Radiographic Diagnosis of Simulated External Root Resorption in Multi-Rooted Teeth: The Influence of Spatial Resolution.
The aim of this study was to evaluate the influence of spatial resolution (line pairs per millimetre - lp/mm) on the diagnosis of simulated external root resorption (ERR) in multi-rooted teeth by using digital periapical radiography. Forty human mandibular molars (80 roots) were used. The roots were divided into the following groups (n = 10): control without root filling (WORF), control with root filling (WRF), small ERRWORF, small ERR-WRF, moderate ERR-WORF, moderate ERR-WRF, extensive ERR-WORF and extensive ERR-WRF. Four digital radiographs (phosphor storage plates - PSP system) were taken of each tooth in three angulations. The PSPs were scanned with 10, 20, 25 and 40 lp/mm. All images were assessed by three endodontists who used a five-point scale for presence and absence of ERR and classified its location (cervical, middle or apical third). ROC curves and one-way ANOVA were performed (p < 0.01). Diagnosis of ERR in nonroot-filled teeth showed higher values of sensitivity for 20 lp/mm and higher values of both specificity and accuracy for 40 lp/mm. In root-filled teeth, sensitivity and accuracy were higher for 25 lp/mm and spatial resolution had no influence on specificity. The best resolution for diagnosis of small and extensive ERR was 25 lp/mm, whereas for moderate ERR, it was 40 lp/mm. Cervical ERR was the most difficult to diagnose, regardless of the spatial resolution. Higher spatial resolutions have improved the radiographic diagnosis of simulated ERR in multi-rooted teeth and this should be considered when performing digital radiographs.


Excessive gestational weight gain and chronic disease risk.
Excessive deposition of central body and abdominal (centripetal) fat early in life often will presage the later development of cardiovascular and metabolic diseases. Data from urban, low-income women from Camden, New Jersey, were used to examine the influence of gestational weight gain on patterns of weight change and fat deposition in 118 young women followed over two consecutive pregnancies. Adjusting for confounding factors, there was a significant (P < 0.05) dose-response relationship between the amount of gestational gain (in the subsequent pregnancy) and increases in postpartum weight compared with the postpartum in the prior pregnancy: +1.5 kg with a low gain, +2.9 kg with recommended amounts of gain, and +7.9 kg with excessive gain. Excessive gain (18+ kg) was common (18%) in the sample. The incidence of "new" obesity (body mass index [BMI] >29.0 in the subsequent postpartum but not the index postpartum) increased significantly with gestational gain: 4.7% with low gain, 7.0% with recommended gains, and 25.0% with excessive gain. There were similar dose-response increases related to gestational weight gain in all skinfolds (suprailiac, subscapular, and triceps) and the sum of the skinfolds. However, in women with excessive gains, fat was increased disproportionately at upper (+52%) and lower (+48%) central body sites, compared with the periphery (+27%), and compared with increases in women with lesser gestational gains. Thus, excessive gestational weight gain, which is common among low-income women, may be a factor which promotes obesity and a centripetal fat pattern during the reproductive years, thereby increasing the risk for cardiovascular and metabolic diseases in later life. © 1996 Wiley-Liss, Inc.


Heterogeneous impact of methadone on the QTc interval: what are the practical implications?
Methadone is associated with prolongation of the corrected QT interval (QTc) and torsade de pointes in case series, cross sectional studies, a prospective cohort study, and one randomized trial. It has recently been suggested that methadone promoted sudden cardiac death based on the absence of structural heart disease in an autopsy cohort. Given increasing data linking methadone to arrhythmia, clinicians must understand whether the relationship is causal, and if so, anticipate the expected frequency of QTc interval prolongation in their patients. To date has not been well characterized. To assess the impact of methadone on the QTc interval, electrocardiography at baseline and 6 months after methadone induction was evaluated from a previously published prospective cohort study of heroin addicts. Absolute increases above categorical QTc thresholds and the proportion with QTc interval increases exceeding 30 and 60 msec were tabulated. Among 151 subjects, 76% experienced an increase in QTc, whereas 24% had no change or a decrease. The proportion exceeding 450 msec increased from 7% at baseline to 19% at 6 months; those exceeding 500 msec increased from 0% to 2%. Although 18% of subjects had an increase in QTc of 30 msec, only 3% had an increase exceeding 60 msec. Most methadone-treated patients develop QTc prolongation. However, critical QTc prolongation (exceeding 500 msec or increases exceeding 60 msec) occurred infrequently. This highlights the heterogeneity of QTc interval changes and measurement variability but also implies that electrocardiography screening among opioid dependent patients would only occasionally require methadone discontinuation.


Towards sensitive, high-throughput, biomolecular assays based on fluorescence lifetime.
Time-resolved fluorescence detection for robust sensing of biomolecular interactions is developed by implementing time-correlated single photon counting in high-throughput conditions. Droplet microfluidics is used as a promising platform for the very fast handling of low-volume samples. We illustrate the potential of this very sensitive and cost-effective technology in the context of an enzymatic activity assay based on fluorescently-labeled biomolecules. Fluorescence lifetime detection by time-correlated single photon counting is shown to enable reliable discrimination between positive and negative control samples at a throughput as high as several hundred samples per second.


Anaplastic giant cell tumor with mucinous cystadenocarcinoma of the ovary. Origin of the giant cells.
The present case is that of a 27 years old woman who had received right oophorectomy for ovarian cancer nine years previously. The histological diagnosis at that time was mucinous cystadenocarcinoma with anaplastic areas. The patient expired ten years after oophorectomy due to widespread metastases of the tumor. Review of the histological slides revealed ovarian giant cell tumor which was considered to be of epithelial origin differing from those appearing in giant cell tumor of bone.


Macroalgal release of dissolved organic carbon in coral reef and its interaction with the bacteria associated with the coral Porites lutea.
Macroalgae supersede corals in the reefs worldwide, converting the coral-dominant systems into algal-dominant ones. Dissolved organic carbon (DOC) released by macroalgae play a prominent role in degrading the coral reefs by stimulating the bacterial growth and metabolism. However, the long-term remineralization of macroalgal DOC and their contribution to the carbon pool are least studied. In this study, we quantified the DOC released by five species of macroalgae that affected live corals through their physical contact and their subsequent remineralization for 100 days by coral mucus bacteria. Also, we analyzed the changes in bacterial community structure after 30 days of exposure to the macroalgal DOC. All the macroalgae released a significant amount of DOC ranging from 2.2 ± 0.17 to 8.1 ± 0.36 μmol C g-1 h-1 (mean ± SD). After 100 days, between 9.2 and 30.9% of the macroalgal DOC remained recalcitrant to bacterial remineralization. There was no apparent change in the dominant bacterial groups exposed to the DOC released by the green macroalgae Caulerpa racemosa and Halimeda sp. In comparison, the Proteobacteria group decreased with a prominent increase in the Firmicutes, Planctomycetes, and Bacteroidetes group in the samples exposed to DOC released by the brown macroalgae Turbinaria ornata, Sargassum tenerrimum, and Padina gymnospora. These inclusive data suggest that the DOC released by different species of macroalgae differed on their lability to microbial mineralization and highlight the comparable patterns in microbial responses to macroalgal exudates across different species.


Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group.
This report details the patterns of tumor recurrence in two prospective randomized studies involving 551 patients with histologically proven unresectable or medically inoperable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Patients were treated according to two protocols, depending on the stage of the tumor: (1) Patients with T1, 2, 3-NO, 1, 2 tumors were randomized to four different regimens: 4000 cGy split course (2000 cGy in five fractions, per 1 week, 2 weeks rest and additional 2000 cGy in five fractions, per 1 week) or 4000, 5000, or 6000 cGy continuous courses, five fractions per week. (2) Patients with T4, any N or N3, any T stage tumors were randomized to be treated with 3000 cGy tumor dose (TD), ten fractions in 2 weeks, 4000 cGy split course (described above), or 4000 cGy continuous course. In the patients with less advanced tumors (Study 1) the intrathoracic failure rate within the irradiated volume was 48% with 4000 cGy continuous, 38% with 4000 cGy split course or 5000 cGy continuous, and 27% for patients receiving 6000 cGy continuous course. The failure rate in the nonirradiated lung ranged from 25% to 30% in the various groups. Patients with adenocarcinoma or large cell undifferentiated carcinoma had better intrathoracic tumor control (35%) than those with squamous cell carcinoma (20%). The incidence of distant metastases was 75% to 80% in all histologic groups. Distant metastases appeared sooner after therapy in the patients with adenocarcinoma or large cell undifferentiated carcinoma. The initial failure rate in the brain was 7% in patients with squamous cell carcinoma, 19% with adenocarcinoma, and 13% in patients with large cell carcinoma. The ultimate incidence of brain metastases was 16% in squamous cell carcinoma, and 30% for adenocarcinoma or large cell undifferentiated carcinoma. Higher doses of irradiation will be necessary in order to improve the intrathoracic tumor control. Clinical trials by the Radiation Therapy Oncology Group, some of them involving multiple daily fractionation, are in progress. Furthermore, because of the high incidence of distant metastases, effective systemic cytotoxic agents are critically needed to improve survival of lung cancer patients. The high frequency of brain metastases suggests that, as in small cell carcinoma of the lung, elective irradiation of the brain may be necessary, if not to improve survival to enhance the quality of life of patients with adenocarcinoma and large cell carcinoma.


