Study protocol: Neuro-inflammatory parameters as mediators of the relationship between social anxiety and itch intensity: A cross-sectional, controlled laboratory study in patients with psoriasis and healthy skin controls.
Psoriasis (PSO) is a disease that in the majority of patients is accompanied by itch, which imposes a great burden and positively relates to anxiety. Social anxiety, a facet of anxiety associated with social withdrawal, may be a predictor of itch intensity in this patient group. Moreover, anxiety is linked to the secretion of neuroendocrine and inflammatory parameters such as substance P (SP), interleukin (IL)-6 and IL-17, which are also related to itch. In this research project, we investigate first, whether there is a direct relationship between social anxiety and itch intensity in patients with PSO and second whether the secretion of SP, IL-6 and IL-17 in the skin mediates this relationship. Additionally, PSO-patients are compared to healthy skin controls regarding their level of social anxiety, itch intensity and the secretion of SP, IL-6 and IL-17. For study 1, we aim to recruit 250 psoriasis patients and 250 healthy skin controls who complete questionnaires to assess social anxiety, itch intensity and control variables (e.g. sociodemographic variables and severity of PSO). A linear hierarchic regression will be used to determine whether social anxiety significantly contributes to itch intensity. In study 2, we plan to apply the suction blister method to 128 patients and healthy skin controls recruited from study 1 to determine SP, IL-6 and IL-17 in tissue fluid extracted from the skin. A mediation analysis will be conducted using the SPSS-macro PROCESS to test whether the relationship between social anxiety and itch is mediated by SP, IL-6 and IL-17. DRKS00023621 (study 1) and DRKS00023622 (study 2).


Three-dimensional structural analysis reveals a Cdk5-mediated kinase cascade regulating hepatic biliary network branching in zebrafish.
The intrahepatic biliary network is a highly branched three-dimensional network lined by biliary epithelial cells, but how its branching patterns are precisely established is not clear. We designed a new computer-based algorithm that quantitatively computes the structural differences of the three-dimensional networks. Utilizing the algorithm, we showed that inhibition of Cyclin-dependent kinase 5 (Cdk5) led to reduced branching in the intrahepatic biliary network in zebrafish. Further, we identified a previously unappreciated downstream kinase cascade regulated by Cdk5. Pharmacological manipulations of this downstream kinase cascade produced a crowded branching defect in the intrahepatic biliary network and influenced actin dynamics in biliary epithelial cells. We generated larvae carrying a mutation in cdk5 regulatory subunit 1a (cdk5r1a), an essential activator of Cdk5. cdk5r1a mutant larvae show similar branching defects as those observed in Cdk5 inhibitor-treated larvae. A small-molecule compound that interferes with the downstream kinase cascade rescued the mutant phenotype. These results provide new insights into branching morphogenesis of the intrahepatic biliary network.


[Scope and method of image registration and clinical target volume margin for central-type non-small cell lung cancer in image-guided radiotherapy].
To determine the influence of different registration scopes and methods on kilo-voltage cone beam CT (kVCBCT) image and CT image and to estimate the appropriate clinical target volume (CTV)-to-planned target volume (PTV) margin for central-type non-small cell lung cancer in image-guided radiation therapy (IGRT). Twenty-six patients with central-type non-small cell lung cancer (NSCLC) who received IGRT were enrolled in this study and totally 104 flames of kVCBCT scanning acquired before radiotherapy were analyzed. First, registrations were performed by gray plus manual match and were compared among different registration scopes of tumor and tumor plus vertebra. Then, the results of registration as well as time cost using tumor plus vertebra as registration scope were compared among different registration methods of gray plus manual match and bone plus manual match. At last, 200 registrations using tumor plus vertebra as the registration scope performed by bone plus manual match were recorded and the CTV-to-PTV margin was calculated. There was no significant difference in X, Y and Z translational and rotational movements between the registration scopes of tumor and tumor plus vertebra when gray plus manual match was used as the registration method (P>0.05). The registration results of gray plus manual match and bone plus manual match were equal when tumor plus vertebra was used as the registration scope (P>0.05), but the time cost of bone plus manual match [(1.9±0.3) min] was shorter than that of gray plus manual match [(3.1±0.2) min]. The CTV-to-PTV margins were 5.3, 4.9 and 5.7 mm in X, Y, and Z directions respectively. For central-type NSCLC, tumor and vertebra can be used as registration scope and the bone plus manual match is suggested in IGRT. To avoid errors, we suggest a CTV-to-PTV margin of 6 mm.


33K protein--an inhibitory factor of tubulin polymerization in porcine brain.
A factor (33K protein) that modulates tubulin polymerization in vitro has been purified to homogeneity from porcine brain by ammonium sulfate fractionation and Whatman DE52, Toyo-pearl HW65C and Bio-Gel A 0.5 m column chromatographies. The purified fraction was free of nucleic acids and sugars. The activity of the purified 33K protein is pronase E sensitive but apparently heat- and trypsin-resistant though it undergoes tryptic digestion. The 33K protein inhibits polymerization of brain microtubule proteins in a dose-dependent manner and partially depolymerizes preformed microtubules. It also inhibits polymerization of purified starfish tubulin and microtubule elongation involving fragellar outer doublet microtubules and purified porcine brain tubulin. This suggests that the target of the 33K protein is tubulin rather than microtubule-associated proteins. The 33K protein causes incomplete depolymerization of microtubules and a new steady state is quickly attained which is apparently independent of microtubule mass concentration. Divalent cations such as calcium and magnesium do not modulate the inhibitory activity of the 33K protein.


Considering waning immunity to better explain dengue dynamics.
Life-long serotype-specific immunity following dengue virus infection may not always occur, but the true extent of this effect is unknown. Analysis of more than 20 years of monotypic epidemics in the isolated French Polynesian islands revealed that whilst the risk of symptomatic dengue infection did conform to the classical paradigms of homotypic immunity and increased disease risk in heterotypic secondary infections, incorporation of waning immunity improved the ability of epidemiological models to capture the observed epidemic dynamics. Not only does this show how inclusion of waning immunity into classical models can reveal important facets of the immune response to natural dengue virus infection, it also has significant ramifications for vaccine development and implementation in dengue endemic areas.


Preparation and creativity help EDs 'beat the heat'.
Don't wait for a heat wave or dire weather forecasts to start preparing. It will get hot sometime each year. Set up parallel processing systems to handle the additional influx of heat-injured patients. Train pre-hospital providers to be aware of and report the home circumstances of patients. Pre-stock cooling blankets. If you don't have any, obtain industrial fans from environmental services.


Elucidating the Role of Hydrogen Bonding in the Optical Spectroscopy of the Solvated Green Fluorescent Protein Chromophore: Using Machine Learning to Establish the Importance of High-Level Electronic Structure.
Hydrogen bonding interactions with chromophores in chemical and biological environments play a key role in determining their electronic absorption and relaxation processes, which are manifested in their linear and multidimensional optical spectra. For chromophores in the condensed phase, the large number of atoms needed to simulate the environment has traditionally prohibited the use of high-level excited-state electronic structure methods. By leveraging transfer learning, we show how to construct machine-learned models to accurately predict the high-level excitation energies of a chromophore in solution from only 400 high-level calculations. We show that when the electronic excitations of the green fluorescent protein chromophore in water are treated using EOM-CCSD embedded in a DFT description of the solvent the optical spectrum is correctly captured and that this improvement arises from correctly treating the coupling of the electronic transition to electric fields, which leads to a larger response upon hydrogen bonding between the chromophore and water.


PET of brain amyloid and tau in mild cognitive impairment.
Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer's disease that accumulate in the cortical regions of the brain in persons with mild cognitive impairment who are at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal proteins are potentially useful in developing surrogate markers for drug discovery and diagnostics. We enrolled 83 volunteers with self-reported memory problems who had undergone neurologic and psychiatric evaluation and positron-emission tomography (PET). On the basis of cognitive testing, 25 volunteers were classified as having Alzheimer's disease, 28 as having mild cognitive impairment, and 30 as having no cognitive impairment (healthy controls). PET was performed after injection of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro. All subjects also underwent 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance imaging (MRI). Global values for FDDNP-PET binding (average of the values for the temporal, parietal, posterior cingulate, and frontal regions) were lower in the control group than in the group with mild cognitive impairment (P<0.001), and the values for binding in the group with mild cognitive impairment were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET binding differentiated among the diagnostic groups better than did metabolism on FDG-PET or volume on MRI. FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer's disease and those with no cognitive impairment. This technique is potentially useful as a noninvasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles.


Quinoline, Coumarin and Other Heterocyclic Analogs Based HIV-1 Integrase Inhibitors.
Human Immunodeficiency Virus Type 1 Integrase or HIV-1 integrase (IN) is a 288 amino acid protein that incorporates the retrotranscribed viral DNA into the host chromosomal DNA. Over the past 30 years, large number of derivatives have been evaluated for their inhibitory potential against IN. There is vast literature available which need to be collated to help scientists plan the future drug design. This review discusses the reports of past 25 years on analogs of quinoline, coumarin and other related heterocycles, which exhibit low micromolar inhibitory potency against IN.


Reducing the risk of HIV infection during pregnancy among South African women: a randomized controlled trial.
Mpumalanga Province, South Africa has one of the highest HIV/AIDS diagnosis rates among pregnant women (~29.4%). This study sought to enhance male involvement in pregnancy to increase HIV disclosure, sexual communication, HIV knowledge and reduce unprotected sex. Participants attending Antenatal Clinics (ANC) completed HIV counseling and testing and were enrolled with male partners (n=239 couples, 478 individuals). Twelve ANCs were randomly assigned to provide a prevention of mother-to-child transmission (PMTCT) intervention or the standard of care, health education sessions plus PMTCT. Participants were assessed at baseline and post-intervention (approximately 6-8 weeks post-baseline) on demographics, sexual behavior, HIV-related knowledge, and conflict resolution strategies. Experimental participants increased HIV knowledge, use of negotiation, and decreased intimate partner violence. Additionally, they were more likely to have increased condom use from baseline to post-intervention (OR=5.1, 95% CI=[2.0, 13.3]). Seroconversions in the control condition exceeded experimental (6 vs. 0). HIV serostatus disclosure to partner did not increase over time for men or women within the experimental or control condition. Male involvement in pregnancy may be an important strategy to reduce sexual risk behavior and HIV transmission. Results support the utility of group interventions to enhance communication and HIV knowledge among pregnant couples.


