A genome-wide association study coupled with machine learning approaches to identify influential demographic and genomic factors underlying Parkinson's disease.
Background: Despite the recent success of genome-wide association studies (GWAS) in identifying 90 independent risk loci for Parkinson's disease (PD), the genomic underpinning of PD is still largely unknown. At the same time, accurate and reliable predictive models utilizing genomic or demographic features are desired in the clinic for predicting the risk of Parkinson's disease. Methods: To identify influential demographic and genomic factors associated with PD and to further develop predictive models, we utilized demographic data, incorporating 200 variables across 33,473 participants, along with genomic data involving 447,089 SNPs across 8,840 samples, both derived from the Fox Insight online study. We first applied correlation and GWAS analyses to find the top demographic and genomic factors associated with PD, respectively. We further developed and compared a variety of machine learning (ML) models for predicting PD. From the developed ML models, we performed feature importance analysis to reveal the predictability of each demographic or the genomic input feature for PD. Finally, we performed gene set enrichment analysis on our GWAS results to identify PD-associated pathways. Results: In our study, we identified both novel and well-known demographic and genetic factors (along with the enriched pathways) related to PD. In addition, we developed predictive models that performed robustly, with AUC = 0.89 for demographic data and AUC = 0.74 for genomic data. Our GWAS analysis identified several novel and significant variants and gene loci, including three intron variants in LMNA (p-values smaller than 4.0e-21) and one missense variant in SEMA4A (p-value = 1.11e-26). Our feature importance analysis from the PD-predictive ML models highlighted some significant and novel variants from our GWAS analysis (e.g., the intron variant rs1749409 in the RIT1 gene) and helped identify potentially causative variants that were missed by GWAS, such as rs11264300, a missense variant in the gene DCST1, and rs11584630, an intron variant in the gene KCNN3. Conclusion: In summary, by combining a GWAS with advanced machine learning models, we identified both known and novel demographic and genomic factors as well as built well-performing ML models for predicting Parkinson's disease.


Nine steps to proteomic wisdom: A practical guide to using protein-protein interaction networks and molecular pathways as a framework for interpreting disease proteomic profiles.
A major aim of proteomic profiling of disease is to uncover the mechanistic basis of a given pathology. High-throughput experimental techniques continue to advance rapidly, but are still plagued by high rates of false negatives, false positives, and other spurious findings. By reducing a disease profile to a subset of differentially expressed proteins and determining functional over-representation, one can often make a reasonable first-pass assessment as to what might be happening in disease. Integrating mRNA expression patterns together with prior knowledge of protein-protein interaction networks and biological pathway information goes a step further, providing clues into the core processes that are aberrant in the disease state, and indicating which cellular functions are activated or repressed as a maladaptive pathophysiological response. This multi-step framework allows one to hypothesize as to possible cause and effect of pathology, and highlights potentially instructive pathways or sub-networks for subsequent experimental validation. Indeed, efficiently exploiting data regarding the myriad of physical and genetic interactions among expressed gene products, in parallel with the systematic sampling of genetic variation among diverse human populations, promises to revolutionize our current understanding of disease action at a deeper molecular level.


[The Relationship of Enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum Intestinal Colonization with Colorectal Cancer: A Case-Control Study Performed with Colon Biopsies].
In recent years, it has been shown that some bacteria may be associated with colorectal cancer (CRC). In this study, it was aimed to investigate the role of Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis (ETBF) in the etiology of CRC by comparing the amounts of these bacteria in colon biopsy tissues of patients with CRC and healthy individuals. The amounts of F.nucleatum and ETBF were determined by quantitative polymerase chain reaction (qPCR) in colon biopsy samples taken from 35 CRC and 35 healthy individuals, and the results were compared in the patient and control groups. The detection rate and amounts of F.nucleatum were found to be statistically significantly higher in tissues of female patients with CRC compared to male patients (p= 0.003, p= 0.013, respectively). There was no statistically significant difference between the tissues of female and male patients with CRC in terms of detection rate and amount of ETBF (p= 0.521, p= 0.515, respectively). It was found that in the 50-74 age group, the amount of ETBF was statistically significantly higher in women and men with CRC compared to the controls (p= 0.005, p= 0.047, respectively), while the amount of F.nucleatum was statistically significantly higher in female patients compared to controls. However, no difference was found between male patients and controls (p= 0.009, p= 0.083). It was determined that the detection rate and amount of F.nucleatum in the tissues of patients with CRC, regardless of age and gender, were not statistically different from the controls (p= 0.473, p= 0.995, respectively), however, the detection rate of ETBF and the amount of ETBF were found to be statistically significantly higher (p= 0.002, p= 0.004, respectively). It has been determined that ETBF can play a role in the etiology of CRC in both men and women, and F.nucleatum only in women, in the age range of 50-74 years, when routine screenings for CRC are performed.


A Versatile Ligand Platform for Palladium- and Nickel-Catalyzed Ethylene Copolymerization with Polar Monomers.
The ability to carry out transition-metal-catalyzed copolymerizations of olefins with polar monomers is a great challenge in the field of olefin polymerization. Palladium has been the dominant player in this field, while its low-cost nickel counterpart has only achieved very limited success. We report the synthesis and evaluation of a highly versatile platform based on diphosphazane monoxide ligands. Both palladium and nickel catalysts bearing these ligands mediate the copolymerization of ethylene with a number of fundamental polar monomers.


Amylin found in amyloid deposits in human type 2 diabetes mellitus may be a hormone that regulates glycogen metabolism in skeletal muscle.
Diabetes-associated peptide has recently been isolated and characterized from the amyloid of the islets of Langerhans in type 2 (non-insulin-dependent) diabetics, and immunoreactivity with antibodies to the peptide has been demonstrated in islet B cells of both normal and type 2 diabetic subjects. In view of the evidence presented in this paper that this 37-amino acid peptide may be a hormone present in normal individuals, we now propose the name "amylin" to replace "diabetes-associated peptide." Because increased amylin, deposited as amyloid within the islets of Langerhans, is characteristic of type 2 diabetes, the study below was performed to examine the possible effects of amylin on peripheral glucose metabolism. Whole amylin was synthesized by using solid-phase techniques, with formation of the disulfide linkage by oxidation in dilute aqueous solution and recovery of the peptide by lyophilization. The effects of amylin on glucose metabolism were studied in two preparations in vitro, isolated rat soleus muscle strips and isolated rat adipocytes. In skeletal muscle exposed to 120 nM amylin for 1 hr, there was a marked decrease in both basal and submaximally insulin-stimulated rates of glycogen synthesis, which resulted in significant reduction in the rates of insulin-stimulated glucose uptake. In muscles treated with amylin there was no response at the concentration of insulin required to stimulate glucose uptake half-maximally in untreated (control) muscles. In marked contrast, amylin had no effect on either basal or insulin-stimulated rates of glucose incorporation into either CO2 or triacylglycerol in isolated adipocytes. Therefore, amylin may be a factor in the etiology of the insulin resistance in type 2 diabetes mellitus, as both deposition of the peptide in islet amyloid and decreased rates of glucose uptake and glycogen synthesis in skeletal muscle are characteristic of this condition.


Bilateral stress-fracture of the calcaneal tubercle.
A case of bilateral stress fracture of the calcaneal tubercle (beak-fractures) in a 67-year-old woman is presented. The pathogenesis and treatment are discussed, followed by some general considerations on stress fractures.


Regulation of the immunostimulatory activity of rat pulmonary interstitial dendritic cells by cell-cell interactions and cytokines.
Pulmonary dendritic cells (DC) are potent antigen-presenting cells that are thought to play a critical role in the initiation of immune responses within the lung. Because the lung is both a site of entry into the body for microbial pathogens and the organ of gas exchange, pulmonary immune responses must be meticulously regulated to achieve a balance between host defense and respiration. The initial interaction of DC with T cells in the lung is an excellent point at which to control local immune responses. Studies of the regulation of DC accessory cell function have been greatly hampered by difficulties in obtaining pure populations of pulmonary DC that have not been subjected to prolonged incubations during which the DC may undergo functional alteration. We now describe a method for isolating pulmonary DC from the rat that yields 1 x 10(5) cells/rat with > 90% purity. These cells are potent accessory cells, inducing T cell proliferation in a mixed leukocyte reaction (MLR) at a stimulator-to-responder ratio of 1:1,000. This method, which involves flow cytometric separation of nonphagocytic cells that stain brightly for class II MHC (OX6) from a population of low-density pulmonary interstitial cells, avoids extended incubations at 37 degrees C and thus allows study of a relatively pure population of cells that have functional capacities resembling those of naive cells from the normal lung. With these cells, we demonstrate that the functional capacity of pulmonary DC as stimulator cells in an MLR is significantly increased by exposure to the cytokines interleukin-1 or granulocyte/macrophage colony-stimulating factor (GM-CSF) and by culture with interstitial, but not alveolar, macrophages. Furthermore, DC are heterogeneous with respect to the cell surface expression of receptor for GM-CSF, and this expression is subject to modulation in cell culture. From these studies, we conclude that the immunostimulatory capacity of pulmonary DC is a function of local interactions with cytokines and other parenchymal cells. This suggests that DC function may be an important regulatory point for the local control of pulmonary immune responses.


[Breast cancer following breast prosthesis and irradiation in childhood].
The authors report a case of breast cancer developing 7 years after insertion of a breast prosthesis. This patient was 45 years old at the time of this discovery and had received low dose radiation during childhood for a haemolymphangioma of the homolateral axillary region. The possible factors predisposing development of cancer are discussed: haemolymphangioma, low dose axillary irradiation during childhood, peri-prosthetic fibrous capsule. These various points are examined in the light of data from the literature. The conclusions recall the necessity for clinical and radiological follow-up of breast prostheses, preferably performed by a plastic surgeon.


Bioethics as a new human rights emphasis in European research policy.
Although issues of morals and ethics remain largely a national matter, the European Community (EC) and the Council of Europe have taken an increasing interest in identifying and harmonizing the often conflicting policies of the European countries on bioethical matters. This article examines the role these organizations are playing and identifies some of the initiatives that have been taken in specific areas.