Effect of nitrogen dioxide exposure on allergic asthma in a murine model.
The purpose of this study was to examine the effects of NO(2), a major component of air pollution, on airway eosinophilic inflammation and bronchial hyperreactivity, using a mouse model of asthma. BALB/c mice (eight mice per experimental group) were studied in a basic research laboratory at the University of Iowa. Using a standard murine model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal (IP) injections (days 1 and 7) and were challenged with aerosolized OVA (days 13 and 14). Some mice were exposed to NO(2) (2 ppm) in an exposure chamber for 24 h before undergoing OVA aerosol challenge. A control group was exposed to OVA alone. The outcomes assessed included airway inflammation, bronchial hyperreactivity to inhaled methacholine, and goblet cell hyperplasia. We found that NO(2) exposure modestly increased airway neutrophilia but not airway eosinophilia in OVA-exposed mice. These mice exhibited epithelial damage and loss of epithelial mucin. Surprisingly, nonspecific bronchial hyperreactivity (ie, enhanced pause index) was not increased, although baseline smooth muscle tone was increased (p < 0.05) in the mice exposed to NO(2). These data indicate that relatively short-term (24 h) exposure to NO(2) causes epithelial damage, reduced mucin expression, and increased tone of respiratory smooth muscle. Reduced mucin production may be a mechanism of injury following long-term exposure to inhaled NO(2). Despite enhancing epithelial damage in OVA-exposed mice, NO(2) exposure does not otherwise alter the expression of allergen-induced airway responses.


Silipos neck wraps.
Burns of the neck are a problem. Grafted anterior necks can result in disfiguring hypertrophic scar contractures and wrinkling of the graft. The development of contractures can be prevented by effective splinting as soon as possible after the burn and by following a continuous wearing schedule until scar maturation is complete. Traditional neck conformers do not allow free neck rotation and can lead to stiffness as a result of decreased mobility. We used Silipos neck wraps for 10 patients who had good range of motion in the neck and who required pressure only for flattening of grafts and wrinkle prevention. The neck wrap is user-friendly, low in cost, and easy to fabricate and custom-fit for individual patients.


Kinetic analysis of the regulation of the Na+/H+ exchanger NHE-1 by osmotic shocks.
NHE-1 is a ubiquitous, mitogen-activatable, mammalian Na+/H+ exchanger that maintains cytosolic pH and regulates cell volume. We have previously shown that the kinetics of NHE-1 positive cooperative activation by intracellular acidifications fit best with a Monod-Wyman-Changeux mechanism, in which a dimeric NHE-1 oscillates between a low- and a high-affinity conformation for intracellular protons. The ratio between these two forms, the allosteric equilibrium constant L0, is in favor of the low-affinity form, making the system inactive at physiological pH. Conversely the high-affinity form is stabilized by intracellular protons, resulting in the observed positive cooperativity. The aim of the present study was to investigate the kinetics and mechanism of NHE-1 regulation by osmotic shocks. We show that they modify the L0 parameter (865 +/- 95 and 3757 +/- 328 for 500 and 100 mOsM, respectively, vs 1549 +/- 57 in isotonic conditions).This results in an activation of NHE-1 by hypertonic shocks and, conversely, in an inhibition by hypotonic media. Quantitatively, this modulation of L0 follows an exponential distribution relative to osmolarity, that is, additive to the activation of NHE-1 by intracellular signaling pathways. These effects can be mimicked by the asymmetric insertion of amphiphilic molecules into the lipid bilayer. Finally, site-directed mutagenesis of NHE-1 shows that neither its association with membrane PIP2 nor its interaction with cortical actin are required for mechanosensation. In conclusion, NHE-1 allosteric equilibrium and, thus, its cooperative response to intracellular acidifications is extremely sensitive to modification of its membrane environment.


Comparison of Taboo Search Methods for Atomic Cluster Global Optimization with a Basin-Hopping Algorithm.
The basin-hopping algorithm (BHA) allows for the efficient exploration of atomic cluster potential energy surfaces by random perturbations in configuration space, followed by energy minimizations. Here, the taboo search method is incorporated to prevent the search from revisiting recently visited regions of the search space. Two taboo search modes are implemented, one mode resets the search to random coordinates upon encountering the taboo region, while the other simply rejects any proposed move into the taboo region. These two modes are tested and compared on a variety of potential energy surfaces─several clusters where atomic interactions are described by the Lennard-Jones potential, and Au55 where a semi-empirical tight binding potential is used to describe atomic interactions. Some differences in performance between the two taboo search modes were noted for LJ38 and Au55, with the mode that rejects all hops into the taboo region performing better, offering a means to improve the efficiency of the BHA for multifunnel systems. However, both taboo search modes failed to significantly improve performance on multifunnel systems where more than two funnels were present in the system.


Stepwise mutation model and distribution of allelic frequencies in a finite population.
A mathematical theory is developed that enables us to derive a formula for the equilibrium distribution of allelic frequencies in a finite population when selectively neutral alleles are produced in stepwise fashion (stepwise mutation model). It is shown that the stepwise mutation model has a remarkable property that distinguishes it from the conventional infinite allele model (Kimura-Crow model): as the population size increases indefinitely while the product of the effective population size and the mutation rate is kept at a fixed value, the mean number of different alleles contained in the population rapidly reaches a plateau which is not much larger than the effective number of alleles (reciprocal of homozygosity).


Effects of Pulsatility on Arterial Endothelial and Smooth Muscle Cells.
Continuous flow ventricular assist device (CFVAD) support in advanced heart failure patients causes diminished pulsatility, which has been associated with adverse events including gastrointestinal bleeding, end organ failure, and arteriovenous malformation. Recently, pulsatility augmentation by pump speed modulation has been proposed as a means to minimize adverse events. Pulsatility primarily affects endothelial and smooth muscle cells in the vasculature. To study the effects of pulsatility and pulse modulation using CFVADs, we have developed a microfluidic co-culture model with human aortic endothelial (ECs) and smooth muscle cells (SMCs) that can replicate physiologic pressures, flows, shear stresses, and cyclical stretch. The effects of pulsatility and pulse frequency on ECs and SMCs were evaluated during (1) normal pulsatile flow (120/80 mmHg, 60 bpm), (2) diminished pulsatility (98/92 mmHg, 60 bpm), and (3) low cyclical frequency (115/80 mmHg, 30 bpm). Shear stresses were estimated using computational fluid dynamics (CFD) simulations. While average shear stresses (4.2 dynes/cm2) and flows (10.1 mL/min) were similar, the peak shear stresses for normal pulsatile flow (16.9 dynes/cm2) and low cyclic frequency (19.5 dynes/cm2) were higher compared to diminished pulsatility (6.45 dynes/cm2). ECs and SMCs demonstrated significantly lower cell size with diminished pulsatility compared to normal pulsatile flow. Low cyclical frequency resulted in normalization of EC cell size but not SMCs. SMCs size was higher with low frequency condition compared to diminished pulsatility but did not normalize to normal pulsatility condition. These results may suggest that pressure amplitude augmentation may have a greater effect in normalizing ECs, while both pressure amplitude and frequency may be required to normalize SMCs morphology. The co-culture model may be an ideal platform to study flow modulation strategies.


