Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.
Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.


Acoustic far-field prediction based on near-field measurements by using several different holography algorithms.
Near-field acoustical holography (NAH) is a useful tool for sound field reconstruction and sound source identification. In NAH, a basis model is first selected to represent the physical sound field, and then a near-field measurement is made with a microphone array. Next, the parameters in the selected model can be estimated based on the measurements by using an inverse approach, resulting in the sound field near the source being reconstructed so that the sound source location can be identified. But, in addition to being able to reconstruct the near-field of a source, the far-field can also be predicted with the identified sound source model. A significant amount of work has been performed to study the near-field reconstruction capability of different NAH algorithms, but there has been a limited number of publications in which the far-field prediction accuracy, based on the near-field measurement constructed model, has been considered. In the present experimental work, two multi-transducer loudspeakers were placed side-by-side to create a multi-component sound source, and two sets of measurements were conducted: an intensity probe scanned the sound field generated by the loudspeakers in both the near-field (0.05 m) and far-field (0.48 m) such that the true near- and far-field intensity spatial distributions and total sound power could be identified. Then, based on the near-field pressure measurements, four acoustical holography algorithms, statistically optimized near-field acoustical holography, wideband acoustical holography, l1-norm minimization, and a hybrid compressive sampling method were used to predict the near- and far-field sound intensity distributions. The near- and far-field prediction results were compared with the direct measurement, and the sound field reconstruction accuracy was studied. It was found that all of the algorithms were able to reconstruct the near-field well when the near-field measurements were used to construct the model. It was found that with the abovementioned models, far-field reconstructions could correctly predict the spatial sound field distribution, but in all of the cases, the total sound power was underestimated.


String Vessel Formation is Increased in the Brain of Parkinson Disease.
String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.


Effects of resveratrol (trans-3,5,4'-trihydroxystilbene) treatment on cardiac remodeling following myocardial infarction.
Resveratrol (RES; trans-3,5,4'-trihydroxystilbene) has been shown to improve health and slow the progression of disease in various models. Several cardioprotective mechanisms have been identified including antioxidant, anti-inflammatory, and antifibrotic actions. Each of these actions is thought to have the ability to attenuate the pathophysiology underlying the deleterious cardiac structural remodeling that results from acute myocardial infarction (MI). Therefore, we evaluated the effect of resveratrol treatment on the progression of cardiac remodeling after MI. Four groups of rats (sham, n = 6; sham + RES, n = 21; MI, n = 26; MI + RES, n = 24) were treated for 13 weeks, starting 7 days before ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography revealed that resveratrol had no effect on MI-induced left-ventricular and left-atrial dilatation or reduction in left-ventricular fractional shortening. Consistent with these findings, resveratrol did not improve the deterioration of hemodynamic function or reduce infarct size at 12 weeks post-MI. Resveratrol-treated animals did, however, show preserved cardiac contractile reserve in response to dobutamine administration. Radioligand binding revealed that MI reduced beta-adrenergic receptor density. Resveratrol administration increased beta-adrenoceptor density, so that resveratrol-treated MI rats had beta-adrenoceptor densities similar to normal rats. Real-time reverse transcription-polymerase chain reaction revealed that MI-induced changes in sarcoplasmic reticulum Ca2+-ATPase 2 and transforming growth factor beta-1 expression were unaltered by resveratrol, whereas MI-induced increases in atrial natriuretic factor (ANF) and connective tissue growth factor (CTGF) expression were attenuated. Resveratrol treatment does not improve cardiac remodeling and global hemodynamic function post-MI but does preserve contractile reserve and attenuate ANF and CTGF up-regulation.


Predicting regular breast cancer screening in African-American women with a family history of breast cancer.
To evaluate the impact of socioeconomic, personal and affective factors on regular breast cancer screening in at-risk African-American women. The study was a cross-sectional analysis assessing socioeconomic and affective predictors of breast cancer screening practices. Unaffected African-American women ages 40-64 with a family history of breast cancer were recruited from community settings. The main outcome measures were recent mammography, regular mammography and regular breast self-examinations. The majority of women reported having a recent mammogram (73%) and yearly mammograms (71%). More than half (56%) reported monthly breast self-examinations (BSEs). Available health insurance and risk perception had significant independent associations with regular mammography screening so that women having a mammogram every 6-12 months were more likely to have health insurance [odds ratio (OR)=4.99, 95% confidence interval (CI): 1.05-23.52], and women not engaged in regular screenings were less likely to perceive future breast cancer risk (OR=0.10, 95% CI: 0.01-0.96). Access to regular healthcare had a significant independent association with recent mammography so that women having a mammogram in the past 12 months were more likely to have access to regular healthcare (OR=6.59, 95% CI: 1.01-42.79). A significant majority of this subset of African-American women engage in repeat mammography screenings with cognitive and economic factors predicting noncompliance. Additional research with repeat mammography users is required so that regular screening practices can be encouraged among all at-risk women.


Reduced survival of young patients under 55 years with metastatic prostate cancer: a population-based study.
Objective: The aim of this study was to evaluate the prognosis of patients with metastatic prostate cancer (mPCa) in different age groups. Methods: Patients with mPCa from 2004 to 2016 in the Surveillance, Epidemiology and End Results (SEER) database were identified. Seven groups were divided according to the age at diagnosis, including ≤55 years, 56-60 years, 61-65 years, 66-70 years, 71-75 years, 76-80 years and >80 years. Fine and Gray's competing risks model and Kaplan-Meier analysis were conducted to evaluate the cancer-specific survival (CSS). Results: A total of 36231 patients with mPCa were included. The CSS curves of the overall cohort showed that patients aged ≤55 years had significantly worse CSS than patients in age groups of 56-60 [HR:0.93 (0.87~1.00), p=0.039], 61-65 [HR:0.91 (0.85~0.97), p=0.003] and 66-70 [HR:0.90 (0.84~0.96), p=0.001]. After removing patients dead for other reasons, the differences of CSS curves between ≤55 years group and 56-70 years groups were not significant. However, the mean survival time of ≤55 years group (55.78±2.48 months) was still shorter than 56-60 years (57.28±2.35 months), 61-65 years (57.64±2.07 months), and 66-70 years (57.11±2.11 months). When stratified by M stages, similar results were found in M1a, M1b and M1c stage groups. According to Fine-Gray competing risks models, patient ≤55 years featured significantly higher sub-distribution hazard ratio (sdHR) than 61-65 years group [sdHR: 0.94(0.88~1.00); p=0.046]. Conclusions: The mPCa patients ≤55 years seemed to be associated with worse prognosis in comparison with patients aging 56-70 years.


A new lignan from the seeds of Arctium lappa.
A new compound, neoarctin A (1), together with nine known compounds (2-10), were obtained from the ethanolic extract of the seeds of Arctium lappa. The structure of 1 was elucidated on the basis of spectral and chemical evidence.


Characteristics of highly cross-linked polyethylene wear debris in vivo.
Despite the widespread implementation of highly cross-linked polyethylene (HXLPE) liners to reduce the clinical incidence of osteolysis, it is not known if the improved wear resistance will outweigh the inflammatory potential of HXLPE wear debris generated in vivo. Thus, we asked: What are the differences in size, shape, number, and biological activity of polyethylene wear particles obtained from primary total hip arthroplasty revision surgery of conventional polyethylene (CPE) versus remelted or annealed HXLPE liners? Pseudocapsular tissue samples were collected from revision surgery of CPE and HXLPE (annealed and remelted) liners, and digested using nitric acid. The isolated polyethylene wear particles were evaluated using scanning electron microscopy. Tissues from both HXLPE cohorts contained an increased percentage of submicron particles compared to the CPE cohort. However, the total number of particles was lower for both HXLPE cohorts, as a result there was no significant difference in the volume fraction distribution and specific biological activity (SBA; the relative biological activity per unit volume) between cohorts. In contrast, based on the decreased size and number of HXLPE wear debris there was a significant decrease in total particle volume (mm(3)/g of tissue). Accordingly, when the SBA was normalized by total particle volume (mm(3)/gm tissue) or by component wear volume rate (mm(3)/year), functional biological activity of the HXLPE wear debris was significantly decreased compared to the CPE cohort. Indications for this study are that the osteolytic potential of wear debris generated by HXLPE liners in vivo is significantly reduced by improvements in polyethylene wear resistance.


