Initial subsensitivity to anxiolytic treatments on conflict behavior in rats: parametric studies across drug classes.
In conflict paradigms, benzodiazepines (BZs) often exhibit maximal anticonflict effects only after three to four BZ exposures (anxiolytic initial subsensitivity; AIS). The present experiments examined 1) whether AIS occurs with non-BZ anxiolytics and 2) whether prior exposure to non-BZs prevents the occurrence of BZ AIS. Female rats were trained to stable responding levels on a repeated-measures punished drinking paradigm. In Experiment 1, dose-response curves for the effects of the BZs chlordiazepoxide and diazepam, the barbiturates (BBs) pentobarbital and amobarbital, and the non-BZ, non-BB agent carbamazepine were determined in five groups of rats (one group/drug); dose-response curves were determined on two occasions for each drug. There was an AIS with both BZs, with the anticonflict effect being significantly greater for dose-response determination #2. There was no AIS with the BBs (robust and dose-dependent increases in punished responding on both determinations) or with carbamazepine (weak anticonflict effect on both determinations). In Experiment 2, the rats from Experiment 1 received a single-dose challenge with chlordiazepoxide (10 mg/kg). This challenge resulted in a robust anticonflict effect in subjects with a history of repeated BZ treatment; in contrast, subjects with a history of repeated BB or carbamazepine treatment exhibited smaller anticonflict responses. These data suggest that 1) the AIS does not occur with non-BZ anxiolytics and 2) the BZ AIS cannot be prevented by repeated exposure to non-BZs.


Mechanical tension stimulates the transdifferentiation of fibroblasts into myofibroblasts in human burn scars.
Scar formation as a result of burn wounds leads to contraction of the formed granulation tissue, which causes both aesthetic and functional impairment for the patient. Currently, the main treatment methods focus on stretching to prevent tissue contraction. The myofibroblasts play a key role in the contraction of granulation tissue during scar formation, but their presence should normally decrease after wound re-epithelialization. In hypertrophic scars the myofibroblasts persist and is believed to cause further hypertrophy. Previous studies have shown that mechanical tension leads to increased myofibroblast numbers in granulation tissue. In order to evaluate the effect mechanical tension as a result of stretching has on the number of myofibroblasts in burn wound scars, an in vitro model was used. This model used human burn scar biopsies which were stretched and examined after 1 and 6 days to evaluate the effect on the number of myofibroblasts. The stretching caused an increase in the number of myofibroblasts after mechanical stimulation. This indicates that mechanical stimulation using stretching induces fibroblast to myofibroblast transdifferentiation, thus underlining the importance of further investigations of optimal methods of this regime for treating burn scars.


An interesting case of polyostotic fibrous dysplasia: The "pirate sign" evaluated with Tc-99m methylene diphosphonate single-photon emission computed tomography/computerized tomography.
Polyostotic fibrous dysplasia is a rare progressive benign disorder of the bone. Bone scintigraphy is extremely useful in the initial evaluation for identifying the extent of disease. We report a case presenting with pathological fracture of the shaft of the right femur. After treatment of the fracture, bone scintigraphy revealed involvement of multiple bones including the skull and facial bones. The utility of single-photon emission computed tomography/computerized tomography in the evaluation of the extent of skull base involvement is highlighted.


[Testicular yolk sac tumor in children. Current view on diagnosis and treatment].
5 children with yolk-sac tumor of the testis (= infantile embryonal carcinoma) were admitted to our hospital between 1973 and 1981. Evaluation of serum alpha-fetoprotein concentrations and ultrasonography of the retroperitoneal area proved to be extremely valuable to predict the tumor stage in these children. Therapy consisted of high inguinal orchiectomy, retroperitoneal lymphadenectomy and cytostatic chemotherapy in 3 children using the T2-protocol. All children are now between 1 1/2 and 8 years free of recurrence and metastases. Therapy of this tumor ought to be differentiated according to the individual tumor stage. Most patients with stage-I tumor require only radical orchiectomy for cure.


Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs. DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; βSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; βSNP×DHA interaction = 36.2 ml). We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.


Hydrogen bonding in C-substituted nitroanilines: sheets built from alternating R(2)(2)(12) and R(6)(6)(36) rings in 2-bromo-6-cyano-4-nitroaniline.
Molecules of the title compound (systematic name: 2-amino-3-bromo-5-nitrobenzonitrile), C(7)H(4)BrN(3)O(2), are linked by N-H...N and N-H...O hydrogen bonds [H...N 2.19A, N...N 3.019(4)A and N-H...N 157 degree, and H...O 2.17A, N...O 2.854(3)A and N-H...O 134 degree] to form (10-3) sheets built from alternating R(2)(2)(12) and R(6)(6)(36) rings, both of which are centrosymmetric.


Is greater milk production associated with dairy cows who have a greater probability of ruminating while lying down?
The objective of this study was to determine whether associations exist between position while ruminating (lying vs. standing) and milk and component production in dairy cows. Data from 30 lactating Holstein cows were assembled from 2 studies in which cows were milked by automated milking system (AMS) and fed a partial mixed ration (PMR) in feed bins that recorded intake behavior. Rumination and lying behavior were monitored using automated neck- and leg-based sensors, respectively. Each cow was monitored over 2 separate 2-wk treatment periods. To estimate position while ruminating for each 2-h period of the day for each cow, a conditional probability was calculated to determine the probability that any rumination time and lying time were occurring at the same time in any 2-h period. These probabilities (RwL), and all behavioral data, were summarized per cow per 2-h interval, and then averaged per day and per 2-wk period, along with milk yield and component data. Cows averaged (mean ± standard deviation) 1.9 ± 1.1 lactations and 85.5 ± 55.2 d in milk, and weighed 668.5 ± 96.0 kg. Data included rumination time (557.7 ± 41.1 min/d), lying time (703.9 ± 65.3 min/d), idle standing time (520.1 ± 83.2 min/d), PMR feeding time (204.7 ± 48.5 min/d), PMR dry matter intake (DMI; 21.8 ± 4.6 kg/d), AMS pellet provision (4.6 ± 1.6 kg/d), total DMI (26.4 ± 4.5 kg/d), milk yield (42.4 ± 7.2 kg/d), milk fat content (3.75 ± 0.51%), and milk protein content (3.21 ± 0.32%). Greater rumination time and lying time were associated with greater RwL probability (mean = 0.19 ± 0.02; range = 0.14 to 0.23). The RwL probability tended to be positively associated with total DMI and milk fat content, was associated with milk protein content, but was not associated with any measures of milk yield. The results indicate that in a free-traffic AMS, cows who have greater probability of ruminating while lying down spend more time ruminating and lying, and tend to consume more total dry matter and produce milk with greater components.


Colorimetric sensor based on biogenic nanomaterials for high sensitive detection of hydrogen peroxide and multi-metals.
Hydrogen peroxide (H2O2) and heavy metals, which are among the wastes of the industrial sector, become a threat to living things and the environment above certain concentrations. Therefore, the detection of both H2O2 and heavy metals with simple, low-cost, and fast analytical methods has gained great importance. The use of nanoparticles in colorimetric sensor technology for the detection of these analytes provides great advantages. In recent years, green synthesis of nanomaterials with products that can be considered biowaste is among the popular topics. In this study, silver/silver chloride nanoparticles (Ag@AgCl NPs) were synthesized using the green synthesis method as an eco-friendly and cheap method, the green algae extract was used as a reducing agent. The characterization of Ag@AgCl nanoparticles and green algae extract was carried out with several techniques such as Transmission Electron Microscopy (TEM), UV-Visible spectrometry (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction patterns (XRD) methods were used for characterization. According to TEM analysis, the Ag@AgCl NPs typically spherical in form and range in size from 4 to 10 nm, and UV-vis showed the formation of surface plasmon resonance (SPR) of the Ag@AgCl between 400 and 450 nm. In addition, its activity as a colorimetric sensor for hydrogen peroxide (H2O2) and multi-metal detection was evaluated. Interestingly, Ag/AgCl NPs caused different color formations for 3 metals simultaneously in the sensor study for heavy metal detection, and Fe3+, Cu2+, and Cr6+ ions were detected. The R2 values for H2O2, Fe3+, Cu2+, and Cr6+ were 0.9360, 0.9961, 0.9787, and 0.9625 the limit of detection (LOD) was 43.75, 1.69, 3.18, and 5.05 ppb (ng/mL), respectively. It was determined that Ag@AgCl NPs have the potential to be used as a colorimetric sensor for the detection of H2O2 and heavy metals from wastewater.


Evaluation of constraints to water quality improvements in the Western Lake Erie Basin.
Severe environmental and health impacts have been experienced in the Western Lake Erie Basin (WLEB) because of eutrophication and associated proliferation of harmful algae blooms. Efforts to improve water quality within the WLEB have been on-going for several decades. However, water quality improvements in the basin have not been realized as anticipated. In this study, factors affecting water quality within the WLEB were evaluated with a view to differentiating their impacts and informing further assessments in the basin. Over the long-term (1966-2015) and basin-wide, total annual precipitation increased significantly by about 2.4 mm/year while mean monthly streamflows also increased during the same period although the increase was not significant (p = 0.36). There was, however, a significant increase in spring streamflows during this period (p = 0.003). Patterns in water quality parameters showed significant reductions in total suspended solids (TSS) (p < 0.001) and total phosphorus (TP) (p = 0.018) while soluble reactive phosphorus (SRP) increased significantly (p < 0.001), and in particular from about 1995. Results of near-term (2005-2015) analysis showed a non-significant (p = 0.262) reduction in TSS concentrations of about 0.25 mg/L/year. TP concentrations did not vary substantially during the same period while a 0.11 mg/L/year increase in nitrate and a 0.001 mg/L/year increase in SRP were observed, with increases in nitrates being significant (p = 0.013). TP and SRP concentrations, however, remained high within the basin with daily values ranging between 0.03 and 1.84 mg/L and less than 0.002-0.52 mg/L, respectively. Basin-wide, both spring precipitation and spring streamflows increased significantly during the period 2005-2015 (p < 0.001). Overall, no substantial changes in land use were observed, suggesting that water quality responses might be attributable to management. Based on recent data, corn acreage in the basin and fertilizer applied to corn increased by 33% and 10% respectively. Combined Sewer Overflows (CSOs) and impoundments were also important factors due to their prevalence in the basin. Based on the analysis, changes in agricultural management, increase in spring precipitation, CSOs, legacy phosphorus, and the presence of dams were thought to present constraints to water quality improvements despite conservation efforts within the basin.