How to choose the best journal for your case report.
Since the establishment of the Journal of Medical Case Reports in 2006, the number of journals that publish case reports has increased rapidly, and most of these journals are open access. Open access publishing usually requires authors to pay publication fees while offering the articles online, free of charge, and free of most copyright and licensing restrictions. The movement for open access has gained support in the research community, with the publishers BioMed Central and PLOS ONE becoming leaders in scientific publishing in their number of articles and citations. As the number of open access publishers has exploded, so too has the number of publishers that act in bad faith to profit from the open access model. Simple guidelines have been developed and resources are available to help authors choose a suitable journal for publication of their case reports.


Effect of inositol hexakisphosphate on the EPR properties of the nitric oxide derivative of ferrous dromedary (Camelus dromedarius) hemoglobin. Evidence for two polyanion binding sites.
The effect of inositol hexakisphosphate on the EPR properties of the nitric oxide derivative of ferrous dromedary (Camelus dromedarius) hemoglobin has been investigated at 110 K. In the absence of inositol hexakisphosphate, the nitrosyl derivative of dromedary hemoglobin shows an EPR spectrum with a rhombic shape and a weak hyperfine splitting in the gz region, a feature that is generally taken as characteristic of the high-affinity state of tetrameric hemoproteins. On addition of 1 mole of inositol hexakisphosphate/tetramer, three new hyperfine lines (Az = 1.7 mT), centered at gz = 2.01, appear; this type of spectrum is indicative of the low-affinity state of hemoglobins. A further addition of inositol hexakisphosphate, corresponding to a 20-fold molar excess, completely reverses the polyphosphate-dependent transition, giving an EPR spectrum that is exactly superimposable to that observed in the absence of the allosteric effector, i.e., is typical of the high-affinity state of the macromolecule. Both in the absence and presence of inositol hexakisphosphate, the EPR spectra are virtually independent of pH in the range explored (from 5.5 to 7.5). These results, taken together with the behavior of the nitric oxide derivative of human hemoglobin, provide further evidence for the existance in dromedary hemoglobin of two polyanion binding sites that affect in an opposite way the conformational equilibrium of the macromolecule.


Syntheses, structures, and optical properties of novel zinc(ii) complexes with multicarboxylate and N-donor ligands.
Five novel coordination polymers [Zn(2)(OA)(4,4'-bipy)(H(2)O)].0.5(4,4'-bipy), [Zn(2)(OA)(dib)(H(2)O)].H(2)O, [Zn(2)(OA)(bbi)(2)].3H(2)O, [Zn(2)(OA)(phen)(2)(H(2)O)] and [Zn(4)(OA)(2)(2,2'-bipy)(2)(H(2)O)].2H(2)O were obtained by hydrothermal reactions of Zn(NO(3))(2).6H(2)O with a V-shaped multicarboxylate ligand 3,3',4,4'-oxydiphthalic acid (H(4)OA) and a series of N-donor ligands, namely 4,4'-bipyridine (4,4'-bipy), 1,4-di(1-imidazolyl)benzene (dib), 1,1'-(1,4-butanediyl)bis(imidazole) (bbi), 1,10-phenanthroline (phen), 2,2'-bipyridine (2,2'-bipy). The structures of the complexes were established by single-crystal X-ray diffraction analysis. Complex exhibits a robust 3D porous structure with uncoordinated 4,4'-bipy molecules filling the cavities. Complexes and show a complicated 3D framework, while complexes and have a 2D network and a 1D helical chain structure, respectively. The results indicate that the multicarboxylate OA(4-) ligand can adopt varied coordination modes in the formation of the complexes and the influence of the N-donor ligand on the structure of the complexes is discussed. The photoluminescence properties of H(4)OA and were studied in the solid state at room temperature. Moreover, nonlinear optical measurements showed that displayed a second-harmonic-generation (SHG) response of 0.5 times of that for urea. The results suggested that the configuration and flexibility of the ligands play a key role in directing the related properties of the complexes.


NEGATIVE FREQUENCY-DEPENDENT SELECTION BY POLLINATORS ON ARTIFICIAL FLOWERS WITHOUT REWARDS.
Many species of nonmodel deceptively pollinated orchids are polymorphic for corolla color. These species are pollinated by naive insects searching for nectar, and are not mimics. It has been suggested that the foraging behavior of insect pollinators during the avoidance learning process results in these stable corolla color polymorphisms; for this to occur pollinators must induce negative frequency-dependent selection on corolla color. Therefore the hypothesis that pollinator behavior results in a preference for rare color morphs of deceptive species was tested experimentally. Bumblebees (Bombus terrestris) foraged in the laboratory on arrays of artificial flowers with different corolla color morphs. Morphs were varied in frequency, and bumblebee preferences were recorded on arrays where morphs did and did not contain sucrose solution rewards. Bumblebees preferred the most common color morph when flowers contained sucrose solution rewards, but overvisited rare morphs when sampling flowers that contained no rewards. Bumblebees also tended to move between unlike color morphs when these were unrewarding, suggesting that a probabilistic sampling strategy was adopted. Thus experiments demonstrated that pollinator behavior could result in a selective advantage for rare color morphs of plant species that are pollinated by deception without mimicry, which would induce negative frequency-dependent selection on corolla color. The observed pollinator behavior could allow stable corolla color polymorphisms to be maintained by selection in nonmodel deceptively pollinated species.


Association between lower plasma adiponectin levels and higher plasma thrombin generation parameters in men with type 2 diabetes: role of plasma triglycerides.
Previous studies showed a significant association between lower plasma adiponectin levels and higher risk of adverse cardiovascular outcomes in patients with and without type 2 diabetes mellitus (T2DM). Presently, it is uncertain whether lower plasma adiponectin levels are associated with greater plasma thrombin generation in patients with T2DM. We studied 82 middle-aged men with non-insulin-treated T2DM [mean age ± SD: 64.1 ± 8 years; median duration of diabetes: 12.5 (inter-quartile range 6-19) years; mean hemoglobin A1c 7.0 ± 0.7%], consecutively attending our diabetes outpatient service over a 6-month period. Using the newly developed fully automated thrombin generation analyzer ST Genesia®, we measured the plasma parameters lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP) in all participants. In univariable linear regression analyses, lower plasma adiponectin levels were significantly associated with higher plasma thrombin generation parameters, as reflected by higher values of PH (Pearson's r coefficient = - 0.228, p = 0.039) and EPT (r = - 0.293, p = 0.007). Plasma adiponectin levels were not significantly associated with other thrombin generation parameters (LT and TP). Notably, the significant associations of plasma adiponectin levels with thrombin PH and EPT values persisted after adjustment for age and adiposity measures, but they were lost after additional adjustment for plasma triglycerides. Our findings show for the first time the existence of a significant association between lower levels of plasma adiponectin and greater plasma thrombin generation (as assessed by the ST Genesia® analyzer) in men with non-insulin-treated T2DM, which appears to be largely mediated by plasma triglycerides.


Clinical and neuroimaging characteristics of Chinese dementia with Lewy bodies.
Dementia with Lewy bodies (DLB) is the second most common subtype of degenerative dementia. To our knowledge, available information about the clinical features of DLB in China remains limited. Our study therefore aimed to address this issue. Thirty-seven Chinese patients with probable DLB were recruited for this study. All subjects underwent neuropsychological assessment by trained neurologists, as well as undergoing MRI, 11C-PIB PET scans for Aβ deposition and 18F-FDG PET scans for regional cerebral glucose metabolism. Our results showed that the gender ratio of patients was 16:21 (F:M). The mean age of onset was 69.5 ± 9.0 years and the mean age at diagnosis was 71.8 ± 9.1 years. At diagnosis, the prevalence of three core clinical features of DLB was: 64.9% for fluctuating cognition, 73.0% for visual hallucinations and 62.2% for parkinsonism. The result from 11C-PiB PET and 18F-FDG PET scans confirmed Aβ deposition in the cortex and demonstrated hypometabolism in the bilateral temporoparietooccipital region, the frontal lobe, the insular lobe, and the posterior cingulate, precuneus and caudate nuclei. Our study elucidated the clinical features of Chinese DLB patients, and will improve the understanding and the early diagnosis of DLB in Chinese patients.


[CNS prophylaxis in acute lymphoblastic leukemia (author's transl)].
Results of CNS prophylaxis of 43 LLA children are studied. Prognostic characteristics of the group, follow-up time, and controls made are reported. Prophylaxis was made with intrathecal methotrexate associated to craneal (24 patients) or craneospinal irradiation. There was a 13% of meningosis between three and 27 months of the first complete remission. There were no differences of effectiveness between the two methods of treatment. The side effects were mild. Fifty five percent of patients showed fever, and vomits after intrathecal methotrexate injections, and 16% somnolence postradiotherapy syndrome. There were two more severe complications, one sepsis and one necrotizing leukoencephalopathy.


