Motor neuron columns in the lumbar spinal cord of the rat.
The location in the rat spinal cord of motor neurons innervating 23 muscles or muscle groups of the hind limb has been determined by using retrograde transport of horseradish peroxidase. The motor neurons supplying a single muscle form a discrete longitudinal column in the lateral ventral horn. The columns extend through up to three adjacent spinal segments and their longitudinal location varies by as much as one segment in different animals. The relative positions of the columns supplying different muscles and their transverse location in the spinal cord are very consistent between individuals and a stereotaxic map has been constructed. This is briefly compared with descriptions from other species. Counts of the numbers of motor axons in seven different muscles nerves have been made with the aid of acetylcholinesterase histochemistry to identify the motor component. The numbers of motor neuron somata labelled with horseradish peroxidase are on average 70% of the axon counts.


Sphingosine-1-Phosphate Receptor Modulator, FTY720, Improves Diastolic Dysfunction and Partially Reverses Atrial Remodeling in a Tm-E180G Mouse Model Linked to Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disorder, primarily involving mutations in sarcomeric proteins. HCM patients present with hypertrophy, diastolic dysfunction, and fibrosis, but there is no specific treatment. The sphingosine-1-phosphate receptor modulator, FTY720/fingolimod, is approved for treatment of multiple sclerosis. We hypothesize that modulation of the sphingosine-1-phosphate receptor by FTY720 would be of therapeutic benefit in sarcomere-linked HCM. We treated mice with an HCM-linked mutation in tropomyosin (Tm-E180G) and nontransgenic littermates with FTY720 or vehicle for 6 weeks. Compared with vehicle-treated, FTY720-treated Tm-E180G mice had a significant reduction in left atrial size (1.99±0.19 [n=7] versus 2.70±0.44 [n=6] mm; P<0.001) and improvement in diastolic function (E/A ratio: 2.69±0.38 [n=7] versus 5.34±1.19 [n=6]; P=0.004) as assessed by echocardiography. Pressure-volume relations revealed significant improvements in the end-diastolic pressure volume relationship, relaxation kinetics, preload recruitable stroke work, and ejection fraction. Detergent-extracted fiber bundles revealed a significant decrease in myofilament Ca2+-responsiveness (pCa50=6.15±0.11 [n=13] versus 6.24±0.06 [n=14]; P=0.041). We attributed these improvements to a downregulation of S-glutathionylation of cardiac myosin binding protein-C in FTY720-treated Tm-E180G mice and reduction in oxidative stress by downregulation of NADPH oxidases with no changes in fibrosis. This is the first demonstration that modulation of S1PR results in decreased myofilament-Ca2+-responsiveness and improved diastolic function in HCM. We associated these changes with decreased oxidative modification of myofilament proteins via downregulation of NOX2. Our data support the hypothesis that modification of sphingolipid signaling may be a novel therapeutic approach in HCM.


The influence of adenosine on intermediary metabolism of isolated hepatocytes.
The effect of adenosine was tested on the energetic metabolism of fed rat liver cells after isolation. The cells were incubated in a buffered saline medium with glucose (5 mM) and adenosine (1 mM) for 30 minutes at 37 degrees C. This increased the concentration of the adenylic nucleotides ATP (+57 per cent, ADP (+39 per cent). Cyclic AMP was increased (+50 per cent) and the intracellular inorganic phosphate decreased (-22 per cent). These changes were accompaned by a decrease of glycogenolysis, glucose consumption and lactate production. Measurement of glycolytic intermediates showed decreased concentrations of fructose 1,6-bis-phosphate and 3-phosphoglycerate proportional to the increase in ATP concentration. The near-equilibrium of the glyceraldehyde 3-phosphate dehydrogenase-phosphoglycerate kinase system was not modified by adenosine. The decrease of the NAD+/NADH ratio along with the increase of the ATP/ADP X PO4 ratio explains the decrease of 3-phosphoglycerate. The decrease in glucose consumption can be explained by the cross over at the phosphofructokinase stage with the decrease of fructose 1,6-bisphosphate. The major part of adenosine was deaminated as indicated by an increase in the production of ammonia and urea. The effects of inosine, or adenosine along with an inhibitor of adenosine deaminase (pentostatin) suggest that adenosine acts on the glucose consumption through adenylic nucleotides. However the increase of the adenylic nucleotide level cannot totally explain the other metabolic changes: decrease of the NAD+/NADH cytoplasmic ratio, constancy of this ratio in mitochondria, decrease of gluconeogenesis from lactate. A direct action of adenosine can therefore be expected.


[Effect of tetrandrine on bax, bcl-2 and TGF-β2 mRNA expressions in cultured human Tenon's capsule fibroblasts].
To investigate the effect of tetrandrine (Tet) on the expression of bax, bcl-2, and transforming growth factor-β2 (TGF-β2) mRNA in cultured human fibroblasts of Tenon's capsules (TCFS) and explore its possible mechanism. The third passage of TCFS cultured in vitro were exposed to 1×10(-5) mol/L Tet for 24 h, and real-time fluorescence quantitative PCR was used to detect the changes in the expressions of bax, bcl-2, and TGF-β2 mRNA. The expression level of bax mRNA was obviously higher, while bcl-2 and TGF-β2 mRNA levels were significantly lower in Tet-treated TCFS than those in the control cells (P<0.05). Tet can inhibit the proliferation of TCFS possibly by reducing the expressions of bcl-2 and TGF-β2 mRNA, enhancing the expression of bax mRNA and inducing cell apoptosis, suggesting its potential in preventing fibrous scar formation after glaucoma filtration surgery.


RRM1, ERCC1 and TS1 Immunofluorescence Expression in Leiomyosarcoma: A Tissue Microarray Study with Clinical Outcome Correlation Analysis.
ERCC1, RRM1 and TS1 are reportedly linked to chemotherapy resistance in lung and other cancers. However, there are currently no studies reporting the relationship between these genes and clinical parameters in leiomyosarcomas. This study investigated the expression pattern of ERCC1, RRM1 and TS1 in forty-four leiomyosarcoma samples by the use of tissue microarray (TMA), immunofluorescence and AQUA methods. The results were then analyzed for expression level and correlations were made with clinical outcome to determine their potential prognostic value in leiomyosarcoma. In the forty-four samples studied, the expression level of these three proteins can be well quantified in the AQUA system and reflected by the AQUA score. RRM1 and ERCC1 expression levels did not show any relationship with overall survival. However, a correlation was found between TS1 expression in the cytoplasm and overall survival. The high expression group had a shorter overall survival time (log-rank p = 0.0498). This trend was confirmed by the Cox proportional hazards model. The poor overall survival of leiomyosarcoma is linked to TS1 cytoplasm expression which may be useful in predicting prognoses of this tumor, methods targeting expression of TS1 may lead to improved overall survival in leiomyosarcoma, though more detailed information regarding treatment information and a larger sample size is needed to confirm this phenomenon.


Probable exclusion of juvenile neuronal ceroid lipofuscinosis in a fetus at risk: an interim report.
In a family with two children affected by juvenile neuronal ceroid lipofuscinosis (JNCL) an attempt was made at the prenatal diagnosis of the disorder. The following tissues from the fetus at risk were investigated by electron microscopy and were found to be free of fingerprint profiles and curvilinear bodies, typical for JNCL: uncultivated amniotic fluid cells, lymphocytes isolated from fetal blood, and fetal skin biopsy specimens. The child was born at the 34th week of gestation and was clinically normal at the age of 15 months. Postnatally, lymphocytes (isolated at the age of 6 and 15 months) and skin tissue (taken at the age of 15 months) were found to be morphologically normal. It is highly unlikely that the child is affected but definite proof of the absence of JNCL remains difficult at this age.


First Evaluations and Cryopreservation of Semen Samples from Sunda Clouded Leopards (Neofelis diardi).
A better understanding of semen characteristics and resilience to freezing temperatures is necessary before developing assisted reproductive techniques and systematic biobanking for the Sunda clouded leopard. The objective of this study was to evaluate for the first time the semen and sperm quality (in fresh and frozen samples) of two captive Sunda clouded leopards in Malaysia. A total of 17 examinations of the reproductive tract (using ultrasonography) and electro-ejaculations were performed on the two leopards over a 2-year period. Samples obtained from Leopard 1 (8 years old) varied in terms of volume (402 ± 92 µL), pH (7.9 ± 0.9), sperm motility (54.5 ± 24.2%), sperm concentration (122.4 ± 84.7 × 106 sperm/mL), normal morphology (23.9 ± 12.3%), and viability (55.2 ± 18.2%). Midpiece defects represented the most common structural abnormality followed by abnormal tail and head defects. Samples from Leopard 2 (11 year old with abnormal testicular tissue) were of lesser quality. Two frozen semen samples from Leopard 1 were thawed and examined for acrosome integrity. Post-thawed samples contained <10% of motile spermatozoa but almost 50% of abnormal acrosomes. The present results emphasized the high incidence of structurally-abnormal spermatozoa, similar to the mainland clouded leopard. Post-thaw evaluations showed that the few surviving spermatozoa could potentially be used for in vitro fertilization or sperm injection. However, more individuals must be studied to validate those first findings that are exciting but still preliminary.


Association of De Ritis ratio with oncological outcomes in patients with non-muscle invasive bladder cancer (NMIBC).
The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut-off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut-off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02-1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65-1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00-1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.


Immunochemical determinant of Candida parapsilosis.
Acetolysis of Candida parapsilosis cell-wall D-mannan, obtained by alkali extraction and purified as a copper complex, gave six oligosaccharides by Bio-Gel P-2 filtration. Their chemical structure was examined by 1H-n.m.r. spectroscopy, methylation analysis, and partial acid hydrolysis. The structures of the penta- and hexa-saccharide were alpha-D-Manp-(1 leads to 3)-alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 2)-D-Man (M5) and alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 3)-alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 2)-alpha-D-Manp-(1 leads to 2)-D-Man (M6), respectively. Inhibition of the oligosaccharides with anti-C. parapsilosis serum and homologous D-mannan indicated that although M5 and M6 exhibited strong inhibitory-activity, M6 was the more effective inhibitor, and suggested that M6 may be the immunodominant or may be responsible for the specificity of C. parapsilosis mannan in the precipitin-reaction system, or both.


