Hydrosilane/Organoiodine Coupling-Enabled Studies of Organosilane Physical Properties.
ConspectusThis Account summarizes recent developments in metal-mediated coupling reactions between hydrosilanes and aryl iodides in the presence of Pd(P(t-Bu)3)2 and base. Alkylated organosilanes are obtained when Pt(P(t-Bu)3)2 and a base are employed in reactions between hydrosilanes and aliphatic iodides. These transformations show unusual reactivity compared to the typical behavior of hydrosilanes toward organoiodides in the presence of PdCl2 or PtCl2, and they proceed in high yields under mild conditions. In addition, the reaction demonstrates (1) high functional group tolerances, (2) stepwise introduction of substituents onto silicon atoms from secondary silanes, and (3) transformation without cleavage of weak Si-Si σ bonds in the molecules.This transformation can serve as a powerful tool for the synthesis of functional organosilicon compounds. The advantage is the flexibility in the molecular structure due to the large size compared to carbon. These compounds have relatively sparse packing in the crystalline state, unlike π-conjugated molecules, which induce dense π-π interactions. Consequently, they have significantly different physical properties in solution and in the solid state. Among them, aromatic disilanes and oligosilanes are important substance groups, because the conjugated chain within these molecules expands due to σ-π interaction between Si-Si σ bond and π orbital of aromatic ring. σ-π Conjugation is most efficient when the dihedral angle between the aromatic ring and the Si-Si bond is 90°, resulting in the overlap of σ orbital and π orbital. The conformational structure, packing, and physical properties of these compounds can change in tandem in response to external stimuli through a crystal phase transition. The interlocking changes in structure and physical properties are reversible, easily returning to their original state with different external stimulus. This account covers several important aspects, including solid-state emission with high fluorescence intensity, aggregation-induced emission (AIE) in water-THF system, mechanochromic fluorescence, organic light emitting diode (OLED), second harmonic generation (SHG) and thermosalient phenomena.This reaction can synthesize optically active tertiary and quaternary silanes by the enantioselective arylation of secondary silanes with aryl iodides using a palladium catalyst modified with a TADDOL-derived amide phosphoric acid ester as a chiral ligand. These optically active compounds can be used as useful circularly polarized luminescence (CPL) materials due to their strong luminescence intensity (Φ) and luminescence dissymmetry factor (glum) attributed to the chiral silicon atom. The efficient synthesis of sila-pharmaceuticals using this method as a key step is also described.The technique enables the design and synthesis of various silicon-containing bioactive substances and medical chemicals. Through the synthesis of organosilane compounds using this method, it is anticipated that the development of functional organic silanes will accelerate their practical applications in a wide range of fields.


Hyaluronan is a prerequisite for ductal branching morphogenesis.
Hyaluronan, a macromolecular carbohydrate polymer of the extracellular matrix is prominent early in embryogenesis, coinciding with rapid tissue growth. CD44, the predominant receptor for hyaluronan on vertebrate cells, is a variably expressed transmembrane glycoprotein. Mouse anterior prostate glands obtained at various postnatal time points were examined for the expression of hyaluronan and CD44. Reverse transcriptase polymerase chain reaction analysis was used to map the temporal regulation of specific CD44 variant isoforms. In each age group, hyaluronan was localized exclusively in the stromal matrix. Hyaluronan was greatly reduced in the later ages and was entirely absent around the developmentally quiescent proximal regions of the ducts. Early in prostate development, CD44 was prominent in the mesenchyme. However, in the later phases, CD44 expression became associated with membranes of epithelial cells. The role of hyaluronan-CD44 interactions in ductal branching morphogenesis was studied by serum-free organ culture of mouse anterior prostate. In the presence of optimal levels of testosterone, the organs underwent ductal branching morphogenesis. Treatment with either neutralizing anti-CD44 antibodies, hyaluronan hexasaccharides or the enzyme hyaluronidase inhibited androgen-stimulated ductal branching morphogenesis. These results are suggestive of the significant role played by hyaluronan-CD44 interactions in mediating androgen-induced prostatic growth and morphogenesis.


Genetics and social class.
To assess claims that genes are a major determinant of social class. Using genetic epidemiological principles, five claims on the role of genes in determining social class are examined: (1) traits that run in families are usually inherited; (2) complex traits can be explained by alleles at a single gene locus; (3) complex traits are transmitted intact from one generation to the next; (4) natural selection explains social advantage. (5) Heritability estimates provide a valid estimate of the importance of genes in explaining complex human traits or behaviour. (1) Traits that run in families can result from environmental exposures that differ by social class. (2) The protein encoded by any single gene has too narrow a range of biological activity to explain traits as complex as social status. (3) Because alleles at different gene loci are transmitted independently, genetic inheritance cannot explain why offspring display the same complex traits as their parents. (4) The propagation of mutations that might result in a selective advantage takes much longer than the time for which any social class has achieved or maintained dominance. (5) Heritability measures are accurate only when environment is maintained constant. This is impossible in evaluating human traits. The roots of social class differences do not lie in our genes. Consequently, genetics cannot be used as a justification for maintaining a ruling class, limiting procreation among the poor, or minimising social support programmes.


The Pre and Post Massage Test (PPMT): a simple screen for prostatitis.
The segmented quantitative culture technique originally described more than 25 years ago is acknowledged as the best test to diagnose prostatitis. However, it, is not widely used in clinical practice. This is especially true in primary care settings, but even most urologists appear to have abandoned the procedure. Herein is proposed a simple and cost-effective screen for prostatitis, which involves the culture and microscopic examination of urine before and after prostatic massage. This Pre and Post Massage Test (PPMT) was applied to a personal series of 53 patients and 59 patients from the literature in whom the results of the segmented cultures are available and the results were reevaluated. In this selected patient population the PPMT alone led to the same diagnosis in 102 (91.1%). Within the expected limitations of this retrospective review, the calculated sensitivity and specificity of the PPMT were both 91%. This report should provoke researchers to review their prostatitis data, stimulate discussion, and hopefully convince physicians that adoption of a simpler diagnostic plan for prostatitis is far superior to doing no workup at all.


Host antigens on avian oncoviruses: evidence for virus envelope antigens related to specific chicken erythrocyte membrane antigens.
Avian sarcoma viruses (ASV) of subgroups A to D, produced by chick embryo fibroblasts (CEF), are inactivated to a high degree by rabbit antisera to the membrane antigens of adult chicken and chick embryo erythrocytes, notably by antisera to an antigen of embryo erythrocytes, which is lost by adult erythrocytes and to another antigen specific to the latter erythrocytes. Contrary to virus inactivation by anti-CEF serum reported earlier, virus inactivation by the antisera to these two age-specific antigens does not require complement and is not paralleled by virolysis but by aggregation of virions. The two antigens related, or identical, to the age-specific erythrocyte membrane antigens thus shown to be present on the virus envelope do not pre-exist, or pre-exist only in a low amount, on the CEF membrane, since the virus-inactivating capacity of their antisera is not removed by absorption with CEF. Their appearance on the virus does not depend on cell transformation but only on infection, since both antigens are found on a ts ASV mutant produced at restrictive temperature by untransformed CEF and the virus-inactivating capacity of their antisera is removed by absorption with CEF infected with Rous-associated virus (RAV-1). These findings suggest that infection of CEF by avian oncoviruses may elicit the appearance, or enhance the expression at the cell surface of antigens characteristic of another cell type which may contribute to the formation of specific virus budding sites.


Hydrogen-saturated saline protects intensive narrow band noise-induced hearing loss in guinea pigs through an antioxidant effect.
The purpose of the current study was to evaluate hydrogen-saturated saline protecting intensive narrow band noise-induced hearing loss. Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections (1 ml/100 g) 3 days before and 1 h before narrow band noise exposure (2.5-3.5 kHz 130 dB SPL, 1 h). The guinea pigs in the control group received no treatment. The hearing function was assessed by the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) recording. The changes of free radicals in the cochlea before noise exposure, and immediately and 7 days after noise exposure were also examined. By Scanning electron microscopy and succinate dehydrogenase staining, we found that pre-treatment with hydrogen-saturated saline significantly reduced noise-induced hair cell damage and hearing loss. We also found that the malondialdehyde, lipid peroxidation, and hydroxyl levels were significantly lower in the hydrogen-saturated saline group after noise trauma, indicating that hydrogen-saturated saline can decrease the amount of harmful free radicals caused by noise trauma. Our findings suggest that hydrogen-saturated saline is effective in preventing intensive narrow band noise-induced hearing loss through the antioxidant effect.


Quinolines as chemotherapeutic agents for leishmaniasis.
The development of leishmanicidal quinolines and their in vitro (promastigote and amastigote) and, where applicable, in vivo activities are reviewed. This survey provides a direct comparison of bioactivity across different species(e.g. L. donovani, L. amazonensis, L. chagasi, L infantum), and in different animal models (e.g. L. donovani Balb/c mice and L. donovani infected hamsters). The progress of selected quinolines through pre-clinical development and phase I/II trials, and the lead quinoline drugs sitamaquinine and Imiquimod, are discussed in conjunction with delivery systems and combination therapies.