Vascular Access in Percutaneous Coronary Intervention of Chronic Total Occlusions: A State-of-the-Art Review.
The outcomes of chronic total occlusion percutaneous coronary intervention have considerably improved during the last decade with continued emphasis on improving procedural safety. Vascular access site bleeding remains one of the most frequent complications. Several procedural strategies have been implemented to reduce the rate of vascular access site complications. This state-of-the-art review summarizes and describes the current evidence on optimal vascular access strategies for chronic total occlusion percutaneous coronary intervention.


Molecular biology of prion protein and its first homologous protein.
Conformational conversion of the normal cellular isoform of prion protein, PrP(C), a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into the abnormally folded, amyloidogenic prion protein, PrP(Sc), plays a pivotal role in the pathogenesis of prion diseases. It has been suggested that PrP(C) might be functionally disturbed by constitutive conversion to PrP(Sc) due to either the resulting depletion of PrP(C) or the dominant negative effects of PrP(Sc) on PrP(C) or both. Consistent with this, we and others showed that mice devoid of PrP(C) (PrP-/-) spontaneously developed abnormal phenotypes very similar to the neurological abnormalities of prion diseases, supporting the concept that functional loss of PrP(C) might at least be partly involved in the pathogenesis of the diseases. However, no neuronal cell death could be detected in PrP-/- mice, indicating that the functional loss of PrP(C) alone might not be enough to induce neuronal cell death, one of major pathological hallmarks of prion diseases. Interestingly, it was recently shown that the first identified PrP-like protein, termed PrPLP/Doppel (Dpl), is neurotoxic in the absence of PrP(C), causing Purkinje cell degeneration in the cerebellum of mice. Although it is not understood if PrP(Sc) could have a neurotoxic potential similar to PrPLP/Dpl, it is very interesting to speculate that accumulation of PrP(Sc) and the functional disturbance of PrP(C), both of which are caused by constitutive conversion, might be required for the neurodegeneration in prion diseases.


Adrenal medullary disease in multiple endocrine neoplasia, type 2: pheochromocytoma and its precursors.
Multiple endocrine neoplasia, type 2 (MEN-type 2), designates the syndrome of medullary thyroid carcinoma, pheochromocytoma, and occasional parathyroid hyperplasia. The thyroid carcinoma, which is usually bilateral and multicentric, is preceded by multifocal C-cell hyperplasia. The adrenal gland manifests pheochromocytoma, which is frequently bilateral and multicentric, and may be malignant. To test the hypothesis that diffuse adrenal medullary hyperplasia is a precursor of pheochromocytoma in this syndrome, we studied the adrenal glands of 19 patients who had MEN-type 2. The findings in the adrenal medulla in these 19 patients were: synchronous bilateral pheochromocytoma in 9 (metastatic in 3); asynchronous bilateral pheochromocytoma in 1 (metastatic); unilateral pheochromocytoma with contralateral diffuse and nodular hyperplasia in 2; unilateral pheochromocytoma with contralateral diffuse hyperplasia in 2; unilateral pheochromocytoma in 1; bilateral nodular hyperplasia in 1; bilateral diffuse hyperplasia in 1; and no abnormality in 2. This spectrum of adrenal medullary pathology suggests that diffuse and nodular medullary hyperplasia are precursors of pheochromocytoma in MEN-type 2.


Greater inadvertent muscle damage in direct anterior approach when compared with the direct superior approach for total hip arthroplasty.
We wished to quantify the extent of soft-tissue damage sustained during minimally invasive total hip arthroplasty through the direct anterior (DA) and direct superior (DS) approaches. In eight cadavers, the DA approach was performed on one side, and the DS approach on the other, a single brand of uncemented hip prosthesis was implanted by two surgeons, considered expert in their surgical approaches. Subsequent reflection of the gluteus maximus allowed the extent of muscle and tendon damage to be measured and the percentage damage to each anatomical structure to be calculated. The DA approach caused substantially greater damage to the gluteus minimus muscle and tendon when compared with the DS approach (t-test, p = 0.049 and 0.003, respectively). The tensor fascia lata and rectus femoris muscles were damaged only in the DA approach. There was no difference in the amount of damage to the gluteus medius muscle and tendon, piriformis tendon, obturator internus tendon, obturator externus tendon or quadratus femoris muscle between approaches. The posterior soft-tissue releases of the DA approach damaged the gluteus minimus muscle and tendon, piriformis tendon and obturator internus tendon. The DS approach caused less soft-tissue damage than the DA approach. However the clinical relevance is unknown. Further clinical outcome studies, radiographic evaluation of component position, gait analyses and serum biomarker levels are necessary to evaluate and corroborate the safety and efficacy of the DS approach. Cite this article: Bone Joint J 2016;98-B1036-42.


Activity of aqueous extract of the bark of Vitex doniana on uterine muscle response to drugs.
The activity of Vitex doniana on the uterine muscle response was investigated. The bark of Vitex doniana was extracted in boiled water at 100 degrees C, and the extracted solution filtered and centrifuged with refrigeration. The extract prepared from the dry powder extract was tested on uterine muscle strip preparations. The bark extract of Vitex doniana was analysed elementally and found to contain much more potassium and phosphate than calcium, magnesium, zinc and iron. The presence of potassium ions in excess may also be partly responsible for the effect of the crude extract on uterine muscle activity. In another study, Vitex doniana extract induced graded uterine muscle contractions and also potentiated the contractile effects of prostaglandins, ergometrine and oxytocin. However, the potentiating effect was not significant on the contractile responses to acetylcholine and potassium chloride. The investigation therefore suggests that the effect of the Vitex doniana bark extract may be not only voltage operated but may act via uterotonic receptors. Therefore, the use of Vitex doniana to control postpartum bleeding after child birth may be justified.


Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea-pig airways.
We examined the effect of ibudilast, an antiasthma drug, on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation of Evans blue dye. After intravenous pretreatment with atropine (1 mg/kg) and propranolol (1 mg/kg), bilateral vagal stimulation significantly increased nonadrenergic noncholinergic (NANC)-mediated leakage of dye in the trachea (Tr), the main bronchi (MB), and the central (cIPA) and peripheral (pIPA) intrapulmonary airways. Ibudilast (1.0 to 100 micrograms/kg given intravenously) did not affect basal leakage, but it significantly inhibited NANC-mediated plasma extravasation in a dose-dependent manner, with a maximal inhibition of 74.0% (Tr, p < 0.05), 89.1% (MB, p < 0.05), 91.4% (cIPA, p < 0.01), and 84.3% (pIPA, p < 0.05) at 100 micrograms/kg. Plasma extravasation induced by exogenous substance P (1 microgram/kg given intravenously) was not inhibited by ibudilast. Glibenclamide, an inhibitor of ATP-sensitive potassium channels, blocked the inhibitory effect of ibudilast. We conclude that ibudilast inhibits neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals via an ATP-sensitive potassium channel.


A Systematic Review and Meta-Analysis of the Data Behind Current Recommendations for Corticosteroids in Non-HIV-Related PCP: Knowing When You Are on Shaky Foundations.
Randomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic review and meta-analysis characterizing adjunctive corticosteroids for NH-PCP. We searched MEDLINE from 1966 through 2015. Data on clinical outcomes from NH-PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. Our search yielded 5044 abstracts, 277 articles were chosen for full review, and 6 articles described outcomes in moderate to severe NH-PCP. Studies were limited by variable definitions, treatment selection bias, concomitant infections and small sample size. Individual studies reported shorter intensive care unit stay and duration of mechanical ventilation of patients given adjunctive corticosteroids. There was no association between corticosteroids and survival in NH-PCP (odds ratio, 0.66; 95% confidence interval, 0.38-1.15; P = 0.14). The literature does not support an association between adjunctive corticosteroids and survival from NH-PCP but data are limited and findings should not be considered conclusive. Further research with improved methodology is needed to better understand the role of adjunctive corticosteroids for NH-PCP.


Synthesis, properties, and NMR studies of a C8-phenylguanine modified oligonucleotide that preferentially adopts the Z DNA conformation.
Carcinogenic aryl hydrazines produce C8-arylated purine adducts. The effect of these adducts on DNA conformation and their role in hydrazine carcinogenesis are unknown. Here, we describe a new synthetic route to produce these adducts that is also compatible with the synthesis of the corresponding phosphoramidites needed for oligonucleotide synthesis. Two oligonucleotides were prepared, an unmodified oligonucleotide, d((5)(')CGCGCGCGCG(3)(')), and a C8-phenylguanine modified oligonucleotide, d((5)(')CGCGCGCGCG(3)(')) (G = 8-phenylguanine). These oligonucleotides were compared using thermal denaturation, circular dichroism, NMR, and molecular modeling. The phenyl modification destabilizes the B DNA form and stabilizes the Z DNA form such that the B:Z ratio is near one under physiological conditions. In light of recent studies that show a role for Z DNA in gene expression and cell transformation, Z DNA stabilization by C8-arylguanine formation from aryl hydrazines may be relevant to their role in carcinogenesis.


Tendonitis of the branches of insertion of the superficial digital flexor tendon in horses.
To describe clinical findings, ultrasonographic features and outcome of injury to the branches of insertion of the superficial digital flexor (SDF) tendon in horses. Retrospective study of 14 cases. Fourteen Thoroughbred horses with tendonitis affecting the branches of insertion of the SDF tendon were examined for lameness, location and amount of swelling, and the presence of other musculoskeletal abnormalities. The flexor tendons were assessed by ultrasonographic examination, and recommendations were made for management of the cases. Outcome was assessed by re-examination of some horses, direct communication with the owner or trainer, and examination of race records. The lateral SDF branch was affected in 10 horses; the medial branch in three, and both branches in one horse. Two horses had concurrent injuries to the SDF tendon in the metacarpal region of the contralateral limb. Ultrasonographic findings included swelling of the affected SDF branch, peritendinous fluid accumulation, disruption of normal fibre alignment on sagittal scan, and variable loss of echogenicity. As healing occurred, there was return of normal echogenicity, but normal fibre alignment did not return completely and apparent adhesions formed between the affected SDF branch and adjacent structures. Seven of 10 horses which returned to their previous use were able to compete without further tendon injury. Recurrence of injury occurred in one case, and another two horses developed tendonitis in the metacarpal region. One horse was retired from racing but was able to compete at dressage without recurrence of injury. Two horses were retired for breeding without returning to training, and one horse was sold and lost to follow up but did not race. The prognosis is fair for return to previous use following injury to the branches of insertion of the SDF tendon in athletic horses.


