The association of cryoglobulinaemia with sustained virological response in patients with chronic hepatitis C.
Previous reports suggest cryoglobulinemia might influence the hepatitis C virus (HCV) infection clinical course and treatment response but this association has not been thoroughly evaluated. We aimed to assess the relationship between cryoglobulinemia and sustained viral response (SVR) in patients treated for HCV infection. We included patients with HCV infection treated from January 2003 through December 2006. Biochemical analyses, detection cryoglobulinemia, and liver biopsies were performed prior to treatment. Genotype 1 or 4 infections received Peg-interferon (IFN) alpha-2a or -2b for 48 weeks; genotypes 2 or 3 received IFN alpha for 24 weeks. All patients also received ribavirin. Of 329 enrolled patients, 242 (73%) were male and the median age was 43 years. Cryoglobulinemia was detected in 196 (59.6%) patients; liver biopsy was performed in 301. Multivariate analysis showed an association of cryoglobulinemia with severe active necroinflammation (A3) (adjusted odds ratio [AOR] = 9.48; 95% confidence interval [CI]: 1.50-59.92) and rheumatoid factor (RF) level (AOR = 1.01; 95% CI: 1.00-1.02). Variables associated with advanced fibrosis were age, aspartate aminotransferase and alkaline phosphatase levels, alcohol use, and presence of diabetes. Variables independently associated with SVR were cryoglobulinemia (AOR = 2.33, 95% CI: 1.26-4.32), absence of cirrhosis (AOR = 4.5, 95% CI: 1.4-14.80), and RF level (AOR = 1.008, 95% CI: 1.001-1.014). Our findings suggest cryoglobulinemia is associated with severe necroinflammatory activity in HCV-infected patients. We also provide the first evidence for an association between cryoglobulinemia and higher SVR rates, highlighting its potential role as a prognostic factor for treatment response.


A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers.
MicroRNA (miRNA)-binding site polymorphisms that could contribute to disease risk and prognosis are rapidly being identified and investigated as this genetic variation may have a potentially profound impact on human health. A recently described variant allele in the KRAS 3' untranslated region that arises in the let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression in lung cancer was examined for its association with the occurrence of head and neck squamous cell carcinoma (HNSCC). We examined the prevalence of the KRAS-LCS6 variant allele in a population-based case-control study of HNSCC to determine if this KRAS-LCS6 genotype was associated with disease occurrence and patient survival. Although the KRAS-LCS6 variant genotype was not associated with the overall risk of HNSCC, cases with the KRAS-LCS6 variant genotype had significantly reduced survival [hazard ratio (HR), 1.6; 95% confidence interval (CI), 1.0-2.5] in models controlled for confounders of survival. This risk was greatest in cases of oral cavity carcinoma (HR, 2.7; 95% CI, 1.4-5.3). These data demonstrate that cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease.


A Nucleus-Encoded Chloroplast Phosphoprotein Governs Expression of the Photosystem I Subunit PsaC in Chlamydomonas reinhardtii.
The nucleo-cytoplasmic compartment exerts anterograde control on chloroplast gene expression through numerous proteins that intervene at posttranscriptional steps. Here, we show that the maturation of psaC mutant (mac1) of Chlamydomonas reinhardtii is defective in photosystem I and fails to accumulate psaC mRNA. The MAC1 locus encodes a member of the Half-A-Tetratricopeptide (HAT) family of super-helical repeat proteins, some of which are involved in RNA transactions. The Mac1 protein localizes to the chloroplast in the soluble fraction. MAC1 acts through the 5' untranslated region of psaC transcripts and is required for their stability. Small RNAs that map to the 5'end of psaC RNA in the wild type but not in the mac1 mutant are inferred to represent footprints of MAC1-dependent protein binding, and Mac1 expressed in bacteria binds RNA in vitro. A coordinate response to iron deficiency, which leads to dismantling of the photosynthetic electron transfer chain and in particular of photosystem I, also causes a decrease of Mac1. Overexpression of Mac1 leads to a parallel increase in psaC mRNA but not in PsaC protein, suggesting that Mac1 may be limiting for psaC mRNA accumulation but that other processes regulate protein accumulation. Furthermore, Mac 1 is differentially phosphorylated in response to iron availability and to conditions that alter the redox balance of the electron transfer chain.


Complete Stress-Strain Curves of Self-Compacting Steel Fiber Reinforced Expanded-Shale Lightweight Concrete under Uniaxial Compression.
To expand the structural application of steel fiber reinforced expanded-shale lightweight concrete (SFRELC), a self-compacting SFRELC with high-workability was developed based on previous research. As part of the investigation, the present study focuses on the adaptability of formulas used for the complete stress-strain curves of steel fiber reinforced lightweight-aggregate concrete and conventional concrete under uniaxial compression. On the basis of mix proportion of SFRELC, self-compacting SFRELC was designed with the volume fraction of steel fiber as 0%, 0.4%, 0.8%, 1.2%, 1.6%, and 2.0%. Eighteen cylindrical specimens with dimensions of Φ150 mm × 300 mm were tested to measure the uniaxial compressive stress-strain curves of self-compacting SFRELC. Results indicated that, with the increasing volume fraction of steel fiber, the compressive strain at the peak-stress of the stress-strain curve increased, while the slope of the descending portion decreased. This increased the energy absorption of self-compacting SFRELC with a higher compression toughness. With a comparison of test results between four groups of calculation models, a group of formulas is selected to express the complete stress-strain curves of self-compacting SFRELC under uniaxial compression.


Psychiatry of old age: from section to faculty.
To describe the processes that led to formation of the RANZCP Faculty of Psychiatry of Old Age (FPOA). Two criteria needed to be fulfilled before Faculty status could be approved. One was to demonstrate a recognised body of knowledge concerning psychiatry of old age, and the other was to be able to offer a comprehensive training program in this subspecialty. On 1 January 1999, FPOA came into existence.


Body weight, dieting, and eating disorder symptoms among college students, 1982 to 1992.
The authors sought to examine changes in prevalence of dieting behavior and eating disorder symptoms from 1982 to 1992. In 1982, 625 women and 276 men participated in a study examining body weight, eating habits, dieting tendencies, and eating disorder symptoms. Ten years later 564 women and 235 men at the same college completed a nearly identical survey. Similar random sampling methods were used for both studies. All respondents were classified into one of five groups (nondieter, dieter, problem dieter, subclinical eating disorder, or eating disorder according to DSM-III-R criteria). On almost all measures there were significant reductions of problematic eating behaviors and disordered attitudes about body, weight, and shape from 1982 to 1992. The estimated prevalence of bulimia nervosa dropped from 7.2% to 5.1% for women and from 1.1% to 0.4% for men. Binge eating, vomiting, diuretic use, and diet pill use also declined for women during this period. Significantly fewer women and men reported chronic dieting in 1992 than in 1982, and there was evidence of improved body image for both sexes. Subjects in 1992 also reported healthier eating habits in terms of dietary intake and meal regularity. Finally, women in 1992 were more likely to be overweight and were, on average, five pounds heavier than their 1982 counterparts. The prevalence of problematic eating behaviors and eating disorder symptoms appears to be abating. However, they remain a significant problem that affects a substantial segment of this population.


Impaired Left Atrial Performance Resulting From Age-Related Arial Fibrillation Is Associated With Increased Fibrosis Burden: Insights From a Clinical Study Combining With an in vivo Experiment.
Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.


Synthesis, Properties and Bioimaging Applications of Silver-Based Quantum Dots.
Ag-based quantum dots (QDs) are semiconductor nanomaterials with exclusive electrooptical properties ideally adaptable for various biotechnological, chemical, and medical applications. Silver-based semiconductor nanocrystals have developed rapidly over the past decades. They have become a promising luminescent functional material for in vivo and in vitro fluorescent studies due to their ability to emit at the near-infrared (NIR) wavelength. In this review, we discuss the basic features of Ag-based QDs, the current status of classic (chemical) and novel methods ("green" synthesis) used to produce these QDs. Additionally, the advantages of using such organisms as bacteria, actinomycetes, fungi, algae, and plants for silver-based QDs biosynthesis have been discussed. The application of silver-based QDs as fluorophores for bioimaging application due to their fluorescence intensity, high quantum yield, fluorescent stability, and resistance to photobleaching has also been reviewed.


The temporal relationship between mental health service use and stalking perpetration.
Mental disorder is common among people who stalk. However, the nature of this association is unclear and it is not known whether the commencement of stalking is associated with symptoms of disorder. This study used a longitudinal design to examine the association between the onset and cessation of stalking behavior and indicators of mental disorder in the form of mental health service use. Data linkage was used to explore public mental health service use among 157 people who engaged in stalking in Melbourne, Australia. Mental health service use across the lifetime, 5 months prior to stalking onset, between the onset and cessation of stalking (during stalking) and 5 months post-stalking was identified. Mixed regression models tested temporal associations between types of mental health service use (acute vs continuing care) and onset and cessation of stalking in a subsample of 130 participants where dates of the stalking episode were available. A total of 105 (67%) participants had lifetime use of public mental health services, while 15% accessed mental health services in the 5 months prior to (N = 19) or during the stalking (N = 20) and 22% (N = 29) used services in the 5 months after the stalking ceased. Odds of using acute mental health services and average monthly rate of use were highest during the stalking. Odds and average monthly rate of using continuing care were highest after the episode ceased. Most people who stalk have used public mental health services, but a minority access services immediately prior to or during the stalking episode. Acute service use was more common during the stalking, while use of continuing care services was more common after the stalking ceased. These findings provide preliminary support for a temporal relationship between acute mental disorder and stalking behavior.