Vestibular consequences of mild traumatic brain injury and blast exposure: a review.
The purpose of this article is to review relevant literature on the effect of mild traumatic brain injury (mTBI) and blast injury on the vestibular system. Dizziness and imbalance are common sequelae associated with mTBI, and in some individuals, these symptoms may last for six months or longer. In war-related injuries, mTBI is often associated with blast exposure. The causes of dizziness or imbalance following mTBI and blast injuries have been linked to white matter abnormalities, diffuse axonal injury in the brain, and central and peripheral vestibular system damage. There is some evidence that the otolith organs may be more vulnerable to damage from blast exposure or mTBI than the horizontal semicircular canals. In addition, benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder following head injury that is treated effectively with canalith repositioning therapy. Treatment for (non-BPPV) mTBI-related vestibular dysfunction has focused on the use of vestibular rehabilitation (VR) augmented with additional rehabilitation methods and medication. New treatment approaches may be necessary for effective otolith organ pathway recovery in addition to traditional VR for horizontal semicircular canal (vestibulo-ocular reflex) recovery.


Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy.
Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction < 45%), diastolic dysfunction (time constant of left ventricular relaxation > 55 milliseconds, left ventricular end-diastolic pressure > 18 mm Hg), and left ventricular hypertrophy (left ventricular mass index > 120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m2. The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.


Transient expression of red and yellow fluorescent protein vectors in HCT-8 cells infected with Cryptosporidium parvum.
Electroporation in combination with the red and yellow fluorescent protein (RFP and YFP, respectively) reporter systems results in transient gene expression in HCT-8 cell lines infected and uninfected with Cryptosporidium parvum. Conditions are described allowing efficient electroporation of HCT-8 cell monolayers in a commercial electroporation device (180 kV/cm voltage, 250 microF capacitance, and 0 ohm (ohm) resistance resulting in a time constant of 0.4 ms.). Fluorescent microscopy showed that uninfected HCT-8 cell monolayers achieved higher gene transfer and expression efficiencies than HCT-8 cells infected with C. parvum under similar conditions. Real-time melting curve and quantitation analysis of reverse transcription polymerase chain reaction amplicons are presented for the detection of all mRNA sample levels. Our findings demonstrate that C. parvum infection of HCT-8 cells may negatively affect the transient expression of RFP and YFP plasmids. The focus of this study was to achieve transient expression of reporter genes in HCT-8 cell lines and provide the basis for further analyses of gene regulation in protozoan. These approaches may provide to understanding the feasibility of gene transfer and expression efficiencies HCT-8 cell cultures by RFP and YFP containing the CMV promoter; they could serve as tools for gene transfer in mammalian cell.


Impact of fellowship training on clinical practice of orthopaedic sports medicine.
Approximately 90% of current orthopaedic graduates are engaging in fellowship training, with sports medicine being the most commonly chosen specialty. The purpose of this study was to evaluate the impact of fellowship training on clinical decision-making by fellowship-trained sports medicine surgeons. A survey was designed to assess the importance of fellowship on common clinical decisions made in the nonoperative and surgical treatment of knee, shoulder, and elbow disorders. The survey also included questions for the respondents on their comfort level with a variety of routine and complex surgical procedures. The survey was sent to alumni of 113 orthopaedic sports medicine programs across the United States. Completed surveys were returned by 310 surgeons who had been in practice for an average of 9.0 years. They represented alumni of twenty-nine orthopaedic sports medicine fellowship programs across sixteen states. Fellowship was considered very important for surgical decision-making in the knee and shoulder. For nonoperative treatment, fellowship had a greater impact on shoulder disorders than on knee or elbow disorders. Fellowship was significantly more important than residency (p < 0.001) for determining preferred surgical equipment, implants, and braces. Among the surgical procedures assessed, respondents were least comfortable with the treatment of multi-ligamentous knee injuries, posterior cruciate ligament injuries, and shoulder instability with bone loss. Fellowship has a significantly higher impact than residency on industry-related decision-making. Fellowship-trained sports surgeons should consider seeking additional training in the treatment of multi-ligamentous knee injuries, posterior cruciate ligament injuries, shoulder instability with bone loss, and elbow disorders. The current findings were limited by the relatively small respondent pool, which represented only 26% of sports medicine fellowship programs in the United States.


Soybean β-conglycinin bromelain hydrolysate stimulates cholecystokinin secretion by enteroendocrine STC-1 cells to suppress the appetite of rats under meal-feeding conditions.
A peptic digest of soybean β-conglycinin (BconP) suppresses the appetite in rats through cholecystokinin (CCK) secretion by enteroendocrine cells. We investigate in this study more appetite-suppressing hydrolysates. β-Conglycinin hydrolyzed with food-processing proteases thermolysin (BconT), bromelain (BconB), chymotrypsin, protease S, and protease M was examined for CCK-secreting activity in a CCK-producing cell line for comparison with BconP. The potent CCK-releasing hydrolysates were then tested for their suppression of the food intake by rats. BconB, BconT, and BconP stimulated high CCK secretion, with the highest by BconB. Orogastric preloading by BconB, but not by BconT, suppressed the 60-min food intake. A meal-feeding trial twice a day in the morning (a.m.) and evening (p.m.) for 10 d showed that BconB preloading before every meal attenuated the p.m. meal size, but not that a.m., resulting in an overall reduction of the daily meal size. These results demonstrate that the bromelain hydrolysate of β-conglycinin having potent CCK-releasing activity suppressed the appetite of rats under meal-feeding conditions.


Leptographium sinoprocerum sp. nov., an undescribed species associated with Pinus tabuliformis-Dendroctonus valens in northern China.
During a study of ophiostomatoid fungi associated with the invasive pest Dendroctonus valens in the Pinus tabuliformis ecosystem in northern China, a multigenic (ITS2-LSU, beta-tubulin and EF1-alpha) phylogenetic analysis and examination of morphological features revealed in addition to Leptographium procerum the occurrence of an undescribed species. The new species, Leptographium sinoprocerum, belongs to the L. procerum-L. profanum clade. Both L. procerum and L. sinoprocerum are similar to each other and occur sympatrically in the ecosystem studied. Nevertheless L. sinoprocerum can be distinguished from L. procerum by shorter conidiophore stipes arising from both submerged and aerial hyphae, slightly more oblong conidia, a granular ornamentation on the submerged hyphae and dark olivaceous colonies on MEA.


Evolutionary origin of a periodical mass-flowering plant.
The evolutionary origin of periodical mass-flowering plants (shortly periodical plants), exhibiting periodical mass flowering and death immediately after flowering, has not been demonstrated. Within the genus Strobilanthes (Acanthaceae), which includes more than 50 periodical species, Strobilanthes flexicaulis on Okinawa Island, Japan, flowers gregariously every 6 years. We investigated the life history of S. flexicaulis in other regions and that of closely related species together with their molecular phylogeny to reveal the evolutionary origin of periodical mass flowering. S. flexicaulis on Taiwan Island was found to be a polycarpic perennial with no mass flowering and, in the Yaeyama Islands, Japan, a monocarpic perennial with no mass flowering. Molecular phylogenetic analyses indicated that a polycarpic perennial was the ancestral state in this whole group including S. flexicaulis and the closely related species. No distinctive genetic differentiation was found in S. flexicaulis among all three life histories (polycarpic perennial, monocarpic perennial, and periodical plant). These results suggest that among S. flexicaulis, the periodical mass flowering on Okinawa Island had evolved from the polycarpic perennial on Taiwan Island via the monocarpic perennial in the Yaeyama Islands. Thus, the evolution of life histories could have taken at the level of local populations within a species.


Orthostatic hypotension in patients with dementia: clinical features and response to treatment.
To evaluate orthostatic hypotension (OH) prevalence, risk factors, signs and symptoms, and treatment response in patients with dementia. No previous studies had systematically delineated the clinical features of OH in patients with dementia and determined the effects of treatment. Diagnosing this treatable disorder may prevent the severe consequences of falls, syncope, confusion, ischemic brain injury, and death; mortality risk rises with worsening OH. Lesser consequences include skin injuries, sprains, fractures, and subdural hematomas. We reviewed the charts of 188 patients with dementia who had been treated by author D.F., a solo neurologist/neurobehaviorist. About half of the patients had been diagnosed with OH. D.F. had treated the OH until the patients had much improved blood pressure and symptoms, were asymptomatic, or no longer met OH diagnostic criteria. We collected data on diagnoses, blood pressures, and clinical features before and after treatment. Our patients' most frequent OH signs and symptoms were mental fluctuations (65.6% of patients), excessive sleeping in chairs (29.2%), slow falls without losing consciousness (20.8%), lethargy or fatigue (15.6%), and dizziness (13.5%). All 5 of these signs and symptoms improved significantly with treatment. Patients with dementia were less likely to have traditional OH symptoms like dizziness than to have mental fluctuations and confusion, drowsiness, and slow falls. Blaming these problems on worsening dementia and neglecting OH as a potential cause may delay diagnosis and specific treatments that can improve patients' safety, daily function, and quality of life.