Contrasting nutrient distributions during dry and rainy seasons in coastal waters of the southern Gulf of Mexico driven by the Grijalva-Usumacinta River discharges.
Globally, nutrient river discharges drive water quality of coastal ecosystems, and excess nutrients can cause eutrophication impacts. The Grijalva-Usumacinta River System (GURS) discharges in the southern Gulf of Mexico (SGoM) and it is the second largest riverine input to the Gulf. To study how contrasting GURS freshwater flow between rainy and dry seasons affects nutrients concentrations in the receiving coastal ecosystem, we evaluated nutrient variability in the water column during both seasons. High inorganic nutrients and total phosphate outline the rivers discharge plumes during rainy season, and were significantly higher than during the dry season throughout the study area, suggesting contrasting seasonal nutrient discharge of the GURS to coastal waters. On average the GURS discharged 141,123 t N yr-1 6893 t P yr-1 and 928,904 t Si yr-1 to SGoM. These results contribute with a nutrient baseline in the SGoM that could be useful for GURS decision-makers.


Dissociation between intracellular calcium mobilization and insulin secretion in isolated rat islets of Langerhans.
The neuropeptide bombesin provoked a dose-dependent stimulation of 45Ca2+ efflux from pre-loaded islets of Langerhans. This response occurred rapidly, was not sustained and did not depend on the presence of extracellular calcium, suggesting that it resulted from the mobilization of intracellular calcium stores. Under conditions when large increases in 45Ca2+ efflux were observed, bombesin completely failed to stimulate the rate of insulin secretion. Similar results were also obtained with the muscarinic cholinergic agonist, carbachol. The data suggest that the release of calcium from intracellular pools is not sufficient to induce an increase in insulin secretion in normal islet cells.


Serum cotinine as a marker of environmental tobacco smoke exposure in epidemiological studies: the experience of the MATISS project.
To describe serum cotinine levels in a rural Italian population and to examine its usefulness as an epidemiologic biomarker of nicotine exposure, cross-sectional data collected in 1993 for the MATISS Project (2098 men and 1352 women, aged 20-79 years) were used. The study population consisted of 977 current smokers, 882 nonsmokers reporting exposure to environmental tobacco smoke (ETS) and 1520 nonsmokers reporting no ETS exposure. Mean values of serum cotinine measured by radioimmunoassay for never smokers, ex-smokers and current smokers (including four categories of cigarette consumption), and for categories of ETS exposure in all nonsmokers were calculated. In univariate analysis, there was a positive association between self-reported nicotine exposure and serum cotinine levels in all groups. Using self-reported status as truth, sensitivity and specificity for various cotinine cutoff points were estimated to distinguish nonsmokers from smokers. The value of 15 ng/mL represented the best combined levels of sensitivity (95%) and specificity (96%). Using this cutoff point, the overall misclassification rate for self-reported nonsmokers was 2.1% and about two times greater for the more vs. the less educated. In multivariate analysis, reported ETS exposure among nonsmokers was significantly associated with serum cotinine even after adjusting for age, socio-demographic and behavioural factors, though the strength of the association was not strong. In conclusion, serum cotinine represents a reliable epidemiological marker of nicotine intake and may be helpful when studying ETS exposure. Improved information collection is needed to reduce misclassification among nonsmokers and enhance our understanding of the relationship between ETS and cotinine measures.


Radical excision of malignant sacral tumors using a modified threadwire saw.
Surgical treatment of malignant sacral tumors is difficult, and has a high rate of recurrence. The aim of this study was to examine the wide margin of large and small malignant sacral tumors using a threadwire saw (T-saw). We devised a flexible silver guide probe connected to a modified threadwire saw by a suture thread to perform osteotomies. We operated on 10 patients with sacral tumors using this device. The sacral excisions were performed via a posterior approach by four surgeons (two on each side) working simultaneously. We obtained a wide margin in all cases and no recurrence, after a mean follow-up of 4 years 2 months (range, 1 year 8 months-7 years 8 months). In one case, one nerve root on the right side was injured. Our new method is easier and faster than the conventional method in cases in which bilateral sacral nerve root canals require sectioning, and it produces a wide tumor margin.


Sociodemographic disparity in the nutritional status among children and adolescents in Zhejiang Province.
To explore the sociodemographic disparity in the nutritional status including BMI, vitamin D and vitamin A status among children and adolescents in Zhejiang Province. Weight, height serum 25-hydroxyvitamin D, and serum retinol were assessed in 2818 children and adolescents (6-17 years of age), using ten investigation sites in Zhejiang Province including urban and rural areas data from the China National Nutritional Study 2016-2017, which is a nationally representative cross-sectional study, to form provincial representative sample of Zhejiang Province. Sociodemographic disparity was explored. The prevalence of low weight, eutrophic, overweight and obese were 6.7%, 70.4%, 11.6%, and 11.2%, respectively. Significant difference was observed on BMI between males and females (P < 0.05), and between urban and rural areas (P < 0.05). The prevalence of vitamin D deficiency, inadequacy, normal and appropriate were 1.8%, 34.9%, 46.4% and 16.9%, respectively. Significant difference was observed on the concentration of 25-hydroxyvitamin D (25(OH)D) both between genders and between living areas (P < 0.05). The prevalence of vitamin A deficiency, marginal deficiency and appropriate were 4.5%, 24.7%, and 70.9%, respectively. Significant difference was observed on the concentration of retinol between living area (P < 0.05). Overweight and obesity, deficiency and inadequacy of vitamin D, deficiency and marginal deficiency of vitamin A were prevalent among children and adolescents. There were disparities between genders and between living areas on the nutritional status. Regional and sex-specific guidelines and public health policies for children and adolescent nutrition are needed.


Inhibitors for protein-tyrosine kinases, ST638 and genistein: induce differentiation of mouse erythroleukemia cells in a synergistic manner.
In order to investigate the biochemical nature of intracellular cascades leading to cellular differentiation in vitro, we examined the effect of inhibitors of protein phosphorylation on terminal erythroid differentiation of mouse erythroleukemia (MEL) cells. We have found that specific inhibitors of protein phosphorylation at tyrosine residues, ST638 and genistein, effectively induce differentiation in a synergistic manner with an agent which blocks DNA replication such as mitomycin C (MMC). Based upon these findings, the possible involvement of protein phosphorylation (and dephosphorylation) at tyrosine residues in differentiation is discussed.


Characteristics of fathers with depressive symptoms.
Extensive research shows maternal depression to be associated with poorer child outcomes, and characteristics of these mothers have been described. Recent research describes associations of paternal depressive symptoms and child behavioral and emotional outcomes, but characteristics of these fathers have not been investigated. This study describes characteristics of fathers with depressive symptoms in the USA. Utilizing data from 7,247 fathers and mothers living in households with children aged 5-17 years who participated in the Medical Expenditure Panel Survey 2004-2006, the Patient Health Questionnaire-2 was used to assess parental depressive symptoms, the Short Form-12 was used to examine paternal and maternal physical health, the Columbia Impairment Scale was used to measure child behavioral or emotional problems, and the Children with Special Health Care Needs Screener was used to identify children with special health care needs. In multivariate analyses, poverty (AOR 1.52; 95% CI 1.05-2.22), maternal depressive symptoms (AOR 5.77; 95% CI 4.18-7.95), living with a child with special health care needs (AOR 1.42, 95% CI 1.04-1.94), poor paternal physical health (AOR 3.31; 95% CI 2.50-4.38) and paternal unemployment (AOR 6.49; 95% CI 4.12-10.22) were independently associated with increased rates of paternal depressive symptoms. These are the first data that demonstrate that poverty, paternal physical health problems, having a child with special health care needs, maternal depressive symptoms, and paternal unemployment are independently associated with paternal depressive symptoms, with paternal unemployment associated with the highest rates of such problems.


Dynamic assessment of human sperm DNA damage II: the effect of sperm concentration adjustment during processing.
To evaluate the effect of sperm concentration adjustment in human ejaculates on the sperm DNA quality and longevity. Semen samples were obtained from 30 donors with a normal spermiogram. Following centrifugation, the sperm pellet was resuspended in PBS, and the sperm concentration adjusted to 200, 100, 50, 25, 12, and 6 × 106/mL. Each set of samples was incubated at 37 °C for 24 h, and the sperm DNA damage was assessed using the chromatin-dispersion test following 0 h, 2 h, 6 h, and 24 h of incubation. Sperm DNA fragmentation (SDF) did not differ between the selected experimental conditions at T0; however, Kaplan-Meier estimates for survival showed significant differences with respect to the dilution and time (all P values were smaller than .001). DNA fragmentation in semen samples adjusted to 200 × 106/mL was approximately 3.3 times higher when compared to samples containing 25 × 106/mL and 3.9 higher in comparison with samples adjusted to 12 × 106/mL following 2 h of in vitro incubation. Although there was evidence of individual variation in SDF during the incubation period, the general finding was that lower sperm concentrations resulted in a slower rate of DNA fragmentation. Incubation of spermatozoa for ART purposes should be done following a concentration adjustment below 25 × 106/mL in order to avoid a higher susceptibility of the sperm DNA molecule towards fragmentation.