Perceived brightness of incandescent and LED aviation signal lights.
Aviation signal lights using light emitting diodes (LEDs) are commonly perceived as brighter than those using incandescent sources, even at the same measured intensity. In general, saturated colors, like those produced by LEDs, appear brighter than less saturated lights, like those produced by incandescent sources. We describe a series of experiments quantifying the brightness of simulated blue, white, and green LED signal lights relative to incandescent signal lights of the same hue. Simulated signal lights and arrays were compared against dark and against dimly lighted backgrounds, and through simulated fog. The results confirm that LED signal lights are brighter than incandescent signals at matched luminous intensities. Brightness relationships were unaffected by background light level, and by the number of signals viewed, but the simulated fog reduced the brightness difference between the incandescent and LED signal lights. The present results could not be accurately predicted by several previously published models of brightness appearance, probably because of differences in experimental conditions. We present a new model that can be used to predict signal light brightness for blue, white, and green signal colors. Except for very short-wavelength blue signal lights, the model was able to accurately predict the present brightness data as well as those from previously published independent experiments. This validation lends confidence to the generality of the model for predicting blue, white, and green signal light brightness, but different colors (e.g., yellow or red) remain to be tested and modeled using this approach.


High-performance size exclusion chromatography with a multi-wavelength absorbance detector study on dissolved organic matter characterisation along a water distribution system.
This study examined the associations between dissolved organic matter (DOM) characteristics and potential nitrification occurrence in the presence of chloramine along a drinking water distribution system. High-performance size exclusion chromatography (HPSEC) coupled with a multiple wavelength detector (200-280nm) was employed to characterise DOM by molecular weight distribution, bacterial activity was analysed using flow cytometry, and a package of simple analytical tools, such as dissolved organic carbon, absorbance at 254nm, nitrate, nitrite, ammonia and total disinfectant residual were also applied and their applicability to indicate water quality changes in distribution systems were also evaluated. Results showed that multi-wavelength HPSEC analysis was useful to provide information about DOM character while changes in molecule weight profiles at wavelengths less than 230nm were also able to be related to other water quality parameters. Correct selection of the UV wavelengths can be an important factor for providing appropriate indicators associated with different DOM compositions. DOM molecular weight in the range of 0.2-0.5kDa measured at 210nm correlated positively with oxidised nitrogen concentration (r=0.99), and the concentrations of active bacterial cells in the distribution system (r=0.85). Our study also showed that the changes of DOM character and bacterial cells were significant in those sampling points that had decreases in total disinfectant residual. HPSEC-UV measured at 210nm and flow cytometry can detect the changes of low molecular weight of DOM and bacterial levels, respectively, when nitrification occurred within the chloraminated distribution system.


Community-based service learning in the engaged university.
The engaged university expands the concept of service learning to include a redesigned approach to teaching, research, and service functions that leads to a productive involvement with communities. This article describes an ongoing community partnership that models the best-practice aspects of the engaged university.


Truth and Myth of Phase Coexistence in Methylammonium Lead Iodide Perovskite Thin Film via Transmission Electron Microscopy.
Hybrid organic-inorganic perovskites have attracted substantial interest as the most favorable prospective material for efficient photovoltaic and optoelectronic devices. However, their extreme sensitivity to electron beam radiation makes it difficult to obtain their intrinsic structure by transmission electron microscopy and can even lead to significant misidentifications. In 2018, the coexistence of methylammonium lead iodide (MAPbI3 ) in the cubic and tetragonal phase using electron microscopy and electron diffraction techniques was reported in article "Self-Organized Superlattice and Phase Coexistence inside Thin Film Organometal Halide Perovskite". Herein, however, that claim is challenged by comparing their experimental data to simulated diffraction patterns and arguing that their perovskite samples may have been damaged due to excessive electron beam irradiation. Consequently, true phase coexistence was not observed in that previously reported work, rather merely the decomposition products of MAPbI3 .


Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD.
Adipose tissue-derived "stem cells" have been increasingly used by "stem-cell clinics" in the United States and elsewhere to treat a variety of disorders. We evaluated three patients in whom severe bilateral visual loss developed after they received intravitreal injections of autologous adipose tissue-derived "stem cells" at one such clinic in the United States. In these three patients, the last documented visual acuity on the Snellen eye chart before the injection ranged from 20/30 to 20/200. The patients' severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, or lens dislocation. After 1 year, the patients' visual acuity ranged from 20/200 to no light perception.


Combination of Sorafenib, Camrelizumab, Transcatheter Arterial Chemoembolization, and Stereotactic Body Radiation Therapy as a Novel Downstaging Strategy in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Case Series Study.
Although the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT). This retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated. Of the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3-4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever (n = 4, 33.3%), followed by skin reaction (n = 3, 25%). A combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events.


Analysis of scientific production in otolaryngology in Spain in the period 2011-2015.
Publishing in scientific journals is an indicator of hospital quality and has become a standard of excellence for medical doctors and institutions. The aim of the study is to identify the scientific publications performed by Otolaryngology Departments in Spain within the period 2011-2015 and to compare them to a previous period between 1998-2002. Original papers published by Otolaryngology Departments in Spain in PubMed within 2011-2015 were retrieved. They were classified according to the type of journal published (international or Acta ORL Española) and the following subspecialty areas: Otology, Audiology and Neuro-Otology, Head and Neck Surgery (including Oncology), Rhinology and Paediatric ENT. Hospitals were ranked according to: number of original papers, accumulated impact factor and total number of publications. Between 2011 and 2015, 49342 publications were included in PubMed, 1.44% from Otolaryngology Departments in Spain. Between 1998 and 2002, 3.80% publications were from Spanish ENT departments. Of the 712 papers published within the period 2011-2015, 389 were published in Acta ORL Española and 323 in international journals. From the latter, 20.7% belong to the Otology area, 19.2% to Audiology-Neuro-otology, 30.6% to Head and Neck Surgery, 15.2% to Rhinology and 3.4% to Paediatric ENT. Five tertiary centres published at least 10 original papers in the same period. Spanish otolaryngology's contribution to international journals has decreased in the last 12 years. A few institutions are responsible for the majority of publications and they have notably increased the cumulative impact factor.


Some growth points in African child development research.
We reflect on ways in which research presented in earlier chapters responds to challenges of generating an African child development field and identify additional issues calling for the field's attention. The chapters collectively display a variety of African contexts and reflexive evidence of the authors' African cultural roots. Connecting research with African audiences demands cooperative communication between educational practitioners and parents with low literacy, and cross-sector communication among professionals. Intracultural exploration of factors influencing the pattern of human development has begun to document the potential of indigenous African cultures as a fund of resources for enhancing child development. Priority topics for future African developmental research include multilingualism, musical performance, socially distributed caregiving, and the relation between adolescence and economic activity. Integration of multiple disciplines in the application of research-based principles to service delivery in the fields of community-based (re)habilitation and early childhood care and education calls for researcher collaboration with practitioners.


[GM1-gangliosidosis knockout mouse].
We generated a beta-galactosidosis mouse by gene targeting in an embryonic stem cell. Clinical, pathological, and biochemical analyses revealed that this mouse is a useful animal model to study the pathogenesis and therapy of human GM1-gangliosidosis.


Investigation and Demonstration of Catalyst/Initiator-Driven Selectivity in Thiol-Michael Reactions.
Thiol-Michael "click" reactions are essential synthetic tools in the preparation of various materials including polymers, dendrimers, and other macromolecules. Despite increasing efforts to apply thiol-Michael chemistry in a controlled fashion, the selectivity of base- or nucleophile-promoted thiol-Michael reactions in complex mixtures of multiple thiols and/or acceptors remains largely unknown. Herein, we report a thorough fundamental study of the selectivity of thiol-Michael reactions through a series of 270 ternary reactions using 1H NMR spectroscopy to quantify product selectivity. The varying influences of different catalysts/initiators are explored using ternary reactions between two Michael acceptors and a single thiol or between a single Michael acceptor and two thiols using three different catalysts/initiators (triethylamine, DBU, and dimethylphenylphosphine) in chloroform. The results from the ternary reactions provide a platform from which sequential quaternary, one-pot quaternary, and sequential senary thiol-Michael reactions were designed and their selectivities quantified. These results provide insights into the design of selective thiol-Michael reactions that can be used for the synthesis and functionalization of multicomponent polymers and further informs how catalyst/initiator choice influences the reactivity between a given thiol and Michael acceptor.