A gas trapping method for high-throughput metabolic experiments.
Research into cellular metabolism has become more high-throughput, with typical cell-culture experiments being performed in multiwell plates (microplates). This format presents a challenge when trying to collect gaseous products, such as carbon dioxide (CO2), which requires a sealed environment and a vessel separate from the biological sample. To address this limitation, we developed a gas trapping protocol using perforated plastic lids in sealed cell-culture multiwell plates. We used this trap design to measure CO2 production from glucose and fatty acid metabolism, as well as hydrogen sulfide production from cysteine-treated cells. Our data clearly show that this gas trap can be applied to liquid and solid gas-collection media and can be used to study gaseous product generation by both adherent cells and cells in suspension. Since our gas traps can be adapted to multiwell plates of various sizes, they present a convenient, cost-effective solution that can accommodate the trend toward high-throughput measurements in metabolic research.


Violence and HIV-related risk among young men who have sex with men.
Limited research has been conducted on threats or violence by family members and sexual partners against young men who have sex with men (MSM). Young MSM, aged 15-22 years, who attended public venues in New York City were enrolled in an anonymous, cross-sectional HIV seroprevalence and risk-behavior study. About two-thirds (68%) of the young MSM reported ever experiencing threats or violence from either family or partners and 25% reported threats or violence by both family and partners. In multivariate analysis, threats or violence by partners was significantly associated with older age, a history of forced sex and a history of running away from home. Recent unprotected anal sex and club drug use were significantly associated with a history of threats or violence by both family and partners. HIV prevention interventions need to include multiple factors that may have an impact on risk, including substance use and abuse, anti-violence and other mental-health issues.


Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton relaxation mechanisms and optimal MR imaging parameters.
To investigate the proton relaxation mechanisms and the optimal MR imaging parameters in superparamagnetic iron oxide (SPIO)-enhanced MR imaging of liver injury. A liver injury model was created in the rat using carbon tetrachloride. The T1 and T2 relaxation effects of SPIO in normal and injured liver were estimated by ex vivo relaxometry. In vivo laser confocal microscopy of the liver was performed to simulate the distribution and clustering of SPIO particles in the hepatic macrophages. SPIO-enhanced MR imaging (1.5T) of normal and diseased rats was performed with variable parameters. The liver specimens were prepared for histopathological examination. Histopathological and laser confocal microscopic findings showed diffuse macrophage distribution but decreased intracellular clustering of SPIO in injured liver. Ex vivo relaxometry showed sustained T1 and T2 relaxation effects of SPIO in liver injury. On MR images obtained with moderate echo time (spin echo [SE] 2000/40 and gradient echo [GRE] 130/9.0/60 degrees), injured liver showed significantly lower decrease in signal-to-noise ratio (SNR) than the normal liver, whereas little difference in SNR was found between the normal and injured liver on heavily T2-(SE 2000/80) and T1-weighted (SE 300/11 and GRE 130/2.0/90 degrees) MR images. Pulse sequences with a moderately long echo time (TE) may be more appropriate than heavily T1- or T2-weighted images for distinguishing normal and injured liver in SPIO-enhanced MR imaging because of the maintained T1 and T2 relaxation effect but decreased T2* relaxation effect of SPIO in injured liver.


[Study on bisphenol A induced primary cultured mesencephalic neuronal cell injury by oxidative stress].
To investigate the effect and mechanism of bisphenol A, a common EDCs, on the primary cultured mesencephalic neuronal cell injury. mesencephalic neuronal cells were obtained from embryonic 14-15 day SD fetuses and were cultured in serum free medium for 4 or 7 days in vitro, 1,10,25,50 and 100 micromol/L bisphenol A were added to the medium and intracellular ROS, SOD, MDA, GSH were measured after 24 or 48hours, respectively. Flow cytometry was used to detect the neuronal cell apoptosis. Tyrosine hydroxylase immunohistochemistry was used to identity and count the ratio of dopaminergic neuronal cell. The intracellular ROS was dose dependently increased by bisphenol A in all treated groups, and it appeared to be a nonselective effect when the concentration of bisphenol A were higher than 50 micromol/L, and concomitantly decreased SOD, GSH and increased MDA. The apoptotic neuronal cells were significantly increased at 501 micromol/L and 100 micromol/L. The ratio of Tyrosine hydroxylase positive neuronal cell was dose dependently decreased with the concentration of bisphenol A. ROS induced by bisphenol A may play a major role in its cytotoxicity on dopaminergic neuronal cell.


[New approaches to obtaining vaccines for preventing serum hepatitis type B].
A comparative study of the antigenic and immunogenic properties of hepatitis B virus surface antigen (HBsAg) and a glycopeptide containing protective antigenic determinant "a" (aAg) isolated from purified HBsAg structures was carried out. In contrast to HBsAg structures, aAg preparations contained no antigens of normal human serum. Anti-aAg antisera unlike immune sera against HBsAg contained no antibody against normal serum proteins. The aAg preparations were at least as immunogenic as HBsAg for laboratory animals. Inoculation of aAg-immunized mice with 125I-HBsAg resulted in no accumulation of the label in the kidneys whereas it was demonstrated in the animals immunized with HBsAg. The prospects of using minimal antigenic structures carrying protective antigenic determinants as split-HBV vaccines are discussed.


A Model for Identifying Optimal Patients for Primary Tumor Resection in Patients With Metastatic Bladder Cancer.
A survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection. Patients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004-2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model. A total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan-Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p < 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection. A practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.


Ligand-dependent transcriptional induction of lethal autophagy: A new perspective for cancer treatment.
Dendrogenin A (DDA) is a mammalian metabolite that displays anticancer and chemopreventive properties in mice. At the cancer cell level, DDA induces differentiation and death. We investigated herein the nature of DDA cytoxicity in cancer cells. We showed that DDA triggers biochemical and cellular features of macroautophagy/autophagy and that autophagy is cytotoxic. DDA induces both the accumulation of pro-lysosomal sterols and stimulates the expression of regulators of autophagy such as NR4A, LC3 and TFEB through binding to the liver X receptor (LXR), a ligand-dependent transcription factor consisting of 2 isoforms, NR1H2 and NR1H3. These effects are not observed with canonical LXR agonists such as the oxysterol 22(R)-hydroxycholesterol or the synthetic molecules T0901317 and GW3965. DDA effects were measured on melanoma and acute myeloid leukemia cells including patient-derived leukemia cells in vitro and in vivo. Importantly the induction of lethal autophagy kills cells independently of their cytogenetic subgroups and does not differentiate bulk cancer cells from cancer cell progenitors. Together these data show that DDA drives LXR to induce the expression of autophagic genes leading to cancer cells death. This opens up new perspectives for cancer treatment.


Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursus maritimus).
Reproductive organs from 55 male and 44 female East Greenland polar bears were examined to investigate the potential negative impact from organohalogen pollutants (OHCs). Multiple regressions normalizing for age showed a significant inverse relationship between OHCs and testis length and baculum length and weight, respectively, and was found in both subadults (dichlorodiphenyl trichloroethanes, dieldrin, chlordanes, hexacyclohexanes, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)) and adults (hexachlorobenzene [HCB]) (all p < 0.05). Baculum bone mineral densities decreased with increasing chlordanes, DDTs, and HCB in subadults and adults, respectively (all p < 0.05). In females, a significant inverse relationship was found between ovary length and sigma PCB (p = 0.03) and sigma CHL (p < 0.01), respectively, and between ovary weight and sigma PBDE (p < 0.01) and uterine horn length and HCB (p = 0.02). The study suggests thatthere is an impact from xenoendocrine pollutants on the size of East Greenland polar bear genitalia. This may pose a riskto this polar bear subpopulation in the future because of reduced sperm and egg quality/quantity and uterus and penis size/robustness.


Viability and function dynamics of circulating versus endometrial polymorphonuclear leukocytes in postpartum dairy cows with subclinical or clinical endometritis.
We aimed to compare the viability of circulating polymorphonuclear leukocyte (cPMN) and endometrial PMN (ePMN) and their function dynamics in postpartum dairy cows with subclinical (SCE) or clinical endometritis (CE). To do so, blood samples from 38 Holstein cows were collected at -7, 9, 21, and 36 d relative to calving, and endometrial cytology samples from 32 Holstein cows were harvested at 9, 21, and 36 d postpartum. Uterine health status was assessed at 36 d postpartum, and cows were classified as healthy (absence of abnormal vaginal discharge and ≤5% ePMN), SCE (absence of abnormal vaginal discharge and >5% ePMN), or CE (mucopurulent or purulent vaginal discharge and >5% ePMN). Viability (viable, apoptotic, and necrotic) and function parameters phagocytosis (PC), oxidative burst, and intracellular proteolytic degradation were evaluated for cPMN via flow cytometry. For ePMN, only viability and PC were evaluated. The association of cPMN and ePMN viability and functional parameters with reproductive tract health classification were fitted in mixed linear regression models, accounting for repeated measures, sampling day, and interactions of reproductive tract status and day. Cows with CE had a lower proportion of cPMN viability (84.5 ± 2.1%; least squares means ± standard error) and a higher proportion of apoptosis (14.4 ± 2.0%) than healthy (92.4 ± 1.3 and 6.7 ± 1.3%, respectively) or SCE (95.3 ± 2.4 and 3.8 ± 2.3%, respectively) at 9 d postpartum. Interestingly, cPMN intracellular proteolytic degradation was lower [6.2 ± 0.1 median fluorescence intensity (MFI)] in SCE compared with healthy (6.7 ± 0.08 MFI) or CE (6.8 ± 0.1 MFI) at d 9 postpartum. No other differences in cPMN function were found among experimental groups. The proportion of necrotic ePMN was higher for healthy (49.6 ± 5.1%) than SCE (27.4 ± 7.3%) and CE (27.7 ± 7.3%) cows at 36 d postpartum. Also, at 36 d postpartum, the proportion of ePMN performing PC was higher in CE (47.0 ± 8.6%) than in healthy (18.4 ± 7.6%) cows, but did not differ from SCE cows (25.9 ± 8.7%). Results of the present study suggest that cPMN viability and function at 9 d postpartum are associated with the development of uterine disease. Furthermore, ePMN at 36 d postpartum are mostly necrotic in healthy cows but viable and functional in cows with CE, probably due to active uterine inflammation. Remarkably, ePMN in cows with SCE at 36 d postpartum are also mostly viable but seem to display a numerically lower proportion of PC compared with ePMN in CE cows.