The Photovoltaic Cell Based on CIGS: Principles and Technologies.
Semiconductors used in the manufacture of solar cells are the subject of extensive research. Currently, silicon is the most commonly used material for photovoltaic cells, representing more than 80% of the global production. However, due to its very energy-intensive and costly production method, other materials appear to be preferable over silicon, including the chalcopyrite-structured semiconductors of the CIS-based family (Cu(In, Ga, Al) (Se, S)2). Indeed, these compounds have bandwidths between 1 eV (CuInSe2) and 3 eV (CuAlS2), allowing them to absorb most solar radiation. Moreover, these materials are currently the ones that make it possible to achieve the highest photovoltaic conversion efficiencies from thin-film devices, particularly Cu(In, Ga)Se2, which is considered the most efficient among all drifts based on CIS. In this review, we focus on the CIGS-based solar cells by exploring the different layers and showing the recent progress and challenges.


Radiographic characterization of the B2 glenoid: the effect of computed tomographic axis orientation.
Glenoid retroversion may accelerate glenoid loosening after total shoulder arthroplasty. Accurate measurement of preoperative glenoid deformity is critical for decision-making and prognostication. The purpose of this study was to determine whether glenoid version, inclination, and depth and humeral subluxation measurements on computed tomography (CT) scan slices oriented in the plane of the body differ from those oriented in the scapular plane and those obtained by automated 3-dimensional reconstruction software in the setting of a biconcave B2-type glenoid. Thirty-one preoperative CT scans in patients undergoing total shoulder arthroplasty with Walch B2-type glenoids underwent a standardized measurement protocol by 3 observers. Glenoid version, inclination, and depth and humeral subluxation were measured on 2-dimensional CT images in the plane of the body, on 2-dimensional images in the plane of the scapula, and by a validated, automated 3-dimensional software program. Correction of CT slice axis into the plane of the scapula decreased measured retroversion by 2.4° to 4.7° (P < .004) and inclination by 21° (P < .001). Whereas uncorrected version measurements do not differ from automated software measurements, corrected measurements do (P < .001). Whereas corrected inclination measurements do not differ from automated measurements, uncorrected measurements do (P < .001). Automated measurements differed from both corrected and uncorrected subluxation (P < .001 in both cases). If CT images are not reoriented into the plane of the scapula, version and inclination will be significantly overestimated. In the setting of a retroverted, deformed glenoid, automated software may produce similar inclination measurements to corrected 2-dimensional CT, but it produces significantly altered measurements of version and subluxation.


Spontaneous otoacoustic emission frequency is modulated by heartbeat.
Detailed analysis of spontaneous otoacoustic emissions (SOAEs) in human subjects revealed that all stable SOAEs sufficiently above the noise floor to permit appropriate analysis have sidebands at multiples of approximately 1 Hz. This is consistent with the hypothesis that SOAEs are modulated by heartbeat. Simultaneous measurement of the rate of blood flow to the thumb and the separation of the spectral sidebands demonstrated that they covary (r = 0.982, p < 5 x 10(-10)). An adaptive least-squares fit (LSF) paradigm was developed to facilitate the measurement of the instantaneous frequency and amplitude of the signals. A combination of traditional spectral analyses and new LSF analyses showed that the sideband generation stems from frequency modulation of the emissions. If there is any amplitude modulation correlated with the blood flow, it is below the noise floor of the analysis. The frequency of the emission was at a minimum when the blood flow was maximal. Examination of alternative mechanisms using computer simulations suggests that these changes stem from changes of 10-100 ppm in the mass of the basilar membrane.


Empyema necessitans caused by Mycobacterium tuberculosis in an immunocompetent patient.
A 22-year-old man, a recent immigrant from Mexico, was admitted to a Wisconsin hospital because of a swelling of the chest wall and right axilla. Originally, it was thought to be a skin infection with Staphylococcus aureus. When the treatment was unsuccessful, the patient returned to the hospital and the abscesses were found to have been caused by Mycobacterium tuberculosis. Furthermore, there were pleural collections and it was thought that he had a manifestation called empyema necessitans, an extension of purulent pleural liquid through adjacent tissues to form an abscess on the thoracic wall.


Evidence that neurites in human epiretinal membranes express melanopsin, calretinin, rod opsin and neurofilament protein.
We have previously identified neurofilament-protein-containing neurites in human epiretinal membranes (ERMs). The aim of this study was to further characterise these neurites by examining the expression of additional specific proteins in human ERMs and to correlate this expression with various retinal disease conditions. Epiretinal membranes originating from 43 patients with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) or with no known pathology (idiopathic epiretinal membrane; iERM) were removed during vitrectomy at varying durations after diagnosis and immediately placed in fixative. The membranes were labelled immunohistochemically with different combinations of antibodies to the proteins melanopsin, calretinin and neurofilament (to identify subclasses of ganglion cells), rod opsin (to identify rod photoreceptors), synaptophysin and synaptic vesicle glycoprotein 2A (SV2) (identifies synaptic vesicles) and vimentin (identifies glial cells). Anti-melanopsin-, anti-calretinin-, anti-neurofilament- and anti-rod-opsin-labelled neurites were routinely observed in the epiretinal membranes. Their presence did not appear to correlate with a specific disease condition or duration of the membrane. Generally neurites were observed in regions of glial cells. Based on the expression of selected markers for neurites, we show neurite processes in human ERMs of various aetiologies originating from rod photoreceptors and different populations of retinal ganglion cells, although there was no obvious correlation with specific disease condition. In addition, synaptophysin and SV2 labelling was observed associated with all types of neurites, indicating the presence of at least one component necessary for synaptic transmission. Our data suggest that the adult human retina retains a significant capacity for neuronal remodelling under various disease conditions.


Development of a Curcumin Bioadhesive Monolithic Tablet for Treatment of Vaginal Candidiasis.
The present investigation was designed to formulate a natural tablet for the treatment of vaginal candidiasis in order to eliminate side effects that are caused by existing antifungal drugs. Curcumin has promising antifungal activity in comparison with the existing azole antifungal drugs. Bioadhesive curcumin vaginal tablets were prepared by direct compression with different ratios of biadhesive polymers like xanthan gum, guar gum and HPMC. Curcumin tablets were characterized by studies of friability, hardness, hydration, DSC, mucoadhesion, In-vitro release and antifungal activity. DSC and FT-IR data indicate there was no interaction between the drug and the excipients and also polymer concentration has some effects on melting point of curcumin. Formulation F3 showed the best results in terms of swelling and mucoadhesion together with prolonged drug release. The antifungal activity of the Curcumin tablet has demonstrated a significant effect against Candida albicans. Hence, the study indicates the possible and effective use of curcumin bioadhesive monolithic vaginal tablet for vaginal candidiasis as a promising natural antifungal treatment.


Whole cell recording and conductance measurements in cat visual cortex in-vivo.
Long and stable recordings of post-synaptic, action and membrane potentials from visual cortical neurons in-vivo, are possible with the patch-clamp technique. These are comparable to the whole-cell configuration, but with an incomplete seal. EPSPs and IPSPs of normal time course and up to several mV can be recorded. DC potentials ranged from - 30 to - 60 mV and input resistances from 50 to 150 M omega. Injected currents have the same effect as if applied intracellularly. Membrane conductance after electrical stimulation of the lateral geniculate nucleus is increased during the first 20 ms, but decreases from 60 to about 130 ms, during return of the membrane potential to its resting level. The recording method is compared to other intracellular recording techniques in-vivo and in-vitro.


Assessment of the value of a competitive protein binding radioassay of folic acid in the detection of folic acid deficiency.
The diagnostic value of the Becton Dickinson Radioassay Kit (125I) for the the assay of red cell folate has been investigated. The assay was acceptable with regards to precision but was non-linear with changing packed cell volume. Sensitivity of the assay was satisfactory, with 24 of 25 folate deficient patients giving red cell folate values which fell below the reference range. Specificity of the assay in the detection of folate deficiency was less satisfactory. As with microbiological assays, a considerable proportion of vitamin B12 deficient patients had low red cell folate values. In addition, low concentrations were found in 12% of patients who were unlikely to be deficient in either vitamin B12 or folic acid.


[All-on-4 occlusion study: using T-Scan Ⅲ occlusal analysis system].
To investigate the occlusal force distribution and the characteristics of the occlusion time of patients with All-on-4 rehabilitation at different occlusion position using T-Scan Ⅲ occlusal analysis system. Thirteen volunteers with All-on-4 rehabilitation were included in this study. T-Scan Ⅲ occlusal analysis system was used to measure the occlusal force distribution and the time character of the patients at intercuspal position, protrusive position, and lateral excursive position. Maximum intercuspation: the left and right premolars took most of the occlusal force, namely (17.3±3.1)%, (15.8 ± 4.6)%, (15.5 ± 2.2)% and (15.2 ± 5.5)% (24, 25, 14, 15), the implants areas including the premolar and anterior teeth took (64.0±6.7)%, (19.2±8.0)% of occlusal force. The left and right sides took the respective percentages of (50.5±6.1)%, (49.5±6.1)%, and there was no difference. Protrusion position: the region (11, 12, 21, 22) commitment to take the percentage of (90.4±27.7)%. Occlusion time: 0.18(0.11, 0.26) s, disclusion time: 0.52 (0.35, 1.14) s . At the left and right lateral position, 8 patients were single teeth-supported occlusion, 5 patients were group fuctional occlusion, the average occlusion time was 0.20(0.13, 0.34) s, and DT was 1.07 (0.58, 1.46) s. At maximum intercuspation: the implants areas including the premolar and anterior teeth were the occlusal force centers; the force concentrated in the area (11, 12, 21, 22) at the protrusion position. The lateral occlusal pattern shows multiformity.