The genome of the Black Bengal goat (Capra hircus).
Black Bengal goat (Capra hircus), a member of the Bovidae family with the unique traits of high prolificacy, skin quality and low demand for food is the most socioeconomically significant goat breed in Bangladesh. Furthermore, the aptitude of adaptation and disease resistance capacity of it is highly notable which makes its whole genome information an area of research interest. The genomic DNA of a local (Chattogram, Bangladesh) healthy male Black Bengal goat (Capra hircus) was extracted and then sequenced. Sequencing was completed using the Illumina HiSeq 2500 sequencing platform and the draft assembly was generated using the "ARS1" genome as the reference. MAKER gene annotation pipeline was utilized to annotate 26,458 gene models. Genome completeness was assessed using BUSCO (Benchmarking Universal Single-Copy Orthologs) which showed 82.5% completeness of the assembled genome.


Arterial injuries.
The authors review arterial injuries in 68 patients treated at Maisonneuve-Rosemont Hospital in Montreal between 1975 and 1982. Penetrating trauma caused 54.4% of these injuries, which consisted of either laceration or intimal tear with thrombosis. Arterial injuries of the extremities were predominant (58.8%). Associated injuries were frequent. Surgical repair was effected in 60 patients. End-to-end anastomosis, angioplasty and venous or prosthetic bypass grafting were the techniques used. Postoperative complications occurred in 37% of the patients. Overall mortality was 19% and was related mainly to aortic injury. The amputation rate for arterial injuries of the extremities was 15%. Prompt recognition and treatment of arterial injuries are important in order to achieve the best results.


Reactive lymphoid hyperplasia of the liver: a case report and review of literature.
A case of a 53-year-old female patient with reactive lymphoid hyperplasia (RLH), clinically designated as pseudolymphoma of the liver is described in this article. The patient was admitted to our hospital for further evaluation of hepatic tumors incidentally discovered at another hospital. Various diagnostic methods, including ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and hepatic angiography displayed three small lesions in the liver with outstanding findings consistent with hepatocellular carcinoma (HCC). Surgical resection was performed and the three lesions were microscopically diagnosed as RLH of the liver. The lesions comprised a massive infiltration of lymphoid cells with follicles and hyalinized inter-follicular spaces. Immunohistochemical examination revealed that infiltrating lymphocytes had no prominent nuclear atypia and polyclonality. RLH of the liver is a very rare condition and only twelve cases have been reported in the English literature. Majority of the reported cases were middle-aged women and about half of them had some immunologic abnormalities such as autoimmune thyroiditis, Sjogren's syndrome, primary immunodeficiency, primary biliary cirrhosis. Since they are often clinically misdiagnosed as HCC, surgery is the choice of treatment for these patients. Although their pathology resembles malignant lymphoma, the clinical course is completely benign. The authors propose that RLH of the liver can be discriminated from HCC by its clinical features.


Training With Direct Versus Indirect Spatial Stimulus-Response Compatibility in Combat Sports.
The study examined effects of spatial stimulus-response compatibility on response time and response accuracy in 20 novice combat sport athletes. Two equivalent groups, based on initial reaction time measures, were required to perceive and move quickly and accurately in response to an unspecific visual stimulus presented on a large screen during the two types of perceptual training in eight laboratory sessions. One group reacted by moving the fist toward the stimulus location on the target (direct compatibility condition). Another group was required to move the fist away from target in the opposite direction (indirect compatibility condition). Specifically, the indirect compatibility group achieved faster reaction times than the direct compatibility group during the two posttests containing video-projected attacks of the opponents, and in one of the two posttests containing real opponents' attacks. Results seem to reveal higher combat performance against real opponents when athletes trained with an indirect stimulus-response compatibility condition.


Enhanced Association of Tau Pathology and Cognitive Impairment in Mild Cognitive Impairment Subjects with Behavior Symptoms.
Mild cognitive impairment (MCI) individuals with neuropsychiatric symptoms (NPS) are more likely to develop dementia. We sought to understand the relationship between neuroimaging markers such as tau pathology and cognitive symptoms both with and without the presence of NPS during the prodromal period of Alzheimer's disease. A total of 151 MCI subjects with tau positron emission tomographic (PET) scanning with 18F AV-1451, amyloid-β (Aβ) PET scanning with florbetapir or florbetaben, magnetic resonance imaging, and cognitive and behavioral evaluations were selected from the Alzheimer's Disease Neuroimaging Initiative. A 4-group division approach was proposed using amyloid (A-/A+) and behavior (B-/B+) status: A-B-, A-B+, A+B-, and A+B+. Pearson's correlation test was conducted for each group to examine the association between tau deposition and cognitive performance. No statistically significant association between tau deposition and cognitive impairment was found for subjects without behavior symptoms in either the A-B-or A+B-groups after correction for false discovery rate. In contrast, tau deposition was found to be significantly associated with cognitive impairment in entorhinal cortex and temporal pole for the A-B+ group and nearly the whole cerebrum for the A+B+ group. Enhanced associations between tauopathy and cognitive impairment are present in MCI subjects with behavior symptoms, which is more prominent in the presence of elevated amyloid pathology. MCI individuals with NPS may thus be at greater risk for further cognitive decline with the increase of tau deposition in comparison to those without NPS.


Pyrite sulfur isotopes reveal glacial-interglacial environmental changes.
The sulfur biogeochemical cycle plays a key role in regulating Earth's surface redox through diverse abiotic and biological reactions that have distinctive stable isotopic fractionations. As such, variations in the sulfur isotopic composition (δ34S) of sedimentary sulfate and sulfide phases over Earth history can be used to infer substantive changes to the Earth's surface environment, including the rise of atmospheric oxygen. Such inferences assume that individual δ34S records reflect temporal changes in the global sulfur cycle; this assumption may be well grounded for sulfate-bearing minerals but is less well established for pyrite-based records. Here, we investigate alternative controls on the sedimentary sulfur isotopic composition of marine pyrite by examining a 300-m drill core of Mediterranean sediments deposited over the past 500,000 y and spanning the last five glacial-interglacial periods. Because this interval is far shorter than the residence time of marine sulfate, any change in the sulfur isotopic record preserved in pyrite (δ34Spyr) necessarily corresponds to local environmental changes. The stratigraphic variations (>76‰) in the isotopic data reported here are among the largest ever observed in pyrite, and are in phase with glacial-interglacial sea level and temperature changes. In this case, the dominant control appears to be glacial-interglacial variations in sedimentation rates. These results suggest that there exist important but previously overlooked depositional controls on sedimentary sulfur isotope records, especially associated with intervals of substantial sea level change. This work provides an important perspective on the origin of variability in such records and suggests meaningful paleoenvironmental information can be derived from pyrite δ34S records.


Bacillus cereus may produce two or more diarrheal enterotoxins.
Bacillus cereus strains were tested for production of diarrheal enterotoxin by the reverse passive latex agglutination test and for presence of B. cereus enterotoxin gene (bceT) by polymerase chain reaction. About 50% of 56 B. cereus strains reacted positive in broth culture in the reverse passive latex agglutination test, while the bceT gene was detected in 41.1%. Sixteen percent of the strains were positive for both diarrheal enterotoxin and bceT gene. A 741 bp probe prepared from the polymerase chain reaction product detected bceT gene in all strains that were positive with the polymerase chain reaction. This study indicates a likelihood of two or more enterotoxins being produced by B. cereus which may be involved in causing diarrheal type food poisoning.


[Clinical study of aortitis syndrome].
Aortitis syndrome (Takayasu arteritis) is found frequently in Japan and it affects often young female. It was reported first by Takayasu in 1908 and thereafter many studies were performed about this disease. Consequently, it became clear that this is chronic inflammatory disease of unknown origin and it affects thoracic aorta, abdominal aorta, its branches and pulmonary artery, the lesion of which may show occlusion or dilatation. It shows many various symptoms and physical findings, which are pulselessness and vascular bruit at lesion etc., serum inflammatory reaction and angiography are important for its diagnosis. Medical control for inflammation at active phase and necessary surgical treatment at stable phase are the principle for its treatment.


Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function.
Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS-) induced maturation of dendritic cells (DCs) in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG) E2 in this process. In vivo, early administration of murine and human ASCs (hASCs) ameliorated myelin oligodendrocyte protein- (MOG35-55-) induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+) DCs in draining lymph nodes (DLNs). In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.


Extraosseous Spread of Multiple Myeloma Mimicking Pancoast Tumor.
A 55-year-old man presented with upper backache for one month, inability to move both the lower limbs for two weeks and retention of urine for five days. Examination revealed spastic paraplegia and reduced breath sounds in the right upper zone. Initial imaging revealed a soft tissue lesion in the apex of the right lung, suggesting a Pancoast tumor. It also showed a lytic, expansile lesion of the T2 vertebra extending to the right second posterior rib on subsequent imaging. High serum calcium, M-spike in beta-gamma globulin region on serum electrophoresis, 50%-60% plasmacytoid cells on bone marrow aspiration, concertina collapse of the vertebral body, and pattern of neurological deficit pointed towards multiple myeloma. T2 corpectomy and mesh cage placement, C7-T4 posterior stabilization, and resection of the second rib were done. Histopathology confirmed multiple myeloma. Postoperatively, the patient was managed with radiotherapy and bortezomib. The patient had a good neurological recovery. Timely intervention is critical for disease control and leads to better recovery.


Ocular nonsuicidal self-injury in a teenager.
A 14-year-old male teen presented with unilateral episcleritis, unresponsive to topical and systemic corticosteroid therapy, without a history of ocular trauma or evidence for systemic diseases. The presence of foreign bodies in the conjunctival mucus of the hyperemic fornix has been noticed during one of the follow-up examinations. The toxicological analysis of conjunctival mucus revealed the presence of ethylene glycolmonomethyl ether and triethilene glicolebuthyl ether, used as solvents in nail polish removers and all-purpose cleaners. An unexpected etiology of chemical self-inflicted episcleritis was determined. The teen was admitted to a psychological assessment, after which a psychotherapeutic treatment was recommended. Episcleritis is characterized by the acute onset of ocular pain and redness, with a frequent recurrent and stressful course. Since it can be associated with life-threatening systemic vasculitides, a prompt, aggressive immunosuppressive therapy may be considered, both for the ocular inflammation and for the underlying systemic condition. Rarely episcleritis does not improve despite topical and systemic therapy, administered in a stepladder way. The reported teenager case needed a complex multidisciplinary approach to achieve the correct diagnosis and to avoid unnecessary treatments. In the case of recognized "nonsuicidal self-injury," a psychological evaluation is strongly recommended, to identify and address underlying neuropsychiatric problems.


[Possible interesting dietetic effects of lactulose as a feed additive in pig feed].
In reared piglets (n = 10), fattening pigs (n = 20) and sows (n = 8) the effects of lactulose as feed additive on the quality and composition of chyme and faeces were tested to find out potential dietetic advantages of its use. The lactulose concentration in the diets varied between 27-29 g/kg dry matter in piglets and fattening pigs and 55-140 g/kg dry matter in the diet of sows. In piglets and fattening pigs the lactulose intake did not alter the dry matter content and pH in faeces; in spite of the higher concentration lactulose did not result in diarrhea in sows or adult minipigs, there was only a slight decrease in the dry matter content of faeces. In contrast to findings in human beings only traces of lactulose reached the hind gut, although higher lactulose concentrations were measured at the end of the small intestine (in piglets: 10-40 g, in fattening pigs 40-70 g lactulose per kg dry matter of chyme). The oral intake of lactulose did not increase the concentration of lactic acid or volatile fatty acids in the content of the small intestine and did not reduce the pH in the chyme, but in the contents of cecum and colon ascendens higher concentrations of volatile fatty acids were measured (in piglets: significantly higher values, in fattening pigs slightly increased concentrations). In piglets as well as in fattening pigs lactulose resulted in reduced concentrations of ammonia in the content of small and large intestine, further more the concentrations of lipopolysaccharides were increased in the colonal chyme, when pigs ingested the lactulose containing diet. Due to the fact that only small amounts of lactulose reached the hind gut there are doubts, whether lactulose has comparable dietetic effects in pigs as known from human beings (for example laxative effects, forced elimination of bacteria like salmonella). The results obtained here in pigs underline the necessity of experimental studies in the target species (including parameters of digestive physiology, chemical/microbial composition of the chyme) before substances are used and recommended for dietetic purposes in feeding practice. In spite of generally adopted similarity of the alimentary tract in pigs and human beings there are eventually some important differences within the intestine, its digestive capacity or in reactions on ingested substances leading to unexpected results.


Kinetic Uptake Studies of Powdered Materials in Solution.
Challenges exist for the study of time dependent sorption processes for heterogeneous systems, especially in the case of dispersed nanomaterials in solvents or solutions because they are not well suited to conventional batch kinetic experiments. In this study, a comparison of batch versus a one-pot setup in two variable configurations was evaluated for the study of uptake kinetics in heterogeneous (solid/solution) systems: (i) conventional batch method; (ii) one-pot system with dispersed adsorbent in solution with a semi-permeable barrier (filter paper or dialysis tubing) for in situ sampling; and (iii) one-pot system with an adsorbent confined in a semi-permeable barrier (dialysis tubing or filter paper barrier) with ex situ sampling. The sorbent systems evaluated herein include several cyclodextrin-based polyurethane materials with two types of phenolic dyes: p-nitrophenol and phenolphthalein. The one-pot kinetics method with in situ (Method ii) or ex situ (Method iii) sampling described herein offers significant advantages for the study of heterogeneous sorption kinetics of highly dispersed sorbent materials with particles sizes across a range of dimensions from the micron to nanometer scale. The method described herein will contribute positively to the development of advanced studies for heterogeneous sorption processes where an assessment of the relative uptake properties is required at different experimental conditions. The results of this study will be advantageous for the study of nanomaterials with significant benefits over batch kinetic studies for a wide range of heterogeneous sorption processes.


[Executive functions in young patients with unipolar depression].
Neuropsychological deficits associated with unipolar depression are seen in a broad range of cognitive domains. Executive deficits may be prominent in depression. Investigation of executive functions in younger adult patients with unipolar depression has been the focus of our study. Twenty-two consecutively depressive inpatients (24-36 years) and 21 healthy control subjects, matched on age, gender, education and verbal IQ were included in the study. Neuropsychological tests for executive functions were applied to all subjects. Unipolar young depressives showed significantly reduced number of completed categories and more trials for completion of the first category on Wisconsin Card Sorting Test (WCST). No difference of tasks assessing the short-term memory, total errors on WCST, perseverative and non-perseverative errors, and of both phonemic and semantic conditions of verbal fluency was found between groups. The results suggested that unipolar depressives had specific cognitive style characterized by "negative cognitive set" (stronger negative reaction to negative feedback) and by failure to use negative feedback to improve their performance.


Development of Multiple-Lesion Basal Cell Carcinoma of the Skin: A Comprehensive Review.
An interesting clinical feature of basal cell carcinoma (BCC) of the skin is a marked variation in tumor number, sites, and accrual. Some individuals develop only a single BCC lesion with no impact on health status, while a significant proportion is affected repeatedly with new primary tumors at various body sites. Approximately 29% of patients with a first BCC will develop at least 1 more lesion during their lifetime. The candidate predictors for multiple BCC development include younger age and a superficial BCC subtype at the time of the first diagnosis, red hair phenotype, initial or frequent tumor location on the trunk or on the upper limbs, and male gender. The pathogenesis of multiple BCC development does not seem to be related to greater UVR exposure. Individual genetic susceptibility may have a greater impact than extrinsic factors. In clinical practice, it is meaningful to estimate the probability of new BCC development in patients who have an initial lesion. A reliable prediction model for individualized risk stratification remains a subject of continued research; however, a focus on the risk factor profile is beneficial for clinical screening and may help clinicians to determine the individuals who should be followed up more closely.