Metformin beyond diabetes: pleiotropic benefits of metformin in attenuation of atherosclerosis.
Clinical studies show that metformin attenuates all‐cause mortality and myocardial infarction compared with other medications for type 2 diabetes, even at similar glycemic levels. However, there is paucity of data in the euglycemic state on the vasculoprotective effects of metformin. The objectives of this study are to evaluate the effects of metformin on ameliorating atherosclerosis. Using ApoE−/− C57BL/6J mice, we found that metformin attenuates atherosclerosis and vascular senescence in mice fed a high‐fat diet and prevents the upregulation of angiotensin II type 1 receptor by a high‐fat diet in the aortas of mice. Thus, considering the known deleterious effects of angiotensin II mediated by angiotensin II type 1 receptor, the vascular benefits of metformin may be mediated, at least in part, by angiotensin II type 1 receptor downregulation. Moreover, we found that metformin can cause weight loss without hypoglycemia. We also found that metformin increases the antioxidant superoxide dismutase‐1. Pleiotropic effects of metformin ameliorate atherosclerosis and vascular senescence.


Object-based attention and visual area LO.
We investigated the neural basis of so-called "object-based attention" by examining patient D.F., who has visual form agnosia caused by bilateral damage to the lateral occipital (LO) area of the ventral visual stream. We tested D.F.'s object-based attention in two ways. In the first experiment, we used a spatial cueing procedure to compare the costs associated with shifting attention within versus between two separate outline figures. D.F. did not show the normal advantage of within-object over between-object attention shifts. In the second experiment, we used a complementary paradigm in which two separate stimuli, presented either on the same or on different objects, have to be identified as the same or different, We found no evidence for the normal pattern of superior performance for within versus between figure comparisons. In a third experiment, we checked that D.F. showed normal shift costs for invalid as opposed to valid cueing in a standard Posner spatial attention task. In a final experiment, we compared horizontal versus vertical attention shifting in group of healthy controls without the presence of outline rectangles, and found that their pattern of shift costs was indistinguishable from that seen in D.F. when the rectangles were present (Experiment 1). We conclude that whilst D.F. has a normal spatial orienting system this is completely uninfluenced by object structure. We suggest that area LO may mediate form processing precisely at the stage where visual representations normally influence the spread of attention.


A sub-region combination scheme for spatial coding in a high-frequency SSVEP-based BCI.
Objective.In studying the spatial coding mechanism of visual evoked potentials, it is significant to construct a model that shows the relationship between steady-state visual evoked potential (SSVEP) responses to the local and global visual field stimulation. In order to investigate whether SSVEPs produced by sub-region stimulation can predict that produced by joint region stimulation, a sub-region combination scheme for spatial coding in a high-frequency SSVEP-based brain-computer interface (BCI) is developed innovatively.Approach.An annular visual field is divided equally into eight sub-regions. The 60 Hz visual stimuli in different sub-regions and joint regions are presented separately to participants. The SSVEP produced by the sub-region stimulation is superimposed to simulate the SSVEP produced by the joint region stimulation with different spatial combinations. A four-class spatially-coded BCI paradigm is used to evaluate the simulated classification performance, and the performance ranking of all simulated SSVEPs is obtained. Six representative stimulus patterns from two performance levels and three stimulus areas are applied to the online BCI system for each participant.Main results.The experimental result shows that the proposed scheme can implement a spatially-coded visual BCI system and realize satisfactory performance with imperceptible flicker. Offline analysis indicates that the classification accuracy and information transfer rate (ITR) are 89.69 ± 8.75% and 24.35 ± 7.09 bits min-1with 3 s data length under the 3/8 stimulus area. The online BCI system reaches an average classification accuracy of 87.50 ± 9.13% with 3 s data length, resulting in an ITR of 22.48 ± 6.71 bits min-1under the 3/8 stimulus area.Significance.This study proves the feasibility of using the sub-region's response to predict the joint region's response. It has the potential to extend to other frequency bands and lays a foundation for future research on more complex spatial coding methods.


Internal and External Training Workload Quantification in 4 Experienced Paracanoeing Athletes.
Paracanoeing is one of the adapted sports eligible for different motor impairments. The acute:chronic workload ratio (ACWR) is an index between acute and chronic training workload. However, no studies have analyzed this variable in paracanoeing, relating it with training recovery markers. This study aimed to quantify the internal (session rating of perceived exertion) and external (distance traveled and total training time) training workloads in 4 experienced paracanoe athletes over 9 months and 5 canoeing events. Cross-sectional study. Rehabilitation Hospital Network, Paralympic Program. Four experienced paracanoe athletes participated in 36 weeks of training for 5 events. The daily and weekly training workload, monotony, ACWR, distance, and total training time were described for all the training phases. The perceived recovery status scale (PRS) and medicine ball throw (MBT) were used to quantify recovery. The average daily and weekly training workload varied from 213.1 to 239.3 and 767.3 to 1036.8 arbitrary units, respectively. Average ACWR results ranged from 0.96 to 1.10 in the 4 athletes, findings that were outside the safety zone in 38% of the training weeks. All the correlations between MBT and PRS were classified as weak (ρ between .20 and .39, P > .05). ACWR showed a very weak correlation with MBT and moderately and highly significant correlations with PRS in 2 athletes, respectively. The training workloads of 4 paracanoe athletes may serve as a comparison with other periodization models. Pretraining recovery assessments (MBT and PRS) exhibited a low, nonsignificant correlation. However, ACWR correlated significantly with PRS in 2 athletes and might be a suitable tool for daily training adjustments.


Inhibition of centrosomal protein 164 sensitizes rhabdomyosarcoma cells to radiotherapy.
Rhabdomyosarcoma is the second most common malignant tumor of the heart in infants and children and cannot often be resected completely. Chemotherapy and radiotherapy have a critical role in relieving symptoms and prolonging survival; therefore, enhancing the sensitivity of rhabdomyosarcoma to radiotherapy is an important area of investigation in order to improve the prognosis of patients. It has been reported that centrosomal protein 164 (CEP164) has a key role in the DNA damage-activated signaling cascade. CEP164 is often overexpressed in tumors and is associated with poor prognosis in various types of cancer. In the present study, the influence of CEP164 on the radiosensitivity of rhabdomyosarcoma cells was investigated. Results demonstrated that CEP164 is involved in the radiation-induced cellular response. CEP164 is increased upon radiation and influences the cell cycle, cell viability and cell apoptosis. CEP164 depletion enhanced cellular sensitivity to radiation, promoted cell apoptosis, decreased cell viability and induced gap 2/mitosis arrest of the cell cycle. The present study identified the function of CEP164 in radiation resistance in rhabdomyosarcoma, providing a potential therapeutic target for rhabdomyosarcoma treatment by disrupting CEP164.


[Recurrent varices at the groin and popliteal fossa after surgical treatment].
Patients who undergo surgery involving the groin and the popliteal fossa often develop recurrent varices which require careful management. Several surveys using various classification systems have estimated the prevalence of recurrent varices after groin and popliteal surgery. Patients may seek medical care for various reasons: unsightly recurrent varicose veins, vein-related symptoms, appearance of cutaneous or subcutaneous changes, concerns about the health risk related to their veins or limitation of activity. Recurrent varices may also be found at routine follow-up examinations. An analysis of recurrence at this location reveals three main mechanisms: incomplete resection of the saphenofemoral or saphenopopliteal junctions in patients with an initially incompetent terminal valve. The persisting reflux feeds the tributaries connected at the saphenous stump; the second mechanism is related to neovascularisation that reconnects the deep venous system with the superficial network; the neo-veins are valveless. This phenomenon appears to be more frequent when the resection of the saphenous vein ending has been complete; the third mechanism is due to a tactical error; the refluxive pelvic veins that had not been diagnosed feed the varices. Duplex scanning identifies the different possible mechanisms and provides anatomical and hemodynamic data. Interventional treatment methods after varices recurrence are redosurgery, sclerotherapy and pelvic vein embolization when they are at issue. All these methods are described in details. Results provided by these treatments are analysed. Unfortunately no randomized control study enables grade A or B recommendations. Personally we suggest that ultrasound guided foam sclerotherapy should be the first-line treatment except when duplex scanning reveals an intact incompetent saphenous stump at the saphenofemoral junction or/and saphenopopliteal junction with a massive reflux filling the varicose network.


Stress distribution of endodontically treated teeth with titanium alloy post and carbon fiber post with different alveolar bone height: A three-dimensional finite element analysis.
A three-dimensional (3D) finite element analysis (FEA) on the stress distribution of endodontically treated teeth with titanium alloy post and carbon fiber post with different alveolar bone height. The 3D model was fabricated using software to represent an endodontically treated mandibular second premolar with post and restored with a full ceramic crown restoration, which was then analyzed using FEA using FEA ANSYS Workbench V13.0 (ANSYS Inc., Canonsburg, Pennsylvania, U.S.A) software. The FEA showed the maximum stresses of 137.43 Mpa in dentin with alveolar bone height of 4 mm when the titanium post was used, 138.48 Mpa when carbon fiber post was used as compared to 105.91 Mpa in the model with alveolar bone height of 2 mm from the cement enamel junction (CEJ) when the titanium post was used and 107.37 Mpa when the carbon fiber post was used. Stress was observed more in alveolar bone height level of 4 mm from CEJ than 2 mm from CEJ. Stresses in the dentin were almost similar when the carbon fiber post was compared to titanium post. However, stresses in the post and the cement were much higher when titanium post was used as compared to carbon fiber post.