Long-term treatment of bromocriptine-intolerant prolactinoma patients with CV 205-502.
Prolactin-secreting pituitary adenomas are an importance cause of male and female infertility. Dopaminergic drug therapy is the cornerstone of treatment. However, the currently available drugs, particularly bromocriptine, are associated with frequent adverse effects. In this study we evaluated the efficacy and safety of long-term treatment with a new dopaminergic agent, CV 205-502 (CV) in prolactinoma patients previously intolerant of bromocriptine. Nine patients (five male, four female) were treated for up to 39 months. Six had macroprolactinomas, and three had microprolactinomas; four had had previous transphenoidal surgery. Prolactin levels, tumor size and pituitary function were determined before treatment. These parameters and indices of drug toxicity were monitored at regular intervals. Prolactin decreased from 546 +/- 381 (SE) to 19.3 +/- 9.4 micrograms/L on CV doses ranging from 75 to 600 micrograms orally, given at bedtime (percent decrease, 37-99; mean +/- SE, 87 +/- 6.5%). Levels were normalized in six patients. Twenty-four-hour prolactin profiles documented adequate suppression with a single daily dose. All clinical symptoms related to hyperprolactinemia subsided. One accidental pregnancy occurred, and two other women had normalization of menstrual function. One man regained a normal sperm count. Of the four patients who presented with arrested puberty, only the one without previous surgery completed normal puberty during CV treatment. Mild drug-related adverse effects were reported by three patients. Dose reduction eliminated the adverse effects with adequate prolactin suppression in two; the third stopped treatment. Tumor size decreased in three of six macroprolactinoma patients. Liver and kidney function, hematocrit, WBC and platelet counts, EKG and urinalysis remained normal in all.(ABSTRACT TRUNCATED AT 250 WORDS)


Unjamming in models with analytic pairwise potentials.
Canonical models for studying the unjamming scenario in systems of soft repulsive particles assume pairwise potentials with a sharp cutoff in the interaction range. The sharp cutoff renders the potential nonanalytic but makes it possible to describe many properties of the solid in terms of the coordination number z, which has an unambiguous definition in these cases. Pairwise potentials without a sharp cutoff in the interaction range have not been studied in this context, but should in fact be considered to understand the relevance of the unjamming phenomenology in systems where such a cutoff is not present. In this work we explore two systems with such interactions: an inverse power law and an exponentially decaying pairwise potential, with the control parameters being the exponent (of the inverse power law) for the former and the number density for the latter. Both systems are shown to exhibit the characteristic features of the unjamming transition, among which are the vanishing of the shear-to-bulk modulus ratio and the emergence of an excess of low-frequency vibrational modes. We establish a relation between the pressure-to-bulk modulus ratio and the distance to unjamming in each of our model systems. This allows us to predict the dependence of other key observables on the distance to unjamming. Our results provide the means for a quantitative estimation of the proximity of generic glass-forming models to the unjamming transition in the absence of a clear-cut definition of the coordination number and highlight the general irrelevance of nonaffine contributions to the bulk modulus.


The Role of Txnip in Mitophagy Dysregulation and Inflammasome Activation in Diabetic Retinopathy: A New Perspective.
Mitochondria are responsible for bioenergetics, metabolism and apoptosis signals in health and disease. The retina being a part of the central nervous system consumes large amounts of glucose and oxygen to generate ATP via the mitochondrial oxidative phosphorylation for its phototransduction and visual function. During ATP generation, electrons leak from the mitochondrial electron transport chain, which is captured by molecular oxygen to produce reactive oxygen species (ROS). These mtROS damage mitochondrial proteins, mtDNA, and membrane lipids and release them in the cytosol. Mitochondrial components are recognized as danger-associated molecular patterns (DAMPS) by cytosolic pattern recognition receptors such as NOD-like receptors, NLRP3 inflammasomes. They process pro-caspase-1 to active caspase-1, which cleaves pro-inflammatory IL-1β o mature IL-1β causing inflammation and cell death by pyroptosis. To counter the damaging action of mtROS and inflammasomes in fully differentiated cells in the retina, the removal of the damaged and dysfunctional mitochondria by a double-membrane autophagic process via lysosomal degradation called mitophagy is critical for mitochondrial homeostasis and cell survival. Nonetheless, under chronic diseases including diabetic retinopathy (DR), mitophagy dysregulation and NLRP3 inflammasome activation exist, which cause premature cell death and disease progression. Recently, the thioredoxin-interacting protein TXNIP, which is strongly induced by diabetes and inhibits anti-oxidant function of thioredoxin, has been implicated in mitochondrial dysfunction, mitophagic dysregulation and NLRP3 inflammasome activation in DR. Therefore, TXNIP silencing or pharmacological inhibition may normalize mitophagic flux and NLRP3 inflammasome activation, which will prevent or slow down the progression of DR.


Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition.
An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.


Estimation of vegetation indices for high-throughput phenotyping of wheat using aerial imaging.
Unmanned aerial vehicles offer the opportunity for precision agriculture to efficiently monitor agricultural land. A vegetation index (VI) derived from an aerially observed multispectral image (MSI) can quantify crop health, moisture and nutrient content. However, due to the high cost of multispectral sensors, alternate, low-cost solutions have lately received great interest. We present a novel method for model-based estimation of a VI using RGB color images. The non-linear spatio-spectral relationship between the RGB image of vegetation and the index computed by its corresponding MSI is learned through deep neural networks. The learned models can be used to estimate VI of a crop segment. Analysis of images obtained in wheat breeding trials show that the aerially observed VI was highly correlated with ground-measured VI. In addition, VI estimates based on RGB images were highly correlated with VI deduced from MSIs. Spatial, spectral and temporal information of images contributed to estimation of VI. Both intra-variety and inter-variety differences were preserved by estimated VI. However, VI estimates were reliable until just before significant appearance of senescence. The proposed approach validates that it is reasonable to accurately estimate VI using deep neural networks. The results prove that RGB images contain sufficient information for VI estimation. It demonstrates that low-cost VI measurement is possible with standard RGB cameras.


Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability.
Blood concentration of vitamin A (VA), which is present as different molecules, i.e., mainly retinol and provitamin A carotenoids, plus retinyl esters in the postprandial period after a VA-containing meal, is affected by numerous factors: dietary VA intake, VA absorption efficiency, efficiency of provitamin A carotenoid conversion to VA, VA tissue uptake, etc. Most of these factors are in turn modulated by genetic variations in genes encoding proteins involved in VA metabolism. Genome-wide association studies (GWAS) and candidate gene association studies have identified single nucleotide polymorphisms (SNPs) associated with blood concentrations of retinol and β-carotene, as well as with β-carotene bioavailability. These genetic variations likely explain, at least in part, interindividual variability in VA status and in VA bioavailability. However, much work remains to be done to identify all of the SNPs involved in VA status and bioavailability and to assess the possible involvement of other kinds of genetic variations, e.g., copy number variants and insertions/deletions, in these phenotypes. Yet, the potential usefulness of this area of research is exciting regarding the proposition of more personalized dietary recommendations in VA, particularly in populations at risk of VA deficiency.


Surgical treatment of oroantral fistulas: a clinical study of 23 cases.
Oroantral communication can be defined as a pathologic space created between the maxillary sinus and the oral cavity. This communication and subsequent formation of a chronic oroantral fistula is a common complication often encountered by oral and maxillofacial surgeons. Although various techniques have been proposed in published studies, long-term successful closure of oroantral fistulas is still one of the most difficult problems confronting the surgeon working in the oral and maxillofacial region. The decision of which treatment modality to use is influenced by many factors, such as the amount and condition of tissue available for repair, the size and location of the defect, the presence of infection, the time to the diagnosis of the fistula, and, even, the surgeon's past experience. In the present study, 23 patients with a chronic oroantral fistula who underwent surgical correction at Istanbul University Faculty of Dentistry, Department of Oral and Maxillofacial Surgery from 2002 to 2009 were included. The fistulas were treated with a buccal advancement flap in 10 patients and a palatal island flap in 13 patients. The advantages, limitations, and complications of each technique are discussed.


Depolarized light scattering versus optical Kerr effect spectroscopy of supercooled liquids: comparative analysis.
Recently, heterodyne-detected optical Kerr effect (HD-OKE) spectroscopy was used to study dynamics of supercooled molecular liquids. The studies revealed an apparently new physical phenomenon that had not been reported before from the related depolarized light scattering (DLS), namely, an intermediate power law (nearly logarithmic decay) of the response functions [H. Cang et al., J. Chem. Phys. 118, 2800 (2003)]. Conceptually, HD-OKE and DLS data reflect optical anisotropy fluctuations mainly due to molecular reorientation dynamics in time and frequency domains, respectively. The above-mentioned effects are revealed in the mesoscopic range less, similar1 GHz ( greater, similar100 ps), where no direct comparison of the techniques was reported. In this Communication, we attempt such a comparison of exemplifying HD-OKE literature data of the glass-forming salol (phenyl salicylate), benzophenone, and liquid-crystal forming 4-cyano-4(')-pentylbiphenyl with DLS data of the same systems that we measured down to ca. 200 MHz by a combined tandem Fabry-Perot interferometer plus tandem-grating-monochromator technique. Generally, we find a satisfactory agreement, albeit in some cases with subtle differences at frequencies greater, similar10 GHz. We conclude that, in the mesoscopic dynamic range, HD-OKE and DLS studies provide consistent and comparable information, and therefore their conclusions must agree. We argue that the intermediate power law of HD-OKE is in essence a manifestation of the excess wing of the corresponding frequency-domain data, known long since from broadband dielectric spectroscopy and anticipated from DLS studies of supercooled liquids.


[Realization of reproductive function and hormonally active ovarian tumors].
Reproductive function was studied in 438 women with practically all histotypes of hormone-producing tumors of the ovaries (141-theca cell, 97-granulosa cell, 14-mixed theca-granulosa cell, 11-masculinizing and 26-Brenner tumors). The said function was reduced in 141 reproductive patients (48.8%). It was shown that hormone producing tumors of the ovary do not cause reproductive function to decline. Conversely, it was infrequent or no births in the young age that could have been a factor of tumorigenesis.


3-D Volume Assessment of the Corpus Callosum and Cerebellar Vermis Using Various Volume Acquisition and Post-Processing Protocols.
To determine which 3-D techniques are most effective for "real time" prenatal ultrasound assessment of the corpus callosum and cerebellar vermis. A prospective study involving 100 consecutive normal singleton pregnancies attending routine anomaly scan at 19-23 weeks' gestation. Midsagittal structures of the fetal brain were assessed using six different methods of 3-D image acquisition and three post-processing techniques. The quality of the resulting images were then assessed and scored by a second operator. The significance of the difference between various techniques was assessed using the Friedman test. The best method for visualization of both corpus callosum and cerebellar vermis in one image involved 3-D acquisition in a sagittal plane through the sagittal suture with manipulated 3-D OVIX™ (Oblique View eXtended Imaging) reconstruction. Five other methods scored closely and were not significantly different; all were based on 3-D acquisition in the sagittal plane through either sagittal suture or anterior fontanel. We have applied described techniques for 3-D central nervous system volume acquisition and have shown that the best method of assessment, allowing assessment of both the corpus callosum and the cerebellar vermis, involves midsagittal acquisition through the sagittal suture with 3-D OVIX reconstruction. This technique can be applied successfully in 83% of cases.