Effect of Water Adsorption on the Photoluminescence of Silicon Quantum Dots.
The optical properties of silicon quantum dots (Si QDs) are strongly influenced by circumjacent surface-adsorbed molecules, which would highly affect their applications; however, water, as the ubiquitous environment, has not received enough attention yet. We employed the time-dependent density functional calculations to investigate the water effect of photoluminescence (PL) spectra for Si QDs. In contrast with the absorption spectra, PL spectra exhibit distinct characteristics. For Si32H38, PL presents the single maximum in the dry and humid environment, while the emission spectrum displays a dual-band fluorescence spectroscopy in the low-humidity environment. This phenomenon is also observed in the larger Si QDs. The distinct character in spectroscopy is dominated by the stretching of the Si-Si bond, which could be explained by the self-trapped exciton model. Our results shed light on the Si-water interaction that is important for the development of optical devices based on Si-coated surfaces.


T1rho, T2 and focal knee cartilage abnormalities in physically active and sedentary healthy subjects versus early OA patients--a 3.0-Tesla MRI study.
(1) To assess the degree of focal cartilage abnormalities in physically active and sedentary healthy subjects as well as in patients with early osteoarthritis (OA). (2) To determine the diagnostic value of T2 and T1rho measurements in identifying asymptomatic physically active subjects with focal cartilage lesions. Thirteen asymptomatic physically active subjects, 7 asymptomatic sedentary subjects, and 17 patients with mild OA underwent 3.0-T MRI of the knee joint. T1rho and T2 values, cartilage volume and thickness, as well as the WORMS scores were obtained. Nine out of 13 active healthy subjects had focal cartilage abnormalities. T1rho and T2 values in active subjects with and without focal cartilage abnormalities differed significantly (p < 0.05). T1rho and T2 values were significantly higher (p < 0.05) in early OA patients compared to healthy subjects. T1rho measurements were superior to T2 in differentiating OA patients from healthy subjects, yet T1rho was moderately age-dependent. (1) Active subjects showed a high prevalence of focal cartilage abnormalities and (2) active subjects with and without focal cartilage abnormalities had different T1rho and T2 composition of cartilage. Thus, T1rho and T2 could be a parameter suited to identify active healthy subjects at higher risk for developing cartilage pathology.


ASSESSMENT OF NUTRITIONAL STATUS OF CHILDREN AND ADOLESCENTS WITH SPASTIC QUADRIPLEGIC CEREBRAL PALSY.
Due to several factors, such as gastrointestinal's diseases and difficulty in feeding, children with Spastic Quadriplegic Cerebral Palsy tend to present nutritional deficits. To assess the nutritional status of pediatric patients with Spastic Quadriplegic Cerebral Palsy according to reference curves for this population and with the measures of folds and circumferences, obtained by the upper arm circumference and triceps skin fold. The data were obtained from: knee-height, estimated height, weight, upper arm circumference, and triceps skin fold. Values of folds and circumferences were compared with Frisancho, and specific curves for these patients were used as reference. The relationship between the values in the growth curve for healthy children, Z-Score, and comparison with the reference curve were verified by Fisher's exact test. We adopted the significance level of 5%. We evaluated 54 patients. The mean age was 10.2 years, and 34 were male, 25 fed by gastrostomy and 29, orally. The frequency of low weight by the reference curve was 22.22%. More than half of the patients presented the parameters indicating lean mass below the 5th percentile. The height of all patients was classified as adequate for the age by the reference curve. Low weight was found in 22% of patients, and there is a greater tendency to present reduced muscle mass and increased fat mass, showing the need for evaluation and appropriate interventions for patients with Spastic Quadriplegic Cerebral Palsy.


Low-molecular-weight glutenin subunits from the 1U genome of Aegilops umbellulata confer superior dough rheological properties and improve breadmaking quality of bread wheat.
Wheat-related genomes may carry new glutenin genes with the potential for quality improvement of breadmaking. In this study, we estimated the gluten quality properties of the wheat line CNU609 derived from crossing between Chinese Spring (CS, Triticum aestivum L., 2n = 6x = 42, AABBDD) and the wheat Aegilops umbellulata (2n = 2x = 14, UU) 1U(1B) substitution line, and investigated the function of 1U-encoded low-molecular-weight glutenin subunits (LMW-GS). The main quality parameters of CNU609 were significantly improved due to introgression of the 1U genome, including dough development time, stability time, farinograph quality number, gluten index, loaf size and inner structure. Glutenin analysis showed that CNU609 and CS had the same high-molecular-weight glutenin subunit (HMW-GS) composition, but CNU609 carried eight specific 1U genome-encoded LMW-GS. The introgression of the 1U-encoded LMW-GS led to more and larger protein body formation in the CNU609 endosperm. Two new LMW-m type genes from the 1U genome, designated Glu-U3a and Glu-U3b, were cloned and characterized. Secondary structure prediction implied that both Glu-U3a and Glu-U3b encode subunits with high α-helix and β-strand content that could benefit the formation of superior gluten structure. Our results indicate that the 1U genome has superior LMW-GS that can be used as new gene resources for wheat gluten quality improvement. © 2017 Society of Chemical Industry.


Stochastic imputation for integrated transcriptome association analysis of a longitudinally measured trait.
The mechanistic pathways linking genetic polymorphisms and complex disease traits remain largely uncharacterized. At the same time, expansive new transcriptome data resources offer unprecedented opportunity to unravel the mechanistic underpinnings of complex disease associations. Two-stage strategies involving conditioning on a single, penalized regression imputation for transcriptome association analysis have been described for cross-sectional traits. In this manuscript, we propose an alternative two-stage approach based on stochastic regression imputation that additionally incorporates error in the predictive model. Application of a bootstrap procedure offers flexibility when a closed form predictive distribution is not available. The two-stage strategy is also generalized to longitudinally measured traits, using a linear mixed effects modeling framework and a composite test statistic to evaluate whether the genetic component of gene-level expression modifies the biomarker trajectory over time. Simulations studies are performed to evaluate relative performance with respect to type-1 error rates, coverage, estimation error, and power under a range of conditions. A case study is presented to investigate the association between whole blood expression for each of five inflammasome genes with inflammatory response over time after endotoxin challenge.


Associations between USF1 gene variants and cardiovascular risk factors in the Quebec Family Study.
Cardiovascular (CVD) risk factors are under the influence of environmental and genetic factors. Human upstream transcription factor 1 gene (USF1) encodes for a transcription factor, which modulates the expression of genes involved in lipid and carbohydrate metabolic pathways. The aim of this study was to test the hypothesis that USF1 gene variants are associated with CVD risk factors in the Quebec Family Study (QFS). USF1 has been sequenced in 20 QFS subjects with high plasma apolipoprotein B100 (APOB) levels (>1.14 g/l) and small, dense low-density lipoprotein (LDL) particles (> or =250.7 Angstroms and < or =255.9 Angstroms), as well as in five subjects with larger LDL particles. Ten variants were identified in non-coding regions of USF1. Two of these polymorphisms (intron 7 c.561-100 G>A, and exon 11 c.*187 C>T) as well as the c.-56 A>G polymorphism, were genotyped and analyzed in 760 subjects from QFS. Association studies showed that women with c.561-100 A/A and c.*187 T/T genotypes had more favorable adiposity indices (<0.04). In summary, significant associations between relatively common USF1 genetic variants and CVD risk factors were observed in French Canadians.


Ultrafast electrical spectrum analyzer based on all-optical Fourier transform and temporal magnification.
Real-time electrical spectrum analysis is of great significance for applications involving radio astronomy and electronic warfare, e.g. the dynamic spectrum monitoring of outer space signal, and the instantaneous capture of frequency from other electronic systems. However, conventional electrical spectrum analyzer (ESA) has limited operation speed and observation bandwidth due to the electronic bottleneck. Therefore, a variety of photonics-assisted methods have been extensively explored due to the bandwidth advantage of the optical domain. Alternatively, we proposed and experimentally demonstrated an ultrafast ESA based on all-optical Fourier transform and temporal magnification in this paper. The radio-frequency (RF) signal under test is temporally multiplexed to the spectrum of an ultrashort pulse, thus the frequency information is converted to the time axis. Moreover, since the bandwidth of this ultrashort pulse is far beyond that of the state-of-the-art photo-detector, a temporal magnification system is applied to stretch the time axis, and capture the RF spectrum with 1-GHz resolution. The observation bandwidth of this ultrafast ESA is over 20 GHz, limited by that of the electro-optic modulator. Since all the signal processing is in the optical domain, the acquisition frame rate can be as high as 50 MHz. This ultrafast ESA scheme can be further improved with better dispersive engineering, and is promising for some ultrafast spectral information acquisition applications.


