The effects of hydroalcoholic extract of Allium elburzense Wendelbo bulb on dexamethasone-induced dyslipidemia, hyperglycemia, and oxidative stress in rats.
Recent evidences have suggested the beneficial cardiovascular effects of some plants belonging to the genus Allium. The present study is an attempt to investigate the effects of hydroalcoholic extract of Allium elburzense bulb on dexamethasone-induced dyslipidemia in rats. Total phenolic content of A. elburzense bulb hydroalcoholic extract was determined using Folin-Ciocalteu method. Thirty-six male Wistar albino rats in 6 groups were studied. Group 1 (dyslipidemic control) received dexamethasone (10 mg/kg/day, s.c.) for 7 days, groups 2-4 (treated) received dexamethasone and simultaneously treated orally with 100, 200, or 400 mg/kg of A. elburzense extract, group 5 (normal control) received a single daily injection of normal saline (1 mL/kg, s.c.) and the vehicle orally, and group 6 (reference) received dexamethasone and atorvastatin (40 mg/kg) orally. At the end of experiment, blood glucose, lipid profile, and malondialdehyde (MDA) levels were assessed in serum samples. Livers were processed for histopathological examination. Total phenolic content of A. elburzense extract was estimated to be 33.52 ± 1.3% mg gallic acid equivalent/g of the dried plant extract. The plant extract significantly reduced serum blood glucose, triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and MDA levels and increased the high density lipoprotein-cholesterol level and also improved liver steatosis compared to the dyslipidemic control group. These results suggest the hydroalcoholic extract of A. elburzense bulb has anti-dyslipidemic, anti-hyperglycemic, and antioxidant effects on rats receiving high doses of dexamethasone.


Lifetime Prevalence of Victimization and Perpetration as Related to Men's Health: Clinical Insights.
Violence is a known risk factor for health problems. In this epidemiological study across 5,385 male patients, we investigate the prevalence of perpetrated violence, exposure to violence, their overlap and the relationship between violence, mental, and psychosomatic health, as well as adverse health behaviors, such as self-harming behavior and the consumption of drugs. Participants completed an anonymous questionnaire addressing violence experience (i.e., both expose and perpetration), age of victimization/perpetration, frequency, and perceived severity of violence exposure. We considered physical, psychological as well as sexual violence. Information on health status and adverse health behaviors complemented the data. Results showed that 48.4% of the sample reported having experienced violence (perpetration, victimization, or both). The victim-perpetrator overlap formed the largest group, in which the incidence of having experienced multiple types of violence was significantly higher compared to victims and perpetrators. The age-crime curve flattened more slowly with increasing age in this group. Although the perceived severity of exposure to violence is lower in the overlap group, its health status and adverse health behaviors were worse. Interventions should focus on this group since they constitute a burden for the healthcare system.


Human platelets express heat shock protein receptors and regulate dendritic cell maturation.
Immunizations using the endoplasmic reticulum-resident heat shock protein Gp96 induce specific immune responses. Specificity is based on the major histocompatibility complex class I-restricted cross-presentation of Gp96-associated peptides derived from endogenous proteins. Initiation of the immune response depends on the ability of Gp96 to induce the production of proinflammatory cytokines by macrophages and dendritic cells (DCs) and of their maturation in a fashion presumably independent of associated peptide. Both events are mediated by Gp96 receptors on antigen-presenting cells. It is known that Gp96 is released from cells at necrosis induced, for example, by virus infection. Although this event supports the efficient induction of immune responses, it might also interfere with processes that are susceptible to chronic inflammation, such as wound healing after tissue damage. Therefore, Gp96-mediated stimulation of the immune system requires tight regulation. Here we show that human thrombocytes specifically interact with Gp96 and that binding of Gp96 to platelets is enhanced more than 10-fold on activation by thrombin. Gp96 interferes with neither thrombin-induced platelet activation nor platelet aggregation. However, the presence of platelets during Gp96-mediated DC activation reduces the secretion of proinflammatory cytokines and the activation of DCs. This effect is independent of soluble platelet factors and cell-to-cell contact between DCs and thrombocytes. Thus, we provide evidence for a regulatory mechanism that neutralizes Gp96 molecules systemically, especially in the blood. This effect might be of significance in wounds in which chronic inflammation and immune responses against autoantigens have to be prevented.


Bovine Herpesvirus-4-Based Vector Delivering Peste des Petits Ruminants Virus Hemagglutinin ORF Induces both Neutralizing Antibodies and Cytotoxic T Cell Responses.
Peste des Petits Ruminants Virus (PPRV) is an extremely infective morbillivirus that primarily affects goats and sheep. In underdeveloped countries where livestock are the main economical resource, PPRV causes considerable economic losses. Protective live attenuated vaccines are currently available but they induce antibody responses similar to those produced in PPRV naturally infected animals. Effective vaccines able to distinguish between vaccinated and naturally infected animals are required to PPRV control and eradication programs. Hemagglutinin (H) is a highly immunogenic PPRV envelope glycoprotein displaying both hemagglutinin and neuraminidase activities, playing a crucial role in virus attachment and penetration. In this study, a recombinant Bovine Herpesvirus-4 (BoHV-4)-based vector delivering an optimized PPRV-Hemagglutinin expression cassette, BoHV-4-A-PPRV-H-ΔTK, was assessed in immunocompetent C57BL/6 mice. BoHV-4-A-PPRV-H-ΔTK-immunization elicited both cellular and humoral immune responses with specific T cell, cytotoxic T lymphocyte, and sero-neutralizing antibody against PPRV. These data suggest recombinant BoHV-4-A-PPRV-H-ΔTK as an effective vaccine candidate to protect against PPRV herd infection and potentially applicable for eradication programs.


Growth factors induce the improved cardiac remodeling in autologous mesenchymal stem cell-implanted failing rat hearts.
Therapeutically delivered mesenchymal stem cells (MSCs) improve ventricular remodeling. However, the mechanism underlying MSC cardiac remodeling has not been clearly determined. Congestive heart failure (CHF) was induced in rats by cauterization of the left ventricular free wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 d after injury. Ten weeks later, when compared with sham operation, CHF significantly increased nucleus mitotic index, capillary density, and expression of insulin-like growth factor 1, hepatocyte growth factor and vascular endothelial growth factor in the border zone (P<0.01) and decreased each of them in the remote myocardium (P<0.05 or P<0.01). MSC implantation in CHF dramatically elevated expression of these growth factors in the remote myocardium and further elevated their expression in the border zone when compared with CHF without MSC addition (P<0.05 or P<0.01). This was paralleled by a higher nucleus mitotic index and a significantly increased capillary density both in the remote myocardium and in the border zone, and by a lower percentage of area of collagen and a higher percentage of area of myocardium in the border zone (P<0.05 or P<0.01), and cardiac remodeling markedly improved. Autologous MSC implantation promoted expression of growth factors in rat failing myocardium, which might enhance cardiomyogenesis and angiogenesis, and improved cardiac remodeling.


Allelic differences in the brain-derived neurotrophic factor Val66Met polymorphism in late-life depression.
The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with cognitive and neuroimaging changes. The authors examined the relationship between this polymorphism and depression in an elderly sample, hypothesizing that the Met66 allele would be associated with late-life depression. A total of 245 elderly depressed white subjects and 94 elderly comparison white subjects completed clinical assessments and provided a blood sample for genotyping. Subjects were dichotomized as either homozygous for the Val66 allele or Met66 allele carriers. Gene frequencies were compared between groups, with separate analyses examining for differences in gene frequencies based on age of depression onset, family history, and depression history. Logistic regression models examined the relationship between genotype and depression after controlling for age, sex, and race. Depressed subjects were more likely to be Met66 allele carriers than were comparison subjects (38.8% versus 24.4%; chi(2) = 6.13, 1 df, p = 0.0133). This relationship remained significant after controlling for covariates (Wald chi(2) = 5.10, 1 df, p = 0.024; odds ratio: 1.92, 95% confidence interval: 1.09-3.38). There were no significant relationships between genotype and age of onset, number of episodes, or family history of depression. Met66 allele carriers have almost double the odds of having geriatric depression than do Val66 allele homozygotes. This polymorphism was unrelated to other clinical characteristics of depression in later life.


A novel in-situ Raman spectroscopic cell for aqueous geochemistry at the solid-liquid interface.
In-situ Raman spectroscopy has the potential to be a powerful technique for monitoring geochemical reactions at a solid-liquid interface in real time. In this article, we present the development and testing of an in-situ Raman spectroscopic cell, which can be used for reaction systems at moderate temperatures and pressure [<1000 psi (6.89 MPa), <100 °C, relevant to subsurface geologic systems] and can hold samples large enough for chemical mapping of heterogeneous rock surfaces. The system is validated by measuring the temperature-dependent conversion of gypsum to calcite over time. Near total conversion of gypsum to calcite on the mineral surface took 29 hours at room temperature and 150 minutes at 100 °C, corresponding to an 11.6-fold increase in the conversion rate. We anticipate that this cell can be an important tool in quantifying the rates of carbon mineralization relevant to geologic carbon sequestration, particularly for the elevated rates recently observed in mafic/ultramafic rocks.


Minimal Risk Level Derivation for Cadmium: Acute and Intermediate Duration Exposures.
The Agency for Toxic Substances and Disease Registry (ATSDR) lists cadmium as one of its priority hazardous substances. The agency conducted a comprehensive literature review of cadmium and used the information to develop a toxicological profile that identified the full range of health effects associated with exposure to cadmium. It included an assessment that identified screening levels, termed health guidance values or minimal risk levels (MRLs), below which adverse health effects are not expected. In this paper, we describe how MRLs for cadmium are derived. For the acute inhalation MRL, the traditional no observed adverse effect level or lowest observed adverse effect level (NOAEL/LOAEL) approach is used; for the oral intermediate MRL, the benchmark dose (BMD) approach is used. MRLs were developed for the most sensitive route-specific end points, other than mortality and cancer that were sufficiently supported and justified by the data. These included an acute duration (1-14 day exposure) inhalation MRL of 0.03 µg Cd/m3 for alveolar histiocytic infiltration and focal inflammation in alveolar septa and an intermediate duration (15-365 day exposure) oral MRL of 0.5 µg Cd/kg/day for decreased bone mineral density.