Inhibition of NF-kappaB and Akt pathways by an antibody-avidin fusion protein sensitizes malignant B-cells to cisplatin-induced apoptosis.
Multiple myeloma (MM) is an incurable disease of malignant plasma cells. Recent therapeutic advancements have resulted in improved response rates, however, there is no improvement in overall survival, therefore, new therapeutics are needed. Since the transferrin receptor is upregulated on the surface of MM cells, we previously developed an antibody fusion protein consisting of an IgG3 specific for the human transferrin receptor 1 (TfR1, CD71) genetically fused to avidin at its carboxy-terminus (ch128.1Av). We have previously shown that ch128.1Av exhibits intrinsic cytotoxicity against certain malignant B-cells by disrupting the cycling of the TfR and decreasing TfR cell surface expression resulting in lethal iron starvation. In addition, ch128.1Av can sensitize malignant cells to apoptosis induced by gambogic acid, a herbal drug used in Chinese medicine. In this study, we hypothesized that ch128.1Av may also sensitize drug-resistant malignant B-cells to chemotherapeutic agents by inhibiting key survival pathways. In this study we show that ch128.1Av sensitizes malignant B-cells to apoptosis induced by cisplatin (CDDP). The sensitization by ch128.1Av resulted in the inhibition of the constitutively activated Akt and NF-kappaB survival/antiapoptotic pathways and downstream decreased expression of antiapoptotic gene products such as BclxL and survivin. The direct role of the inhibition of the Akt and NF-kappaB pathways by ch128.1Av in CDDP-mediated cytotoxicity was demonstrated by the use of specific chemical inhibitors and siRNA which mimicked the effects of ch128.1Av. Overall, this study provides evidence of the therapeutic potential of ch128.1Av as a chemo-sensitizing agent in drug-resistant tumor cells.


LiDAR-camera-system-based unsupervised and weakly supervised 3D object detection.
LiDAR camera systems are now becoming an important part of autonomous driving 3D object detection. Due to limitations in time and resources, only a few critical frames of the synchronized camera data and acquired LiDAR points may be annotated. However, there is still a large amount of unannotated data in practical applications. Therefore, we propose a LiDAR-camera-system-based unsupervised and weakly supervised (LCUW) network as a novel 3D object-detection method. When unannotated data are put into the network, we propose an independent learning mode, which is an unsupervised data preprocessing module. Meanwhile, for detection tasks with high accuracy requirements, we propose an Accompany Construction mode, which is a weakly supervised data preprocessing module that requires only a small amount of annotated data. Then, we generate high-quality training data from the remaining unlabeled data. We also propose a full aggregation bridge block in the feature-extraction part, which uses a stepwise fusion and deepening representation strategy to improve the accuracy. Our comparative, ablation, and runtime test experiments show that the proposed method performs well while advancing the application of LiDAR camera systems.


[Pain perioperative in surgery of the hand].
Pain has to be treated during the perioperative period. The recent improvement in pain treatment results from a better understanding of pain mechanisms, strict evaluations and appropriate protocols for pain management. Mainly nociceptive, postoperative pain looks more and more like neuropathic pain when it persists or increases. Therefore, analgesics are no more effective and antihyperalgesiant drugs must use. Preventive treatments have to be considered first as the best pain treatment. Basically, perioperative pain has to be understood as a standard quality management by the medical and surgical team.


Interleukin-6 Inhibitor Suppresses Hyperalgesia Without Improvement in Osteoporosis in a Mouse Pain Model of Osteoporosis.
The aim of this study was to evaluate skeletal pain associated with osteoporosis and examine the inhibitory effect of interleukin-6 (IL-6) on pain in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated by examining pain-related behavior and immunohistochemistry. The effects of IL-6 receptor inhibitor (IL-6i) on these parameters were also assessed. Eight-week-old female ddY mice were ovariectomized and assigned to three groups: OVX mice treated with vehicle (OVX); OVX mice treated with alendronate (OVX-ALN); and OVX mice treated with anti-IL-6 receptor (anti-IL-6R) antibody (OVX-IL6i). Sham-operated mice were treated with vehicle. Immediately after surgery, vehicle, ALN, or anti-IL-6R antibody was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was examined using von Frey filaments. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally with micro-computed tomography. Calcitonin gene-related peptide (CGRP) expression in L3-L5 dorsal root ganglion (DRG) neurons was examined using immunohistochemistry. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs with upregulation of CGRP expression in the DRG neurons innervating the hindlimbs. ALN treatment prevented bone loss, but anti-IL-6R antibody treatment had no effect on bone morphometry compared with that of the OVX group. However, mechanical hyperalgesia and CGRP expression were significantly decreased in the OVX-IL6i and OVX-ALN groups compared with those in the OVX group. Although anti-IL-6R antibody treatment had no effect on ovariectomy-induced bone loss, the treatment prevented ovariectomy-induced mechanical hyperalgesia in the hindlimbs and suppressed CGRP expression in DRG neurons. The results suggest that IL-6 is one of the causes of postmenopausal osteoporotic pain, and anti-IL-6R antibody might preserve bone health and decrease osteoporotic pain.


Important elements of the Americans With Disabilities Act for persons with diabetes.
Having diabetes can have profound implications for individuals in the workplace. Due to the increasing number of people who are diagnosed with this disease and the often complex treatment it requires, this issue continues to pose challenges for not only employees with this illness, but also for their employers. The 1990 Americans with Disabilities Act (ADA) was influential in promoting accommodations for and nondiscrimination against people with diabetes in the workplace. This article discusses 3 of the elements that can make it difficult for persons with diabetes to file a successful claim under the ADA. These important elements include employee disability status, the ability to perform essential job functions, and direct threat concerns.


How I do it: Lymphangiography.
Lymphangiography, despite advances in cross-sectional imaging, remains a useful tool in the diagnosis and therapeutic intervention of lymphatic vessel damage, such as high output chylothorax. This article describes our technique for this procedure.


Effect of staining solutions on color of pre-reacted glass-ionomer containing composites.
This study investigated the color stability of pre-reacted glass-ionomer containing composite restoratives. The materials evaluated included one regular (Beautifil II [BF]), two flowable (Beautifil Flow [F02, F10]) and two recently introduced flowable "plus" (Beautifil Flow Plus [F00, F03]) pre-reacted glass-ionomer containing composite restoratives. Twelve specimens of each material (A3 shade) were fabricated, allowed to set for 24 h at 37°C and randomly divided into 4 groups. After baseline spectrophotometric (Crystaleye, Olympus) color measurements, specimens were immersed in water, cola, red wine and coffee for 7 days. Post-immersion color measurements were taken and color changes (ΔE) were computed accordingly. Statistical analysis was done using ANOVA and post-hoc Scheffe's test (p<0.05). For pre-reacted glass-ionomer containing composites, color changes after immersion in coffee and red wine were significantly greater than in cola and water. Differences in ΔE values between materials were solution dependent. The least color change was generally observed with the flowable "plus" pre-reacted glass-ionomer containing composites.


A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer.
This phase II trial evaluated the efficacy and safety of cetuximab combined with FOLFOX6 (leucovorin [LV] 5-fluorouracil [5-FU]/oxaliplatin) in the first-line treatment of patients with advanced or metastatic colorectal cancer. Patients with locally advanced or metastatic CRC who had received no previous therapy for advanced disease were treated with cetuximab at a loading dose of 400 mg/m2 followed by 250 mg/m2 weekly and a FOLFOX6 regimen every 2 weeks consisting of oxaliplatin 85 mg/m2, LV 400 mg/m2, and 5-FU bolus 400 mg/m2 followed by 5-FU continuous infusion 2400 mg/m2 over 46 hours. A total of 82 eligible patients were enrolled; epidermal growth factor receptor expression was positive in 67 patients. The overall response rate was 44.8%. In addition, 30 patients (44.8%) in the evaluable population experienced stable disease. Median time to progression or death was 9.3 months (95% CI, 7.0-11.3 months), and median survival was 21.7 months (95% CI, 17.5-27.8 months). Patients who experienced skin toxicity had a statistically significant and longer median survival time than those patients with no skin toxicity (P = .0001). The most commonly observed toxicities were neutropenia (65%), fatigue (56.3%), diarrhea (53.8%), nausea (50%), acneiform rash (41.3%), and stomatitis (35%). Our results demonstrate that cetuximab can be safely combined with FOLFOX6 for the first-line treatment of patients with metastatic CRC (mCRC). The efficacy parameters are similar to other first-line regimens in mCRC. Because of the emergence of KRAS as a predictive marker, this regimen has promise in KRAS wild-type mCRC.


IMP dehydrogenase-linked retinitis pigmentosa.
Many retinal diseases are caused by mutations in photoreceptor-specific proteins. However, retinal disease can also result from mutations in widely expressed proteins. One such protein is inosine monophosphate dehydrogenase type 1 (IMPDH1), which catalyzes a key step in guanine nucleotide biosynthesis and also binds single-stranded nucleic acids. The pathogenic IMPDH1 mutations are in or near the CBS domains and do not affect enzymatic activity. However, these mutations do decrease the affinity and specificity of single-stranded nucleic acid binding. These observations suggest that IMPDH1 has a previously unappreciated role in RNA metabolism that is crucial for photoreceptor function.


[The effect of miramistin on the phagocytic activity of urethral neutrophil granulocytes].
Secondary immunodeficiency, one of whose manifestations is depressed phagocytic activity of urethral neutrophilic granulocytes, develops in patients with chronic urethroprostatitis. Miramistin exerts a dose-dependent stimulating effect on the urethral neutrophilic granulocytes; the maximum stimulating effect is observed when phagocytes are treated with 0.001% solution of the drug.