MicroRNA-191, acting via the IRS-1/Akt signaling pathway, is involved in the hepatic insulin resistance induced by cigarette smoke extract.
Cigarette smoke causes insulin resistance, which is associated with type 2 diabetes mellitus (T2DM). However, the mechanism by which this occurs remains poorly understood. Because the involvement of microRNAs (miRNAs) in the development of insulin resistance is largely unknown, we investigated, in hepatocytes, the roles of miR-191 in cigarette smoke extract (CSE)-induced insulin resistance. In L-02 cells, CSE not only decreased glucose uptake and glycogen levels but also reduced levels of insulin receptor substrate-1 (IRS-1) and Akt activation, effects that were blocked by SC79, an activator of Akt. CSE also increased miR-191 levels in L-02 cells. Furthermore, the inhibition of miR-191 blocked the decreases of IRS-1 and p-Akt levels, which antagonized the decreases of glucose uptake and glycogen levels in L-02 cells induced by CSE. These results reveal a mechanism by which miR-191 is involved in CSE-induced hepatic insulin resistance via the IRS-1/Akt signaling pathway, which helps to elucidate the mechanism for cigarette smoke-induced T2DM.


Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.
Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far. In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.


Aerosol jet printing polymer dispersed liquid crystals on highly curved optical surfaces and edges.
We demonstrate a new technique for producing Polymer Dispersed Liquid Crystal (PDLC) devices utilising aerosol jet printing (AJP). PDLCs require two substrates to act as scaffold for the Indium Tin Oxide electrodes, which restricts the device geometries. Our approach precludes the requirement for the second substrate by printing the electrode directly onto the surface of the PDLC, which is also printed. The process has the potential to be precursory to the implementation of non-contact printing techniques for a variety of liquid crystal-based devices on non-planar substrates. We report the demonstration of direct deposition of PDLC films onto non-planar optical surfaces, including a functional device printed over the 90° edge of a prism. Scanning Electron Microscopy is used to inspect surface features of the polymer electrodes and the liquid crystal domains in the host polymer. The minimum relaxation time of the PDLC was measured at 1.3 ms with an 800 Hz, 90 V, peak-to-peak (Vpp) applied AC field. Cross-polarised transmission is reduced by up to a factor of 3.9. A transparent/scattering contrast ratio of 1.4 is reported between 0 and 140 V at 100 Hz.


Increasing incidence of inflammatory bowel disease among young men in Korea between 2003 and 2008.
Temporal trends in incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) can provide valuable clues about etiology. Korea has a draft system, and every male must fulfill his military service. However, according to military rules, patients with CD and UC are not conscripted into the army, and when the disease is diagnosed during military service, patients are relieved from military duties. Such policies provide a unique opportunity to determine the incidence of CD and UC among young men in Korea. We studied the incidence of CD and UC over time in Korea, a rapidly developing country. The Armed Forces Medical Command of the Republic of Korea Army provided lists of members who were relieved from military duties due to diagnoses of CD and UC between 2003 and 2008. During this 6-year period, there were 96 incident cases of CD and 104 incident cases of UC. For the 6-year period, the adjusted mean annual incidence rates of CD and UC per 100,000 persons were 3.2 and 3.5, respectively. When analyzed by 2-year intervals, the mean annual incidence of CD and UC increased, from 1.8 and 1.7 per 100,000 persons in 2003-2004, to 2.7 and 3.3 per 100,000 persons in 2005-2006, and to 5.1 and 5.4 per 100,000 persons in 2007-2008, respectively. Incidence of CD and UC among young men is rapidly increasing in Korea, which strongly suggests an environmental contribution to the disease.


Geography and host biogeography matter for understanding the phylogeography of a parasite.
The co-evolution between hosts and parasites has long been recognized as a fundamental driver of macro-evolutionary patterns of diversification. The effect of co-differentiation on parasite diversification is, however, often confounded by underlying geographic patterns of host distribution. In order to disentangle the confounding effects of allopatric versus host speciation, the mitochondrial cytochrome b (cyt b) gene was sequenced in seventy individuals of the parasitic nematode genus Heligmosomoides sampled in the six Apodemus mice species common in the western Palearctic region. The nuclear internal transcribed spacers (ITS) 1 and 2 were also sequenced in fifteen parasites to confirm the mitochondrial data. All lineages differentiated according to a geographic pattern and independently from the sampled host species. This suggests that host speciation did not involve concurrent parasite speciation. However, the geographic distribution range of some parasite lineages mirrors that of A. sylvaticus lineages in SW Europe, and that of A. flavicollis lineages in the Balkans and in the Middle East. Thus, regional co-differentiation likely occurred between the parasite and the two sister Apodemus hosts in different parts of their distribution range. We suggest that differences in regional abundances of A. sylvaticus and A. flavicollis are responsible for generating this pattern of regional co-differentiation. This study highlights the importance of integrating both geography and biogeographic information from potential hosts to better understand their parasite phylogeography.


Beta-analogs of PLG (L-prolyl-L-leucyl-glycinamide): ex-chiral pool syntheses and dopamine D2 receptor modulating effects.
Starting from (S)- and (R)-aspartic acid enantiomerically pure beta-proline derivatives were synthesized. These chiral building blocks were transformed into beta-analogs of the dopamine receptor modulating peptide PLG. According to dopamine receptor binding studies, significant enhancement of [3H]pramipexole binding was observed for the isomeres 1a,b and 2a-c. The derivative 1b revealed an activity comparable to PLG.


Early contrast enhancement of acoustic neuroma.
The changes of the enhancement of the lesion with time after intravenous administration of contrast medium were measured with computed tomography (CT) in 23 cases of acoustic neuroma. The pattern of high initial enhancement followed by a fairly rapid decrease is confirmed. A more rigorous study of the enhancement pattern using a mathematical description of the enhancement curve of the tumor as well as a measurement of the individual blood enhancement curve is discussed.


Meta-analysis of pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy.
Pancreaticoduodenectomy is the primary treatment for periampullary cancer. Associated morbidity is high and often related to pancreatic anastomotic failure. This paper compares rates of pancreatic fistula, morbidity and mortality after pancreaticoduodenectomy in patients having reconstruction by pancreaticogastrostomy with those in patients having reconstruction by pancreaticojejunostomy. A meta-analysis was performed of all large cohort and randomized controlled trials carried out since 1990. Eleven articles were identified for inclusion: one prospective randomized trial, two non-randomized prospective trials and eight observational cohort studies. The meta-analysis revealed a higher rate of pancreatic fistula associated with pancreaticojejunostomy reconstruction (relative risk (RR) 2.62 (95 per cent confidence interval (c.i.) 1.91 to 3.60)). A higher overall morbidity rate was also demonstrated in this group (RR 1.43 (95 per cent c.i. 1.26 to 1.61)), as was a higher mortality rate (RR 2.51 (95 per cent c.i. 1.61 to 3.91)). Current literature suggests that the safer means of pancreatic reconstruction after pancreaticoduodenectomy is pancreaticogastrostomy, but much of the evidence comes from observational cohort study data.


Preparation of aloe polysaccharide/honey/PVA composite hydrogel: Antibacterial activity and promoting wound healing.
Maintaining a moist and sterile environment is conducive to accelerating wound healing. To develop a natural wound dressing with good water retention capacity and antibacterial activity, we prepared a novel natural multifunctional hydrogel for infected wound healing, which combines the advantages of Aloe polysaccharide (AP) and honey. AP was extracted from Aloe barbadensis, and its structure was characterized by fourier transform infra-red (FT-IR) spectoscopy and nuclear magnetic resonance (NMR) spectroscopy. AP is an acetylated mannan composed of (1 → 4)β-Manp, which is acetylated at C-2, C-3 and C-6 positions. AP/Honey@PVA hydrogel was prepared by cross-linking AP, honey, PVA with borax, which has good mechanical strength and excellent biocompatibility for blood cells, NIH-3T3 cells and L929 cells. The hydrogels showed significant inhibitory effect on Staphylococcus aureus, Escherichia coli and Candida albicans, as well as accelerated the healing of infected full-thickness wound. This study reveals the structure of AP and proves that AP and honey composite hydrogel has potential application prospect in the therapy of infected wounds.


Detection of electrostatic molecular binding using the water proton signal.
Saturation transfer MRI has previously been used to probe molecular binding interactions with signal enhancement via the water signal. Here, we detail the relayed nuclear overhauser effect (rNOE) based mechanisms of this signal enhancement, develop a strategy of quantifying molecular binding affinity, i.e., the dissociation constant ( KD$$ {K}_D $$ ), and apply the method to detect electrostatic binding of several charged small biomolecules. Another goal was to estimate the detection limit for transient receptor-substrate binding. The signal enhancement mechanism was quantitatively described by a three-step magnetization transfer model, and numerical simulations were performed to verify this theory. The binding equilibria of arginine, choline, and acetyl-choline to anionic resin were studied as a function of ligand concentration, pH, and salt content. Equilibrium dissociation constants ( KD$$ {K}_D $$ ) were determined by fitting the multiple concentration data. The numerical simulations indicate that the signal enhancement is sufficient to detect the molecular binding of sub-millimolar (∼100 μM) concentration ligands to low micromolar levels of molecular targets. The measured rNOE signals from arginine, choline, and acetyl-choline binding experiments show that several magnetization transfer pathways (intra-ligand rNOEs and intermolecular rNOEs) can contribute. The rNOEs that arise from molecular ionic binding were influenced by pH and salt concentration. The molecular binding strengths in terms of KD$$ {K}_{\mathrm{D}} $$ ranged from 70-160 mM for the three cations studied. The capability to use MRI to detect the transient binding of small substrates paves a pathway towards the detection of micromolar level receptor-substrate binding in vivo.