Fetal thrombocytopenia.
In idiopathic thrombocytopenic purpura, the low risk of fetal bleeding in the perinatal period does not justify routine cordocentesis. Platelet counts of second newborns correlates well with that of their siblings. In neonatal alloimmune thrombocytopenia, the initial platelet count at cordocentesis in the second trimester is low in the next pregnancy. Weekly high doses of intravenous gammaglobulin to the mother results in a rise of fetal platelet count in approximately 70% of cases and may protect the fetus against intracranial haemorrhage in cases without significant platelet rise. With the exception of cases with a prior infant with spontaneous fetal intracranial haemorrhage, the use of diagnostic fetal blood sampling to confirm neonatal alloimmune thrombocytopenia is controversial.


[Imaging of femur head necrosis using MR tomography].
Magnetic resonance tomography (MR) was used to examine the femoral heads of 20 normals and of 56 patients with diseases of the femoral head, including Perthe's disease (four cases), adult necrosis of the femoral head (39 cases) and pain of unknown cause (13 cases). Femoral head necrosis and Perthe's disease regularly produce reduced signal intensity. The localisation of the areas of necrosis can be determined accurately in the coronary and sagittal plane. In 11 femoral heads, necrosis could be demonstrated unequivocally by MR in the presence of normal radiographic findings. Follow-up of nine patients with negative MR findings and indefinite symptoms confirmed the absence of necrosis.


Infrared identification of the σ-complex of Cl-C6H6 in the reaction of chlorine atom and benzene in solid para-hydrogen.
The reaction of a chlorine atom with benzene (C6H6) is important in organic chemistry, especially in site-selective chlorination reactions, but its product has been a subject of debate for five decades. Previous experimental and theoretical studies provide no concrete conclusion on whether the product is a π- or σ-form of the Cl-C6H6 complex. We took advantage of the diminished cage effect of para-hydrogen (p-H2) to produce Cl in situ to react with C6H6 (or C6D6) upon photolysis of a Cl2/C6H6 (or C6D6)/p-H2 matrix at 3.2 K. The infrared spectrum, showing intense lines at 1430.5, 833.6, 719.8, 617.0, and 577.4 cm(−1), and several weaker ones for Cl-C6H6, and the deuterium shifts of observed new lines unambiguously indicate that the product is a 6-chlorocyclohexadienyl radical, i.e., the σ-complex of Cl-C6H6. Observation of the σ-complex rather than the π-complex indicates that the σ-complex is more stable in solid p-H2 at 3.2 K. The spectral information is crucial for further investigations of the Cl + C6H6 reaction either in the gaseous or solution phase.


Converging prescription brand shares as evidence of physician learning.
Within a drug category, there is an optimal brand the physician could choose to prescribe based on the patient's particular condition and characteristics. Physicians desire to prescribe the best brand for each patient for professional, moral, and legal reasons. Ideally, detailing provides information that supports this effort. This study finds that, over time, the proportion of prescriptions written for each brand moves toward a stable distribution--a convergence in which each brand's share in the category appears to match the proportion of prescription writing opportunities where the brand is the best choice for the patient. Detailing supports this convergence.


Development of the Evolve toothbrush: laboratory evaluations of gingival margin cleaning and subgingival access.
The Evolve toothbrush has been developed with three heads that adjust to the tooth shape with brushing. With the exertion of gentle pressure on the center head against the tooth cusps, the two outer heads bend and conform to the tooth anatomy at the gingival areas around each tooth. In preliminary clinical observations, decreased plaque and improved gingival appearance was observed after one and two weeks of unsupervised product use. The purpose of this laboratory research was to evaluate the ability of the Evolve toothbrush bristles to remove artificial plaque deposits at and around the gingival margin (Gingival Margin Cleaning, GMC), and to gain access into and remove artificial plaque deposits from under the gingival margin (Subgingival Access, SA) using standardized, published methods. In the first two laboratory studies conducted, two toothbrush products, the new Evolve and the standard American Dental Association toothbrush (ADA) were evaluated for GMC and SA. In the third assay, three toothbrushes, the Evolve, Oral-B CrossAction, and the Sonicare Elite, were evaluated for SA. Each toothbrush product group was evaluated for 24 assessments using clinical tooth brushing motions on posterior tooth shapes under wet brushing conditions. In all laboratory tests conducted, the Evolve toothbrush had significantly (p < 0.001) greater efficacy compared to the other toothbrushes tested. The Evolve toothbrush warrants further clinical evaluations as it is believed these future findings will further substantiate those of the initial testing, and demonstrate the Evolve's ability to help improve oral and overall health.


Alpha suppression over parietal electrode sites predicts decisions to trust.
Decisions to trust help form the basis of relationships and society yet little is known about their neurophysiology. We told participants they were playing a coin toss game with a trustworthy and an untrustworthy person and measured their neural activity with EEG as they decided whether to trust those fictitious interaction partners. Target people ostensibly correctly reported the outcome of a coin toss on 66% of trials. Behaviorally, participants probability matched and chose to trust the reported coin flips from each profile equally by the end of 100 trials. Electrophysiologically, there were reliable differences in the pattern of oscillatory activity in the alpha band (8-13Hz) over parietal electrode sites 1-3 s prior to their trust decisions. Specifically, for trustworthy profiles, there was greater alpha suppression for trust decisions vs. distrust decisions. Conversely, for untrustworthy profiles there was greater alpha suppression for distrust decisions vs. trust decisions. This differential activity (trust minus distrust) also predicted the number of trust decisions made. Our results indicate that the intentions to trust people form very early in the processing stream and manifest as alpha suppression over parietal cortex.


Enantioselective Synthesis of Ten-Membered Lactones via Palladium-Catalyzed [5 + 5] Annulation.
Ten-membered lactones are the core units of many biologically active natural products but with a great synthetic challenge. Based on the principle of vinylogy, novel types of cyclic vinylogous anhydrides have been designed as five-carbon carbonyl synthons, further applied in [5 + 5] annulation with vinylethylene carbonates under chiral palladium catalysis. This strategy features excellent regioselectivity, mild conditions, and broad substrate scope, affording a range of spiro ten-membered lactones bearing oxindole and pyrrolidinone motif in excellent yield (up to 99%) with moderate to high enantioselectivity (up to 89% ee).


Stigma Sensitivity and the Duration of Temporary Closure Are Affected by Pollinator Identity in Mazus miquelii (Phrymaceae), a Species with Bilobed Stigma.
A sensitive bilobed stigma is thought to assure reproduction, avoid selfing and promote outcrossing. In addition, it may also play a role in pollinator selection since only pollinators with the appropriate body size can trigger this mechanism. However, no experimental study has investigated how the sensitive stigma responds to different pollinators and its potential effects on pollination. Mazus miquelii (Phrymaceae), a plant with a bilobed stigma was studied to investigate the relationship between stigma behaviors and its multiple insect pollinators. The reaction time of stigma closure after touched, duration of temporary closure, and factors determining permanent closure of the stigma were studied when flowers were exposed to different visitors and conducted with hand pollination. Manual stimulation was also used to detect the potential differences in stigmas when touched with different degrees of external forces. Results indicated that, compared to pollinators with a small body size, larger pollinators transferred more pollen grains to the stigma, causing a rapid stigma response and resulting in a higher percentage of permanent closures. Duration of temporary closure was negatively correlated with the speed of stigma closure; a stigma that closed more rapidly reopened more slowly. Manual stimulation showed that reaction time of stigma closure was likely a response to external mechanical forces. Hand pollination treatments revealed that the permanent closure of a stigma was determined by the size of stigmatic pollen load. For large pollinators, the speedy reaction of the stigma might help to reduce pollen loss, enhance pollen germination and avoid obstructing pollen export. Stigmas showed low sensitivity when touched by inferior pollinators, which may have increased the possibility of pollen deposition by subsequent visits. Therefore, the stigma behavior in M. miquelii is likely a mechanism of pollinator selection to maximize pollination success.


Medical temporal-knowledge discovery via temporal abstraction.
Medical knowledge includes frequently occurring temporal patterns in longitudinal patient records. These patterns are not easily detectable by human clinicians. Current knowledge could be extended by automated temporal data mining. However, multivariate time-oriented data are often present at various levels of abstraction and at multiple temporal granularities, requiring a transformation into a more abstract, yet uniform dimension suitable for mining. Temporal abstraction (of both the time and value dimensions) can transform multiple types of point-based data into a meaningful, time-interval-based data representation, in which significant, interval-based temporal patterns can be discovered. We introduce a modular, fast time-interval mining method, KarmaLego, which exploits the transitivity inherent in temporal relations. We demonstrate the usefulness of KarmaLego in finding meaningful temporal patterns within a set of records of diabetic patients; several patterns seem to have a different frequency depending on gender. We also suggest additional uses of the discovered patterns for temporal clustering of the mined population and for classifying multivariate time series.