Differential upregulation of extracellular matrix molecules associated with the appearance of granule cell dispersion and mossy fiber sprouting during epileptogenesis in a murine model of temporal lobe epilepsy.
We have investigated changes in the extracellular matrix of the hippocampus associated with the early progression of epileptogenesis in a murine model of temporal lobe epilepsy using immunohistochemistry. In the first week following intrahippocampal injection of the glutamate agonist, domoate, there is a latent period at the end of which begins a sequential upregulation of extracellular matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning with neurocan and tenascin-C. This expression precedes the characteristic dispersion of the granule cell layer which is evident at 14 days post-injection when the first recurrent seizures can be recorded. At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of these molecules is localized differentially in the epileptogenic dentate gyrus, especially in the sprouting molecular layer, where a strong upregulation of phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it appears that granule cell layer dispersion is accompanied by a general increase in the ECM, while mossy fiber sprouting in the molecular layer is associated with a more restricted repertoire. In contrast to these changes, the expression of the ECM glycoproteins, laminin and fibronectin, both of which are frequently implicated in tissue remodelling events, showed no changes associated with either granule cell dispersion or mossy fiber sprouting, indicating that the epileptogenic plasticity of the hippocampus is accompanied by ECM interactions that are characteristic of the CNS.


Adenocarcinoma of the minor duodenal papilla: report of a case.
We report a rare case of adenocarcinoma of the minor papilla of the duodenum treated with transduodenal minor papillectomy. A 64-year-old woman was treated for an asymptomatic duodenal tumor detected on gastroduodenoscopy. Endoscopy showed a 15-mm sessile mass in the descending duodenum proximal to the major papilla. The major papilla was a villous 24-mm-diameter polypoid tumor. Histopathologic examination of the biopsy specimen showed tubular adenoma with moderate epithelial atypia. Transduodenal major and minor papillectomies were performed. The orifice of the duct of Santorini and the pancreatic duct were re-approximated to the duodenal wall to prevent acute pancreatitis caused by scarring and stenosis of the duct orifice. Histological findings were consistent with well-differentiated adenocarcinoma limited to the minor duodenal papilla, without infiltration of the duodenal wall submucosa, and confirmed complete resection. The patient had an uneventful postoperative course and has remained asymptomatic, without evidence of tumor recurrence or stenosis of the pancreatic duct orifice, for 4 years.


Modulating rhodopsin receptor activation by altering the pKa of the retinal Schiff base.
The visual pigment rhodopsin is a seven-transmembrane (7-TM) G protein-coupled receptor (GPCR). Activation of rhodopsin involves two pH-dependent steps: proton uptake at a conserved cytoplasmic motif between TM helices 3 and 6, and disruption of a salt bridge between a protonated Schiff base (PSB) and its carboxylate counterion in the transmembrane core of the receptor. Formation of an artificial pigment with a retinal chromophore fluorinated at C14 decreases the intrinsic pKa of the PSB and thereby destabilizes this salt bridge. Using Fourier transform infrared difference and UV-visible spectroscopy, we characterized the pH-dependent equilibrium between the active photoproduct Meta II and its inactive precursor, Meta I, in the 14-fluoro (14-F) analogue pigment. The 14-F chromophore decreases the enthalpy change of the Meta I-to-Meta II transition and shifts the Meta I/Meta II equilibrium toward Meta II. Combining C14 fluorination with deletion of the retinal beta-ionone ring to form a 14-F acyclic artificial pigment uncouples disruption of the Schiff base salt bridge from transition to Meta II and in particular from the cytoplasmic proton uptake reaction, as confirmed by combining the 14-F acyclic chromophore with the E134Q mutant. The 14-F acyclic analogue formed a stable Meta I state with a deprotonated Schiff base and an at least partially protonated protein counterion. The combination of retinal modification and site-directed mutagenesis reveals that disruption of the protonated Schiff base salt bridge is the most important step thermodynamically in the transition from Meta I to Meta II. This finding is particularly important since deprotonation of the retinal PSB is known to precede the transition to the active state in rhodopsin activation and is consistent with models of agonist-dependent activation of other GPCRs.


Polysaccharide-Based Membranes in Food Packaging Applications.
Plastic packaging is essential nowadays. However, the huge environmental problem caused by landfill disposal of non-biodegradable polymers in the end of life has to be minimized and preferentially eliminated. The solution may rely on the use of biopolymers, in particular polysaccharides. These macromolecules with film-forming properties are able to produce attracting biodegradable materials, possibly applicable in food packaging. Despite all advantages of using polysaccharides obtained from different sources, some drawbacks, mostly related to their low resistance to water, mechanical performance and price, have hindered their wider use and commercialization. Nevertheless, with increasing attention and research on this field, it has been possible to trace some strategies to overcome the problems and recognize solutions. This review summarizes some of the most used polysaccharides in food packaging applications.


Dynamic changes in rumen fermentation and bacterial community following rumen fluid transplantation in a sheep model of rumen acidosis: implications for rumen health in ruminants.
Over the years, rumen fluid transplantation (RT) has been successfully applied to treat acute rumen acidosis in ruminants, but how it functions in the ruminal microbial homeostasis and host function remains largely unknown. Here, we investigated the dynamic changes of rumen fermentation and bacterial communities following RT and its beneficial effects on rumen epithelial morphology and function in a sheep model of rumen acidosis. The results showed that RT resulted in dynamic changes in rumen fermentation and increased the concentrations of total volatile fatty acid, acetate, propionate, and butyrate, but it decreased the levels of lactate and LPS in the rumen. Illumina MiSeq Sequencing data showed that RT facilitated rapid rebuilt of ruminal bacterial homeostasis (8 d in control vs. 2 d in RT) from a markedly dysbiotic acidosis state to a healthy level (similar with those of donors). At the genus level, RT increased the relative abundance of unclassified Bacteroidales, unclassified Prevotellaceae, unclassified Ruminococcaceae, and Acetitomaculum. Additionally, RT also accelerated recovery of the predicted metagenomic function of ruminal bacteria. Rumen papillae morphology results showed that RT alleviated the damage of rumen epithelia induced by acute rumen acidosis and increased the length of rumen papillae. Furthermore, real-time PCR results showed that RT modulated mRNA expression of genes related to cytokines and tight junctions in the rumen epithelia. In summary, these results reveal that RT accelerates recovery of rumen fermentation and bacterial homeostasis and modulates rumen epithelial morphology and function for sheep suffering from rumen acidosis.-Liu, J., Li, H., Zhu, W., Mao, S. Dynamic changes in rumen fermentation and bacterial community following rumen fluid transplantation in a sheep model of rumen acidosis: implications for rumen health in ruminants.


A relativistic DFT study of one-bond fluorine-X indirect spin-spin coupling tensors.
The relativistic zeroth-order regular approximation (ZORA) DFT method was employed to investigate indirect spin-spin coupling tensors involving fluorine, (1)J(X, F). The relative contributions of the mechanisms contributing to (1)J(X, F) are discussed, with special attention paid to the magnitude and origin of the anisotropy in this tensor, DeltaJ. This quantum chemical study demonstrates that, for the systems investigated, the ZORA-DFT method reproduces the magnitude of (1)J(X, F)(iso) and indicates that DeltaJ(X, F) is of the same order of magnitude as (1)J(X, F)(iso). Several examples are provided that demonstrate the importance of considering contributions of DeltaJ to the experimental measurement of effective dipolar coupling constants, R(eff). Given the difficulties with determining DeltaJ experimentally and the promising computational results, we suggest that the quantum chemical calculation of (1)J(X, F) be used as a complementary tool to aid in the analysis of data from NMR experiments designed to measure dipolar coupling constants.


Lipidoid Nanoparticles for siRNA Delivery to the Intestinal Epithelium: In Vitro Investigations in a Caco-2 Model.
Short interfering ribonucleic acid (siRNA) therapeutics show promise for the treatment of intestinal diseases by specifically suppressing the expression of disease relevant proteins. Recently, a class of lipid-like materials termed "lipidoids" have been shown to potently deliver siRNA to the liver and immune cells. Here, we seek to establish the utility of lipidoid nanoparticles (LNPs) in the context of siRNA delivery to the intestinal epithelium. Initial studies demonstrated that the siRNA-loaded LNPs mediated potent, dose dependent, and durable gene silencing in Caco-2 intestinal epithelial cells, with a single 10 nM dose depressing GAPDH mRNA expression for one week. Transfection with siRNA-loaded LNPs did not induce significant cytotoxicity in Caco-2 cells or alter intestinal barrier function. Protein silencing was confirmed by Western blotting, with the lowest levels of GAPDH protein expression observed five days post-transfection. Together, these data underscore the potential of LNPs for the treatment of intestinal disorders.


Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells.
CD4+CD25+ regulatory T cells play an important role in peripheral tolerance. Upon T cell receptor (TCR)-mediated activation, the cells fail to proliferate but are induced to have a suppressor function. The intracellular signaling events that lead to their responses have not been elucidated. In this study, we have examined the proximal TCR signaling events in freshly isolated human CD4+CD25+ regulatory T cells after TCR ligation. In contrast to CD4+CD25- T cells, TCR ligation of CD4+CD25+ regulatory T cells by anti-CD3 cross-linking resulted in a lower calcium influx and extracellular signal-regulated kinase 1/2 phosphorylation. Examination of the CD3zeta chain phosphorylation status indicated that CD4+CD25+ regulatory T cells have poor phosphorylation of the protein and consequently, reduced recruitment of zeta-associated protein-70 to the TCR immunoreceptor tyrosine motif. The adaptor protein, Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa, which relays signals to downstream signaling components, also showed reduced phosphorylation, which correlated with reduced VAV guanine nucleotide exchange factors association. Consistent with other findings, the defect is accompanied with impaired actin cap formation, implicating a failure of actin remodeling of the cells. Together, our results demonstrate that CD4+CD25+ regulatory T cells have altered TCR proximal signaling pathways, which could be critical for inducing the distinct behavior of these cells.


The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel.
The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The outer membrane protein A (OmpA) domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work, we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans (EM) rash in Europe. Structural characterization of one these proteins (BAPKO_0422) by SAXS and CD indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25×45 Å (1 Å=0.1 nm). Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal phenylalanine residue commonly found in Proteobacterial OM proteins is replaced by isoleucine/leucine or asparagine. BAPKO_0422 is demonstrated to bind human factor H (fH) and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value.