Citrus-Gene interaction and melanoma risk in the UK Biobank.
High citrus consumption may increase melanoma risk; however, little is known about the biological mechanisms of this association, or whether it is modified by genetic variants. We conducted a genome-wide analysis of gene-citrus consumption interactions on melanoma risk among 1563 melanoma cases and 193 296 controls from the UK Biobank. Both the 2-degrees-of-freedom (df) joint test of genetic main effect and gene-environment (G-E) interaction and the standard 1-df G-E interaction test were performed. Three index SNPs (lowest P-value SNP among highly correlated variants [r2 > .6]) were identified from among the 365 genome-wide significant 2-df test results (rs183783391 on chromosome 3 [MITF], rs869329 on chromosome 9 [MTAP] and rs11446223 on chromosome 16 [DEF8]). Although all three were statistically significant for the 2-df test (4.25e-08, 1.98e-10 and 4.93e-13, respectively), none showed evidence of interaction according to the 1-df test (P = .73, .24 and .12, respectively). Eight nonindex, 2-df test significant SNPs on chromosome 16 were significant (P < .05) according to the 1-df test, providing evidence of citrus-gene interaction. Seven of these SNPs were mapped to AFG3L1P (rs199600347, rs111822773, rs113178244, rs3803683, rs73283867, rs78800020, rs73283871), and one SNP was mapped to GAS8 (rs74583214). We identified several genetic loci that may elucidate the association between citrus consumption and melanoma risk. Further studies are needed to confirm these findings.


Atrial and ventricular myosins from human hearts. II. Isoenzyme distribution after myocardial infarction.
Human atrial and ventricular myosins were prepared from autopsy specimens from subjects with coronary heart disease. Cardiac myosin light chain isotypes were resolved using two-dimensional gel electrophoresis, whereas myosin isozymes were detected by pyrophosphate gel electrophoresis. Myocardial infarction and associated work overload cause a transition in the light chain complements of the myosins. Thus ventricular myosin light chains were found in pressure overloaded atria and atrial light chains have also been identified in the infarct ventricle of the human heart. Two molecular isoenzymes of the human atrial myosin, the relative proportions of which are changed after infarction, were separated under non-dissociating conditions by gel electrophoresis. A decrease in HA-3 and a corresponding increase in HA-1 were observed. Ventricular hypertrophy in patients with coronary insufficiency induces a second ventricle isomyosin, called HV-1, with the same electrophoretic mobility as HA-1. The relative part of this myosin type amounts to 20%. Comparative peptide mapping studies were carried out on myosin subfragment-1 preparations from normal and infarct ventricles. In the primary structures, the chymotrypsic digestions produced slight differences. These data demonstrate the heterogeneity of human atrial and ventricular myosins in patients with coronary heart disease.


Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy.
Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised "tube-breathing" circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37-41] weeks, birthweight of 3.1 [2.2-4.0] kg, and postnatal age of 33 (21-62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112). Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response. What is Known: • Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. • The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. What is New: • We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in newborns with second-hand smoke exposure during pregnancy, in infants whose mothers smoked, and in controls (non-smoke exposed). • Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was associated with a delayed newborn ventilatory response.


Effect of electric fields strength on soil factors and microorganisms during electro-bioremediation of benzo[a]pyrene-contaminated soil.
Electro-bioremediation is a promising technology for remediating soils contaminated with polycyclic aromatic hydrocarbons (PAHs). However, the resulting electrokinetic effects and electrochemical reactions may inevitably cause changes in soil factors and microorganism, thereby reducing the remediation efficiency. To avoid negative effect of electric field on soil and microbes and maximize microbial degradability, it is necessary to select a suitable electric field. In this study, artificial benzo [a]pyrene (BaP)-contaminated soil was selected as the object of remediation. Changes in soil factors and microorganisms were investigated under the voltage of 1.0, 2.0, and 2.5 V cm-1 using chemical analysis, real-time PCR, and high-throughput sequencing. The results revealed noticeable changes in soil factors (pH, moisture, electrical conductivity [EC], and BaP concentration) and microbes (PAHs ring-hydroxylating dioxygenase [PAHs-RHDα] gene and bacterial community) after the application of electric field. The degree of change was related to the electric field strength, with a suitable strength being more conducive to BaP removal. At 70 d, the highest mean extent of BaP removal and PAHs-RHDα gene copies were observed in EK2.0 + BIO, reaching 3.37 and 109.62 times those in BIO, respectively, indicating that the voltage of 2.0 V cm-1 was the most suitable for soil microbial growth and metabolism. Changes in soil factors caused by electric fields can affect microbial activity and community composition. Redundancy analysis revealed that soil pH and moisture had the most significant effects on microbial community composition (P < 0.05). The purpose of this study was to determine the appropriate electric field that could be used for electro-bioremediation of PAH-contaminated soil by evaluating the effects of electric fields on soil factors and microbial communities. This study also provides a reference for efficiency enhancement and successful application of electro-bioremediation of soil contaminated with PAHs.


Measurement Properties of the 15-Item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in Family Caregivers of Patients with Heart Diseases.
To evaluate the measurement properties of the 15-item Singapore Caregiver Quality of Life Scale (SCQOLS-15) in family caregivers of patients with heart diseases. The SCQOLS-15 survey was self-administered by family caregivers of patients with chronic heart diseases, at baseline and 1 week later. The criterion validity of SCQOLS-15 and its domain scores was assessed by calculating the Spearman correlation coefficient (ρ) with the Brief Assessment Scale for Caregivers (BASC), Caregiver Reaction Assessment (CRA), and their sub-scores. Known-group validity was assessed using the New York Heart Association (NYHA) functional class. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). Of the 327 caregivers included, 65% were adult children and 28% were spouses. The distribution of NYHA classes of the patients was I: 27%, II: 40%, III: 24%, and IV: 9%. There was a positive correlation between the SCQOLS-15 and BASC total scores (ρ = 0.7). SCQOLS-15 domain scores were also correlated with BASC and CRA sub-scores as per a priori hypotheses, with absolute values of ρ ranging from 0.4 to 0.6. The mean values of SCQOLS-15 total and all domain scores were lower among caregivers of patients with NYHA class III/IV compared to those of class I/II patients (each P < 0.05). Among 146 caregivers who completed the follow-up and self-rated a stable quality-of-life, ICCs for test-retest reliability of SCQOLS-15 total and all domain scores were ≥ 0.8. The SCQOLS-15 is a valid and reliable instrument for measuring the quality of life in caregivers of heart disease patients.


Morphology and axon terminal pattern of glutamate decarboxylase-immunoreactive cell types in the white matter of the cat occipital cortex during early postnatal development.
During early postnatal development glutamate decarboxylase (GAD)-immunoreactive (ir) neurons are present in the white matter of the kitten occipital cortex. Most neurons are located below layer VI in the 'upper subplate' zone, others are located deeper in the white matter. In animals at postnatal (P) days 10 and 20 we classified two cell types on the basis of their axonal pattern. One type, the axonal loop cells, displays loops of 180 degrees formed either by the main axonal stem or by a major recurrent collateral. The neurons do not form terminals in the white matter. The other type, the local axon cells, have frequently branching axons giving rise to terminal varicosities contacting other white matter neurons in a basket-like manner. The local cells form terminal plexuses which occupy the white matter of younger kittens and are concentrated in a 100-150 micron wide zone subjacent to layer VI. In P48 kittens, density and width of the plexus is reduced and axonal loop cells and the local axon cells have disappeared. Some GAD-ir white matter neurons observed at this age have large fusiform somata and straight projecting axons. The origin and fate of the early postnatal white matter neurons will be discussed.


[Pre-implantation genetic testing: Comparison between cleavage stage and blastocyst biopsy].
Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through in vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries or even from one center to another. In ours, biopsies are preferably performed on day 3 embryos, but also at the blastocyst stage on day 5. The blastocyst biopsy often requires systematic freezing of the embryos before obtaining the genetic results, whereas day 3 biopsy allows fresh embryo transfer of the healthy or balanced embryo after getting the genetic results. We wanted to compare the chances of success for couples performing PGT in our center according to the day of the biopsy. For this, we carried out a retrospective monocentric study including all PGT cycles performed between 2016 and 2019 divided into two groups: day 3 or day 5 biopsy. There was no significant difference in terms of live birth rate (P=0.7375) after fresh embryo transfers, as well for pregnancy rates, clinical pregnancy rates, implantation rates and miscarriage rates. On the other hand, we observed higher live birth rates after frozen-thawed embryo transfer when the biopsy was performed on day 5 rather on day 3 (P=0.0001). We also wanted to assess what was the most efficient biopsy strategy in our laboratory. Our rates of useful embryos were similar regardless of the day of the biopsy (34% in D3 and 37.7% in D5, P=0.244). No statistical difference was found in the number of unnecessarily biopsied embryos in the two groups. But still, the percentage of embryos biopsied on D5 and immediately frozen was 42.8% (118 blastocysts), while no embryo biopsied on D3 led to this case. Therefore, our results are in favor of generalization of the D5 biopsy as the international standard. However, the organizational, financial and logistical implications that this technic would impose make it unsystematic in our center.