Estimation of rates-across-sites distributions in phylogenetic substitution models.
Previous work has shown that it is often essential to account for the variation in rates at different sites in phylogenetic models in order to avoid phylogenetic artifacts such as long branch attraction. In most current models, the gamma distribution is used for the rates-across-sites distributions and is implemented as an equal-probability discrete gamma. In this article, we introduce discrete distribution estimates with large numbers of equally spaced rate categories allowing us to investigate the appropriateness of the gamma model. With large numbers of rate categories, these discrete estimates are flexible enough to approximate the shape of almost any distribution. Likelihood ratio statistical tests and a nonparametric bootstrap confidence-bound estimation procedure based on the discrete estimates are presented that can be used to test the fit of a parametric family. We applied the methodology to several different protein data sets, and found that although the gamma model often provides a good parametric model for this type of data, rate estimates from an equal-probability discrete gamma model with a small number of categories will tend to underestimate the largest rates. In cases when the gamma model assumption is in doubt, rate estimates coming from the discrete rate distribution estimate with a large number of rate categories provide a robust alternative to gamma estimates. An alternative implementation of the gamma distribution is proposed that, for equal numbers of rate categories, is computationally more efficient during optimization than the standard gamma implementation and can provide more accurate estimates of site rates.


First trimester isolated fetal nuchal lucency: significance and outcome.
In this study, we determined the outcome in cases of isolated nuchal lucency seen sonographically in the first trimester in fetuses without karyotypic abnormalities. We reviewed all cases of isolated localized fetal nuchal lucency (3 mm or greater) in 9 to 14 week fetuses over a 4 year period. Fetuses with additional sonographic abnormalities were excluded. The width of the nuchal lucency at initial sonogram as well as findings on subsequent scans were tabulated. Karyotypic, pathologic, and clinical follow-up data were obtained. Of 44 fetuses with an isolated, localized first trimester nuchal lucency, one was lost to follow-up and two were excluded owing to pregnancy termination without karyotype or pathologic analysis, thus resulting in 41 fetuses in our study group. Five fetuses (12%) had abnormal karyotypes. Twenty-seven of the remaining 36 fetuses had normal karyotypes, eight others showed no evidence of aneuploidy at birth, and one patient underwent spontaneous abortion prior to a karyotypic analysis. Among the 36 fetuses without evidence of aneuploidy, six had a poor outcome: two were spontaneous abortions, one was a therapeutic abortion of a fetus with hydrops and a pericardial effusion seen on fetopsy; one fetus died at birth of pulmonary hypoplasia associated with autosomal recessive polycystic kidney disease, and one fetus each had Noonan syndrome, and Joubert syndrome. In addition, three patients delivered their infants prematurely. Overall, 32 of 41 fetuses survived, and two (6%) were abnormal. Excluding premature infants, 27 were normally grown, term survivors. We conclude that other than having an increased risk for aneuploidy, fetuses with isolated nuchal lucency are also at risk for spontaneous miscarriage, premature delivery, and congenital anomalies unassociated with an abnormal karyotype.


Disturbance decreases genotypic diversity by reducing colonization: Implications for disturbance-diversity feedbacks.
One objective of eco-evolutionary dynamics is to understand how the interplay between ecology and evolution on contemporary timescales contributes to the maintenance of biodiversity. Disturbance is an ecological process that can alter species diversity through both ecological and evolutionary effects on colonization and extinction dynamics. While analogous mechanisms likely operate among genotypes within a population, empirical evidence demonstrating the relationship between disturbance and genotypic diversity remains limited. We experimentally tested how disturbance altered the colonization (gain) and extinction (loss) of genets within a population of the marine angiosperm Zostera marina (eelgrass). In a 2-year field experiment conducted in northern California, we mimicked grazing disturbance by migratory geese by clipping leaves at varying frequencies during the winter months. Surprisingly, we found the greatest rates of new colonization in the absence of disturbance and that clipping had negligible effects on extinction. We hypothesize that genet extinction was not driven by selective mortality from clipping or from any stochastic loss resulting from the reduced shoot densities in clipped plots. We also hypothesize that increased flowering effort and facilitation within and among clones drove the increased colonization of new genets in the undisturbed treatment. This balance between colonization and extinction resulted in a negative relationship between clipping frequency and net changes in genotypic richness. We interpret our results in light of prior work showing that genotypic diversity increased resistance to grazing disturbance. We suggest that both directions of a feedback between disturbance and diversity occur in this system with consequences for the maintenance of eelgrass genotypic diversity.


Inhibitory effect of novobiocin on ribonucleic acid synthesis during germination of Bacillus subtilis spores.
Novobiocin inhibited ribonculeic acid synthesis during germination of Bacillus subtilis spores. Transcription of certain kinds of genes probably required a preceding conformational change in deoxyribonucleic acid.


Functional polymers for growth and stabilization of CsPbBr3 perovskite nanoparticles.
We introduce an approach to synthesize polymer-stabilized CsPbBr3 perovskite nanoparticles (NPs) using ammonium bromide-functionalized polymers as both bromide precursors and stabilizing ligands. The polymer-passivated NPs exhibit significant advantages over conventional perovskite NPs owing to their facile dispersion in polymer matrices and enhanced optoelectronic stability.


Post-photorefractive Keratectomy Pain and Corneal Sub-basal Nerve Density.
The perceived and reported pain of patients receiving photorefractive keratectomy (PRK) widely varies. We assessed the potential role of the subbasal nerve plexus density as a predictor of postoperative pain level. Consecutive patients scheduled to undergo PRK at the Refractive Surgery Clinic of Farabi Eye Hospital, Tehran, were approached. Forty-nine myopic left eyes from 49 patients who consented to undergo scanning slit confocal microscopy assessments preoperatively were included. ImageJ (1.48v) was used to measure the captured subbasal nerve length. Postoperative pain intensity was assessed by the Visual Analog Scale (VAS) (score range: 0 for no pain to 10 for the maximum possible) on the next day of surgery. The mean age of the patients was 27.55 (range: 19-40) years. The median reported pain level was 5. Approximately 32.7% of the subjects reported a pain score of 6 or higher. Mean nerve density was 19.54 (range: 14.34-24.73) mm/mm2. Nerve density was not correlated with the reported intensity of pain (P = 0.172). However, pain was correlated with the reported ocular discomfort, i.e., a pooled index of foreign body sensation, photophobia, burning sensation, and tearing (P < 0.001), and also with the pooled index of ocular inflammatory signs (conjunctival injection and eyelid edema) (P = 0.027). Crude density of corneal nerves may not be a good predictor of post-PRK pain while wearing bandage contact lenses. The predominant pain mechanism appears to be of an inflammatory nature (not nociceptive or neuropathic).


SAFETY AND SEROLOGICAL RESPONSE TO MULTIVALENT CANINE DISTEMPER VIRUS VACCINE IN RED FOXES (VULPES VULPES).
Canine distemper virus (CDV) vaccination using commercial vaccines has been recommended as a useful preventive tool in zoological collections worldwide for the past 30 yr. Zoological facilities have not conducted studies to assess the effectiveness and safety of the multivalent Recombitek C6 and C8 in nondomestic carnivores. They are the only CDV recombinant vaccines available in Latin America. Seventeen clinically healthy red foxes born in Buin Zoo were divided into three groups and administered 1 ml of Recombitek C6 vaccine. Group A consisted of three animals of 9 mo of age without previous vaccination (WPV) that received a single dose. Group B consisted of four animals of 10 mo of age WPV; they received a series of three doses with a 21-day interval between doses. Group C consisted of eight animals > 1 yr of age that had received a previous vaccination > 1 yr ago; they received a single-dose booster vaccination. Titers for antibodies against CDV were measured by a serum neutralization test. All animals remained clinically healthy throughout the study period and without clinical signs of disease. Only two foxes (group C) did not show any increase in the antibody titer to the vaccine. All animals of groups A and B seroconverted at 21 days after the first vaccination. Only two animals (both from group B) showed an adequate antibody protective response (titers >100) after 180 days. Absence of adverse reactions in red foxes included in this study supports the safety and apparently nondeleterious effect of CDV recombinant vaccine reported in other nondomestic carnivores. Low antibody response and lack of persistence in the serological response 6 mo after vaccination with a single dose suggested limited protective benefits in this species. Additional research is needed to confirm the antibody titer response to multiple vaccinations in this species.


[Association of genetic and mechanical factors with age of onset of knee osteoarthritis].
To analyze the relationship of genetic and mechanical factors with age of onset of knee osteoarthritis (OA). Cross-sectional and longitudinal studies were conducted in 863 patients with knee OA and 999 age-matched controls from Chinese Han population with complete clinical data. Single nucleotide polymorphisms of + 104T/C in rs143383 of the growth differentiation factor 5 (GDF5) gene and the aspartic acid repeat polymorphism of the asporin gene ASPN were genotyped by taqman probe and polyacrylamide gel electrophoresis respectively. Body mass index (BMI) in subjects with knee OA was significantly higher than that in controls (P< 0.01). Obesity (BMI≥ 25) was a high risk factor for knee OA (P< 0.01). Regression analysis showed that there was a certain correlation between the BMI and age of onset of the knee OA (Pearson= 0.15, P< 0.01). To analyze the BMI distribution, the two groups were subgrouped by age with 5-year interval. The BMI in early-onset patients was lower than that in the late-onset patients (F= 2.497, P= 0.011). However, there was no significant difference in the control subgroups. Frequencies of the GDF5 and ASPN alleles distributed differently between the early- and late-onset patients (P< 0.05). Genetic factors play an important role in knee osteoarthritis of early-onset patients, whereas mechanical factor play an important part in knee osteoarthritis of late-onset patients.