Thrombotic Microangiopathy Causing Acute Kidney Injury in a COVID-19 Patient.
Acute Kidney Injury (AKI) in COVID-19 patients is common and independently associated with higher mortality. The pathophysiology of AKI is multifactorial and may be either direct viral trophism or immune mediated injury and hypercoagulability. This case highlights AKI in a young female with severe COVID-19 due to complement-3 mediated thrombotic microangiopathy with pre-existing chronic kidney disease likely because of IgA nephropathy.


Study of the Interfacial Bond Behavior between CFRP Grid-PCM Reinforcing Layer and Concrete via a Simplified Mechanical Model.
This paper presents the results of pull-out tests conducted to investigate the interfacial bond behavior between a carbon-fiber-reinforced polymer (CFRP) grid-polymer cement mortar (PCM) reinforcing layer and existing concrete, and proposes a simplified mechanical model to further study the interface bond mechanism. Four specimens composed of a CFRP grid, PCM, and concrete were tested. The influence of the type of CFRP grid and the grid interval on the interface bond behavior was discussed. The failure patterns, maximum tensile loads, and CFRP grid strains were obtained. The change process of interface bond stress was investigated based on the grid strain analysis. In addition, the simplified mechanical model and finite element model (FEM) were emphatically established, and the adaptability of the simplified mechanical model was validated through the comparative analysis between the FEM results and the test results. The research results indicate that a CFRP grid with a larger cross-sectional area and smaller grid interval could effectively improve the interface bond behavior. The tensile stress was gradually transferred from the loaded edge to the free edge in the CFRP grid. The interface bond behavior was mainly dependent on the anchorage action of the CFRP grid in the PCM, and the bond action between the PCM and the concrete. The FEM results were consistent with the test results, and the simplified mechanical model with nonlinear springs could well describe the interface bond mechanism between the CFRP grid-PCM reinforcing layer and concrete.


[Causative agents of superficial mycoses isolated in Dakar, Senegal: Retrospective study from 2011 to 2015].
Superficial fungal infections, particularly of the skin, scalp and nails are very common and have been reported worldwide. The most common causative agents of these mycoses are dermatophytes, yeasts and molds. However, these agents vary with time and depend on many factors including the geography. The objective of this study was to identify the causative agents of superficial mycoses diagnosed at the Le Dantec University Hospital in Dakar (Senegal). The study concerned 1851 outpatients received in the parasitological and mycological laboratory of Le Dantec hospital during the period from January 2011 to December 2015. Every patient benefited from direct examination and mycological culture. Among the 1851 patients, 633 were confirmed with superficial mycoses and the prevalence was 34.2 %. The age of patients ranged from two months to 81 years with a mean age of 31 years. Superficial mycoses were found more in women (70.3 %) than men (29.7 %) and a little more than thirty-nine percent (39.3 %) were adults. The causative agents identified were: dermatophytes (58 %), yeast (36.7 %) and non-dermatophytic filamentous fungi (NDFF, 5.3 %). The most isolated species were: Candida albicans (26.9 %), Trichophyton soudanense (24.9 %) and T. rubrum (13.7 %). These fungi were responsible for different clinical aspects, isolated and other associated. Among the isolated clinical aspects, those affecting hair (tinea capitis) were by far the largest with 44.8 %, followed by tinea unguium (34.5 %). Associations were especially type of tinea capitis and tinea manuum (2.4 %) and toenails onychomycosis associated with interdigital tinea pedis (2.7 %). Tinea capitis agents were exclusively dermatophytes and the predominant agent was T. soudanense with 47,8 %. Tinea unguium agents were yeast (79 %), dermatophytes (18 %) or NDFF (3 %) and the most found species was C. albicans (63.9 %). Dermatophytes, yeasts and molds were respectively found more in children and young adults, older adults and young adults and older adults and the elderly. In definitive, these epidemiological data should enable better diagnostic and therapeutic management of superficial mycoses.


Predictable Location of Breast Sensory Nerves for Breast Reinnervation.
The sensory innervation to the breast originates from the medial and lateral cutaneous branches of the third to fifth intercostal nerves, which are at risk for injury or loss during mastectomy. Providing reinnervation after mastectomy was introduced almost 20 years ago, but it is not widely performed, perhaps because of the difficulty of locating a recipient nerve. The authors have performed cadaveric dissections to allow for precise anatomical localization of the lateral intercostal branch providing breast sensation. Bilateral chest dissections were performed on 10 female cadavers. The lateral intercostal nerve providing sensation to breast tissue was identified. The distances from the sternum, the midclavicular line, and the lateral pectoralis minor-in addition to nerve diameter-were measured. The nerve was successfully identified bilaterally in all cadavers. The majority of nerves (16 of 20) exited from under the fourth rib. The average distance from the sternum was 13.1 ± 1.3 cm (range, 10 to 15 cm) and the average distance from the midclavicular line was 11.8 ± 2.2 cm (range, 8 to 16 cm). The nerve exited at the lateral border of the pectoralis minor or within 2 cm from the lateral border for all cadavers. The diameter of the nerve was consistently 2 mm. The nerve traveled under the thoracodorsal vessels, aiding in identification. The authors identified the predictable location of the lateral intercostal nerve providing sensation to the breast. The authors hope that by enabling surgeons to locate this nerve, more well-conducted studies will be performed investigating techniques and outcomes for breast reinnervation.


Individual recovery of health-related quality of life during 18 months post-burn using a retrospective pre-burn measurement: an exploratory study.
This study explored the individual trajectories of health-related quality of life (HRQL) compared to recalled pre-burn level of HRQL and investigated whether burn severity and post-traumatic stress disorder (PTSD) symptoms increase the risk of not returning to pre-burn level of HRQL. Data were obtained from 309 adult patients with burns in a multicenter study. Patients completed the EQ-5D-3L questionnaire with a Cognition bolt-on shortly after hospital admission, which included a recalled pre-injury measure, and, again, at 3, 6, 12 and 18 months post-burn. Burn severity was indicated by the number of surgeries, and PTSD symptoms were assessed with the IES-R at three months post-burn. Pre- and post-injury HRQL were compared to norm populations. Recalled pre-injury HRQL was higher than population norms and HRQL at 18 months post-burn was comparable to population norms. Compared to the pre-injury level of functioning, four HRQL patterns of change over time were established: Stable, Recovery, Deterioration, and Growth. In each HRQL domain, a subset of patients did not return to their recalled pre-injury levels, especially with regard to Pain, Anxiety/Depression, and Cognition. Patients with more severe burns or PTSD symptoms were less likely to return to pre-injury level of functioning within 18 months post-burn. This study identified four patterns of individual change. Patients with more severe injuries and PTSD symptoms were more at risk of not returning to their recalled pre-injury HRQL. This study supports the face validity of using a recalled pre-burn HRQL score as a reference point to monitor HRQL after burns.


Lysozyme crystal growth kinetics in microgravity.
Mach-Zehnder interferometry is applied to quantitatively characterize growth of lysozyme crystals in microgravity. Experiments were performed by the Free Interface Diffusion technique into APCF FID reactors using large seeds. Tracking of the experiments using interferometry allowed to monitor the onset of supersaturation and the seed growth. A large and stable concentration depletion zone around the growing crystal developed, whose time evolution was analyzed. The interferograms were analyzed taking into account finite thickness of the cell by integrating the concentration over the straight lines through the optical path. It was concluded that there may be a quasi-steady state growth mode at the stage when the spacial concentration distribution did not change but its absolute value over all the cell was slowly diminishing. From this portion of the data, an estimate was made of the dimensionless parameter beta R/D where beta is the face kinetic coefficient, R is the effective crystal size and D is the lysozyme diffusivity in solution, as followed from the steady state model. For the assumed quasi steady state data portion, the parameter varies between 0.7 and 0.9 suggesting mixed diffusion-interface kinetic controlled growth.


Antioxidant protection against organic and inorganic oxygen radicals by normal human plasma: the important primary role for iron-binding and iron-oxidising proteins.
Normal human plasma contains numerous high and low molecular mass redox active molecules that are able to react rapidly with organic and inorganic oxygen radicals. The ability of such plasma molecules to substantially inhibit, or delay, free radical mediated oxidation of added substrates has led to their classification as important biological antioxidants. Using phospholipids to detect organic oxygen radicals, and deoxyribose to detect inorganic oxygen radicals, we here show that the primary antioxidants of normal human plasma reside mainly in two plasma proteins representing no more than 4% of the total proteins present. The iron-binding properties of transferrin and the iron-oxidising properties of caeruloplasmin, at a reaction dilution of 1:50, offer considerable protection against organic and inorganic oxygen radicals generated by iron and ascorbate. Plasma thiol group-containing molecules, at concentrations well below those that would be required to compete with the detector molecule (based on known second order rate constants for reaction with hydroxyl radicals) inhibited damage to deoxyribose, but stimulated damage to phospholipids.


Nontuberculous Mycobacteria Isolated from Tuberculosis Suspects in Ibadan, Nigeria.
In Nigeria, one of the highest tuberculosis (TB) burdened nations, sputum smear microscopy is routinely employed for TB diagnosis at Directly Observed Treatment Short-Course (DOTS) Centers. This diagnostic algorithm does not differentiate Mycobacterium tuberculosis complex (MTC) from nontuberculous mycobacteria (NTM). Between December 2008 and January 2009, consecutive patients diagnosed with TB were screened for inclusion at 10 DOTS centers in Ibadan, Nigeria. To verify Mycobacterium species in patients diagnosed, we cultured and identified mycobacterial isolates using PCR, line probe assay, and spoligotyping techniques. From 48 patients screened, 23 met the inclusion criteria for the study. All the 23 study patients had a positive culture. Overall, we identified 11/23 patients (48%) with MTC only, 9/23 (39%) with NTM only, and 3/23 (13%) with evidence of both MTC and NTM. Strains of MTC identified were Latin American Mediterranean (LAM) genotype (n = 12), M. africanum (n = 1), and the genotype family T (n = 1). Four M. avium-intracellulare-M. scrofulaceum complexes, one M. chelonae complex, one M. abscessus, and one M. intracellulare were identified. Our findings underscore the need to incorporate molecular techniques for more precise diagnosis of TB at DOTS centers to improve clinical outcomes and safe guard public health, particularly in TB endemic countries.


