GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation.
Gangliosides are a family of sialic acid-containing glycosphingolipids that are highly enriched in the mammalian nervous system. In particular, b- and c-series gangliosides, all of which contain alpha-2,8 sialic acids, have been considered to play important roles in adhesion, toxin-binding, neurite extension, cell growth and apoptosis. However, the neurobiological functions of these series of gangliosides remain largely unknown. To clarify the function of b- and c-series gangliosides in pain sensation in vivo, we generated mice in whom the gene for the alpha-2,8-sialyltransferase (GD3 synthase), which is responsible for the generation of all b-series gangliosides as well as c-series gangliosides, was disrupted. Compared to the wild-type mice, the mutant mice exhibited increased sensory responses to thermal and mechanical stimuli as measured by a hot plate test and von Frey test. In contrast, the mutant mice showed decreased responses during the late phase of the formalin test. Paw edema and Fos expression in the spinal cord after formalin injection were significantly decreased in the mutant mice compared to the wild-type mice. No significant differences in the conduction velocity of the sciatic nerve, and no apparent morphologic differences in the spinal cord and the sciatic nerve were detected between the wild-type and the mutant mice. These results suggested that b- and c-series gangliosides are critical in the development and/or maintenance of the sensory nervous system responsible for the transmission of acute pain sensation and pain modulation. Moreover, they play an important role in the development of hyperalgesia induced by inflammation.


Pyridine-4-carboxamidoxime N-oxide.
Our work in the area of synthesis of metal-organic frameworks (MOFs) based on organic N-oxides led to the crystallization of pyridine-4-carboxamidoxime N-oxide. Herein we report the first crystal structure of the title compound, C6H7N3O2 [systematic name: (Z)-4-(N'-hy-droxy-carbamimido-yl)pyridine N-oxide]. The hy-droxy-carbamimidoyl group is essentially coplanar with the aromatic ring, r.m.s.d. = 0.112 Å. The compound crystallizes in hydrogen-bonding layers built from the formation of strong O-H⋯O hydrogen bonds between the oxime oxygen atom and the oxygen atom of the N-oxide, and the formation of N-H⋯O hydrogen bonds between one amine nitro-gen atom and the N-oxide oxygen atom. These combined build R 3 4(24) ring motifs in the crystal. The crystal structure has no π-π inter-actions.


Exploring the Role of Antioxidants to Combat Oxidative Stress in Malaria Parasites.
Malaria, a global challenge, is a parasitic disease caused by Plasmodium species. Approximately 229 million cases of malaria were reported in 2019. Major incidences occur in various continents, including African and Eastern Mediterranean Continents and South-East Asia. Despite the overall decline in global incidence from 2010 to 2018, the rate of decline has been almost constant since 2014. The morbidity and mortality have been accelerated due to reactive oxygen species (ROS) caused by oxidative stress generated by the parasite responsible for the destruction of host metabolism and cell nutrients. The excessive release of free radicals is associated with the infection in the animal or human body by the parasites. This may be related to a reduction in nutrients required for the generation of antioxidants and the destruction of cells by parasite activity. Therefore, an intensive literature search has been carried out to find the natural antioxidants used to neutralize the free radicals generated during malarial infection. The natural antioxidants may be useful as an adjuvant treatment along with the antimalarial chemotherapeutics to reduce the death rate and enhance the success rate of malaria treatment. In this manuscript, an attempt has been made to provide significant insight into the antioxidant activities of herbal extracts against malaria parasites.


Prospective validation of quantitative CEA mRNA detection in peritoneal washes in gastric carcinoma patients.
Prediction of peritoneal relapse is extremely important for gastric cancer patients after curative surgery. The present study prospectively validates the prognostic ability of quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes by real-time reverse transcriptase-polymerase chain reaction. Based on a retrospective study of 197 curatively resected gastric cancer patients (training set), we determined a cutoff value of CEA mRNA using receiver-operating characteristic curve. We used this cutoff value to validate the risk of peritoneal recurrence in a new cohort of 86 gastric cancer patients (validation set) between July 2000 and December 2002 in a prospective study. During the median 30 months of postoperative surveillance, 20 of the 86 patients died, and 13 of the 20 developed peritoneal metastases. Peritoneal recurrence-free survival as well as overall survival was significantly worse in patients with positive CEA mRNA (P<0.0001). Multivariate analysis with the Cox proportional hazards model showed that positive CEA mRNA was a significant independent risk factor with both survival (P=0.0130) and peritoneal recurrence-free survival (P=0.0006) as end points. These results indicate that quantitation of CEA mRNA in peritoneal washes is a reliable prognostic indicator of peritoneal recurrence in the clinical setting.


Predictors of outcome after surgery with disc prosthesis and rehabilitation in patients with chronic low back pain and degenerative disc: 2-year follow-up.
A prospective study to evaluate whether certain baseline characteristics can predict outcome in patients treated with disc prosthesis or multidisciplinary rehabilitation. Secondary analysis of 154 patients with chronic low back pain (LBP) for at least 1 year and degenerative discs originally recruited for a randomized trial. Outcome measures were Oswestry Disability Index (ODI) dichotomized to < or ≥15 points improvement and whether subjects were working at 2-year follow-up. A multiple logistic regression analysis was used. In patients treated with disc prosthesis, long duration of LBP and high Fear-Avoidance Beliefs for work (FABQ-W) predicted worse ODI outcome [odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.2-3.2 and OR = 1.7, CI 1.2-2.4 for every 5 years or 5 points]. Modic type I or II predicted better ODI outcome (OR = 5.3, CI 1.1-25.3). In patients treated with rehabilitation, a high ODI, low emotional distress (HSCL-25), and no daily narcotics predicted better outcome for ODI (OR = 2.5, CI 1.4-4.5 for every 5 ODI points, OR = 2.1, CI 1.1-5.1 for every 0.5 HSCL points and OR = 23.6, CI 2.1-266.8 for no daily narcotics). Low FABQ-W and working at baseline predicted working at 2-year follow-up after both treatments (OR = 1.3, CI 1.0-1.5 for every 5 points and OR = 4.1, CI 1.2-13.2, respectively). Shorter duration of LBP, Modic type I or II changes and low FABQ-W were the best predictors of success after treatment with disc prosthesis, while high ODI, low distress and not using narcotics daily predicted better outcome of rehabilitation. Low FABQ-W and working predicted working at follow-up.


Chicken orthologues of mammalian imprinted genes are clustered on macrochromosomes and replicate asynchronously.
In the chicken genome, most orthologues of mouse imprinted genes are clustered on macrochromosomes. Only a few orthologues are located in the microchromosome complement. Macrochromosomal and, to a lesser extent, microchromosomal regions containing imprinted gene orthologues exhibit asynchronous DNA replication. We conclude that highly conserved arrays of imprinted gene orthologues were selected during vertebrate evolution, long before these genes were recruited for parent-specific gene expression by genomic imprinting mechanisms. Evidently, the macrochromosome complement provides a better chromatin environment for the establishment of asynchronous DNA replication and imprinted gene expression later in evolution than microchromosomes.


Studies on the surface coat of Paramecium aurelia. II. Relationship to the immobilization antigen.
Correlations between the presence of surface coat and immobilization antigen of Paramecium tetraurelia were studied. Supravital, partial removal of the surface coat resulted in accelerated response of monobacterially and axenically grown cells to the homologous antiserum. Ciliates pretreated with trypsin or pronase (0.5 mg/ml for 45 min at 0-4 degrees C) were immobilized approximately twice as fast as untreated control cells. The probable localization of at least part, of the immobilization antigen within the surface coat of P. tetraurelia is discussed.


Antenatal corticosteroids: are incomplete courses beneficial?
To assess the effectiveness of an incomplete course of antenatal corticosteroids on perinatal morbidity and mortality. METHOSD: We studied consecutive neonates born at 23-34 weeks' gestation between January 1, 1998, and July 31, 2002. The study population was divided into a group exposed to one 12-mg dose of betamethasone before delivery and a non-corticosteroid-exposed group, which were compared for various perinatal outcome variables. The Student t test, chi(2), Fisher exact tests, and logistic regression were used for analysis. One hundred twenty-five neonates (55.6%) were exposed to one 12-mg dose of betamethasone before delivery, whereas 104 neonates (45.4%) did not receive antenatal corticosteroids. Mean gestational age at delivery (28.4 +/- 3.1 weeks versus 29.7 +/- 3.5 weeks, P =.002) and birth weight (1189 +/- 409 g versus 1289 +/- 441 g, P =.07) were lower among the steroid-exposed group. Adjusting for gestational age, one dose of betamethasone was associated with significant reduction in the need for vasopressors (odds ratio [OR] 0.35; 95% confidence interval [CI] 0.14, 0.85; P =.02), the rate of intraventricular hemorrhage (OR 0.42; 95%CI 0.19, 0.92; P =.03), and neonatal death (OR 0.31; 95% CI 0.11, 0.86; P =.02). There were no differences between groups in the rate of clinical and histological chorioamnionitis, low Apgar scores, postnatal surfactant exposure, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus, retinopathy of prematurity, and neonatal sepsis. An incomplete course of antenatal corticosteroids is associated with reduction in the need for vasopressors, the rate of intraventricular hemorrhage, and neonatal death in preterm neonates.


The efficacy of anterior open bite closure when using Invisalign's optimized extrusion versus conventional attachments.
Clear aligners are reported to control anterior open bites. Despite this, anterior extrusion remains difficult with aligners. Optimized extrusion attachments on incisors may facilitate anterior extrusion to correct open bite with Invisalign. The aim of this retrospective study was to compare the efficacy of anterior open bite correction with Invisalign when using optimized extrusion versus conventional attachments. This was a retrospective cohort study. The pre- and post-treatment intraoral scans of patients with anterior open bite treated with Invisalign aligners were assessed. Patients were divided into two groups: group A, patients with horizontal conventional attachments and group B, patients with optimized extrusion attachments on incisors. The pre and post-treatment overbite and the planned overbite change were measured and compared between the groups. Descriptive statistics were computed and statistical significance was set at P < 0.05. A total of 86 patients were included. Both groups showed significant increases in overbite, but there was no difference in the open bite correction efficacy in patients with conventional versus optimized attachments. Shorter treatment times for open bite closure were reported for patients with optimized attachments. Anterior open bite can be corrected regardless of the attachment type. Optimized attachments are no more effective than using conventional attachments in incisor extrusion to correct open bite. Patients with anterior open bite with optimized attachments observed shorter treatment times for overbite correction. When correcting anterior open bite with Invisalign, the attachment type does not improve the success rate. Optimized extrusion attachments on incisors may shorten the treatment time compared to conventional attachments.


