSec22 and VdSyn8, or the exocyst subunit, VdExo70, also arrested delivery of the secreted proteins inside the hyphopodium. Reduced virulence was observed when cotton roots were infected with VdΔsep5, VdΔsec22, VdΔsyn8 and VdΔexo70 mutants compared to infection with the isogenic wild-type V592. Taken together, our data demonstrate that the hyphal neck is an important site for protein secretion during plant root infection, and that the multiple secretory routes are involved in the secretion.


Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients.
Few studies have examined the lung virome in health and disease. Outcomes of lung transplantation are known to be influenced by several recognized respiratory viruses, but global understanding of the virome of the transplanted lung is incomplete. To define the DNA virome within the respiratory tract following lung transplantation we carried out metagenomic analysis of allograft bronchoalveolar lavage (BAL), and compared with healthy and HIV+ subjects. Viral concentrates were purified from BAL and analyzed by shotgun DNA sequencing. All of the BAL samples contained reads mapping to anelloviruses, with high proportions in lung transplant samples. Anellovirus populations in transplant recipients were complex, with multiple concurrent variants. Quantitative polymerase chain reaction quantification revealed that anellovirus sequences were 56-fold more abundant in BAL from lung transplant recipients compared with healthy controls or HIV+ subjects (p < 0.0001). Anellovirus sequences were also more abundant in upper respiratory tract specimens from lung transplant recipients than controls (p = 0.006). Comparison to metagenomic data on bacterial populations showed that high anellovirus loads correlated with dysbiotic bacterial communities in allograft BAL (p = 0.008). Thus the respiratory tracts of lung transplant recipients contain high levels and complex populations of anelloviruses, warranting studies of anellovirus lung infection and transplant outcome.


Evidence that the immunosuppressive effects of FK506 and cyclosporine are identical.
The fungal metabolite FK506 was discovered because it shared an important property, the ability to inhibit production of IL-2, with another well-known immunosuppressive fungal metabolite, CsA. FK506 has, since its isolation, also been shown to share other immunosuppressive effects with CsA. This study was performed to further investigate the in vitro immunological properties of FK506, in comparison with and in combination with CsA, to evaluate the plausibility that their mechanisms of action were identical or similar, in spite of their different molecular structures. The ability to inhibit several responses of human peripheral blood lymphocytes to mitogenic and alloantigenic stimulation was explored. Synergistic effects of the two drugs were extensively studied, since this would provide additional information regarding their mechanisms of action. Also, similar immunosuppressive properties would enable the use of the two drugs in combination. We found that FK506 and CsA had very similar mechanisms of action and additive effects were recorded.


In vitro and in vivo model systems for studying enteropathogenic Escherichia coli infections.
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) belong to a group of bacteria known as attaching and effacing (A/E) pathogens that cause disease by adhering to the lumenal surfaces of their host's intestinal epithelium. EPEC and EHEC are major causes of infectious diarrhea that result in significant childhood morbidity and mortality worldwide. Recent advances in in vitro and in vivo modeling of these pathogens have contributed to our knowledge of how EPEC and EHEC attach to host cells and subvert host-cell signaling pathways to promote infection and cause disease. A more detailed understanding of how these pathogenic microbes infect their hosts and how the host responds to infection could ultimately lead to new therapeutic strategies to help control these significant enteric pathogens.


Optical and microstructural properties of ZnO/TiO2 nanolaminates prepared by atomic layer deposition.
ZnO/TiO2 nanolaminates were grown on Si (100) and quartz substrates by atomic layer deposition at 200°C using diethylzinc, titanium isopropoxide, and deionized water as precursors. All prepared multilayers are nominally 50 nm thick with a varying number of alternating TiO2 and ZnO layers. Sample thickness and ellipsometric spectra were measured using a spectroscopic ellipsometer, and the parameters determined by computer simulation matched with the experimental results well. The effect of nanolaminate structure on the optical transmittance is investigated using an ultraviolet-visible-near-infrared spectrometer. The data from X-ray diffraction spectra suggest that layer growth appears to be substrate sensitive and film thickness also has an influence on the crystallization of films. High-resolution transmission electron microscopy images show clear lattice spacing of ZnO in nanolaminates, indicating that ZnO layers are polycrystalline with preferred (002) orientation while TiO2 layers are amorphous.