MHC class I limits hippocampal synapse density by inhibiting neuronal insulin receptor signaling.
Proteins of the major histocompatibility complex class I (MHCI) negatively regulate synapse density in the developing vertebrate brain (Glynn et al., 2011; Elmer et al., 2013; Lee et al., 2014), but the underlying mechanisms remain largely unknown. Here we identify a novel MHCI signaling pathway that involves the inhibition of a known synapse-promoting factor, the insulin receptor. Dominant-negative insulin receptor constructs decrease synapse density in the developing Xenopus visual system (Chiu et al., 2008), and insulin receptor activation increases dendritic spine density in mouse hippocampal neurons in vitro (Lee et al., 2011). We find that genetically reducing cell surface MHCI levels increases synapse density selectively in regions of the hippocampus where insulin receptors are expressed, and occludes the neuronal insulin response by de-repressing insulin receptor signaling. Pharmacologically inhibiting insulin receptor signaling in MHCI-deficient animals rescues synapse density, identifying insulin receptor signaling as a critical mediator of the tonic inhibitory effects of endogenous MHCI on synapse number. Insulin receptors co-immunoprecipitate MHCI from hippocampal lysates, and MHCI unmasks a cytoplasmic epitope of the insulin receptor that mediates downstream signaling. These results identify an important role for an MHCI-insulin receptor signaling pathway in circuit patterning in the developing brain, and suggest that changes in MHCI expression could unexpectedly regulate neuronal insulin sensitivity in the aging and diseased brain.


Factors influencing the implementation of clinical guidelines for health care professionals: a systematic meta-review.
Nowadays more and more clinical guidelines for health care professionals are being developed. However, this does not automatically mean that these guidelines are actually implemented. The aim of this meta-review is twofold: firstly, to gain a better understanding of which factors affect the implementation of guidelines, and secondly, to provide insight into the "state-of-the-art" regarding research within this field. A search of five literature databases and one website was performed to find relevant existing systematic reviews or meta-reviews. Subsequently, a two-step inclusion process was conducted: (1) screening on the basis of references and abstracts and (2) screening based on full-text papers. After that, relevant data from the included reviews were extracted and the methodological quality of the reviews was assessed by using the Quality Assessment Checklist for Reviews. Twelve systematic reviews met our inclusion criteria. No previous systematic meta-reviews meeting all our inclusion criteria were found. Two of the twelve reviews scored high on the checklist used, indicating only "minimal" or "minor flaws". The other ten reviews scored in the lowest of middle ranges, indicating "extensive" or "major" flaws. A substantial proportion (although not all) of the reviews indicates that effective strategies often have multiple components and that the use of one single strategy, such as reminders only or an educational intervention, is less effective. Besides, characteristics of the guidelines themselves affect actual use. For instance, guidelines that are easy to understand, can easily be tried out, and do not require specific resources, have a greater chance of implementation. In addition, characteristics of professionals - e.g., awareness of the existence of the guideline and familiarity with its content - likewise affect implementation. Furthermore, patient characteristics appear to exert influence: for instance, co-morbidity reduces the chance that guidelines are followed. Finally, environmental characteristics may influence guideline implementation. For example, a lack of support from peers or superiors, as well as insufficient staff and time, appear to be the main impediments. Existing reviews describe various factors that influence whether guidelines are actually used. However, the evidence base is still thin, and future sound research - for instance comparing combinations of implementation strategies versus single strategies - is needed.


Death patterns among Nigerian leaders.
The aim of this study is to establish the patterns of death amongst Nigerian leaders since independence, thus providing a feasible avenue to avoid their recurrence if possible especially amongst the political elite who currently hold power. Using available unclassified authentic public information, all leaders who had ruled Nigeria since her independence on 1 October, 1960 until her 45th birthday on 1 October 2005, irrespective of whether they are dead or alive were included. Data was extracted and analyzed. On 1 October 2005, Nigeria celebrated 45 years as a sovereign nation. Within this period, the country has had eleven leaders, all of whom were men. Only three (27.3%) were civilians, while eight (72.7%) were army generals. Of the eleven leaders, four (36.4%) had died before Nigeria reached its 45th birthday and all of these four (100%) died while still in office. Three of the dead leaders (75%) were assassinated, while one (25%) died suddenly in mysterious circumstances, believed to be the result of poisoning by unknown external powerful interest groups. Three of the deaths (75%) occurred during violent periods of Nigeria's checkered history (1966-1970 and 1993-1999), showing that periods of national and international strife appeared to be the weakest link in chains of events that led to their death while in office. Autopsies were neither requested nor performed on any of the dead leaders, signifying an entrenched culture of nonchalance, a lack of a coordinated national coroner's law and contempt for accurate and detailed death records. Worse still, no valid tenable death certificate has ever been issued. In other words, no attempt has been made to determine the cause of death of four of the nation's former leaders. Only hurried national burials were accorded two (50%) of them while the other two (50%), who died in the coup and revenge coup of 1966, were completely neglected, and not even given a decent national burial. The facts identified above will serve as a landmark to highlight an existing problem, and thus bring the issue to the attention of policy-makers and the political elite. The overall expected benefit is that nations like Nigeria can focus on the issue of orderly succession and the peaceful handing-over of government to duly transparently elected national leaders and all efforts should be made to avoid holding on to power unnecessarily. The tenets of democracy shall be upheld and transparent elections take place so as to reduce national tension and strife to the barest minimum. We also strongly recommend a review and improvement of Nigeria's national coroner's laws.


Accumulation of isolevuglandin-modified protein in normal and fibrotic lung.
Protein lysine modification by γ-ketoaldehyde isomers derived from arachidonic acid, termed isolevuglandins (IsoLGs), is emerging as a mechanistic link between pathogenic reactive oxygen species and disease progression. However, the questions of whether covalent modification of proteins by IsoLGs are subject to genetic regulation and the identity of IsoLG-modified proteins remain unclear. Herein we show that Nrf2 and Nox2 are key regulators of IsoLG modification in pulmonary tissue and report on the identity of proteins analyzed by LC-MS following immunoaffinity purification of IsoLG-modified proteins. Gene ontology analysis revealed that proteins in numerous cellular pathways are susceptible to IsoLG modification. Although cells tolerate basal levels of modification, exceeding them induces apoptosis. We found prominent modification in a murine model of radiation-induced pulmonary fibrosis and in idiopathic pulmonary fibrosis, two diseases considered to be promoted by gene-regulated oxidant stress. Based on these results we hypothesize that IsoLG modification is a hitherto unrecognized sequelae that contributes to radiation-induced pulmonary injury and IPF.


Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies.
The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.


Attempts to produce granulomatous colitis in Boxer dogs with a mycoplasma.
Four of six Boxer dogs with granulomatous colitis had mycoplasmas in the colon and three in the draining lymph node as well. One isolate identical with Mycoplasma strain HRC-689 was inoculated into the colon of five Boxer dogs at eight weeks of age; four controls were inoculated with medium. Animals were killed at two week intervals and examined. The mycoplasma strain produced changes of the colon characterized by lymphocytic infiltration of mucosa, lymphocytic submucosal perivasculitis, and enlargement of colonic lymphoid nodules but granulomatous colitis did not occur. The experimental dogs developed antibodies, and dogs from a kennel with a high prevalence of colitis cases had high antibody titers against strain HRC-689.


Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis.
Pattern reversal visual evoked potentials (PRVEPs) have a well-documented role in diagnosis of multiple sclerosis (MS), but their value as a visual function surrogate remains controversial. We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a phase III trial of interferon beta-1a (Avonex). Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated for P100 latency, amplitude, and waveform morphology. Two summary scores were created: for Score A, abnormal latencies, morphologies, and amplitudes of each individual eye were added; for Score B, abnormal latencies, morphologies, and amplitude ratio between eyes was determined. Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously. At the follow-up exam, over 75% of patients had abnormal PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was significantly correlated with EDSS, BPF, CLA, cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC. The results indicate that PRVEP measures MS-related pathology, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.


Three-dimensional immobilization of beta-galactosidase on a silicon surface.
Many alternative strategies to immobilize and stabilize enzymes have been investigated in recent years for applications in biosensors. The entrapment of enzymes within silica-based nanospheres formed through silicification reactions provides high loading capacities for enzyme immobilization, resulting in high volumetric activity and enhanced mechanical stability. Here we report a strategy for chemically associating silica nanospheres containing entrapped enzyme to a silicon support. beta-galactosidase from E. coli was used as a model enzyme due to its versatility as a biosensor for lactose. The immobilization strategy resulted in a three-dimensional network of silica attached directly at the silicon surface, providing a significant increase in surface area and a corresponding 3.5-fold increase in enzyme loading compared to enzyme attached directly at the surface. The maximum activity recovered for a silicon square sample of 0.5 x 0.5 cm was 0.045 IU using the direct attachment of the enzyme through glutaraldehyde and 0.16 IU when using silica nanospheres. The immobilized beta-galactosidase prepared by silica deposition was stable and retained more than 80% of its initial activity after 10 days at 24 degrees C. The ability to generate three-dimensional structures with enhanced loading capacity for biosensing molecules offers the potential to substantially amplify biosensor sensitivity.


Overview: cytomegalovirus and the herpesviruses in transplantation.
Herpesviruses infect most animal species. Infections due to the eight human herpesviruses (HHV) are exacerbated by immunosuppression in organ transplantation. The special features of the herpesvirus life cycle include the ability to establish latent, nonproductive infection and the life-long capacity for reactivation to productive, lytic infection. Interactions between latent virus and the immune system determine the frequency and severity of symptomatic infections. The immunologic and cellular effects of herpesvirus infections contribute to risk for opportunistic infections and graft rejection. Among the most important advances in transplantation are laboratory assays for the diagnosis and monitoring of herpesvirus infections and antiviral agents with improved efficacy in prophylaxis and therapy. For herpes simplex virus, varicella zoster virus and cytomegalovirus, these advances have significantly reduced the morbidity of infection. The syndromes of EBV-associated posttransplant lymphoproliferative disorders (PTLD) and Kaposi's sarcoma remain important complications of immunosuppression. The epidemiology and essential biology of human herpesvirus is reviewed.