T cell responses to respiratory syncytial virus fusion and attachment proteins in human peripheral blood mononuclear cells.
The cellular immune response to respiratory syncytial virus (RSV) is considered important in both protection and immunopathogenesis. We have studied the HLA class I- and class II-restricted T cell responses to RSV fusion (F) and attachment (G) proteins in peripheral blood mononuclear cells (PBMCs) obtained from healthy young adults. PBMCs were stimulated with autologous cells infected with recombinant modified vaccinia virus Ankara (rMVA) expressing RSV F (rMVA-F) or G (rMVA-G). In rMVA-F-stimulated bulk cultures F-specific CD4(+) and CD8(+) T cell responses were demonstrated, whereas in rMVA-G-stimulated cultures only G-specific CD4(+) T cell responses were detected. Using a set of overlapping peptides spanning the F protein, a number of the F-specific T cell responses could be mapped to different antigenic regions, whereas for the G protein only CD4(+) T cell responses recognizing the central conserved domain could be detected. These results suggest that the RSV glycoprotein-specific T cell response is directed to a number of different epitopes. Further studies must be performed to confirm the apparent inability of the RSV G protein to induce CD8(+) T cell responses. The rMVA-based in vitro stimulation protocol will be useful to define protein-specific T cell responses in different viral systems.


PADI2 Polymorphisms Are Significantly Associated With Rheumatoid Arthritis, Autoantibodies Serologic Status and Joint Damage in Women from Southern Mexico.
The enzymes of the family peptidylarginine deiminases (PADs) have an important role in the pathogenesis of rheumatoid arthritis (RA) due to their association with the anti-citrullinated protein antibodies (ACPA) production. To evaluate the association between single-nucleotide polymorphisms (SNPs) in the PADI2 gene and RA susceptibility, related clinical parameters, and the serologic status of autoantibodies in a women population with RA from southern Mexico, a case-control study was conducted (case n=229; control n=333). Sociodemographic characteristics were evaluated, along with clinical parameters, inflammation markers, the levels of ACPAs as anti-cyclic citrullinated peptides (anti-CCPs), anti-modified citrullinated vimentin (anti-MCV), and rheumatoid factor (RF). Genomic DNA was extracted from peripheral blood, and three SNPs of the PADI2 gene (rs1005753, rs2057094, and rs2235926) were performed by qPCR using TaqMan probes. The data analysis reveals that the carriers of the T allele for rs2057094 and rs2235926 presented an earlier onset of the disease (β= -3.26; p = 0.03 and β = -4.13; p = 0.015, respectively) while the carriers of the T allele for rs1005753 presented higher levels of anti-CCPs (β= 68.3; p = 0.015). Additionally, the T allele of rs2235926 was associated with a positive RF (OR = 2.90; p = 0.04), anti-MCV (OR = 2.92; p = 0.05), and with the serologic status anti-CCP+/anti-MCV+ (OR = 3.02; p = 0.03), and anti-CCP+/anti-MCV+/RF+ (OR = 3.79; p = 0.004). The haplotypes GTT (OR =1.52; p = 0.027) and TTT (OR = 1.32; p = 0.025) were associated with the presence of RA. In addition, in this study the haplotype TTT is linked to the presence of radiographic joint damage defined by a Sharp-van der Heijde score (SHS) ≥2 (OR = 1.97; p = 0.0021) and SHS ≥3 (OR = 1.94; p = 0.011). The haplotype TTT of SNPs rs1005753, rs2057094, and rs2235926 of the PADI2 gene confers genetic susceptibility to RA and radiographic joint damage in women from southern Mexico. The evidence reveals that SNPs of the PADI2 gene favors the presence of a positive serologic status in multiple autoantibodies and the clinical manifestations of RA at an early onset age.


New Mn12 clusters with tunable oxidation states via the use of N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine.
Room-temperature reactions of N,N,N',N'-tetrakis(2-hydroxyethyl)ethylenediamine with manganese(II) salts yield a novel family of Mn(12) clusters incorporating the same Mn(12)O(4) core and tunable oxidation states of Mn(III)(x)Mn(II)(12-x) (x = 8, 10, and 12). Magnetic susceptibility data indicate that the spin of the ground state increases as the number of Mn(III) ions is increased, leading to increases in the magnitude of the out-of-phase ac susceptibility signal as the number of Mn(III) ions is increased.


Parental cannabis abuse and accidental intoxications in children: prevention by detecting neglectful situations and at-risk families.
Cannabis intoxication in toddlers is rare and mostly accidental. Our objectives were to focus on the characteristics and management of children under the age of 6 years who were admitted to our emergency department with cannabis poisoning reported as accidental by parents, and to point out the need to consider accidental cannabis ingestions as an indicator of neglect. The medical records of children hospitalized for cannabis poisoning in a pediatric emergency department from January 2007 to November 2012 were retrospectively evaluated. Data collected included age, sex, drug ingested, source of drug, intentional versus accidental ingestion, pediatric intensive care unit or hospital admission, treatment and length of hospital stay, toxicology results, and rate of child protectives services referral. Twelve toddlers (4 boys and 8 girls; mean age, 16.6 months) were included. All had ingested cannabis. Their parents reported the ingestion. Seven children experienced drowsiness or hypotonia. Three children were given activated charcoal. Blood screening for cannabinoids, performed in 2 cases, was negative in both, and urine samples were positive in 7 children (70%). All children had favorable outcomes after being hospitalized from 2 to 48 hours. Nine children were referred to social services for further assessment before discharge. Cannabis intoxication in children should be reported to child protection services with the aim of prevention, to detect situations of neglect and at-risk families. Legal action against the parents may be considered. Accidental intoxication and caring parents should be no exception to this rule.


Treatment of infrainguinal arterial thromboembolic acute occlusions with the Aspirex® mechanical thrombectomy device.
In this study, we investigated the safety and effectiveness of the Aspirex® mechanical thrombectomy system for the treatment of acute infrainguinal arterial thromboembolic occlusions. We retrospectively identified consecutive patients at our clinic with infrainguinal thromboembolic acute occlusions treated with the Aspirex® mechanical thrombectomy device. Primary end points included technical success, defined as the complete revascularization of the acutely occluded vessel, and clinical success, defined as the absence of amputation within 60 d. Secondary end points included 1-year embolized vessel primary patency. Twenty-four patients with infrainguinal arterial acute thromboembolic occlusions were treated with the mechanical thrombectomy system (five infrapopliteal, 12 femoropopliteal and seven popliteal). Technical success occurred in 18 patients (75%), and clinical success occurred in 24 (100%). The 1-year embolized vessel primary patency rate was 75% (n = 18). The 1-year limb salvage rate was 95.8% (n = 23). The use of the Aspirex® mechanical thrombectomy is effective for the management of acute thromboembolic occlusions of infrainguinal arteries. Caution is needed when using it in smaller vessels, particularly distally below the knee.


Aortic dissection and bicuspid aortic valve: an autopsy study.
Medico-legal post-mortems referred to the Department of Pathology, for the histopathological examination, revealed six cases of acute aortic dissection--two in isolation, three in combination with congenital bicuspid aortic valve; and one isolated case of congenital bicuspid aortic valve. One case of isolated aortic dissection was associated with Marfan's syndrome; and one case of aortic dissection with bicuspid aortic valve was associated with polycystic kidneys. History of hypertension could be elicited in two cases. Cystic medial degeneration of aorta was seen in three cases; one of which was associated with Marfan's syndrome. All five cases of aortic dissection belonged to type II of DeBakey classification.


Formulation and Processing Strategies to Reduce Acrylamide in Thermally Processed Cereal-Based Foods.
Acrylamide, a thermal process contaminant, is generated in carbohydrate-rich foods processed at high temperatures (above 120 °C). Since acrylamide indicates a human health concern, the acrylamide contents of various foods and the dietary exposure of the population to acrylamide are very well investigated. Commonly consumed foods in the daily diet of individuals such as bakery products, potato products and coffee are major dietary sources of acrylamide. In recent years, dietary exposure levels of the population and mitigation measures for reducing acrylamide in different food products have gained importance to decrease the public's exposure to acrylamide. Since the complete elimination of acrylamide in foods is not possible, various mitigation measures to reduce acrylamide to levels as low as reasonably achievable have been developed and applied in the food industry. Mitigation strategies should be applied according to the different product categories during agricultural production, formulation, processing and final consumer preparation stages. The aim of this review is to evaluate formulation and processing strategies to reduce acrylamide in various cereal-based food products and to discuss the applicability of mitigation measures in the food industry by taking into consideration the organoleptic properties, nutritional value, cost and regulations in the light of current knowledge.


Comparison of the effects of spinal anesthesia, paracervical block and general anesthesia on pain, nausea and vomiting, and analgesic requirements in diagnostic hysteroscopy: A non-randomized clinical trial.
The aim of this study was to compare the effect of spinal anesthesia (SPA), paracervical block (PB), and general anesthesia (GA), on pain, the frequency of nausea and vomiting and analgesic requirements in diagnostic hysteroscopy. This single-center, non-randomized, parallel-group, clinical trial was conducted on 66 diagnostic hysteroscopy candidates who were selected by convenience sampling at Fatemieh Hospital, in Hamadan, Iran, in 2021. The mean pain score during recovery and the need for analgesic injections was found to be significantly higher in the GA group compared to that in the SPA group (pain: 3.77 ± 2.25 vs. 0.10 ± 0.30, P < 0.001), (analgesic: 50 vs. 0%, P < 0.001) and PB group (pain: 3.77 ± 2.25 vs. 0.90 ± 1.37, P < 0.001), (analgesic 50 vs. 10%, P < 0.001), respectively. However, no statistically significant difference was observed between the mean pain score between SPA and PB groups (0.10 ± 0.30 vs. 0.90 ± 1.3, P = 0.661). In addition, there were no significant differences between groups on nausea/vomiting after operation (P = 0.382). In adjusted regression analysis (adjusting for age, weight, gravid, abortion, and cause of hysteroscopy), the odds ratio (OR) of pain score during recovery was increased in PB (OR: 4.471, 95% CI: 1.527-6.156, P = 0.018) and GA (OR: 8.406, 95% CI: 2.421-9.195, P = 0.001) groups compared with the SPA group. However, in adjusting based on times of surgery duration, anesthesia duration, recovery and return of motor function, the ORs of pain score between groups was not statistically significant. Despite reduced pain during recovery in patients receiving SPA, duration of anesthesia, recovery period, and return of motor function were significantly prolonged compared to those receiving PB or GA. It seems that PB with less recovery time and faster return of motor function than SPA and also mild pain during recovery compared to GA can be a good option for hysteroscopy. http://www.irct.ir, identifier IRCT20120915010841N26.


miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway.
This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.