The influence of coastal upwelling on the functional structure of rocky intertidal communities.
Relationships between organisms at all trophic levels are influenced by the primary productivity of the ecosystem, and factors which enhance rates of primary production may modify trophic relationships and community structure. Nutrient enrichment of intertidal and nearshore waters leads to enhanced production by intertidal algae, and it was hypothesized that where rocky shores are washed by nutrient-rich upwelled waters, the intertidal communities should show a characteristic functional structure, based on the effects of enhanced primary production. Study sites were chosen on rocky shores in southern Africa, central Chile and the Canary Islands, in areas with and without coastal upwelling, and mid-shore community structure at these sites was analysed in terms of the abundance of certain functional guilds of organisms.It was found that algal cover and the biomass of herbivorous limpets supported per unit area on rocky shores were significantly greater in regions of coastal upwelling than in regions where upwelling did not occur. Ground cover by sessile filter-feeding organisms was significantly greater on shores in non-upwelled areas. However, correspondence analysis showed no functional aspect of intertidal community structure that was characteristic of coasts washed by upwelled waters. Primary reasons for this are probably the large variations in the nature of nutrient enrichment that accompanies upwelling, and in the nutrient status of non-upwelled areas. Other factors are man's exploitation of intertidal organisms and differences in the genetic origins of the intertidal species involved.


Mechanical and Thermal Sensory Testing in Normal Chondrodystrophoid Dogs and Dogs with Spinal Cord Injury caused by Thoracolumbar Intervertebral Disc Herniations.
Intervertebral disc herniation is a common cause of spinal cord injury (SCI) causing paralysis and sensory loss. Little quantitative information is available on the loss and recovery of sensation in dogs with SCI. To determine whether quantitative sensory testing (QST) can be used to establish thermal and mechanical sensory thresholds in chrondrodystrophoid dogs and compare thresholds among normal dogs and dogs with different grades of SCI. Thirty-three client-owned chondrodystrophoid dogs: 15 normal and 18 SCI dogs. Thermal testing was performed by placing a hot (49°C) and cold (5°C) probe on the dorsal metatarsus and mechanical thresholds were tested using calibrated forceps to apply force to the lateral digit. Stimuli were applied until acknowledged, and response rate, latency, and force applied to response were recorded. Test-retest repeatability was determined by calculating intraclass correlation coefficients. Response rates were compared using logistic regression and thresholds were compared using Kaplan-Meier Survival curves. Testing was feasible with moderate repeatability. Thresholds and response rates were significantly different between normal and SCI dogs for all modalities (P < .001). When dogs were grouped by their clinical grade, each grade was significantly different from normal dogs, and cold stimuli differentiated among all grades. Sensory thresholds can be measured reliably in chondrodystrophoid dogs and are altered by SCI. The differences in sensation among neurologic grades indicate that these techniques can be used to further characterize recovery of SCI dogs.


Pronounced dilatation of Cowper's gland duct manifest as a perineal mass: a recommendation for management.
It is generally accepted that large dilatations of Cowper's gland duct presenting as a perineal mass should be managed by perineal excision. Experience with such a case suggests that if the lesion also is visualized endoscopically, transurethral unroofing should be the initial choice of management.


Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. III. AYC aqueous coating onto granules and film formation mechanism of AYC.
From the viewpoint of effective utilization of natural resources and development of new pharmaceutical materials, acid-treated yeast cell wall (AYC) was prepared via a novel approach involving acidification of brewers' yeast cell wall. AYC aqueous dispersion containing 5% (w/v) AYC and 0.5% (w/v) glycerol was prepared. Subsequently, AYC was coated onto core granules containing acetaminophen (AAP). Spray mist size under various spray conditions and viscosity of the AYC aqueous dispersion at various AYC concentrations were measured. AYC spray mists were optically observed. The surface of AYC cast film and AYC-coated granules were observed with a confocal scanning laser microscope. We attempted to show the utility of AYC as a novel material for granule coating, following the tablet coating in our previous report. In addition, the film formation mechanism of AYC was investigated. A smooth surface of the AYC-coated granules was obtained at a coating ratio of only 5%, which generally requires approximately 15-30% coating against the core granule weight, with no aggregation. These results are attributable to the fact that the granules were coated with a large number of small mists of AYC and the coating progressed efficiently, and the thin film layer of AYC was formed on the granules by mutual tangling of the hydrogel layers of AYC polysaccharides. AAP release from AYC-coated granules was obviously rapid, suggesting the high utility of AYC as a coating material for the rapidly releasing granules.


Histogenesis of the chequered pattern of ivory of the African elephant (Loxodonta africana).
This study aimed to propose a hypothesis on the events which lead to the development of the characteristic chequered pattern of elephant ivory. Twenty fragments of ivory and six elephant tusks were obtained through the National Parks Board of South Africa. Polished surfaces were prepared in sagittal and longitudinal planes and the characteristics of the distinctive chequered pattern described. Light- and electron-microscopical techniques and image analyses were employed to determine the morphological basis of the pattern and to describe the spatial distribution, density and morphology of the dentinal tubules. These investigations showed that the distinctive pattern was the result of the sinusoidal, centripetal course followed by dentinal tubules. The apical, slanted part of the sinusoidal curve is the result of the centripetally moving odontoblast, which, during formation of ivory, progresses towards the centre of the tusk on a decreasing circumference. It is suggested that this leads to cell crowding, increased pressure between odontoblasts and subsequent apical movement of their cell bodies, cell degeneration and fusion. Odontoblastic degeneration and fusion probably relieve the pressure between the crowded odontoblasts by reducing their numbers and the remaining odontoblasts now orientate their centripetal course towards the tip of the tusk, thereby forming the anterior-directed part of the sinusoidal path of the tubule. As odontoblasts progress centripetally the diameter of the pulpal cavity decreases further and the processes of apical movement, fusion and degeneration of odontoblasts are repeated. This occurs until the pulpal cavity is obliterated.


Randomized comparison of Vasoseal and Angioseal closure devices in patients undergoing coronary angiography and angioplasty.
AngioSeal (AS) and VasoSeal (VS) are collagen-based arterial closure devices utilized to achieve earlier hemostasis and ambulation in diagnostic and interventional percutaneous procedures. To our knowledge, there has been no randomized studies comparing these two devices as approved for use in the United States. One hundred fifty-seven patients were randomized to receive either the 8 Fr AS (n = 79) or VS (n = 78) closure device. Data on 95 patients who had coronary angiography (49 AS, 46 VS) and 55 patients who underwent angioplasty (28 AS, 27 VS) were completed. Heparin was not administered during the coronary angiogram procedure. The activated clotting time was kept at approximately 300 sec during angioplasty. Patients on coumadin or GP IIb/IIIa platelet inhibitors were not included in this study. The time unit interval to achieve hemostasis in this study was based on the time the AS tension spring was left over the common femoral artery following collagen deployment as per the manufacturer's instructions (20 min). Time to hemostasis, time to ambulation, and major and minor complications were prospectively recorded. Two-tailed t-test and chi-square analysis were performed on continuous and dichotomous variables, respectively. For the angiogram-only subgroup, time (min) to hemostasis (20.51 +/- 4.36 vs. 18.59 +/- 11.77; P = 0.30) and ambulation (145.71 +/- 124 vs. 109.89 +/- 60.37; P = 0.075) were not statistically different for the AS and VS, respectively. Similarly, for the angioplasty subgroup, time (min) to hemostasis (24.23 +/- 12.70 vs. 19.57 +/- 2.27; P = 0.077) and ambulation (607.32 +/- 344.22 vs. 486.48 +/- 200.37; P = 0.12) were not statistically different for both AS and VS, respectively. Furthermore, there were no statistical differences in deployment failure, major, minor, or total complication rates between the two devices. In the absence of GP IIb/IIIa inhibitors, VS and the 8 Fr AS devices have statistically similar time to hemostasis and ambulation as well as device failures and complication rates following coronary angiography and angioplasty.


Effect of xanthan gum on the release of strawberry flavor in formulated soy beverage.
The effects of xanthan gum on the release of strawberry flavor compounds in formulated soy protein isolate (SPI) beverage were investigated by headspace gas chromatography (GC). Seven strawberry flavor compounds (limonene, ethyl hexanoate, (Z)-3-hexenyl acetate, ethyl 2-methylbutanoate, ethyl butanoate, (Z)-3-hexen-1-ol and diacetyl) could be detected by GC and hence analyzed the gas-matrix partition coefficients (K). The release of flavor compounds was restrained in SPI and/or xanthan gum solution. The retention of (Z)-3-hexen-1-ol, limonene and diacetyl significantly changed (p<0.05) with increasing xanthan gum concentrations. Presence of any other esters led to suppression of the release of ester compounds in water and SPI solution. The less-volatiles (γ-decalactone, methyl cinnamate, hexanoic acid, 2-methyl butyric acid and furaneol) accelerated the release of ester compounds to some extent in different matrices. The above results demonstrated that presence of SPI and xanthan gum could bring about an imbalance in the strawberry flavor.


Interleukin 7 receptor alpha Thr244Ile genetic polymorphism is associated with susceptibility and prognostic markers in breast cancer subgroups.
Interleukin-7 (IL-7) exerts crucial functions on lymphoid cells' development and maintenance. In breast cancer (BC), IL-7 promotes growth of tumor cells in culture through the activation of JAK1/3-STAT5 and PI3K/AKT pathways, and expression of IL-7 signaling components was associated with worst prognosis. AC>T polymorphism (rs6897932; Thr244Ile) at exon 6 of IL-7 receptor alpha (IL-7Rα) gene (IL7RA) shifts the balance between the membrane-bound and soluble IL-7Rα splicing variants and was previously associated with autoimmune diseases, but has not been studied in cancer, including BC, so far. Therefore, the present study aimed to investigate the possible association of this polymorphism with the susceptibility and clinicopathological parameters of BC subgroups. IL7RA Thr244Ile was genotyped through PCR-RFLP in 403 women without neoplasia, no personal history of malignancy or family history of BC and in 338 BC patients with clinicopathological data available. BC patients were stratified according to their positivity for estrogen (ER) and/or progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Age-adjusted logistic regression was performed for case-control analyses, and correlations with clinicopathological parameters were assessed through Kendall's Tau-b coefficient. All analyses were two-tailed and had 95% confidence interval. In ER-PR-HER2- BCs, TT genotype was associated with increased susceptibility both in genotypic (TT vs. CC: OR=3.07; CI=1.01-9.38; p=0.05) and recessive (TT vs. CC+CT: OR=3.59; CI=1.19-10.85; p=0.02) models and negatively correlated with disease stage (Tau-b=-0.27; p=0.05). Whereas T allele was positively correlated with histopathological grade (Tau-b=0.29; p=0.03) and lymph node metastasis (Tau-b=0.35; p=0.02) in ER/PR+HER2+BCs and with Ki67 (Tau-b=0.51; p=0.008) in ER-PR-HER2+ subgroup. These data indicate that IL-7Rα is involved in BC, and that IL7RA polymorphism may play distinct roles in breast carcinogenesis according to BC subtype, pointing this genetic variant as an interesting marker for breast carcinogenesis to be validated by further mechanistic and prospective studies with larger samples.