Temperature dependence of binding and catalysis for the Cdc25B phosphatase.
Using a combination of steady-state and single-turnover kinetics, we probe the temperature dependence of substrate association and chemistry for the reaction of Cdc25B phosphatase with its Cdk2-pTpY/CycA protein substrate. The transition state for substrate association is dominated by an enthalpic barrier (DeltaH(++) of 13 kcal/mol) and has a favorable entropic contribution of 4 kcal/mol at 298 K. Phosphate transfer from Cdk2-pTpY/CycA to enzyme (DeltaH(++) of 12 kcal/mol) is enthalpically more favorable than for the small molecule substrate p-nitrophenyl phosphate (DeltaH(++) of 18 kcal/mol), yet entropically less favorable (TDeltaS(++) of 2 vs. -6 kcal/mol at 298 K, respectively). By measuring the temperature dependence of binding and catalysis for several hotspot mutants involved in binding of protein substrate, we determine the enthalpy-entropy compensations for changes in rates of association and phosphate transfer compared to the wild type system. We conclude that the transition state for enzyme-substrate association involves tight and specific contacts at the remote docking site and that phospho-transfer from Cdk2-pTpY/CycA to the pre-organized active site of the enzyme is accompanied by unfavorable entropic rearrangements that promote rapid product dissociation.


Optimization of critical medium components for enhancing antibacterial thiopeptide nocathiacin I production with significantly improved quality.
Nocathiacin I, a glycosylated thiopeptide antibiotic, displays excellent antibacterial activities against multidrug resistant bacterial pathogens. Previously, a novel nocathiacin I formulation for intravenous administration has been successfully developed and its aqueous solubility is greatly enhanced for clinical application. The purpose of the present study was to increase the fermentation titer of nocathiacin I and reduce or eliminate analogous impurities by screening the medium ingredients using response surface methodology. After a sysmatic optimization, a water-soluble medium containing quality-controllable components was developed and validated, resulting in an increase in the production of nocathiacin I from 150 to 405.8 mg·L-1 at 150-L scale. Meanwhile, the analogous impurities existed in reported processes were greatly reduced or eliminated. Using optimized medium for fermentation, nocathiacin I with pharmaceutically acceptable quality was easily obtained with a recovery of 67%. In conclusion, the results from the present study offer a practical and efficient fermentation process for the production of nocathiacin I as a therapeutic agent.


Unified Asymmetric Total Syntheses of (-)-Alotaketals A-D and (-)-Phorbaketal A.
The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (-)-alotaketals A-D and (-)-phorbaketal A were accomplished [29-31 steps from (-)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C-H oxidation, and 3) olefin cross-metathesis to install the different side chains.


[Usefulness of color vision test for early detection of neurological damages by neurotoxic substances].
This paper reviews the published literature that is concerned with color vision impairment from industrial and environmental exposure to neurotoxic substances, and we evaluated whether testing for color vision impairment could be an affordable procedure for assessing these neurotoxic effects. In general, most cases of congenital color vision impairment are red-green, and blue-yellow impairment is extremely rare. However, most of the acquired color vision impairment that is related to age, alcohol or environmental factors is blue-yellow impairment. Therefore, many studies have been performed to identify this relationship between exposure to neurotoxic substances, such as organic solvents and heavy metals, and the prevalence of blue-yellow color vision impairment. The test for color vision impairment is known to be very sensitive to the early signs of nervous system dysfunction and this can be useful for making the early diagnosis of neurotoxic effects from exposure to very low concentrations of toxic substances.


Direct identification of Mycobacterium haemophilum in skin lesions of immunocompromised patients by PCR-restriction endonuclease analysis.
PCR-restriction endonuclease analysis (PRA) was used for direct identification of Mycobacterium haemophilum in clinical specimens from immunocompromised patients. PRA correctly identified M. haemophilum in four smear-positive specimens. Direct identification by PRA takes 2 to 3 working days compared to the 3 to 5 weeks required for culture isolation and identification by conventional methods.


An alternative approach to aldol reactions: gold-catalyzed formation of boron enolates from alkynes.
A new method for enolate generation via the gold-catalyzed addition of boronic acids to alkynes is reported. The formation of boron enolates from readily accessible ortho-alkynylbenzeneboronic acids proceeds rapidly with 2 mol % PPh(3)AuNTf(2) at ambient temperature. The enolates undergo aldol reaction with an aldehyde present in the reaction mixture to give cyclic boronate esters, which can be subsequently transformed into phenols, biaryls, or dihydrobenzofurans via oxidation, Suzuki-Miyaura, or intramolecular Chan-Lam coupling, respectively. A combined gold/boronic acid catalyzed aldol condensation reaction of an alkynyl aldehyde was also successfully achieved.


Robust Bayesian fusion of continuous segmentation maps.
The fusion of probability maps is required when trying to analyse a collection of image labels or probability maps produced by several segmentation algorithms or human raters. The challenge is to weight the combination of maps correctly, in order to reflect the agreement among raters, the presence of outliers and the spatial uncertainty in the consensus. In this paper, we address several shortcomings of prior work in continuous label fusion. We introduce a novel approach to jointly estimate a reliable consensus map and to assess the presence of outliers and the confidence in each rater. Our robust approach is based on heavy-tailed distributions allowing local estimates of raters performances. In particular, we investigate the Laplace, the Student's t and the generalized double Pareto distributions, and compare them with respect to the classical Gaussian likelihood used in prior works. We unify these distributions into a common tractable inference scheme based on variational calculus and scale mixture representations. Moreover, the introduction of bias and spatial priors leads to proper rater bias estimates and control over the smoothness of the consensus map. Finally, we propose an approach that clusters raters based on variational boosting, and thus may produce several alternative consensus maps. Our approach was successfully tested on MR prostate delineations and on lung nodule segmentations from the LIDC-IDRI dataset.


Comparison of synchronization of circadian corticosteroid rhythms by photoperiod and food.
Under conditions of feeding at will and normal light-dark alternation, rats consume the major portion of their daily food intake during the dark period and the circadian peak of plasma corticosteroid concentrations and of body temperature levels occurs just prior to or subsequent to the time of light-dark transition. Both light-dark transition and time of food presentation have been implicated as "Zeitgebers" in determining the phase of these two circadian rhythms. THE PRESENT DATA INDICATE THE FOLLOWING: (i) The time of food presentation appears to be a more potent synchronizer of the phase of plasma corticosteroid levels than is the light-dark cycle. This has been demonstrated in rats under conditions in which light-dark phase shift has been dissociated from a concomitant shift of time of eating. In contrast, under such conditions, the rhythm of body temperature appears to be more tightly coupled to the light-dark cycle. This illustrates that the time of food ingestion and the peak of body temperature rhythms can be uncoupled and that the phasing effects of restricted food ingestion on corticosteroid rhythms does not extend to body temperature rhythms. It also suggests the presence of different control mechanisms and/or pathways for corticosteroid and body temperature rhythms as well as the use of different pathways by different Zeitgebers. (ii) Rats maintained in constant dim light with free access to food exhibit aperiodic feeding behavior; plasma corticosteroid concentrations and body temperature levels are also aperiodic. Imposition of a restricted period of food access under such constant light conditions is associated with the appearance of a circadian periodicity of both plasma corticosteroid concentrations and body temperature levels, with peaks, respectively, just before and after the time of food presentation. This represents an additional example of food entrainment of previously aperiodic functions, similar to the food entrainment we have described in animals rendered aperiodic by lesions of the suprachiasmatic nucleus.


Antibodies to phosphatidylserine/prothrombin (aPS/PT) enhanced the diagnostic performance in Chinese patients with antiphospholipid syndrome.
Increasing evidence has highlighted the role of non-criteria antiphospholipid antibodies (aPLs) as important supplements to the current criteria aPLs for the diagnosis of antiphospholipid syndrome (APS). In this retrospective study, we evaluated the clinical relevance of antibodies to phosphatidylserine/prothrombin (aPS/PT) in Chinese patients with APS. A total of 441 subjects were tested, including 101 patients with primary APS (PAPS), 140 patients with secondary APS (SAPS), 161 disease controls (DCs) and 39 healthy controls (HCs). Serum IgG/IgM aPS/PT was determined by ELISA. The levels of IgG/IgM aPS/PT were significantly increased in patients with APS compared with DCs and HCs. IgG and IgM aPS/PT were present in 29.7% and 54.5% of PAPS, and 42.1% and 53.6% of SAPS, respectively. For diagnosis of APS, IgG aCL exhibited the highest positive likelihood ratio (LR+) of 21.60, followed by LA (13.84), IgG aβ2GP1 (9.19) and IgG aPS/PT (8.49). aPS/PT was detected in 13.3% of seronegative PAPS patients and 31.3% of seronegative SAPS patients. LA exhibited the highest OR of 3.64 in identifying patients with thrombosis, followed by IgG aCL (OR, 2.63), IgG aPS/PT (OR, 2.55) and IgG aβ2GP1 (OR, 2.33). LA and IgG aCL were correlated with both arterial and venous thrombosis, whereas IgG aPS/PT and IgG aβ2GP1 correlated with venous or arterial thrombosis, respectively. Our findings suggest that the inclusion of IgG/IgM aPS/PT may enhance the diagnostic performance for APS, especially in those in whom APS is highly suspected, but conventional aPLs are repeatedly negative. In addition, IgG aPS/PT may contribute to identify patients at risk of thrombosis.