Blood flow rate, temperature, oxygen tension and consumption in the skin of adults measured by a heated microcathode oxygen electrode.
Reliable transcutaneous measurements of arterial oxygen tension are based on a maximum skin blood flow rate which is created by heating the skin, typically at an electrode temperature of 44 to 45 degrees C. This increase in skin blood flow rate creates an arterialization of the oxygen tension in the capillaries and the surrounding tissue. The heat conducted to the skin surface is removed by a combination of convection (skin perfusion) and conduction to the deeper layers of the skin. This heat transport to and through the skin surface causes a measurable temperature profile from the electrode surface to the capillary layer. By a blood flow cessation it is possible to change the temperature profile because the convective part of the heat consumption is eliminated and the conductive part can then be measured and subtracted. Using the forearm as measuring area and a heated tc-PO2 electrode several observations were made. The mean temperature gradient over epidermis down to the capillary layer at an electrode temperature of 43, 44, and 45 degrees C was 2.1, 2.4 and 2.7 degrees C, respectively. The change in temperature profile caused by the blood flow cessation enabled primarily an estimation of the skin blood flow rate by temperature measurements, ranging from 0.07 to 0.24 ml.cm-2.min-1. Increasing blood flow rates correlated to increasing tc-PO2 values. By means of a dynamically, thermally shielded tc-PO2 electrode it was possible to determine the skin blood flow rates in the same arbitrary units computed on the basis of the heat dissipation to the skin surface. Furthermore, it was possible to correlate these blood flow estimations to the cutaneous blood flow rates measured by 133Xe washout technique. By increasing the electrode temperature the cutaneous blood flow rates increased from 12 to 50 ml.(100 g)-1.min-1. It was possible to calculate a conversion factor on the basis of the correlation between the heat determinations of the skin blood flow rate and the 133Xe measurements. Using this conversion factor the highest blood flow rate did not exceed 55 ml.(100 g)-1.min-1. The subcutaneous blood flow rate increased accordingly with increasing electrode temperature. It was concluded that the measured heat consumption of the skin is effected by the heat removing capacity of the cutaneous as well as the subcutaneous blood flow. The cutaneous blood flow, however, was considered predominant in the transport of heat from the skin surface. By 50 times of stripping the skin surface, the cornified epidermal membrane was removed. This procedure increased the tc-PO2 values by on an average 3.6 kPa (27.1 mmHg).(ABSTRACT TRUNCATED AT 400 WORDS)


Oestradiol assays: applications and guidelines for the provision of a clinical biochemistry service.
This paper reports on the provision of a clinical biochemistry service for serum oestradiol. The pathophysiology and recognised applications of oestradiol assays are discussed and the current availability of assay reagents and methodologies reviewed. Data are presented on the analytical performance of assays for serum oestradiol in the UK External Quality Assessment Scheme (UKEQAS) and general guidance is offered to laboratories providing a diagnostic service for this analyte.


Sox7 is dispensable for primitive endoderm differentiation from mouse ES cells.
Primitive endoderm is a cell lineage segregated from the epiblast in the blastocyst and gives rise to parietal and visceral endoderm. Sox7 is a member of the SoxF gene family that is specifically expressed in primitive endoderm in the late blastocyst, although its function in this cell lineage remains unclear. Here we characterize the function of Sox7 in primitive endoderm differentiation using mouse embryonic stem (ES) cells as a model system. We show that ectopic expression of Sox7 in ES cells has a marginal effect on triggering differentiation into primitive endoderm-like cells. We also show that targeted disruption of Sox7 in ES cells does not affect differentiation into primitive endoderm cells in embryoid body formation as well as by forced expression of Gata6. These data indicate that Sox7 function is supplementary and not essential for this differentiation from ES cells.


How Different Molecular Architectures Influence the Dynamics of H-Bonded Structures in Glass-Forming Monohydroxy Alcohols.
Primary alcohols have been an active area of research since the beginning of the 20th century. The main problem in studying monohydroxy alcohols is the molecular origin of the slower Debye relaxation, whereas the faster process, recognized as structural relaxation, remains much less investigated. This is because in many primary alcohols the structural process is strongly overlapped by the dominating Debye relaxation. Additionally, there is still no answer for many fundamental questions concerning the origin of the molecular characteristic properties of these materials. One of them is the role of molecular architecture in the formation of hydrogen-bonded structures and its potential connection to the relaxation dynamics of Debye and structural relaxation processes. In this article, we present the results of ambient and high-pressure dielectric studies of monohydroxy alcohols with similar chemical structures but different carbon chain lengths (2-ethyl-1-butanol and 2-ethyl-1-hexanol) and positions of the OH- group (2-methyl-2-hexanol and 2-methyl-3-hexanol). New data are compared with previously collected results for 5-methyl-2-hexanol. We note that differences in molecular architecture have a significant influence on the formation of hydrogen-bonded structures, which is reflected in the behavior of the Debye and structural relaxation processes. Intriguingly, studying the relaxation dynamics in monohydroxy alcohols at high pressures of up to p = 1700 MPa delivers a fundamental bridge to understand the potential connection between molecular conformation and its response to the characteristic properties of these materials.


Circadian rhythm of the angiotensin converting enzyme (ACE) activity in serum of healthy adult subjects.
Angiotensin converting enzyme (ACE) activity was measured in the peripheral serum of 10 healthy, diurnally-active and nocturnally-resting adult subjects (5 women and 5 men). Blood was drawn serially at 4-h intervals throughout a 24-h cycle with the subjects hospitalized and synchronized. They were not kept in recumbency. Data were evaluated by conventional statistical analysis and by single- and population mean- cosinor procedures. A low-amplitude circadian rhythm was statistically validated for the group. Acrophase was located in the afternoon, at about 1630. The recognition that ACE activity oscillates physiologically in the peripheral blood according to a circadian rhythm may serve to amplify the clinical use of ACE measurements.


Alignment-free estimation of nucleotide diversity.
Sequencing capacity is currently growing more rapidly than CPU speed, leading to an analysis bottleneck in many genome projects. Alignment-free sequence analysis methods tend to be more efficient than their alignment-based counterparts. They may, therefore, be important in the long run for keeping sequence analysis abreast with sequencing. We derive and implement an alignment-free estimator of the number of pairwise mismatches, . Our implementation of , pim, is based on an enhanced suffix array and inherits the superior time and memory efficiency of this data structure. Simulations demonstrate that is accurate if mutations are distributed randomly along the chromosome. While real data often deviates from this ideal, remains useful for identifying regions of low genetic diversity using a sliding window approach. We demonstrate this by applying it to the complete genomes of 37 strains of Drosophila melanogaster, and to the genomes of two closely related Drosophila species, D.simulans and D.sechellia. In both cases, we detect the diversity minimum and discuss its biological implications.


Management of skin disease in patients with lupus erythematosus.
Skin disease in patients with lupus erythematosus may be subdivided into two broad categories - those represented by a 'specific' histopathology, the interface dermatitis, and those with changes that are not specific to lupus erythematosus, for example, vasculitis, mucin infiltration, etc. The specific skin lesions that are most common are discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE). Evaluation will allow the treating physician to assign a prognosis. Cutaneous lesions can generally be managed with standard therapies. Patients with discoid LE and subacute cutaneous LE are generally photosensitive, and therefore sunscreens, protective clothing and behavioural alteration should be discussed with all patients. Topical corticosteroids are a standard form of therapy, but 'newer' agents such as retinoids, calcipotriene and tacrolimus might be effective. Antimalarial agents are generally effective. Attempts to reduce or stop smoking may aid in the control of cutaneous LE. The choice of alternative therapy is personal, and discussions of the risks and benefits should be carefully documented.


Clinical and laboratory data of primary hemophagocytic lymphohistiocytosis: A retrospective review of the Turkish Histiocyte Study Group.
This study analyzes the clinical and laboratory findings of children with primary hemophagocytic lymphohistiocytosis (HLH) followed in various referral centers of Turkey. A simple three-page questionnaire prepared by the Turkish Histiocyte Study Group was used for documentation of patient data. Age at diagnosis varied from 0.6 to 78 months (median±SD, 16.5±26.1). Sex distribution was almost equal (F/M=10/12). The frequencies of parental consanguinity and sibling death in the family history were 100% and 81.1%, respectively. The most common clinical findings were hepatomegaly (100%) and fever (95%). The most common laboratory findings were anemia (100%), hyperferritinemia (100%) and thrombocytopenia (90.9%). Triglyceride and total bilirubin levels in the deceased versus surviving group appear to be high (triglyceride: 394±183 mg/dl, 289±7 mg/dl; total bilirubin: 2.7±6.9 mg/dl, 0.5±1.2 mg/dl, respectively). We concluded that fever, hepatosplenomegaly, anemia, thrombocytopenia, and hyperferritinemia are the most common clinical and laboratory findings in primary HLH. Increased triglyceride and total bilirubin level at the time of diagnosis might be an indicator of poor prognosis in HLH.


Brain Painting: First Evaluation of a New Brain-Computer Interface Application with ALS-Patients and Healthy Volunteers.
Brain-computer interfaces (BCIs) enable paralyzed patients to communicate; however, up to date, no creative expression was possible. The current study investigated the accuracy and user-friendliness of P300-Brain Painting, a new BCI application developed to paint pictures using brain activity only. Two different versions of the P300-Brain Painting application were tested: A colored matrix tested by a group of ALS-patients (n = 3) and healthy participants (n = 10), and a black and white matrix tested by healthy participants (n = 10). The three ALS-patients achieved high accuracies; two of them reaching above 89% accuracy. In healthy subjects, a comparison between the P300-Brain Painting application (colored matrix) and the P300-Spelling application revealed significantly lower accuracy and P300 amplitudes for the P300-Brain Painting application. This drop in accuracy and P300 amplitudes was not found when comparing the P300-Spelling application to an adapted, black and white matrix of the P300-Brain Painting application. By employing a black and white matrix, the accuracy of the P300-Brain Painting application was significantly enhanced and reached the accuracy of the P300-Spelling application. ALS-patients greatly enjoyed P300-Brain Painting and were able to use the application with the same accuracy as healthy subjects. P300-Brain Painting enables paralyzed patients to express themselves creatively and to participate in the prolific society through exhibitions.


An investigation of the potential application of chitosan/aloe-based membranes for regenerative medicine.
A significant number of therapeutics derived from natural polymers and plants have been developed to replace or to be used in conjunction with existing dressing products. The use of the therapeutic properties of aloe vera could be very useful in the creation of active wound dressing materials. The present work was undertaken to examine issues concerning structural features, topography, enzymatic degradation behavior, antibacterial activity and cellular response of chitosan/aloe vera-based membranes. The chitosan/aloe vera-based membranes that were developed displayed satisfactory degradation, roughness, wettability and mechanical properties. A higher antibacterial potency was displayed by the blended membranes. Moreover, in vitro assays demonstrated that these blended membranes have good cell compatibility with primary human dermal fibroblasts. The chitosan/aloe vera-based membranes might be promising wound dressing materials.