A new distinctively banded-species of Panaqolus (Siluriformes: Loricariidae) from the western Amazon Basin in Peru.
Panaqolus albivermis is described as a new species based on four specimens from the San Alejandro River, a tributary of the upper Ucayali River in central Peru. Panaqolus albivermis is diagnosed from all other Panaqolus except P. maccus by having head, body, and fins with widely separated small white to yellow spots, vermiculations, and/or thin oblique bands on a black base (vs. exclusively small white to yellow spots on a black base in P. alboinaculatus, generally broad oblique bands of alternating light to dark brown in P. changae, P. gnomus, P purusiensis, and a uniformly dark gray to black body color in P. dentex, P. koko, and P. nocturnus); P. albivernis can be diagnosed from P. maccus by having a black base color (vs. brown), by having parallel dentary tooth cups (vs. acute intermandibular tooth cup angle), and by having a larger known adult body size (95.8 mm SL vs. 84.8).


Discrimination of intact and injured Listeria monocytogenes by Fourier transform infrared spectroscopy and principal component analysis.
Fourier transform infrared spectroscopy (FT-IR, 4000-600 cm(-)(1)) was used to discriminate between intact and sonication-injured Listeria monocytogenes ATCC 19114 and to distinguish this strain from other selected Listeria strains (L. innocua ATCC 51742, L. innocua ATCC 33090, and L. monocytogenes ATCC 7644). FT-IR vibrational overtone and combination bands from mid-IR active components of intact and injured bacterial cells produced distinctive "fingerprints" at wavenumbers between 1500 and 800 cm(-)(1). Spectral data were analyzed by principal component analysis. Clear segregations of different intact and injured strains of Listeria were observed, suggesting that FT-IR can detect biochemical differences between intact and injured bacterial cells. This technique may provide a tool for the rapid assessment of cell viability and thereby the control of foodborne pathogens.


Two naturally occurring mutant insulin receptors phosphorylate insulin receptor substrate-1 (IRS-1) but fail to mediate the biological effects of insulin. Evidence that IRS-1 phosphorylation is not sufficient for normal insulin action.
Two naturally occurring mutant insulin receptors, Arg-1174 --> Gln and Leu-1178 --> Pro, found in patients with dominantly inherited Type A insulin resistance, showed unusual signaling properties when stably expressed in Chinese hamster ovary (CHO) cells. Both mutant receptors were expressed on the cell surface and bound insulin normally, but showed markedly impaired autophosphorylation in response to insulin. In addition, the in vitro tyrosine kinase activity of both mutant receptors toward an artificial substrate was also severely impaired. Despite these defects of kinase activity, anti-phosphotyrosine immunoblotting of whole cell lysates and anti-phosphotyrosine immunoprecipitation of 32P-labeled cells showed insulin-stimulated tyrosine phosphorylation of a protein of approximately 185 kDa to an extent comparable to that seen in CHO cells expressing wild-type human insulin receptors. Anti-insulin receptor substrate-1 (IRS-1) immunoprecipitation followed by anti-phosphotyrosine immunoblotting confirmed that this tyrosine-phosphorylated protein was IRS-1. In contrast, CHO cells expressing an insulin receptor mutated at the ATP binding site (Lys-1030 --> Arg) showed no insulin-stimulated autophosphorylation or phosphorylation of IRS-1. Despite exhibiting apparently normal insulin stimulation of IRS-1 tyrosine-phosphorylation, cells expressing the Arg-1174 --> Gln or Pro-1178 --> Leu receptors showed marked impairment in insulin stimulation of glycogen synthesis, thymidine incorporation, and activation of MAP kinase. The inability of these mutant receptors to signal normally to metabolic and mitogenic responses suggests that insulin-stimulated tyrosine phosphorylation of IRS-1 alone is insufficient to fully mediate insulin action.


Anti-T cell receptor monoclonal antibody prolongs transgene expression following adenovirus-mediated in vivo gene transfer to mouse synovium.
There are no cures for rheumatoid arthritis (RA) or other inflammatory autoimmune arthropathies. Gene transfer to the synovium would allow administration of anti-inflammatory gene products directly to the articular space where they could exert a local down-regulatory effect on the autoimmune process. Several well-characterized murine models of arthritis closely resemble RA immunologically, genetically, and histopathologically. To determine whether the mouse could serve as a model for gene transfer to the synovium, a methodology was developed to reproducibly inject a 5-microliter volume into the articular space of the mouse knee. Using this approach, Av1LacZ4, an E1a-E3-deleted adenoviral (Ad5) vector expressing the lacZ transgene, was delivered intra-articularly (5 x 10(8) pfu). lacZ expression was observed in the articular synovium for at least 14 days. Biochemical quantitation demonstrated a gradual loss of transgene expression, associated with an early, predominantly neutrophilic, inflammatory response that progressed to a lymphocytic infiltrate, followed by gradual resolution over a 3-week period. Pretreatment with the anti-TCR monoclonal antibody (mAb) H57 resulted in a significant reduction in lymphocytic infiltration and a prolongation of transgene expression. These data demonstrate that transgenes can be delivered to the mouse knee joint space, affording a powerful tool to test the potential of gene therapy as a therapeutic modality for RA. As in other systems, the immune response against recombinant adenoviral vectors may limit the extent and duration of gene expression in the synovium. Anti-T cell mAbs may be useful in inhibiting this immune response.


Venous plasma nicotine correlates of hormonal effects of tobacco smoking.
The present study resolves some of the discrepancies in the literature by correlating the effects of tobacco smoking on hormone release with venous plasma nicotine levels. Cortisol, prolactin, and beta-endorphin concentrations were measured. Habitual male tobacco users smoked denicotinized (very low nicotine) and average nicotine cigarettes in the morning after overnight tobacco abstinence. Several venous blood samples were withdrawn before and during the smoking sessions for subsequent analyses. The increases in plasma nicotine correlated well with plasma cortisol and prolactin levels (correlation coefficients r=0.66 and 0.53, respectively, p<0.05). This study quantifies the well known increase in plasma cortisol and prolactin after nicotine postsmoking for about 1h with peak plasma levels up to 35 ng/ml. Contrary to most abused drugs which release dopamine and decrease prolactin, nicotine concentration correlated with increased prolactin release. Increases in maximal plasma beta-endorphin levels following tobacco smoking were barely statistically significant with insufficient data to obtain a correlation coefficient.


Strongyloides stercoralis hyperinfection in an unconscious diabetic patient with dermatomyositis.
A case of Strongyloides stercoralis hyperinfection in a patient with dermatomyositis and diabetes mellitus is herein reported. The case was a 60-year-old female admitted due to watery diarrhea and unconsciousness. She had a 10-year history of chronic immunosuppressive therapy including methotrexate and prednisolone for dermatomyositis. Stool parasitological examination revealed numerous rhabditiform larvae of threadworm "S. stercoralis." Larva in stool sample was characterized by sequencing of mitochondrial DNA. After treatment with ivermectin, the patient recovered without evidence of S. stercoralis in follow-up stool samples. In endemic areas, stool examination for detection of S. stercoralis should be performed on a regular basis for all patients receiving immunosuppressive therapy, as early detection and treatment are necessary to minimize complications of severe strongyloidiasis.


Optical fractal synthesizer: concept and experimental verification.
An application of optical parallel processing in the generation of fractal images is presented. Iterated function systems [M. Barnsley, Fractals Everywhere (Academic, Boston, Mass., 1988), Chap. 3] are the basis of the operation, which can be easily implemented with optical techniques. An optical fractal synthesizer is considered to compute iterated function systems effectively with the advantages of optical processing in data continuity as well as parallelism. As an instance of the optical fractal synthesizer, an experimental system consisting of two optical subsystems for affine transformation and a TV-feedback line is constructed. Several experimental results verify the principle and show the processing capability of the optical fractal synthesizer.


Anti-CD45 antibody enhances lipoxygenase pathway of human naïve mononuclear cells and cyclooxygenase pathway of neutrophils.
Anti-CD45 antibody exhibits multiple biological effects on human mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). We intended to determine whether anti-CD45 antibody could affect arachidonic acid metabolism and thereby, the interactions between human naïve MNC and PMN. Human naïve MNC and PMN were incubated with monoclonal anti-human CD45 IgG F(ab')(2) antibody or non-specific IgG F(ab')(2) for 30 min. The mRNA expression of cyclooxygenase type 1 (COX-1), type 2 (COX-2), 5-lipoxygenase (5-LOX) and leukotriene A(4) hydrolase (LTA(4) hydrolase) in both cells was detected by RT-PCR and quantified by densitometric determination. The presence of COX-1 and COX-2 molecules in the cells was detected by Western blot. The concentration of PGE(2) and LTB(4) in cultured supernatants was measured by EIA kits. Anti-CD45 IgG F(ab')(2) up-regulated LTA(4) hydrolase mRNA expression and LTB(4) production, but down-regulated COX-1 and COX-2 mRNA expression and PGE2 production, of naïve MNC compared to non-specific IgG F(ab')(2). In contrast, a reverse modulation by the specific antibody on PMN was observed including up-regulation of cyclooxygenase pathway and down-regulation of lipoxygenase pathway. A novel activity of anti-CD45 with reverse modulation on cyclooxygenase/lipoxygenase pathways was found such that the expression of COX-1 and COX-2 in PMN, and 5-LOX and LTA(4) hydrolase in MNC were enhanced.