Optic atrophies in metabolic disorders.
Optic nerve involvement in metabolic disorders often results from apoptosis of cells that form or support the optic nerve, the retinal ganglion cell (RGC) axons, the myelin-forming oligodendrocytes, or the supporting vascular system. Given their high energy demands and the long course of their axons, RGCs are particularly sensitive to intracellular metabolic defects. Defects in energy metabolism, formation of reactive oxygen species, and storage of metabolites can all cause apoptosis of RGCs, decreased myelin formation of oligodendrocytes and increased pressure on the optic nerve. Clinically, the loss of RGC axons manifests as pale optic nerves. In general, the ophthalmologist can identify the underlying cause of an optic atrophy by careful examination, neuro-imaging, and family history. In some cases, however, the diagnosis proves elusive. In these instances, and especially when optic atrophy is accompanied by other systemic involvement, a metabolic disorder should be considered. Here, we review the underlying mechanisms of optic atrophy and its significance in metabolic disorders. Early identification of optic atrophy aids the diagnosis and subsequent management of the underlying condition, including anticipation of symptoms, genetic counseling, and possible therapeutic interventions. For many metabolic disorders, molecular testing is available.


Public attitudes toward increasing the price of alcoholic beverages.
Approximately half of all respondents surveyed in Ontario are satisfied with current pricing of alcoholic beverages, and approximately two-thirds of all drinkers surveyed would pay more if higher prices would help reduce the prevalence of alcoholism.


A Rare Nonsense Mutation in the Glucokinase Regulator Gene Is Associated With a Rapidly Progressive Clinical Form of Nonalcoholic Steatohepatitis.
We report on the presence of a rare nonsense mutation (rs149847328, p.Arg227Ter) in the glucokinase regulator (GCKR) gene in an adult patient with nonalcoholic fatty liver disease (NAFLD), morbid obesity, and type 2 diabetes; this patient developed a progressive histological form of the disease. Analysis of paired (5 years apart) liver biopsies (at baseline and follow-up) showed progression of simple steatosis to severe nonalcoholic steatohepatitis and cirrhosis. Study design involved an initial exploration that consisted of deep sequencing of 14 chromosomal regions in 96 individuals (64 of whom were patients with NAFLD who were diagnosed by liver biopsy that showed the full spectrum of histological severity). We further performed a replication study to explore the presence of rs149847328 that included a sample of 517 unrelated individuals in a case-control study (n = 390), including patients who were morbidly obese (n = 127). Exploration of sequence variation by next-generation sequencing of exons, exon-intron boundaries, and 5' and 3' untranslated regions of 14 genomic loci that encode metabolic enzymes of the tricarboxylic acid cycle revealed the presence of heterozygosity for the p.Arg227Ter mutation, the frequency of which is 0.0003963 (4:10,000; Exome Aggregation Consortium database). GCKR protein expression was markedly decreased in the liver of the affected patient compared with patients with NAFLD who carry the wild-type allele. Sequencing of the same 14 genomic loci in 95 individuals failed to reveal the rare mutation. The rarity of p.Arg227Ter was confirmed in a more extensive screening. Conclusion: While rare variants/mutations are difficult to detect in even reasonably large samples (frequency of the mutant allele of p.Arg227Ter was ~1:1,000 in our data set), the presence of this mutation should be suspected as potentially associated with NAFLD, particularly in young adults at the extreme of histological phenotypes. Hepatology Communications 2018;0:0-0).


Effects of a preoperative individualized exercise program on selected recovery variables for cardiac surgery patients: A pilot study.
Research on preoperative individualized exercise prescription (PIEP) for heart surgery patients in Taiwan is lacking. Thus, the purpose of this study was to examine the feasibility of a PIEP in the Taiwanese population. A quasi-experimental design, using purposive sampling, was conducted. Thirty-five patients were recruited, of whom 15 chose to participate in the experimental (PIEP training plus usual care) group, and 20 chose to participate in the control (usual care) group. The effects of the intervention were determined by pulmonary complication-related parameters and quality of life. The development and process of PIEPs suitable for cardiac patients was described in this study. The results reveal that the two-week exercise-training program contributed to a decreased peak respiratory exchange ratio (RER) after the surgery and earlier ambulation. The effectiveness of PIEPs in improving the quality of life in cardiac surgery patients was validated. This study may also contribute as a reference of the PIEP effect on patients to the healthcare providers.


Association between defect morphology and healing of intrabony defects treated with minimally invasive non-surgical therapy: A pilot exploratory analysis of two cohorts.
The aim of this study was to explore the associations between defect morphology (defined by clinical and radiographic parameters) and the healing of periodontal intrabony defects treated with minimally invasive non-surgical therapy (MINST). MINST has shown to result in favorable clinical and radiographic improvements in intrabony defects. However, it is not clear which types of intrabony defects are most suitable for this treatment. Clinical and radiographic analyses were carried out in a total of 71 intrabony defects treated with MINST belonging to two previously published studies. Baseline defect characteristics were analyzed and related to clinical and radiographic outcomes at 12 months post-MINST with or without adjunctive enamel matrix derivative. No associations were detected between defect depth, angle and predicted number of walls and clinical and radiographic healing 12 months post-MINST. No evidence emerged for associations between defect characteristics and healing following MINST. These data seem to suggest that factors other than defect morphology may influence treatment response to MINST.


The effects of a DTNBP1 gene variant on attention networks: an fMRI study.
Attention deficits belong to the main cognitive symptoms of schizophrenia and come along with altered neural activity in previously described cerebral networks. Given the high heritability of schizophrenia the question arises if impaired function of these networks is modulated by susceptibility genes and detectable in healthy risk allele carriers. The present event-related fMRI study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 of the DTNBP1 (dystrobrevin-binding protein 1) gene on brain activity in 80 subjects while performing the attention network test (ANT). In this reaction time task three domains of attention are probed simultaneously: alerting, orienting and executive control of attention. Risk allele carriers showed impaired performance in the executive control condition associated with reduced neural activity in the left superior frontal gyrus [Brodmann area (BA) 9]. Risk allele carriers did not show alterations in the alerting and orienting networks. BA 9 is a key region of schizophrenia pathology and belongs to a network that has been shown previously to be involved in impaired executive control mechanisms in schizophrenia. Our results identified the impact of DTNBP1 on the development of a specific attention deficit via modulation of a left prefrontal network.


Influence of Teucrium polium L. essential oil on the oxidative stability of canola oil during storage.
The susceptibility of Teucrium polium essential oil (EO) as an antioxidant for canola oil was studied. Major compounds of the EO were 11-acetoxyeudesman-4-α-ol (26.3%) and α-bisabolol (24.6%). Different concentrations (200, 600 and 1200 ppm) of EO and synthetic antioxidant BHA (200 ppm) were added to canola oil and incubated for 60 days at room temperature. Acid value (AV), peroxide value (PV), carbonyl value (CV), iodine value (IV), total phenolics (TP), total polar compounds (TPC) and oxidative stability index (OSI) of canola oil were determined. Antioxidant capacity of the EO was measured by DPPH and β-carotene-linoleic acid assays. Results exhibited that DPPH and β-carotene-linoleic acid experiment detections on the EO were analogous in high concentrations to those detected on BHA. Moreover, incorporated EO samples had better AV, PV, CV, IV, TP and TPC than control. EO at concentration of 600 ppm indicated higher antioxidant activity in canola oil compared with BHA.


From distributions of deviance to definitions of difference: past and future mental health geographies.
This paper reviews research in mental health geography that has examined landscapes of deinstitutionalisation, community care and everyday social life. It complements Philo's (1997, Across the water: reviewing geographical studies of asylums and other mental health facilities. Health and Place 3, 73-89) review of geographical studies concerned with asylums and other mental health facilities. Offering an interpretation of developments in this research sub-field, it charts a 'first wave' and a 'second wave' of inquiries, identifying shifts of substantive emphasis, theoretical approach and methodological practice. The gains and drawbacks of both 'waves' are discussed, with particular attention to absences both in what is researched and in the extent of political and policy engagement. The possible contours of a 'third wave' mental health geography, building on the strengths of earlier research but addressing new questions in new ways, are outlined in conclusion.


The Orthology Ontology: development and applications.
Computational comparative analysis of multiple genomes provides valuable opportunities to biomedical research. In particular, orthology analysis can play a central role in comparative genomics; it guides establishing evolutionary relations among genes of organisms and allows functional inference of gene products. However, the wide variations in current orthology databases necessitate the research toward the shareability of the content that is generated by different tools and stored in different structures. Exchanging the content with other research communities requires making the meaning of the content explicit. The need for a common ontology has led to the creation of the Orthology Ontology (ORTH) following the best practices in ontology construction. Here, we describe our model and major entities of the ontology that is implemented in the Web Ontology Language (OWL), followed by the assessment of the quality of the ontology and the application of the ORTH to existing orthology datasets. This shareable ontology enables the possibility to develop Linked Orthology Datasets and a meta-predictor of orthology through standardization for the representation of orthology databases. The ORTH is freely available in OWL format to all users at http://purl.org/net/orth . The Orthology Ontology can serve as a framework for the semantic standardization of orthology content and it will contribute to a better exploitation of orthology resources in biomedical research. The results demonstrate the feasibility of developing shareable datasets using this ontology. Further applications will maximize the usefulness of this ontology.