Photoemission study of the electronic structure and charge density waves of Na2Ti2Sb2O.
The electronic structure of Na2Ti2Sb2O single crystal is studied by photon energy and polarization dependent angle-resolved photoemission spectroscopy (ARPES). The obtained band structure and Fermi surface agree well with the band structure calculation of Na2Ti2Sb2O in the non-magnetic state, which indicates that there is no magnetic order in Na2Ti2Sb2O and the electronic correlation is weak. Polarization dependent ARPES results suggest the multi-band and multi-orbital nature of Na2Ti2Sb2O. Photon energy dependent ARPES results suggest that the electronic structure of Na2Ti2Sb2O is rather two-dimensional. Moreover, we find a density wave energy gap forms below the transition temperature and reaches 65 meV at 7 K, indicating that Na2Ti2Sb2O is likely a weakly correlated CDW material in the strong electron-phonon interaction regime.


Spontaneous nutrient recovery and disinfection of aquaculture wastewater via Mg-coconut shell carbon composites.
Aquaculture wastewater contained large amounts of pathogenic microorganisms, nitrogen (N) and phosphorus (P). In this study, the nutrient recoveries and wastewater disinfection were simultaneously achieved using Mg-coconut shell carbon (Mg-CSC). The composites were prepared by a ball milling method. The hydrogen peroxide (H2O2) was in-situ generated by the dissolved oxygen reduction driven by Mg corrosion on the CSC surface, which inactivated the microorganisms. Besides that, Mg corrosion provided sufficient Mg ions and appropriate pH conditions for struvite formation. The results show that 5.4-log E.coli removal was achieved under different conditions. Improving the Mg/CSC ratio and composite dosage could shorten the time required for disinfection. In addition to H2O2, singlet oxygen played a critical role. Reactive oxygen species destroyed the cellular structure and killed the bacteria. The recoveries of NH4+-Nand P under certain conditions were about 60% and 91%, respectively. An increased composite dosage could improve the recovery ratio of P. Excessive dosages were not beneficial for removing NH4+-N. The characterization result revealed that struvite crystals were the main precipitates on the CSC surface. The Mg-CSC composites also revealed satisfied nutrient recovery and disinfection performances in the real aquaculture wastewater treatment process.


Spectrum of causes of intestinal obstruction in adult Nigerian patients.
To present changes in the cause of intestinal obstruction in an African setting. Consecutive cases of acute intestinal obstruction from 1985 to 1994. Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. Adult patients with clinical and radiological evidence of intestinal obstruction. There were 99 patients (60 males) aged 15 - 101 years (mean age 45 years). The majority of patients were young and middle-aged adults. Main causes of obstruction included adhesion (N = 44), volvulus (N =15), external hernias (N = 11), colorectal carcinoma (N = 10) and intussusception (N = 8). Approximately two-thirds of patients (28/44) with adhesion had had previous abdominal operations. The overall mortality was 14%, mainly owing to strangulation obstruction and colonic malignancy. The increasing role of adhesions as a cause of acute intestinal obstruction demands greater need for routine preventive measures against adhesion formation.


Longitudinal Assessment of Retinal Nerve Fiber Layer and Ganglion Cell Complex Thicknesses in Patients With Large Optic Disc Cups and Normal Intraocular Pressure and Visual Fields.
The thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and ganglion cell complex (GCC) did not change during 5 years in physiological large disc cupping. We evaluated longitudinal changes in the thicknesses of the cpRNFL and GCC in large disc cupping with a normal intraocular pressure (IOP) (<21 mm Hg) and visual field. This retrospective, consecutive case series study included 269 eyes of 269 patients with large disc cupping and normal IOP. We analyzed patient demographics, IOP, central corneal thickness, vertical cup-to-disc ratios using color fundus photography, the thicknesses of the cpRNFL and GCC using RTVue-100, and mean deviation using visual field examinations. The differences in IOP, vertical cup-to-disc ratios, and mean deviation between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the cpRNFL thickness were 106.5±8.5 and 105.1±9.3 μm, respectively; differences between the baseline and each follow-up visit were not statistically significant. The baseline average and mean average at 60 months follow-up of the GCC thickness were 82.8±9. and 81.5±9.2 μm, respectively; differences between baseline and each follow-up visit were not statistically significant. The thicknesses of the cpRNFL and GCC did not change in well-maintained optic nerve head findings with normal IOP and visual field during a 5-year follow-up period. Optical coherence tomography evaluations of the thicknesses of the cpRNFL and GCC help accurately diagnose physiological optic disc cupping.


Separating Behaviours and Adverse Consequences in the Problem Gambling Severity Index (PGSI): A Confirmatory Factor Analysis and Rasch Analysis.
The Problem Gambling Severity Index (PGSI) is considered the "gold standard" for measuring problem gambling. The PGSI provides a single score summed across nine items. The nine items of the PGSI comprise two subdomains: problematic behaviours and adverse consequences. The aim of the present study was to compare evidence of a one-factor structure to evidence of a two-factor structure representing the two subdomains. With a sample of 1,251 bettors, we conducted confirmatory factor analyses and Rasch analyses to assess evidence supporting the one-factor and the two-factor structures. In addition, stochastic search variable selection was conducted with the total PGSI score, PGSI behaviour score, and PGSI adverse consequences score as separate outcomes to examine whether information is lost when collapsing the two subdomains into a single factor. Overall, there was stronger support of a two-factor structure than a one-factor structure. However, the two-factors were highly correlated with one another and shared most predictors except for one. We recommend continued use of the one-factor structure of the PGSI unless one aims to better understand the relationship between problematic behaviours and adverse consequences.


Experimental and theoretical studies of linear and non-linear optical properties of novel fused-triazine derivatives for advanced technological applications.
Controlling photophysical properties is critical for the continued development of electroluminescent devices and luminescent materials. The preparation and study of novel molecules suitable as luminescent for the development of optoelectrical devices have recently received a lot of attention. Even though the as-triazine unit is a good building block for organic active substances, it is rarely used in this context. We created here novel bis-triazine derivative dyes in the far UV-Vis range by alkylation of triazine-thione derivatives with appropriate dibromo compounds. At the B3LYP/6-311**G(d,p) basis set, their optimal molecular structures were obtained. DFT technique confirmed that the new triazine derivatives are in noncoplanar with one of the two phenyl rings and the triazine plane rotating out by 102.09. Also, depending on the energy gap difference between HOMO and LUMO, some important parameters including chemical potential (π), electronegativity (χ), and chemical hardness (η) were calculated. The compounds may be readily polarized and have significant NLO characteristics, as seen by the tiny HOMO-LUMO energy gap. The calculated values for the polarizability (α) of the two new triazine derivatives have the range 6.09-10.75 × 10-24 (esu). The emission peaks seemed to move to the long-wavelength (redshift), with a rise in the fluorescence band, suggesting that the singlet excited state is more polar than the ground state. The influence of solvent polarity and the intermolecular charge transfer (ICT) processes are reflected in the photophysical properties of new fused triazine derivatives. These properties such as extinction coefficient, absorption and emission cross-sections, fluorescence quantum yield, fluorescence lifetime, oscillator strength, the dipole moment, radiative decay rate constant, the energy yield of fluorescence, and the attenuation length were assessed and discussed.


Are cancer patients at higher suicide risk than the general population?
The aims were to test whether suicide is more prevalent among cancer patients than among the general population, whether the association changes over time, and whether the risk depends on the severity of the cancer disease. A register study was carried out, where standardized suicide rates for different cancer sites were analysed by sex, time periods (1965-74, 1975-84, and 1985-94), and five-year survival rates. The setting was the Swedish population from 1965 to 1999. The cohort studied was 1,031,919 cancer cases and 2,587,152 person-years. The main outcome measure was the standardized mortality ratio (SMR) with the world population as standard population. Cancer patients run a higher risk of suicide than the general population. The suicide rate ratio between male cancer patients and the general population was about 2.5 in 1965-74, which thereafter reduced to about 1.5 in 1985-94. The suicide rate among female cancer patients was in excess of 2.9 in 1965-74 and 2.3 in 1985-94. In fact, a slightly higher rate for women was observed for 1985-94 than for 1975-84. There is also a strong negative association between survival rates and suicide rates, i.e. suicide rates are higher for severe cancer sites with low survival rates. Our findings support the hypothesis that cancer patients run greater risks of committing suicide than the general population does. The severity of the cancer increases the suicide risk. More attention to cancer patients' psychological and care situation is called for.


Clinical and regulatory features of drugs not initially approved by the FDA.
US Food and Drug Administration (FDA) denials of New Drug Applications (NDAs) are often controversial, yet little is known about the basis and characteristics of these decisions. We reviewed new drugs and biologics evaluated by FDA advisory committees between 2007 and 2009 and found that half (27/52, 52%) were unapproved in the first cycle. By 2013, 63% had been approved. Products with initial safety concerns (62%) were much more likely to be approved eventually than drugs with efficacy concerns (8%).


Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study.
This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI. MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.