Catalytic oxidation of acetaminophen by tyrosinase in the presence of L-proline: a kinetic study.
A kinetic study of acetaminophen oxidation by tyrosinase in the presence of a physiological nucleophilic agent such as the amino acid L-proline is performed in the present paper. The o-quinone product of the catalytic activity, 4-acetamido-o-benzoquinone, becomes unstable through the chemical addition of L-proline, in competition with the nucleophilic addition of hydroxide ion from water. In both cases, the catechol intermediate, 3(')-hydroxyacetaminophen, is generated, as can be demonstrated by liquid chromatography. When the effect of the presence of the nucleophilic agent on the time course of the enzymatic reaction was kinetically analyzed, it was seen to decrease the duration of the lag period and increase the steady-state rate. Rate constants for the reaction of 4-acetamido-o-benzoquinone with water and L-proline were also determined. The results obtained in this paper open a new possibility to acetaminophen toxicity, that has been attributed hitherto to its corresponding p-quinone, N-acetyl-p-benzoquinone imine.


Synthesis of oxidized β-cyclodextrin with high aqueous solubility and broad-spectrum antimicrobial activity.
Oxidized β-cyclodextrins with different oxidation levels were prepared using hydrogen peroxide as the oxidant and copper sulfate as the catalyst. The physicochemical, antimicrobial and antifungal properties of oxidized β-cyclodextrin were systematically studied. The results showed that the oxidation level of oxidized β-cyclodextrin was successfully controlled by adjusting the dosage of hydrogen peroxide. The aqueous solubility of oxidized β-cyclodextrin was highly improved as expected. However, oxidation changed the morphology and partly reduced the crystallinity of oxidized β-cyclodextrin due to the introduced carbonyl and carboxyl groups. It is interesting that oxidized β-cyclodextrin presented a broad-spectrum antimicrobial activity, which was efficiently improved with the increasing oxidation level. Growth of A. niger spores was efficiently inhibited in the presence of oxidized β-cyclodextrin. Moreover, oxidized β-cyclodextrin could effectively extend the storage time of apple. In summary, oxidized β-cyclodextrin shows potential as antimicrobial and antifungal agents in food industry.


Effects of Brazilin on the phospholipase A2 activity and changes of intracellular free calcium concentration in rat platelets.
Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6 H)-tetrol) inhibited thrombin-,collagen- and ADP-induced aggregation of washed rat platelets. Thrombin- and collagen-induced ATP release were also inhibited by brazilin in a concentration-dependent manner. Brazilin inhibited the formation of platelet thromboxane A2 caused by thrombin, whereas it had no effect on the prostaglandin D2 formation. Brazilin inhibited [3H]-arachidonic acid liberation from membrane phospholipids of thrombin-stimulated platelets. Brazilin inhibited the rise of intracellular free calcium caused by thrombin. These results indicate that the inhibition of phospholipase (PLA2) activity and [Ca2+]i elevation might be at least a part of antiplatelet mechanism of brazilin.


Is it necessary to close the peritoneum over the deep inguinal ring during laparoscopic orchidopexy?
During laparoscopic orchidopexy, some authors routinely close the peritoneum over the area of the deep inguinal ring (DIR). We report our experience, to determine whether leaving the peritoneum over the DIR without closure is associated with an increase in the occurrence of postoperative inguinal hernia. This is a retrospective review of patients who underwent laparoscopy for impalpable testes in 2004-2010. The patients were divided into two groups: I) cases in whom the peritoneum over the DIR was routinely closed, and II) cases in whom the DIR was left without closure. The patients were followed up in the outpatient clinic. During the study period, 442 boys underwent laparoscopy for 570 impalpable testes. The testis was found to be 'vanishing' or 'atrophic' in 182 (32%). The mobilized testis passed through the anatomical DIR in 198 (51%), and through a new deep ring in 190 (49%). The DIR was closed (I) in 178 (46%) and left open (II) in 210 (54%) cases. On follow up (mean 50 months for I and 41 months for II), there were no cases of inguinal hernia. Closing the peritoneum over the area of the DIR may not be necessary, even in cases where the testis has to be passed through a medially created new deep ring, because of a short cord.


Fusion glycoprotein (F) of rinderpest virus: entire nucleotide sequence of the F mRNA, and several features of the F protein.
The full-length cDNA corresponding to the mRNA for the fusion protein of rinderpest virus (RV) was cloned and its complete nucleotide sequence was determined. The mRNA for the F protein was composed of 2359 nucleotides and contained a single large open reading frame which was capable of encoding 566 amino acids with a molecular weight (MW) of 58,929. The RV-F mRNA had a long noncoding region at the 5' end (586 bases) which was C-rich like the measles virus (MV)-F mRNA but they did not appear to be homologous with each other. Their secondary structure with long G-C stems suggested that they are easily folded. The coding region of RV-F mRNA was significantly homologous with that of MV-F; 74% of the nucleotides and 79.0% [corrected] of the amino acids were identical. The predicted RV-F protein had a basic amino acid region (104-108) which may be cleaved by protease to yield an activated form of F1,2. Three regions (1-19, 109-133, 418-513) were highly hydrophobic, and the N-terminal hydrophobic region of F1 or the positions of cysteines were significantly conserved compared with those of the other paramyxovirus F proteins. Three potential sites for glycosylation existed only in the F2 protein. Several features of the predicted RV-F protein were confirmed in polyacrylamide gel electrophoresis.


A comparison of vascularized and conventional sural nerve grafts.
Long-term results of a randomized series of 27 vascularized and 22 conventional sural nerve grafts in patients with comparable upper extremity injuries are reported. Recovery speed and outcome depended on (1) whether or not there was an overlying skin defect, (2) how the defect was closed, and (3) which nerve was injured and at what level. Generally, a vascularized nerve graft is indicated when the nerve gap is more than 6 cm and is associated with a massive skin defect or the graft is performed after reimplantation. Otherwise, results achieved with a conventional graft are equally good.


Reliability of individual acceleration-speed profile in-situ in elite youth soccer players.
The aims of this study were to describe differences in the acceleration-speed (A-S) profile in-situ and to assess the week-to-week reliability of the A-S profile in-situ over a given training cycle of elite youth soccer players, in relation to the number of sessions included and analyse the effect of the inclusion or not of a specific sprint session. In this retrospective study, 18 male elite U19 football players (179.4 ± 7.1 cm; 69.0 ± 9.5 kg) participated. GPS data collected from three consecutive typical training weeks were used to calculate different combinations of A-S profile in-situ variables (theoretical maximal acceleration [A0], theoretical maximal speed [S0] and the slope of the acceleration-speed [ASslope]). The number (and content) of sessions affected mainly S0 while A0 remained similar with or without a sprint session. The reliability of the A-S profile in-situ is more related to the spread of points rather than a specific number of sessions (and thus points) and was improved when a high percentage of maximum speed (i.e. ≥ 95%) was reached. The present study showed low week-to-week variability for A0, S0 and ASslope. However, practitioners need to make sure that the values cover a sufficient range of raw data [20-95% of maximum speed] to build a clear and consistent linear regression, and in turn extrapolate meaningful A-S profile values.


Effects of nocturnal intraperitoneal administration of cholecystokinin in rats: simultaneous increase in sleep, increase in EEG slow-wave activity, reduction of motor activity, suppression of eating, and decrease in brain temperature.
Rats received an i.p. injection of cholecystokinin-octapeptide sulfate ester (CCK; 4, 10 or 50 micrograms/kg) or physiological saline at dark onset, and the 24-h sleep-wake cycle (12-h-dark and 12-h-light phases), spontaneous motor activity and brain temperature (Tbr) were recorded. EEG activity was studied through spectral analysis for 2.5 h, and food intake was measured at the end of postinjection hour 1. In response to CCK, non-REM sleep increased at the expense of wakefulness, and the sleep-promoting effect was substantiated by an increase in EEG slow-wave activity. Motor activity, Tbr and food intake decreased. The effects vanished in postinjection hour 2; the diurnal rhythms were not modified. The changes varied as a function of the dose: the effects were significant following 10 micrograms/kg, and even higher in response to 50 micrograms/kg CCK. The results indicate that i.p. CCK definitely promotes non-REM sleep. This effect may belong to the behavioral sequence elicited by the peptide, which is often attributed to satiety. As evidenced by the reduction of Tbr, CCK also exerts strong autonomic actions, which might interfere with the behavioral responses.


Canadian general surgeons' opinions about clinical practice audit.
The objective of this study was to explore the opinions of Canadian surgeons about their knowledge regarding clinical practice audit (CPA), existing audit tools, experience with CPA, barriers to implementation, and concerns about consequences of CPA implementation. A 20-question survey was distributed to members of the Canadian Association of General Surgeons. Of the surveys distributed, 108 were completed, a response rate of 13.5%. The mean age of the participants was 44 years (SD, 12). Familiarity with common audit tools ranged from 4% to 28%, with 41% familiar with none and 44% having previously performed CPA. Most respondents believed that CPA should be mandatory (48%); that CPA is best done by self (34%); and that the Ministry of Health ought to pay for CPA (35%). Using a Likert scale, we found that a majority of respondents felt that CPA is effective in changing both clinical practice (73%) and patient outcomes (57%) and that barriers included time constraints (91%), cost (62%), resources (91%), and inadequate documentation (57%). A majority of respondents would participate in CPA if the data were reviewed by themselves (93%), their department (82%), the Royal College (51%), or provincial organizations (48%) as long as the data were not made available to the public (42%), the ministry of health (48%), or hospital administration (47%). Canadian surgeons perceive usefulness in clinical audit but have limited knowledge about available audit tools and resources. The creation of a national auditing system combined with strategies for effective implementation of this system is the stepping-stone in this process.


[Problems in drug prescribing. Structure of the prescription for individually prepared drugs].
The authors give an account of the structure of different drug forms within the framework of individually prepared drugs based on an analysis of 7862 prescriptions made in 1985. They analyze the structure in relation to the territory and type of pharmacies. Ointments were most frequent by prescribed (31.6%), followed by solutions for external use.