Ecological dynamics of terrestrial and freshwater ecosystems across three mid-Phanerozoic mass extinctions from northwest China.
The Earth has been beset by many crises during its history, and yet comparing the ecological impacts of these mass extinctions has been difficult. Key questions concern the kinds of species that go extinct and survive, how communities rebuild in the post-extinction recovery phase, and especially how the scaling of events affects these processes. Here, we explore ecological impacts of terrestrial and freshwater ecosystems in three mass extinctions through the mid-Phanerozoic, a span of 121 million years (295-174 Ma). This critical duration encompasses the largest mass extinction of all time, the Permian-Triassic (P-Tr) and is flanked by two smaller crises, the Guadalupian-Lopingian (G-L) and Triassic-Jurassic (T-J) mass extinctions. Palaeocommunity dynamics modelling of 14 terrestrial and freshwater communities through a long sedimentary succession from the lower Permian to the lower Jurassic in northern Xinjiang, northwest China, shows that the P-Tr mass extinction differed from the other two in two ways: (i) ecological recovery from this extinction was prolonged and the three post-extinction communities in the Early Triassic showed low stability and highly variable and unpredictable responses to perturbation primarily following the huge losses of species, guilds and trophic space; and (ii) the G-L and T-J extinctions were each preceded by low-stability communities, but post-extinction recovery was rapid. Our results confirm the uniqueness of the P-Tr mass extinction and shed light on the trophic structure and ecological dynamics of terrestrial and freshwater ecosystems across the three mid-Phanerozoic extinctions, and how complex communities respond to environmental stress and how communities recovered after the crisis. Comparisons with the coeval communities from the Karoo Basin, South Africa show that geographically and compositionally different communities of terrestrial ecosystems were affected in much the same way by the P-Tr extinction.


Spatial Proteome Reorganization of a Photosynthetic Model Cyanobacterium in Response to Abiotic Stresses.
Spatial proteome reorganization in response to a changing environment represents a different layer of adaptation mechanism in addition to differential expression of a subset of stress responsive genes in photosynthetic organisms. Profiling such reorganization events is critically important to extend our understanding how photosynthetic organisms adapt to adverse environments. Thus, we treated a unicellular photosynthetic model cyanobacterium, Synechocystis sp. PCC 6803 (hereafter referred to as Synechocystis), with five different types of abiotic stresses including nitrogen starvation, iron deficiency, cold, heat, and darkness, and systematically identified proteins showing stress-induced differential expression and/or redistribution between the membrane and the soluble fractions using a quantitative proteomics approach. A number of proteins showing such a redistribution in response to a single or multiple types of abiotic stresses were identified. These include 12 ribosomal proteins displaying unanimous cold-induced redistribution to the membrane and the protein FurA, a master regulator of iron acquisition, displaying iron deficiency- and nitrogen starvation-induced redistribution to the membrane. Such findings shed light on a novel regulatory mechanism underlying the corresponding stress responses, and establish the results in the present study as an important resource for future studies intended to understand how photosynthetic organisms cope with adverse environments.


Quantitative material characterization from multi-energy photon counting CT.
To quantify the concentration of soft-tissue components of water, fat, and calcium through the decomposition of the x-ray spectral signatures in multi-energy CT images. Decomposition of dual-energy and multi-energy x-ray data into basis materials can be performed in the projection domain, image domain, or during image reconstruction. In this work, the authors present methodology for the decomposition of multi-energy x-ray data in the image domain for the application of soft-tissue characterization. To demonstrate proof-of-principle, the authors apply several previously proposed methods and a novel content-aware method to multi-energy images acquired with a prototype photon counting CT system. Data from phantom and ex vivo specimens are evaluated. The number and type of materials in a region can be limited based on a priori knowledge or classification strategies. The proposed difference classifier successfully classified the image into air only, water+fat, water+fat+iodine, and water+calcium regions. Then, the content-aware material decomposition based on weighted least-square optimization generated quantitative maps of concentration. Bias in the estimation of the concentration of water and oil components in a phantom study was <0.10 ± 0.15 g/cc on average. Decomposition of ex vivo carotid endarterectomy specimens suggests the presence of water, lipid, and calcium deposits in the plaque walls. Initial application of the proposed methodology suggests that it can decompose multi-energy CT images into quantitative maps of water, adipose, iodine, and calcium concentrations.


RNA Primer Extension Hinders DNA Synthesis by Escherichia coli Mutagenic DNA Polymerase IV.
In Escherichia coli the highly conserved DNA damage regulated dinB gene encodes DNA Polymerase IV (DinB), an error prone specialized DNA polymerase with a central role in stress-induced mutagenesis. Since DinB is the DNA polymerase with the highest intracellular concentrations upon induction of the SOS response, further regulation must exist to maintain genomic stability. Remarkably, we find that DinB DNA synthesis is inherently poor when using an RNA primer compared to a DNA primer, while high fidelity DNA polymerases are known to have no primer preference. Moreover, we show that the poor DNA synthesis from an RNA primer is conserved in DNA polymerase Kappa, the human DinB homolog. The activity of DinB is modulated by interactions with several other proteins, one of which is the equally evolutionarily conserved recombinase RecA. This interaction is known to positively affect DinB's fidelity on damaged templates. We find that upon interaction with RecA, DinB shows a significant reduction in DNA synthesis when using an RNA primer. Furthermore, with DinB or DinB:RecA a robust pause, sequence and lesion independent, occurs only when RNA is used as a primer. The robust pause is likely to result in abortive DNA synthesis when RNA is the primer. These data suggest a novel mechanism to prevent DinB synthesis when it is not needed despite its high concentrations, thus protecting genome stability.


Religious Affiliation, Daily Spirituals, and Private Religious Factors Promote Marital Commitment Among Married Couples: Does Religiosity Help People Amid the COVID-19 Crisis?
Religious studies are a vital branch of social science that seeks to explain the beliefs of human society and deals with the practices and beliefs of individuals. This distinctive study focuses on such influential aspects of a healthy life, which could play a vital role in the marital quality and matrimonial commitment of individuals. The study principally focused on inspecting the role of religiosity in healthy marital commitment among individuals. It is a distinctive and central value in regulating a healthy social life. This research designed a conceptual model for assessing marital commitment, and the study model comprised two primary variables. The study received datasets through a survey questionnaire based on participants from five private and public sectors. The research study conducted an empirical analysis to test the proposed conceptual framework. The findings exhibited that the value of the R 2 model was 0.484, meaning the level of religiosity had a substantial impression on healthy and lasting marital commitment. According to the final outline of the model factors associated with building religious support factors (β = 0.491), the marital commitment had a better and healthier impact. The goodness-of-fit of the measurement of the conceptual model showed a value of 0.51, which indicated that the theoretical model had sufficient consistency and rationality, and accurately fitted the data. Such an advanced statistical model is missing from the previous literature. The study results provide helpful insight to elucidate the social dynamics of marital commitment. The findings designate that religious practices strengthen and promote nuptial commitment. The study is novel in the context of religiosity impact on martial commitment with a cultural background of Pakistan. The generalizability of the study does not apply to the entire population or other regions. Future studies can investigate other religious variables to explore further research findings. The findings are helpful for decision-makers and policymakers to concentrate on marital issues and challenges confronted by couples worldwide.


A modelling approach to the dynamics of gait initiation.
Gait initiation is an integral and complex part of human locomotion. In this paper, we present a novel compliant-leg model-based approach to understanding the key phases of initiation, the nature of the effective forces involved in initiation, and the importance of the anticipatory postural adjustments (APAs). The results demonstrate that in the presence of APAs, we observe a change in the characteristic of forcing required for initiation, and the energetic cost of gait initiation is also reduced by approximately 58%. APAs also result in biologically relevant leg landing angles and trajectories of motion. Furthermore, we find that a sublinear functional relationship with the velocity error from steady state predicts the required force, consistent with an open loop control law basis for gait initiation.


Prenatal alcohol exposure and early postnatal changes in the developing nerve-muscle system.
Extensive research on prenatal alcohol exposure has proven the potent teratogenicity of this substance of abuse. Children born to alcoholic mothers are often diagnosed with fetal alcohol syndrome (FAS). Those afflicted with FAS often have muscle weakness, muscle wasting, and atrophy. This study assessed the effects of prenatal alcohol exposure on the developing rat neuromuscular system. Pregnant Sprague-Dawley rats were injected intraperitoneally with 1.0 ml of 20% ethyl alcohol/100 gm body weight. Unexposed rats served as controls. The offspring were killed 2, 3, 4, and 5 weeks after birth, and their body weights were recorded. The tibialis anterior (TA) and extensor digitorum longus (EDL) muscles were recovered and weighed. The TA muscles were histochemically stained by silver cholinesterase in order to study the pattern of innervation. The EDL muscles were processed and stained by hematoxylin-eosin. The number and size of the EDL muscle fibers was quantified. The sciatic nerve was also removed and stained by Swank and Davenport's method to demonstrate the myelin pattern. Assessment at the neuromuscular junction showed a higher proportion of endplates polyneuronally innervated in the alcohol-exposed rats. The muscle weights, as well as the number and size of the muscle fibers, were significantly reduced in these animals. A light-microscopy examination of the nerve sections revealed alterations in the connectivity of myelin. The finding that a higher proportion of endplates were polyneuronally innervated in the alcohol-exposed rats indicates that the maturation process of the neuromuscular system was delayed, thus confirming the deleterious effects of alcohol on growth and maturation of the nerve-muscle system.