Quantitative insights into major constituents contained in or released by electronic cigarettes: Propylene glycol, vegetable glycerin, and nicotine.
Generally, the liquid used in electronic cigarettes (E-cigarettes), which is also called E-liquid, is composed of propylene glycol (PG), vegetable glycerin (VG), and nicotine, with many other miscellaneous ingredients. E-liquid is consumed mainly in the form of aerosol via inhalation by the e-cigarette user. The amount and composition of the aerosol generated during its consumption depend on various factors. In this study, the three major constituents (PG, VG, and nicotine) of E-cigarettes were analyzed in both liquid and aerosol samples from 50 commercial products. Their concentrations in the liquid (and aerosol at 3.4 V) samples were 538 (4 6 7), 482 (4 4 9), and 8.75 mg g-1 (7.91 mg g-1), respectively. The nicotine levels in the E-liquids measured in this study were normally 1.2 times greater than those specified by the manufacturers. Furthermore, the amount of liquid consumed increased proportionally as the voltage of the E- cigarette increased. The consumption rate of VG increased as the voltage of the E-cigarette increased, whereas that of PG and nicotine decreased. The results of our study confirm that the amounts of PG and VG generated through the use of E-cigarettes are noticeably larger than those from other tobacco products (such as traditional tobaccos and heat-not-burn products), although no such trend was evident in case of nicotine.


Survival Outcomes of Lung Transplant Recipients From Donors With Abnormal Kidney Function.
Recovering lungs with pulmonary edema due to abnormal kidney function is considered one of the expanded selection criteria for lung transplant. The aim of this study is to assess lung transplant recipients' survival from donors with abnormal kidney function and to determine differences in lung recovery rates from donors with and donors without abnormal kidney function. We reviewed the United Network for Organ Sharing registry for first-time adult lung transplant donors and recipients from June 2005 to March 2017. Donor kidney function was categorized into three groups based on estimated glomerular filtration rate: group I, greater than 60 mL/min; group II, 15 to 59 mL/min; and group III, less than 15 mL/min. Recipient survival was stratified based on estimated glomerular filtration rate using Kaplan-Meier. A multivariate Cox Regression model with known risk factors that affect survival was used to compare survival among groups. Comparison of lung recovery among the three groups was also performed. Lung recovery rates were 29.7% (15,670 of 52,747), 19.4% (3879 of 20,040), and 18.1% (704 of 3898) for groups I, II, and III, respectively. The 1-, 3-, and 5-year recipient survival rates were 86.2%, 69.2%, and 55.7% for group I; 84.9%, 66.9%, and 53.8% for group II; and 85.5%, 65.3%, and 50.3% for group III, respectively (adjusted P = .25; multivariate Cox regression method). When group I was used as reference, the adjusted hazard ratio for group II was 1.04 (95% CI, 0.98-1.10) and for group III, it was 1.08 (95% CI, 0.96-1.23), after adjusting with the multivariate Cox regression model. There was no significant difference in lung recipient survival. The lung recovery rate from donors with abnormal kidney function was lower compared with that of donors with normal kidney function.


Evaluation of the Portable Next-Generation VECTRA H2 3D Imaging System for Measuring Upper Eyelid Area and Volume.
Although a portable 3-dimensional (3D) imaging system has been used for periocular measurement analysis, this system has yet to be tested and validated for periocular area and volume measurements. The aim of this study was to define the upper eyelid and upper eyelid fold region through a modified landmark strategy and validate a portable 3D imaging system for area and volume measurements in this periocular region. Eighty-one healthy adult Caucasians underwent 3D facial imaging with the VECTRA M3 (static) and VECTRA H2 (portable) 3D imaging systems (Canfield Scientific, Inc., Parsippany, NJ). Subsequently, the upper eyelid and upper eyelid fold regions were selected according to a modified landmark localization strategy. Direct measurements of area and volume were performed to assess intrarater, interrater, intramethod, and intermethod reliability, and to compare the agreement between the 2 devices. The VECTRA M3 and H2 showed high reliability on upper eyelid area measurements. Excellent intra-, inter-, and intramethod reliability agreements were observed in intraclass correlation coefficient; very good agreement in intrarater reliability was observed in the relative error of measurement (REM) and relative technical error of measurement (rTEM); and good inter- and intramethod reliability were observed in the REM and rTEM. For area measurement of the upper eyelid fold, the intrarater, interrater, and intramethod reliability of the M3 was lower than that of the H2. Both systems had poor intrarater, interrater, and intramethod reliability for volume measurements in the upper eyelid and upper eyelid fold region. This new portable 3D imaging system achieved excellent or very good reliability values for standardized direct measurements of the upper eyelid and upper eyelid fold region, although volume measurements seem less reliable.


A singular nitric oxide synthase with a globin domain found in Synechococcus PCC 7335 mobilizes N from arginine to nitrate.
The enzyme nitric oxide synthase (NOS) oxidizes L-arginine to NO and citrulline. In this work, we characterise the NOS from the cyanobacteria Synechococcus PCC 7335 (SyNOS). SyNOS possesses a canonical mammalian NOS architecture consisting of oxygenase and reductase domains. In addition, SyNOS possesses an unusual globin domain at the N-terminus. Recombinant SyNOS expressed in bacteria is active, and its activity is suppressed by the NOS inhibitor L-NAME. SyNOS allows E. coli to grow in minimum media containing L-arginine as the sole N source, and has a higher growth rate during N deficiency. SyNOS is expressed in Synechococcus PCC 7335 where NO generation is dependent on L-arginine concentration. The growth of Synechococcus is dramatically inhibited by L-NAME, suggesting that SyNOS is essential for this cyanobacterium. Addition of arginine in Synechococcus increases the phycoerythrin content, an N reservoir. The role of the novel globin domain in SyNOS is discussed as an evolutionary advantage, conferring new functional capabilities for N metabolism.


Evolution of multiple genome mutations during long-term persistent infection by vesicular stomatitis virus.
Persistent infection of BHK21 cells was established with cloned vesicular somatitis virus plus purified Dl particles and maintained in vitro for over 5 years. After 1 year of persistence, the infectious virus RNA genome had evolved several oligonucleotide map changes, and numerous changes had accumulated by 3.5 years. Additional evolution occurred by the fourth year and continued until the fifth year. In contrast, repeated passage of virus in acute infections of several cell types in vitro or in vivo did not lead to detectable oligonucleotide map changes. The short Dl particle originally used to co-infect with infectious virus in establishing persistent infection has been displaced by an ever present and constantly changing population of other Dl particles of differing sizes and radically differing oligonucleotide maps. We conclude that the genomes of both infectious VSV and its Dl particles undergo continuous evolutionary change during years of persistence. In the infectious virus, these changes involve hundreds of mutations which are usually expressed as poorly replicating, temperature-sensitive, small plaque mutants. These are stable mutants which do not revert to wild-type when passaged repeatedly in acute infections at 37 or 33 degrees C. It appears that the sequestered intracellular environment of persistently infected cells favors rapid and continuous virus evolution.


Comparison of visibility and diagnostic capability of noninvasive coronary angiography by eight-slice multidetector-row computed tomography versus conventional coronary angiography.
The usefulness of multidetector-row computed tomography (MDCT) for visualization of coronary arteries has been reported; however, little is known about the diagnostic capability of noninvasive coronary angiography (CA) using 8-detector row CT. We investigated the visualization and diagnostic values of 8-slice MDCT-CA. Twenty-five consecutive patients who underwent conventional CA were investigated. The entire heart was scanned for approximately 20 seconds. Images were created using different reconstruction methods (half-scan and multisectors) followed by image creation during different time windows of the cardiac cycle. The data set containing the fewest artifacts was selected, then reformatted images were created and evaluated. In 348 segments in 25 subjects as determined by conventional CA, 258 segments (74.1%) were judged visible by MDCT-CA. Lower visibility was observed in segments with smaller diameters. Visibility in segments with diameters of > or =2.0 mm was 85.8% (212 of 247 segments). Patients with higher mean heart rates and a larger range of heart rate alteration during the breath-holding scan time had lower visibility. The most frequent cause for invisibility was "adjacent structure" (47%), followed by "small diameter" (33%), and "motion artifact" (16%), suggesting that motion artifacts were reduced by multisector reconstruction and search for the best-optimized time window. MDCT-CA detected 27 of 37 significant stenotic lesions (73%) that had a diameter reduction of >50% and correctly judged 226 of 311 segments (72.7%) as normal. Sensitivity, specificity, and accuracy of the visualized segments by MDCT-CA was 90% (27 of 30 segments), 99.1% (226 of 228 segments), and 98.1% (253 of 258 segments), respectively. Low visibilities in the left circumflex artery and distal and small segments are limitations of 8-slice MDCT-CA because of limited spatial resolution.


A methodological note on mail survey response rates.
Five mail surveys of broadcast managers during the 1990s yielded consistently low response rates. Implications for research are discussed.


Genome-wide comparative analysis ofbone morphogenetic proteins: genomic structure, phylogeny, and expression patterns in the golden pompano,Trachinotus ovatus(Linnaeus, 1758).
Bone morphogenetic proteins (BMPs) play important roles in various physiological processes, especially during the formation and maintenance of various organs. In this study, we first obtained and characterized twenty BMP genes from the Trachinotus ovatus genome (designated as ToBMPs). Sequence alignment and phylogenetic analysis both indicated that the predicted amino acid sequences of ToBMP were highly conserved with corresponding homologs of other species. Moreover, a comparative analysis was performed with seven representative vertebrate genomes and found difference in number of BMP3 genes in different species, which three members, BMP3a, BMP3b-1, and BMP3b-2, existed in diploid T. ovatus, but there were four and two members in tetraploidized Cyprinus carpio (BMP3a-1, BMP3a-2, BMP3b-1, and BMP3b-2) and diploid Danio rerio (BMP3a and BMP3b), respectively. The amino acid alignment and genomic structure analysis of ToBMP3 also suggested that the BMP3 gene had expanded in T. ovatus. Furthermore, tissue expression patterns were assessed for the small intestine, liver, white muscle, brain, spleen, fin, gill, head kidney, stomach, blood, and gonads. It was discovered that BMP1, BMP2, BMP3a, BMP4, BMP6, BMP7b, BMP11, and BMP16 were ubiquitously expressed in all the tissues tested. To study the regulatory function of BMP in response to the intake of different types of food, the expression changes in BMP mRNAs were detected by qRT-PCR, and the results showed that the majority of the BMP genes had the highest mRNA levels in the small intestine and liver after ingesting pelleted feed. Our data provide a useful resource for further studies on how paralogous genes may have different expression profiles in T. ovatus.