Anesthetic management of two cases of Bardet-Biedl syndrome for renal transplantation.
Bardet-Biedl syndrome (BBS) is a multisystem autosomal recessive disorder with clinical and genetic heterogeneity. It is a type of ciliopathy characterized by retinal dystrophy, central obesity, polydactyly, cognitive impairment, and gonadal and renal dysgenesis. It has been suggested that the involved proteins attach to the basal body of ciliated cells making this a disorder of ciliary dysfunction. We report two cases of typical BBS in a 17-year-old female and 29-year-old male patient, who presented for live-related renal transplant. We discuss the relevant points of the syndrome regarding anesthetic management.


Alcohol consumption in the elderly and risk of dementia related death--a Norwegian prospective study with a 17-year follow-up.
The aim of this study was to determine the association between alcohol intake and risk of dementia related death, taking into account relevant confounding and mediating factors. Data was obtained from a Norwegian prospective study with a 17-year follow-up. The study population comprised 25,635 participants aged between 60 and 80 years at the time of examination from the Cohort of Norway (CONOR). Cox regression was used to investigate the association between alcohol use and dementia related death. Nearly half (12,139) of the study population died during follow-up, of which 1,224 had a diagnosis of dementia on their death certificate. The risk of dementia related death was significantly higher among abstainers than among individuals that drank alcohol once per month (HR = 1.33, 95% CI = 1.14-1.56, p < 0.001, in a fully adjusted model). Respondents with missing information regarding alcohol consumption (representing 5% of the study population) had the highest risk of dementia related death (HR = 1.60, 95% CI = 1.28-2.00, p < 0.001) and also significantly higher mortality rates due to alcohol-related causes (HR = 1.41, 95% CI = 1.03-1.93, p = 0.031) and other causes (HR = 1.32, 95% CI = 1.21-1.43, p < 0.001), all compared to those drinking alcohol no more than once per month. These findings suggest that the risk of dementia related death is significantly higher among elderly abstainers than among those who drink alcohol, after adjusting for relevant confounders. However, care should be taken in interpretation of data due to missing information on drinking frequency, as this missing-group might have a large share of the heavy drinkers in the study cohort.


Unconventional T cells in brain homeostasis, injury and neurodegeneration.
The interaction between peripheral immune cells and the brain is an important component of the neuroimmune axis. Unconventional T cells, which include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, γδ T cells, and other poorly defined subsets, are a special group of T lymphocytes that recognize a wide range of nonpolymorphic ligands and are the connection between adaptive and innate immunity. Recently, an increasing number of complex functions of these unconventional T cells in brain homeostasis and various brain disorders have been revealed. In this review, we describe the classification and effector function of unconventional T cells, review the evidence for the involvement of unconventional T cells in the regulation of brain homeostasis, summarize the roles and mechanisms of unconventional T cells in the regulation of brain injury and neurodegeneration, and discuss immunotherapeutic potential as well as future research goals. Insight of these processes can shed light on the regulation of T cell immunity on brain homeostasis and diseases and provide new clues for therapeutic approaches targeting brain injury and neurodegeneration.


E-health literacy and associated factors among Korean adults during the COVID-19 pandemic: age-group differences.
The purpose of this study was to compare the mean scores of e-health literacy, health information, social relationships, and psychological status between younger, middle-aged, and older Korean adults during the COVID-19 pandemic and to identify the factors associated with e-health literacy as well as the moderating effect of age on the association between health information factors and e-health literacy. We used a cross-sectional survey of 2400 Korean adults aged 20 years or older residing in Seoul. Descriptive statistics, ANOVA, chi-square test, and hierarchical multiple regression analyses were used to analyze the data. Findings demonstrated an age-group difference in the mean score of e-health literacy with the older group having lower e-health literacy than the other groups. Health information, social support, and COVID-19-related anxiety were associated with e-health literacy and a moderating effect of age on the association between sources of health information and e-health literacy was also identified among the three age subgroups. This study emphasizes the importance of identifying e-health-related risk factors leading to health disparities between age groups.


Immunological effects of captopril.
The effect of captopril treatment on natural killer activity and mitogen-induced lymphocyte blastogenesis was studied in man. No significant change in immune reactivity was found either in short term (one hour after ingestion of 25 mg) or long term (after two weeks, 50 mg daily) treatment.


Infrared dynamic polarizability of HD+ rovibrational states.
A calculation of dynamic polarizabilities of rovibrational states with vibrational quantum number v = 0-7 and rotational quantum number J = 0,1 in the 1sσ(g) ground-state potential of HD(+) is presented. Polarizability contributions by transitions involving other 1sσ(g) rovibrational states are explicitly calculated, whereas contributions by electronic transitions are treated quasi-statically and partially derived from existing data [R. E. Moss and L. Valenzano, Mol. Phys., 2002, 100, 1527]. Our model is valid for wavelengths >4 μm and is used to assess level shifts due to the blackbody radiation (BBR) electric field encountered in experimental high-resolution laser spectroscopy of trapped HD(+) ions. Polarizabilities of 1sσ(g) rovibrational states obtained here agree with available existing accurate ab initio results. It is shown that the Stark effect due to BBR is dynamic and cannot be treated quasi-statically, as is often done in the case of atomic ions. Furthermore it is pointed out that the dynamic Stark shifts have tensorial character and depend strongly on the polarization state of the electric field. Numerical results of BBR-induced Stark shifts are presented, showing that Lamb-Dicke spectroscopy of narrow vibrational optical lines (∼10 Hz natural linewidth) in HD(+) will become affected by BBR shifts only at the 10(-16) level.


The effects of hypoxic acidemia on left ventricular end-systolic elastance in fetal sheep.
Using the conductance catheter technique, we measured the effects of hypoxic acidemia on left ventricular end-systolic elastance in anesthetized, 133-d gestation, in utero fetal sheep (n = 7). Conductance and Millar catheters were introduced into the left ventricle through a carotid artery cutdown. Fetuses were rendered progressively hypoxic and acidemic by placental embolization with repeated injections of 5 x 10(5) 50-microns plastic spheres every 15 min via a catheter placed in the fetal abdominal aorta. We recorded pressure-volume data and arterial blood gases at 15-min intervals. End-systolic elastance was computed using a single-beat method of extrapolating maximum isovolumic pressure. A mean of five boluses was required to cause fetal death. Placental embolization caused progressive fetal acidemia. Mean baseline fetal arterial pH was 7.32 +/- 0.06 (mean +/- SD) and gradually decreased with embolization (p < 0.0001). A linear relationship was found to exist between elastance and pH with a mean decrease of 0.46 kPa/mL per 0.1-unit drop in pH (r = 0.96; p < 0.0001). Despite the decrease in end-systolic elastance, stroke volume and left-ventricular output were maintained due to a parallel decrease in afterload. The decrease in end-systolic elastance was gradual and extended over the entire clinically important range of pH, rather than being a terminal event. This study, which, to our knowledge, is the first to use the conductance catheter to measure fetal left ventricular function demonstrates that hypoxic acidemia adversely affects myocardial contractility assessed by end-systolic elastance.


Clinically driven design of multi-scale cancer models: the ContraCancrum project paradigm.
The challenge of modelling cancer presents a major opportunity to improve our ability to reduce mortality from malignant neoplasms, improve treatments and meet the demands associated with the individualization of care needs. This is the central motivation behind the ContraCancrum project. By developing integrated multi-scale cancer models, ContraCancrum is expected to contribute to the advancement of in silico oncology through the optimization of cancer treatment in the patient-individualized context by simulating the response to various therapeutic regimens. The aim of the present paper is to describe a novel paradigm for designing clinically driven multi-scale cancer modelling by bringing together basic science and information technology modules. In addition, the integration of the multi-scale tumour modelling components has led to novel concepts of personalized clinical decision support in the context of predictive oncology, as is also discussed in the paper. Since clinical adaptation is an inelastic prerequisite, a long-term clinical adaptation procedure of the models has been initiated for two tumour types, namely non-small cell lung cancer and glioblastoma multiforme; its current status is briefly summarized.


Tactile sensory coding during development: signaling capacities of neurons in kitten dorsal column nuclei.
The functional maturation of cuneate neurons was studied using reproducible tactile stimulation procedures and quantitative assessment of coding capacities in anesthetized (N2O/O2 plus barbiturate infusion) or decerebrate cats from six different age groups; neonatal (1-5 days), 10-15, 25-30, 55-63, and 83-90 days, and an adult group. Cuneate neurons were distinguished from input fibers to the nucleus on criteria of spike configuration and time course and on response profiles. Extracellular spike durations underwent a progressive shortening with age, reaching the adult range at approximately 3 mo when background activity levels also reached maturity. Despite an increase in conduction-path length, response latencies decreased to adult values by 25-30 days of age, presumably reflecting the increased conduction velocity in the input fibers. In each age group three functional classes of neurons responsive to tactile stimulation of the footpads were identifiable. One consisted of slowly adapting neurons whose stimulus-response relations resembled those of the adult in responsiveness and dynamic range by 25-30 days postnatal age. The remaining neurons were purely dynamically sensitive, but among them two classes could be distinguished by their differential sensitivity to cutaneous vibration, one receiving rapidly adapting (RA) fiber input the other pacinian corpuscle (PC) input. The combined bandwidth of vibration sensitivity in dynamically sensitive cuneate neurons expands from approximately 5-300 Hz in the neonate to the mature range of 5-1,000 Hz by 1 mo of age. The PC class of cuneate neurons showed an upward shift in peak sensitivity from 30-200 Hz in the neonate to 100-300 Hz at 10-15 days, reaching adult values of 200-600 Hz by 25-30 days. Over this period absolute thresholds dropped by an order of magnitude at 200-500 Hz reflecting the threshold trends in primary PC fibers. During the first 1-2 postnatal months, the capacity of cuneate PC neurons to signal information in a pattern code about vibration frequencies around 300 Hz is restricted because of poor phase locking and low responsiveness, which preclude an impulse periodicity reflecting the vibratory frequency.(ABSTRACT TRUNCATED AT 400 WORDS)