The capBCA Locus is Required for Intracellular Growth of Francisella tularensis LVS.
Francisella tularensis is the causative agent of tularemia and a category A bioterrorism agent. The molecular basis for the extreme virulence of F. tularensis remains unclear. Our recent study found that capBCA, three neighboring genes, are necessary for the infection of F. tularensis live vaccine strain (LVS) in a respiratory infection mouse model. We here show that the capBCA genes are necessary for in vivo growth of F. tularensis LVS in the lungs, spleens, and livers of BALB/c mice. Unmarked deletion of capBCA in type A strain Schu S4 resulted in significant attenuation in virulence although the level of the attenuation in Schu S4 was much less profound than in LVS. We further demonstrated that CapB protein is produced at a low level under the in vitro culture conditions, and capB alone is necessary for in vivo growth of F. tularensis LVS in the lungs of BALB/c mice. Finally, deletional mutations in capB alone or capBCA significantly impaired intracellular growth of F. tularensis LVS in cultured macrophages, thus suggesting that the capBCA genes are necessary for intracellular adaptation of F. tularensis. The requirement of this gene locus in intracellular adaption at least in part explains the significant attenuation of F. tularensis capBCA mutants in virulence.


Laparoscopic Total Gastrectomy in Elderly Patients (≥70 Years) with Gastric Carcinoma: A Retrospective Study.
To compare the surgical outcomes of laparoscopic total gastrectomy between elderly and non-elderly patients. Between 2008 and 2015, a total of 273 patients undergoing laparoscopic total gastrectomy for gastric carcinoma were divided into two age groups: elderly (≥70 years, n=71) vs. non-elderly (<70 years, n=172). Postoperative outcomes, including length of hospital stay, morbidity, and mortality were compared between the groups. The elderly group showed a significantly higher rate of comorbidities and American Society of Anesthesiologists scores than those in the non-elderly group. No significant differences were found with respect to lymphadenectomy or combined organ resection between the groups. After surgery, the elderly group showed a significantly higher incidence of grade III and above complications than the non-elderly group (15.5% vs. 4.1%, P=0.003). Among the complications, anastomosis leakage was significantly more common in the elderly group (9.9% vs. 2.9%, P=0.044). Univariate and multivariate analyses showed that old age (≥70 years) was an independent risk factor (odds ratio=4.42, 95% confidence interval=1.50~13.01) for postoperative complications of grade III and above. Elderly patients are more vulnerable to grade III and above complications after laparoscopic total gastrectomy than non-elderly patients. Great care should be taken to prevent and monitor the development of anastomosis leakage in elderly patients after laparoscopic total gastrectomy.


The Double Donut: A Safe and Simple Option for Immediate Nipple Areolar Complex Reconstruction in Skin-Sparing Mastectomy Patients With Contraindications to Nipple-Sparing Mastectomy.
Restoration of the nipple areolar complex (NAC) has been shown to improve quality of life (QoL) in post-mastectomy patients. Despite expansion of nipplesparing mastectomy inclusion criteria, many patients remain ineligible and are relegated to bilateral skin-sparing mastectomy. In this study, we evaluated immediate NAC reconstruction with the double donut areolar graft and split nipple composite graft reconstruction (DDSNS). A single-center prospective study was performed for patients undergoing immediate post-mastectomy reconstruction with the DDSNS technique. Demographics and post-reconstruction endpoints were collected, focusing on aesthetic and functional outcomes. A total of 31 patients and 62 breasts underwent immediate reconstruction with the DDSNS technique. Four of 62 (6.4%) nipple composite grafts and 1 of 62 (1.6%) areolar grafts experienced partial graft loss. All incidents of initial loss healed to a satisfactory result. All patients were able to proceed with adjuvant therapy, if indicated, without delay. The DDSNS technique can be successfully applied to achieve cosmetically satisfactory results in the post-mastectomy patient. This technique has shown reliable outcomes with respect to graft success and patient satisfaction with their NAC reconstruction.


Over-Expression of Cyclooxygenase-2 in Colorectal Cancer Patients.
Background: Colorectal carcinoma (CRC) is the most common neoplasm of the gastrointestinal tract. COX-2 plays an important role in CRC development and is a key target for the regression of colorectal tumorigenesis by nonsteroidal anti-inflammatory drugs. The present study was conducted to examine the relationship of the levels of COX-2 in CRC patients with the clinico-pathological parameters and also to assess its usefulness as a potential biomarker for diagnosis of CRC. Methods: Prior to surgery, 30 CRC patients were enrolled and the samples from colon tumors and surrounding tissues were taken after they underwent surgical intervention at PGIMER, Chandigarh. mRNA expression levels of COX-2 were examined in 30 CRC and adjacent normal colonic mucosa by quantitative polymerase chain reaction (qPCR). The expression of COX-2 was assessed by immunohistochemical method using rabbit polyclonal antibodies against human COX-2 protein. Results: The quantitative relative expression of COX-2 mRNA was observed to be significantly higher (p<0.05) in colorectal cancer tissues as compared to adjacent normal colon tissues. Also, female CRC patients showed significantly higher (p<0.009) expression of COX-2 mRNA vis-a-vis male colorectal cancer patients. This is the first study which has reported a direct relationship between COX-2 mRNA expressions in male colorectal cancer patients versus females. Further, immunohistochemistry of COX-2 confirmed the quantitative real time-PCR findings. Conclusion: Our study shows that COX-2 over expression in colorectal carcinoma patients is closely associated with clinico-pathological parameters and is more pronounced in males versus females. Further, COX-2 mRNA expression can serve as a potential biomarker for the diagnosis of CRC.


Insulin resistance due to a defect distal to the insulin receptor: demonstration in a patient with leprechaunism.
We have studied a 2-year-old girl with acanthosis nigricans, glucose intolerance, marked hyperinsulinemia, and somatic features characteristic of the leprechaunism syndrome. Circulating plasma insulin levels were increased up to 50-fold and the patient showed a blunted hypoglycemic response to an injection of exogenous insulin (0.2 units/kg), indicating the presence of severe insulin resistance. Insulin purified from the patient's plasma was normal on the basis of chromatographic, electrophoretic, and immunologic criteria. Furthermore, the purified insulin competed effectively with (125)I-labeled insulin for binding to insulin receptors on cultured IM-9 lymphocytes and rat fat cells and also exhibited normal biological potency when tested on rat fat cells. Anti-insulin receptor and anti-insulin antibodies were not detected in the patient's plasma, and plasma levels of glucagon, growth hormone, and cortisol were normal. Insulin binding to the patient's circulating monuclear leukocytes was only slightly depressed into the low normal range and could not account for the severe insulin resistance. Studies on the patient's fibroblasts revealed normal levels of insulin receptors but a total absence of insulin's ability to accelerate glucose transport. Because rates of glucose transport and metabolism were normal in the basal state in the absence of insulin, we conclude that this patient's insulin resistance is due to an inherited cellular defect in the coupling mechanism between occupied insulin receptors and the plasma membrane glucose transport system.


High-energy phonon branches of an individual metallic carbon nanotube.
We present excitation-energy dependent Raman measurements between 2.05 and 2.41 eV on the same individual carbon nanotube. We find a change in the Raman frequencies of both the D mode (63 cm(-1)/eV) and the high-energy modes. The observed frequencies of the modes at approximately 1600 cm(-1) as a function of laser-energy map the phonon dispersion relation of a metallic tube near the Gamma point of the Brillouin zone. Our results prove the entire first-order Raman spectrum in single-wall carbon nanotubes to originate from double-resonant scattering. Moreover, we confirm experimentally the phonon softening in metallic tubes by a Peierls-like mechanism.


Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer.
Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal cancer (CRC) progression by single-cell RNA sequencing. We identified six clusters of tumor infiltrating ILCs with unique features. ILC1s expressed inhibitory receptors and underwent inhibitory functional conversion at the late stage of CRC. ILC2s were classified into three subsets (called ILC2-A, -B, -C), of which ILC2-C subset could facilitate tumor progression. HS3ST1 and PD1 were highly expressed in ILC2s of late stage CRC tumors and deficiency of HS3ST1 or PD1 in ILC2s suppressed tumor growth. Moreover, ILC3s transdifferentiated into ILCregs during CRC progression and ILCregs promoted tumor growth. Of note, TGF-β signaling initiated the conversion of ILC3s to ILCregs and blockade of TGF-β signaling could disrupt the ILCreg transdifferentiation and inhibited tumor growth. Thus, intervention of ILC conversions might be a potential strategy for CRC immunotherapy.


Carcinoma of the ampulla of Vater: expression of cancer-associated antigens inversely correlated with prognosis.
To obtain some useful pathologic indicators for predicting the prognosis in carcinomas of the ampulla of Vater, we analyzed 24 surgically resected ampullary carcinomas pathologically with immunohistochemistry of cancer-associated antigens. Pancreatic invasion, lymph node metastasis, and histology of the tumor were significantly correlated with poor prognosis (p less than 0.01), but the size or ulceration of the tumor did not significantly affect the prognosis (p less than 0.05). Immunohistochemically, diffuse positivity for anti-CA19-9 monoclonal antibody was demonstrated in 10 carcinomas and that for anti-carcinoembryonic antigen (CEA), in 10. Eight of them showed synchronously diffuse immunoreactivities for both antigens. Although there was no significant correlation between diffuse positivity for CA19-9 and pathologic factors, CA19-9-positive cases exhibited significantly poor prognoses (p less than 0.01). Diffuse positivity for CEA was correlated with pancreatic invasion (p less than 0.05) and poor prognosis (p less than 0.05). Immunohistochemical study of cancer-associated antigens may disclose some malignant potential of ampullary carcinoma other than that expressed in the morphology. Furthermore, because of the consistency of staining results, immunohistochemistry of cancer-associated antigens may also be useful in predicting preoperatively the prognosis of ampullary carcinoma in biopsied materials.