Rat strain comparisons on drug and sleep sensitive behaviors.
Rat swimming behaviors have been productive in both sleep research and neuropharmacology. In this report, both of these areas are addressed in the context of inbred strain effects. Thirty-two rats from three stocks were tested in a seven day, repeated measures design. Each rat swam for 5 min each day in shallow 25 degrees C water. There were significant differences between inbred stocks on two measures which can be related to both REM sleep deprivation and adrenergic drug effects. Nonsignificant strain differences were found on two other behaviors which also lack significance under REM sleep deprivation and atropine sulfate treatments. It is concluded that there may be differential stress affecting the treatment-sensitive and the change-resistant behaviors.


Isopropanol ingestion: case report with pharmacokinetic analysis.
An unusual case of acute isopropanol overdose which occurred within the confines of the emergency department is reported. Serial serum concentrations of isopropanol and its metabolite acetone were followed for 43 hours. Pharmacokinetic analysis is presented, as well as a brief literature review of diagnosis and management. CNS toxicity was related mainly to isopropanol concentrations. The calculated half-life of isopropanol was 7.3 hours. Because of the pharmacokinetic profile of isopropanol, management decisions regarding the use of hemodialysis should be made within one to two hours of patient presentation.


Draft Genome Sequence of Flavobacteriumpsychrophilum Strain SSADA-1411, Isolated from an Ayu (Plecoglossus altivelis altivelis) Migrating Downriver To Spawn in the Shimanto River, Kochi, Japan.
Here, we report the draft genome sequence and annotation of Flavobacterium psychrophilum strain SSADA-1411. This strain was isolated from the skin ulcer of an ayu (Plecoglossus altivelis altivelis) migrating downriver to spawn in the lower Shimanto River, in western Kochi Prefecture on Shikoku Island in Japan.


Multidimensional-Taylor-network-based robust optimal tracking control for MIMO nonlinear discrete-time systems.
In practical engineering, system control is indispensable. However, due to the influence of model uncertainty, speed unavailability, input nonlinearity (such as actuator dead zone/fault), and multi-input coupling, the control results are not satisfactory. In this paper, a robust optimal tracking control strategy is proposed for a class of nonlinear multi-input-multi-output discrete-time systems with unknown uncertainties. This control strategy is to minimize the cost function in the process of uncertainty processing and stabilize the closed-loop system by establishing an adaptive controlling approach based on a combination of actor MTN and critic MTN based on the Multi-dimensional Taylor Network (MTN). By using the approximation property of MTN, the optimal control signal is generated by action MTN, which is used to approach the controller, and the cost function is approximated by critic MTN, which is tuned online because the cost function cannot be obtained in hands-on experience. By designing a new cost function, the amount of calculation in the control process is reduced, and the adaptive critic design control idea is integrated into the controller design to deal with the uncertainty of the system. The simulation results verify the effectiveness of the control strategy proposed in the essay.


SAMe treatment prevents the ethanol-induced epigenetic alterations of genes in the Toll-like receptor pathway.
Prior studies showed that Toll-like receptor (TLR) signaling pathway genes were upregulated in the liver of rats fed ethanol, but not in rats fed ethanol plus S-adenosylmethionine (SAMe). These results were obtained using a PCR microplate array analysis for TLRs and associated proteins such as proinflammatory cytokines and chemokine mRNA levels. A large number of genes were upregulated by the ethanol diet, but not the ethanol plus SAMe diet. In the present study, using the same experimental rat livers, DNA methylation analysis was done by using an Epitect Methyl DNA Restriction Kit (Qiagen, 335451) (24 genes). The results of all the genes combined show a highly significant increase in methylation in the ethanol-fed group of rats, but not in the dextrose-fed, SAMe-fed or ethanol plus SAMe-fed groups of rats. There was also an increase in DNA methylation in rats with high blood alcohol levels compared to a rat with a low blood alcohol level. The individual genes that were upregulated as indicated by the increased mRNA measured by qPCR correlated positively with the increased methylation of the DNA of the corresponding genes as follows: Cd14, Hspa1a, Irf1, Irak1, Irak2, Map3k7, Myd88, Pparα, Ripk2, Tollip and Traf6.


A novel bidirectional regulation mechanism of mancozeb on the dissemination of antibiotic resistance.
The high abundance of antibiotic resistance genes (ARGs) in the fungicide residual environment, posing a threat to the environment and human health, raises the question of whether and how fungicide promotes the prevalence and dissemination of antibiotic resistance. Here, we reported a novel mechanism underlying bidirectional regulation of a typical heavy-metal-containing fungicide mancozeb on the horizontal transfer of ARGs. Our findings revealed that mancozeb exposure significantly exerted oxidative and osmotic stress on the microbes and facilitated plasmid-mediated ARGs transfer, but its metallic portions (Mn and Zn) were potentially utilized as essential ions by microbes for metalating enzymes to deal with cellular stress and thus reduce the transfer. The results of transcriptome analysis with RT-qPCR confirmed that the expression levels of cellular stress responses and conjugation related genes were drastically altered. It can be concluded mancozeb bidirectionally regulated the ARGs dissemination which may be attributed to the diverse effects on the microbes by its different portions. This novel mechanism provides an updated understanding of neglected fungicide-triggered ARGs dissemination and crucial insight for comprehensive risk assessment of fungicides.


Comparative analysis of fecal metabolite profiles in HFD-induced obese mice after oral administration of huangjinya green tea extract.
To explore the impact of Huangjinya on metabolic disorders and host endogenous metabolite profiles, high-fat diet (HFD)-fed mice were administrated with Huangjinya green tea extract (HGT) at the dose of 150 or 300 mg/kg for 9 weeks. Epigallocatechin gallate was the main catechin derivative, followed by epigallocatechin and catechin presented in HGT, which contained high levels of free amino acids (50.30 ± 0.60 mg/g). HGT significantly alleviated glucose and insulin intolerance, reduced hepatic lipid accumulation and liver steatosis, and prevented white adipose tissue expansion in HFD-fed mice. Untargeted mass spectrometry-based metabolomics analysis revealed that HGT reduced the abundance of fecal branched-chain amino acids, aromatic amino acids, sphingolipids, and most acyl cholines, modulated bile acid metabolism by increasing chenodeoxycholate and reducing cholic acid content, and increased unsaturated fatty acids content. Fatherly, HGT activated insulin/PI3K/Akt and AMPK signaling pathways in the liver, reduced adipogenic and lipogenic genes expression, and promoted the genes expression related to lipolysis and adipocyte browning in white adipose tissue, contributed to improving metabolic syndrome in HFD-fed mice. The current study reported the impact of HGT supplementation on endogenous metabolite profiles, and highlights the positive roles of HGT in preventing diet-induced obesity and the related metabolic disorders.


Illness perceptions, mood and quality of life: a systematic review of coronary heart disease patients.
To examine published literature investigating the relationship between illness perceptions, mood and quality of life (QoL) in coronary heart disease (CHD) populations. Key databases were systematically searched (CINAHL, Medline, PsycINFO, Scopus and Web of Science) for studies matching the inclusion criteria between November 2011 and February 2012. References of included studies were examined and key authors contacted. Studies were subject to a quality control check. 21 studies met the inclusion criteria. A synthesis of the results found that illness perceptions were correlated to and predicted QoL and mood across CHD diagnoses. Specific illness perceptions (control, coherence and timeline) were found to be important for patients that had experienced an unexpected medical event, such as myocardial infarction. The results of this study provide support that illness perceptions are related to outcomes across CHD populations and disease progression, however the results do not selectively support one particular model. Recommendations are consistent with cardiac rehabilitation guidelines. Further research should focus on the systemic impact of illness perceptions.


Sources of social support as determinants of psychiatric morbidity after severe life events: prospective cohort study of female employees.
The aim of this study was to study prospectively the associations between sources of social support, life events, and psychiatric morbidity, as explicated in the chronic strain and the stress-buffering hypotheses. Psychiatric morbidity and sources of social support were assessed at Time 1 and 3 years later at Time 2 among 4250 female municipal employees. At Time 2, the participants were also asked about their preceding life events during the year. After adjustment for baseline characteristics, low support from one's partner, coworkers, and supervisor at Times 1 and 2 was positively associated with psychiatric morbidity at Time 2 (OR = 1.1-1.6). The support of friends at Time 1 lowered the risk of psychiatric morbidity after death or severe illness in the family and after interpersonal conflict. High postevent network heterogeneity also lowered the risk of psychiatric morbidity after financial difficulty. For the remaining 33 combinations between different sources of social support and life events, no corresponding interactions were found. The observed associations support the chronic strain hypothesis, but the support for the stress-buffering hypothesis was limited.


Single-port robotic-assisted partial nephrectomy: initial clinical experience and lessons learned for successful outcomes.
The Intuitive Surgical DaVinci SP ("Single Port") robotic platform was approved in 2014, but, recently, there has been a dissemination of the technology with multiple urological procedures successfully adapted to this robot. There are some important differences from prior models. We aimed to share our early outcomes and lessons learned for performing successful single-port robotic-assisted partial nephrectomy (SP-RAPN). This study is a retrospective review of sequential SP-RAPN cases between 7/2019 and 3/2020. We extracted patient characteristics and early surgical outcomes. Surgical tips and tricks were recorded during these cases and compiled. SP-RAPN was successfully completed in 12 patients. Patients mean age was 57.8 ± 11.0 years and median ASA score was 2. Mean tumor size was 3.1 ± 2.2 cm. The average OR Time was 172 ± 41 min and EBL was 68 ± 75 mL. All cases had warm ischemia time < 25 min. Tumor pathology included 8 RCC (6 pT1a, 1 pT1b, 1 pT2a), 2 AML, and 2 oncocytoma. There were no complications. Our top surgical tips involved: (1) patient positioning, (2) port placement, (3) insufflation, (4) air docking, (5) assistant port placement, (6) dynamic arm control, (7) hilar clamping, (8) camera relocation, (9) tumor excision, and (10) extraction and port closure. SP-RAPN is safe and feasible in this series. There are advantages and disadvantages to this platform. As the technology matures and techniques evolve, SP-RAPN may become more appealing. Future studies should focus on long-term outcomes and cost-effectiveness of the SP system.