Expression Pattern of Scavenger Receptors and Amyloid-β Phagocytosis of Astrocytes and Microglia in Culture are Modified by Acidosis: Implications for Alzheimer's Disease.
The pathological hallmarks of Alzheimer's disease (AD) are amyloid-β (Aβ) plaques, neurofibrillary tangles, and glia activation. The pathology also includes vascular amyloidosis and cerebrovascular disease. Vascular compromise can result in hypoperfusion, local tissue hypoxia, and acidosis. Activated microglia and astrocytes can phagocytose Aβ through membrane receptors that include scavenger receptors. Changes in glial cells induced by extracellular acidosis could play a role in the development of AD. Here, we assess whether extracellular acidosis changes glial cell properties relevant for Aβ clearance capacity. Incubation of glial cells on acidified culture medium (pH 6.9 or 6.5) for 24-48 h resulted in decreased cell diameter, with thinner branches in astrocytes, slight reduction in cell body size in microglia, a transient decrease in astrocyte adhesion to substrates, and a persistent decrease in microglia adhesion compared with control media (pH 7.4). Astrocyte Aβ phagocytosis decreased at pH 6.9 and 6.5, whereas microglia phagocytosis only transiently decreased in acidified media. Scavenger receptors class B member I (SR-BI) increased and scavenger receptors-macrophage receptors with collagenous structures (SR-MARCO) decreased in astrocytes cultured at pH 6.5. In contrast, in microglia exposed to pH 6.5, expression of SR-BI and SR-MARCO increased and fatty acid translocase (CD-36) decreased. In conclusion, the acidic environment changed the adhesiveness and morphology of both microglia and astrocytes, but only astrocytes showed a persistent decrease in Aβ clearance activity. Expression of scavenger receptors was affected differentially in microglia and astrocytes by acidosis. These changes in scavenger receptor patterns can affect the activation of glia and their contribution to neurodegeneration.


The prevalence of diabetes in a Swedish population of 280,411 inhabitants. A report from the Skaraborg Diabetes Registry.
To estimate the prevalence of known diabetes in a Swedish county (Skaraborg) and to evaluate capture-recapture methods for validation of the diabetes prevalence. Four sources were used to find known diabetic patients: 1) the Skaraborg Diabetes Registry (SDR), a case-finding inventory, 2) an administrative hospital registry, 3) a registry for the retinopathy screening program, and 4) a pharmacy prescription inventory. The capture-recapture method was applied to various combinations of sources to determine the prevalence of diabetes. The completeness of the SDR was 88.4 +/- 1.3%, indicating a diabetes prevalence of 3.20 +/- 0.08%. When the SDR was not used as one of the sources, the estimated prevalence varied between 2.2 and 4.5%. A case-finding registry is important in reliably estimating the prevalence of diabetes.


Novel Stress-Inducible Antisense RNAs of Protein-Coding Loci Are Synthesized by RNA-Dependent RNA Polymerase.
Our previous study identified approximately 6,000 abiotic stress-responsive noncoding transcripts existing on the antisense strand of protein-coding genes and implied that a type of antisense RNA was synthesized from a sense RNA template by RNA-dependent RNA polymerase (RDR). Expression analyses revealed that the expression of novel abiotic stress-induced antisense RNA on 1,136 gene loci was reduced in the rdr1/2/6 mutants. RNase protection indicated that the RD29A antisense RNA and other RDR1/2/6-dependent antisense RNAs are involved in the formation of dsRNA. The accumulation of stress-inducible antisense RNA was decreased and increased in dcp5 and xrn4, respectively, but not changed in dcl2/3/4, nrpd1a and nrpd1b RNA-seq analyses revealed that the majority of the RDR1/2/6-dependent antisense RNA loci did not overlap with RDR1/2/6-dependent 20-30 nt RNA loci. Additionally, rdr1/2/6 mutants decreased the degradation rate of the sense RNA and exhibited arrested root growth during the recovery stage following a drought stress, whereas dcl2/3/4 mutants did not. Collectively, these results indicate that RDRs have stress-inducible antisense RNA synthesis activity and a novel biological function that is different from the known endogenous small RNA pathways from protein-coding genes. These data reveal a novel mechanism of RNA regulation during abiotic stress response that involves complex RNA degradation pathways.


[The neurosurgical therapy of trigeminal neuralgia].
The Trigeminal Neuralgie (TN) is he most common cause of facial pain with an incidence of 27 per 100'000 patients per year. The symptoms are paroxysmal stabbing, tearing, and burning pain usually in the area of the second and third trigeminal nerve, that can be provoked by drinking, shaving, chewing or talking. If the classical drug therapy with anticonvulsants is not sufficient or must be discontinued due to side effects, then the retrosigmoidal craniotomy and micro-vascular decompression in vascular-nerve-contact ot partial rhizotomy are good pain-free procedures. Such operations are of low risk in the hands of experienced neurosurgeons and possible to be carried out even in elderly patients. A high percentage of free of complaints postoperative and low recurrence rate legitimate this method.


Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab.
B cell depletion, most commonly with rituximab, is an evolving therapeutic approach in SLE. Infusion reactions after rituximab are common, and may prevent re-treatment in patients who previously demonstrated beneficial response. We have used ofatumumab, a fully humanized anti-CD20 mAb, as an alternative B cell-depleting agent in patients with SLE who are rituximab-intolerant due to severe infusion reactions. A single-centre retrospective case series of 16 patients were treated with ofatumumab for SLE between 2012 and 2015. Ofatumumab infusion was well tolerated in 14/16 patients, in whom the median age was 34 (range 19-55) and the median duration of SLE 9.2 years (0.6-28.5). The cohort was heavily pre-treated, with 50% having prior CYC exposure, and a median cumulative dose of prior rituximab 4 g (1-6). Twelve patients were treated for LN, one for extra-renal flare and one for remission maintenance. B cell-depletion was achieved in 12/14 patients, with comparable reconstitution kinetics to a previous cohort treated with rituximab at our centre, and was associated with improvements in serological markers of disease activity, including ANA, anti-dsDNA antibody and complement levels. Half of the patients with LN achieved renal remission by 6 months. Progressive disease that was unresponsive to augmented immunosuppression with CYC was seen in five patients. During long-term follow-up (median 28 months), five grade III infections were reported, and there were no malignancies or deaths. In this pre-treated cohort with long-standing SLE, ofatumumab was a well-tolerated, safe and effective alternative to rituximab for B cell-depletion therapy.


[Type IV collagenase activities in human colorectal cancers and its role in cancer invasion and metastasis].
In 36 patients with colorectal cancers, type IV collagenase activities were measured in cancer and non-cancer tissues for evaluating its role in the process of cancer invasion and metastasis. The colorectal cancer tissues revealed remarkably higher activities than the distant normal and tumor-neighboring mucosa (p < 0.001). The activities in the colorectal cancer tissues with high-grade histological venous invasion were higher than those with low-grade histological venous invasion (p < 0.005). But no differences of the activities were found between patients with and without hepatic metastasis. These results suggest that the type IV collagenase plays an important role in the cancer invasion to the blood vessels around the primary site in colorectal cancers.


Instrument and methods for surface dilatational rheology measurements.
We describe an instrument combining the advantages of two methods, axisymmetric drop shape analysis for well-deformed drops and capillary pressure tensiometry for spherical drops, both used for measuring the interfacial tension and interfacial rheological parameters. The rheological parameters are the complex interfacial elasticity, and the surface elasticity and viscosity of Kelvin-Voigt and Maxwell rheological models. The instrument is applicable for investigation of the effect of different types of surfactants (nonionic, ionic, proteins, and polymers) on the interfacial rheological properties both of air/water and oil/water interfaces, and of interfaces between liquids with equal mass densities. A piezodriven system and a specially designed interface unit, implemented in the instrument, ensure precise control for standard periodic waveforms of surface deformation (sine, square, triangle, and sawtooth) at a fixed frequency, or produce surface deformation at constant rate. The interface unit ensures accurate synchronization between the pressure measurement and the surface control, which is used for real-time data processing and feedback control of drop area in some of the applications.


Synthesis and evaluation of nicotine analogs as neuronal nicotinic acetylcholine receptor ligands.
A series of 3'-, 4'-, and 5'-substituted nicotine analogs have been synthesized and evaluated as ligands of the neuronal nicotinic acetylcholine receptor. The compounds prepared were found to have binding affinities ranging from 4 to 3500 nM. The results indicate that only a small substituent or functionality is well tolerated at the C4' position of nicotine and that binding affinity is affected by both steric and electronic properties of the substituent. On the other hand, the C3' and C5' positions seem to be the more sensitive toward bulky substituents. The best compound, 4'-methylnicotine, is nearly equipotent to nicotine. It possesses the most favorable binding affinity.


To Reconstruct or Not: A Case of Acute Reconstruction of the Forearm Interosseous Membrane with CMC Mini Tight Rope.
Essex Lopresti fractures are rare injuries of the forearm. Extent of damage to the interosseous membrane (IOM) in this setting is variable and can lead to disabling sequelae when not recognized and managed appropriately. While chronic reconstruction for longitudinal radioulnar dissociation is well studied, acute reconstruction of the membrane is infrequently documented and surgical techniques vary. There are only five documented cases of acute IOM reconstruction for Essex Lopresti injuries (ELIs). This is the first described case using a mini suture-button construct in conjunction with a radial head replacement and distal radioulnar joint (DRUJ) pinning, while also providing long-term radiographic and functional follow-up of 2 years. We present a case of a 40-year-old male who sustained an Essex Lopresti fracture that was acutely recognized and surgically managed with a radial head replacement, DRUJ pinning, and acute reconstruction of the IOM with a Mini TightRope suture button construct. We also provide a post-operative rehabilitation protocol with early range of motion and pin removal. At our final 2-year postoperative follow-up, the patient demonstrated excellent functional outcomes. This case illustrates that a CMC Mini TightRope can be used for acute reconstruction of the IOM in the setting of ELIs which allows for early range of motion and DRUJ pin removal due to the maintenance of longitudinal radioulnar reduction.