Gender-, side- and site-dependent variations in human perioral spatial resolution.
Twenty-eight right-handed, young adults participated in a sensory testing experiment to evaluate spatial resolution at 10 positionally matched sites on the right- and left-hand sides of the face. An adaptive psychophysical (i.e. tracking) procedure was used to estimate the threshold spatial separation for perceiving two points of contact at each site. Estimates of the threshold at one site on both sides of the face were also obtained with a method-of-limits procedure similar to that employed for clinical evaluation of patients. In addition, each individual was asked to rate (i) his(her) overall facial sensitivity to touch and (ii) the degree to which he(she) could discern subtle changes in lip, cheek and chin position during speech, chewing and facial expression. Analysis of the estimates of the threshold separation obtained with the tracking procedure revealed a significant effect of gender (p < 0.04) and of site (p < 0.001). Females were more spatially sensitive than males: average threshold separations were 1.55 mm less. Most notably, the threshold increased ninefold with distance posterolaterally from the oral opening. The vermilion of the upper lip was the most spatially sensitive site (population geometric mean = 2.4 mm) and the preauricular skin the least spatially sensitive site (20.9 mm). Significant effects of side and of interactions among gender, side and site were not observed. The estimates obtained with the method-of-limits procedure were very similar to those obtained with the tracking procedure: the latter were 0.67 mm less on the average. Individuals' ratings of overall facial sensitivity to touch were similar for males and females (p > 0.70). Females, however, reported greater ability to discern subtle changes in lip, cheek and chin position than males (p < 0.03). The ratings of this sensory function correlated negatively with the estimates of the threshold separation on the vermilion of the upper lip (p < 0.03).


Cardiovascular effectiveness of glucagon-like peptide 1 receptor agonists versus dipeptidyl peptidase-4 inhibitors in type 2 diabetes: A meta-analysis based on propensity score-matched studies.
Glucagon-like peptide 1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are two novel classes of hypoglycemic agents. The relative cardiovascular effectiveness between these two drug classes in patients with type 2 diabetes (T2D) is unestablished due to the absence of large cardiovascular outcome trials directly comparing DPP-4i with GLP-1RA. We aimed to incorporate large propensity score-matched cohort studies to conduct a meta-analysis, to determine the relative effectiveness of GLP-1RA versus DPP-4i on cardiovascular endpoints in T2D patients. Compared to DPP-4i, GLP-1RA was associated with the significantly lower risks of major adverse cardiovascular events [MACE] (HR 0.76, 95% CI 0.63-0.92), cardiovascular mortality (HR 0.59, 95% CI 0.37-0.95), myocardial infarction (HR 0.89, 95% CI 0.80-0.98), stroke (HR 0.86, 95% CI 0.76-0.96), and all-cause mortality (HR 0.63, 95% CI 0.42-0.96) in T2D patients; whereas these two drug classes had the similar risk of hospitalization for heart failure [HHF] (HR 0.95, 95% CI 0.77-1.16). Meta-regression analyses showed that six factors (i.e., mean age, female proportion, cardiovascular disease proportion, heart failure proportion, and the proportions of receiving metformin and insulin at baseline) did not significantly affect the effects of GLP-1RA on MACE and HHF (P ≥ 0.076). This meta-analysis provides the direct evidence regarding the relative cardiovascular effectiveness of GLP-1RA versus DPP-4i from real-world studies, and its findings suggest that among T2D patients GLP-1RA should be considered in preference to DPP-4i as for preventing atherosclerotic cardiovascular events and death in clinical practice.


Ethnic and Gender Diversity in Radiology Fellowships.
The purpose of the study is to assess ethnic and gender diversity in US radiology fellowship programs from 2006 to 2013. Data for this study was obtained from Journal of the American Medical Association supplements publications from 2005 to 2006 to 2012-2013 (Gonzalez-Moreno, Innov Manag Policy Pract. 15(2):149, 2013; Nivet, Acad Med. 86(12):1487-9, 2011; Reede, Health Aff. 22(4):91-3, 2003; Chapman et al., Radiology 270(1):232-40, 2014; Getto, 2005; Rivo and Satcher, JAMA 270(9):1074-8, 1993; Schwartz et al., Otolaryngol Head Neck Surg. 149(1):71-6, 2013; Simon, Clin Orthop Relat Res. 360:253-9, 1999) and the US census 2010. For each year, Fisher's exact test was used to compare the percentage of women and under-represented minorities in each Accreditation Council for Graduate Medical Education (ACGME)-certified radiology fellowship to the percentage of women and under-represented minorities in (1) all ACGME-certified radiology fellowships combined, (2) radiology residents, (3) ACGME-certified fellows in all of medicine combined, (4) ACGME-certified residents in all of medicine combined, and (5) graduating medical students. Chi-Squared test was used to compare the percentage of women and under-represented minorities and the 2010 US census. p < 0.05 was used as indicator of significance. Interventional radiology and neuroradiology demonstrated the highest levels of disparities, compared to every level of medical education. Abdominal and musculoskeletal radiology fellowships demonstrated disparity patterns consistent with lack of female and URM medical graduates entering into radiology residency. All radiology fellowships demonstrated variable levels of gender and ethnic disparities. Outreach efforts, pipeline programs, and mentoring may be helpful in addressing this issue.


The mPower study, Parkinson disease mobile data collected using ResearchKit.
Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health.


Renal medullary oxygenation decreases with lower body negative pressure in healthy young adults.
One in three Americans suffer from kidney diseases such as chronic kidney disease, and one of the etiologies is suggested to be long-term renal hypoxia. Interestingly, sympathetic nervous system activation evokes a renal vasoconstrictor effect that may limit oxygen delivery to the kidney. In this report, we sought to determine if sympathetic activation evoked by lower body negative pressure (LBNP) would decrease cortical and medullary oxygenation in humans. LBNP was activated in a graded fashion (LBNP; -10, -20, and -30 mmHg), as renal oxygenation was measured (T2*, blood oxygen level dependent, BOLD MRI; n = 8). At a separate time, renal blood flow velocity (RBV) to the kidney was measured (n = 13) as LBNP was instituted. LBNP significantly reduced RBV (P = 0.041) at -30 mmHg of LBNP (Δ-8.17 ± 3.75 cm/s). Moreover, both renal medullary and cortical T2* were reduced with the graded LBNP application (main effect for the level of LBNP P = 0.0008). During recovery, RBV rapidly returned to baseline, whereas medullary T2* remained depressed into the first minute of recovery. In conclusion, sympathetic activation reduces renal blood flow and leads to a significant decrease in oxygenation in the renal cortex and medulla.NEW & NOTEWORTHY In healthy young adults, increased sympathetic activation induced by lower body negative pressure, led to a decrease in renal cortical and medullary oxygenation measured by T2*, a noninvasive magnetic resonance derived index of deoxyhemoglobin levels. In this study, we observed a significant decrease in renal cortical and medullary oxygenation with LBNP as well as an increase in renal vasoconstriction. We speculate that sympathetic renal vasoconstriction led to a significant reduction in tissue oxygenation by limiting oxygen delivery to the renal medulla.


Chemical aspects of self-etching enamel-dentin adhesives: a systematic review.
The paper gives an overview on the components and the polymer chemical aspects of currently used self-etching enamel-dentin primers/adhesives. In addition, the contribution of new adhesives monomers and cross-linkers exhibiting enhanced hydrolytic stability than methacrylates to improve the performance of single-bottle adhesives is discussed. Information from original scientific papers or reviews about enamel-dentin adhesives, the patent literature concerning dental adhesives and manufacturer information of commercial self-etching adhesives were included in this review. The most efficient self-etching enamel-dentin adhesives are based on strongly acidic adhesive monomers, containing dihydrogenphosphate, phosphonic acids or carboxylic acid groups. Serious problems of single-bottle water-based, strongly acidic self-etching enamel-dentin adhesives arise both from the hydrolytic instability of the methacrylate monomers used and the side reaction of the applied initiator components. The stability of the self-etching enamel-dentin adhesives can be improved by using new acrylic ether phosphonic acids or mono- or difunctional acrylamides, while more stable and compatible components have to be developed in the future.


Platelet crossmatch evaluation in refractory hematologic patients.
Although previous investigators have attempted to identify platelet crossmatching methods that could be used routinely for pretransfusion testing, such studies have excluded patients with underlying clinical conditions inherently associated with low corrected platelet increments. Because many refractory hematologic patients have such underlying conditions, we decided to assess the usefulness of platelet crossmatching (in addition to HLA matching) in determining the posttransfusion corrected platelet count increment in eight medically complicated patients who received a total of 35 single-donor platelet transfusions. In this limited study, the predictive value of a negative crossmatch was only 55%, whereas that of a positive crossmatch was 88%. The test used had a sensitivity of 65% and a specificity of 83%. The results of our study suggest that platelet crossmatching may be a useful additional study for predicting the outcome of transfusion--even in medically complex cases--if it can be done rapidly and relatively inexpensively.


Histochemical study of epididymal secretions in the lizard, Lacerta vivipara. Localization of lectin-binding sites.
The epididymis of lizards elaborates voluminous secretory granules made of a central core and a peripheral vacuole which in the species Lacerta vivipara contain respectively an insoluble protein (protein H) and a soluble protein (protein L). After their discharge these secretions mix with spermatozoa. In order to detect the presence of carbohydrates in these secretions, lectins isolated from Canavalia ensiformis (con A) and from eleven other plants (lentil, soja, pea, gorse and several mushrooms), conjugated to fluorescein isothiocyanate, have been utilized in light-microscopic histochemical investigations of frozen sections from Lacerta vivipara epididymis. Whereas lectins having affinity for L-fucose, lactose, D-galactose and N-acetyl-D-galactosamine bound to central cores, lectins having affinity to D-glucose, N-acetylglucosamine and chitobiose bound to the peripheral vacuole. D-mannose or D-glucose seem to be present both in central cores and in peripheral vacuoles.