Variations in institutional review board reviews of a multi-center, Emergency Department (ED)-based genetic research protocol.
In the United States, institutional review boards (IRBs) oversee the scientific, ethical, and regulatory aspects of research conducted on human subjects. Institutional variations in the interpretation and application of federal and local regulations concerning genetic testing can have significant impact on the implementation of such studies. We assessed variability in IRB review of a multi-center Emergency Department-based study examining genotypic and phenotypic predictors of pain and psychological outcomes after minor motor vehicle collision (Project CRASH). This is one of the first multi-center genetic research protocols based solely in the Emergency Department (ED). We performed an observational study of sites participating in Project CRASH. We collected IRB information and correspondence from each site. We collected data that included information regarding institution demographics, original IRB application characteristics, subsequent IRB correspondence, and time interval between submission and approval. Descriptive statistics were used in analysis. All sites that initially agreed to participate in Project CRASH also participated in this study (n = 7). The time interval in receiving IRB approval varied between 20-760 days (median 105, IQR 21-225). One site appeared to be an outlier (760 days). The most commonly requested changes were changes to the consent form. Institutional interpretation of regulations regarding our ED-based genetic study was highly variable. Although the majority of our results are consistent with other similar published studies, the mean time interval for approval for this genetic study is far greater than other reported studies.


Growth kinetics and power laws indicate distinct mechanisms of cell-cell interactions in the aggregation process.
Cellular aggregation is a complex process orchestrated by various kinds of interactions depending on the environment. Different interactions give rise to different pathways of cellular rearrangement and the development of specialized tissues. To distinguish the underlying mechanisms, in this theoretical work, we investigate the spontaneous emergence of tissue patterns from an ensemble of single cells on a substrate following three leading pathways of cell-cell interactions, namely, direct cell adhesion contacts, matrix-mediated mechanical interaction, and chemical signaling. Our analysis shows that the growth kinetics of the aggregation process are distinctly different for each pathway and bear the signature of the specific cell-cell interactions. Interestingly, we find that the average domain size and the mass of the clusters exhibit a power law growth in time under certain interaction mechanisms hitherto unexplored. Further, as observed in experiments, the cluster size distribution can be characterized by stretched exponential functions showing distinct cellular organization processes.


Potentiation of bromotrichloromethane hepatotoxicity and lethality by chlordecone preexposure in the rat.
These studies were designed to provide dose-response relationships for chlordecone (CD) potentiation of BrCCl3 hepatotoxicity in male rats using biochemical, functional and histopathological parameters. The influence of this interaction on BrCCl3 lethality was also examined. Male Sprague-Dawley rats (175-200 g) received a single ip dose of 1, 5, 10, 15 or 25 microL BrCCl3/kg following a 15 day dietary pretreatment of 0 or 10 ppm CD. Twenty four hrs after BrCCl3 challenge, biliary excretion of phenolphthalein glucuronide (PG), bile flow, serum transaminases (SGOT and SGPT), serum ICD and OCT were examined as functional and biochemical indices of hepatic injury. Effect of CD on 48 hr LD50 of BrCCl3 was also examined using the method of moving averages. With the exception of 1 microL BrCCl3/kg dose which had no effect, CD-BrCCl3 combination resulted in potentiation of hepatotoxicity by all parameters examined. Activity of all the serum enzymes was elevated in a dose related manner. A dose related decrease in the biliary excretion of PG and bile flow was observed. These effects were more pronounced at the higher doses of BrCCl3. Extensive centrilobular necrosis was observed in the animals given CD-BrCCl3 combination and the necrogenic effect was more severe at the doses of 15 microL and 25 microL BrCCl3/kg. BrCCl3-lethality was increased 5-fold by CD as indicated by the decreased LD50. The results suggest that CD-induced BrCCl3 toxicity is manifested both in the form of hepatotoxicity and lethality and since the hepatic functional status is greatly compromised, the CD potentiated hepatic failure is related to lethality.


Simultaneous determination of seven alkaloids in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study after oral administration of Cerebralcare Granule.
An ultra fast liquid chromatography-tandem mass sepectrometry (UFLC-MS/MS) method was developed for simultaneous determination of seven active alkaloid components (tetrahydropalmatine, corydaline, α-allocryptopine, tetrahydroberberine, tetrahydrocoptisine, tetrahydrocolumbamine and dehydrocorydaline) in rat plasma after oral administration of Cerebralcare Granule. Plasma samples were pretreated by protein precipitation with acetronitrile containing the internal standard diazepam. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with gradient elution using mobile phase consisting of acetonitrile -0.1% formic acid in water at a flow rate of 0.3mL/min. The detection was performed on an electrospray ionization triple quadrupole tandem mass spectrometer using multiple reaction monitoring (MRM) with positive ionization mode. The established method was fully validated and proved to be sensitive and specific with lower limits of quantification (LLOQs) all less than 0.0265ng/mL in rat plasma. Good linearities of seven alkaloids were obtained in respective concentration ranges (r>0.9923). The intra- and inter-day precisions were below of 15% for all the seven alkaloids in terms of relative standard deviation (RSD), and the accuracies were ranged from -2.7% to 8.3% in terms of relative error (RE). Extraction recovery, matrix effect and stability were within the required limits in rat plasma. The validated method was successfully applied to investigate the pharmacokinetics of the seven alkaloids in rat plasma after oral administration of Cerebralcare Granule (CG).


Autoinjector - A smart device for emergency cum personal therapy.
Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases.


Using contingent choice methods to assess consumer preferences about health plan design.
American insurers are designing products to contain health care costs by making consumers financially responsible for their choices. Little is known about how consumers will view these new designs. Our objective is to examine consumer preferences for selected benefit designs. We used the contingent choice method to assess willingness to pay for six health plan attributes. Our sample included subscribers to individual health insurance products in California, US. We used fitted logistic regression models to explore how preferences for the more generous attributes varied with the additional premium and with the characteristics of the subscriber. High quality was the most highly valued attribute based on the amounts consumers report they are willing to pay. They were also willing to pay substantial monthly premiums to reduce their overall financial risk. Individuals in lower health were willing to pay more to reduce their financial risk than individuals in better health. Consumers may prefer tiered-benefit designs to those that involve overall increases in cost sharing. More consumer information is needed to help consumers better evaluate the costs and benefits of their insurance choices.


Consequences of Insurance Coverage Delays and Denials for Patients With Hereditary Angioedema.
Hereditary angioedema (HAE) is a rare and potentially fatal genetic disease associated with recurrent and unpredictable episodes of angioedema. Although modern therapies have dramatically increased quality of life, insurance changes, delays, and denials are becoming more common. To examine the impact of insurance delays and denials on patient health and well-being. A total of 20 patients with HAE (type 1 and 2) who recently experienced insurance delays or denials completed an online survey, and 19 participated in a follow-up focus group. The survey and focus group addressed the impact of insurance challenges on the use of health care services, work/school attendance, and anxiety. Three independent reviewers coded each focus group transcript using a thematic saturation approach. A total of 70% of participants reported an increased frequency of angioedema attacks resulting from insurance delays or denials. More than 50% missed work/school days because of increased attacks, and 90% reported greater anxiety. Twenty-five percent of respondents reported more urgent care or emergency department visits. In focus groups, participants identified specific ways that losing access to medication had a negative impact on their health, family, and work/school life. Insufficient notification of health insurance policy changes and the time and effort required to regain access to medications compounded patients' frustration and anxiety. Insurance delays and denials have significant impacts on individuals with HAE including (1) increased urgent care and emergency department visits, (2) missed work/school days, (3) higher levels of anxiety, and (4) a negative impact on family life.


Thyroid dysfunction and nodular goiter in hemodialysis and peritoneal dialysis patients.
To investigate the prevalence of nodular goiter and thyroid dysfunction in uremic patients undergoing hemodialysis (HD) and peritoneal dialysis. Cross-sectional study. Single dialysis unit and outpatient clinic. The study included 221 patients [143 HD and 78 continuous ambulatory peritoneal dialysis (CAPD) patients] along with 135 consecutively selected outpatients as controls. Ultrasonography was used to detect patients' thyroid function and nodular goiter. Nodular goiter was detected in 54.8% of the uremic patients and in 21.5% of the controls. Uremic patients had higher prevalence of thyroid dysfunction, which included reduced serum concentration of total T3, total T4, and free T4, and increased serum level of TSH. Hypothyroidism was also observed more frequently in uremic patients than in the control group (5.4% vs 0.7%, p < 0.05). Nodular goiter was more frequently found in females than in males (63.5% vs 48%, p < 0.05). Moreover, the prevalence of nodular goiter increased with age (p < 0.02) in uremic patients. Hemodialysis patients had a higher frequency of reduced total T3 level (46.9% vs 29.5%, p < 0.02). However, CAPD patients had lower T4 levels (6.23+/-1.82 microg/dL vs 7.15+/-1.99 microg/dL, p < 0.05). Because of the high incidence of hypothyroidism and nodular goiter in uremic patients, screening of thyroid function and goiter detection with ultrasound should be considered in evaluation of end-stage renal disease patients.


Residue dynamics and dietary risk assessment of new formulation of novaluron and lambda cyhalothrin on tomato.
Presence of residues on food commodities is major bottleneck of insecticide use under good agricultural practices (GAPs). The use of less persistent with two different mode of action insecticide is novel approach of getting maximum insect control without developing insecticide resistance. Novaluron, an insect growth disruptor and lambda cyhalothrin, a nerve poison has been used widely for the management of lepidopteran pests. Dissipation and consumer risk analysis studies were carried out on a new combination product of novaluron and lambda cyhalothrin are used for control insects of tomato at recommended standard dose of 71 + 14 g/ha and double dose of 142 + 28 g/ha of active ingredients. Extraction and cleanup of sample residues was done using QuEChERS technique and analyzed in GC-ECD. The residues of novaluron were dissipated within 10 to 15 days, and the residues of lambda cyhalothrin were at 7 to 10 days, both at the standard and double the standard dose, following a first order reaction kinetics. Analysis of risk and hazard quotient revealed that the test insecticides do not pose any dietary risk to consumer as TMDI < MPI and HQ < 1.