Multiple subtypes of endothelin receptors in human and porcine tissues: characterization by ligand binding, affinity labeling, and regional distribution.
To characterize the properties and the distribution of endothelin (ET) receptor subtypes, we have examined the ligand selectivity and the molecular weight (Mr) of [125I]ET-1 and [125I]ET-3 binding sites in various tissues of human and pigs. ET-1 and ET-2 showed almost identical potencies in displacing the bound [125I]ET-1 in all of the tissues examined. ET-3, sarafotoxin S6b (SRTX-b), and sarafotoxin S6C (SRTX-c) displaced the [125I]ET-1 with nearly the same sensitivity as ET-1 (IC50 = 0.07-3.0 nM) in brain, kidney, liver, and adrenal, whereas the three peptides showed very weak competition (IC50 = 40-500 nM) against [125I]ET-1 binding in atria, aorta, lung, stomach, and uterus. The Bmax value for [125I]ET-3 was 83% of that for [125I]ET-1 in human liver membranes, whereas the Bmax for [125I]ET-3 was only 12% of that for [125I]ET-1 in human atrial membranes. [125I]ET-3 bound to liver and atrial membranes was displaced by ET/SRTX isopeptides almost equipotently. Two proteins with Mr of 110 and 50 kDa were specifically affinity-labeled with [125I]ET-1 in porcine lung membranes. The above findings indicated that two distinct subclasses of ET receptors, namely ET-1/ET-2-specific and ET/SRT family common receptors, were distributed in various proportions in mammalian tissues.


The siesta and ambulatory blood pressure: is waking up the same in the morning and afternoon?
We have shown previously that blood pressure (BP) reduction after the siesta is similar to that after night sleep. As cardiovascular events cluster around morning waking hours, when there is a sharp rise of BP and heart rate (HR), the double-product of which is a major determinant of cardiac oxygen consumption, we also investigated changes after the siesta. Twenty-four-hour ambulatory BP monitorings of 156 consecutive patients referred for evaluation of hypertension who reported the siesta (afternoon nap) were analysed. The mean daytime awake BP and HR were 145 +/- 18/80 +/- 10 mm Hg and 71 +/- 11 beats per minute (bpm). During night sleep and the siesta BP decreased significantly (P < 0.00001) to 126 +/- 20/67 +/- 10 and 125 +/- 17/65 +/- 10 mm Hg, respectively. HR decreased during the siesta (69 +/- 11 bpm; P < 0.00001) but even more so (P < 0.00001) during the night (62 +/- 8 bpm; P < 0.00001). When normotensive subjects (n = 38), untreated (n = 33) and treated hypertensives (n = 85) were evaluated separately, they all had similar trends. However, when percentage rise over the sleeping baseline was considered, there were no significant differences in the rise of BP after the siesta and night sleep. The rise in HR for the normotensives and treated hypertensives was 16% and 8%, respectively, higher in the morning than after the siesta (P < 0.0004 and P < 0.001, respectively). The double-product increased significantly more in the morning than after the siesta (both P < 0.0001) in the normotensives (by 20%) and treated hypertensives (by 10%). In untreated hypertensives the rise in HR and double-product was no different between the time periods. In conclusion, there is a higher rise of HR and double-product in the morning. The relatively lower rise after the siesta may indicate a lesser increase in cardiac oxygen consumption and, therefore, lesser potential for acute ischemia.


[ITS2 sequence analysis and identification of medicinal Artemisia plants].
Artemisia hedinii occupies an important position in the Tibetan medicine. Plants in Artemisia vary a lot and are widely distributed in the Qinghai-Tibet Plateau, many plants in Artemisia look similar, making traditional identification methods laborious. In this article, ITS2 sequences were used as DNA barcoding to identify four kinds of confusable Tibetan medicine plants in Artemisia, aiming to establish a rapid and accurate identification methods. Twenty-one samples in Artemisia were collected from the Qinghai-Tibet Plateau, ITS2 sequence PCR amplification and sequencing were conducted after the extraction of DNA. Another 11 sequence downloaded from Genbank were added to the analysis. Genetic distance calculation and analysis, building Neighbor Joining (NJ) phylogenetic tree were conducted by MEGA 6.0, also comparison of secondary structures of ITS2 sequences among samples. A. hedinii, A. annua, A. dubia and A. argyi shared close genetic distance, but the maximum distance between the four species was much greater than the minimum distance within each species, NJ tree showed that the four species went to four separate branches, differences among secondary structures of ITS2 sequences also made it clear to identify these medical plants. It could be an accurate and rapid method for identification and recognition, as well as the evolutionary relationships between the species by using ITS2 sequence as DNA barcode for plants of Tibetan Artemisia. The study provides theoretical basis for quality control, medication safety and rational exploitation.


Drosophila actin-Capping Protein limits JNK activation by the Src proto-oncogene.
The Src family kinases c-Src, and its downstream effectors, the Rho family of small GTPases RhoA and Jun N-terminal kinase (JNK) have a significant role in tumorigenesis. In this report, using the Drosophila wing disc epithelium as a model system, we demonstrate that the actin-Capping Protein (CP) αβ heterodimer, which regulates actin filament (F-actin) polymerization, limits Src-induced apoptosis or tissue overgrowth by restricting JNK activation. We show that overexpressing Src64B drives JNK-independent loss of epithelial integrity and JNK-dependent apoptosis via Btk29A, p120ctn and Rho1. However, when cells are kept alive with the Caspase inhibitor P35, JNK acts as a potent inducer of proliferation via activation of the Yorkie oncogene. Reducing CP levels direct apoptosis of overgrowing Src64B-overexpressing tissues. Conversely, overexpressing capping protein inhibits Src64B and Rho1, but not Rac1-induced JNK signaling. CP requires the actin-binding domain of the α-subunit to limit Src64B-induced apoptosis, arguing that the control of F-actin mediates this effect. In turn, JNK directs F-actin accumulation. Moreover, overexpressing capping protein also prevents apoptosis induced by ectopic JNK expression. Our data are consistent with a model in which the control of F-actin by CP limits Src-induced apoptosis or tissue overgrowth by acting downstream of Btk29A, p120ctn and Rho1, but upstream of JNK. In turn, JNK may counteract the effect of CP on F-actin, providing a positive feedback, which amplifies JNK activation. We propose that cytoskeletal changes triggered by misregulation of F-actin modulators may have a significant role in Src-mediated malignant phenotypes during the early stages of cellular transformation.


Nuclear localization of glyceraldehyde-3-phosphate dehydrogenase is not involved in the initiation of apoptosis induced by 1-Methyl-4-phenyl-pyridium iodide (MPP+).
Nuclear localization of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is implicated in the process of apoptosis. To study the function of GAPDH, we expressed GAPDH C-terminally fused with or without nuclear localization signal (NLS) in SH-SY5Y and NB41A3 cells using a retrovirus expression system. GAPDH carrying NLS (GAPDH-NLS) was expressed mainly in the nucleus. However, expression of GAPDH-NLS did not cause any difference in cell survival rate as compared to that of the vector alone or GAPDH without NLS. Treatment with 1-Methyl-4-phenyl-pyridium iodide (MPP+) caused no difference in the cell survival rate or in the pattern or extent of apoptosis among the three transductants. In the cells expressing GAPDH without NLS, MPP+ did not cause visible translocation of GAPDH into nucleus before the onset of apoptosis. Since GAPDH is known to comprise a CRM1-mediated nuclear export signal, we blocked the nuclear export of GAPDH by treatment with leptomycin B, an inhibitor of CRM1-mediated nuclear export. The treatment did not cause any difference in apoptosis among the three transductants. An additional treatment with MPP+ induced no apoptotic difference in these cells. Thus, we have concluded that a simple nuclear localization of GAPDH does not induce apoptosis, and that MPP+-induced apoptosis is not caused by nuclear translocation of GAPDH.


[Hybrid room - the new standard for cooperation of cardiosurgeon, anaesthesiologist and invasive cardiologist in treating difficult, complex cardiovascular patients].
The concept of hybrid room is to combine capabilities of cardiosurgery operating room and fully equipped cathlab. Since May 2011, an ultramodern hybrid room has been working, in our center. The cases reported in this article show the possibilities of cooperation of cardiosurgeons, anaesthesiologists and invasive cardiologists in performing difficult, complex cardiovascular interventions. In near future the capabilities of hybrid room will allow to perform simultaneously a number of complex cardiovascular procedures. It should not only shorten the time of hospitalisation but also substantially improve the patients comfort.


[Relationship of adiponectin and visfatin with fetus intrauterine growth].
To explore the correlation between adipocyte factors (adiponectin and visfatin) and fetus intrauterine growth. Enzyme immunoassay was used to measure the adiponectin and visfatin levels in maternal and umbilical serum from 14 women with fetal growth restriction (FGR group), 14 women with macrosomia (macrosomia group) and 14 normal pregnant women (control group). The correlations of cord serum adiponectin and visfatin with maternal serum adiponectin and visfatin were analyzed. (1) Serum visfatin levels in FGR mothers [(41.4 +/- 5.5)] microg/L were significantly higher than that in control women [(34.7 +/- 4.9) microg/L] and macrosomia mothers [(37.3 +/- 4.4) microg/L; P < 0.01, P < 0.05]. Serum adiponectin levels in macrosomia mothers [(4.1 +/- 1.3) mg/L] were significantly lower than that in control women [(6.6 +/- 1.5) mg/L] and FGR mothers [(6.4 +/- 1.3) mg/L; P < 0.01]. (2) Serum visfatin levels in FGR babies [(58.1 +/- 7.6) microg/L] were significantly increased than that in control newborns [(42.6 +/- 7.8) microg/L] and macrosomia babies [(48.5 +/- 9.1) microg/L; P < 0.01, P < 0.05]. Serum adiponectin levels in macrosomia babies [(6.5 +/- 1.3) mg/L] were significantly decreased than that in control newborns [(7.7 +/- 1.5) mg/L] and FGR babies [(7.7 +/- 1.0) mg/L; P < 0.05, P < 0.05]. (3) Maternal serum visfatin levels were positively correlated with umbilical serum visfatin levels (r = 0.720, P < 0.01). Umbilical serum adiponectin levels were higher than that in maternal serum, but there were no relationship between them (r = 0.301, P > 0.05). The changes of visfatin and adiponectin levels may be related to the occurrence of FGR and fetal macrosomia.