How to play the game of medical education: Sociocultural analyses of educational difficulties among medical residents.
This article was migrated. The article was marked as recommended. Medical residents in difficulty struggle to comply with educational requirements. They pose a liability to patient safety and they have problems to adapt to the professional role of a doctor. Consequently, being a resident in difficulty may cause identity crisis and have the potential to disrupt the resident's professional identity as a doctor. Only few studies explore the tipping point between becoming a resident in difficulty or not, and these studies rarely reflect the surrounding sociocultural aspects of the residents' difficulties such as organisational culture in the workplace. This article explores how medical residency training culture influence on residents' risk of ending in difficulty. Our study was based on six focus-group interviews with residents (n=28) and in-depth interviews with residents in difficulty (n=10). The interpretation of data employed sociologist Pierre Bourdieu's theoretical framework around dispositions. Across the data, we identified four themes: Conflicting games in the field of medical education, altruism, organisational hierarchy, and coping with stress. We found a (mis)match between legitimate rules in the field of medicine and the residents' dispositions to appreciate those rules. These results can inform clinical supervisors and consultants in their decisions for supporting residents in difficulty and increasing educational achievement among struggling residents.


Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled Trial.
Oxidant stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light decreases its peroxide content, which has nutrition and biochemical benefits in animals and humans. This study aims at determining whether full light protection of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low-birth-weight infants. Multicenter randomized controlled trial of photoprotection, using amber bags and tubing initiated during compounding of PN and maintained throughout infusion in the light-protected (LP) group. The control group (light exposed [LE]) received PN exposed to ambient light. Depending on centers, lipids were infused either separately or as all-in-one PN. In total, 590 infants born <30 weeks gestational age were included. At randomization, LE and LP groups did not differ clinically except for maximal FiO2 before 12 hours. The rate of BPD/death was not different between groups at 28 days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE, P = .55). Multivariate analysis showed no significant effect of photoprotection on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio, 0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in-one PN vs those who received lipids separately. This study did not show significant beneficial effects of photoprotection. Since the decreased rate of BPD/death found with all-in-one PN relates to a center-dependent variable, this warrants further investigation.


The crystal structure of the complex of Zea mays alpha subunit with a fragment of human beta subunit provides the clue to the architecture of protein kinase CK2 holoenzyme.
The crystal structure of a complex between the catalytic alpha subunit of Zea mays CK2 and a 23-mer peptide corresponding the C-terminal sequence 181-203 of the human CK2 regulatory beta subunit has been determined at 3.16-A resolution. The complex, composed of two alpha chains and two peptides, presents a molecular twofold axis, with each peptide interacting with both alpha chains. In the derived model of the holoenzyme, the regulatory subunits are positioned on the opposite side with respect to the opening of the catalytic sites, that remain accessible to substrates and cosubstrates. The beta subunit can influence the catalytic activity both directly and by promoting the formation of the alpha2 dimer, in which each alpha chain interacts with the active site of the other. Furthermore, the two active sites are so close in space that they can simultaneously bind and phosphorylate two phosphoacceptor residues of the same substrate.


Tissue-specific p53 expression in the nervous system.
P53 is a transcription factor that has been found to be expressed in association with cell proliferation and apoptosis. Previously, bacterial chloramphenicol acetyl transferase (CAT) enzymatic expression was predominantly found in the testes of p53 promoter driven-CAT transgenic mice. In the current study, we extended this study to survey p53 expression across both the central and peripheral nervous systems of the same strain of transgenic mice as well as their parental strain. High levels of p53 promoter driven-CAT activity was observed in the cerebellum, hippocampus, hypothalamus, pons, thalamus and upper cerebral spine. Furthermore, we consistently found unexpectedly high levels of p53 promoter-driven CAT expression in the eyes. These observations were reinforced by p53 protein analysis using a p53 pan ELISA assay. Immunohistochemical studies confirmed and further defined p53 expression in several regions of the nervous system. Significantly, p53 promoter-driven CAT expression was visualized in the Ammon horn of the hippocampus, in the Purkinje cells of the cerebellum and in the cornea as well as in the retina of the eye. Furthermore, strong p53 protein expression was found in the cornea of the parental mouse strain. p53 ELISA demonstrated a profile of p53 protein concentration, which correlate well with the high p53 promoter-driven CAT activities observed in the cerebellum, hindbrain, hypothalamus, thalamus, hippocampus, whole eyes as well as with the low CAT activities observed in the cortex and spinal cord. In both of these assays considerable p53 promoter activity and p53 protein levels were found in post-mitotic non-dividing cells.


High frequency top-down junction-less silicon nanowire resonators.
We report here the first realization of top-down silicon nanowires (SiNW) transduced by both junction-less field-effect transistor (FET) and the piezoresistive (PZR) effect. The suspended SiNWs are among the smallest top-down SiNWs reported to date, featuring widths down to ~20 nm. This has been achieved thanks to a 200 mm-wafer-scale, VLSI process fully amenable to monolithic CMOS co-integration. Thanks to the very small dimensions, the conductance of the silicon nanowire can be controlled by a nearby electrostatic gate. Both the junction-less FET and the previously demonstrated PZR transduction have been performed with the same SiNW. These self-transducing schemes have shown similar signal-to-background ratios, and the PZR transduction has exhibited a relatively higher output signal. Allan deviation (σA) of the same SiNW has been measured with both schemes, and we obtain σ(A) ~ 20 ppm for the FET detection and σ(A) ~ 3 ppm for the PZR detection at room temperature and low pressure. Orders of magnitude improvements are expected from tighter electrostatic control via changes in geometry and doping level, as well as from CMOS integration. The compact, simple topology of these elementary SiNW resonators opens up new paths towards ultra-dense arrays for gas and mass sensing, time keeping or logic switching systems on the SiNW-CMOS platform.


Covid-19 Social Distancing Interventions by Statutory Mandate and Their Observational Correlation to Mortality in the United States and Europe.
Evaluate the correlation between statutory social distancing interventions and Covid-19 mortality independently in both the United States and Europe. The study is presented as a potential methodology to evaluate the effectiveness of statutory social distancing policy. Twenty-seven states in the United States and, separately, 12 European countries were selected which had clearly defined and dated establishment of statewide or national mandates for social distancing measures from the Institute for Health Metrics and Evaluation (IHME) data. Mandated social distancing measures considered in this study include: School closures, Prohibition on mass gatherings, business closures, stay at home orders, severe travel restrictions, and closure of non-essential businesses. The state/country Covid-19 peak mortality rate (PMR) was defined as the initial averaged normalized maximum during which social distancing mandates were in effect. Mandate-days were defined as the total days legislative mandates were in place to the PMR. The normalized peak mortality rate in the US and in Europe did not demonstrate a statistically significant correlation to the total mandate days (R-squared=0.053, p=0.246, R-squared=2.4E-06, p=0.996). A significant correlation was found between normalized mortality rate and state/country population density (R-squared=0.524, p=0.00002,R-squared=0.397, p=0.0281). The analysis appears to suggest no mandate effective reduction in Covid-19 mortality rate to its defined initial peak when interpreting their mean-effect. A strong correlation to population density suggests human interaction frequency does affect the peak mortality rate.


Bog Microtopography and the Climatic Sensitivity of Testate Amoeba Communities: Implications for Transfer Function-Based Paleo-Water Table Reconstructions.
Although the use of sub-fossil testate amoebae as a proxy for raised bog hydrology in Holocene paleoecological studies is well-established, some detailed aspects of species-environment relationships remain under-researched. One such issue is the effect of bog surface microtopography on the climatic sensitivity of testate amoeba communities. Although it has been suggested that some microforms-especially hummocks-may be less sensitive to climatic forcing than others, this has rarely been objectively tested. To investigate this, subfossil testate amoebae assemblages have been examined in a series of shallow cores collected along a hummock-lawn-hollow transect from a bog in central Ireland and the resulting reconstructed water table records, dated using 210Pb, have been compared with instrumental weather data. Testate amoebae communities in the hollow microform were found to be significantly less diverse than those in the hummock and lawn, and both the hummock and lawn showed statistically significant correlations with instrumental temperature and precipitation data. Therefore, whilst the suggestion that paleoecological investigations should target intermediate bog microforms remains sound, the notion that hummock-based testate amoebae hydrological data are climatically-insensitive is challenged.