Cold exposure or norepinephrine injections altered melatonin levels in the quail retina.
The possible involvement of ambient temperature and norepinephrine on daytime levels of retinal melatonin were investigated in quails. For a minimum of 1 week, experimental animals were housed under constant room temperature of 23 +/- 2 degrees C and a daily 12:12 h light-dark cycle with light on at 06.00-18.00 h. The quails were then transferred to a cold room of 4 degrees C and cold-exposed for 0, 30, 60, 90 and 120 min. Retina samples were subsequently collected at mid-light for melatonin radioimmunoassay. An initial decline of melatonin was detected in the cold treated birds after 30 min of exposure. Thereafter prolongation of cold stimulation produced significant increases in the levels of retinal melatonin. In the second experiment, intra-peritoneal norepinephrine injections (0, 1, 10 and 100 micrograms/bird) at mid-light were found to increase the levels of retinal melatonin in quails. We postulate the cold-induced increase of retinal melatonin may be attributed to an augmented level of catecholamines released as a general neuroendocrine response to temperature decrements.


Immunology in the clinic review series; focus on cancer: glycolipids as targets for tumour immunotherapy.
Research into aberrant glycosylation and over-expression of glycolipids on the surface of the majority of cancers, coupled with a knowledge of glycolipids as functional molecules involved in a number of cellular physiological pathways, has provided a novel area of targets for cancer immunotherapy. This has resulted in the development of a number of vaccines and monoclonal antibodies that are showing promising results in recent clinical trials.


The acute effects of ultraviolet-B radiation on c-myc and c-Ha ras expression in normal human epidermis.
It is well known that ultraviolet radiation (UVR) causes DNA damage due to the formation of photoproducts which result in the inhibition of DNA synthesis. It has been reported that DNA damage by physical agents such as UVR and chemical carcinogens induces alteration of certain gene expressions. Recently the transient induction of c-myc and c-Ha ras proto-oncogene expressions has been observed in a human keratinocyte cell line in vitro. The present study was designed to investigate whether the induction of these proto-oncogenes occurs in normal human epidermis after UVR in vivo and to relate these findings to DNA synthesis. C-myc and c-Ha ras transcripts were detected throughout human epidermis before and after UVR. C-myc expression increased significantly 5 h after two times the minimal erythema dose (2 x MED) of UVR, while DNA synthesis of the irradiated skin had recovered from the UVR-induced inhibition. The intensity of c-Ha ras expression remained unchanged at both 5 and 24 h after UVR. These results suggest that the c-myc gene plays an important role in the recovery of keratinocytes from acute damage following UVR.


The Viability of an Artificial Intelligence/Machine Learning Prediction Model to Determine Candidates for Knee Arthroplasty.
The purpose of this study is to assess the viability of a knee arthroplasty prediction model using 3-view X-rays that helps determine if patients with knee pain are candidates for total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), or are not arthroplasty candidates. Analysis was performed using radiographic and surgical data from a high-volume joint replacement practice. The dataset included 3 different X-ray views (anterior-posterior, lateral, and sunrise) for 2,767 patients along with information of whether that patient underwent an arthroplasty surgery (UKA or TKA) or not. This resulted in a dataset including 8,301 images from 2,707 patients. This dataset was then split into a training set (70%) and holdout test set (30%). A computer vision model was trained using a transfer learning approach. The performance of the computer vision model was evaluated on the holdout test set. Accuracy and multiclass receiver operating characteristic area under curve was used to evaluate the performance of the model. The artificial intelligence model achieved an accuracy of 87.8% on the holdout test set and a quadratic Cohen's kappa score of 0.811. The multiclass receiver operating characteristic area under curve score for TKA was calculated to be 0.97; for UKA a score of 0.96 and for No Surgery a score of 0.98 was achieved. An accuracy of 93.8% was achieved for predicting Surgery versus No Surgery and 88% for TKA versus not TKA was achieved. The artificial intelligence/machine learning model demonstrated viability for predicting which patients are candidates for a UKA, TKA, or no surgical intervention.


Localization of foetal antigen 2 (FA-2) in foetal and adult human skin.
Foetal antigen 2 (FA-2) is a connective-tissue-associated antigen isolated from second trimester human amniotic fluid. FA-2 has an alpha-electrophoretic mobility and is a single-chain molecule with a molecular weight of 26 kDa as determined by polyacrylamide gel electrophoresis (PAGE). Using indirect immunofluorescence and the immunoperoxidase technique, FA-2 was found to be in the lamina densa/sublamina densa region of the basement membrane zone (BMZ) in adult as well as in foetal skin. FA-2 was found throughout the dermis in foetal skin, whereas in adult skin it was found to be associated with the BMZ and around the blood vessels, hair follicles and eccrine glands. Intracellular FA-2 antigen was demonstrated in proliferating fibroblasts by the indirect immunoperoxidase technique and immunoelectron microscopy of the fibroblasts revealed staining of the antigen in the cisternae of the rough endoplasmatic reticulum at the trans-side of the Golgi complex as well as in vesicles close to the plasma membranes. FA-2, a hitherto undescribed antigen associated with human BMZ, is probably being synthesized by proliferating fibroblasts.


[Multiple sclerosis: atrophy of the corpus callosum and psychosyndrome].
Examination with magnetic resonance imaging of 176 patients with multiple sclerosis showed that corpus callosum (CC) atrophy is common. The thinning of the CC depends on the extension of the coalescent periventricular white matter changes. A highly significant association was found between CC-atrophy and, the severity of organic mental disorder.


In Situ Splitting of the Cadaver Liver for Two Adult Recipients by LDLT Technique.
To expand the donor pool, split liver transplantation is conventionally performed for one adult and one pediatric recipient. Application of this technique for two adult recipients can produce remarkable impact on the waiting list. Proper donor and recipient selection is crucial for the favorable outcome following full-right and full-left liver split. Right lobe adult to adult living donor liver transplantation (LDLT) is essentially a full right and full left split. However, LDLT techniques have not been used for full right and left split. We performed in situ splitting of the whole liver using LDLT techniques from a hemodynamically stable young deceased donor and transplanted into two adult recipients, both with model for end-stage liver disease score of 17. The transection was carried out through the midplane of liver, generating a right lobe and a left lobe graft. Both the recipients had uneventful postoperative recovery. At ten months of follow up, both the recipients are doing well with good liver function. Based on the concept of living related liver transplantation, our case explores the technical feasibility of full-right and full-left in situ liver split.


Accidental intravenous administration of enteral feeds by a patient with cystic fibrosis.
Young adults with cystic fibrosis are actively encouraged to take increasing self-responsibility, both at home and in hospital, for their often complicated therapeutic regimens. Many patients manage both their intravenous antibiotics and overnight enteral feeds. In our unit strict training protocols are followed to ensure that patients fully understand, and can safely perform, any procedure for which they will subsequently be responsible. Nonetheless, a 21-year-old man with cystic fibrosis admitted for treatment of his acute respiratory deterioration inadvertently attached his disconnected nasogastric feeding line to his intravenous access site during the night. Approximately 500 ml of enteral feed was administered intravenously with subsequent fevers, rigors, tachycardia, and vomiting. This is the first report of the patient, rather then the medical staff, inadvertently connecting the enteral feeding line to the intravenous access site.


Proximity-Dependent Biotinylation (BioID) of Integrin Interaction Partners.
Integrins are heterodimeric adhesion receptors that maintain cell-extracellular matrix (ECM) interactions in diverse tissue microenvironments. They mediate cell adhesion and signaling through the assembly of large cytoplasmic multiprotein complexes that focally connect with the cytoskeleton. Integrin adhesion complexes (IAC) are specialized by the type of integrin-ECM contact and are sensitive to mechanical forces. Thus, they encrypt context-dependent information about the microenvironment in their composition. Signals mediated through IACs modulate many aspects of cell behavior, which allows cells to adapt to their surroundings. To gain insights into their function, IACs have been isolated from cultured cells and explored by proteomics. IACs are insoluble by nature and held together by transient/weak interactions, which makes it challenging to isolate intact IACs. Usually all IACs coupled to a specified ECM, which may employ different integrins, are isolated. Here we describe an alternative method based on proximity-dependent biotin identification (BioID), where specific integrin interaction partners are labeled in live cells and isolated without the need to isolate intact IACs.


Benzimidazole-4,7-diones as inhibitors of protozoal (Toxoplasma gondii) purine nucleoside phosphorylase.
Benzimidazole-4,7-diones derivatives substituted at 1- and/or 2-position have been synthetized and tested as inhibitors of purine nucleoside phosphorylase (PNP), isolated from two strains of Toxoplasma gondii (RH and ME 49). They were identified as inhibitors of both enzymes.


Non-invasive assessment of motor unit activation in relation to motor neuron level and lesion location in stroke and spinal muscular atrophy.
Neuromuscular disorders e.g. spinal muscular atrophy and stroke have a negative impact on functional movement capability. These disorders affect lower and upper motor neurons respectively. In this study high spatial resolution electromyography was used to record the motor unit activity in 3 groups: healthy subjects, a spinal muscular atrophy group and a stroke group. 7 clinically sensitive parameters were used to analyze the activation patterns of a few motor units. In the case of spinal muscular atrophy there was no effect on motor unit activation but on their number. Stroke was characterized by fewer active motor units and a significantly reduced firing rate with low variability. The results suggest, that for stroke, information from the brain is modified thereby resulting in motor units firing at their natural frequency. Thus, high spatial resolution electromyography and the chosen parameters facilitate non-invasive, objective differentiation and analysis of the activation patterns of motor units in neuromuscular disorders.