[Gene therapy of haemophilia - has the cure come within reach?]
Haemophilia is a bleeding disorder (usually congenital) caused by the deficiency of coagulation factor VIII (haemophilia A) or IX (haemophilia B). The genes encoding factors VIII and IX are located on the X chromosome, so the symptoms of congenital haemophilia A and B occur predominantly in males. Recurring episodes of spontaneous bleeding into joints are the main symptom of haemophilia, which lead to haemophilic artropathy. Historically, patients with haemophilia were treated with whole blood transfusions and then with blood plasma. The first big breakthrough in treatment efficacy was the advent of cryoprecipitate, followed by lyophilized coagulation factor concentrates, derived from plasma. The latter dramatically improved patients' quality of life and allowed for prophylactic self-infusions at home (home treatment). Since the 1990s, the standard treatment has also included recombinant coagulation factor concentrates derived from cell cultures. Today, the main challenges are the need for frequent venipunctures (factor concentrates must be administered intravenously) to maintain successful prophylaxis and emergence of neutralizing antibodies in response to exogenous coagulation factors. Several novel recombinant factors with extended half-life were approved in recent years. Clinical trials of other new technologies are ongoing. These are non-replacement therapies with different mechanisms of action (e.g. emicizumab, a bispecific antibody that mimics the procoagulant activity of factor VIII; fitusiran, siRNA downregulating antithrombin III) and gene therapies using AAV vectors.


Who is likely to quit nursing jobs? A study in the Turkish Republic of Northern Cyprus.
The study reported in this article examines the nature of relationships between organizational and personal resources and nurses' turnover intentions. A sample of 124 nurses in the Turkish Republic of Northern Cyprus serves as the study setting. Results of the study reveal that a form of organizational support (empowerment) and two personal resources (customer orientation, job resourcefulness) are the best predictors of turnover intentions. Implications of these results are discussed and avenues for future research are offered.


Stimuli-responsive polyelectrolyte polymer brushes prepared via atom-transfer radical polymerization.
We present an account of our research into polyelectrolyte polymer brushes that are capable of acting as stimuli-responsive films. We first detail the synthesis of poly(acrylic acid) polymer brushes using ATRP in a "grafting from" strategy. Significantly, we employed a chemical-free deprotection step that should leave the anchoring ester groups intact. We have demonstrated how these polymer assemblies respond to stimuli such as pH and electrolyte concentration. We have used poly(acrylic acid) polymer brushes for the synthesis of metallic nanoparticles and review this work. We have used XPS, ATR-FTIR, and AFM spectroscopy to show the presence of silver and palladium nanoparticles within polymer brushes. Finally, we report the synthesis of AB diblock polyampholyte polymer brushes that represent an extension of polyelectrolyte polymer brushes.


Craniofacial surgery for craniosynostosis: functional and morphological results.
The functional and morphological aspects of craniosynostoses are reviewed, based on a series of 462 operations, 350 intra-cranial pressure recordings and 300 I.Q. assessments. Increased intracranial pressure and mental impairment are linked. The frequency of intracranial hypertension is higher when more than one suture is involved, but even monosutural craniosynostoses can be affected. Increased intracranial pressure had mental deficiency are more frequent after one year of age than before. Surgery lowers the intracranial pressure and halts the mental regression. The younger the patient is at the time of surgery, the better the results. Surgery does not improve the I.Q. once it is already impaired. Morphological results of frontocranial remodeling are good and remain so with growth. Facial anomalies associated with craniosynostoses improve after early frontocranial remodeling, except for the severe midface retrusion of Crouzon's disease and Apert's syndrome that need in most cases a supplementary midface advancement.


Estimating population density for disease risk assessment: The importance of understanding the area of influence of traps using wild pigs as an example.
Population density is a key driver of disease dynamics in wildlife populations. Accurate disease risk assessment and determination of management impacts on wildlife populations requires an ability to estimate population density alongside management actions. A common management technique for controlling wildlife populations to monitor and mitigate disease transmission risk is trapping (e.g., box traps, corral traps, drop nets). Although abundance can be estimated from trapping actions using a variety of analytical approaches, inference is limited by the spatial extent to which a trap attracts animals on the landscape. If the "area of influence" were known, abundance estimates could be converted to densities. In addition to being an important predictor of contact rate and thus disease spread, density is more informative because it is comparable across sites of different sizes. The goal of our study is to demonstrate the importance of determining the area sampled by traps (area of influence) so that density can be estimated from management-based trapping designs which do not employ a trapping grid. To provide one example of how area of influence could be calculated alongside management, we conducted a small pilot study on wild pigs (Sus scrofa) using two removal methods 1) trapping followed by 2) aerial gunning, at three sites in northeast Texas in 2015. We estimated abundance from trapping data with a removal model. We calculated empirical densities as aerial counts divided by the area searched by air (based on aerial flight tracks). We inferred the area of influence of traps by assuming consistent densities across the larger spatial scale and then solving for area impacted by the traps. Based on our pilot study we estimated the area of influence for corral traps in late summer in Texas to be ∼8.6km2. Future work showing the effects of behavioral and environmental factors on area of influence will help mangers obtain estimates of density from management data, and determine conditions where trap-attraction is strongest. The ability to estimate density alongside population control activities will improve risk assessment and response operations against disease outbreaks.


Collaborative drug therapy management by pharmacists--2003.
Since publication of the initial ACCP position statement on CDTM by pharmacists in 1997, the public, government, and much of the health care community at large have come to better appreciate the growing complexity of providing effective and safe drug therapy in today's health care environment. Increased interest in the issues of cost and quality of drug use is evident in the increasing coverage of the issue in the lay press and professional literature. This represents real progress, as well as real opportunity, for pharmacists. It also heightens the potential for a better understanding of the vital role that pharmacists can play in addressing these concerns. The percentage of patients who take several drugs for chronic diseases will continue to increase. Based on current trends, the number of patients who lack adequate access to care, or who receive either suboptimal, inappropriate, or unnecessarily expensive drug therapy for their acute and chronic diseases, will increase. Even as financial and human resources are increasingly strained within the current health care system, costs will continue to rise unless changes are made. Fortunately, qualified pharmacists are prepared, capable, and willing to help address a significant portion of these challenges. The public, many health care providers, some legislators, and a few insurers now recognize that pharmacists, because of their education and training in drug therapy, are well positioned both to accept additional responsibility for patient care and to provide services that make a real difference in health care quality and outcomes. The health care programs administered by the U.S. Public Health Service, the armed forces, and the Veterans Health Administration, as well as 38 states, now support pharmacist participation in CDTM. Pharmacists, working in an interdisciplinary structure with physicians and other health care providers, have demonstrated that they can improve the effectiveness, efficiency, and safety of drug therapy by providing CDTM. It is time to incorporate this valuable professional skill of the contemporary pharmacist as a core component of the delivery of health care services.


In vivo ruminal degradation characteristics and apparent digestibility of low-quality prairie hay for steers consuming monensin and Optimase.
Seven ruminally cannulated crossbred steers (BW = 720 ± 62 kg) were used in a randomized crossover design (4 periods, each 18 d) to evaluate in vivo rumen characteristics and apparent digestibility of steers consuming low-quality prairie hay and 1 of 4 isonitrogenous protein supplements. Treatments included 1) 40% CP (DM basis) cottonseed meal and wheat middlings-based supplement (Control), 2) a cottonseed meal and wheat middlings-based supplement with slow-release urea and a fibrolytic feed enzyme (Optimase; Alltech, Inc., Nicholasville, KY) designed to replace 30% of plant-based CP provided in the Control (OPT), 3) the Control plus 0.40 mg∙kg BW∙d monensin (Rumensin 90; Elanco Animal Health, Greenfield, IN; MON), and 4) the OPT plus 0.40 mg∙kg BW∙d monensin (COMBO). Steers were allowed ad libitum access to prairie hay (5.0% CP and 76% NDF) and were provided each respective supplement at 0800 h daily at a rate of 1.0 g/kg of BW. Steers were adapted to diets for 10 d before sample collection. Beginning on d 11, DMI was measured and samples were collected to determine apparent digestibility. On d 15 of the 18-d period, rumen fluid was collected 10 times over a 24-h period. Forage DMI was greater ( ≤ 0.02) for steers consuming the OPT compared with steers consuming the MON or COMBO, although forage DMI was not different ( = 0.10) among steers consuming the Control compared with steers consuming the OPT, MON, or COMBO. Steers fed the MON and COMBO had lower ( ≤ 0.05) passage rate compared with steers fed the Control and the OPT. The MON-fed steers had lower ( = 0.01) ruminal pH and increased ( = 0.03) propionate as a percentage of total VFA production. A time × treatment ( = 0.01) interaction was observed for ruminal NH-N due to a rapid (0 to 1 h after feeding) increase followed by a quick (1 to 4 h after feeding) decline in NH-N by steers consuming the OPT and COMBO that was not observed for steers consuming all other treatments. Apparent digestibility of DM ( = 0.01) and NDF ( = 0.03) were improved for steers fed the COMBO supplement compared with steers consuming all other experimental supplements. This work suggests that the OPT may be an effective replacement for a portion of supplemental degradable intake protein in low-quality forage. Further research is necessary to determine if the combination of monensin and the Optimase consistently improves low-quality forage utilization.


The PEL1 gene (renamed PGS1) encodes the phosphatidylglycero-phosphate synthase of Saccharomyces cerevisiae.
Phosphatidylglycerophosphate (PG-P) synthase catalyzes the synthesis of PG-P from CDP-diacylglycerol and sn-glycerol 3-phosphate and functions as the committed and rate-limiting step in the biosynthesis of cardiolipin (CL). In eukaryotic cells, CL is found predominantly in the inner mitochondrial membrane and is generally thought to be an essential component of many mitochondrial functions. We have determined that the PEL1 gene (now renamed PGS1), previously proposed to encode a second phosphatidylserine synthase of yeast (Janitor, M., Jarosch, E., Schweyen, R. J., and Subik, J. (1995) Yeast 13, 1223-1231), in fact encodes a PG-P synthase of Saccharomyces cerevisiae. Overexpression of the PGS1 gene product under the inducible GAL1 promoter resulted in a 14-fold increase in in vitro PG-P synthase activity. Disruption of the PGS1 gene in a haploid strain of yeast did not lead to a loss of viability but did result in a dependence on a fermentable carbon source for growth, a temperature sensitivity for growth, and a petite lethal phenotype. The pgs1 null mutant exhibited no detectable in vitro PG-P synthase activity and no detectable CL or phosphatidylglycerol (PG); significant CL synthase activity was still present. The growth arrest phenotype and lack of PG-P synthase activity of a pgsA null allele of Escherichia coli was corrected by an N-terminal truncated derivative of the yeast PG-P synthase. These results unequivocally demonstrate that the PGS1 gene encodes the major PG-P synthase of yeast and that neither PG nor CL are absolutely essential for cell viability but may be important for normal mitochondrial function.