Sensors for the quantification, localization and analysis of the dynamics of plant hormones.
Plant hormones play important roles in plant growth and development and physiology, and in acclimation to environmental changes. The hormone signaling networks are highly complex and interconnected. It is thus important to not only know where the hormones are produced, how they are transported and how and where they are perceived, but also to monitor their distribution quantitatively, ideally in a non-invasive manner. Here we summarize the diverse set of tools available for quantifying and visualizing hormone distribution and dynamics. We provide an overview over the tools that are currently available, including transcriptional reporters, degradation sensors, and luciferase and fluorescent sensors, and compare the tools and their suitability for different purposes.


Coding of tone-pulse amplitude by single neurons in auditory cortex of albino rats (Rattus norvegicus).
We examined the neural representation of tone pulse amplitude in the auditory cortex of anesthetized albino rats. Rate-level functions for monaural, contralateral CF tones were obtained from single neurons. Most of these functions were saturating and monotonic in shape. The dynamic ranges of these functions were typically 5 to 35 dB in breadth, although the tail of this distribution extended to beyond 60 dB. The neurons with the widest dynamic ranges were usually those with the lowest CF thresholds. Nonmonotonic neurons were uncommon, and the nonmonotonicity was not as well developed as that seen in the cortex of cats and monkeys. For two individual rats, data are presented for neurons tuned to the same tone frequency in a single cerebral hemisphere. The CF thresholds of these neurons varied over a 50 dB range, and their collective dynamic ranges spanned at least 70 dB. These data provide a minimum estimate of the dynamic range of the cortical code for tone pulse amplitude in the rat. They suggest that there may be no serious mismatch between the neural and behavioral amplitude dynamic ranges.


Mechanism of microbial production of acetoin and 2,3-butanediol optical isomers and substrate specificity of butanediol dehydrogenase.
3-Hydroxybutanone (Acetoin, AC) and 2,3-butanediol (BD) are two essential four-carbon platform compounds with numerous pharmaceutical and chemical synthesis applications. AC and BD have two and three stereoisomers, respectively, while the application of the single isomer product in chemical synthesis is superior. AC and BD are glucose overflow metabolites produced by biological fermentation from a variety of microorganisms. However, the AC or BD produced by microorganisms using glucose is typically a mixture of various stereoisomers. This was discovered to be due to the simultaneous presence of multiple butanediol dehydrogenases (BDHs) in microorganisms, and AC and BD can be interconverted under BDH catalysis. In this paper, beginning with the synthesis pathways of microbial AC and BD, we review in detail the studies on the formation mechanisms of different stereoisomers of AC and BD, summarize the properties of different types of BDH that have been tabulated, and analyze the structural characteristics and affinities of different types of BDH by comparing them using literature and biological database data. Using microorganisms, recent research on the production of optically pure AC or BD was also reviewed. Limiting factors and possible solutions for chiral AC and BD production are discussed.


[Depressive symptoms in elderly persons: comparison between rural and urban populations].
The aim of this article is to compare the prevalence of depressive symptoms and its correlates in an urban and a rural sample of 2797 persons of age 65 and over living in Southwest France. The crude prevalence rate of elevated depressive symptomatology, evaluated by the Center of Epidemiological Studies Depression (CESD) scale was 14.1% and 13.9% respectively in the rural and the urban area. After adjusting for potential confounders, the risk of elevated depressive symptoms is slightly higher in the urban area (p = 0.09). Factors found to be associated with the level of depression are the same in the rural and the urban area, and the magnitude of the effects is comparable. These results are compared with those of other studies and the observed differences are discussed.


Rh(III)-Catalyzed C-H Activation/Cycloisomerization of N-Phenoxyacetamides with Enynones for One-Pot Assembly of Furylated 2-Alkenylphenols.
An efficient and practical procedure for one-pot assembly of furylated 2-alkenylphenols has been achieved via the Cp*CyRh-catalyzed regioselective redox-neutral C-H activation/5-exo-dig cyclization cascade using N-phenoxyacetamides and enynones as the viable substrates. The synthetic application of such a protocol has also been demonstrated to highlight the versatility of this transformation.


Investigating the molecular basis of multiple insecticide resistance in a major malaria vector Anopheles funestus (sensu stricto) from Akaka-Remo, Ogun State, Nigeria.
Understanding the mechanisms used by Anopheles mosquitoes to survive insecticide exposure is key to manage existing insecticide resistance and develop more suitable insecticide-based malaria vector control interventions as well as other alternative integrated tools. To this regard, the molecular basis of permethrin, DDT and dieldrin resistance in Anopheles funestus (sensu stricto) at Akaka-Remo was investigated. Bioassays were conducted on 3-5-day-old adult An. funestus (s.s.) mosquitoes for permethrin, DDT and dieldrin susceptibility test. The molecular mechanisms of mosquito resistance to these insecticides were investigated using microarray and reverse transcriptase PCR techniques. The voltage-gated sodium channel region of mosquitoes was also screened for the presence of knockdown resistance mutations (kdr west and east) by sequencing method. Anopheles funestus (s.s.) population was resistant to permethrin (mortality rate of 68%), DDT (mortality rate of 10%) and dieldrin (mortality rate of 8%) insecticides. Microarray and RT-PCR analyses revealed the overexpression of glutathione S-transferase genes, cytochrome P450s, esterase, trypsin and cuticle proteins in resistant mosquitoes compared to control. The GSTe2 was the most upregulated detoxification gene in permethrin-resistant (FC = 44.89), DDT-resistant (FC = 57.39) and dieldrin-resistant (FC = 41.10) mosquitoes compared to control population (FC = 22.34). The cytochrome P450 gene, CYP6P9b was also upregulated in both permethrin- and DDT-resistant mosquitoes. The digestive enzyme, trypsin (hydrolytic processes) and the cuticle proteins (inducing cuticle thickening leading to reduced insecticides penetration) also showed high involvement in insecticide resistance, through their overexpression in resistant mosquitoes compared to control. The kdr east and west were absent in all mosquitoes analysed, suggesting their non-involvement in the observed mosquito resistance. The upregulation of metabolic genes, especially the GSTe2 and trypsin, as well as the cuticle proteins is driving insecticide resistance of An. funestus (s.s.) population. However, additional molecular analyses, including functional metabolic assays of these genes as well as screening for a possible higher cuticular hydrocarbon and lipid contents, and increased procuticle thickness in resistant mosquitoes are needed to further describe their distinct roles in mosquito resistance.


The Intergenerational Cycle of Obesity and Its Implications for Nursing Care of Childbearing Women.
Despite intensive focus and interventions at societal and individual levels, more than a third of people in the United States are overweight or obese, and childhood/adolescent obesity rates have dramatically increased during the past three decades. Biomedical research has shown a clear link between the prenatal environment and lifetime adiposity. Children born to overweight and obese women with impaired glucose metabolism show cardiometabolic consequences throughout their life spans that, in turn, affect their children's adiposity. Awareness of this intergenerational cycle of obesity can prompt nurses to intervene in the preconception, prenatal, and postnatal phases.


89Zr-Onartuzumab PET imaging of c-MET receptor dynamics.
c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of 89Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent 89Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent 89Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, 89Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that 89Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status.


Botryoid odontogenic cyst: report of a case with extensive epithelial proliferation.
Botyroid odontogenic cyst (BOC) is considered a rare multilocular variant of the lateral periodontal cyst. In this report; clinical and histopathological features of a case of BOC found in mandibular mental region of a 32-year-old woman is presented. There was a multilocular radiolucency extending from the roots of the right premolar to the left premolar, involving almost the whole height of the mandible. Histologically, there was extensive intraluminal epithelial proliferation in the lining and MIB-1 positive cells were noted in the basal layer.


Sair teeth-the hell o'a' diseases.
A discussion of a poem about toothache, written in Scots and published in 1917 and a comparing it to Robert Burns' Address to the Toothache.


[Immune response of donors during immunization with staphylococcus anatoxin].
The content of antistaphylococcal antitoxins--antialphastaphylolysins was examined in the blood serum of three groups of blood donor volunteers. It is shown that volunteer blood donors immunized according to two schemes with prophylactic purposes may be a source of antistaphylococcal plasma. Additionally antistaphylococcal plasma may be obtained from non-immune donors showing high titers of antialphastaphylolysins revealed by the screening method.


Lipid Profile in Children With Thalassemia: A Prospective Observational Study From Eastern India.
This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients.


Resistance and growth of Fusarium species in contact lens disinfectant solutions.
To compare the biocidal efficacy of contact lens care solutions against clinical isolates and the American Type Culture Collection (ATCC) 36031 reference strain of Fusarium species and to determine the ability of the organism to survive and grow in such systems. The ISO 14729 reference method to assess biocidal efficacy was applied to the purified conidial form of 10 strains of Fusarium species. Six multipurpose disinfectant solutions (MPDSs), a one-step hydrogen peroxide (Per-1) system, a hydrogen peroxide-sodium chlorite (Per-2) system, and a one-step povidone iodine (PI) system were compared. Challenge organism viability was determined at various intervals, including the manufacturers' recommended disinfection time for the products (4 to 6 hours) and thereafter to 21 days. All MPDSs achieved a 3- to 4-log10 reduction in viability of ATCC 36031 within the recommended disinfection time of 6 hours. For the clinical strains, MPDS-1 (PQ-1 + alexidine) and MPDS-2 (PQ-1 + PHMB) produced 3 to 5 log₁₀ kill after 6 hours. Multipurpose disinfectant solution 3 (PQ-1 + Aldox 0.0006%), MPDS-4 (PQ-1 + Aldox 0.0005% + C-9 ED3A), and MPDS-5 (PQ-1 + Aldox 0.0005%) showed reduced efficacy for the same two strains, with 0.6 to 1.7 log₁₀ kill. Multipurpose disinfectant solution 6 (PHMB) gave 1.6 log₁₀ for one strain and 3 to 4 log₁₀ for the remainder. Growth in all the MPDS was not detected up to 21 days incubation. Per-1 showed less than 1 log₁₀ kill at 6 hours for six of 10 strains, including ATCC 36031, and growth (1.2 to 2.7 log₁₀) occurred with three of 10 strains by 7 days. Per-2 gave less than or equal to 0.5 log₁₀ kill after 6- or 24-hour exposure without growth. The PI system showed 4 to 5 log₁₀ kill for all strains tested by the first time point of 4 hours. However, with the exception of ATCC 36031, growth (1.7 to 4.0 log₁₀) occurred with all strains by 7 days in PI. All MPDSs were effective against the ATCC 36031 reference strain of Fusarium solani. However, reduced efficacy was found for some MPDSs against the clinical isolates. Unlike MPDSs, peroxide- and povidone iodine-based systems have no continued antimicrobial presence once neutralized, and this can allow growth of surviving Fusarium in the solution. Accordingly, lenses should be subject to fresh disinfection if stored in such solutions for extended periods.