A scattering filter for energy-dispersive optics.
A filtering technique to remove parasitic scattering from X-ray absorption spectra that are acquired in energy-dispersive mode has been developed and tested at the European Synchrotron Radiation Facility. The improved set-up removes small-angle scattering of the sample or the windows of sample cells which may spoil the energy resolution or reduce the intensity of prominent features in the absorption spectrum, such as the white line at the Pt L(III) edge. The sample is placed behind the curved monochromator and between two plane perfect crystals in the Bonse-Hart configuration. The dispersion of the Bonse-Hart double-crystal camera is matched to the dispersion of the curved monochromator by inclining the scattering planes of the two optical elements against each other.


Electrostatically Enhanced 3- and 4-Pyridyl Borate Salt Nucleophiles and Bases.
A variety of electrostatically enhanced 3- and 4-pyridylborate salt catalysts are reported and show significant improvement over an activated noncharged neutral control compound. Their nucleophilicity in a stoichiometric SN2 reaction and catalytic performance in a urethane synthesis are evaluated along with three methods for rapidly evaluating the basicity of these species. That is, qualitative titrations in CH2Cl2 and CHCl3 were carried out, two separate solution-state IR studies in CCl4 and CDCl3 are reported, and the proton affinities of the anionic components of the salts were computed. Charge differences between the anion and its protonated zwitterionic conjugate acid are evaluated along with the highest occupied molecular orbitals of the anions in relationship to some of the surprising reactivity findings that were observed in the two kinetic studies.


Megaduodenum with Duodenal Diospyrobezoars.
Bezoars are retained masses of ingested materials accumulating within the gastrointestinal track. While gastric bezoars are often observed, duodenal bezoars are rarely reported. A 77-year-old man who had frequently consumed persimmons and had never undergone gastric surgery had symptoms of epigastric pain and early satiety for 10 days. Esophagogastroduodenoscopy showed many diospyrobezoars in a severely distended duodenal bulb, otherwise known as megaduodenum. The patient's treatment consisted of repeated endoscopic removal of the bezoars by using a retrieval net.


Postoperative intussusception in children with enterostomy.
Postoperative intussusception (POI) is an uncommon but important cause of postoperative intestinal obstruction. We describe three cases of intussusception, which developed after major abdominal surgery. Two of the patients were premature newborns whose conditions were complicated by necrotizing enterocolitis and accepted ostomy. The other case involved a patient with Hirschsprung's disease who had had a previous colostomy and accepted Duhamel pull through procedure. Postoperative intussusception is a rare complication of pediatric abdominal surgery and may occur in premature infants. The ostomy may be the predisposing factor of these patients.


Machine learning approaches to diagnosis and laterality effects in semantic dementia discourse.
Advances in automatic text classification have been necessitated by the rapid increase in the availability of digital documents. Machine learning (ML) algorithms can 'learn' from data: for instance a ML system can be trained on a set of features derived from written texts belonging to known categories, and learn to distinguish between them. Such a trained system can then be used to classify unseen texts. In this paper, we explore the potential of the technique to classify transcribed speech samples along clinical dimensions, using vocabulary data alone. We report the accuracy with which two related ML algorithms [naive Bayes Gaussian (NBG) and naive Bayes multinomial (NBM)] categorized picture descriptions produced by: 32 semantic dementia (SD) patients versus 10 healthy, age-matched controls; and SD patients with left- (n = 21) versus right-predominant (n = 11) patterns of temporal lobe atrophy. We used information gain (IG) to identify the vocabulary features that were most informative to each of these two distinctions. In the SD versus control classification task, both algorithms achieved accuracies of greater than 90%. In the right- versus left-temporal lobe predominant classification, NBM achieved a high level of accuracy (88%), but this was achieved by both NBM and NBG when the features used in the training set were restricted to those with high values of IG. The most informative features for the patient versus control task were low frequency content words, generic terms and components of metanarrative statements. For the right versus left task the number of informative lexical features was too small to support any specific inferences. An enriched feature set, including values derived from Quantitative Production Analysis (QPA) may shed further light on this little understood distinction.


Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis.
We conducted a prospective randomized trial of propranolol for the prevention of recurrent variceal bleeding in 48 patients with cirrhosis of the liver. During a follow-up period of up to 21 months, 12 of 26 patients in the propranolol group and 11 of 22 in the control group had rebleeding from esophageal varices. There was no significant difference in rebleeding between the two groups. This contrasts with a previous report of the efficacy of propranolol in preventing recurrent gastrointestinal bleeding in alcoholic cirrhosis. The difference in results may be due to the inclusion in our study of patients with other causes of cirrhosis and more severe liver disease. Propranolol may not be indicated for the prophylaxis of variceal rebleeding in such patients, and we advocate that its use be limited at present to controlled clinical trials.


Gap junction structure: unraveled, but not fully revealed.
Gap junction channels facilitate the intercellular exchange of ions and small molecules, a process that is critical for the function of many different kinds of cells and tissues. Recent crystal structures of channels formed by one connexin isoform (connexin26) have been determined, and they have been subjected to molecular modeling. These studies have provided high-resolution models to gain insights into the mechanisms of channel conductance, molecular permeability, and gating. The models share similarities, but there are some differences in the conclusions reached by these studies. Many unanswered questions remain to allow an atomic-level understanding of intercellular communication mediated by connexin26. Because some domains of the connexin polypeptides are highly conserved (like the transmembrane regions), it is likely that some features of the connexin26 structure will apply to other members of the family of gap junction proteins. However, determination of high-resolution structures and modeling of other connexin channels will be required to account for the diverse biophysical properties and regulation conferred by the differences in their sequences.


Circadian rhythm changes in blood pressure and heart rate during the first year after heart transplantation.
Heart transplant recipients (n = 11) were studied before discharge from the hospital and 1, 3, 6, and 12 months after transplantation to (1) examine systolic and diastolic blood pressure and heart rate circadian patterns, (2) detect the presence or absence of nocturnal declines, and (3) describe changes in the mean levels of systolic blood pressure, diastolic blood pressure, and heart rate. An ambulatory blood pressure-monitoring system was used to record blood pressure and heart rate at 1-hour intervals for up to 48 hours. Data were analyzed with descriptive and independent t-test statistics, as well as cosinor analysis for rhythmicity. The majority of the patients had significant (p < 0.05) circadian rhythms for systolic and diastolic blood pressure and heart rate throughout the study, but at times the systolic and diastolic blood pressure acrophases were found to be phase shifted to earlier or later along the time axis (e.g., peak values occurring at 3 AM rather than later in the morning or early afternoon), such that no relationships were found between circadian rhythms and nocturnal declines. More "normal" circadian rhythms were observed for heart rate than for systolic and diastolic blood pressures. The development of hypertension (systolic/diastolic blood pressures > 140/90 mm Hg) was common and by 6 months and 1 year after transplantation 8 of the 10 patients remaining in the study were hypertensive. Increases in mean heart rate of approximately 18% (ranging from 2% to 46%) were also observed during the first postoperative year.


Fermentation of xylose causes inefficient metabolic state due to carbon/energy starvation and reduced glycolytic flux in recombinant industrial Saccharomyces cerevisiae.
In the present study, comprehensive, quantitative metabolome analysis was carried out on the recombinant glucose/xylose-cofermenting S. cerevisiae strain MA-R4 during fermentation with different carbon sources, including glucose, xylose, or glucose/xylose mixtures. Capillary electrophoresis time-of-flight mass spectrometry was used to determine the intracellular pools of metabolites from the central carbon pathways, energy metabolism pathways, and the levels of twenty amino acids. When xylose instead of glucose was metabolized by MA-R4, glycolytic metabolites including 3- phosphoglycerate, 2- phosphoglycerate, phosphoenolpyruvate, and pyruvate were dramatically reduced, while conversely, most pentose phosphate pathway metabolites such as sedoheptulose 7- phosphate and ribulose 5-phosphate were greatly increased. These results suggest that the low metabolic activity of glycolysis and the pool of pentose phosphate pathway intermediates are potential limiting factors in xylose utilization. It was further demonstrated that during xylose fermentation, about half of the twenty amino acids declined, and the adenylate/guanylate energy charge was impacted due to markedly decreased adenosine triphosphate/adenosine monophosphate and guanosine triphosphate/guanosine monophosphate ratios, implying that the fermentation of xylose leads to an inefficient metabolic state where the biosynthetic capabilities and energy balance are severely impaired. In addition, fermentation with xylose alone drastically increased the level of citrate in the tricarboxylic acid cycle and increased the aromatic amino acids tryptophan and tyrosine, strongly supporting the view that carbon starvation was induced. Interestingly, fermentation with xylose alone also increased the synthesis of the polyamine spermidine and its precursor S-adenosylmethionine. Thus, differences in carbon substrates, including glucose and xylose in the fermentation medium, strongly influenced the dynamic metabolism of MA-R4. These results provide a metabolic explanation for the low ethanol productivity on xylose compared to glucose.