Non-alcoholic Fatty Liver Disease and Alcohol-Related Liver Disease: Two Intertwined Entities.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with a prevalence of 25-30%. Since its first description in 1980, NAFLD has been conceived as a different entity from alcohol-related fatty liver disease (ALD), despite that, both diseases have an overlap in the pathophysiology, share genetic-epigenetic factors, and frequently coexist. Both entities are characterized by a broad spectrum of histological features ranging from isolated steatosis to steatohepatitis and cirrhosis. Distinction between NAFLD and ALD is based on the amount of consumed alcohol, which has been arbitrarily established. In this context, a proposal of positive criteria for NAFLD diagnosis not considering exclusion of alcohol consumption as a prerequisite criterion for diagnosis had emerged, recognizing the possibility of a dual etiology of fatty liver in some individuals. The impact of moderate alcohol use on the severity of NAFLD is ill-defined. Some studies suggest protective effects in moderate doses, but current evidence shows that there is no safe threshold for alcohol consumption for NAFLD. In fact, given the synergistic effect between alcohol consumption, obesity, and metabolic dysfunction, it is likely that alcohol use serves as a significant risk factor for the progression of liver disease in NAFLD and metabolic syndrome. This also affects the incidence of hepatocellular carcinoma. In this review, we summarize the overlapping pathophysiology of NAFLD and ALD, the current data on alcohol consumption in patients with NAFLD, and the effects of metabolic dysfunction and overweight in ALD.


Crosswalk of participation self-report measures for aphasia to the ICF: what content is being measured?
Community participation is of importance to people with aphasia, who are at risk of becoming socially isolated. This study investigates the content of measures of community and social participation for this population by crosswalking items to the ICF. This will evaluate: (1) to what extent the included assessments assessed participation only, (2) what content appeared most frequently and (3) which response formats were utilised. Instruments were identified from four systematic reviews and a literature search. 111 instruments that were self-reported, developed for adults and published in English were identified. Items were linked to ICF domains, and third-level categories of the Activities and Participation chapter. Ninety instruments (2426 items) were included. Of these, 29 instruments contained over 50% participation items. The most frequently included participation categories in this subset were education, paid employment, recreation, socialising, being a carer, relating with friends, family and spouses, volunteer work, managing finances, community life, civic duties, human rights and religion/spirituality. Self-care, mobility and domestic life concepts were also frequently reported. Commonly used response formats were restriction, frequency and satisfaction. Few instruments solely assessed participation according to our operationalisation. This study provides a list of possible measures for use in assessing participation. Implications for Rehabilitation Participation restriction, as defined by the International Classification of Functioning, Disability and Health, is a key concern for people with aphasia. By conducting the crosswalk, we have identified that self-report measures of participation vary widely in content and response metrics, and often include activity, body function, environmental and quality of life items. This review may assist Rehabilitation researchers and clinicians in choosing a measure of participation restriction for people with aphasia and other populations by listing instruments with over 50% participation content. These results also indicate that the construct of participation needs to be adequately and uniformly defined so that the ICF to be used effectively as a framework for health status measurement.


Heat-shock protein 27 is phosphorylated in gemcitabine-resistant pancreatic cancer cells.
Gemcitabine (2'-deoxy-2'-difluorodeoxycytidine: Gemzar) (GEM) appears to be the only effective anticancer drug for pancreatic cancer, but it has little impact on outcome due to a high level of inherent and acquired tumor resistance. Our previous proteomic study demonstrated that the expression of three spots of heat-shock protein 27 (HSP27) was increased in GEM-resistant pancreatic cancer cells and could play a role in determining the sensitivity of pancreatic cancer to GEM. In the present study, using one-dimensional and two-dimensional Western blotting, we elucidated that these three spots of HSP27 were phosphorylated in GEM-resistant pancreatic cancer cell line, KLM1-R. Phosphorylated HSP27 may play an important role in the resistance to GEM, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with GEM.


Seroprevalence of SARS-CoV-2 antibodies and retrospective mortality in two African settings: Lubumbashi, Democratic Republic of the Congo and Abidjan, Côte d'Ivoire.
Although seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan. The studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan). In Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey. Although circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.


[Heterochromatic regions in corn A- and B- chromosomes].
A collection of maize forms from the Vavilov All-Russia Institute of Plant Breeding (VIR) was studied. We compared variation in the following traits: the number and size of heterochromatic knob regions (HKRs) of chromosomes of mother pollen cells at pachytene depending on the presence (B+) or absence (B0) of B-chromosomes; size of B-chromosomes (general, of heterochromatic part); and the frequency of B+ plants in groups of forms contrasting in the HKR number (10-15, 4-10, 2-7, 1-4). It was shown that B chromosomes had statistically significantly different effects on HKR polymorphism, relative heterochromatin "content" in the cell of multiknob and knobless forms, selection of plants for early ear flowering in these forms. The combination of maximum (and minimum) sizes of heterochromatic regions of A- and B-chromosomes was established; the genomic level of control of the trait is suggested. The role of the relationship of polymorphism at heterochromatic regions of A- and B-chromosomes between them and with the systems of maize reproduction is considered as a mechanism of maintenance of optimum plant heterozygosity via adaptive ontogenetic redistribution of heterochromatin among loci, chromosomes, and gametes.


Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.
Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.


IgE antibody responses in cerebrospinal fluids relate to the brain pathologic injury of hosts with Angiostrongylus cantonensis infection.
The immunoglobulin E (IgE) response to Angiostrongylus cantonensis infection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice. BALB/c (high susceptibility), CBA (medium), and C57BL/6 and C57BL/10 (resistance) strain mice were used in this study. The levels of IgM, IgG, and IgE in the serum and cerebrospinal fluid (CSF) from infected mice were compared. A. cantonensis-reactive antigens from BALB/c and C57BL/6 mice CSF were also analyzed. Antibodies against fifth-stage larvae (L5) antigens increased in mice CSF, particularly IgE, relate to worm rejection and the susceptibility of different mouse strains. The increased IgE level in BALB/c mice CSF is lower than that from others, suggesting IgE response in brain is more important than that in serum. Anti-L5 and anti-excretory/secretory (ES) antigen IgE and IgG responses in CSF were analyzed. In addition, the antibody-dependent eosinophil-mediated cytotoxicity induced by anti-excretory/secretory (ES) antigen antibodies may be the reason of severe brain inflammation in infected BALB/c mice. IgE and IgG antibodies against a 105 kDa protein of L5 antigen was detected at week 3 post-infection in C57BL/6 mice and week 5 post-infection in BALB/c mice. We suggest that 105 kDa protein is related with the antibody response of A. cantonensis-infected mice. We found that IgE antibodies in mice CSF against L5 antigens related to worm rejection in mice brains. This study may help to identify specific angiostrongyliasis markers that can be applied for clinical diagnosis and treatment in future.


Oil-in-Water Emulsion MF59 Increases Germinal Center B Cell Differentiation and Persistence in Response to Vaccination.
Induction of persistent protective immune responses is a key attribute of a successful vaccine formulation. MF59 adjuvant, an oil-in-water emulsion used in human vaccines, is known to induce persistent high-affinity functional Ab titers and memory B cells, but how it really shapes the Ag-specific B cell compartment is poorly documented. In this study, we characterized the Ab- and Ag-specific B cell compartment in wild-type mice immunized with HlaH35L, a Staphylococcus aureus Ag known to induce measurable functional Ab responses, formulated with MF59 or aluminum salts, focusing on germinal centers (GC) in secondary lymphoid organs. Taking advantage of single-cell flow cytometry analyses, HlaH35L-specific B cells were characterized for the expression of CD38 and GL-7, markers of memory and GC, respectively, and for CD80 and CD73 activation markers. We demonstrated that immunization with MF59-, but not aluminum salt-adjuvanted HlaH35L, induced expanded Ag-specific CD73(+)CD80(-) GC B cells in proximal- and distal-draining lymph nodes, and promoted the persistence of GC B cells, detected up to 4 mo after immunization. In addition to increasing GC B cells, MF59-adjuvanted HlaH35L also increased the frequency of T follicular helper cells. This work extends previous knowledge regarding adaptive immune responses to MF59-adjuvanted vaccines, and, to our knowledge, for the first time an adjuvant used in human licensed products is shown to promote strong and persistent Ag-specific GC responses that might benefit the rational design of new vaccination strategies.


[The use of cefotaxime on patients admitted to the internal medicine service of a general hospital. An analysis from the viewpoint of health economics].
Cefotaxime is a widely employed antibiotic in hospital practice, leading to an important economical cost. We analyse the adequacy of the indications of cefotaxime in our Internal Medicine Unit along a two month period. The records of the 54 patients treated with cefotaxime along a two month period were retrospectively reviewed to establish the adequacy of the prescriptions by checking them with a list of indications based on widely used bibliographical sources. Cefotaxime prescription was considered inadequate because of its inefficiency in 15 out of the 54 patients studied (28%). They were all patients admitted because of bronchitic relapses of chronic obstructive lung disease ("COLD") without radiological evidence of pneumonic consolidation. We calculate that using a more efficient antibiotic alternative could lead to a decrease of a 3.6 to 7.53% in the total pharmaceutical expenses of our unit along the study period. We conclude that the unnecessary routine use of cefotaxime may lead to an avoidable important increase in sanitary costs.