Differential Effects of Prior Influenza Exposures on H3N2 Cross-reactivity of Human Postvaccination Sera.
Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched strains can lead to reduced protection. Humans have complex influenza exposure histories that increase with age, which may lead to different postvaccination responses to emerging influenza variants. Recent observational studies also suggest that prior vaccination may influence the performance of current seasonal vaccines. To elucidate the effects of age and influenza preexposures on cross-reactivity of vaccination-induced human antibodies, we generated antigenic maps based on postvaccination hemagglutination inhibition titers against representative H3 variants circulating during the 2015-2016, 2014-2015, and 2012-2013 influenza seasons. Antigenic maps determined using sera from subjects 18-64 and ≥65 years of age correlated well with each other but poorly with those determined using sera from children. Antigenic maps derived from human postvaccination sera with H1 influenza preexposure also correlated poorly with those derived from sera with neither H1 nor type B influenza preexposure, and the correlation lessened considerably over time. In contrast, antigenic maps derived from human postvaccination sera with only type B influenza preexposure consistently showed good correlation with those derived from sera with neither H1 nor type B influenza preexposure. Our results suggest an age-specific difference in human postvaccination responses. Our findings also suggest that prior exposure to H1 or type B influenza may differentially affect cross-reactivity of vaccination-induced H3-specific hemagglutination inhibition antibody responses, and consequently might affect vaccine effectiveness. Our study highlights the need to study the impact of prior exposure on influenza vaccine performance.


Why are nonlinear fits to data so challenging?
Fitting model parameters to experimental data is a common yet often challenging task, especially if the model contains many parameters. Typically, algorithms get lost in regions of parameter space in which the model is unresponsive to changes in parameters, and one is left to make adjustments by hand. We explain this difficulty by interpreting the fitting process as a generalized interpolation procedure. By considering the manifold of all model predictions in data space, we find that cross sections have a hierarchy of widths and are typically very narrow. Algorithms become stuck as they move near the boundaries. We observe that the model manifold, in addition to being tightly bounded, has low extrinsic curvature, leading to the use of geodesics in the fitting process. We improve the convergence of the Levenberg-Marquardt algorithm by adding geodesic acceleration to the usual step.


Effect of repeated ether anesthesias on the mono-oxygenase system of rat liver S-9 fraction.
This study was designed to investigate the effect of ether anesthesia in rats, before i.p. injections to induce the mono-oxygenase enzyme system, on biochemical properties of liver S9 fractions. Aminopyrine N-demethylase and rho-nitroanisole O-demethylase activity levels, their stability, and lipid peroxidation were determined in S9 fractions after etherization (about 1 min in ether vapor chamber daily for 3 consecutive days, before i.p. injections of Na-phenobarbital and beta-naphthoflavone) and compared with controls receiving the same injections without etherization. The activities were slightly (but not significatively) enhanced after this treatment, but stability was markedly and significatively greater after 1 h of incubation in the conditions of the liver microsomal assay (+ 14.8% and + 74.7%, respectively); lipid peroxidation was strongly and significatively depressed (-76.0%). Etherization sufficient to kill the animals on the 4th day resulted in equally active but less stable S9 fraction enzymes. Dimethylnitrosamine (as a standard premutagen) was assayed with the D7 strain of Saccharomyces cerevisiae using S9 fractions obtained from both anesthetized and nonanesthetized rats. According to biochemical data, results obtained with S9 from partially anesthetized rats were comparable with the conventional ones (S9 from nonanesthetized rats). On the contrary, the use of more prolonged ether anesthesia, including one on the day the animals are killed, gives S9 fraction significantly less effective. We conclude that if brief etherizations are used, for i.p. injections only, the S9 fractions obtained are entirely satisfactory and the procedures involved in production are simplified; the additional animal treatment (etherization) must be specified.


Clinical application of polymerase chain reaction amplification to diagnosis of herpes virus infection.
Amplification of viral DNA offers a potentially sensitive and specific method for identifying herpes viruses in pathologic specimens. The purpose of this study is to assess the value of polymerase chain reaction amplification of DNA as a diagnostic test for herpes virus in pathologic specimens. The purpose of this study is to assess for herpes virus infections. We examined 79 paraffin-embedded tissue samples from 43 patients and 55 viral culture samples from 45 patients. Herpes virus DNA in the specimens was amplified by polymerase chain reaction. Using paraffin-embedded tissue on which a diagnosis of herpes virus was made by morphologic criteria, 11 of 19 patients had herpes virus DNA identified by PCR; herpes virus DNA was not identified in any of 35 negative control specimens. Herpes virus DNA was also identified by polymerase chain reaction in all of the positive herpes virus culture specimens. Of 29 culture negative specimens, herpes virus DNA was identified in six. We conclude that polymerase chain reaction is useful to establish or confirm the presence of a herpes virus infection in paraffin-embedded tissue samples and that it is more sensitive than viral culture.


Zinc and infection: a review.
Dietary zinc deficiency is widespread in developing countries and is often aggravated by intercurrent acute and chronic infections. Recent studies have demonstrated that zinc supplementation can significantly reduce the morbidity and mortality of apparently well-nourished children and shorten the time to recovery from acute infectious diseases. This review summarises current knowledge of the role of zinc in childhood diarrhoea, acute respiratory infections and malaria, and its potential role in diseases associated with impaired cellular immunity, namely tuberculosis, lepromatous leprosy and leishmaniasis, and explores avenues for future research.


Photothermoelectric Effects and Large Photovoltages in Plasmonic Au Nanowires with Nanogaps.
Nanostructured metals subject to local optical interrogation can generate open-circuit photovoltages potentially useful for energy conversion and photodetection. We report a study of the photovoltage as a function of illumination position in single-metal Au nanowires and nanowires with nanogaps formed by electromigration. We use a laser scanning microscope to locally heat the metal nanostructures via excitation of a local plasmon resonance and direct absorption. In nanowires without nanogaps, where charge transport is diffusive, we observe voltage distributions consistent with thermoelectricity, with the local Seebeck coefficient depending on the width of the nanowire. In the nanowires with nanogaps, where charge transport is by tunneling, we observe large photovoltages up to tens of mV, with magnitude, polarization dependence, and spatial localization that follow the plasmon resonance in the nanogap. This is consistent with a model of photocurrent across the nanogap carried by the nonequilibrium, "hot" carriers generated upon plasmon excitation.


Efficacy of brief telephone psychotherapy with callers to a suicide hotline.
The efficacy of two types of theapy conducted exclusively over the telephone was studied. Clients (N=55) were recruited from a pool of callers to a suicide hotline and were randomly assigned to a waiting list control (WC) or Solution Focused Brief Therapy (SFBT) or Common Factors Therapy (CFT). It was hypothesized that improvements would be significantly higher in the two therapy conditions compared to the waitlist control and SFBT would be significantly more efficacious than CFT. Results confirmed that improvement was significantly higher in the two treatment conditions compared to the waitlist control, but no difference in improvement was found between SFBT and CFT. The implications of these findings for suicide hotlines are discussed.


Healing of intrabony defects following surgical treatment with or without an Er:YAG laser.
The aim of this controlled, parallel design clinical study was to compare the healing of intrabony periodontal defects following treatment with access flap surgery with and without debridement with an Er:YAG laser. Twenty-three patients each of whom exhibited one deep intrabony defect were randomly treated with either access flap surgery followed by root surface and defect debridement using an Er:YAG laser (KEY3) (160 mJ, 10 Hz) (test), or with access flap surgery followed by root surface and defect debridement using hand and ultrasonic instruments (control). The following clinical parameters were recorded at baseline and at 6 months: plaque index; gingival index; bleeding on probing; probing depth (PD); gingival recession; and clinical attachment level (CAL). The primary outcome variable was CAL. No statistically significant differences between the groups were found at baseline. No serious adverse events were observed after any of the treatments. The results have shown that in the test group the PD decreased from 7.8+/-1.3 to 4.1+/-1.3 mm (p<0.001) and the CAL changed from 9.8+/-2.9 to 7.2+/-2.5 mm (p<0.001). In the control group the PD decreased from 7.8+/-0.8 to 4.6+/-1.6 mm (p<0.001) and the CAL changed from 9.2+/-1.2 to 7.7+/-1.6 mm (p<0.01). The test group displayed a higher tendency for CAL gain, although this tendency did not prove to be statistically significant. Within the limits of the present study, it can be concluded that: (i) at 6 months following treatment both therapies led to significant improvements of the investigated clinical parameters, and (ii) an Er:YAG laser may represent a suitable alternative for defect and root surface debridement in conjunction with periodontal surgery.


New insights into the spatial organization, stratigraphy and human occupations of the Aceramic Neolithic at Ganj Dareh, Iran.
The Aceramic Neolithic site of Ganj Dareh (Kermanshah, Iran) is arguably one of the most significant sites for enhancing our understanding of goat domestication and the onset of sedentism. Despite its central importance, it has proven difficult to obtain contextually reliable data from it and integrate the site in regional syntheses because it was never published in full after excavations ceased in 1974. This paper presents the Ganj Dareh archive at Université de Montréal and shows how the documentation and artifacts it comprises still offer a great deal of useful information about the site. In particular, we 1) present the first stratigraphic profile for the site, which reveals a more complex depositional history than Smith's five-level sequence; 2) reveal the presence of two possible pre-agricultural levels (H-01 and P-01); 3) explore the spatial organization of different levels; 4) explain possible discrepancies in the radiocarbon dates from the site; 5) show some differences in lithic technological organization in levels H-01 and P-01 suggestive of higher degrees of residential mobility than subsequent phases of occupation at the site; and 6) reanalyze the burial data to broaden our understanding of Aceramic Neolithic mortuary practices in the Zagros. These data help refine our understanding of Ganj Dareh's depositional and occupational history and recenter it as a key site to improve our understanding the Neolithization process in the Middle East.