Association of the HtrA1 rs11200638 Polymorphism with Neovascular Age-Related Macular Degeneration in Indonesia.
The aim of this study was to investigate the association of the HtrA1 rs11200638 polymorphism with neovascular age-related macular degeneration (nAMD) in Indonesia. This case-control study included 80 patients with nAMD and 85 controls. Demographic parameters and whole blood were collected from each participant. Genomic DNA was extracted and used to assess the rs11200638 genotype by PCR and restriction enzyme digestion. Associations between the HtrA1 rs11200638 polymorphism and other risk factors for susceptibility to nAMD were assessed using the logistic regression model. Significant allelic associations between the HtrA1 polymorphism and nAMD were detected (odds ratio [OR] 8.67; 95% confidence interval [CI] 4.88-15.41; P < 0.001). Genotype analysis showed a statistical difference between the nAMD group and the control group (P < 0.001). In the multiple adjusted logistic regression model, people with the AA genotype were more likely to have nAMD although there was a wide confidence interval (OR 19.65; 95% CI 4.52-85.38; P < 0.001). Our findings show that the risk of nAMD increased in the presence of risk alleles of HtrA1 rs11200638.


Gene expression of different adipose tissues of severely obese women with or without a dysmetabolic profile.
Despite well-established variations in the health risks posed by visceral vs. subcutaneous abdominal (SCABD) fat depots, surprisingly little is known on the differences within a given adipose tissue (AT) among severely obese patients displaying varying metabolic dysfunction. We thus compared, by quantitative PCR, the expression profile of a number of genes in the SCABD, omental (OME), and mesenteric (MES) depots of severely obese women with (DYS; n = 25) or without (NDYS; n = 23) a dysmetabolic profile. Fasting insulinemia and HOmeostasis Model Assessment-insulin resistance (HOMA-IR) were higher and plasma adiponectin level lower in DYS women (p < 0.05). Among enzymes involved in fatty acid metabolism and local cortisol production, phosphodiesterase-3B expression was lower in SCABD and MES fat, while 11β-hydroxysteroid dehydrogenase type 1 mRNA levels were higher in visceral depots of DYS women (p < 0.05). Regarding vascular homeostasis and inflammation, plasminogen activator inhibitor-1 and interleukin-6 mRNA levels were higher in OME fat, while adiponectin expression was lower in SCABD and OME ATs of DYS women (p < 0.05). Finally, HOMA-IR was positively associated with SCABD AT IL6 mRNA, only in DYS women (r = 0.47; p < 0.05). In conclusion, although metabolic and secretory characteristics of all depots vary with subjects' metabolic profile, we find little evidence for a protective role of SCABD AT and no evidence for a further deleterious role of MES fat in DYS vs. NDYS severely obese women. Regional variation in the overall gene expression revealed that OME and MES fat were more closely related to each other in DYS women, while SCABD and MES depots showed greater resemblance in NDYS women.


Numerical deconvolution to enhance sharpness and contrast of portal images for radiotherapy patient positioning verification.
The quality of megavoltage clinical portal images is impaired by physical and geometrical effects. This image blurring can be corrected by a fast numerical two-dimensional (2D) deconvolution algorithm implemented in the electronic portal image device. We present some clinical examples of deconvolved portal images and evaluate the clinical advantages achieved by the improved sharpness and contrast. The principle of numerical 2D image deconvolution and the enhancement of sharpness and contrast thereby achieved are shortly explained. The key concept is the convolution kernel K(x,y), the mathematical equivalent of the smearing or blurring of a picture, and the computer-based elimination of this influence. Enhancements of sharpness and contrast were observed in all clinical portal images investigated. The images of fine bone structures were restored. The identification of organ boundaries and anatomical landmarks was improved, thereby permitting a more accurate comparison with the x-ray simulator radiographs. The visibility of prostate gold markers is also shown to be enhanced by deconvolution. The blurring effects of clinical portal images were eliminated by a numerical deconvolution algorithm that leads to better image sharpness and contrast. The fast algorithm permits the image blurring correction to be performed in real time, so that patient positioning verification with increased accuracy can be achieved in clinical practice.


Analysis of proteins by agarose native gel electrophoresis in the presence of solvent additives.
Solvent additives, including NaCl, arginine hydrochloride (ArgHCl), glycine and sucrose, are used to enhance protein stability or reduce protein aggregation. Here, we studied the effects of these additives on proteins using agarose native gel electrophoresis. Since these additives are used at relatively high concentration, we first confirmed that they do not interfere with the performance of the native gel electrophoresis. Agarose native gel electrophoresis showed that aggregation of bovine serum albumin (BSA) induced by heating was slightly reduced by NaCl and ArgHCl. On the contrary, glycine and sucrose had marginal effects. ArgHCl and NaCl promoted heat aggregation of monoclonal antibody (mAb), while glycine and sucrose stabilized the native mAb. Arginine methyl ester inhibited heat aggregation of lysozyme and, to a much lesser extent, BSA. These results show that agarose native gel electrophoresis can be used to analyze the effects of solvent additives on proteins subjected to heat stresses. SYPRO Orange that stains only unfolded proteins confirmed unfolded structures of soluble aggregates.


Effectiveness and cost-effectiveness of sector-independent treatment coordination for people with substance-related disorders following an online assessment (ASSIST): study protocol for a randomized controlled trial.
The implementation of person-centred, need-oriented and flexible care for people with substance-related problems is often insufficient, in large part due to the complexity of addiction support services among different providers. A standardized online assessment and subsequent sector-independent treatment coordination could provide individuals with more appropriate services, thereby making better use of individual services and leading to a more effective addiction support system as a whole. The aim of this study is to determine the effectiveness and cost-effectiveness of sector-independent treatment coordination following an online assessment, in comparison with the current standard of care and treatment process in Germany. The sample size of this randomized, controlled trial has been set to a total of 400 participants with substance-related problems. Participants living in Stuttgart, Germany, will be randomly allocated to (1) the intervention group with immediate online assessment and subsequent sector-independent treatment coordination (ASSIST) or (2) the waitlist group. Participants in the waitlist group will initially remain in usual care and only be provided with the online assessment 6 months later. Short-term effects (over 2 months) and medium-term effects (over 6 months) of ASSIST will be compared between the intervention and the waitlist groups. The primary outcome is improved treatment satisfaction. Secondary outcomes include improved subjective quality of life and empowerment, reductions in patients' substance use, unmet needs and illness-related clinical and social impairment. Health economic evaluation as well as quantitative and qualitative process evaluations will be conducted. The results of this study are expected to provide information on whether sector-independent treatment coordination following an online assessment contributes to improved health care service provision for people with substance-related problems. This randomized controlled trial will help identify facilitators and barriers to the sustainable implementation of a cross-sectoral care concept in substance abuse services. German Clinical Trial Register DRKS00026996 . Registered on 29 October 2021.


Becoming a midwife: A survey study of midwifery alumni.
Becoming a competent midwife is a complex process. The aim of midwifery education is to support the development of competence in midwifery skills, knowledge and to prepare graduates to meet the responsibilities inherent in the midwifery role. To explore the experiences of our alumni midwives, ask how well they perceived their midwifery programme had prepared them for beginning midwifery practice and to identify any curriculum changes, or postgraduate study topics, that would support the transition to midwifery practice. An online survey was conducted with alumni of a Bachelor of Midwifery programme (New Zealand) who graduated between 2011 and 2014. The quantitative data were analysed using descriptive statistics, and a general inductive approach was used to develop themes from the qualitative data in the comment boxes. Forty-two alumni viewed becoming a midwife as a blend/combination of: (1) gaining the knowledge and practical skills required for the profession; (2) management skills in areas of running a business, working with other people, navigating local procedures and processes effectively, and balancing work with personal life; (3) gaining confidence in one's competence, and (4) having support along the way. Competence in current evidence-based midwifery knowledge and practice is important in educating midwifery students. However, to transition to practice, a supportive environment is needed to assist midwives to develop self-management, business skills, and the confidence to negotiate and collaborate with colleagues and other health professionals. Not only did midwifery knowledge and practice skills matter for alumni, but also the acquisition of management skills, strategies for building confidence, and ongoing support. Content that facilitates these requirements should be included in midwifery programmes to support the transition from student to practitioner.


The effects of aerobic physical exercises on body image among women with polycystic ovary syndrome.
Both physical and mental health care for women with polycystic ovary syndrome (PCOS) require a multidisciplinary approach. We evaluated the effects of continuous (CAT) and intermittent (IAT) aerobic training in different protocols that measure body image, anxiety, depression and sexual dysfunction in women with PCOS. In this controlled clinical trial, women with PCOS were randomly allocated for 16 weeks to 1 out of 3 groups: CAT (n = 28), IAT (n = 29), or control group (CG, n = 30). For data collection, we used the Body Shape Questionnaire (BSQ), Figure Rating Scale (FRS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Measurement Scales (HADS). No effects of CAT, IAT or CG groups were identified in the perceptual dimension of body image. The dis(satisfaction) grade improved after exercise in the CAT group (p ≤ 0.01) compared to the CG, as well as improved within CAT and IAT groups. Total FSFI, and HADS-A and HADS-D scores improved after exercise in the both groups. At baseline and after the study period, there were positive correlations between scores for dis(satisfaction), HADS-A and HADS-D scores. HADS-A and HADS-D scores had a negative correlation with FSFI total in the IAT (p = =0.02) group compared to the CG, as well as within CAT and IAT groups. The participants were not matched for body mass index (normal, overweight and obese) which may interfere on body image dimensions. Aerobic exercise improves sexual function and indices related to anxiety and depression. Likewise, it interferes in cognitive-affective dimension of the body image.