Polysciosides J and K, two new oleanane-type triterpenoid saponins from the leaves of Polyscias fruticosa (L.) harms. cultivating in An Giang Province, Viet Nam.
For the first time, the phytochemical constituents of the leaves of Polyscias fruticosa (L.) Harms. cultivating in An Giang Province, Viet Nam were investigated and led to purify two new oleanane-type triterpenoid saponins, named polyscioside J (1) and polyscioside K (2) together with two known saponins, ladyginoside A (3) and chikusetsusaponin IVa (4) using variously chromatographic methods. Saponin (4) was reported for the first time from this species. Their structures were verified by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with previous literatures.


Assessment of CSF dynamics and venous flow in the superior sagittal sinus by MRI in idiopathic intracranial hypertension: a preliminary study.
A velocity-sensitive magnetic resonance imaging (MRI) phase-mapping method was used for non-invasive study of cerebrospinal fluid (CSF) flow in the cerebral aqueduct, for indirect calculation of supratentorial CSF production, and for measurement of blood flow in the superior sagittal sinus (SSS). We examined 12 patients with idiopathic intracranial hypertension (IIH; pseudotumour cerebri), and 10 healthy volunteers. The peak caudal and rostral CSF flow in the aqueduct during the cardiac cycle did not differ significantly between the patients and the volunteers. A significant correlation was found between the CSF volume flow amplitude and the resistance to cerebrospinal fluid outflow in the patients (p < 0.05). The calculated mean supratentorial CSF production rate was 0.79 ml/min in the patients and 0.70 ml/min in the controls, but this difference was not statistically significant. However, the MRI measurements suggested CSF hypersecretion in three patients, whereas increased transependymal passage of CSF could have been the cause of negative calculated CSF production rates in two others. A tendency towards lower mean blood flow in the SSS (mean 345 ml/min) in the patients than in the controls (mean 457 ml/min) was found, and in two patients showed very low values. We showed that MRI phase-mapping may be used to study the relative importance of the pathophysiological factors thought to play a role in the development of IIH.


Hydrolysis of hydrophobic poly(2-oxazoline)s and their subsequent modification via aza-Michael addition.
Partially hydrolysed poly(2-oxazoline)s possess unique properties. However, much of the focus in this area has been on water soluble poly(2-oxazoline)s. Where hydrophobic poly(2-oxazoline)s have been used, this is often for selective hydrolysis. However, hydrolysis of very hydrophobic polymers could lead to interesting solution behaviour. Herein, we describe universal conditions for the hydrolysis of poly(2-alkyl-2-oxazoline)s suitable for both hydrophobic and hydrophilic 2-oxazolines. We show that the system utilised gives comparable rates to that of water alone for poly(2-ethyl-2-oxazoline). In addition, poly(2-fatty acid-2-oxazoline) was hydrolysed using the developed system and was found to proceed in a controlled manner allowing the targeting of specific degrees of hydrolysis, albeit much slower than for poly(2-ethyl-2-oxazoline). Finally, we demonstrate the partial functionalisation of poly(2-oxazoline)-poly(ethylene imine) co-polymers via aza-Michael addition.


Non-Hodgkin lymphoma in children: a 20-year population-based epidemiologic study in western Sweden.
The aim of this study was to investigate incidence, clinicopathologic features, prognostic risk factors, and long-term survival in non-Hodgkin lymphoma (NHL) in a 20-year population-based study of children using Swedish health care organizations and their central registry for childhood malignancies. The hospital registry, the Cause of Death Registry, and the two established Swedish registries for malignancy (the Swedish Cancer Registry and the National Registry for Solid Tumours in Childhood) were searched for children in western Sweden with NHL diagnosed from 1975 to 1994. The clinical files of all children with NHL were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. All sections from paraffin-embedded blocks of tumors with a diagnosis of malignant lymphoma were collected and reexamined histopathologically and immunohistochemically. To guarantee that no patients with NHL were misdiagnosed, a reexamination of other childhood malignancies collected from these registries was also performed. Median follow-up duration of surviving patients is 10 years. The annual incidence of NHL in children younger than 15 years of age was 9/million children, representing 6% of all childhood malignancies during the investigation time. The male-female ratio was 4.1:1.0. Immunologic marker studies were available for 64 of the 77 NHLs: 41 patients had B-cell, 17 had T-cell, and 6 had Ki-1-positive anaplastic large cell lymphoma (ALCL). Two patients with Ki-1-positive ALCL were originally thought to have malignant histiocytosis and Langerhans cell histiocytosis (LCH), respectively. Treatment was the most significant prognostic factor; event-free survival (EFS) was 19% in the preprotocol era (1975 to 1979) and 74% from 1980 to 1994. Other than treatment, stage was the most significant prognostic factor; EFS was 86% for patients (1980 to 1994) with stage I or II disease and 64% for patients with stage III or IV disease, with a dismal prognosis for children with initial involvement of the bone marrow or central nervous system (EFS was 38% and 20%, respectively). Bulky disease and performance state at diagnosis were independent prognostic factors. The patterns of relapse, including early recurrence of the B-cell lymphomas, are in accordance with previous experience. The incidence of NHL was found to be somewhat higher than reported in our previous Nordic study. The higher incidence found in this study might be the result of the thorough data collection (based on hospital registry and cross-checked with all registries for malignant diseases in Sweden) or because reexamination of the tissue material was performed. A more pronounced male predominance than found in previous investigations was observed. The immunophenotypic distribution and the stage distribution is in accordance with earlier investigations. Treatment was the most important factor affecting outcome. A dramatic improvement of survival was seen with the introduction of intensive therapy; treatment success can be expected in 86% of children with localized disease and 64% of children with extensive disease. The absence of improvement in survival despite further treatment stratification with the introduction of the BFM protocol for B-cell-NHL is surprising. LSA2L2-like protocols seem to be as effective. Future studies on treatment of NHL must also concentrate on reducing the intensity of therapy in patients with lower risk disease to minimize late toxic effects.


Usefulness and feasibility of comprehensive and less comprehensive vocational rehabilitation for patients with chronic musculoskeletal pain: perspectives from patients, professionals, and managers.
To explore the usefulness and feasibility of a comprehensive vocational rehabilitation (C-VR) program and less comprehensive (LC-VR) program for workers on sick leave due to chronic musculoskeletal pain, from the perspective of patients, professionals, and managers. Semi-structured interviews were held with patients, professionals, and managers. Using topic lists, participants were questioned about barriers to and facilitators of the usefulness and feasibility of C-VR and LC-VR. Thirty interviews were conducted with thirteen patients (n = 6 C-VR, n = 7 LC-VR), eight professionals, and nine managers. All interviews were transcribed verbatim. Data were analyzed by systematic text condensation using inductive thematic analysis. Three themes emerged for usefulness ("patient factors," "content," "dosage") and six themes emerged for feasibility ("satisfaction," "intention to continue use," "perceived appropriateness," "positive/negative effects on target participants," "factors affecting implementation ease or difficulty," "adaptations"). The patients reported that both programs were feasible and generally useful. The professionals preferred working with the C-VR, although they disliked the fixed and uniform character of the program. They also mentioned that this program is too extensive for some patients, and that the latter would probably benefit from the LC-VR program. Despite their positive intentions, the managers stated that due to the Dutch healthcare system, implementation of the LC-VR program would be financially unfeasible. The main conclusion of this study is that it is not useful to have one VR program for all patients with CMP and reduced work participation, and that flexible and tailored-based VR are warranted.Implications for rehabilitationBoth comprehensive and less comprehensive vocational rehabilitation are deemed useful for patients with chronic musculoskeletal pain and reduced work participation. Particular patient factors, for instance information uptake, discipline, willingness to change, duration of complaints, movement anxiety, obstructing thoughts, and willingness to return to work might guide the right program for the right patient.Both comprehensive and less comprehensive vocational rehabilitation are deemed feasible in practice. However, factors such as center logistic (schemes, rooms, professionals available) and country-specific healthcare insurance and sickness compensation systems should foster the implementation of less comprehensive programs.


Molecular dynamics simulations of gas separations using faujasite-type zeolite membranes.
Gas separations with faujasite zeolite membranes have been examined using the method of molecular dynamics. Two binary mixtures are investigated, oxygen/nitrogen and nitrogen/carbon dioxide. These mixtures have been found experimentally to exhibit contrasting behavior. In O(2)/N(2) mixtures the ideal selectivity (pure systems) is higher than the mixture selectivity, while in N(2)/CO(2) the mixture selectivity is higher than the ideal selectivity. One of the key goals of this work was to seek a fundamental molecular level understanding of such divergent behavior. Our simulation results (using previously developed intermolecular models for both the gases and zeolites investigated) were found to replicate this experimental behavior. By examining the loading of the membranes and the diffusion rates inside the zeolites, we have been able to explain such contrasting behavior of O(2)/N(2) and N(2)/CO(2) mixtures. In the case of O(2)/N(2) mixtures, the adsorption and loading of both O(2) and N(2) in the membrane are quite competitive, and thus the drop in the selectivity in the mixture is primarily the result of oxygen slowing the diffusion of nitrogen and nitrogen somewhat increasing the diffusion of oxygen when they pass through the zeolite pores. In N(2)/CO(2) systems, CO(2) is rather selectively adsorbed and loaded in the zeolite, leaving very little room for N(2) adsorption. Thus although N(2) continues to have a higher diffusion rate than CO(2) even in the mixture, there are so few N(2) molecules in the zeolite in mixtures that the selectivity of the mixture increases significantly compared to the ideal (pure system) values. We have also compared simulation results with hydrodynamic theories that classify the permeance of membranes to be either due to surface diffusion, viscous flow, or Knudsen diffusion. Our results show surface diffusion to be the dominant mode, except in the case of N(2)/CO(2) binary mixtures where Knudsen diffusion also makes a contribution to N(2) transport.