Cardiovascular and antidepressant effects of imipramine in the treatment of secondary depression in patients with ischemic heart disease.
The authors report on 12 men with ischemic heart disease who developed secondary depression following myocardial infarction or coronary artery bypass-graft surgery and were treated with imipramine hydrochloride for 4 weeks. Imipramine had an antiarrhythmic effect, manifested by reduction in premature ventricular contractions during treatment. This drug did not produce clinically significant disturbances in cardiac conduction, but orthostatic hypotension led to early termination of the drug treatment in 1 subject. Imipramine treatment was associated with significant improvement in both observer-rated and patient-rated depression scales.


Ocular higher-order aberrations in myopia and skiascopic wavefront repeatability.
To study the distribution of ocular higher-order aberrations (HOAs) in a myopic population and to assess the repeatability of HOA measurements determined by a commercially available skiascopic wavefront sensor. Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, Israel. Ocular HOAs were examined 3 times across a 6.0 mm naturally dilated pupil in 61 eyes using the Optical Path Difference (OPD)-scan wavefront aberrometer. Root-mean-square (RMS) values of HOAs, total spherical aberration (TSA), total coma (TC), and total trefoil (TT) were analyzed. Correlation analysis was performed to assess the aberration symmetry between right and left eyes. The repeatability of the OPD-scan measurements was assessed by calculating Pearson r correlation coefficients between each pair of measurements and the interclass correlation coefficients between the 3 measurements of each score. The mean RMS values of HOAs, TSA, TC, and TT were 0.347 microm +/- 0.252 (SD), 0.120 +/- 0.174 microm, 0.165 +/- 0.168 microm, and 0.252 +/- 0.157 microm, respectively. The HOAs, TSA, TC, and TT changed slightly and not significantly with increasing refractive error (all P>.05). The RMS level of HOAs and TTR of the 3rd measurement was significantly different from the 1st and 2nd measurements (P<.05), with overall low correlation between the 3 measurements for the HOAs, TSA, TC, and TT. The ocular wavefront aberrations varied greatly from subject to subject. Ocular HOAs were not correlated with refractive error. The repeatability of HOAs measurements with the OPD-aberrometry was low.


Protein kinase CK2: signaling and tumorigenesis in the mammary gland.
Breast cancer is a major cause of cancer death in women, and the genetic abnormalities leading to the common sporadic forms of the disease are still under active investigation. CK2 has been reported to be upregulated in human breast cancer, which these studies confirm; CK2 is also upregulated in rat carcinogen-induced breast tumors. Transgenic mice overexpressing CK2alpha in the mammary gland develop mammary hyperplasia, dysplasia, and eventually adenocarcinomas, demonstrating that dysregulated expression of CK2 can contribute to transformation of the mammary epithelium. These mammary tumors have evidence of activation of the Wnt and NFkappaB pathways and upregulation of c-Myc. CK2 is capable of phosphorylating the key signaling molecule in the Wnt pathway, the transcriptional cofactor beta-catenin, and regulating its turnover. CK2 is known to phosphorylate IkappaB and thereby regulate basal NFkappaB levels; in the mammary cell lines and tumors, CK2 activity correlates with NFkappaB levels and inhibition of CK2 downregulates NFkappaB. Thus, CK2 may promote breast cancer through dysregulation of key pathways of transcriptional control in the mammary epithelium, and inhibition of CK2 has a potential role in the treatment of breast and other cancers.


Effect of a dexamethasone Sinu-Foam™ middle meatal spacer on endoscopic sinus surgery outcomes: a randomized, double-blind, placebo-controlled trial.
Off-label drug eluting middle-meatal spacers have shown promising results for improving clinical outcomes following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). This study evaluates a dexamethasone Sinu-Foam™ spacer following ESS for CRS without nasal polyposis (CRSsNP). Patients with CRSsNP (n = 36) were enrolled into a double-blind, placebo-controlled trial and randomized into either a treatment arm (dexamethasone Sinu-Foam™ mixture; n = 18) or placebo arm (Sinu-Foam™ alone; n = 18). Therapeutic outcomes were evaluated at 1 week, 4 weeks, and 3 months using sinonasal endoscopy and graded using the Lund-Kennedy scoring system. Postoperative care included nasal saline irrigations and a short course of systemic steroids. All patients completed the study follow-up period. Both study arms experienced significant improvement in endoscopic grading over the study duration (p < 0.001). There was no difference in average endoscopic scores between the treatment and placebo groups at 1 week, 4 weeks, and 3 months (all p > 0.489). This study demonstrated that an off-label drug-eluting middle-meatal spacer of dexamethasone and Sinu-Foam™ does not improve endoscopic outcomes in the early postoperative period following ESS when combined with postoperative saline irrigations and a short course of systemic steroids.


A novel conjugated polymer fluorescence probe for the detection of copper ions in aqueous media.
A novel ionic conjugated polymer fluorescent probe (IP) containing fluorenyls and imines was synthesized through a simple condensation method for the rapid detection of Cu2+. The probe exhibited a selective quenching response toward Cu2+over other common metal ions in phosphate-buffered saline (PBS) at a pH of 7. Moreover, the fluorescence intensity ofIPwas linearly proportional to the concentration of Cu2+when it ranged from 1 to 10μM, and the limit of detection for Cu2+was 0.45μM. Furthermore, the quenched fluorescence ofIPby Cu2+was recovered after adding amino acids or ethylenediaminetetraacetic acid (EDTA), indicating that the probe could be recycled and is promising to reduce the detection cost of Cu2+in real samples.


Conserved and unique functions of NIN-like proteins in nitrate sensing and signaling.
Nitrogen is the most abundant element in the atmosphere and serves as the foundation block of life, including plants on earth. Unlike carbon fixation through photosynthesis, plants rely heavily on external supports to acquire nitrogen. To this end, plants have adapted various strategies such as forming mutualistic relationships with nitrogen-fixing bacteria and evolving a large regulatory network that includes multiple transporters, sensors, and transcription factors for fine-tuning nitrate sensing and signaling. Nodule Inception (NIN) and NIN-like protein (NLP) are central in this network by executing multiple functions such as initiating and regulating the nodule symbiosis for nitrogen fixation, acting as the intracellular sensor to monitor the nitrate fluctuations in the environment, and activating the transcription of nitrate-responsive genes for optimal nitrogen uptake, assimilation, and usage. The involvement of NLPs in intracellular nitrate binding and early nitrate responses highlight their pivotal role in the primary nitrate response (PNR). Genome-wide reprogramming in response to nitrate by NLP is highly transient and rapid, requiring regulation in a precise and dynamic manner. This review aims to summarize recent progress in the study of NIN/NLP for a better understanding of the molecular basis of their roles and regulations in nitrate sensing and signaling, with the hope of shedding light on increasing biological nitrogen fixation and improving nitrogen use efficiency (NUE) to minimize fertilizer input in agriculture.


A randomized controlled clinical trial of a hypothermically stored amniotic membrane for use in diabetic foot ulcers.
Aim: Determine the effectiveness of hypothermically stored amniotic membrane (HSAM) versus standard of care (SOC) in diabetic foot ulcers (DFUs). Methods: A randomized controlled trial was conducted on 76 DFUs analyzed digitally. Results: Cox wound closure for HSAM (38 wounds) was significantly greater (p = 0.04) at weeks 12 (60 vs 38%), and 16 (63 vs 38%). The probability of wound closure increased by 75% (Hazard Ratio = 1.75; 95% CI: 1.16-2.70). HSAM showed >60% reductions in area (82 vs 58%; p = 0.02) and depth (65 vs 39%; p = 0.04) versus SOC. Conclusion: HSAM increased frequency and probability of wound closure in DFUs versus SOC.


Genome-wide CRISPR-cas9 knockout screening identifies GRB7 as a driver for MEK inhibitor resistance in KRAS mutant colon cancer.
Targeting the KRAS pathway is a promising but challenging approach for colorectal cancer therapy. Despite showing potent efficacy in BRAF-mutated melanoma, MEK inhibitors appeared to be tolerated by colorectal cancer cells due to their intrinsic compensatory signaling. Here, we performed genome-wide CRISPR/Cas9 screening in the presence of MEK inhibitor to identify genes that are synthetically lethal with MEK inhibition in CRC models harboring KRAS mutations. Several genes were identified as potential functional drivers, which were significantly enriched in the GRB7-mediated RTK pathway. Loss-of-function and gain-of-function assays validated that GRB7 potently rendered CRC cells primary resistance to MEK inhibitors through the RTK pathway. Mass spectrum analysis of GRB7 immunoprecipitates revealed that PLK1 was the predominant interacting kinase of GRB7. Inhibition of PLK1 suppressed downstream signaling of RTK, including FAK, STAT3, AKT, and 4EBP1. The combination of PLK1 and MEK inhibitors synergistically inhibited CRC cell proliferation and induced apoptosis in vitro and in vivo. In conclusion, we identified GRB7-PLK1 as a pivotal axis mediating RTKs, resulting in MEK inhibitor tolerance. PLK1 is therefore a promising target for synergizing MEK inhibitors in the clinical treatment of CRC patients harboring KRAS mutations.


Response of blood and brain cholinesterase to dermal exposure of bromophos in the rat.
Response of cholinesterase to dermal exposure of acute, single and multiple doses of Bromophos in the female rat has been studied. Dose-response studies (50-4000 mg/kg body weight, 24 h exposure) showed that plasma cholinesterase was most sensitive to inhibition in vivo, followed by the brain and erythrocyte acetylcholinesterase. The ID50 values for the in vivo cholinesterase inhibition were 10.1, 576.1 and 1938.0 mg/kg body weight for the plasma, brain and erythrocytes, respectively. In time-course studies after a single sublethal dose of 1000 mg/kg body weight (24 h) of Bromophos, the serum and brain cholinesterase were rapidly inhibited reaching a maximum at 16 h. Recovery was complete in the case of serum at 14 days post-exposure, whereas the brain enzyme was not fully recovered at 21 days. In a subacute study, daily dermal application of 50 mg/kg body weight of Bromophos for 5 and 10 days, resulted in high inhibition of the serum cholinesterase and brain acetylcholinesterase, the former being more marked which was reversible after 10 or 15 days of post-exposure period. Very low levels of dermal exposure of Bromophos (10-50 mg/kg body weight) for 17 days caused pronounced depression of serum cholinesterase which completely recovered in 15 days after cessation of exposure suggesting that the serum cholinesterase could serve as the most sensitive diagnostic indicator of Bromophos exposure.