Congenital dermoid sinus of anterior chest: Case report and review of literature.
Congenital dermoid sinus which is a rare congenital anomaly of the anterior chest wall (CDACR) is frequently misdiagnosed or mistreated. This report aims to raise awareness about this condition and share experience based on a demarcation technique for anomalous tissue. A case of surgically treated CDACR in our clinic and subsequently confirmed through histopathology was chosen. Health records such as, demographics, visits, imaging modalities, management, outcome, and histopathology were reviewed of the patient. Our patient aged 4 years underwent ultrasonography, which revealed a dermoid sinus on her right anterior chest. This diagnosis was later confirmed via histopathology after the excision of the sinus, which was facilitated by a mix of methylene blue and fibrin glue. The incision healed well without any complications. Thus, it was found that CDACRs are those rare congenital anomalies requiring immediate excision to prevent recurrent infections or complications. Knowing how to identify and deal with them is essential.


Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand.
Peripheral neuropathy following cisplatin treatment is a major limiting factor in cisplatin chemotherapy of cancer patients. We investigated the pathomechanism underlying cisplatin neuropathy using a mouse dorsal root ganglion neuron-neuroblastoma hybrid cell line (N18D3) developed in our laboratory. DNA fragmentation, a characteristic feature of apoptosis, was induced in hybrid neurons following treatment with cisplatin. Accumulation of p53, Fas, and Fas ligand (Fas-L) was also demonstrated in these neurons. Preincubation with N-acetylcysteine (NAC), a precursor of glutathione, blocked cisplatin-induced apoptosis completely, whereas Trolox, a vitamin E analogue, blocked it partially. Cisplatin-induced p53 accumulation was suppressed by NAC treatment, whereas p53 accumulation was retarded by Trolox treatment. In contrast, neither NAC nor Trolox showed any inhibitory effect on cisplatin-induced Fas/Fas-L accumulation. These results suggest that the neuroprotective effects of antioxidants against cisplatin-induced neurotoxicity in hybrid neurons are mediated mainly through the inhibition of p53 accumulation but not of Fas/Fas-L accumulation by these antioxidants.


Independent release of peptide YY (PYY) into the circulation and ileal lumen of the awake dog.
Peptide YY (PYY) is a recently discovered polypeptide found in the endocrine cells of the distal small intestine, colon, and rectum. This study was designed to evaluate the postprandial release of PYY into the peripheral blood and the ileal lumen in response to different ingested nutrients. Six adult conditioned mongrel dogs had 25-cm distal ileal Thiry-Vella segments surgically constructed. After a 2-week postoperative recovery period the animals were fed meals consisting of protein (2 g/kg), fat (5 g/kg), or glucose (1.5 g/kg). Circulating and ileal intraluminal PYY concentrations were measured by a sensitive radioimmunoassay developed in our laboratory. Significant increases in circulating PYY levels were seen only after the fat meal in dogs. Ileal intraluminal PYY concentrations were significantly greater than those concentrations seen in the peripheral blood. A significant rise in ileal intraluminal PYY was seen only after the glucose meal without concomitant changes in circulating PYY. These findings document independent release mechanisms of PYY into the circulation and ileal lumen of the awake dog. We believe that the release of PYY into the canine circulation and into the ileal lumen after feeding may be dependent on the type of nutrient ingested and may serve to regulate the diverse physiologic roles of PYY in the gastrointestinal tract.


Automated Video Tracking of Autistic Children's Movement During Caregiver-Child Interaction: An Exploratory Study.
Objective, quantitative measures of caregiver-child interaction during play are needed to complement caregiver or examiner ratings for clinical assessment and tracking intervention responses. In this exploratory study, we examined the feasibility of using automated video tracking, Noldus EthoVision XT, to measure 159 2-to-7-year-old autistic children's patterns of movement during play-based, caregiver-child interactions and examined their associations with standard clinical measures and human observational coding of caregiver-child joint engagement. Results revealed that autistic children who exhibited higher durations and velocity of movement were, on average, younger, had lower cognitive abilities, greater autism-related features, spent less time attending to the caregiver, and showed lower levels of joint engagement. After adjusting for age and nonverbal cognitive abilities, we found that children who remained in close proximity to their caregiver were more likely to engage in joint engagement that required support from the caregiver. These findings suggest that video tracking offers promise as a scalable, quantitative, and relevant measure of autism-related behaviors.


High-flow nasal cannula support therapy: new insights and improving performance.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .


Platelet-Rich Plasma Treatment for Accelerated Androgenetic Alopecia Pattern Hair Loss After COVID-19 Infection: A Case Series.
Hair-related manifestations such as alopecia areata or telogen effluvium were reported during COVID-19 disease. Accelerated hair loss with androgenetic alopecia (AGA) pattern or management has not been discussed before. This study aimed to examine the accelerated AGA pattern hair loss and management with PRP treatment. This study was designed prospectively and nine patients included to study confirmed PCR test for COVID-19 infection. Patients underwent platelet-rich plasma (PRP) injections for 4 sessions. Results were accessed with the hair pull test (HPT) and self-administered hair growth questionnaire (HGQ). Nine patients were admitted with complaints of hair loss after an average of 220 ± 24.2 (min: 182 max: 264) day after recovery of COVID-19. Mean age of the patients was 33.8 ±8.4 years old (min: 26, max: 52). Six (66.7%) patients were male, and three (33.3%) of them were female. HPT score decreased to 6.0 ± 1.6 after the first PRP application (p = 0.007, CI 95%:2.7-5.2) and decreased to 1.2 ± 0.8 after the last PRP session (p = 0.008, CI 95%: 6.4-11.1). Five (55.5%) of the patients described the treatment as "very effective" after treatment with HGQ. Accelerated hair loss associated with COVID-19 continues in long term and PRP treatment provides a satisfactory solution.


Thebaine induces anaphylactic reactions via the MRGPRX2 receptor pathway on mast cells.
Morphine derivatives are clinically important anesthetic and sedative drugs, which often show anaphylactic side effects. Mas-related G-protein coupled receptor member X2 (MRGPRX2) triggers mast cell degranulation, which is important process in anaphylactic reactions. MRGPRX2-HEK293 and LAD2 cell membrane chromatographic (CMC) models were used to screen morphine derivatives binding to MRGPRX2. Furthermore, most morphine derivatives significantly enhanced Ca2+ mobilization. More importantly, thebaine was found to effectively promote histamine release. Thebaine induced the increased release of β-hexosaminidase and high secretion level of cytokines, confirming that thebaine could further trigger anaphylactic reactions and promote subsequent inflammatory reactions. Moreover, the ability of thebaine inducing degranulation and the release of allergenic mediators in mast cells was significantly decreased after MRGPRX2 knockdown, which proved that MRGPRX2 is the key media for thebaine-induced anaphylactic reactions. Significant hind paw swelling and hypothermia in mice after injecting thebaine suggested that thebaine could trigger anaphylactic reactions in vivo.


The DYW-class PPR protein MEF7 is required for RNA editing at four sites in mitochondria of Arabidopsis thaliana.
In plant mitochondria and plastids, RNA editing alters about 400 and about 35 C nucleotides into Us, respectively. Four of these RNA editing events in plant mitochondria specifically require the PPR protein MEF7, characterized by E and DYW extension domains. The gene for MEF7 was identified by genomic mapping of the locus mutated in plants from EMS treated seeds. The SNaPshot screen of the mutant plant population identified two independent EMS mutants with the same editing defects as a corresponding T-DNA insertion line of the MEF7 gene. Although the amino acid codons introduced by the editing events are conserved throughout flowering plants, even the combined failure of four editing events does not impair the growth efficiency of the mutant plants. Five nucleotides are conserved between the four affected editing sites, but are not sufficient for specific recognition by MEF7 since they are also present at three other sites which are unaffected in the mutants.


A new Drusinae species from the western Alps with comments on the subfamily and an updated key to filtering carnivore larvae of Drusinae species (Insecta: Trichoptera: Limnephilidae).
A new Drusinae species, Drusus katagelastos sp. nov., of the Drusus chapmani Species Complex, is described based on a male and associated larvae. Adult-larval association was achieved through DNA barcoding. The male of the new species differ from that of its congeners in the formation of the intermediate appendages and parameres. Information on the morphology of the larva is given, and important diagnostic features are discussed. In the context of filtering carnivore Drusinae, the larva of the new species can be separated from other filtering carnivore species by the dense cover of long translucent bristles within the frontal cavity surrounded by a circular corona of long bristles. Drusus katagelastos sp. nov. is known from only northwestern Italy (Piemonte).


Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences.
Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process. Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0-100 mm), global activity (GAF, 0-100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0-96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed. Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20-123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6-11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = -0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men. Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.