Arteriovenous fistula outcomes in the elderly.
Over several decades, there has been an increase in the number of elderly patients requiring hemodialysis. These older patients typically have an increased incidence of comorbidities including diabetes, hypertension, and peripheral vascular disease. We undertook a systematic review of the current literature to assess outcomes of arteriovenous fistula (AVF) formation in the elderly and to compare the results of radiocephalic AVFs vs brachiocephalic AVFs in older patients. A literature search was performed using MEDLINE, Embase, PubMed, and the Cochrane Library. All retrieved articles published before December 31, 2014 (and in English) primarily describing the creation of hemodialysis vascular access for elderly patients were considered for inclusion. We report pooled AVF patency rates and a comparison of radiocephalic vs brachiocephalic AVF patency rates using odds ratios (ORs). Of 199 relevant articles reviewed, 15 were deemed eligible for the review. The pooled 12-month primary and secondary AVF patency rates were 53.6% (95% confidence interval [CI], 47.3-59.9) and 71.6% (95% CI, 59.2-82.7), respectively. Comparison of radiocephalic vs brachiocephalic AVF patency rates demonstrated that radiocephalic AVFs have inferior primary (OR, 0.72; 95% CI, 0.55-0.93; P = .01) and secondary (OR, 0.76; 95% CI, 0.58-1.00; P = .05) patency rates. This meta-analysis confirms that adequate 12-month primary and secondary AVF patency rates can be achieved in elderly patients. Brachiocephalic AVFs have both superior primary and secondary patency rates at 12 months compared with radiocephalic AVFs. These important data can inform clinicians' and patients' decision-making about suitability of attempting AVF formation in older persons.


A Human Support Robot for the Cleaning and Maintenance of Door Handles Using a Deep-Learning Framework.
The role of mobile robots for cleaning and sanitation purposes is increasing worldwide. Disinfection and hygiene are two integral parts of any safe indoor environment, and these factors become more critical in COVID-19-like pandemic situations. Door handles are highly sensitive contact points that are prone to be contamination. Automation of the door-handle cleaning task is not only important for ensuring safety, but also to improve efficiency. This work proposes an AI-enabled framework for automating cleaning tasks through a Human Support Robot (HSR). The overall cleaning process involves mobile base motion, door-handle detection, and control of the HSR manipulator for the completion of the cleaning tasks. The detection part exploits a deep-learning technique to classify the image space, and provides a set of coordinates for the robot. The cooperative control between the spraying and wiping is developed in the Robotic Operating System. The control module uses the information obtained from the detection module to generate a task/operational space for the robot, along with evaluating the desired position to actuate the manipulators. The complete strategy is validated through numerical simulations, and experiments on a Toyota HSR platform.


Functional proteomic and structural insights into molecular recognition in the nitrilase family enzymes.
Nitrilases are a large and diverse family of nonpeptidic C-N hydrolases. The mammalian genome encodes eight nitrilase enzymes, several of which remain poorly characterized. Prominent among these are nitrilase-1 (Nit1) and nitrilase-2 (Nit2), which, despite having been shown to exert effects on cell growth and possibly serving as tumor suppressor genes, are without known substrates or selective inhibitors. In previous studies, we identified several nitrilases, including Nit1 and Nit2, as targets for dipeptide-chloroacetamide activity-based proteomics probes. Here, we have used these probes, in combination with high-resolution crystallography and molecular modeling, to systematically map the active site of Nit2 and identify residues involved in molecular recognition. We report the 1.4 A crystal structure of mouse Nit2 and use this structure to identify residues that discriminate probe labeling between the Nit1 and Nit2 enzymes. Interestingly, some of these residues are conserved across all vertebrate Nit2 enzymes and, conversely, not found in any vertebrate Nit1 enzymes, suggesting that they are key discriminators of molecular recognition between these otherwise highly homologous enzymes. Our findings thus point to a limited set of active site residues that establish distinct patterns of molecular recognition among nitrilases and provide chemical probes to selectively perturb the function of these enzymes in biological systems.


[Mechanism of epimedium flavonoids in regulating immuno-senescence via nuclear factor-kappa B related signal transduction pathway].
To explore the mechanism of epimedium flavonoids (EF) in regulating immunosenescence via nuclear factor-kappa B (NF-kappaB) related signal transduction pathway. (1) The apoptosis index (AI) of splenic lymphocyte in aged rats was monitored by flow cytometry, that of young rats was taken as control. (2) The differential expression profile of NF-kappaB related signals in aged rats allocated in the control group (aged rats, group A), the EF treated group (group B), the PDTC (a NF-kappaB inhibitor) treated group (group C) and the PDTC plus EF treated group (group D), was determined and the main significant molecules in them were analyzed with gene microarray of 96 genes related to NF-kappaB signal pathway. Excessive apoptosis of T lymphocyte cell was seen in aged rats, and it was significantly suppressed in group B and D. In group B, 73 genes were up-regulated to different extent, including 10 of the NF-kappaB/Rel/IB gene family, transduction signal molecule member of NIK/IKK/I B/Rel/NF-kappaB, NF-kappaB regulatory target genes, trans-membrane receptors, transcription factors, and receptor protein, etc. But the up-regulation on NF-kappaB gene family could not be seen in group C and that on others were also alleviated, while in the group D, the NF-kappaB gene family and its related transduction pathway were still activated to some extent. The NF-kappaB gene family showed a markedly common feature after EF intervention, either used alone or in combination with PDTC, i.e. the significant upregulated NF-kappaB1, NF-kappaB2, Rel B and I Bepsilon, and activated NIK/IKK/I B/Rel/NF-kappaB pathway. EF can suppress the excessive apoptosis of splenic lymphocyte in aged rats and activate Rel/NF-kappaB/ I B/IKK and their signal transduction pathway to up-regulate NF-kappaB through adjusting I Bepsilon and I Balpha, which may be the essential mechanism of EF in rebuilding the immune homeostasis of T lymphocyte apoptosis and retarding immunosenescence.


Stress hormone is implicated in satellite-caller associations and sexual selection in the Great Plains toad.
The effects of androgens on male-typical traits suggest that variation among males in circulating levels can play a major role in sexual selection. We examined whether variation in vocal attractiveness is attributable to differences in androgen levels among Great Plains toads (Bufo cognatus). We found that noncalling "satellite" males practicing an alternative mating tactic were more likely to associate with males producing long calls. However, callers with satellites did not have higher androgen levels than callers without satellites. Rather, callers with satellites had significantly lower corticosterone (CORT) levels than callers without satellites. A CORT manipulation experiment suggested that differences in calls for males with and without satellites were related to differences in CORT levels. Furthermore, there was a negative correlation between CORT level and call duration within most nights of chorus activity. However, the correlation was weak for the pooled data (across all nights), suggesting that local environmental and/or social factors also affect call duration. Last, we show that females preferred broadcast calls of longer duration, characteristic of males with satellites and low CORT. These results imply that satellites optimize their reproductive success by associating with males producing long calls. However, this association should negatively affect the fitness of attractive callers.


Assignment of the true and processed genes for human glycine decarboxylase to 9p23-24 and 4q12.
Southern analysis using a human glycine decarboxylase cDNA probe and genomic DNA preparations from Chinese hamster-human hybridoma cell lines demonstrated that on the segregated human chromosomes, 4 and 9, there are glycine decarboxylase cDNA-related sequences. The finding is confirmatory of the fact that fragments of both the true and processed genes for this protein have been cloned. Since one of four HindIII fragments revealed in the present Southern analysis matched requirements for the property expected from the restriction map reported for the processed gene, this was located on chromosome 4. The three remaining signals were consequently ascribed to fragments from the true gene on chromosome 9. Fluorescence in situ hybridization using the genomic clones assigned the true and processed genes to 9p23-24 and 4q12, respectively.


[Viral hemorrhagic fever].
Viral haemorrhagic fevers, such as Lassa fever and yellow fever, cause tens of thousands of deaths annually outside the Netherlands. The viruses are mostly transmitted by mosquitoes, ticks or via excreta of rodents. Important to travellers are yellow fever, dengue and Lassa and Ebola fever. For yellow fever there is an efficacious vaccine. Dengue is frequently observed in travellers; prevention consists in avoiding mosquito bites, the treatment is symptomatic. Lassa and Ebola fever are extremely rare among travellers; a management protocol can be obtained from the Netherlands Ministry of Health, Welfare and Sports. Diagnostics of a patient from the tropics with fever and haemorrhagic diathesis should be aimed at treatable disorders such as malaria, typhoid fever, rickettsiosis or bacterial sepsis, because the probability of such a disease is much higher than that of Lassa or Ebola fever.


Fulminant Respiratory Failure Caused by Anti-asparaginyl tRNA Synthetase (Anti-KS) Antibody Syndrome-related Interstitial Lung Disease.
Anti-asparaginyl transfer RNA (tRNA) synthetase (KS) antibodies, detected in <5% patients with anti-aminoacyl-tRNA synthetase antibody syndrome, are strongly associated with interstitial pneumonia but not myositis and skin symptoms. A recent report suggested that most patients with interstitial pneumonia and anti-KS antibody (KS-ILD) may present with chronic disease. We herein report a rare case of severe acute respiratory failure in a KS-ILD patient requiring extracorporeal membrane oxygenation (ECMO). ECMO is useful for facilitating not only lung rest until recovery but also the definitive diagnosis and treatment of ILD. KS-ILD can develop acutely with fulminant respiratory failure, as observed in this case.


Saikosaponin D Inhibited IL-1β Induced ATDC 5 Chondrocytes Apoptosis In Vitro and Delayed Articular Cartilage Degeneration in OA Model Mice In Vivo.
Osteoarthritis (OA) is the most common joint disease in the elderly, characterized by cartilage degradation and proliferation of subchondral bone. The pathogenesis of OA involves a variety of inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. From the molecular mechanism, the nuclear factor-erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway and the expression of ROS regulated the production of the above inflammatory mediators. Saikosaponin D (SSD), which is an active ingredient isolated from Bupleurum, has various biological functions. In this study, IL-1β was used as a pro-inflammatory factor to create an in vitro OA model. According to the results of high-density culture, qPCR, ROS measurement, Western blot, and immunofluorescence, SSD activated the Nrf2/HO-1/ROS axis, inhibited the production of inflammatory mediators, and protected against ECM destruction. The DMM mouse model was used as a model of OA in mice. From the results of safranin O/fast green staining, hematoxylin-eosin staining, tartrate-resistant acid phosphatase (TRAP) staining, and OARSI scores, SSD protected against the mice knee articular cartilage degeneration and reduced the number of osteoclasts in the subchondral bone. Experimental results found that SSD suppressed IL-1β-induced differentiated ATDC 5 chondrocytes apoptosis via the Nrf2/HO-1/ROS axis in vitro. SSD delayed the progression of OA in DMMs model mice in vivo. Therefore, SSD has the potential to become a drug for clinical treatment of OA.