Expression of the histo-blood group ABO gene defined glycosyltransferases in epithelial tissues.
The histo-blood group ABO carbohydrate antigens are differentially expressed in epithelia in close correlation with cellular differentiation. In order to gain insight into the biosynthetic regulation of these carbohydrate antigens, we correlated the expression of A carbohydrate antigens with that of the A gene defined glycosyl-transferase by immunohistology of human oral epithelia using monoclonal antibodies. In glandular epithelium the A transferase was found in mucous cells similar to that of the A carbohydrate antigens. In stratified non-keratinized squamous epithelium the A transferase was expressed only in spinous cell layers, which is in accordance with the appearance of the A carbohydrate antigens in these more mature cell layers. This simultaneous acquisition of the primary and secondary gene product of a glycosyltransferase gene, provides evidence that the well-defined sequential expression of histo-blood group carbohydrate antigens in stratified squamous epithelium may be directly regulated at the transcriptional level of the glycosyltransferase. Future studies will address the mechanism behind loss of A antigens in premalignant lesions and carcinomas.


Patent foramen ovale and decompression sickness in sports divers.
Patency of the foramen ovale (PFO) may be a cause of unexplained decompression sickness (DCS) in sports divers. To assess the relationship between PFO and DCS, a case-control study was undertaken in a population of Belgian sports divers. Thirty-seven divers who suffered from neurological DCS were compared with matched control divers who never had DCS. All divers were investigated with transesophageal contrast echocardiography for the presence of PFO. PFO size was semiquantified on the basis of the amount of contrast passage. Divers with DCS with lesions localized in the high cervical spinal cord, cerebellum, inner ear organs, or cerebrum had a significantly higher prevalence of PFO than divers with DCS localizations in the lower spinal cord. For unexplained DCS (DCS without commission of any diving procedural errors), this difference was significant for large PFOs only. We conclude that PFO plays a significant role in the occurrence of unexplained cerebral DCS, but not of spinal DCS. We further stress the importance of standardization and semiquantification of future PFO studies that use transesophageal contrast echocardiography.


Epiretinal membrane inflammatory cell density might reflect the activity of proliferative diabetic retinopathy.
Diabetic retinopathy (DR) has features of chronic low-grade inflammation. The purpose of our study was to investigate whether the presence of inflammatory cells in fibrovascular membranes (FVMs) from patients with proliferative diabetic retinopathy (PDR) is associated with the activity of PDR and visual acuity improvement after vitreoretinal surgery. Forty FVMs from 40 patients with PDR were obtained during vitrectomy, prepared by using the agar sandwich method, and examined using light microscope and immunohistochemistry methods to define the presence and density of inflammatory cells: CD45+ cells (leukocytes), CD4+ cells (T helper lymphocytes), CD8+ cells (T cytotoxic lymphocytes), CD19+ cells (B lymphocytes), and CD14+ cells (monocytes/macrophages). For each FVM, the inflammatory cell density defined as numerical areal density was calculated. The number of vessels was defined as the volume density of vessels. Among 40 patients with PDR, 33 patients had active PDR and 7 quiescent PDR. Significant differences in cell densities for CD4+, CD8+, and CD19+ cells were observed between patients with active and quiescent PDR. B lymphocytes were present in membranes of active PDR only. No correlation was observed between numerical areal density of inflammatory cells and the volume density of vessels. No association was found between visual acuity improvement after surgery and cell densities. Lymphocyte infiltration of FVMs might be associated with the activity of retinopathy but not with visual acuity improvement after surgery.


Ultrasonic excitation of a bubble near a rigid or deformable sphere: implications for ultrasonically induced hemolysis.
A number of independent studies have reported increased ultrasound bioeffects, such as hemolysis and hemorrhage, when ultrasound contrast agents are present. To better understand the role of cavitation in these bioeffects, one- and two-dimensional models have been developed to investigate the interactions between ultrasonically excited bubbles and model "cells." First, a simple one-dimensional model based on the Rayleigh-Plesset equation was developed to estimate upper bounds for strain, strain rate, and areal expansion of a simulated red blood cell. Then, two-dimensional boundary element models were developed (with DynaFlow Inc.) to obtain simulations of asymmetric bubble dynamics in the presence of rigid and deformable spheres. The deformable spherical "cell" was modeled using Tait's equation of state for water, with a membrane approximated by surface tension that increases linearly with areal expansion. The presence of a rigid or deformable sphere had little effect on the bubble expansion, but caused an asymmetric collapse and jetting for the conditions considered. Predicted membrane areal expansions were found to be below critical values for hemolysis reported in the literature for the cases considered near the inertial cavitation threshold.


[Treatment of gigantocellular tumor of the tibia metaphysis by means of the Ilizarov method--a case study].
The authors show a 36-year old female patient with a gigantocellular tumor of the distal metaphysis of the left tibia (stage III by Campanacci). A 7.6 cm long distal articular defect of the tibia has been formed by radical segmentary resection. The defect was compensated by the extension of the rest of the tibia; whereas the support function of the limb was provided through tibio-talar arthrodesis. 5.5 years after the surgery, there are no signs of local relapses; the patient walks without any orthopedic aids and works at the same job as prior to the operation.


Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study.
Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, and second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. Diagnostic test study. A university research laboratory. From November 2014 to April 2016. Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. ROTEM was triggered with 2.5 pmol l of tissue factor and 10 μmol l of phospholipid vesicles. Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. Modified ROTEM allowed detection of as little as 25 ng ml FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml in whole blood with 90% sensitivity and 85% specificity. Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood.


[THE GUT FEELING OF THE EYES: GUT-EYE AXIS].
In intestinal diseases there are ophthalmological abnormalities. In celiac disease, for example, the eyes' pathologies are expressed by motoric, neurological, inflammatory, autoimmune, vision sharpness, dryness, redness, conjunctivitis and cataract tendency etc. It appears that intestinal luminal components and processes can irradiate to peripheral organs, including to the eyes, inducing functional abnormalities in this target organ. The present review describes the luminal and mucosal constituents and processes, the sensing mechanisms of those generated signals and the routes to deliver those messages to remote organs, eyes included. The gut-eye axis is very challenging and its exploration might bring future therapeutic strategies to treat ophthalmological disease.


Divinyl sulfone as a postdigestion modifier for enhancing the a(1) Ion in MS/MS and postsource decay: potential applications in proteomics.
Divinyl sulfone reacts at pH 8-9 with the alpha-amino groups of N-terminal residues, proline, the epsilon-amino groups of lysine, and the histidine side chains of peptides. This reaction leads to great enhancement of the abundance of the normally weak or missing "a(1)" fragment ion in MS/MS analysis defining the N-terminal residue of a peptide in a digest. This provides "one-step Edman-like" information that, together with a fairly accurately determined mass, often enables one to correctly identify a protein or family of proteins. The applicability of this procedure in proteomics was demonstrated with several peptides and tryptic digests of protein mixtures by LC-MS/MS experiments using a QTOF and MALDI-PSD analyses. Advantages of this approach are its simple chemistry, retention of charge multiplicity, and possibly, shortening of database search time. Used with other MS/MS data, it provides higher confidence in the scores and identification of a protein found in peptide mass fingerprinting. Moreover, this approach has an advantage in "de novo" sequencing due to its ability to decipher the first amino acid of a peptide whose information is normally unavailable in MS/MS spectra.


Benzimidazole and piperidine containing novel 1,2,3-triazole hybrids as anti-infective agents: Design, synthesis, in silico and in vitro antimicrobial efficacy.
Cu alkyne-azide cycloaddition was used to easily synthesize a library of novel heterocycles containing benzimidazole and piperidine based 1,2,3-triazole(7a-7l) derivatives. The synthesized analogs were characterized by various spectroscopic techniques like FTIR, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass spectrometry. All these novel bioactive compounds (7a-7l) were evaluated for in vitro antibacterial and antifungal efficacy. Compound 7k exhibited appreciable potent activity against Escherichia coli strain. Compounds 7a, 7b, 7f, and 7i showed excellent potent activity against all bacterial strains. Compound 7b, 7c, 7d, and 7g derivatives showed excellent effects when tested in vitro for antifungal activity against various fungal strains. Additionally, a molecular docking investigation revealed that compound 7k has the ability to bind to the active site of the E. coli DNA gyrase subunit protein and form hydrogen bonds with significant amino acid residues Asp73 and Asp49 in the active sites. In a 100 ns molecular dynamics simulation, the E. coli DNA gyrase protein's steady capacity to bind compound 7k was shown by the low measured root mean square deviation, which was an indication of the complex's conformational stability.


Needs of the elderly and the politics of health care. The social context of changes in the delivery system.
The emergence of the elderly as a substantial subgroup within the population has been identified as signaling a crisis for the health care system. This article places recent changes in health care financing for the elderly in the context of biomedical, demographic, and social factors. These factors, in turn, are related to the larger economic and political structures that have shaped our national health care policies and programs. Current policies and programs are inadequate in meeting the needs of the elderly because they provide a limited array of services. This article also examines how the needs of the elderly have been portrayed to support age-based entitlements to limited health care coverage, irrespective of need across age strata. Physical therapists can use their understanding of the genesis of particular public policies to assist in developing a health care system that is responsive to the needs of all members of society.


Infantile-onset inflammatory bowel disease has variable long-term outcomes.
Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study. Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded. Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection. The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis.


Effect of Detoxified Nano Sulfur Supplementation on the Growth, Nutrient Digestibility, Meat Quality, Excreta Microbes, Gas Emissions, and Blood Profiles of Broilers.
A 35-day experiment was conducted to evaluate the effects of the supplementation of mineral detoxified sulfur dispersion ((DSD); Patent No.: 10-1997773) on the growth performance, meat quality, excreta microbiota, gas emissions, nutrient digestibility, and blood profiles of broilers. In total, 720 one-day-old ROSS 308 broilers, with an initial body weight of 41.9±0.8 g, were divided into two (2) treatment groups with 20 replicate pens/groups composed of 18 birds per pen. Treatments consisted of 1) CON (the control), normal drinking water and 2) TRT (the treatment group), CON+0.001% DSD (1000:1 dilution ratio). Average daily feed intake (ADFI) and feed conversion ratio (FCR) increased in the TRT group (P<0.05) between days 1 to 7 and days 7 to 21 of the experimental period. Similarly, body weight gain (BWG) showed a significant increase (P<0.05) in the DSD-supplemented group throughout in the length of the experiment. With regard to meat quality, redness (a*) was higher, while drip loss was lower, on the 7th day in the DSD group. Furthermore, DSD supplementation increased (P<0.05) Lactobacillus excreta but decreased E. coli concentrations in the TRT group compared to the CON group. Notably, nutrient digestibility, excreta gas emission, and blood profiles did not show any significant differences (P>0.05). DSD supplementation, administered through drinking water, has a positive impact on the growth performance, meat quality, and excreta microbiota of broiler chickens.