Expression analysis of chitinase upon challenge inoculation to Alternaria wounding and defense inducers in Brassica juncea.
Chitinases are the hydrolytic enzymes which belong to the pathogenesis-related (PR) protein family and play an important role not only in plant defense but also in various abiotic stresses. However, only a limited number of chitinase genes have been characterised in B. juncea. In this study, we have characterised B. juncea class IV chitinase gene (accession no EF586206) in response to fungal infection, salicylic acid (SA), jasmonic acid (JA) treatments and wounding. Gene expression studies revealed that the transcript levels of Bjchitinase (BjChp) gene increases significantly both in local and distal tissues after Alternaria infection. Bjchitinase gene was also induced by jasmonic acid and wounding but moderately by salicylic acid. A 2.5 kb class IV chitinase promoter of this gene was isolated from B. juncea by Genome walking (accession no KF055403.1). In-silico analysis of this promoter revealed a number of conserved cis-regulatory elements related to defense, wounding and signalling molecules like SA, and JA. For validation, chitinase promoter was fused to the GUS gene, and the resultant construct was then introduced into Arabidopsis plants. Histochemical analysis of T2 transgenic Arabidopsis plants showed that higher GUS activity in leaves after fungal infection, wounding and JA treatment but weakly by SA. GUS activity was seen in meristematic tissues, young leaves, seeds and siliques. Finally investigation has led to the identification of a pathogen-inducible, developmentally regulated and organ-specific promoter. Present study revealed that Bjchitinase (BjChp) promoter is induced during biotic and environmental stress and it can be used in developing finely tuned transgenics.


The pull of magnetism: a look at the standards and the experience of a western academic medical center hospital in achieving and sustaining Magnet status.
Many hospitals are working to improve the work environment for their staff. Research has indicated a linkage between work environment characteristics and patient outcomes and this research along with the nursing shortage has been the impetus for focusing on improving the work environment. The authors described the experience of an academic medical center hospital in achieving Magnet hospital status. The process and the required resources and support are discussed. Outcome data from staff nurses regarding their perception of the work environment in a Magnet hospital are presented.


Remote afterloading techniques for the treatment of nasopharyngeal and endometrial cancer.
Simple methods of delivering intracavitary radiation to the nasopharynx and endometrium using remote afterloading apparatus are described. Considerable flexibility of isodose distribution is possible at both sites even without refinement of the systems described.


Construction of controlled-NOT gate based on microwave-activated phase (MAP) gate in two transmon system.
We experimentally constructed an all-microwave scheme for the controlled-NOT (cNOT) gate between two superconducting transmon qubits in a three dimensional cavity. Our cNOT gate is based on the microwave-activated phase (MAP) gate, which requires an additional procedure to compensate the accumulated phases during the operation of the MAP gate. We applied Z-axis phase gates using microwave hyperbolic secant pulse on both qubits with adequate rotation angles systematically calibrated by separate measurements. We evaluated the gate performance of the constructed cNOT gate by performing two-qubit quantum process tomography (QPT). Finally, we present the experimental implementation of the Deutsch-Jozsa algorithm using the cNOT gate.


Adenosine diphosphate-decorated chitosan nanoparticles shorten blood clotting times, influencing the structures and varying the mechanical properties of the clots.
Chitosan nanoparticles (NPs) decorated with adenosine diphosphate (ADP) (ANPs) or fibrinogen (FNPs) were used to fabricate hemostatic NPs that can shorten blood clotting time and prevent severe local hemorrhage. The structure and mechanical properties of the blood clot induced with ANP (clot/ANP) or FNP (clot/FNP) were also investigated. The NPs, ANPs, and FNPs, which had particle sizes of 245.1 ± 14.0, 251.0 ± 9.8, and 326.5 ± 14.5 nm and zeta potentials of 24.1 ± 0.5, 20.6 ± 1.9, and 15.3 ± 1.5 mV (n=4), respectively, were fabricated by ionic gelation and then decorated with ADP and fibrinogen. The zeta potentials and Fourier transform infrared (FTIR) spectroscopy of the NPs confirmed that their surfaces were successfully coated with ADP and fibrinogen. The scanning electron microscope (SEM) micrographs of the structure of the clot induced with "undecorated" chitosan NPs (clot/NP), clot/ANP, and clot/FNP (at 0.05 wt%) were different, after citrated bloods had been recalcified by a calcium chloride solution containing NPs, ANPs, or FNPs. This indicated that many NPs adhered on the membrane surfaces of red blood cells, that ANPs induced many platelet aggregates, and that FNPs were incorporated into the fibrin network in the clots. Measurements of the blood clotting times (Tc) of blood clot/NPs, clot/ANPs, and clot/FNPs, based on 90% of ultimate frequency shifts measured on a quartz crystal microbalance (QCM), were significantly (P<0.05) (n=4) shorter than that of a clot induced by a phosphate-buffered solution (PBS) (clot/PBS) (63.6% ± 3.1%, 48.3% ± 6.2%, and 63.2% ± 4.7%, respectively). The ΔF2 values in the spectra of frequency shifts associated with the propagation of fibrin networks in the clot/ANPs and clot/FNPs were significantly lower than those of clot/PBS. Interestingly, texture profile analysis of the compressional properties showed significantly lower hardness and compressibility in clot/NPs and clot/ANPs (P<0.05 or better) (n=4) compared with clot/PBS and clot/FNPs. Accordingly, among the hemostatic NPs, ANP substantially reduced blood clotting times, ΔF2 values, and compression flow properties of the clot. Hence, ANPs have potential applications for preventing severe local hemorrhage.


Separation of biological proteins by liquid chromatography.
After the success of human genome project, proteome is a new emerging field of biochemistry as it provides the knowledge of enzymes (proteins) interactions with different body organs and medicines administrated into human body. Therefore, the study of proteomics is very important for the development of new and effective drugs to control many lethal diseases. In proteomics study, analyses of proteome is essential and significant from the pathological point of views, i.e., in several serious diseases such as cancer, Alzheimer's disease and aging, heart diseases and also for plant biology. The separation and identification of proteomics is a challenging job due to their complex structures and closely related physico-chemical behaviors. However, the recent advances in liquid chromatography make this job easy. Various kinds of liquid chromatography, along with different detectors and optimization strategies, have been discussed in this article. Besides, attempts have been made to include chirality concept in proteomics for understanding mechanism and medication of various disease controlled by different body proteins.


Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments.
To investigate if needle-immersed vitrification or slow-freezing yields better implantation results for human ovarian tissue and which method benefits more when combined with the "improvement protocol" of host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A. Human ovarian tissue was preserved by needle-immersed vitrification or slow-freezing and transplanted into immunodeficient mice, either untreated (groups A and C, respectively) or treated with the improvement protocol (groups B and D, respectively). Grafted and ungrafted slices were evaluated by follicle counts, apoptosis assay and immunohistochemistry for Ki67 and platelet endothelial cell adhesion molecule (PECAM). Follicle number in the recovered grafts was limited. The number of atretic follicles was significantly higher after vitrification with/without the improvement protocol and slow-freezing than that after slow-freezing + the improvement protocol. Stroma cell apoptosis was the lowest in the group D. PECAM staining showed a peripheral and diffuse pattern in the group D (mostly normal follicular morphology) and a diffuse pattern in all other groups (few follicles, mostly atretic), with significantly higher diffuse levels in the vitrification groups. Ki67 staining was identified in all normal follicles. Follicles did not survive transplantation in the vitrification groups. Ovarian sample preparation with slow-freezing + the improvement protocol appears to yield better implantation outcomes than needle-immersed vitrification with/without the improvement protocol. The real quality of frozen tissue can be assessed only after grafting and not after thawing/warming.


Robust metal ion-chelated polymer interfacial layer for ultraflexible non-fullerene organic solar cells.
Achieving high power conversion efficiency and good mechanical robustness is still challenging for the ultraflexible organic solar cells. Interlayers simultaneously having good mechanical robustness and good chemical compatibility with the active layer are highly desirable. In this work, we present an interlayer of Zn2+-chelated polyethylenimine (denoted as PEI-Zn), which can endure a maximum bending strain over twice as high as that of ZnO and is chemically compatible with the recently emerging efficient nonfullerene active layers. On 1.3 μm polyethylene naphthalate substrates, ultraflexible nonfullerene solar cells with the PEI-Zn interlayer display a power conversion efficiency of 12.3% on PEDOT:PSS electrodes and 15.0% on AgNWs electrodes. Furthermore, the ultraflexible cells show nearly unchanged power conversion efficiency during 100 continuous compression-flat deformation cycles with a compression ratio of 45%. At the end, the ultraflexible cell is demonstrated to be attached onto the finger joint and displays reversible current output during the finger bending-spreading.


Ischemic and inflammatory lung impairment by extracorporeal circulation: effect of PARP-inhibition by INO1001.
Among the complications after cardiac surgery the development of postoperative pulmonary distress is a serious problem. Typically, the patients leave the operating theatre with good blood gas values and O(2)-saturation, but develop their respiratory problems within the next hours/days. We investigated whether extracorporeal circulation may induce biochemical and histological changes in the lungs which may help to explain this development. Piglets (6-10 kg) were anaesthetized using isoflurane and underwent extracorporeal circulation (ECC) with hypothermic (25-28 degrees C) cardioplegic arrest for 90 min followed by 3h reperfusion. An additional group received a poly(ADP-ribose) polymerase (PARP)-Inhibitor, INO1001. Cardiopulmonary monitoring was performed during the whole procedure. Finally, lungs were explanted and investigated by histomorphometry and immunohistology for heat shock protein HSP70 (indicator for cellular damage) and TNFalpha in comparison to normal piglets without ECC. Histologically we found significant swelling of the type I alveocytes (thickness increased from 2.4 to 3.2 microm), interstitial oedema, intra-alveolar erythrocyte (4.8 versus 0.4 erythrocytes/alveole) and granulocyte accumulation and fibrinous exudates. There was a significant up-regulation of TNFalpha and of the cellular repair enzyme HSP70, while in control piglets only minimal levels were observed. INO1001 significantly reduced ECC-induced elevation in TNFalpha and in HSP70. Despite the dramatic changes after heart-lung-machine (HLM), blood gases and gas transport were almost not affected at that time. ECC can lead to early significant histological and histochemical changes which have similarities with a beginning early stage shock lung, although - at 3h reperfusion - gas transport is still sufficient. INO1001 can partially antagonize these changes.