Wanting and Liking: Testing the Factor Structure of The Temporal Experience of Pleasure Scale in Major Depression and Community Samples.
The Temporal Experience of Pleasure Scale (TEPS) is a multidimensional self-report measure that has been used to improve understanding of anticipation ("wanting") and consummation ("liking") of reward. The TEPS has been used to assess anhedonia in clinical depression, but its factor structure has not yet been confirmed in this population. This seems important given mixed findings on the model fit and factor structure of the TEPS in other clinical and community samples. To remedy this, the current study used confirmatory factor analysis to test models of the TEPS items across three studies: (a) in adults with major depression (n = 334), (b) in youth with major depression (n = 305), and (c) in a community sample (n = 320). In summary, the model fit of the two-factor TEPS scales was adequate in depressed and community Australian samples. Nevertheless, some items may require removal or revision based on cultural preferences for pleasurable experiences.


Influence of immune privilege on ocular tumor development.
Mechanisms that maintain ocular immune privilege may contribute to ocular tumor progression by inhibiting tumoricidal immune responses. Consistent with that notion are observations from transplantable tumor models in mice demonstrating that the tumoricidal activity of CD8(+) cytolytic T lymphocytes (CTL) may be inhibited directly by interfering with CTL effector function in the eye or indirectly by abrogating the effector function of CD8+ T cell-activated intratumoral macrophages that are critical for ocular tumor rejection. In addition, epigenetic gene regulation by factors within the ocular tumor environment favors the generation of tumor variants that are resistant to CD8(+) CTL. Intratumoral macrophages may be essential for eliminating these variants because, unlike CTL, their tumoricidal activity is nonspecific. Hence, the inhibition of macrophage effector function within the eye, presumably to preserve immune privilege by minimizing ocular immunopathology, may hasten the outgrowth of tumor escape variants which contributes to ocular tumor progression.


Cytokine-induced procoagulant activity in monocytes and endothelial cells. Further enhancement by cyclosporine.
IL-1, IL-2, and TNF alpha are important biological response modifiers of inflammatory and immunological reactions. Our experiments show that these cytokines are potent inducers of thromboplastin (TPL) activity but that their effects differ with regard to cell type and kinetics in human umbilical vein endothelial cells (HUVEC), monocytes (M), and mononuclear blood cells (MNC). Recombinant IL-1 alpha, rIL-1 beta and rTNF alpha all induced a dose-dependent increase in endothelial cell TPL activity, whereas rIL-2 had essentially no such effect. In the case of M and MNC cultures, IL-1 and IL-2 each induced TPL synthesis, IL-2 somewhat more slowly than IL-1. Special care was taken to exclude the effect of endotoxin present in the IL-1 preparations. Recombinant TNF alpha had a markedly smaller or no effect. When LPS was used to induce TPL synthesis, addition of rTNF alpha further enhanced HUVEC TPL, whereas no effect or a decrease in TPL was seen in MNC and M, especially in the presence of CsA and TNF alpha. Recombinant IL-1 beta also induced the synthesis of clotting factor VII in monocytes, thus allowing the formation of TPL-factor VII complexes, a most powerful trigger of blood clotting. IL-1 alpha, IL-2, and TNF alpha had no effect on the level of factor VII activity. Cyclosporine significantly augmented the level of TPL activity in HUVEC stimulated with rIL-1 alpha, rIL-1 beta, and rTNF alpha and in MNC and M stimulated with rIL-1 alpha, rIL-1 beta, and rIL-2. These actions of cytokines and cyclosporine may contribute significantly to the development of thrombotic reactions and fibrin deposits in transplanted organs, as well as to other pathophysiological pathways where activated clotting factors are involved.


Wide combined thin free SCIA/SIEA flap.
A thin skin flap is often required for optimal resurfacing of particular areas of the body such as oral lining, hands, and feet. Using wide and thin flaps provides a higher level of esthetic and functional results in reconstructive surgery. Recently, the authors also applied the thinning procedure for free SCIA/SIEA flaps. From 2003 to 2006, 11 patients underwent soft tissue reconstruction using thin free SCIA/SIEA flaps. In this procedure, deep subcutaneous fat tissue was removed totally while superficial subcutaneous tissue was thinned and a fat tissue layer was left under the skin to protect the subdermal network. All procedures were performed without using an operating microscope. The flap ranged 10 to 60 cm in length and from 6 to 55 cm in width. Ten flaps survived completely, while 1 occurrence of distal superficial necrosis was observed. No secondary flap defatting or revision was necessary. The free SCIA/SIEA flap may be prepared safely using a simple surgical procedure such as wide and thin flap in reconstructive surgery.


Successful surgical treatment of a giant coronary artery aneurysm presenting with recurrent profuse haemoptysis.
We present the case of successful resection of a giant aneurysm of the LAD presenting with recurrent severe haemoptysis in a 72-year old man. He was admitted to a regional hospital with fever, recurrent bloody sputum, weight loss and left sided chest pain, and developed respiratory failure requiring ventilation. Investigations are summarised and reviewed and the diagnosis was eventually reached by TTE, CT and MRI scans, confirmed by coronary angiography. Successful emergency surgery to resect the aneurysm and put a vein graft to the LAD is described. The presentation and management of coronary giant aneurysm is reviewed.


Targeted nanoparticles modify neutrophil function in vivo.
Neutrophils play critical roles in a broad spectrum of clinical conditions. Accordingly, manipulation of neutrophil function may provide a powerful immunotherapeutic approach. However, due to neutrophils characteristic short half-life and their large population number, this possibility was considered impractical. Here we describe the identification of peptides which specifically bind either murine or human neutrophils. Although the murine and human neutrophil-specific peptides are not cross-reactive, we identified CD177 as the neutrophil-expressed binding partner in both species. Decorating nanoparticles with a neutrophil-specific peptide confers neutrophil specificity and these neutrophil-specific nanoparticles accumulate in sites of inflammation. Significantly, we demonstrate that encapsulating neutrophil modifying small molecules within these nanoparticles yields specific modulation of neutrophil function (ROS production, degranulation, polarization), intracellular signaling and longevity both in vitro and in vivo. Collectively, our findings demonstrate that neutrophil specific targeting may serve as a novel mode of immunotherapy in disease.


Effects of pyrimethamine and sulfadiazine on the intestinal development of Toxoplasma gondii in cats.
Treatment with combined pyrimethamine and sulfadiazine prolonged the pre-patent period and shortened the patent period of cyst-induced toxoplasmosis in cats. Oocyst excretion was inhibited in 3 of 4 cats treated intramuscularly with 2 mg/kg body weight pyrimethamine and 100 mg/kg body weight sulfadiazine but not in 4 cats treated with one-half that dosage. Treatment with 2.2 mg/kg body weight pyrimethamine and 132 mg/kg body weight sulfadiazine mixed in cat food did not inhibit oocyst production but prevented antibody formation. No parasites were found upon histological examination of intramuscularly treated cats on days 3, 5, and 7 after infection. Infection with Toxoplasma gondii induced immunity to an oocyst-producing reinfection in both control and treated cats.


Neurodevelopmental assessment of the young child: the state of the art.
A wide variety of tests are available to assess the central nervous system (CNS) function of the toddler and preschool-aged child. These tests vary as to function; qualities and abilities tapped; facility with which they can be learned, administered, and scored; availability of test materials and manuals or training videos; and strength of standardization and validation data. Some were developed to screen development of large numbers of children. Others were developed to evaluate a child for diagnosis of disability or delineation of a child's strengths and weaknesses. Some broadly screen or assess multiple aspects of development, while some focus on specific abilities. A limitation of all these tests is that they tap only a small portion of a child's abilities at a given point in time. Administration of a variety of different tests provides a more complete evaluation of a child's abilities. Tests that can follow a child's development over time tap into the continuum of human development. The ability to measure various aspects of CNS functional development is a first step in addressing our greatest challenge, how to promote and support a child's development.


HSP27 is involved in the pathogenesis of kidney tubulointerstitial fibrosis.
We hypothesized that heat shock protein 27 (HSP27), a small heat shock protein with actin-remodeling properties, is involved in the pathogenesis of kidney tubulointerstitial fibrosis. We first examined its expression in the rat unilateral ureteral obstruction (UUO) model of kidney fibrosis and epithelial-to-mesenchymal transition (EMT). Immunoblot analyses showed that UUO resulted in significant upregulation of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), total and phosphorylated HSP27, and phosphorylated p38MAPK. Immunofluorescence studies showed that HSP27 costained with TGF-beta1, alpha-SMA, and E-cadherin in areas of tubulointerstitial injury. We next attempted to translate these studies in an in vitro model of EMT using rat proximal tubular epithelial cells (NRK52E). TGF-beta1 (20 ng/ml) treatment resulted in EMT (upregulation of alpha-SMA and downregulation of E-cadherin) and significant upregulation of total and phosphorylated HSP27 and p38MAPK after 3 days. Real-time PCR analyses showed that HSP27, vimentin, and fibronectin increased whereas E-cadherin mRNA levels decreased. Double-staining immunofluorescence studies showed intracytoplasmic colocalization of HSP27 with both F-actin and E-cadherin in cells undergoing EMT. HSP27 overexpression by transient transfection significantly increased E-cadherin while decreasing E-cadherin repressor Snail levels. In aggregate, these studies show that HSP27 is involved in the pathogenesis of TGF-beta1-induced EMT and chronic tubulointerstitial fibrosis. HSP27 overexpression may delay injury by upregulating E-cadherin through downregulation of Snail.


Ethics, practice, and research in public health.
Ethical issues that can arise in distinguishing public health research from practice are highlighted in 2 case studies--an investigation of a tuberculosis outbreak in a prison and an evaluation of a program for improving HIV prevention services. Regardless of whether such public health investigations represent research or practice, we see a need for ethics oversight procedures that reflect actual risks and enable timely responses to crises. Such oversight should accommodate the perspectives of persons and communities affected by public health threats and by governmental responses to those threats; it should further recognize that public health ethics is a distinct field combining bioethics, political philosophy, human rights, and law.