Post-collisional mantle delamination in the Dinarides implied from staircases of Oligo-Miocene uplifted marine terraces.
The Dinarides fold-thrust belt on the Balkan Peninsula resulted from convergence between the Adriatic and Eurasian plates since Mid-Jurassic times. Under the Dinarides, S-wave receiver functions, P-wave tomographic models, and shear-wave splitting data show anomalously thin lithosphere overlying a short down-flexed slab geometry. This geometry suggests a delamination of Adriatic lithosphere. Here, we link the evolution of this continental convergence system to hitherto unreported sets of extensively uplifted Oligocene-Miocene (28-17 Ma) marine terraces preserved at elevations of up to 600 m along the Dinaric coastal range. River incision on either side of the Mediterranean-Black Sea drainage divide is comparable to the amounts of terrace uplift. The preservation of the uplifted terraces implies that the most External Dinarides did not experience substantial deformation other than surface uplift in the Neogene. These observations and the contemporaneous emplacement of igneous rocks (33-22 Ma) in the internal Dinarides suggest that the Oligo-Miocene orogen-wide uplift was driven by post-break-off delamination of the Adriatic lithospheric mantle, this was followed by isostatic readjustment of the remaining crust. Our study details how lithospheric delamination exerts an important control on crustal deformation and that its crustal signature and geomorphic imprint can be preserved for millions of years.


Green beards in the light of indirect genetic effects.
The green-beard effect is one proposed mechanism predicted to underpin the evolution of altruistic behavior. It relies on the recognition and the selective help of altruists to each other in order to promote and sustain altruistic behavior. However, this mechanism has often been dismissed as unlikely or uncommon, as it is assumed that both the signaling trait and altruistic trait need to be encoded by the same gene or through tightly linked genes. Here, we use models of indirect genetic effects (IGEs) to find the minimum correlation between the signaling and altruistic trait required for the evolution of the latter. We show that this correlation threshold depends on the strength of the interaction (influence of the green beard on the expression of the altruistic trait), as well as the costs and benefits of the altruistic behavior. We further show that this correlation does not necessarily have to be high and support our analytical results by simulations.


Comparative effects of vitamin K2 and vitamin E on experimental arteriosclerosis.
The comparative effects of vitamin K2 and vitamin E on aortic calcium (Ca) and inorganic phosphorus (P) levels in the aorta and the elastin fraction (fr.) were investigated in male rats after experimental arteriosclerosis was induced by vitamin D2 with atherogenic diet. Both vitamin K2 (100 mg/kg b.w.) and vitamin E (40 mg/kg b.w.) inhibited the increase of Ca and P in the aorta and the elastin fr. from the arteriosclerotic rats. Vitamin K2 (50 mg/kg b.w.) also suppressed the deposition of Ca and P in the aorta, but there was no change due to vitamin K3 or geranylgeraniol (side chain of vitamin K2) administration. Both vitamin K2 and vitamin E showed lipid radical scavenging activity in the in vitro experiment. However, neither vitamin K3 nor geranylgeraniol exhibited anti-arteriosclerotic or radical scavenging activity under the above experimental conditions. It is suggested that vitamin K2 and vitamin E promoted an antiarteriosclerotic effect by radical scavenging activity. These actions of vitamin K2 are required in the structure of 2-methylnaphtoquinone and its side chain (geranylgeraniol).


Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia.
Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.


Mechanisms of CP190 Interaction with Architectural Proteins in Drosophila Melanogaster.
Most of the known Drosophila architectural proteins interact with an important cofactor, CP190, that contains three domains (BTB, M, and D) that are involved in protein-protein interactions. The highly conserved N-terminal CP190 BTB domain forms a stable homodimer that interacts with unstructured regions in the three best-characterized architectural proteins: dCTCF, Su(Hw), and Pita. Here, we identified two new CP190 partners, CG4730 and CG31365, that interact with the BTB domain. The CP190 BTB resembles the previously characterized human BCL6 BTB domain, which uses its hydrophobic groove to specifically associate with unstructured regions of several transcriptional repressors. Using GST pull-down and yeast two-hybrid assays, we demonstrated that mutations in the hydrophobic groove strongly affect the affinity of CP190 BTB for the architectural proteins. In the yeast two-hybrid assay, we found that architectural proteins use various mechanisms to improve the efficiency of interaction with CP190. Pita and Su(Hw) have two unstructured regions that appear to simultaneously interact with hydrophobic grooves in the BTB dimer. In dCTCF and CG31365, two adjacent regions interact simultaneously with the hydrophobic groove of the BTB and the M domain of CP190. Finally, CG4730 interacts with the BTB, M, and D domains of CP190 simultaneously. These results suggest that architectural proteins use different mechanisms to increase the efficiency of interaction with CP190.


Lydia Holman: community health pioneer.
Trained and inspired by the Henry Street Settlement, this Pennsylvania-born nurse made the health of the people of remote Mitchell County, North Carolina, her life's work. Her courage and persistence attracted the attention of the national press and President Hoover, yet today she is all but forgotten.


Reliability of inspiratory capacity for estimating end-expiratory lung volume changes during exercise in patients with chronic obstructive pulmonary disease.
The inspiratory capacity (IC) maneuver is increasingly used to monitor exercise-induced dynamic hyperinflation in patients with COPD. However, the reliability of this method in patients with COPD exercising to symptom limitation has not been systematically studied and presented. The purpose of the present study was therefore to evaluate the reliability of the IC maneuver in assessing changes in end-expiratory lung volume (EELV) by assessing the pressure developed during IC maneuvers, in patients with COPD during incremental bicycle exercise to exhaustion. Fifteen patients with stable COPD performed bicycle exercise to symptom limitation. During the experiment, the patients performed IC efforts during resting breathing and at the end of each exercise work load. Esophageal pressure (Pes) measured at peak inspired volume plateau (zero flow) was -13.5 +/- 1.9 and -13.4 +/- 1.9 cm H2O (p = 0.79) during IC maneuvers at resting breathing and during the final exercise work load, respectively. When the Pes values at the peak inspired volume plateau during IC efforts at each exercise level were expressed as a percentage of those during resting breathing, the great majority of the ratios were above 90% with the lowest at 84%, and these ratios were independent of exercise intensity. Despite a constant Pes during IC, there was a progressive decrease in IC with increasing exercise work load in most patients, suggesting an increase in EELV. At the highest exercise work load achieved, delta EELV calculated as the decrease in IC was 0.26 +/- 0.06 L (p < 0.001). We conclude that repeated IC maneuver is a simple and reliable method for estimating EELV changes during exercise to exhaustion in patients with COPD.


Gas-chamber mediastinoscopy for dissection of the upper esophagus.
Mediastinoscopy has the potential to bring under view the upper mediastinum, the area most difficult to dissect during transhiatal esophagectomy. The aim of the present study was to evaluate in an animal model the feasibility of the gas-chamber mediastinoscopy technique for dissection of the upper esophagus. Operations were performed in nine Landrace pigs using a 30 degrees laparoscope and conventional 35-cm laparoscopic instruments. Through a left collar incision a virtual space was created with sharp and blunt dissection around the cervical esophagus and insufflated with CO2 at a pressure of 5 mmHg. Using one 10-mm optical trocar and two 5-mm working trocars dissection advanced in the periesophageal space with the aim to reach at least to the tracheal bifurcation. Performed under visual control, the procedure was accurate and safe, the level of tracheal bifurcation being reached in all cases. Anatomical structures such as trachea and its bifurcation, pleura, pericardium, arch of the azygos vein and periesophageal lymph nodes were visible during the operation. There were no major intraoperative incidents and blood loss was minimal. The technique of gas-chamber mediastinoscopy is feasible. It allows a fair amount of freedom of movement for the working instruments and offers a good view on the operative field for a controlled and accurate dissection. Further evaluation in experimental and clinical studies is required to establish the role of this procedure in esophageal surgery.


Clinical applications of power vectors.
The study of infant vision is closely coupled to the study of the refraction, change in refraction over time, and the effect of spectacle correction on visual development. Frequently, reports are limited to descriptions of spherical equivalent or cylinder power without regard to axis, as data are frequently collected in the clinical format of sphere, cylinder, and axis (S, C, A). Conversion from clinical notation to a power vector representation of refraction allows unambiguous description of how refractions change over time and differ between repeated measurements. This article presents a series of examples of Microsoft Excel spreadsheet formulas that make the conversion from clinical notation to power vector format, and provides examples of useful applications of these methods.


Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study.
Statins have been shown to improve hyperandrogenism in women with polycystic ovary syndrome (PCOS). However, their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus. Because women with PCOS are prone to disturbances in glucose metabolism, statin therapy could also have negative effects. Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS. We conducted a randomized, double-blind, placebo-controlled 6-month follow-up study conducted at Oulu University Hospital, Finland. Women with PCOS (Rotterdam criteria) were treated with atorvastatin (20 mg/d, n = 15) or placebo (n = 13) for 6 months. Fasting serum samples were collected at baseline and at 3 and 6 months. Oral and iv glucose tolerance tests were performed at 0 and 6 months. Androgen secretion and glucose metabolism were measured. Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity (insulinogenic and Matsuda indexes) decreased during 6 months of atorvastatin therapy. Serum levels of dehydroepiandrosterone sulfate decreased in the atorvastatin group, whereas no change was observed in serum testosterone levels. Levels of C-reactive protein, total and low-density lipoprotein-cholesterol, and triglycerides decreased significantly during statin therapy. Atorvastatin therapy improves chronic inflammation and lipid profile, but it impairs insulin sensitivity in women with PCOS. Because women with PCOS have an increased risk of developing type 2 diabetes mellitus, the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease, and not only because of PCOS.