Preparation and characterization of neutralizing monoclonal antibodies to feline calicivirus.
Fourteen neutralizing monoclonal antibodies (N-MoAbs) were prepared against the F4 strain of feline calicivirus (FCV), the prototype strain of FCV in Japan, and examined for their ability to neutralize FCV isolates. Neutralization-resistant variants of the F4 strain were selected under the presence of 4 individual N-MoAbs in cell culture systems and used in cross-neutralization tests and enzyme-linked immunosorbent assay with all of the 14 N-MoAbs. The results revealed the identification of at least two antigenic determinants on FCV F4: one being more broadly conserved among FCV isolates than the other. Usefulness of antigenic variants resistant to N-MoAbs for analysis of neutralization determinants on FCV was also demonstrated.


Prevalence and associations of anisometropia with spherical ametropia, cylindrical power, age, and sex in refractive surgery candidates.
To analyze the prevalence and associations of anisometropia with spherical ametropia, astigmatism, age, and sex in a refractive surgery population. Medical records of 27,070 eyes of 13,535 refractive surgery candidates were reviewed. Anisometropia, defined as the absolute difference in mean spherical equivalent powers between right and left eyes, was analyzed for subjective (A(subj)) and cycloplegic refraction (A(cycl)). Correlations between anisometropia (>1 diopter) and spherical ametropia, cylindrical power, age, and sex, were analyzed using χ² and nonparametric Kruskal-Wallis or Mann-Whitney tests and binomial logistic regression analyses. Power vector analysis was applied for further analysis of cylindrical power. Prevalence of A(subj) was 18.5% and of A(cycl) was 19.3%. In hyperopes, logistic regression analysis revealed that only spherical refractive error (odds ratio [OR], 0.72) and age (OR, 0.97) were independently associated with anisometropia. A(subj) decreased with increasing spherical ametropia and advancing age. Cylindrical power and sex did not significantly affect A(subj). In myopes all explanatory variables (spherical power OR, 0.93; cylindrical power OR, 0.75; age OR, 1.02; sex OR, 0.8) were independently associated with anisometropia. Cylindrical power was most strongly associated with anisometropia. Advancing age and increasing spherical/cylindrical power correlated positively with increasing anisometropia in myopic subjects. Female sex was more closely associated with anisometropia. This large-scale retrospective analysis confirmed an independent association between anisometropia and both spherical ametropia and age in refractive surgery candidates. Notably, an inverse relationship between these parameters in hyperopes was observed. Cylindrical power and female sex were independently associated with anisometropia in myopes.


Acute renal and hepatic failure associated with allopurinol treatment.
Hyperuricemia is present in about 5% of the population, and allopurinol is frequently used to treat it. The use of this drug can be associated with a number of side effects, indicating allergic reactions, such as skin rash, reversible after its withdrawal. In some cases more severe hypersensitivity reactions may be seen, such as erythema multiforme exudativum, or Steven-Johnson Syndrome (SJS). Reversible clinical hepatotoxicity, as well as acute renal failure, may also develop after allopurinol therapy. We describe here the case of a 74-year-old woman with chronic renal failure who was admitted to hospital after 1 week of sore throat and fever, presenting mucous membrane lesions, widespread blistering of the skin, evolving to flaccid vesicles and bullae, and extensive epidermal detachment associated with acute renal failure and cholestatic jaundice. A diagnosis of allopurinol-induced toxic epidermal necrolysis (TEN) was established. Allopurinol was discontinued, and intensive care management was required: the patient was successfully treated by using intravenous immunoglobulin (IVIg), standard hemodialysis, and albumin dialysis (Molecular Adsorbents Recirculating System - MARS, Teraklin AG, Rostock, Germany). Allopurinol-induced TEN is extremely rare, however, the survival rate is extremely low. Clinicians should be aware of this potentially severe adverse effect. This report emphasizes the importance of an aggressive pharmacological and dialysis treatment in the case of TEN.


Molecular basis of Lys-63-linked polyubiquitination inhibition by the interaction between human deubiquitinating enzyme OTUB1 and ubiquitin-conjugating enzyme UBC13.
UBC13 is the only known E2 ubiquitin (Ub)-conjugating enzyme that produces Lys-63-linked Ub chain with its cofactor E2 variant UEV1a or MMS2. Lys-63-linked ubiquitination is crucial for recruitment of DNA repair and damage response molecules to sites of DNA double-strand breaks (DSBs). A deubiquitinating enzyme OTUB1 suppresses Lys-63-linked ubiquitination of chromatin surrounding DSBs by binding UBC13 to inhibit its E2 activity independently of the isopeptidase activity. OTUB1 strongly suppresses UBC13-dependent Lys-63-linked tri-Ub production, whereas it allows di-Ub production in vitro. The mechanism of this non-canonical OTUB1-mediated inhibition of ubiquitination remains to be elucidated. Furthermore, the atomic level information of the interaction between human OTUB1 and UBC13 has not been reported. Here, we determined the crystal structure of human OTUB1 in complex with human UBC13 and MMS2 at 3.15 Å resolution. The presented atomic-level interactions were confirmed by surface-plasmon resonance spectroscopy with structure-based mutagenesis. The designed OTUB1 mutants cannot inhibit Lys-63-linked Ub chain formation in vitro and histone ubiquitination and 53BP1 assembly around DSB sites in vivo. Finally, we propose a model for how capping of di-Ub by the OTUB1-UBC13-MMS2/UEV1a complex efficiently inhibits Lys-63-linked tri-Ub formation.


Spontaneous Corneal Graft Reattachment Following Descemet Stripping Automated Endothelial Keratoplasty in Prone Position: A Case Report and Literature Review.
Graft detachment after Descemet stripping automated endothelial keratoplasty (DSAEK) is usually managed with air-bubbling. However, it is an invasive procedure, which can cause corneal endothelial reduction, and requires hospitalization and supine position maintenance. Only few case reports on graft reattachment in the prone position exist, and this is the first report from Japan. An 87-year-old woman presented with sudden pain in her left eye. Examination of her left eye showed a best-corrected vision of 20/50, shallow anterior chamber, cataractous lens, central corneal thickness (CCT) of 630 μm, and corneal endothelial cell count of 467 cells/mm2. She was diagnosed with left-eye bullous keratopathy due to primary angle closure, and DSAEK was performed after cataract surgery. Post-surgery, she touched her left eye due to agitation. Graft adhesion was good until postoperative day 4; however, a partial detachment was observed on day 12. She was instructed to remain in a prone position for as long as possible; on day 22, the graft was reattached, and the CCT improved to 555 μm. Since then, the graft adhesion has been maintained, and her best-corrected vision has improved to 20/30. To date, 5 cases of graft reattachment in the prone position have been reported, with reattachment observed in all cases within 10 days from the onset of detachment, including this case. Re-bubbling is an effective technique; however, it is invasive and may cause additional corneal endothelial loss. Therefore, it may be beneficial to have the patient initially attempt the prone position for reattachment.


[Analysis of risk factors for spontaneous rupture of hepatocellular carcinoma].
To assess the risk factors for spontaneous rupture of hepatocellular carcinoma (SRHC). A retrospective analysis of 34 consecutive patients with SRHC treated by emergency interventional embolization in our hospital from July 2003 to July 2011 was conducted. General condition, laboratory examination and imaging data were analyzed, and compared with the data of 34 patients with primary hepatocellular carcinoma but without rupture, randomly selected from 215 concurrent patients. The patients with SRHC were selected for risk factor analysis, and the non-SRHC patients were taken as control group. No significant difference between the SRHC group and control group was found in age, sex, Child-Turcotte-Pugh (CTP) grade, Barcelona clinic liver cancer (BCLC) stage, HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), glucose (GLU), cirrhosis, portal tumor thrombus, the maximum diameter of tumor, location, and cholecystitis or cholelithiasis. The univariate analysis showed that activated partial thromboplastin time (APTT), lower or normal plasma fibrinogen (FIB) level, alpha fetoprotein (AFP), tumor protrusion > 1 cm above the liver surface were all associated with increased risk of SRHC (P < 0.05). Multivariate analysis only showed that lower or normal level of FIB (P = 0.033) and tumor protrusion > 1 cm above the liver surface (P = 0.041) were significant independent risk factors for SRHC. Lower or normal level of FIB and tumor protrusion > 1 cm above the liver surface are significant independent risk factors for spontaneous rupture of hepatocellular carcinoma.


[Reservoir of tuberculosis infection].
"The reservoir of tuberculous infection" is shown to imply a wider concept than does "the size of bacteria-isolating contingents". It includes a potential reservoir (the population that is infected but not the patients with tuberculosis) and an active one (undetected and detected patients with this disease). To reduce the total incidence of tuberculosis in the population, continuous work as to the potential reservoir should be done, by vigorously detecting those with early-stage disease. Work associated with identification of only those who isolate abundant bacteria and with their abacillation must not be recognized effective in reducing overall morbidity and improving an epidemiological situation as it is directed only against a small portion of an infection reservoir.