Phylogenetic analyses of peanut resistance gene candidates and screening of different genotypes for polymorphic markers.
The nucleotide-binding-site-leucine-rich-repeat (NBS-LRR)-encoding gene family has attracted much research interest because approximately 75% of the plant disease resistance genes that have been cloned to date are from this gene family. Here, we describe a collection of peanut NBS-LRR resistance gene candidates (RGCs) isolated from peanut (Arachis) species by mining Gene Bank data base. NBS-LRR sequences assembled into TIR-NBS-LRR (75.4%) and non-TIR-NBS-LRR (24.6%) subfamilies. Total of 20 distinct clades were identified and showed a high level of sequence divergence within TIR-NBS and non-TIR-NBS subfamilies. Thirty-four primer pairs were designed from these RGC sequences and used for screening different genotypes belonging to wild and cultivated peanuts. Therefore, peanut RGC identified in this study will provide useful tools for developing DNA markers and cloning the genes for resistance to different pathogens in peanut.


Prescribing of nicotine replacement therapy to cardiovascular disease patients in England.
In November 2005 the indications for nicotine replacement therapy (NRT) were broadened in the United Kingdom, making all forms available to patients with stable cardiovascular disease (CVD). This study aimed to estimate the effects of this change on prescribing of NRT to CVD patients in England. Segmented regression analysis of time series of monthly rates of prescribing of NRT. A total of 350 general practices in England included in The Health Improvement Network (THIN), a database of UK electronic primary care records. All adult patients with coronary heart disease (CHD) or stroke registered with a THIN practice in England. The number of patients per 100,000 with CHD and stroke that received a prescription for NRT each month between January 2002 and June 2009. Approximately 1500 per 100,000 smokers with CVD were prescribed NRT per month. Prescribing of NRT to CHD and stroke patients increased until the end of 2005 and subsequently decreased, with no immediate change following the Medicines and Healthcare Regulatory Authority (MHRA) licensing change. Broadening the marketing licence in the United Kingdom for nicotine replacement therapy to allow it to be prescribed to patients with CVD did not increase prescribing rates for this group of patients.


Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti.
The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is the best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. Previous work has evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. Specifically, insulin-fed mosquitoes resulted in reduced virus replication in an RNAi-independent, ERK-mediated JAK/STAT-dependent mechanism. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both RNAi and JAK/STAT antiviral pathways. ZIKV-infected Aedes aegypti were fed blood containing demethylasterriquinone B1 (DMAQ-B1), a potent insulin mimetic, in combination with AKT inhibitor VIII. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti. This effect included a quantitatively greater reduction in salivary gland ZIKV levels up to 11 d post-bloodmeal ingestion, relative to single pathway activation. Together, our study indicates the potential for field delivery of these small molecules to substantially reduce virus transmission from mosquito to human. As infections like Zika virus are becoming more burdensome and prevalent, understanding how to control this family of viruses in the insect vector is an important issue in public health.


Fatty acid pattern of red blood cell membranes and risk of ischemic brain infarction: a case-control study.
The fatty acid composition of red blood cell membranes (which reflects dietary fat intake) was studied in 28 male patients with recent (less than 3 days) ischemic stroke and 56 matched controls. Fifteen fatty acids were measured by means of chromatographic analysis. Percentages of linoleic, 22:5, and 22:6 acids were significantly lower in red blood cell membranes of stroke patients than in those of matched controls. The results suggest that a low unsaturated fatty acid diet could be an independent risk factor for ischemic brain infarction.


Cytokines in Alzheimer's disease and vascular dementia.
The levels of interleukin 1beta, interleukin 6, and interleukin 10 were elevated in the serum of patients with dementia. No statistically significant correlation was recorded in the interleukin levels among patients with Alzheimer's disease and vascular dementia. Also, no significant correlation was observed in the interleukin levels in the serum and the severity of dementia. However, a significant correlation was found between IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels and age. The levels of IL-1beta and IL-6 were positively correlated with hypertension, and IL-2 levels were negatively correlated. No correlation was found between depressive symptoms and levels of cytokines in the serum.


New lesion segmentation for multiple sclerosis brain images with imaging and lesion-aware augmentation.
Multiple sclerosis (MS) is an inflammatory and demyelinating neurological disease of the central nervous system. Image-based biomarkers, such as lesions defined on magnetic resonance imaging (MRI), play an important role in MS diagnosis and patient monitoring. The detection of newly formed lesions provides crucial information for assessing disease progression and treatment outcome. Here, we propose a deep learning-based pipeline for new MS lesion detection and segmentation, which is built upon the nnU-Net framework. In addition to conventional data augmentation, we employ imaging and lesion-aware data augmentation methods, axial subsampling and CarveMix, to generate diverse samples and improve segmentation performance. The proposed pipeline is evaluated on the MICCAI 2021 MS new lesion segmentation challenge (MSSEG-2) dataset. It achieves an average Dice score of 0.510 and F 1 score of 0.552 on cases with new lesions, and an average false positive lesion number n FP of 0.036 and false positive lesion volume V FP of 0.192 mm 3 on cases with no new lesions. Our method outperforms other participating methods in the challenge and several state-of-the-art network architectures.


The anti-inflammatory and analgesic activities of the ethyl acetate extract of Viburnum taitoense Hayata.
Viburnum taitoense Hayata has been used as folk medicine by the minority people in Southwestern China for a long history, especially in Guangxi Zhuang Autonomous Region. The minority in Guangxi including Zhuang, Miao and Yao people use the ethanol extract of V. taitoense Hayata to treat the fracture, kill the pain of rheumatism because of its definite therapeutic effects. So far, the scientific investigation of V. taitoense Hayata is done very little. Here, we first prepared the ethyl acetate extract of V. taitoense (EEVt), secondly measured the contents of phenols, flavonoids, and terpenoids in EEVt, and thirdly, the anti-inflammatory and analgesic activities of EEVt were investigated by invitro model of RAW 264.7 cells and invivo models of inflammation and pain in rats and mice. The contents of phenols, flavonoids, and terpenoids in EEVt were determined by UV spectrophotometry, respectively. The anti-inflammatory effect of EEVt (5, 25, 50, 100, and 200 μg/mL) in vitro was tested by determining its inhibitory effect on the nitric oxide production of RAW264.7 cells activated by lipopolysaccharide (LPS). The anti-inflammatory and analgesic effects of EEVt in vivo were investigated in the following experimental rats and mice models: carrageenan-induced paw edema, corton-oil-induced ear edema, acetic acid writhing test, and formalin pain test. The contents of total phenolic, total flavonoids, and total triterpenoids in V. taitoense were measured to be 3.46 ± 0.04%, 2.38 ± 0.04%, and 14.96 ± 0.17%, respectively. In vitro test showed that EEVt at different tested dosages (5, 25, 50, 100, and 200 μg/mL) had no significant toxicity to RAW264.7 macrophages. At dosages of 37.5 and 75 μg/mL of EEVt significant inhibitory (p < 0.001) on the productions of nitric oxide (NO). High dosage (200 μg/mL) of EEVt displayed highly significant inhibitory (p < 0.001) on the productions of proinflammatory cytokines IL-6, IL-1β, and TNF-α from the LPS-induced RAW264.7 macrophages. EEVt showed obvious anti-inflammatory activity at different time points after carrageenan injection (p < 0.05) in vivo test, and its anti-inflammatory activity reached the strongest 4 h. Similarly, through the ear swelling test, EEVt (200 mg/kg) showed significant (p < 0.05) anti-inflammatory activity. Besides, formalin and acetic acid writhing experiments also showed that EEVt has significant (p < 0.05) analgesic activity. EEVt was confirmed to be definite anti-inflammatory and analgesic effects, and the phytochemicals of EEVt was disclosed to be rich in triterpenoids, which was worthy to be further investigated.


[Optimization in planning and application of 60 Co gamma irradiations - analysis of the problem (author's transl)].
As an aspect of the complex problem of optimization in therapeutical transmission of radiation energy to Man, the dose distribution within a cross-sectional area of the body is considered. For the judgement on optimal dose distributions, involving judgement on irradiation technique, boundary conditions are needed which encompass important parameters of a dose distribution (= criterion for optima). For computer-assisted optimization the boundary conditions are to be scheduled by an appropriate algorithm. The parameters describing a dose distribution are indicated. Practical utilization of computer-assisted optimization of dose is represented by means of two optimization schedules.


Drug treatment of pain in rheumatoid disorders.
The relief of pain remains a delicate balance between the potential toxicity and desired effect of currently available compounds. Physician and patient need to make the optimum use of such therapies. Control of pain and stiffness in rheumatic diseases is a dynamic process. There is a constant need for re-appraisal of aims and objectives and adjustment of treatment according to variations in disease and response. Where 'specific' therapy is available, it is clearly preferable to use it rather than employ large doses of purely symptom-relieving drugs. At present toxicity is inextricably linked to efficacy, and dissociation of these two factors seems unlikely to be achieved in the near future. More efficient 'targeting' of drugs at the site of desired action should help to minimize the adverse effects of therapy. Ultimately the most efficient way of relieving pain and stiffness will be to prevent or suppress the inflammatory disorders which give rise to the symptoms. Unfortunately this is an elusive goal at present.


Correlates of fatigue in Koreans with chronic lung disease.
The purpose of this study is to explain the multidimensional characteristics of fatigue in Korean persons with chronic lung disease. The Unpleasant Symptom Theory by Lenz et al (1995) provided the theoretical framework for the study. A descriptive correlational study design was used. A convenience sample of 128 subjects (age = 64.2 +/- 11.3; forced expiratory volume in 1 second percent predicted value = 64.5 +/- 28.8%) was recruited from the outpatient respiratory clinic at a large university hospital in Korea. Fatigue was measured with the Multidimensional Fatigue Inventory. To identify the factors influencing fatigue, demographic variables, physiological variables, psychological variables, and a situational variable were measured. Subjects had a moderate degree of fatigue in general. The mean score for physical fatigue was relatively higher than that of mental fatigue. Using regression analysis, 48.4% of the variance in overall fatigue was explained by dyspnea and negative mood state. This study provides an understanding of multidimensional characteristics of fatigue experienced by Korean persons with chronic lung disease. It suggests that nurses need to include fatigue in their assessments and develop interventions to decrease dyspnea and negative mood in the management of fatigue.