Transport-dependent anoxic cell injury in the isolated perfused rat kidney.
The hypothesis that decrease in energy demand may prevent anoxic cell damage has been examined in the medullary thick ascending limb of isolated perfused rat kidneys exposed to oxygen deprivation. The effects of decreasing active reabsorptive transport in the medullary thick ascending limb were observed on the extensive damage regularly induced by hypoxic perfusion (gassed with no oxygen) or potassium cyanide. Anoxic injury was consistently attenuated or abolished if reabsorptive transport was decreased with ouabain or furosemide or by halting the glomerular filtration rate with the use of a hyperoncotic medium (nonfiltering kidney). Comparison of the injury generated by warm ischemia for identical time periods showed that complete ischemia does not reproduce the severe lesions seen during hypoxic perfusion. These results suggest that transport activity is a determining factor of anoxic cell death in the thick ascending limb of Henle's loop.


The effectiveness of a fecal diverting device for prevention of septic complications in a dog model of ischemic bowel anastomosis.
A type of bypass tube for a fecal diversion device (FDD) was created to protect colorectal anastomosis. We evaluated the effectiveness of the FDD in an animal study. The study was performed in an experimental animal laboratory of a tertiary referral center hospital. Thirty mongrel dogs were randomized to the FDD or control group (n = 15, each). An ischemic anastomosis model was used to readily produce anastomotic leakage (AL) in both groups. The FDD was fixed intraluminally at 10 cm above the anastomotic site in the FDD group. No protective methods were used in the control group. The postoperative observation period was 3 weeks. The 3 week-survival rates were higher in the FDD group compare with the control group (80%, 12/15 vs. 40%, 6/15; log-rank, P = 0.024). The incidence of AL causing generalized peritonitis was lower in the FDD group than in the control group (20.0%, 3/15 vs. 60.0%, 9/15; P = 0.025) despite the overall incidence of complications being similar in the both groups (53.3%, 8/15 vs. 66.7%, 10/15; P = 0.456). Colonic wall erosions in the FDD fixing area were seen in two subjects (13.3%) in the FDD group. However, the two subjects survived to the end of the experimental period. In the FDD group, five subjects (33.3%, 5/15) did not retain their FDD, and three among them died from generalized peritonitis. This study shows the effectiveness of the FDD at preventing septic complications in a dog model of ischemic bowel anastomosis.


Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met.
Colon cancer prevention currently relies on colonoscopy using white light to detect and remove polyps, but small and flat polyps are difficult to detect and frequently missed when using this technique. Fluorescence colonoscopy combined with a fluorescent probe specific for a polyp biomarker may improve polyp detection. Here we describe GE-137, a water-soluble probe consisting of a 26-amino acid cyclic peptide that binds the human tyrosine kinase c-Met conjugated to a fluorescent cyanine dye. Intravenous administration of GE-137 leads to its accumulation specifically in c-Met-expressing tumors in mice, and it is safe and well tolerated in humans. Fluorescence colonoscopy in patients receiving intravenous GE-137 enabled visualization of all neoplastic polyps that were visible with white light (38), as well as an additional nine polyps that were not visible with white light. This first-in-human pilot study shows that molecular imaging using an intravenous fluorescent agent specific for c-Met is feasible and safe, and that it may enable the detection of polyps missed by other techniques.


Sustainability and Environmental Impact of Ethanol and Oxyhydrogen Addition on Nanocoated Gasoline Engine.
Climate change, clean air, renewable energy, nontoxic surroundings, and the opportunity to live in a healthy community are just few of the issues that environmental sustainability addresses. To improve environmental health and quality of life, several researchers have turned their attention to alternative energy sources like ethanol and oxyhydrogen. In latest years, significant progress has been made in the development of ethanol and hydrogen as clean energy sources. A higher octane rating is achieved by mixing ethanol with gasoline rather than using regular gasoline. A novel mix of oxyhydrogen, ethanol, and gasoline is ecologically friendly while simultaneously increasing the performance of gasoline engines. In this study, a nanoparticle-coated piston on a low heat rejection gasoline engine fuelled by an ethanol-gasoline mix with oxyhydrogen addition was investigated. It has been evaluated that thermal efficiency improved by up to 25% while fuel consumption can be reduced by up to 28% on a volume basis compared to the baseline engine. Furthermore, the decrease in harmful carbon monoxide reached around 10%, and the reduction in unburned hydrocarbon emissions reached 18%.


Non-surgical periodontal treatment reduces cardiovascular risk in refractory hypertensive patients: a pilot study.
To evaluate the effects of non-surgical periodontal treatment on left ventricular mass (LVM), arterial stiffness, systolic and diastolic blood pressure and plasma levels of inflammatory markers (C-reactive protein (CRP), fibrinogen and interleukin-6) in refractory hypertension patients. This interventional prospective cohort pilot study included 26 patients (53.6 ± 8.0 years old) diagnosed with refractory hypertension and generalized chronic periodontitis. Subjects received non-surgical periodontal treatment according to their needs. Plasma levels of systemic inflammation (CRP; fibrinogen and interleukin-6) and established cardiovascular risk factors [systolic and diastolic blood pressure (SBP and DBP), left ventricular mass (LVM) and arterial stiffness] were assessed at three time points (baseline, 3 months after baseline and 6 months after periodontal therapy). Periodontal therapy significantly reduced all cardiovascular risk markers evaluated. Median values of SBP and DBP were reduced by 12.5 mmHg and 10.0 mmHg, respectively, whereas left ventricular mass (LVM) reduced by 12.9 g and pulse wave velocity reduced by 0.9 m/s (p < 0.01). Levels of CRP, IL-6 and fibrinogen lowered by 0.5 mg/dl, 1.4 pg/dl and 37.5 mg/dl (p < 0.01), respectively, 6 months after periodontal therapy. Periodontal therapy significantly reduced levels of CRP, IL-6, fibrinogen, blood pressure, LVM and arterial stiffness, lowering cardiovascular risk in refractory hypertensive patients.


Recombinant tissue-type plasminogen activator: current concepts and guidelines for clinical use in acute myocardial infarction. Part II.
The extraordinarily high prevalence of coronary heart disease, coupled with the alarming incidence of MI in Western society, has encouraged the investigation and development of pharmacologic agents that can be employed widely, quickly, effectively, and safely. Recombinant t-PA has played a vital role in the treatment of MI, restoring coronary arterial patency, limiting infarct size, preserving ventricular function, and improving patient survival. It has been shown to be safe when given to carefully selected patients and, although indications for clinical use have been relatively restricted, they appear to be expanding considerably. Future investigations must continue to focus on patient selection to allow treatment for all patients who would derive benefit and to establish dosing regimens and adjuvant therapies that will maximize coronary reperfusion while concomitantly limiting reocclusion and hemorrhagic complications.


Atlas-based under-segmentation.
We study the widespread, but rarely discussed, tendency of atlas-based segmentation to under-segment the organs of interest. Commonly used error measures do not distinguish between under- and over-segmentation, contributing to the problem. We explicitly quantify over- and under-segmentation in several typical examples and present a new hypothesis for the cause. We provide evidence that segmenting only one organ of interest and merging all surrounding structures into one label creates bias towards background in the label estimates suggested by the atlas. We propose a generative model that corrects for this effect by learning the background structures from the data. Inference in the model separates the background into distinct structures and consequently improves the segmentation accuracy. Our experiments demonstrate a clear improvement in several applications.


Predicting Key Change Events in Emotionally Focused Couple Therapy.
In emotionally focused couple therapy (EFT), the blamer-softening event helps individuals express and respond to partners' unmet attachment needs. This study examined the impact of this event in relation to attachment at intake and changes in marital satisfaction from pre- to posttherapy. Thirty-two couples were provided an average of 21 sessions of EFT. Hierarchical linear modeling revealed that the occurrence of a softening event significantly predicted increased marital satisfaction. Furthermore, the occurrence of a softening event significantly moderated the relationship between attachment avoidance at intake and change in marital satisfaction from pre- to posttherapy. For couples who had a softening event, partners with higher levels of attachment avoidance were less likely to have positive changes in marital satisfaction.


Comparison of graphite materials for targets of laser ion source.
To investigate efficient graphite material for carbon ion production in laser ion source, the plasma properties produced from these materials are measured. Comparing acquired current profile and charge state distribution, the distributions of ions in laser induced plasma from isotropic graphite and single crystal of graphite are different. The produced quantity of C(6+) from isotropic materials is larger than that from single crystal.


Solvent Effect on the Self-Assembly of a Thin Film Consisting of Y-Shaped Copolymer.
The self-assembly of an amphiphilic Y-shaped copolymer consisting of two hydrophilic branches and one hydrophobic branch in a thin film is investigated under different conditions by virtue of mesoscopic computer modelling, accompanied by doping with a single solvent, doping with a binary solvent, and those solvent environments together with the introduction of confinement defined by various acting distances and influencing regions. A cylindrical micellar structure is maintained, as it is in the thin film with the doping of either 10% hydrophobic solvent or 10% hydrophilic solvent, whose structure consists of the hydrophobic core and hydrophilic shell. Attributed to the hydrophobicity/hydrophilia nature of the solvents, different solvents play an obvious role on the self-assembled structure, i.e., the hydrophobic solvent presents as a swelling effect, conversely, the hydrophilic solvent presents as a shrinking effect. Further, the synergistic effect of the binary solvents on the self-assembly produces the lowest values in both the average volumetric size and free energy density when the quantity of hydrophobic solvent and hydrophilic solvent is equivalent. Interestingly, the solvent effect becomes more pronounced under the existent of a confinement. When a lateral-oriented confinement is introduced, a periodically fluctuating change in the cylindrical size occurs in two near-wall regions, but the further addition of either hydrophobic or hydrophilic solvent can effectively eliminate such resulting hierarchical-sized cylinders and generate uniform small-sized cylinders. However, with the introduction of a horizontal-orientated confinement, the copolymers self-assemble into the spherical micellar structure. Moreover, the further addition of hydrophobic solvent leads to a decrease in the average size of micelles via coalescence mechanism, in contrast, the further addition of hydrophilic solvent causes an increase in the average size of micelles via splitting mechanism. These findings enrich our knowledge of the potential for the solvent effect on the self-assembly of amphiphilic copolymer system, and then provide theoretical supports on improving and regulating the mesoscopic structure of nanomaterials.