Overexpression of long intergenic noncoding RNA LINC00312 inhibits the invasion and migration of thyroid cancer cells by down-regulating microRNA-197-3p.
The study evaluated the ability of long intergenic noncoding RNA LINC00312 (LINC00312) to influence the proliferation, invasion, and migration of thyroid cancer (TC) cells by regulating miRNA-197-3p. TC tissues and adjacent normal tissues were collected from 211 TC patients. K1 (papillary TC), SW579 (squamous TC), and 8505C (anaplastic TC) cell lines were assigned into a blank, negative control (NC), LINC00312 overexpression, miR-197-3p inhibitors, and LINC00312 overexpression + miR-197-3p mimics group. The expression of LINC00312, miR-197-3p, and p120 were measured using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation was assessed via CCK8 assay, cell invasion through the scratch test, and cell migration via Transwell assay. In comparison with adjacent normal tissues, the expression of LINC00312 is down-regulated and the expression of miR-197-3p is up-regulated in TC tissues. The dual luciferase reporter gene assay confirmed that P120 is a target of miR-197-3p The expression of LINC00312 and p120 was higher in the LINC00312 overexpression group than in the blank and NV groups. However, the expression of miR-197-3p was lower in the LINC00312 overexpression group than in the blank and NC groups. The miR-197-3p inhibitors group had a higher expression of miR-197-3p, but a lower expression of p120 than the blank and NC groups. The LINC00312 overexpression and miR-197-3p inhibitor groups had reduced cell proliferation, invasion and migration than the blank and NC groups. These results indicate that a LINC00312 overexpression inhibits the proliferation, invasion, and migration of TC cells and that this can be achieved by down-regulating miR-197-3p.


Assignment of Weight-Based Antibody Units for Four Additional Serotypes to a Human Antipneumococcal Standard Reference Serum, 007sp.
The pneumococcal enzyme-linked immunosorbent assay (ELISA) reference standard serum, lot 89SF, had been in use since 1990 and was replaced with a new reference standard serum, 007sp, in 2013. This serum was generated under an FDA-approved clinical protocol where 278 adult volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II and a unit of blood was obtained twice within 120 days following immunization. Pooled serum was prepared from the plasma, filled at 6 ml per vial, and lyophilized. Five independent laboratories participated in bridging the serotype-specific IgG assignments of 89SF to 007sp to establish equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) using the WHO reference ELISA. A subsequent follow-up study established equivalent reference values for an additional seven serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F). In this study, three laboratories assigned weight-based IgG concentrations in micrograms per milliliter of serum to 007sp for four additional serotypes: 2, 9N, 17F, and 20A. This study completes the assignment of serotypes for 89SF to 007sp. In addition, the IgG antibody assignments for a 12-member WHO quality control (QC) serum panel were extended to cover the four additional serotypes. Agreement was excellent, with a concordance correlation coefficient (rc ) of >0.996 when values from each laboratory were compared to the assigned values for the 12 WHO QC sera. The 007sp preparation has replaced 89SF as the pneumococcal reference standard. Sufficient quantities of 007sp are projected to be available for the next 25 years.


In vitro analysis of RQC activities provides insights into the mechanism and function of CAT tailing.
Ribosomes can stall during translation due to defects in the mRNA template or translation machinery, leading to the production of incomplete proteins. The Ribosome-associated Quality control Complex (RQC) engages stalled ribosomes and targets nascent polypeptides for proteasomal degradation. However, how each RQC component contributes to this process remains unclear. Here we demonstrate that key RQC activities-Ltn1p-dependent ubiquitination and Rqc2p-mediated Carboxy-terminal Alanine and Threonine (CAT) tail elongation-can be recapitulated in vitro with a yeast cell-free system. Using this approach, we determined that CAT tailing is mechanistically distinct from canonical translation, that Ltn1p-mediated ubiquitination depends on the poorly characterized RQC component Rqc1p, and that the process of CAT tailing enables robust ubiquitination of the nascent polypeptide. These findings establish a novel system to study the RQC and provide a framework for understanding how RQC factors coordinate their activities to facilitate clearance of incompletely synthesized proteins.


Suppression of Sin3A activity promotes differentiation of pluripotent cells into functional neurons.
Sin3 is a transcriptional corepressor for REST silencing machinery that represses multiple neuronal genes in non-neuronal cells. However, functions of Sin3 (Sin3A and Sin3B) in suppression of neuronal phenotypes are not well characterized. Herein we show that Sin3A knockdown impedes the repressive activity of REST and enhances differentiation of pluripotent P19 cells into electrophysiologically active neurons without inducing astrogenesis. It is also found that silencing Sin3B induces neurogenesis of P19 cells with a lower efficiency than Sin3A knockdown. The results suggest that Sin3A has a more profound effect on REST repressive machinery for silencing neuronal genes in P19 cells than Sin3B. Furthermore, we show that a peptide inhibitor of Sin3A-REST interactions promotes differentiation of P19 cells into functional neurons. Observations made in studies using genetic deletion and a synthetic inhibitor suggests that Sin3A plays an important role in the repression of neuronal genes by the REST regulatory mechanism.


Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes.
Human C5a, a complement-derived anaphylatoxin, is a potent mediator of human leukocyte chemotaxis. Using a homogeneous preparation of C5a that was 125I-labeled, we have demonstrated the presence of a specific cellular receptor for this glycoprotein on intact human polymorphonuclear leukocytes. Cellular uptake of the radiolabeled ligand occurred rapidly and the rate of dissociation was extremely slow. Cellular binding was saturable with respect to 125I-labeled C5a, and half-saturation occurred at a concentration of 3-7 X 10(-9) M. The number of C5a binding sites per cell was estimated as 1-3 X 10(5). The ligand (C5a) displays specific structural features that are required for binding because analogs of C5a such as C5ades Arg or a yeast carboxypeptidase-digested C5a derivative C5a-(I-69) inhibited the binding but C3a anaphylatoxin, which resembles C5a chemically, did not. Both C5a-mediated leukocyte chemotaxis and C5a-induced lysosomal enzyme release from cytochalasin B-treated cells closely paralleled uptake of the ligand, clearly indicating that it is a receptor-C5a interaction that leads to stimulation of these cellular responses.


Non-invasive monitoring of cardiac function through Ballistocardiogram: an algorithm integrating short-time Fourier transform and ensemble empirical mode decomposition.
The Ballistocardiogram (BCG) is a vibration signal that is generated by the displacement of the entire body due to the injection of blood during each heartbeat. It has been extensively utilized to monitor heart rate. The morphological features of the BCG signal serve as effective indicators for the identification of atrial fibrillation and heart failure, holding great significance for BCG signal analysis. The IJK-complex identification allows for the estimation of inter-beat intervals (IBI) and enables a more detailed analysis of BCG amplitude and interval waves. This study presents a novel algorithm for identifying the IJK-complex in BCG signals, which is an improvement over most existing algorithms that only perform IBI estimation. The proposed algorithm employs a short-time Fourier transform and summation across frequencies to initially estimate the occurrence of the J wave using peak finding, followed by Ensemble Empirical Mode Decomposition and a regional search to precisely identify the J wave. The algorithm's ability to detect the morphological features of BCG signals and estimate heart rates was validated through experiments conducted on 10 healthy subjects and 2 patients with coronary heart disease. In comparison to commonly used methods, the presented scheme ensures accurate heart rate estimation and exhibits superior capability in detecting BCG morphological features. This advancement holds significant value for future applications involving BCG signals.


Effect of stall design on dairy calf transition to voluntary feeding on an automatic milk feeder after introduction to group housing.
Automatic milk feeders (AMF) for young dairy calves are widely used in the dairy industry. These feeders are thought to have benefits for calf health and welfare and may reduce labor required for feeding; however, little is known about how calves adapt to feeding with AMF. The objective of this study was to observe the effects of feeding stall design on calves learning to use the AMF. The hypothesis was that solid side stalls, compared with steel bar stalls, would result in a longer latency to approach and feed from the AMF without assistance. A total of 147 Holstein calves (80 male and 67 female) were enrolled at 4 d of age, introduced to a group pen, and, at the same time, trained on an AMF. For training, calves were allowed to suck on the trainer's fingers and guided to the teat. Calves were allocated to 1 of 2 stall designs at the pen level, depending on which treatment cohort they were born into, either with steel bar stall walls (n = 46 male, 34 female calves) or with solid side stall walls (n = 34 male, 33 female calves). For 72 h after introductory training on the AMF, data from the feeders were collected and calf behavior was monitored by video. Outcomes measured included latency to first voluntary visit to the feeder and to first feeding, time spent in the feeder, amount of milk consumed over 72 h, number of retraining sessions required (retrained if <2 L was consumed every 12 h), and exploratory behavior, such as sniffing and licking of the feeder. Data were analyzed using mixed effects linear regression models or a Poisson model for the outcome of retraining. For certain outcomes the effects of stall design interacted with difficulty of training (willingness to enter feeder and drink); for the 38% of calves that were scored as moderately difficult to train on a scale of easy, moderate, or difficult, treatment (stall design) differences were detected. These calves took 2× longer to lick or bite toward the nipple, 2× longer to first voluntarily feeding, and consumed less milk over 72 h following training when trained on the steel bar stall design. These results suggest simple features of a stall may influence how quickly calves learn to use an AMF, but that the influence of stall wall design was affected by how easy calves were to train on the feeder upon initial introduction, which may depend in part on certain aspects of calf temperament. For many calves, solid side stalls at an AMF resulted faster in adaption than the steel bar stalls.


Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.
Testosterone is essential for spermatogenesis and the maintenance of secondary sexual characteristics in males. An important transcription factor, LIM-homeobox gene 9 (Lhx9) is indispensable for testis development and testosterone production; however, post-translational modifications of Lhx9 are largely unknown. Here, for the first time to our knowledge, we demonstrate that the level of Lhx9 protein increases in human chorionic gonadotropin-exposed Leydig cells and can be polyubiquitylated. We found that Smad ubiquitylation regulatory factor 1 (Smurf1), an E3 ubiquitin ligase, targets Lhx9 for ubiquitin-mediated proteasome degradation, thereby negatively modulating its function. Increasing Smurf1 decreases the level of Lhx9 and inhibits the Lhx9 transactivation capacity of steroidogenic factor 1 [nuclear receptor subfamily 5, group A, member 1 (NR5A1)]. In contrast, the depletion of Smurf1 leads to increased expression of Lhx9 protein and enhances testosterone biosynthesis-related gene transcripts [NR5A1, steroidogenic acute regulatory protein, CYP17A1, hydroxy-δ-5-steroid dehydrogenase, hydroxy-δ-5-steroid dehydrogenase isomerase 6, and hydroxysteroid (17-β) dehydrogenase 3] and testosterone production in Leydig cells. Furthermore, we found that Smurf1 knockout mice exhibit higher levels of Lhx9 protein and steroidogenesis, which leads to increased serum testosterone concentration. These findings reveal that Smurf1 promotes Lhx9 ubiquitylation and is involved in testosterone production in Leydig cells directly. Our results provide new insights into the molecular events that play a role in the homeostasis of testosterone levels and may provide a new target for testosterone regulation.-Hu, F., Zhu, Q., Sun, B., Cui, C., Li, C., Zhang, L. Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.