Effects of meaning in life and individual characteristics on dignity in patients with advanced cancer in China: a cross-sectional study.
This study was conducted to evaluate the effects of meaning in life and individual characteristics on dignity in patients with advanced cancer. One hundred sixty-seven patients with advanced cancer participated in this study. Dignity was assessed with the Patient Dignity Inventory (PDI), meaning in life was assessed with the Meaning in Life Scale (MiLS), and performance status was defined as the Karnofsky Performance Status (KPS). Sociodemographic and clinical variables were also measured. Independent T tests and one-way ANOVA were performed for the PDI scores and sociodemographic and clinical variables. Relationships among the PDI, MiLS, and KPS scores were evaluated with bivariate analyses (Spearman rank correlation). A multiple linear regression analysis was conducted to determine the predictors the of PDI score. Patients reported a mean of 4.2 (SD 4.9) problems affecting their sense of dignity; 21.6% reported moderate to severe loss of their sense of dignity. Multivariable regression analyses revealed that a lower MiLS score, younger age, inpatient status, and a lower KPS score predicted the loss of dignity. Stepwise regression showed that 49.8% of dignity-related distress could be explained by the MiLS score, age, inpatient status, and the KPS score. Self-perceived dignity is significantly negatively associated with meaning in life, age, inpatient status, and performance status. The early recognition of risk factors for the loss of dignity and interventions to enhance meaning in life may prevent the loss of dignity in patients with advanced cancer.


Quantitative trait loci affecting clinical mastitis and somatic cell count in dairy cattle.
Norway has a field recording system for dairy cattle that includes recording of all veterinary treatments on an individual animal basis from 1978 onwards. Application of these data in a genome search for quantitative trait loci (QTL) verified genome-wise significant QTL affecting clinical mastitis on Chromosome (Chr) 6. Additional putative QTL for clinical mastitis were localized to Chrs. 3, 4, 14, and 27. The comprehensive field recording system includes information on somatic cell count as well. This trait is often used in selection against mastitis when direct information on clinical mastitis is not available. The absence of common QTL positions for the two traits in our study indicates that the use of somatic cell count data in QTL studies aimed for reducing the incidence of mastitis should be carefully evaluated.


Economic evaluation of applying the Canadian Syncope Risk Score in an Australian emergency department.
To evaluate the Canadian Syncope Risk Score (CSRS) in syncope patients presenting to the ED from an economic perspective, using very-low and low-risk patients (CSRS -3 to 0) as a threshold for avoiding hospital admissions. A decision-analytic model, specifically a decision-tree, was developed to evaluate application of the CSRS. A hypothetical cohort of 1000 patients was modelled based on characteristics and outcome of patients enrolled in a clinical validation study performed alongside this evaluation. Several analytic based approaches were used to handle model outputs and uncertainties. For a cohort of 1000 patients, applying the CSRS was associated with 169 less inpatient admissions from the ED, when compared to usual care. There was also a cost-saving of $8255 per admitted patient, when the CSRS was applied, compared to usual care. Adopting the CSRS was the optimal approach in all scenario analyses and was robust to changes in model parameters. More than three-quarters (78.6%) of all model simulations showed that applying the CSRS is a cost-saving approach to managing syncope. There was high confidence in all results, with the approach using the CSRS reducing the costs and number of syncope-related hospital admissions. Compared to usual care, applying the CSRS appeared as a cost-effective strategy. This new evidence will help decision-makers choose cost-effective approaches for the management of patients presenting to the ED with syncope, as they search for efficient ways to maximise health gain from a finite budget.


Short chain fatty acid in intestinal obstruction.
Short chain fatty acid (SCFA) and enteric bacteria in enteric fluid of 26 patients with non-strangulated intestinal obstruction were investigated. Sixteen to 905 mg/L of SCFA was detected in all the samples and acetic, propionic and lactic acid were prominent in the fraction. Concentration of SCFA reached a peak around the time of operation and then gradually decreased, in most cases. It also gradually decreased with clinical improvement in conservatively treated cases. Cultures of these enteric samples revealed 10(4-11)/ml of SCFA producing bacteria. SCFA may be one factor related to inhibition of water and electrolytes absorption and lead to distention of the bowel.


Erratum: Corregendum to: Propofol regulates miR-1-3p/IGF1 axis to inhibit the proliferation and accelerates apoptosis of colorectal cancer cells.
[This corrects the article DOI: 10.1093/toxres/tfab047.].


Comparison of accuracy between free-hand and surgical guide implant placement among experienced and non-experienced dental implant practitioners: an in vitro study.
This study investigated the accuracy of free-hand implant surgery performed by an experienced operator compared to static guided implant surgery performed by an inexperienced operator on an anterior maxillary dental model arch. A maxillary dental model with missing teeth (No. 11, 22, and 23) was used for this in vitro study. An intraoral scan was performed on the model, with the resulting digital impression exported as a stereolithography file. Next, a cone-beam computed tomography (CBCT) scan was performed, with the resulting image exported as a Digital Imaging and Communications in Medicine file. Both files were imported into the RealGUIDE 5.0 dental implant planning software. Active Bio implants were selected to place into the model. A single stereolithographic 3-dimensional surgical guide was printed for all cases. Ten clinicians, divided into 2 groups, placed a total of 60 implants in 20 acrylic resin maxillary models. Due to the small sample size, the Mann-Whitney test was used to analyze mean values in the 2 groups. Statistical analyses were performed using SAS version 9.4. The accuracy of implant placement using a surgical guide was significantly higher than that of free-hand implantation. The mean difference between the planned and actual implant positions at the apex was 0.68 mm for the experienced group using the free-hand technique and 0.14 mm for the non-experienced group using the surgical guide technique (P=0.019). At the top of the implant, the mean difference was 1.04 mm for the experienced group using the free-hand technique and 0.52 mm for the non-experienced group using the surgical guide technique (P=0.044). The data from this study will provide valuable insights for future studies, since in vitro studies should be conducted extensively in advance of retrospective or prospective studies to avoid burdening patients unnecessarily.


Canine mammary gland tumors.
An understanding of the known biologic facts of this disease and methodical evaluation of the individual patient are necessary prerequisites for outlining rational courses of therapy for dogs afflicted with mammary tumors. Because of the common occurrence of multiple tumors arising at various stages of development simultaneously and the heterogeneity of histology of the complex (mixed tissue types) tumors, presurgical biopsy is recommended only in cases in which mast cell tumor or anaplastic carcinoma is suspected. Although investigative work is being performed regarding the efficacy of chemotherapy, radiation therapy, and immunotherapy, surgery still remains the mainstay in treatment of this condition. No one surgical procedure fits the needs of all patients, although it seems logical to remove as much breast tissue as is reasonable in each circumstance owing to the multicentric nature of the disease. Ovariohysterectomy has not been demonstrated to be of value in treatment of dogs with mammary tumors, but it is a markedly effective method of preventing mammary tumors if it is performed before puberty; it is moderately effective if performed before the dog is 21/2 years of age.


Metabolism of novel anti-HIV agent 3-cyanomethyl-4-methyl-DCK by human liver microsomes and recombinant CYP enzymes.
To investigate the metabolism of 3-cyanomethyl-4-methyl-DCK (CMDCK), a novel anti-HIV agent, by human liver microsomes (HLMs) and recombinant cytochrome P450 enzymes (CYPs). CMDCK was incubated with HLMs or a panel of recombinant cytochrome P450 enzymes including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5. LC-ion trap mass spectrometry was used to separate and identify CMDCK metabolites. In the experiments with recombinant cytochrome P450 enzymes, specific chemical inhibitors combined with CYP antibodies were used to identify the CYP isoforms involved in CMDCK metabolism. CMDCK was rapidly and extensively metabolized by HLMs. Its intrinsic hepatic clearance estimated from the in vitro data was 19.4 mL·min(-1)·kg(-1), which was comparable to the mean human hepatic blood flow rate (20.7 mL·min(-1)·kg(-1)). The major metabolic pathway of CMDCK was oxidation, and a total of 14 metabolites were detected. CYP3A4 and 3A5 were found to be the principal CYP enzymes responsible for CMDCK metabolism. CMDCK was metabolized rapidly and extensively in human hepatic microsomes to form a number of oxidative metabolites. CYP3A4 and 3A5 were the predominant enzymes responsible for the oxidation of CMDCK.


Systematic review on the prevalence of nonalcoholic fatty liver disease in South Korea.
We aimed to conduct a systematic review and a meta-analysis to estimate NAFLD prevalence and its change in Korea. We searched the literature involving NAFLD prevalence in Korea in PubMed, RISS, and KMBASE from inception to June 2017. Studies with subjects with certain disorders, population limitations, or subjects who consume alcohol were excluded. Analysis was stratified by publication year, age, gender, severity, body mass index (BMI), and diagnostic technique. Random-effects models were used to provide point estimates (95% confidence interval) of prevalence with subgroup analysis to account for heterogeneity. A total of 61 studies (837,897 participants) were included. The overall NAFLD prevalence in Korea was 30.3% (men: 41.1%, women: 20.3%), with a slight increase from 29.0% to 31.0% over an approximately 10-year period. BMI significantly affected NAFLD prevalence (≤ or > 25 kg/m2, 12.3% vs. 41.7%, p < 0.001), while women were significantly affected by aging (< or ≥ 50 years, 17.0% vs. 25.8%, p < 0.01). The prevalence of steatosis by severity was 22.6% for mild, 9.8% for moderate to severe and 2.2% for nonalcoholic steatohepatitis (NASH), with different patterns by gender. The current study is the first systematic analysis on NAFLD prevalence in Korea and found a change in NAFLD prevalence during the recent decade.