Nanoscale coatings on wood: polyelectrolyte adsorption and layer-by-layer assembled film formation.
Surface chemistry of wood is based on the exposed surface that is the combination of the intact and cut cellular wall material. It is inherently complex and changes with processing history. Modification of wood surfaces through noncovalent attachment of amine containing water soluble polyelectrolytes provides a path to create functional surfaces in a controlled manner. Adsorption of polyethylenimine (PEI) and polydiallydimethylammonium chloride (PDDA) to wood was quantified as a function of solution conditions (pH and ionic strength). Polycation adsorption was maximized under basic pH without the addition of electrolyte. Added salt either had marginal influence or decreased adsorption of polycation, indicating interactions are strongly influenced by Coulombic forces. PEI adsorption could be modeled by both a Langmuir and Freundlich equations, although the wood surface is known to be heterogeneous. After adsorption of polycations, layer-by-layer assembled films were created on the wood surface. Layered films masked ultrastructural features of the cell wall, while leaving the microscale features of wood (cut lumen walls and openings) evident. These findings revealed for the first time that nanoscale films on wood can be deposited without changing the microscopic and macroscopic texture. Functionalized wood surfaces created by nanoscale films may have a future role in adhesives systems for wood composites, wood protection, and creating new functional features on wood.


Predation on transmission stages reduces parasitism: sea anemones consume transmission stages of a barnacle parasite.
While parasites serve as prey, it is unclear how the spatial distribution of parasite predators provides transmission control and influences patterns of parasitism. Because many of its organisms are sessile, the rocky intertidal zone is a valuable but little used system to understand spatial patterns of parasitism and elucidate the underlying mechanisms driving these patterns. Sea anemones and barnacles are important space competitors in the rocky intertidal zone along the Pacific coast of North America. Anemones are voracious, indiscriminate predators; thus, they may intercept infectious stages of parasites before they reach a host. We investigate whether a sea anemone protects an associated barnacle from parasitism by Hemioniscus balani, an isopod parasitic castrator. At Coal Oil Point, Santa Barbara, California USA, 29% of barnacles were within 1 cm from an anemone at the surveyed tidal height. Barnacles associated with anemones had reduced parasite prevalence and higher reproductive productivity than those remote from sea anemones. In the laboratory, anemones readily consumed the transmission stage of the parasite. Hence, anemone consumption of parasite transmission stages may provide a mechanism by which community context regulates parasite prevalence at a local scale. Our results suggest predation may be an important process providing parasite transmission control.


Paradoxical Leadership and Involvement in Creative Task via Creative Self-Efficacy: A Moderated Mediation Role of Task Complexity.
Modern organizational environments encounter serious competition and paradoxical situations. This study discusses the effect of paradoxical leadership on overcoming competitive and paradoxical situations happening in the Korean workplace. More specifically, it investigates the dynamic relationship between paradoxical leadership and involvement in creative tasks in a Korean context and examines whether creative self-efficacy positively mediates this relationship. Our research design addresses the moderating role and moderated mediating role of task complexity in the relationship between paradoxical leadership and the involvement in creative tasks via creative self-efficacy. The main hypotheses were tested by using a cross-sectional design and administering questionnaires to 268 employees working in Korean firms. Empirical analysis revealed that paradoxical leadership is positively related to involvement in creative tasks and creative self-efficacy and that creative self-efficacy positively mediated the relationship between paradoxical leadership and involvement in creative tasks. Importantly, as the relationship between paradoxical leadership and creative self-efficacy depends on task complexity, the mediated relationship was effective under high task complexity. Uncovering the relationship between paradoxical leadership and involvement in creative tasks with the mediating role of creative self-efficacy and the moderated mediating role of task complexity can provide useful theoretical and managerial implications.