[The influence of diet and physical activity therapy on the body's composition of medium obesity women and men].
In 56 women and 15 men the efficiency of two weeks diet and physical activity therapy was evaluated. The following parameters before and after the therapy were measured: BM, BMI, LBM, WHR and the fat mass (FATkg and FAT%). The subjects were divided into four groups depending on sex: (group of men and group of women), and value of BMI (group of persons with BMI lower than 27 and group of persons with BMI higher than 27). Both, body mass, content of fat and BMI decreased in all groups after two weeks of therapy.


Antioxidant capacity of Typha angustifolia extracts and two active flavonoids.
The pollen of Typha angustifolia L. (Typhaceae) has been used as a traditional Chinese medicine for improving the microcirculation and promoting wound healing. Flavonoids are the main constituent in the plant, but little is known about the antioxidant activity of the principal constituent of the pollen in detail. To assess the antioxidant activities of ethanol and water extracts and two constituents of the pollen. Plant material (1 g) was extracted by 95% ethanol and water (10 mL × 2, 1 h each), respectively. The extracted activities (0.8-2.6 mg/mL) were measured by DPPH and the reducing activity of ferric chloride (1.7-2.6 mg/mL). Typhaneoside and isorhamnetin-3-O-neohesperidoside (I3ON) (2.8-70 μmol/L) were investigated on the relationship between NO, MDA and SOD in HUVECs treated with 100 μg/mL of LPS for 24 h. Nine compounds were identified by UPLC-MS. Ethanol extract showed IC50 values in DPPH (39.51 ± 0.72) and Fe3+ reducing activity (82.76 ± 13.38), higher than the water extract (50.85 ± 0.74) and (106.33 ± 6.35), respectively. Typhaneoside and I3ON promoted cell proliferation at the respective concentration range of 2.8 to 70 μmol/L (p < 0.01). This two compounds decreased MDA (1.91 ± 0.10, 1.80 ± 0.34, p < 0.05) and NO levels (14.64 ± 0.08, 13.10 ± 0.88, p < 0.01), respectively, and increased SOD level (22.94 ± 2.48, 23.57 ± 2.38, p < 0.01) at the concentration of 70 μmol/L compared with LPS group. The constituents from Typha angustifolia could be a novel therapeutic strategy for LPS-induced inflammation.


In vitro assessment of antitumor activities of the PI3K/mTOR inhibitor GSK2126458.
Up-regulation of the PI3K/mTOR (phosphatidylinositol-3' kinase/mammalian target of rapamycin) signaling is common in carcinoma. Consistently, targeting these molecules has been shown to halt the growth of many tumors. The main purpose of this study was to develop surrogate biomarkers of the antitumor activity of PI3K/mTOR inhibitors. Fragments from eight tumors were collected immediately after resection in ice-cold RPMI gassed with 95% O2 :5% CO2. Viability was determined by measuring tumor cellular respiration (mitochondrial O2 consumption). The specimens were incubated at 37°C with and without 50 nM GSK2126458 (a highly potent and selective inhibitor of PI3K/mTOR) for 90 min. The tissue was then processed for histology, measurement of intracellular caspase-3 activity (using the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin), and immunohistochemical detection of the apoptotic biomarkers caspase-3, cytochrome C, and annexin A2. GSK2126458 induced morphologic changes in four tumors (two invasive ductal carcinomas, one invasive lobular carcinoma, and one ovarian dysgerminoma), intracellular caspase-3 activity in three tumors (two invasive ductal carcinomas and one poorly differentiated signet ring adenocarcinoma of gastric origin), and immunohistochemical evidence of apoptosis in at least four tumors (three invasive ductal carcinomas and one adenocarcinoma of gastric origin). Two tumors (ovarian serous carcinoma and moderately differentiated adenocarcinoma of colorectal origin) demonstrated no treatment effect. These preliminary results demonstrate the feasibility of using in vitro biomarkers for detecting antitumor activities of the rapidly emerging PI3K/mTOR inhibitors.


Quantification of Eu3+ in quantum-dye-labeled materials by ashing and dissociation enhancement.
Quantum Dye (QD) is an extremely stable macrocyclic chelate of Eu3+, measurable with a time-resolved fluorometer even without the aid of enhancement solution, albeit at a low sensitivity. However, QD is not easily quantified by the popular dissociation-enhancement methodology (I. Hemmilä et al., 1984, Anal. Biochem. 137, 335-343), because of difficulty in dissociating Eu3+ completely from QD. We found that Eu3+ in QD can be accurately measured by simple ashing followed by the dissociation-enhancement methodology. Validity of the method was tested by determining Eu(NO3)3 with or without ashing and analyzing Eu3+ in other chelates known to be amenable to accurate measurement by the dissociation enhancement.


Chemical modification of protein a chromatography ligands with polyethylene glycol. II: Effects on resin robustness and process selectivity.
We have proposed chemical modification of Protein A (ProA) chromatography ligands with polyethylene glycol (PEGylation) as a strategy to increase the resin selectivity and robustness by providing the ligand with a steric repulsion barrier against non-specific binding. Here, we report on robustness and selectivity benefits for Repligen CaptivA PriMAB resin with ligands modified with 5.2 kDa and 21.5 kDa PEG chains, respectively. PEGylation of ProA ligands allowed the resin to retain a higher percentage of static binding capacity relative to the unmodified resin upon digestion with chymotrypsin, a representative serine protease. The level of protection against digestion was independent of the PEG molecular weight or modification extent for the PEGylation chemistry used. Additionally, PEGylation of the ligands was found to decrease the level of non-specific binding of fluorescently labeled bovine serum albumin (BSA) aggregates to the surface of the resin particles as visualized via confocal laser scanning microscopy (CLSM). The level of aggregate binding decreased as the PEG molecular weight increased, but increasing the extent of modification with 5.2 kDa PEG chains had no effect. Further examination of resin particles via CLSM confirmed that the PEG chains on the modified ligands were capable of blocking the "hitchhiking" association of BSA, a mock contaminant, to an adsorbed mAb that is prone to BSA binding. Ligands modified with 21.5 kDa PEG chains were effective at blocking the association, while ligands modified with 5.2 kDa PEG chains were not. Finally, ligands with 21.5 kDa PEG chains increased the selectivity of the resin against host cell proteins (HCPs) produced by Chinese Hamster Ovary (CHO) cells by up to 37% during purification of a monoclonal antibody (mAb) from harvested cell culture fluid (HCCF) using a standard ProA chromatography protocol. The combined work suggests that PEGylating ProA chromatography media is a viable pathway for increasing both resin lifetime and host cell impurity clearance in downstream bioprocessing.


The effect of age on adenosine A1 receptor function in the rat heart.
Adenosine is an important regulatory metabolite in the heart where it has a cardioprotective function. In the ventricle, the cardioprotective action of adenosine is mediated through the adenosine A1 receptor and inhibition of adenylyl cyclase. In order to investigate the effect of age on adenosine signal transduction in the heart, the effect of specific adenosine A receptor agonists on adenylyl cyclase activity was measured in crude cardiac ventricular membranes isolated from 1-, 6- and 24-month-old Fisher 344 rats. There were no differences in basal cyclase activity with age. Consistent with observations from other laboratories, isoproterenol- and forskolin-stimulated cyclase activity decreased with age. In addition, there was an age-related decline in the capacity of adenosine to inhibit stimulated adenylyl cyclase. The specific A1 adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and N6-p-sulfophenuladenosine (SPA) inhibited isoproterenol- and forskolin-stimulated adenylyl cyclase activity in cardiac membranes from 1-month and 6-month-old rats; however, CPA and SPA did not inhibit adenylyl cyclase in membranes from 24-month-old rats. These data indicate that in addition to the age-related decline in beta-adrenergic receptor function with age, there is also a decrease in adenosine A; receptor-mediated responses. In contrast, carbachol acting through muscarinic receptors, caused the same inhibition of adenylyl cyclase at all ages. Therefore, the age-related decline in inhibitory signal transduction is specific to the adenosine A1 receptor. The age-related defect is probably at the level of the adenosine/receptor interaction and/or the receptor/guanine nucleotide binding protein interaction.


Qualitative detection and quantitative determination of single-walled carbon nanotubes in mixtures of carbon nanotubes with a portable Raman spectrometer.
The main aim of this work is to develop a one-step method for the characterization of mixtures of single- and multi-walled carbon nanotubes using a simple and inexpensive tool, a portable Raman spectrometer. In order to overcome the problem of heat dissipation in solid samples, the suitability of three surfactants-SDS, Triton X-100 and CTAB-to disperse nanotubes has been evaluated. A systematic study of the wavelength and relative intensity of the D and G bands has been carried out with six samples of multiwalled carbon nanotubes (MWNTs) and one of single-walled carbon nanotubes (SWNTs) dispersed in these surfactants, and this has been compared with solid samples. Finally, the possibility has been demonstrated to identify and (semi)quantify the presence of SWNTs in a mixture containing MWNTs.