Molecular cloning and characterization of estrogen, androgen, and progesterone nuclear receptors from a freshwater turtle (Pseudemys nelsoni).
Steroid hormones are essential for the normal function of many organ systems in vertebrates. Reproductive activity in females and males, such as the differentiation, growth, and maintenance of the reproductive system, requires signaling by the sex steroids. Although extensively studied in mammals and a few fish, amphibians, and bird species, the molecular mechanisms of sex steroid hormone (estrogens, androgens, and progestins) action are poorly understood in reptiles. Here we evaluate hormone receptor ligand interactions in a freshwater turtle, the red-belly slider (Pseudemys nelsoni), after the isolation of cDNAs encoding an estrogen receptor alpha (ERalpha), an androgen receptor (AR), and a progesterone receptor (PR). The full-length red-belly slider turtle (t)ERalpha, tAR, and tPR cDNAs were obtained using 5' and 3' rapid amplification cDNA ends. The deduced amino acid sequences showed high identity to the chicken orthologs (tERalpha, 90%; tAR, 71%; tPR, 71%). Using transient transfection assays of mammalian cells, tERalpha protein displayed estrogen-dependent activation of transcription from an estrogen-responsive element-containing promoter. The other receptor proteins, tAR and tPR, also displayed androgen- or progestin-dependent activation of transcription from androgen- and progestin-responsive murine mammary tumor virus promoters. We further examined the transactivation of tERalpha, tAR and tPR by ligands using a modified GAL4-transactivation system. We found that the GAL4-transactivation system was not suitable for the measurement of tAR and tPR transactivations. This is the first report of the full coding regions of a reptilian AR and PR and the examination of their transactivation by steroid hormones.


The occurrence of spermiophagy under natural conditions in the cauda epididymidis of the Cape horseshoe bat (Rhinolophus capensis).
In Cape horseshoe bats large numbers of spermatozoa remain in the cauda epididymidis after copulations have ceased in September. Light microscopy has shown that for 5 months after September phagocytes are present in the lumen of the cauda epididymidis and electron microscopy has shown these cells to be active spermiophages. The large numbers of spermiophages present suggests that these cells could be responsible for removal of most of the excess spermatozoa. Spermiophagy by the epididymal epithelial cells occurs rarely and is not significant in the treatment of excess spermatozoa.


Highly Branched Xylan Made by IRREGULAR XYLEM14 and MUCILAGE-RELATED21 Links Mucilage to Arabidopsis Seeds.
All cells of terrestrial plants are fortified by walls composed of crystalline cellulose microfibrils and a variety of matrix polymers. Xylans are the second most abundant type of polysaccharides on Earth. Previous studies of Arabidopsis (Arabidopsis thaliana) irregular xylem (irx) mutants, with collapsed xylem vessels and dwarfed stature, highlighted the importance of this cell wall component and revealed multiple players required for its synthesis. Nevertheless, xylan elongation and substitution are complex processes that remain poorly understood. Recently, seed coat epidermal cells were shown to provide an excellent system for deciphering hemicellulose production. Using a coexpression and sequence-based strategy, we predicted several MUCILAGE-RELATED (MUCI) genes that encode glycosyltransferases (GTs) involved in the production of xylan. We now show that MUCI21, a member of an uncharacterized clade of the GT61 family, and IRX14 (GT43 protein) are essential for the synthesis of highly branched xylan in seed coat epidermal cells. Our results reveal that xylan is the most abundant xylose-rich component in Arabidopsis seed mucilage and is required to maintain its architecture. Characterization of muci21 and irx14 single and double mutants indicates that MUCI21 is a Golgi-localized protein that likely facilitates the addition of xylose residues directly to the xylan backbone. These unique branches seem to be necessary for pectin attachment to the seed surface, while the xylan backbone maintains cellulose distribution. Evaluation of muci21 and irx14 alongside mutants that disrupt other wall components suggests that mucilage adherence is maintained by complex interactions between several polymers: cellulose, xylans, pectins, and glycoproteins.


Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways.
Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN-beta secretion was detected after RV16 infection. Neutralizing antibody specific to IFN-beta and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN-beta production and RV-induced gene expression. Thus, IFN-beta-dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.


[The pathogenic mechanism and prevention and treatment of muscle contracture after replantation of severed palm or wrist].
To explore the pathogenic mechanism of intrinsic muscle contracture after replantation of severed palm or wrist, and put forward the prevention and treatment methods. From 1985 to 1997, 48 cases were received replantation of severed palm or wrist, among them, 9 cases with thumb adductor contracture and 6 cases with intrinsic muscle contracture were occurred in different degree. Two cases with mild thumb adductor contracture were received conservative treatment, and 7 cases with moderate thumb adductor contracture and 6 cases with intrinsic muscle contracture were received operative treatment. The pathogenic mechanism, clinical results, and prevention methods were studied in those 15 cases. The postoperative function recovery was better in 4 cases, moderate in 5 cases with thumb adductor contracture, and better in 3 cases, moderate in 1 case with intrinsic muscle contracture, and moderate in 1 case, poor in 1 case with intrinsic muscle contracture of cord-like induration. Followed up 1 to 10 years, no recurrence was observed in all of 15 cases. The incidence and degree of thumb adductor contracture and intrinsic muscle contracture were closely related to the ischemia time of replanting graft. Prevention of thumb adductor contracture and intrinsic muscle contracture is most important in severed palm or wrist replantation. When the ischemia time of replanting graft is longer than 12 hours, the effective decompression in myofascial compartment is performed in time to reach satisfactory result.


The triplane variant of the tibial apophyseal fracture: a case report and a review of the literature.
A rare case of tibial apophyseal fracture with extension in the antero-lateral physis and epiphysis in a 17-year-old boy is described. This type of fracture, which can be associated with intra-articular lesions and lesions of the extensor mechanism, resembles the better known distal tibial triplane fracture. Arthroscopic controlled anatomic reduction with restoration of the articular surface was achieved.


Maintenance of pancreatic endocrine cells of the neonatal rat: VII. The effect of 3-amino-3-deoxyglucose on insulin secretion from perifused B cells.
Monolayer cultures of the pancreas of the neonatal rat were maintained in TCM 199 medium, supplemented with 5.5 mM glucose, with or without 5 mM 3-amino-3-deoxyglucose, and perifused to examine the changes which occurred in the insulin secretory response during culture. On day 0, B cells showed a monophasic insulin secretion in response to 16.7 mM glucose, whereas in the presence of 200 nM 12-o-tetradecanoyl phorbol-13-acetate, 40 microM lysophosphatidylcholine, 10 microM forskolin or 1 mM 3-isobutyl-1-methylxanthine, the same dose of glucose stimulated insulin secretion in a biphasic fashion. Under culture conditions without 3-amino-3-deoxyglucose, the response to glucose totally disappeared after 7 days, and that to 10 mM of either leucine or 2-ketoisocaproate was as low as that of day 0. In contrast, B cells that had been cultured for 7 days in medium with 3-amino-3-deoxyglucose showed an adult-like biphasic pattern in response to glucose. When stimulated by glucose at a linear gradient concentration running from 0 to 20 mM, the B cells responded to increasing concentrations of glucose in a dose-dependent fashion. Further, the response of cAMP to glucose was increased by adding forskolin or 3-isobutyl-1-methylxanthine, which also enhanced the secretion of insulin under either a step-wise or slow-rise stimulation with glucose. The effect of 12-o-tetradecanoyl phorbol-13-acetate was also outstanding. Likewise, the addition of either leucine or 2-keptoisocaproate induced a striking increase in the secondary phase secretion as well as promoting the rates of glutamine oxidation within the cells. In conclusion, it is suggested that the high response to a wider variety of stimuli may represent the reaction of neonatal B cells to the cultural milieu rather than a process of physiological development, and these effects exhibited by 3-amino-3-deoxyglucose would be related to a change in the constituents of glycoproteins in the cells.


Shear bond strength of ceramic brackets bonded to surface-treated feldspathic porcelain after thermocycling.
The aim of this study was to evaluate the effect of six different surface conditioning methods on the shear bond strength of ceramic brackets bonded to feldspathic porcelain. A total of 60 feldspathic porcelain disks were fabricated and divided into six subgroups including 10 specimens in each. Specimens were first treated one of the following surface conditioning methods, namely, 37% phosphoric acid (G-H3PO4), 9.4% hydrofluoric acid (G-HF), grinding with diamond burs (G-Grinding), Nd:YAG laser (G-Nd:YAG), Airborne-particle abrasion (G-Abrasion). Specimens were also coated with silane without surface treatment for comparison (G-Untreated). A total of 60 ceramic brackets were bonded to porcelain surfaces with a composite resin and then subjected to thermocycling 2500× between 5°C and 55°C. The shear bond strength test was carried out using a universal testing device at a crosshead speed of 0.5 mm/min. Failure types were classified according to the adhesive remnant index. Analysis of variance and Tukey tests were used for statistical analysis (α = 0.05). Microstructure of untreated and surface-treated specimens was investigated by scanning electron microscopy. Using G-Abrasion specimens resulted in the highest shear bond strength value of 8.58 MPa for feldspathic porcelain. However, the other specimens showed lower values: G-Grinding (6.51 MPa), G-Nd:YAG laser (3.37 MPa), G-HF (2.71 MPa), G-H3PO4 (1.17 MPa), and G-Untreated (0.93 MPa). Airborne-particle abrasion and grinding can be used as surface treatment techniques on the porcelain surface for a durable bond strength. Hydrofluoric acid and phosphoric acid etching methods were not convenient as surface treatment methods for the feldspathic porcelain.