Accuracy in Near-Perfect Virus Phylogenies.
Phylogenetic trees from real-world data often include short edges with very few substitutions per site, which can lead to partially resolved trees and poor accuracy. Theory indicates that the number of sites needed to accurately reconstruct a fully resolved tree grows at a rate proportional to the inverse square of the length of the shortest edge. However, when inferred trees are partially resolved due to short edges, "accuracy" should be defined as the rate of discovering false splits (clades on a rooted tree) relative to the actual number found. Thus, accuracy can be high even if short edges are common. Specifically, in a "near-perfect" parameter space in which trees are large, the tree length $\xi$ (the sum of all edge lengths) is small, and rate variation is minimal, the expected false positive rate is less than $\xi/3$; the exact value depends on tree shape and sequence length. This expected false positive rate is far below the false negative rate for small $\xi$ and often well below 5% even when some assumptions are relaxed. We show this result analytically for maximum parsimony and explore its extension to maximum likelihood using theory and simulations. For hypothesis testing, we show that measures of split "support" that rely on bootstrap resampling consistently imply weaker support than that implied by the false positive rates in near-perfect trees. The near-perfect parameter space closely fits several empirical studies of human virus diversification during outbreaks and epidemics, including Ebolavirus, Zika virus, and SARS-CoV-2, reflecting low substitution rates relative to high transmission/sampling rates in these viruses.[Ebolavirus; epidemic; HIV; homoplasy; mumps virus; perfect phylogeny; SARS-CoV-2; virus; West Nile virus; Yule-Harding model; Zika virus.].


[Standardized sonographic investigation of the lumbar spine in 247 newborns].
Open dysraphism is generally known before birth due to prenatal screening but occult spinal malformation often remains unrecognized. Nevertheless, newborns with occult dysraphism could be easily diagnosed by ultrasound, which might be performed additionally to the neonatal screening of the hips. Early surgical treatment or close neuropediatric follow-ups could be administered as a consequence. As part of a prospective study-design, we screened the spinal cord of 247 newborns by ultrasound. Parents were interviewed about a positive family history, a folate intake during pregnancy, amniocentesis or chorionbiopsy. Clinically, cutaneous stigmata usually associated with occult spinal dysraphism were evaluated. An orthopedic and pediatric examination followed. The sonographic investigation was done in prone position using a newly designed positioning device. The sonographic examination was performed within 5 minutes and longitudinal and transversal pictures were taken for documentation. In all of the 247 examined newborns we were able to visualize the cartilageous structures of the spinal cord and the dural sack detailly. Dependent on the position of the newborn, variations of the width of the dural sack could be noted. Thus a newly designed positioning device helped to standardize the examination situation. We did not find any pathological changes of the spinal cord. Nevertheless ultrasonography provides a useful diagnostic tool in investigating the newborn where occult spinal dysraphism is expected.


A perspective on point of care systems.
Point of care technology is finally being accepted in health care organizations. Portable wireless computers and database interoperability are facilitating this acceptance. Using point of care devices, caregivers can access and input patient data whenever, wherever, and however required. This technology will improve patient data access, improve quality, and reduce costs of health care.


The immune system in cancer metastasis: friend or foe?
Metastatic disease is the leading cause of death among cancer patients and involves a complex and inefficient process. Every step of the metastatic process can be rate limiting and is influenced by non-malignant host cells interacting with the tumor cell. Over a century ago, experiments first indicated a link between the immune system and metastasis. This phenomenon, called concomitant immunity, indicates that the primary tumor induces an immune response, which may not be sufficient to destroy the primary tumor, but prevents the growth of a secondary tumor or metastases. Since that time, many different immune cells have been shown to play a role in both inhibiting and promoting metastatic disease. Here we review classic and new observations, describing the links between the immune system and metastasis that inform the development of cancer therapies.


Epidermal growth factor induces acute matrix contraction and subsequent calpain-modulated relaxation.
During wound healing, dermal fibroblasts switch from a migratory, repopulating phenotype to a contractile, matrix-reassembling phenotype. The mechanisms controlling this switch are unknown. A possible explanation is suggested by the finding that chemokines that appear late in wound repair prevent growth factor-induced cell-substratum de-adhesion by blocking calpain activation. In this study, we tested the specific hypothesis that fibroblast contraction of the matrix is promoted by a pro-repair growth factor, epidermal growth factor, and is modulated by calpain-mediated release of adhesions. We employed an isometric force transduction system designed to measure the contraction of a collagen matrix under tension by a population of NR6 fibroblasts transfected with the human epidermal growth factor receptor. By maintaining a fixed level of strain, we could monitor both the initial contraction and subsequent relaxation of the matrix. Epidermal growth factor stimulated a transient, dose-dependent increase in matrix contraction that peaked within 60 minutes and then decayed over the ensuing 3 to 6 hours. Calpain inhibitor I (ALLN) prevented epidermal growth factor-stimulated cell de-adhesion and resulted in a significantly slower decay of matrix contraction, with only a slight decrease of the peak magnitude of contraction. The mitogen-activated protein kinase kinase-1-selective inhibitor PD 98059 that blocks signaling through the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, required for epidermal growth factor receptor-mediated activation of calpain and de-adhesion, does not significantly affect the magnitude of matrix contraction within minutes of epidermal growth factor addition, but slows the decay similarly to calpain inhibition. Epidermal growth factor receptor signaling thus stimulates the complementary mechanisms of intracellular contractile force generation and calpain-mediated de-adhesion, which are known to coordinately facilitate cell migration. These findings suggest that calpain can act as a functional switch for transmission of intracellular contractile force to the surrounding matrix, with calpain-mediated de-adhesion reducing this transmission and corresponding matrix contraction. Countervailing processes that down-regulate calpain activation can, accordingly, direct the transition of cell function from locomotion to matrix contraction.


Estimation of tumor cell kill from Gompertz growth curves.
The Gompertz function has been found to mathematically describe several types of biologic growth, including the growth of transplantable animal tumors. If it is assumed that treatment (chemotherapy, surgery, x-irradiation) of tumors causes cell death in a relatively short interval and that the surviving cells begin to repopulate immediately, producing tumor growth according to the Gompertz function before treatment, then the displacement in time between the two growth curves may be quantitatively related to tumor cell kill. This theory is developed and compared to bioassay values. It is also shown that tumor cell kill may be determined graphically without the necessity of computer-generated estimates of the Gompertz parameters.


The remembered pursuit task: evidence for segregation of timing and velocity storage in predictive oculomotor control.
Regular, repeated presentation of identical constant-velocity target motion stimuli (ramps) appears to allow build up of an internal store, release of which can be used to generate anticipatory smooth pursuit prior to subsequent target onset. Here, we examine whether release of the anticipatory response can be controlled by timing cues unrelated to the motion stimulus itself. In experiment 1, the target moved in alternate directions and was exposed for 480 ms as it passed through centre; otherwise subjects were in darkness. Inter-stimulus interval (ISI) was either regular (3.6 s) or randomized (2.7-4.3 s). Presentations were given with or without audio cues that occurred at a constant cue time (CT) prior to target appearance. Even when ISI was randomized, cues could be used to generate anticipatory smooth pursuit. Eye velocity (V100) measured 100 ms after target onset (just prior to visual feedback influence) was greater with cues than without and decreased significantly as CT increased from 240-960 ms. In experiment 2, we assessed the effects of fixation between presentations and eccentricity of target starting position, using unidirectional ramps. The target was visible for 400 ms and started on, ended on or straddled the midline. Subjects held fixation on the midline until an audio cue signalled that preparation for ensuing target appearance could begin. There was no difference in V100 between starting positions or between presence/absence of fixation. In experiment 3, we compared the effects of using audio, visual or tactile cues. All types of cue evoked anticipatory smooth pursuit, but the response to the visual cue was significantly delayed compared with the others. However, V100 was not significantly different between cues. In all experiments, V100 was scaled in proportion to target velocity over the range 12.5-50 degrees /s, showing that this was a truly predictive response. The results provide evidence that timing and velocity storage can be independently controlled through different sensory channels and suggest that the two functions are probably carried out by separate neural mechanisms.


[Lipid storage diseases (lipidoses): genetic, biochemical and clinico-chemical aspects].
Lipidoses are genetic diseases due to disease-specific defects in the enzymatic catabolism of lipids, with accumulation of the respective lipid substrate in the nervous system and/or peripheral tissues. The clinical chemical diagnosis of lipidoses can be accomplished by demonstration of the enzyme defect and/or substrate accumulation in body fluids (urine, blood serum), leukocytes, cultured fibroblasts, amniotic fluid cells, or amniotic fluid, respectively. These assays are important with regard to: 1. the specific detection or exclusion of diseases, which are difficult to diagnose by their clinical presentation, 2. prenatal diagnoses, 3. detection of (clinically inconspicuous) heterozygotes (essential for individual genetic counselling), and 4. the biochemical control of dietary treatment in Refsum's disease.