Bone restoration with cemented Exeter universal stem - Three-years longitudinal DEXA study in 165 hips for femur.
The pattern of strain distribution in the proximal femur changes following total hip arthroplasty (THA) and decreases in bone mineral density (BMD) occur around the stem following cemented and uncemented THA. We herein prospectively examined changes in BMD for 3 years after THA with a cemented Exeter universal stem. One hundred and sixty five hips from 150 patients who underwent unilateral THA were included as a cohort. Our patients included 20 men (20 hips) and 130 women (145 hips) with a mean age of 63.9 years. BMD was measured 2 weeks postoperatively (baseline) and 3, 6 12, 18, 24, 30, and 36 months (3 years) after surgery using dual-energy X-ray absorptiometry (DEXA) on the lumbar spine and proximal femur of the operated side according to the Gruen zone classification. We quantified longitudinal changes in BMD for more than 3 years after surgery and detected several factors which affected these changes. In the first year, BMD in the most proximal femur showed a 5.5% reduction at the lateral side (zone 1) and 13% reduction at the medial side (zone 7), with no significant BMD reductions being observed thereafter. BMD reductions at 3 years were the most apparent at the proximal medial part of the femur (zone 7; -10.3%), while BMD ratio change in zone 1 was over the baseline (+2.9%). Especially in zone 7, the BMD ratio decreased with female, decreases in weight, decreases in height, decreases in BMI, and increases in age at the time of surgery. Bone restoration is expected with a cemented Exeter universal stem. Male patients, a younger age, a high body weight, being tall, and a high BMI were identified as factors associated with the restoration of BMD in proximal femur.


Effects of delayed postoperative void and preoperative urologic symptoms on delay in time of discharge for elective lumbar decompression surgery.
Almost half of all patients undergoing lumbar spine surgery have preoperative lower urinary tract symptoms (LUTS). These symptoms could affect postoperative voiding and subsequently length of stay. To investigate the association between preoperative LUTS and time to first void and between time to first void and time to discharge among patients undergoing elective lumbar decompression surgery. Retrospective analysis of prospectively collected data among patients at a single academic medical center. All patients ≥18 years of age undergoing elective lumbar decompression surgery between July 2017 and March 2020. The physiologic measure of a delayed time to first void was defined as an initial postoperative void of > 4 hours after anesthesia stop time. The outcome of prolonged time to discharge was defined as a stay of >24 hours after anesthesia stop time. At their preoperative visit, patients completed the validated International Prostate Symptom Score (IPSS) (range, 0-35 points), which is applicable for LUTS assessment in both sexes. Clinically relevant LUTS are defined as an IPSS score of ≥8. Patients were followed from their preoperative visit to surgery admission discharge. Association of LUTS with time to first void and time to first void with admission discharge were estimated using risk ratios (RR) and 95% confidence intervals (CI) from a multivariable Poisson regression with a robust variance estimate adjusted for potential confounding variables including age, sex, IPSS, and intraoperative Foley catheter use. The analytic cohort included 170 patients with an average age of 57 years and 103 (61%) were men. Preoperative LUTS prevalence was 45%, and 111 (65%) of patients voided within 4 hours after surgery. For patients with preoperative LUTS, the unadjusted RR for a first void of >4 hours was 1.04 (95% CI: 0.82-1.32) (p=.77). Adjustment for age, sex, intraoperative Foley catheter use, revision surgery, previous spine surgery, single versus multiple levels, and lumbar location did not materially alter the risk: the multivariable RR was 1.04 (95% CI: 0.82-1.31) (p=.74). The unadjusted RR for a discharge of > 24 hours for patients with a time to first void of > 4 hours was 2.17 (95% CI: 1.51-3.10) (p<.001). After adjusting for age, sex, intraoperative Foley catheter use, IPSS, revision surgery, previous spine surgery, single versus multiple levels, and lumbar location, the multivariable RR was 1.72 (95% CI: 1.22-2.41) (p=.002). Regardless of preoperative LUTS status, an initial first void of >4 hours after surgery is associated with a longer time to discharge among patients undergoing elective lumbar decompression surgery. Future studies are needed to determine if encouraging early postoperative voiding results in timely discharge and shorter length of stay.


Prognosis of Liver Transplantation for Hepatocellular Carcinoma in Terms of Different Criteria: A Single Center Experience.
Patients undergoing liver transplantation for hepatocellular carcinoma (HCC) within the Milan criteria have an excellent outcome. We developed a program to analyze and prove that the Milan criteria can be expanded safely and effectively. We retrospectively reviewed 117 HCC patients treated with liver transplantation between January 2013 and December 2017. Patients were grouped according to the Milan criteria, the University of California, San Francisco (UCSF) criteria, Up-to-seven criteria and Hangzhou criteria. Tumor-free and overall survival rates were investigated with a Kaplan-Meier analysis. Multivariable regression Cox models produced survival estimates for the patients that exceeded the Milan criteria. The 1-year, 3-year and 5-year overall survival rates of patients fulfilling the Milan criteria (n=44) were 100%, 87.5% and 78.9%, respectively. Compared with the Milan criteria, the UCSF criteria (n=50), Up-to-seven criteria (n=51) and Hangzhou criteria (n=86) provided an expansion of 13.6%, 15.9% and 95.9%, respectively. The 1-year, 3-year and 5-year overall survival rates of patients fulfilling UCSF criteria, Up-to-seven criteria and Hangzhou criteria were 96.0%, 84.9%, 76.9%; 96.1%, 85.2%, 77.6% and 97.7%, 83.9%, 66.7%, respectively (P>0.05). Multifactor Cox regression showed that tumor diameter and microvascular invasion were independent risk factors for survival in patients that exceeded the Milan criteria. Compared with the Milan criteria, the Hangzhou criteria can safely expand the scope of liver transplantation for HCC to a certain extent. By contrast, the UCSF criteria and Up-to-seven criteria result in a limited number of patients which need further expansion. Tumor diameter and microvascular invasion were the independent risk factors for survival in patients that exceeded the Milan criteria.


Cardiac beta-adrenoceptors in chronic uremia: studies in humans and rats.
The purpose of this study was to elucidate whether cardiac beta-adrenergic effects may be blunted in patients on maintenance hemodialysis (HD) and may help to explain autonomic dysfunction. Patients on HD often suffer from autonomic dysfunction. We investigated the cardiovascular response of five HD patients (age: 46.1+/-7.9 years) and six healthy volunteers (age: 48.2+/-7.5 years) to isoprenaline, pirenzepine and phenylephrine. For analysis of underlying mechanisms of beta-adrenoceptor hyporesponsiveness, six-week-old male Wistar rats were rendered uremic by 5/6-nephrectomy (n = 9; SNX) and were killed for removal of the heart after six to seven weeks. Sham-operated rats (n = 15) served as controls. In the patient study, isoprenaline (3.5, 7, 17, 35 ng/kg/min, i.v.) led to an increase in heart rate, and shortening of the heart rate corrected duration of the electromechanical systole (QS2c), both of which were significantly reduced in HD patients. Baroreflex sensitivity was significantly reduced in HD patients. The response to low parasympathomimetic doses of pirenzepine was unchanged. In the rat study, left ventricular strips were placed in an organ bath, electrically driven and exposed to isoprenaline (10(-11) to 10(-6) mol/liter). While pD2 values were unchanged, maximum effect at the highest concentration was significantly reduced in SNX rats. The response to carbachol was not altered, nor was the M2-cholinoceptor density. There was no difference in beta-adrenoceptor density, or in immunodetectable amount of Gs and Gi protein. Activation of adenylyl cyclase evoked by isoprenaline was significantly reduced in left ventricular membranes of SNX rats, whereas effects of 10 micromol/liter GTP, 10 mmol/liter NaF, 10 micromol/liter forskolin and 10 mmol/liter Mn2+ were not altered. Cardiac beta-adrenergic responses are blunted in chronic uremia due to reduced isoprenaline-dependent activation of adenylyl cyclase. This might be caused by an "uncoupling" of the receptor or by an inhibition of the receptor by uremic toxins.


Rhabdomyosarcoma: review of the Children's Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies.
The prognosis for children and adolescents with rhabdomyosarcoma (RMS) has improved with refinements in multi-modal therapy. Since 1972, the Intergroup Rhabdomyosarcoma Study Group (now the Children's Oncology Group Soft-Tissue Sarcoma Committee) has conducted serial studies for RMS. This review describes the IRSG and COG experience with RMS, presents the current risk stratification definitions, and provides rationale for the current generation of COG RMS studies.


Bone mineral content in calcium renal stone formers.
Idiopathic renal calcium stone disease often presents with reduced bone mineral content. Investigations using non-invasive methods for the measurement of bone mineral content (single and dual-photon absorptiometry, dual-energy x-ray absorptiometry, quantitative computed tomodensitometry) show a slight decrease in skeletal mineral content of idiopathic renal stone formers (RSFs). The alterations in bone mineral content in RSFs have different explanations: prostaglandin-mediated bone resorption, subtle metabolic acidosis and 1-25 vitamin D disorders. Bone mineral content is worsened by insufficient dietary calcium leading to a negative calcium balance.