Evaluation of a noninvasive algorithm for differentiation of obstructive and central hypopneas.
The clear discrimination of central and obstructive hypopneas is highly relevant to avoid misinterpretation and inappropriate treatment of complicated breathing patterns. Esophageal manometry is the accepted standard for the differentiation of the phenotypes of sleep apnea. However, it is limited in its use due to poor acceptance by patients and therefore rarely performed in routine clinical practice. Flattening of the inspiratory airflow curve, paradoxical breathing, arousal position, sleep stages, and breathing pattern at the end of the hypopnea can each give hints for the classification of hypopnea. The aim of this study was to evaluate a standardized algorithm combining these polysomnographic parameters for the discrimination of hypopneas in everyday practice. Polysomnography (PSG) and esophageal manometry were performed in 41 patients suspected of having sleep apnea (33 male, 52.3 ± 15.9 yr, body mass index 28.6 ± 4.5 kg/m(2)). Hypopneas were independently discriminated by blinded investigators based on esophageal pressure and the PSG-based algorithm. Only those hypopneas that could be differentiated with both methods were evaluated. There were 1,175 of 1,837 hypopneas (64%) that could be defined by esophageal pressure, 1,812 (98.6%) by the PSG-based algorithm. Using esophageal pressure as a reference, the new algorithm correctly defined 76.9% of central and 60.5% of obstructive hypopneas. The overall accuracy was 68%. The isolated analysis of single PSG parameters revealed a lower accuracy compared with the combined algorithm. The PSG-based algorithm allows for discrimination of most hypopneas. It is advantageous in comparison with esophageal pressure because it is noninvasive and less impaired by artefacts. Therefore, it is a potentially helpful tool for sleep specialists. Randerath WJ; Treml M; Priegnitz C; Stieglitz S; Hagmeyer L; Morgenstern C. Evaluation of a noninvasive algorithm for differentiation of obstructive and central hypopneas. SLEEP 2013;36(3):363-368.


Why aged men become impotent.
Despite frequent erectile impotence in aged men, etiologic data are scarce. We evaluated 121 impotent male veterans (mean age, 68 +/- 5.3 years) to obtain information on potential pathophysiologic mechanisms. Subjects related a complete medical history and underwent physical examination, metabolic assessment, nocturnal penile tumescence monitoring, and vascular and neurologic assessment. The most frequent cause of impotence was the coexistence of neurologic and vascular disorders (30.3%). Other subjects had single causes, including vascular disease (21.1%), diabetic neuropathy (17.1%), nondiabetic neuropathy (10.5%), and psychopathology (9.2%). Remaining patients suffered from adverse drug effects (3.9%), hypogonadism (2.6%), and Peyronie's disease (1.3%). Five patients were objectively impotent on the basis of nocturnal penile tumescence, but otherwise normal. We conclude that geriatric impotence is primarily related to vascular or neurologic dysfunction. However, 15.7% of aged impotent men may have reversible impotence (eg, psychogenic causes or hypogonadism), and an additional 31.5% may have a treatable disorder (eg, penile neuropathy).


Identification of HIV-1 Tat-Associated Proteins Contributing to HIV-1 Transcription and Latency.
Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat. These TAPs also suppress Tat-mediated HIV-1 transcription. Removing suppression of HIV-1 transcription benefits the reversal of post-integrated, latent HIV-1 proviruses. We demonstrate that these transcriptionally suppressing TAPs contribute to HIV-1 latency in Jurkat latency (J-LAT) cells. Therefore, our proteomic analysis highlights the previously unappreciated TAPs that play a role in maintaining HIV-1 latency and can be further studied as potential pharmacological targets for the "shock and kill" HIV-1 cure strategy.


The relationship of performance on the dental admission test and performance on Part I of the National Board Dental Examinations.
Although many schools use scores on the Dental Admission Test (DAT) to evaluate applicants, the association of these scores with students' performance on Part I of the National Board Dental Examinations (NBDE) has not been recently evaluated. In this study, the hypothesis that the DAT scores would be a significant predictor of Part I of the NBDE scores was tested. We analyzed by multiple regression the scores on both examinations for the 114 students matriculating in the University of Mississippi School of Dentistry in 1992, 1993, 1994, and 1995. The results indicate that DAT reading comprehension was a statistically significant predictor (p value less than or equal to 0.05) of all four subtests of Part I of the NBDE. The DAT biology and organic chemistry scores were statistically significant predictors of NBDE biochemistry-physiology, and the DAT quantitative analysis score was a statistically significant predictor of NBDE dental anatomy and occlusion. DAT perceptual ability and general chemistry were not significant predictors.


Inhibitory effect of sarcophytol A on development of spontaneous hepatomas in mice.
The inhibitory effect of sarcophytol A, a cembrane-type diterpene isolated from a marine soft coral, Sarcophyton glaucum, on development of spontaneous hepatomas was investigated in C3H/HeNCrj mice. A total of 80 mice were divided equally into two groups. The experimental and control groups were given basal diets with and without 0.01% sarcophytol A, respectively. At week 65 of the experiment, mice were examined for hepatomas. The percentages of hepatoma-bearing mice of the subgroup with three or more tumors and the tumor diameters of the group treated with sarcophytol A were smaller than those of the control group. Ridit analysis revealed that these differences were statistically significant. The body weight gain, and the food intake were not significantly different between these two groups. Analysis of blood serum revealed that feeding the diet containing 0.01% sarcophytol A for 65 weeks did not show any adverse effects. These results suggest that sarcophytol A inhibits the development of spontaneous hepatomas without toxicity, and should be considered as a possible cancer chemopreventive agent for hepatomas in humans.


Effectiveness of two models of brief family education: retention of gains by family members of adults with serious mental illness.
The retention of benefits from two models of family education was compared with maturational effects in an untreated control group. The three-month interventions showed an initial effect for self-efficacy regarding a mentally ill relative that did not significantly diminish during the following six months. However, no significant differences on this measure were found between the treated groups and the untreated controls. Ways of refining the interventions and measures so as to improve gains and retain them over time are discussed.


Millimeter-wave spectroscopy of CoNO produced by UV laser photolysis of Co(CO)3NO.
The rotational spectrum of cobalt mononitrosyl (CoNO) produced by ultraviolet photolysis of Co(CO)(3)NO was observed in the millimeter-wave region. Seven rotational transitions in the ground state ranging from J = 6-5 to 12-11, with hyperfine splittings due to the Co nucleus (I = 7/2), were detected in a supersonic jet environment, while higher-frequency transitions in the range from J = 29-28 to 35-34 were measured in the ground, nu(1), nu(2), nu(3), and 2nu(2) vibrational states using a free-space absorption cell. It was confirmed from the observed spectral pattern that the CoNO molecule has a linear structure with the electronic ground state of (1)Sigma(+) symmetry. The rotational lines in the 2nu(2)(Sigma) and nu(3) states were observed to be perturbed by Fermi resonance. The equilibrium rotational constant B(e) is determined to be 4682.207(15) MHz. The CoN bond length is derived to be 1.5842 A assuming the NO bond length of 1.1823 A. A large nuclear spin-rotation interaction constant, C(I) = 123.8(11) kHz, was determined, suggesting a (1)Pi electronic excited state lying close to the ground state.


Interaction of H2O and H2S with Cu(111) and the impact of the electric field: the rotating & translating adsorbate, and the rippled surface.
The interactions of H2O and H2S monomers with Cu(111) in the absence and presence of an external electric field are studied using density functional theory. It is found that the adsorption is accompanied by a rippled pattern of the surface Cu atoms and electron accumulation on the surface Cu atoms surrounding the adsorption site. The response of the H2O/Cu(111) and H2S/Cu(111) interfaces to the external electric field is computed up to the field magnitude of 10(10) V m(-1). The results show that H2O rotates and translates much more with an electric field than H2S does. The extent of the surface deformation changes considerably with the applied electric field, which influences the translation pattern of the adsorbates. On the other hand, the rotation of the adsorbates is correlated to the dipole moment of the molecules and their adsorption energies.


Binding of synthetic nanobodies to the SARS-CoV-2 receptor-binding domain: the importance of salt bridges.
In this study, five different SARS-CoV-2 receptor-binding domain (RBD) models were created based on the crystal structures of RBD complexes with two synthetic nanobodies (Sb16 and Sb45). Microsecond all-atom MD simulations revealed that Sb16 and Sb45 substantially stabilized the flexible RBD loop (residues GLU471-SER494) due to the salt bridges and hydrogen bonding interactions between RBD and the synthetic nanobodies. However, the calculation of binding free energy displayed that Sb45 had a higher binding affinity to RBD than Sb16, in agreement with the experimental result. This is because Sb45 has stronger electrostatic attraction to RBD as compared to Sb16. In particular, the salt bridge GLU484-ARG33 in Sb45-RBD is stronger than the GLU484-LYS32 in Sb16-RBD. Furthermore, by comparing the binding affinity of Sb16 for two RBD mutants (E484K and K417N), we found that E484K mutation substantially reduced the binding affinity to Sb16, and K417N mutation had no significant effect, qualitatively in agreement with experimental studies. According to the binding free energy calculation, the strong electrostatic repulsion between LYS32 and LYS484 caused by E484K mutation destroys the salt bridge between LYS32 and GLU484 in the RBD wild type (WT). In contrast, the binding of the K417N mutant to Sb16 effectively maintains the salt bridge between LYS32 and GLU484. Therefore, our research suggests that the salt bridges between RBD and synthetic nanobodies are crucial for binding synthetic nanobodies to RBD, and a SARS-CoV-2 variant can escape neutralization from nanobodies by creating electrostatic repulsion between them.


Antagonistic Interplay Between an Intermolecular CH···O and an Intramolecular OH···O Hydrogen Bond in a 1:1 Complex Between 1,2-Cyclohexanedione and Chloroform: A Combined Matrix Isolation Infrared and Quantum Chemistry Study.
Matrix isolation infrared spectra of a weak C-H···O hydrogen-bonded complex between the keto-enol form of 1,2-cyclohexanedione (HCHD) and chloroform have been measured. The spectra reveal that the intramolecular O-H···O H-bond of HCHD is weakened as a result of complex formation, manifesting in prominent blue shift (∼23 cm-1) of the νO-H band and red shifts (∼7 cm-1) of νC═O bands of the acceptor (HCHD). The νC-H band of donor CHCl3 undergoes a large red shift of ∼33 cm-1. Very similar spectral effects are also observed for formation of the complex in CCl4 solution at room temperature. Our analysis reveals that out of several possible iso-energetic conformational forms of the complex, the one involving antagonistic interplay between the two hydrogen bonds (intermolecular C-H···O and intramolecular O-H···O) is preferred. The combined experimental and calculated data presented here suggest that in condensed media, conformational preferences are guided by directional hyperconjugative charge transfer interactions at the C-H···O hydrogen bonding site of the complex.