[Thinking of therapeutic mechanism of small knife needle in treating closed myofascitis].
The authors investigated and discussed therapeutic mechanism of small knife needle in treating closed myofascitis on the basis of pathomechanism of modern medicine and acupuncture theory of TCM among numbers of clinical cases and experimental data. Therapeutic mechanism lies in 6 aspects: (1) Relieve the energy crisis of tenderness point on muscular fasciae; (2) Affect nervous system and reduce induction of harmful stimulating signal; (3) Inhibit aseptic inflammatory reaction on muscular fasciae; (4) Regulate dynamic equilibrium of soft tissue by cutting scar and releasing the conglutination; (5) Increase patients' regional threshold of feeling; (6) Reduce tension and pressure of soft tissue of tenderness point so as to relieve extrusion of nervus cutaneous.


Fully Oxygen-Tolerant Visible-Light-Induced ATRP of Acrylates in Water: Toward Synthesis of Protein-Polymer Hybrids.
Over the last decade, photoinduced ATRP techniques have been developed to harness the energy of light to generate radicals. Most of these methods require the use of UV light to initiate polymerization. However, UV light has several disadvantages: it can degrade proteins, damage DNA, cause undesirable side reactions, and has low penetration depth in reaction media. Recently, we demonstrated green-light-induced ATRP with dual catalysis, where eosin Y (EYH2) was used as an organic photoredox catalyst in conjunction with a copper complex. This dual catalysis proved to be highly efficient, allowing rapid and well-controlled aqueous polymerization of oligo(ethylene oxide) methyl ether methacrylate without the need for deoxygenation. Herein, we expanded this system to synthesize polyacrylates under biologically relevant conditions using CuII/Me6TREN (Me6TREN = tris[2-(dimethylamino)ethyl]amine) and EYH2 at ppm levels. Water-soluble oligo(ethylene oxide) methyl ether acrylate (average M n = 480, OEOA480) was polymerized in open reaction vessels under green light irradiation (520 nm). Despite continuous oxygen diffusion, high monomer conversions were achieved within 40 min, yielding polymers with narrow molecular weight distributions (1.17 ≤ D̵ ≤ 1.23) for a wide targeted DP range (50-800). In situ chain extension and block copolymerization confirmed the preserved chain end functionality. In addition, polymerization was triggered/halted by turning on/off a green light, showing temporal control. The optimized conditions also enabled controlled polymerization of various hydrophilic acrylate monomers, such as 2-hydroxyethyl acrylate, 2-(methylsulfinyl)ethyl acrylate), and zwitterionic carboxy betaine acrylate. Notably, the method allowed the synthesis of well-defined acrylate-based protein-polymer hybrids using a straightforward reaction setup without rigorous deoxygenation.


Survey of Pacific Egg and Poultry Association Scholarship Recipients (1965-1994).
The Scholarship and Research Foundation of the Pacific Egg and Poultry Association, a West Coast trade association, began awarding scholarships in 1965. The scholarship program was established as a means of rewarding high scholastic performance and encouraging careers in the poultry industries. A survey was conducted of the 1965 to 1994 recipients. During the 30-yr period, the association awarded 513 scholarships. Alumni association offices in western Canada and the United States were able to provide current mailing addresses for 312 of the recipients. A letter was sent to each former recipient requesting information on postdegree career paths. Responses were received from 104 or 33.3% of the individuals. Initial career choices and current occupations were tabulated. Broad occupational choices were categorized as poultry, agriculturally related nonpoultry, nonagricultural, still in school, or unknown. Poultry-related careers were categorized by more specific job definitions: live production, allied industry, extension, research/teaching faculty, and veterinary medicine. The poultry industries attracted 52.9% of the recipients for their first postdegree job. Currently, 50.0% of the recipients are employed by the poultry industries. Of those, 36.5% are in live production, 19.2% in allied industry, 5.8% in extension, 17.3% in research/teaching, and 21.1% in veterinary medicine.


Effects of multiple genetic loci on the pathogenesis from serum urate to gout.
Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (PFDR < 0.05) in the Chinese population for the first time. ABCG2 and a novel gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, PFDR = 3.68E-09; OR = 1.27, PFDR = 0.013, respectively). Also, HNF4G is a novel gene associated with susceptibility to gout (OR = 1.28, PFDR = 1.08E-03). In addition, A1CF and TRIM46 were identified as associated with gout in the Chinese population for the first time (PFDR < 0.05). The present study systematically determined genetic effects on the progression from elevated serum urate to gout and suggests that urate-associated genes functioning as urate transporters may play a specific role in the pathogenesis of gout. Furthermore, two novel gout-associated genes (HNF4G and SLC17A4) were identified.


[4 + 2] cycloadditions of N-alkenyl iminium ions: structurally complex heterocycles from a three-component Diels-Alder reaction sequence.
N-Alkenyl iminium ions serve as conduits to three-component [4 + 2] cycloaddition reactions accessing structurally and stereochemically diverse piperidine derivatives. These cationic 2-azadienes participate in endo- or exo-selective [4 + 2] cycloadditions with electron-rich and neutral alkene dienophiles to generate a tetrahydropyridinium ion as the initial cycloadduct. In situ nucleophilic addition to the cycloaddition-derived iminium ion completes the three-component coupling sequence and affords a versatile synthesis of structurally complex piperidines.


Prediction of Listeria innocua survival in fully cooked chicken breast products during postpackage thermal treatment.
The effectiveness of postpackage hot water thermal treatment on survival of Listeria innocua in fully cooked chicken breast products was investigated at 60, 70, 80, and 90°C. Primary models based on log-linear and Weibull models were used to fit bacterial survival curves at different temperatures. The prediction plot and fit statistics indicated that the Weibull model provided a better fit than the log-linear model and was selected as the primary model. A secondary model based on linear regression was developed to describe the effect of temperature on the kinetic parameters of Listeria innocua survival derived from the Weibull model. The root mean square error and coefficients of determination indicated a good fit of the secondary model. The models were validated by independent data from pilot plant tests, and the values of bias factor and accuracy factor fell into the acceptable range. The models developed in this study can assist poultry producers and risk managers in designing appropriate thermal treatment regimens to minimize the risk associated with Listeria in ready-to-eat poultry products.


What is an "ArchintorTM?" A paradigm shift in teaching, facilitation, and learning: The impact of different types of coursework expectations on classroom network structures.
Hypothetically, a student could attend a class, listen to lectures, and pass the class without knowing or interacting with other students. What happens to the network when the classroom expectations change? For example, there is a coursework expectation that students exchange contact information, or the instructor uses collaborative learning practices. Or what if the principal investigator (PI) of a scientific team goes on a sabbatical? This study uses the framework of classrooms because of their relatability across science. We asked how do different instructor coursework expectations change network structures within a classroom or other learning environments? A social network survey was administered at the start and end of the semester (pre- and post-test) in six university sociology classrooms to explore how expectations impacted the communication and learning networks. We found practical changes in course expectations impact the communication and learning networks, suggesting that instructors, facilitators, and others could be the archintorTM (architect+instructor+facilitator) of the network. Understanding that expectations can impact a network's structure marks a paradigm shift in educational assessment approaches. If the archintorTM has identified the "optimal" network structure, then their task is to design expectations that result in specific interactions that ultimately improve student achievement and success. This work provides recommendations for classroom archintorsTM to create the most impactful classroom networks. Future research should extend beyond education and classroom networks and identify the best or desired networks in other areas like public policy, urban planning, and more. If these "optimal" networks were identified, an archintorTM could design a social network to solve wicked problems, manage a crisis, and create social change.


Antimicrobial susceptibility pattern of bacteria isolated from patients with urinary tract infection.
To determine the antimicrobial susceptibility pattern of bacterial pathogens in the patients of urinary tract infection reporting at a tertiary care hospital. Laboratory based study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from January to December 2012. A total of 440 culture positive bacterial isolates from 1110 urine samples; submitted over a period of one year were included in this study. Identification of bacterial isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive bacterial isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines (CLSI). Out of the 440 culture positive urine samples, 152 (34.6%) were from indoor patients whereas 288 (65.4%) from outdoor patients. Gram negative bacteria accounted for 414 (94%) of the total isolates while rest of the 26 (6%) were Gram positive bacteria. The most prevalent bacterial isolate was Escherichia (E.) coli 270 (61.3%) followed by Pseudomonas (P.) aeruginosa 52 (12%) and Klebsiella (K.) pneumoniae 42 (9.5%). The susceptibility pattern of E. coli showed that 96.2% of the bacterial isolates were sensitive to imipenem, 85.1% to amikacin, 80.7% to piperacillin/tazobactam and 72.6% to nitrofurantoin. In case of P. aeruginsosa, 73% bacterial isolates were sensitive to tazobactam/piperacillin, 69.2% to sulbactam/cefoperazone and 65.38% to imipenem. The antibiogram of K. pneumoniae has revealed that 76.1% of the bacterial isolates were sensitive to imipenem and 52.3% to piperacillin/tazobactam. Nitrofurantoin and imipenem were the most effective antimicrobials amongst the Enterococcus spp. as 92.3% showed susceptibility to this bacterial isolate. Majority of the bacterial isolates were sensitive to imipenem and piperacillin/tazobactam while susceptibility to most of the commonly used oral antibiotics was very low. Among the oral antimicrobials, nitrofurantoin showed good susceptibility against Enterobacteriaceae family and Gram positive organisms.