Selective detection of guanosine-5'-triphosphate and iodide by fluorescent benzimidazolium-based cyclophanes.
New fluorescent benzimidazolium-based receptors selectively display the effective fluorescence quenching effect for biologically important anions, GTP and I(-), in aqueous solution of physiological pH 7.4. These affinities can be attributed to the strong ionic H-bonding along with additional interactions of fluorophore moieties with the nucleic base of GTP and I(-).


dbPHCC: a database of prognostic biomarkers for hepatocellular carcinoma that provides online prognostic modeling.
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a poor prognosis. For decades, more and more biomarkers were found to effect on HCC prognosis, but these studies were scattered and there were no unified identifiers. Therefore, we built the database of prognostic biomarkers and models for hepatocellular carcinoma (dbPHCC). dbPHCC focuses on biomarkers which were related to HCC prognosis by traditional experiments rather than high-throughput technology. All of the prognostic biomarkers came from literatures issued during 2002 to 2014 in PubMed and were manually selected. dbPHCC collects comprehensive information of candidate biomarkers and HCC prognosis. dbPHCC mainly contains 567 biomarkers: 323 proteins, 154 genes, and 90 microRNAs. For each biomarker, the reference information, experimental conditions, and prognostic information are shown. Based on two available patient cohort data sets, an exemplified prognostic model was constructed using 15 phosphotransferases in dbPHCC. The web interface does not only provide a full range of browsing and searching, but also provides online analysis tools. dbPHCC is available at http://lifecenter.sgst.cn/dbphcc/ dbPHCC provides a comprehensive and convenient search and analysis platform for HCC prognosis research. dbPHCC is the first database to focus on experimentally verified individual biomarkers, which are related to HCC prognosis. Prognostic markers in dbPHCC have the potential to be therapeutic drug targets and may help in designing new treatments to improve survival of HCC patients. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.


Regulation of System A amino acid transport in L6 rat skeletal muscle cells by insulin, chemical and hyperthermic stress.
In this study we have investigated the effects of insulin, chemical and hyperthermic stresses upon the activity of the System A amino acid transporter in L6 rat muscle cells. Uptake of alpha-methyl-aminoisobutyric acid (Me-AIB), a non-metabolisable System A substrate, was increased by between 50% and 80% when muscle cells were exposed to a maximally effective concentration of insulin (100 nM), sodium arsenite (ARS, 0.5 mM) or a 42 degrees C heat shock (HS). The observed activation in System A in response to all three stimuli was maximal within 20 min and in the case of insulin and ARS primarily involved an increase in the Vmax of System A transport. In contrast, HS induced significant increases in both Vmax and Km of System A transport suggesting that hyperthermic stress may activate System A by a mechanism distinct from that mediating the effects of insulin and ARS. The hormonal stimulation of System A was blocked by the phosphoinositide 3-kinase (PI3k) inhibitor, wortmannin, but not by rapamycin or PD 98059 which respectively inhibit the mTOR and classical MAP kinase pathways. Exposure of L6 cells to ARS, but not HS, caused a 4.7-fold stimulation in MAPKAP-K2 activity that was blocked by SB 203580, a specific inhibitor of the stress activated protein kinase SAPK2/p38. However, neither SB 203580, rapamycin nor wortmannin were able to suppress the ARS- or HS-induced stimulation in System A transport. In summary, our results demonstrate that activity of the System A transporter can be rapidly upregulated in response to hormonal and stress stimuli through changes in the transport kinetics of the System A carrier. Our data show that whilst the hormonal response is PI3k dependent, the signalling mechanisms which instigate changes in System A activity in response to chemical or hyperthermic stress do not appear to involve PI3k or components of the mTOR, p42/p44 MAP kinase or SAPK2/p38 signalling pathways.


Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein-Taybi and Filippi syndromes.
Rubinstein-Taybi syndrome (RTS, OMIM 180849) and Filippi syndrome (FLPIS, OMIM 272440) are both rare syndromes, with multiple congenital anomalies and intellectual deficit (MCA/ID). We present a patient with intellectual deficit, short stature, bilateral syndactyly of hands and feet, broad thumbs, ocular abnormalities, and dysmorphic facial features. These clinical features suggest both RTS and FLPIS. Initial DNA analysis of DNA isolated from blood did not identify variants to confirm either of these syndrome diagnoses. Whole-exome sequencing identified a homozygous variant in C9orf173, which was novel at the time of analysis. Further Sanger sequencing analysis of FLPIS cases tested negative for CKAP2L variants did not, however, reveal any further variants. Subsequent analysis using DNA isolated from buccal mucosa revealed a mosaic variant in CREBBP. This report highlights the importance of excluding mosaic variants in patients with a strong but atypical clinical presentation of a MCA/ID syndrome if no disease-causing variants can be detected in DNA isolated from blood samples. As the striking syndactyly observed in the present case is typical for FLPIS, we suggest CREBBP analysis in saliva samples for FLPIS syndrome cases in which no causal CKAP2L variant is detected.


Benzoyl peroxide use transiently decreases Cutibacterium acnes load on the shoulder.
Cutibacterium acnes is the most common pathogen in shoulder prosthetic joint infections. Short-contact benzoyl peroxide (BPO) solutions effectively reduce C acnes loads on the shoulder preoperatively. It is unknown how long the effect of BPO lasts. We evaluated C acnes counts 1 week after BPO application. We hypothesized that BPO would decrease C acnes burden with a rebound after 1 week. Screening of 102 healthy volunteers with no history of shoulder surgery or C acnes infection was performed to establish bacterial counts. Thirty-four participants were selected based on an established threshold. Each was given BPO 5% for 3 consecutive days of application on either the left or right shoulder as indicated by a random number generator. Deep sebaceous gland cultures were obtained with a detergent scrub technique before BPO application, after 3 days of use, and 1 week after BPO treatment commenced. The differences between the logarithmic reduction and the logarithmic rebound at the anterior, lateral, and posterior sites were statistically significant. Anteriorly, the average log reduction was -0.44 and the average log rebound was 0.69 (P = .003). Laterally, reduction was -0.64 and rebound was 0.74 (P = .003). Posteriorly, reduction was -0.63 and rebound was 0.78 (P = .008). At the axilla, reduction was -0.40 and rebound was 0.31 (P = .10). The differences in C acnes burden between pretreatment and 1-week counts at all sites were not statistically significant. A significant decrease in C acnes burden occurred after BPO application but was not permanent. Significant rebound occurred just 1 week later.


Chemotaxis radioassays: a simplified, quantitative method using technetium-99m radiocolloid labeled granulocytes.
Selective labeling of phagocytes in human blood can be achieved by incubation of unseparated, heparinized blood with 99mTc-sulfur colloid. We have developed a method for quantitation of granulocyte chemotaxis using granulocytes labeled by this technique. The method was found to be more accurate and less tedious to perform than the conventional Boyden chamber chemotaxis assay. The assay was also less time-consuming and as quantitative as a previously described granulocyte chemotaxis radioassay in which 51Cr-labeled leukocytes were used. The simplicity and reliability of this technique and the ready availability of 99mTc-sulfur colloid may provide one standardized method for granulocyte chemotaxis quantitation in clinical and experimental medicine.


Implantable Devices in Genetic Heart Disease: Disease-Specific Device Selection and Programming.
Diagnosis and risk stratification of rare genetic heart diseases remains clinically challenging. In many cases, there are few data and insufficient numbers to support randomized controlled trials. While implantable cardioverter defibrillator (ICD) use is vital to protect higher-risk individuals from life-threatening ventricular arrhythmias, low-risk individuals also require protection from unnecessary ICDs and their associated complications. Once an ICD has been implanted, appropriate device programming is essential to ensure maximal protection while balancing the risks of inappropriate therapy.


Demands of surgical teams in robotic-assisted surgery: An assessment of intraoperative workload within different surgical specialties.
Current approaches to assessing workload in robotic-assisted surgery (RAS) focus on surgeons and lack real-world data. Understanding how workload varies by role and specialty aids in identifying effective ways to optimize workload. SURG-TLX surveys with six domains of workload were administered to surgical staff at three sites. Staff reported workload perceptions for each domain on a 20-point Likert scale, and aggregate scores were determined per participant. 188 questionnaires were obtained across 90 RAS procedures. Significantly higher aggregate scores were reported for gynecology (Mdn = 30.00) (p = 0.034) and urology (Mdn = 36.50) (p = 0.006) than for general (Mdn = 25.00). Surgeons reported significantly higher scores for task complexity (Mdn = 8.00) than both technicians (Mdn = 5.00) (p = 0.007), and nurses (Mdn = 5.00). Staff reported significantly higher workload during urology and gynecology procedures, and experienced significant differences in domain workload by role and specialty, elucidating the need for tailored workload interventions.


Modified score based on revised Tokuhashi score is needed for the determination of surgical intervention in patients with lung cancer metastases to the spine.
Revised Tokuhashi score (RTS) is no longer accurate to predict the survival of patients with lung cancer metastases to the spine. This study is to identify additional prognostic factors in those patients, develop a modified prognostic score based on RTS, and verify the accuracy of the score in prediction. Our study included patients with lung cancer metastases to the spine who underwent surgery for spine metastasis. Potential prognostic factors were analyzed. Points were allocated for prognostic factors obtained from survival analyses. A modified score was developed by including prognostic factors and their points to RTS. Accuracy of the modified score was evaluated by comparing the coincidence between predicted and observed survival. Kaplan-Meier analysis and Cox regression models were used. Predictive values of scores for 6-month survival were measured via receiver operating characteristic (ROC) curves. Targeted therapy and tumor markers were additional independent prognostic factors. In the modified score, 2 and 1 points were allocated to the new evaluation factors. The points for factors based on RTS remained the same, and two prognostic groups were redefined. For group A patients who were predicted to live for less than 6 months, conservative procedures would be recommended. For group B patients who were predicted to live for 6 months or more, palliative surgery would be recommended. When comparing the modified score to RTS, the area under the receiver operating characteristic curve (AUCROC) and accuracy of score were improved. The modified RTS has improved prognostic accuracy in patients with lung cancer metastases to the spine.


Regional Control and Chemoradiotherapy Dose Response for Clinically Involved Lymph Nodes in Patients with Locally Advanced Endometrial Cancers Who are Not Candidates for Upfront Surgical Staging Extrafascial Hysterectomy.
There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.