An efficient high-speed counter-current chromatography method for the preparative separation of sesquiterpenoids from the rhizomes of Cyperus rotundus L. combined with evaluation of the anti-inflammation activity in vitro and molecular docking.
Cyperus rotundus L. has been extensively used in ancient medication for the treatment of different disorders worldwide, in which sesquiterpenes are the most representative components. In this study, sesquiterpenes were effectively purified by two-dimensional counter-current chromatography in combination with continuous injection and inner-recycling mode with a solvent system of n-hexane/ethyl acetate/methanol/water (1:0.2:1:0.2, v/v/v/v). For one-dimension separation, continuous injection mode was used with three times injection and the inner-recycling mode was adopted for the separation of two mixtures for two-dimensional separation. Finally, four sesquiterpenoids, including scariodione (1), cyperenoic acid (2), scariodione (3), and α-cyperone (4), were obtained with purities over 98%. Mass spectrometry and nuclear magnetic resonance were applied to identify their structures. The results from the anti-inflammation effect with zebrafish demonstrated that cyperenoic acid exhibited stronger anti-inflammation activity. Molecular docking results suggested that cyperenoic acid possessed lower binding energies -9.4545 kcal/mol with 1CX2 to form formed hydrogen bond interaction with ARG120. In general, all the obtained findings proved that the strong anti-inflammation capacity of cyperenoic acid can have the potential of being adopted for treating diseases resulting from inflammation.


Pharmacokinetics and anthelmintic efficacy of febantel in the racing pigeon (Columba livia).
This paper reports on the pharmacokinetics and the efficacy of febantel against Capillaria obsignata and Ascaridia columbae in the racing pigeon. Febantel was rapidly cleared from the circulation and highly metabolized. The efficacy of febantel against Capillaria and Ascaridia was studied on lightly and heavily infected pigeons. The efficacy against Ascaridia was 100% for the faecal egg count reduction (FECR) as well as for the worm reduction in all treated pigeons. After two treatments with febantel against Capillaria in heavily infected pigeons the FECR amounted to 96.7% and worm reduction was 95%. In order to effectively remove both parasites from the host, repeated treatments with febantel at a short interval could be the treatment of choice.


Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids.
The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.


In vitro and in vivo anticandidal activities of alginate-enclosed chitosan-calcium phosphate-loaded Fe-bovine lactoferrin nanocapsules.
To study the in vitro and in vivo anticandidal activity of nanocapsulated bovine lactoferrin. In vitro and in vivo antimicrobial activities were conducted to study the anticandidal activities of nanocapsules (NCs). The NCs showed good anticandidal activities. The disruption of cell wall and cell membrane was noted via microscopy studies. The NCs changed the normal growth profile of Candida albicans. NCs reduced the colony forming unit in kidney and blood samples. Histopathological examination showed better cell structure and coordination compared with untreated mice kidney. NCs also enhanced the natural killing properties of C. albicans by epithelial cells. NCs have effective anticandidal properties and have the potential as a therapeutic agent against candidiasis.


Left systematic mediastinal lymph node dissection.
Sampling, or systematic mediastinal lymph node dissection, is the standard-of-care surgical treatment for early stage non-small cell lung cancer, according to guidelines from the European Society of Thoracic Surgeons. Lymph node status defines disease status and patients' prognosis. In this video tutorial, a radical ipsilateral mediastinal lymph node dissection in a man suffering from a left, centrally located lung adenocarcinoma is presented. Systematic mediastinal lymph node dissection constitutes a high-quality metric for the efficacy of the surgical procedure and is essential to achieving adequate staging and treatment.


Metabolism of beta-hexachlorocyclohexane-14C in rats following low dosing in the daily diet.
beta-Hexachlorocyclohexane-14C (1.5 ppm) was administered in the diet to rats for one week. During the elimination phase three therapeutic agents were fed to enhance the clearance. Renal and fecal excreted radioactive products were collected for 8 weeks and extracted. Although significant differences in the total excreted amount of radioactivity were registered between controls and treated rats, there were no quantitative differences in the extractability of the excreta and no differences in the chemical nature of metabolites found. Radioactivity in urine consisted to 100% of conversion products, about 30% of which were unextractable residues. In the organic soluble fraction the 2,4,6-trichlorophenol was the major metabolite in urine and the only metabolite detected in feces. Minor conversion products of beta-HCH in urine were a trichlorohydroxyme-thoxybenzene, a dichlorophenol and a trace of a tetrachlorocyclohexane-isomer.


Maternal antibodies against Plasmodium spp. in African black-footed penguin (Spheniscus demersus) chicks.
Anti-Plasmodium spp. antibody titers of mating pairs of adult, captive-reared, African black-footed penguins (Spheniscus demersus) and their chicks were determined using the enzyme-linked-immunosorbent assay (ELISA). Two Plasmodium falciparum antigens were used for the ELISA: R32tet32 (sporozoite antigen), and crude red blood cell extract (CRBCE). Eighteen chicks were bled weekly for ten weeks starting with their day of hatching. The yolk sacs of two penguin eggs were biopsed for ELISA-detectable maternal antibodies (MAB). None of the 28 adult penguins were parasitemic by Giemsa-stained thin blood smear; however, all had anti-Plasmodium spp. immunoglobulins reacting with P. falciparum antigens. All 18 newly hatched chicks had anti-Plasmodium spp. MAB while housed in a mosquito-free environment. The level of MAB in the newly hatched chicks was correlated significantly (P < 0.001) with antibody level detected in their female parents (R32tet32: r = 0.87, CRBCE: r = 0.89). No correlation was found between antibody titers of the newly hatched chicks and their male parents. The level of maternal-fetal antibodies was regressed significantly (P < 0.001) over the 10-week period. Penguin chicks over 10 weeks of age had no anti-Plasmodium spp. MAB. Egg-yolk samples had significantly (P < 0.03) higher MAB titers than female parents that laid these eggs.


Uses of dextranomer absorbent pads after cryosurgery of cutaneous malignancies.
Secretion from wounds after cryosurgery of cutaneous malignancies may be excessive and may constitute a problem in management. It was found possible to collect and quantitate such discharges by use of highly hydrophilic dextranomer beads (Debrisan). They were applied in convenient, small "tea-bag" pads. The amount and duration of postoperative oozing was approximately proportional to the sizes of the lesions and more impressive in sites of sparse subcutaneous tissue. The absorbent pads also proved to be effective and safe for use as postoperative dressings.


A systemic review on Liubao tea: A time-honored dark tea with distinctive raw materials, process techniques, chemical profiles, and biological activities.
Liubao tea (LBT) is a unique microbial-fermented tea that boasts a long consumption history spanning 1500 years. Through a specific post-fermentation process, LBT crafted from local tea cultivars in Liubao town Guangxi acquires four distinct traits, namely, vibrant redness, thickness, aging aroma, and purity. The intricate transformations that occur during post-fermentation involve oxidation, degradation, methylation, glycosylation, and so forth, laying the substance foundation for the distinctive sensory traits. Additionally, LBT contains multitudinous bioactive compounds, such as ellagic acid, catechins, polysaccharides, and theabrownins, which contributes to the diverse modulation abilities on oxidative stress, metabolic syndromes, organic damage, and microbiota flora. However, research on LBT is currently scattered, and there is an urgent need for a systematical recapitulation of the manufacturing process, the dominant microorganisms during fermentation, the dynamic chemical alterations, the sensory traits, and the underlying health benefits. In this review, current research progresses on the peculiar tea varieties, the traditional and modern process technologies, the substance basis of sensory traits, and the latent bioactivities of LBT were comprehensively summarized. Furthermore, the present challenges and deficiencies that hinder the development of LBT, and the possible orientations and future perspectives were thoroughly discussed. By far, the productivity and quality of LBT remain restricted due to the reliance on labor and experience, as well as the incomplete understanding of the intricate interactions and underlying mechanisms involved in processing, organoleptic quality, and bioactivities. Consequently, further research is urgently warranted to address these gaps.


Disclosure and nondisclosure of physical health issues in psychodynamic psychotherapy.
In this exploratory study, 54 adult clients seen by 11 therapists in open-ended individual psychodynamic psychotherapy reported about disclosure and nondisclosure of physical health issues (PHI) within psychotherapy. Although clients reported at intake that they had moderately severe PHI, they discussed these issues in therapy only in 12% of sessions, and clients initiated the discussion about these issues nearly 75% of the time. The most frequently disclosed PHI were sleep, weight, illness, and pain. Clients were more likely to disclose if PHI were distressing, related to their mental health, relevant to the psychotherapy process, a priority, and if there was enough time in therapy for discussion. At the client level for disclosed PHI, depth of discussion was associated with client-rated alliance; clients who generally rated the alliance high were those who disclosed about the PHI, initiated the PHI discussion, and were not distressed by the PHI. At the session level, clients rated the alliance higher when they were distressed by the PHI but did not discuss it in depth. For nondisclosed PHI, clients reported a higher alliance if they generally and in particular sessions were not distressed about the PHI. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The pentraxin serum amyloid P component is found in the male genital tract and attached to spermatozoa.
Serum amyloid P component (SAP) belongs to the pentraxin family of proteins, members of which are characterized by radial pentameric structure and calcium-dependent ligand binding. SAP is present in all types of amyloidosis and has been shown to bind to several ligands, but the physiological function of this protein has not been fully elucidated. The present study identified and characterized SAP in human semen and immunolocalized it to the male reproductive tract. SAP was also detected in seminal plasma by immunoblotting and purification by affinity chromatography followed by mass spectrometry. According to electroimmunoassay, the concentration of SAP in semen is approximately 2 mg/L, and flow cytometry revealed SAP attached to the surface of spermatozoa. Moreover, immunohistochemistry showed positive staining of spermatozoa, subsets of epithelial cells, and the stroma of accessory male genital glands and testis. Presence of mRNA supports local production of SAP, as shown with reverse transcription polymerase chain reaction. We identified SAP in a new setting - the human male reproductive system. SAP was detected on ejaculated spermatozoa, in seminal plasma and in tissue sections from the male reproductive tract. Further functional studies are needed to explain the role of SAP in human reproduction.