Headache and neuropsychic disorders in the puerperium: a case report with suspected deficiency of urea cycle enzymes.
An enzymatic abnormality of the urea cycle is a metabolic disorder occasionally seen in adults, but particularly in the puerperium. The main risk is acute hyperammoniemic encephalopathy, leading to psychosis, coma and even death if not diagnosed promptly and treated appropriately. Headache is frequent in the puerperium normally manifesting between 3 and 6 days after delivery. We describe here a 39-year-old woman, who 3 days after delivery presented diffuse tension-type headache and depression, followed by behavioral disorders, psychomotor agitation, epileptic seizures, and finally coma 2 days later. Pregnancy and normal delivery: routine blood chemistry findings, CT scan, MR imaging, angio-MR of the brain, and lumbar puncture were normal. EEG when seizures started, it showed diffuse slowing, as in the case of metabolic encephalopathy. This led us to assay blood ammonia, which was high at >400 mmol. Liver function and abdominal US were normal; hence, we suspected a urea cycle enzymatic abnormality, and requested for genetic tests. These confirmed a congenital primary metabolic deficiency of arginine succinate synthetase, with high citrullinemia (type II, adult form). Dialysis was started promptly, with initially iv arginine, then orally, plus medical therapy for the hyperammoniemia and a low protein diet; plasma ammonia dropped swiftly to normal, and her state of consciousness gradually improved until all the clinical symptoms had resolved. Ammonia assay should always be considered in the first few days of the puerperium in women with headache and behavioral disorders, to exclude an inborn deficiency of the urea cycle, which may have gone unnoticed until then.


Outcomes of Omniflow® II prosthesis used for revascularization in the femoral tract both in infected and non-infected setting.
Evidence regarding the outcomes of Omniflow® II prosthesis in peripheral arterial revascularization at different anatomical sites and for different indications is scarce. Therefore, the aim of this study was to evaluate the outcomes of the Omniflow® II used at various positions within the femoral tract both in infected and non-infected setting. Patients who underwent reconstructive lower leg vascular surgery with implantation of an Omniflow® II from 2014 until 2021 at five medical centers were retrospectively included (N.=142). Patients were subdivided into the following categories: femoro-femoral crossover (N.=19), femoral interposition (N.=18), femoro-popliteal (above-the-knee [N.=25; AK] or below-the-knee [N.=47; BK]), and femoro-crural bypass grafts (N.=33). Primary outcome was primary patency and secondary outcomes included primary assisted patency, secondary patency, major amputation, vascular graft infection, and mortality. Outcomes were compared according to different subgroups and the surgical setting (infected versus non-infected). The median follow-up was 35.0 (17.5-54.3) months. Three years primary patency of 58% was observed for femoro-femoral crossover bypass, 75% for femoral interposition graft, 44% for femoro-popliteal above-the-knee bypass, 42% for femoro-popliteal below-the-knee bypass, and 27% in the femoro-crural position (P=0.006). Freedom from major amputation at three years were 84% for femoro-femoral crossover bypass, 88% for femoral interposition bypass, 90% for femoro-popliteal AK bypass, 83% for femoro-popliteal BK bypass, and 50% for femoro-crural bypass (P<0.001). This study demonstrates the safety and feasibility of the use of Omniflow® II for femoro-femoral crossover-, femoral interposition-, and femoro-popliteal (AK and BK) bypass. Omniflow® II seems to be less suitable for femoro-crural bypass with a significantly lower patency compared to other positions.


Induction of Glutaredoxin Expression in Response to Desiccation Stress in the Foliar Nematode Aphelenchoides fragariae.
Desiccation tolerance plays an important role in the overwinter survival of the foliar nematode Aphelenchoides fragariae. Survival rates of A. fragariae were compared with those of the anhydrobiotic soil-dwelling nematode Aphelenchus avenae after desiccation (90% RH), cold (4°C) and osmotic (500 mM sucrose) stress treatments. A. fragariae formed aggregates during desiccation and showed higher survival rates than A. avenae under desiccation and osmotic stress. Analysis of transcripts with Illumina RNA-seq indicated that glutaredoxin and other antioxidant-related genes were up-regulated under desiccation stress. Quantitative RT-PCR demonstrated 2.8 fold and 1.3 fold up-regulation of a glutaredoxin gene under desiccated and osmotic stress, respectively, suggesting the participation of antioxidant mechanisms in desiccation tolerance of A. fragariae.


Contribution of clinical, metabolic, and genetic factors on hypertension in obese children and adolescents.
The role of ACE gene insertion (I) or deletion (D) polymorphism on blood pressure phenotype is not clear in children. The aim of this work is to examine the association between hypertension and ACE I/D polymorphism, as well as the contribution of clinical and metabolic parameters on blood pressure. The study participants were 199 obese children. Forty-four of them were hypertensive. The hypertensive subjects were older than the normotensive and most of them were pubertal. The prevalence of hypertension in obese subjects with II, ID, and DD genotype was similar. There was no difference between the hypertensive and the normotensive group according to ACE I/D genotype, BMISDS, sex, blood glucose level and total cholesterol levels. In obese children, high IR-HOMA values, puberty, presence of family history for hypertension, hypertriglyceridemia, and low HDL-cholesterol, high triglyceride/HDL-cholesterol ratio were found as increased risk factors of hypertension. In obese children and adolescents, blood pressure did not differ by ACE I/D genotype. The presence of family history, puberty, insulin resistance and hypertriglyceridemia constitute important risk factors for developing hypertension.


ECOLOGY: When Do Many Species Matter?
Ecologists agree that experimental plots of grasses are sometimes more productive when they harbor more species. But some disagree passionately about whether it matters--in other words, whether this proves that biodiversity is critical to ecosystem health (see main text).


Effects of copper sulfate on seedlings of Prosopis pubescens (screwbean mesquite).
Phytoextraction is an established method of removal of heavy metals from contaminated soils worldwide. Phytoextraction is most efficient if local plants are used in the contaminated site. We propose that Prosopis pubescens (Screw bean mesquite) would be a successful phytoextractor of copper in our local soils. In order to determine the feasibility of using Screw bean mesquite, we utilized inductively-coupled plasma-optical emission spectroscopy (ICP-OES) and elemental analysis to observe the uptake of copper and the effects on macro and micro nutrients within laboratory-grown seedlings. We have previously shown that P. pubescens is a hyperaccumulator of copper in soil-grown seedlings. Light and transmission electron microscopy demonstrated death of root cells and ultrastructural changes due to the presence of copper from 50 mg/L - 600 mg/L. Ultrastructural changes included plasmolysis, starch accumulation, increased vacuolation and swollen chloroplasts with disarranged thylakoid membranes in cotyledons. Inductively coupled plasma-optical emission spectroscopy analyses of macro- and micro-nutrients revealed that the presence of copper sulfate in the growth medium of Petri-dish grown Prosopis pubescens seedlings resulted in dramatic decreases of magnesium, potassium and phosphorus. At 500-600 mg/L of copper sulfate, a substantial increase of sulfur was present in roots.


Early and late results following repair of dissections of the descending thoracic aorta.
Management of dissections of the descending thoracic aorta remains controversial, especially with regard to timing and method of repair. To clarify these and other issues we have reviewed our total experience with repair of descending aortic dissections between 1962 and 1983. The 44 men and 20 women had a mean (+/- SEM) age of 59 +/- 2 years (range, 19 to 83 years), and in all patients the dissection originated in and was limited to the aorta distal to the left carotid artery (Stanford type B, DeBakey types IIIa and IIIb). Twenty-nine patients underwent operation within 2 weeks of the onset of symptoms (acute), and the remainder had later repair (chronic). During repair, circulation distal to the aortic cross-clamp was supported with cardiopulmonary bypass or shunt in two thirds of patients. Overall, 18 deaths occurred less than or equal to 30 days postoperatively (operative risk 28%), and risk was higher in acute (45%) than in chronic (14%) dissections. Operative risk was not significantly related to protection of the distal circulation. The most serious postoperative complication was spinal cord ischemia manifested by paraplegia in five patients (8%) and transient or permanent paraparesis in six patients (9%). Risk of spinal cord ischemia was significantly lower in patients who had protection of the distal circulation during operative repair (8% vs. 44%, p = 0.003). Late survival, including hospital deaths, was 49% +/- 7% at 5 years after operation; 22 of the 46 patients who survived repair were found to have aneurysms involving the thoracic and/or abdominal segments of the aorta. Our results indicate that repair of chronic dissection of the thoracic aorta has a lower operative risk than repair of acute dissections, and initial medical management of acute dissection may be indicated if no early complications occur. Risk of spinal cord ischemia is significantly reduced by cardiopulmonary bypass or shunt and is preferred over aortic cross-clamping alone. Finally, these patients require careful long-term follow-up because of the high incidence of residual or recurrent aortic aneurysms.


The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions.
Histone H3K4 methylation is an epigenetic mark associated with actively transcribed genes. This modification is catalyzed by the mixed lineage leukaemia (MLL) family of histone methyltransferases including MLL1, MLL2, MLL3, MLL4, SET1A and SET1B. The catalytic activity of this family is dependent on interactions with additional conserved proteins, but the structural basis for subunit assembly and the mechanism of regulation is not well understood. We used a hybrid methods approach to study the assembly and biochemical function of the minimally active MLL1 complex (MLL1, WDR5 and RbBP5). A combination of small angle X-ray scattering, cross-linking mass spectrometry, nuclear magnetic resonance spectroscopy and computational modeling were used to generate a dynamic ensemble model in which subunits are assembled via multiple weak interaction sites. We identified a new interaction site between the MLL1 SET domain and the WD40 β-propeller domain of RbBP5, and demonstrate the susceptibility of the catalytic function of the complex to disruption of individual interaction sites.