Identification of prolyl hydroxylation modifications in mammalian cell proteins.
Prolyl hydroxylation is a PTM that plays an important role in the formation of collagen fibrils and in the oxygen-dependent regulation of hypoxia inducible factor-α (HIF-α). While this modification has been well characterized in the context of these proteins, it remains unclear to what extent it occurs in the remaining mammalian proteome. We explored this question using MS to analyze cellular extracts subjected to various fractionation strategies. In one strategy, we employed the von Hippel Lindau tumor suppressor protein, which recognizes prolyl hydroxylated HIF-α, as a scaffold for generating hydroxyproline capture reagents. We report novel sites of prolyl hydroxylation within five proteins: FK506-binding protein 10, myosin heavy chain 10, hexokinase 2, pyruvate kinase, and C-1 Tetrahydrofolate synthase. Furthermore, we show that identification of prolyl hydroxylation presents a significant technical challenge owing to widespread isobaric methionine oxidation, and that manual inspection of spectra of modified peptides in this context is critical for validation.


Effect of carbohydrate feedings on muscle glycogen utilization and exercise performance.
Ten men were studied during 4 h of cycling to determine the effect of solid carbohydrate (CHO) feedings on muscle glycogen utilization and exercise performance. In the experimental trial (E) the subjects ingested 43 g of sucrose in solid form along with 400 ml of water at 0, 1, 2 and 3 h of exercise. During the control trial (C) they received 400 ml of an artificially sweetened drink without solid CHO. No differences in VO2, heart rate, or total energy expenditure were observed between trials; however, respiratory exchange ratios were significantly (P less than 0.05) higher during E. Blood glucose was significantly (P less than 0.05) elevated 20 min post-feeding in E; however, by 50 min no differences were observed between trials until 230 min (E = 4.5 +/- 0.2 mmol X l-1 vs C = 3.9 +/- 0.2, means +/- SE; P less than 0.05). Muscle glycogen utilization was significantly (P less than 0.05) lower during E (100.7 +/- 10.2 mmol X kg-1 w.w.) than C (126.2 +/- 5.5). During a sprint (100% VO2max) ride to exhaustion at the end of each trial, subjects performed 45% longer when fed CHO (E = 126.8 +/- 24.7 s vs C = 87.2 +/- 17.5; P less than 0.05). It was concluded that repeated solid CHO feedings maintain blood glucose levels, reduce muscle glycogen depletion during prolonged exercise, and enhance sprint performance at the end of such activity.


Chondrotoxicity of Liposomal Bupivacaine in Articular Chondrocytes: Preliminary Findings.
The chondrotoxicity of local anesthetics has been previously recognized. Recent introduction of a liposomal formulation of bupivacaine has been found to significantly improve postoperative pain control but its effect on chondrocyte viability has yet to be investigated with this new formulation. We sought to assess the in vitro chondrotoxicity of liposomal bupivacaine. Chondrocytes were isolated from articular cartilage from fresh stifle joints and grown in culture medium. Cultured chondrocyte-derived cells (CDCs) were treated with 0.9% normal saline solution, 0.5%, 0.25%, and 0.13% bupivacaine and ropivacaine, 1.3% liposomal bupivacaine for 1 hour. Following treatment, cells were washed and incubated in media for 23 hours. The CDCs were then harvested and viability was assessed by flow cytometry using SYTOX green dead cell stain. Treated CDCs demonstrated a dose-response effect for chondrocyte viability when treated with bupivacaine, ropivacaine, and liposomal bupivacaine. Liposomal bupivacaine demonstrated the highest chondrocyte viability following treatment. Ropivacaine demonstrated higher chondrocyte viability than bupivacaine. Following 1 hour of treatment, liposomal bupivacaine demonstrated the highest chondrocyte viability. Chondrocyte viability was inversely proportional to anesthetic concentration.


Measurements of surface diffusivity and coarsening during pulsed laser deposition.
Pulsed laser deposition (PLD) of homoepitaxial SrTiO(3) 001 was studied with in situ x-ray specular reflectivity and surface diffuse x-ray scattering. Unlike prior reflectivity-based studies, these measurements access both time and length scales of the evolution of the surface morphology during growth. In particular, we show that this technique allows direct measurements of the diffusivity for both inter- and intralayer transport. Our results explicitly limit the possible role of island breakup, demonstrate the key roles played by nucleation and coarsening in PLD, and place an upper bound on the Ehrlich-Schwoebel barrier for downhill interlayer diffusion.


Functionalization of single-walled carbon nanotubes with azides derived from amino acids using click chemistry.
Single-walled carbon nanotubes (SWCNTs) were chemically functionalized with amino acid-based moieties. The covalent functionalization of alkyne-derived SWCNTs with well defined azides derived from amino acids was accomplished through Cu(I)-catalyzed Huisgen [3+2] dipolar cycloaddition click chemistry. Transmission electron microscopy, Raman spectroscopy, and infrared spectroscopic measurements confirmed the functionalization of SWCNTs by organic molecules derived from amino acids, and the resulting material showed some good solubility in the organic solvents such as tetrahydrofuran, CH2Cl2, and CHCl3.


Impact of hypertriglyceridaemia on cardiovascular mortality according to low-density lipoprotein cholesterol in a 15.6-million population.
To assess the association between triglyceride (TG) levels and cardiovascular disease (CVD) mortality concerning low-density lipoprotein cholesterol (LDL-C) and age in the general population. From the Korean National Health Insurance Service database, 15,672,028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios (HRs) for CVD mortality were calculated using Cox models after adjusting for various confounders. During a mean 8.8 years of follow-up, 105,174 individuals died of CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold (ischaemic heart disease [IHD]), 1.24-fold (acute myocardial infarction [AMI]), and 1.10-fold (ischaemic stroke) higher CVD mortality. Haemorrhagic stroke and heart failure were not associated with TG levels. The impact of HTG on CVD weakened but remained present in persons with LDL-C <100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischaemic stroke) higher CVD mortality. The younger population (18 to 44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population. Hypertriglyceridaemia (HTG) independently raises CVD mortality with lingering risks in young and older individuals with low LDL-C levels, suggesting the importance of management of HTG even with controlled LDL-C.


Introduction to special issue: Cultural processes in psychotherapy.
This article introduces the special issue on cultural processes in psychotherapy. The special section was organized to highlight both the clinical and research aspects of the cultural processes in psychotherapy from a variety of different theoretical orientations, perspectives, and methodologies. Additionally, I discuss some ideas for a future culturally focused psychotherapy scholarship. (PsycINFO Database Record


Courtship and copulation in the adult male green anole: effects of season, hormone and female contact on reproductive behavior and morphology.
Interactions among reproductive season, testosterone (T) and female presence were investigated on the structure and function of forebrain and neuromuscular systems controlling courtship and copulation in the green anole lizard. Under breeding (BS) or non-breeding (NBS) environmental conditions, male green anoles were implanted with either T or blank capsules and exposed to one of three female stimulus conditions: physical, visual or no female contact. T and at least visual exposure to females increased courtship displays (extension of a throat fan, or dewlap), and these effects were greater during the BS than NBS. T also facilitated copulation, and did so to a greater extent in the BS. The hormone increased soma size in the preoptic area (POA) and amygdala (AMY), and in the AMY the effects were greater in the BS than NBS. Cross-sectional areas of copulatory organs and associated muscle fibers were enhanced by T, and more so in the BS than NBS. However, no effects on morphology of dewlap motoneurons or muscles or copulatory motoneurons were detected. Thus, (1) changes in behavior and neural and/or muscular morphology are not always parallel and (2) differences in responsiveness to T exist across seasons and among tissues.


PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance.
Antimicrobial peptides are distributed throughout the animal kingdom and are a key component of innate immunity. Salmonella typhimurium regulates mechanisms of resistance to cationic antimicrobial peptides through the two-component systems PhoP-PhoQ and PmrA-PmrB. Polymyxin resistance is encoded by the PmrA-PmrB regulon, whose products modify the lipopolysaccharide (LPS) core and lipid A regions with ethanolamine and add aminoarabinose to the 4' phosphate of lipid A. Two PmrA-PmrB-regulated S. typhimurium loci (pmrE and pmrF) have been identified that are necessary for resistance to polymyxin and for the addition of aminoarabinose to lipid A. One locus, pmrE, contains a single gene previously identified as pagA (or ugd) that is predicted to encode a UDP-glucose dehydrogenase. The second locus, pmrF, is the second gene of a putative operon predicted to encode seven proteins, some with similarity to glycosyltransferases and other complex carbohydrate biosynthetic enzymes. Genes immediately flanking this putative operon are also regulated by PmrA-PmrB and/or have been associated with S. typhimurium polymyxin resistance. This work represents the first identification of non-regulatory genes necessary for modification of lipid A and subsequent antimicrobial peptide resistance, and provides support for the hypothesis that lipid A aminoarabinose modification promotes resistance to cationic antimicrobial peptides.