Influence of disk separation distance on accuracy of the disk approximation test for detection of inducible clindamycin resistance in Staphylococcus spp.
We undertook this study to assess the accuracy of the clindamycin-erythromycin disk approximation test (D-test) for detection of inducible clindamycin resistance in Staphylococcus spp. One hundred sixty-three Staphylococcus aureus and 68 coagulase-negative Staphylococcus (CoNS) spp. which were erythromycin nonsusceptible but clindamycin susceptible were tested using the D-test performed at both 15-mm and 22-mm disk separations and compared with genotyping as the "gold standard." The rate of inducible clindamycin resistance was 96.3% for S. aureus and 33.8% for CoNS spp. The sensitivities of the D-tests performed at 15 mm and 22 mm were 100% and 87.7%, respectively, and specificities were 100% for both. The use of 22-mm disk separation for the D-test to detect inducible clindamycin resistance results in an unacceptably high very major error rate (12.3%). All isolates with false-negative results harbored the ermA gene, and the majority were methicillin-resistant Staphylococcus aureus. False-negative results were associated with smaller clindamycin zone sizes and double-edged zones. We recommend using a disk separation distance of </=15 mm. There is wide geographic variation in the rates of inducible clindamycin resistance, and each laboratory should determine the local rate before deciding whether to either perform the D-test routinely or else report that all erythromycin-resistant S. aureus isolates are also clindamycin resistant.


Proteasome inhibitors as anticancer agents.
The therapeutic targeting of the ubiquitin-proteasome pathway (UPP) through inhibitors of the 20S proteasome core proteolytic activities has revolutionized the treatment of hematological malignancies and is paving the way for its extension to solid tumors. This review covers the progress made in the field of proteasome inhibitors, ranging from the first-generation bortezomib to the latest second-generation inhibitors such as carfilzomib and ixazomib as well as the proteasome inhibitors in clinical phase such as oprozomib and marizomib. The development of selective and potent proteasome inhibitors with improved pharmacological properties is described from the synthesis to their basic biological, and clinical validation. Proteasome inhibitors have transformed the treatment landscape for hematological malignancies and hold great promise for cancer therapy. Combination therapies targeting multiple pathways, the development of novel inhibitors or 'hybrid-inhibitors,' and the optimization of treatment protocols are key areas for future exploration. The extension of proteasome inhibitors for the treatment of solid tumors, and their ability to pass the blood-brain barrier open new possibilities for treating central nervous system cancers. However, managing adverse effects, particularly those affecting the central nervous system, remains a critical consideration and a strategic 'working on' aspect for the near future.


Temporal separation of vesicle release from vesicle fusion during exocytosis.
During exocytosis, vesicles in secretory cells fuse with the cellular membrane and release their contents in a Ca2+-dependent process. Release occurs initially through a fusion pore, and its rate is limited by the dissociation of the matrix-associated contents. To determine whether this dissociation is promoted by osmotic forces, we have examined the effects of elevated osmotic pressure on release and extrusion from vesicles at mast and chromaffin cells. The identity of the molecules released and the time course of extrusion were measured with fast scan cyclic voltammetry at carbon fiber microelectrodes. In external solutions of high osmolarity, release events following entry of divalent ions (Ba2+ or Ca2+) were less frequent. However, the vesicles appeared to be fused to the membrane without extruding their contents, since the maximal observed concentrations of events were less than 7% of those evoked in isotonic media. Such an isolated, intermediate fusion state, which we term "kiss-and-hold," was confirmed by immunohistochemistry at chromaffin cells. Transient exposure of cells in the kiss and hold state to isotonic solutions evoked massive release. These results demonstrate that an osmotic gradient across the fusion pore is an important driving force for exocytotic extrusion of granule contents from secretory cells following fusion pore formation.


Osteoporosis in celiac disease: a Hispanic pilot study.
Osteoporosis has become an issue of worldwide significance. This condition has been demonstrated in Celiac disease (CD) populations in Europe, South America and the United States. However, data from the Hispanic population is limited. Record review containing patients with Celiac disease in a Gastroenterology Clinic to evaluate the association of decreased bone density such as Osteoporosis and Osteopenia in subjects with Celiac disease in the southern population of Puerto Rico. We compared the results of Dual-energy X-ray absorptiometry. Clinical manifestations of CD in Hispanic population are described. Celiac disease data was available for seven patients; of those 6 were female (86%). The average age was 46 yr Most patients were overweight with a body mass index value of 29. CD patients showed abnormalities in hemoglobin, TSH and 25-Hydroxyvitamin D. The screening markers for CD showed a high value on IgA. The data to excel is the association of IgA vs. TSH showing strength of 90%. There was significantly lower bone density in women with Celiac Disease accounting for 86% of the cases. Women with Celiac Disease were associated with lower bone density and a higher prevalence of Osteopenia but not Osteoporosis.


A Phase II Multicenter Trial With Rivaroxaban in the Treatment of Livedoid Vasculopathy Assessing Pain on a Visual Analog Scale.
Livedoid vasculopathy is an orphan skin disease characterized by recurrent thrombosis of the cutaneous microcirculation. It manifests itself almost exclusively in the ankles, the back of the feet, and the distal part of the lower legs. Because of the vascular occlusion, patients suffer from intense local ischemic pain. Incidence of livedoid vasculopathy is estimated to be around 1:100,000. There are currently no approved treatments for livedoid vasculopathy, making off-label therapy the only option. In Europe, thromboprophylactic treatment with low-molecular-weight heparins has become widely accepted. The aim of this trial is the statistical verification of the therapeutic effects of the anticoagulant rivaroxaban in patients suffering from livedoid vasculopathy. We performed a therapeutic phase IIa trial designed as a prospective, one-armed, multicenter, interventional series of cases with a calculated sample size of 20 patients. The primary outcome is the assessment of local pain on the visual analog scale (VAS) as an intraindividual difference of 2 values between baseline and 12 weeks. Enrollment started in December 2012 and was still open at the date of submission. The study is expected to finish in November 2014. Livedoid vasculopathy is associated with increased thrombophilia in the cutaneous microcirculation and the continuous use of anticoagulants helps improve the symptoms. The causes of cutaneous infarctions are heterogenous, but ultimately follow the known mechanisms of the coagulation cascade. Rivaroxaban affects the coagulation cascade and inhibits the factor Xa-dependent conversion of prothrombin to thrombin, thereby considerably reducing the risk of thrombosis. Trial Registration EudraCT Number: 2012-000108-13-DE; https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000108-13 (Archived by WebCite at http://www.webcitation.org/6UCktWVCA); German Clinical Trials Register (DRKS): DRKS00004652; https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004652 (Archived by WebCite at http://www.webcitation.org/6UCIAKyCS).


Unraveling the metabolic network of organic acids in solid-state fermentation of Chinese cereal vinegar.
Shanxi aged vinegar (SAV) is fermented by multispecies microorganism with solid-state fermentation (SSF) technology, which contains a variety of organic acids. However, the metabolic network of them in SSF is still unclear. In this study, metagenomics technology was used to reveal the microbial community and functional genes in SAV fermentation. The metabolic network of key organic acids with taste active value higher than 1 was reconstructed for the first time, including acetate, lactate, malate, citrate, succinate, and tartrate. The results show pyruvate is the core compound in the metabolic network of organic acids. Metabolic pathway of acetate plays a pivotal role in this network, and acetate has regulatory function on metabolism of other organic acids. Acetobacter and Lactobacillus are the predominant genera for organic acid metabolism in SSF of SAV. This is also the first report on metabolic network of organic acids in cereal vinegar, adding new knowledge on the flavor substance metabolism during multispecies fermentation of traditional fermented food.


k-t accelerated aortic 4D flow MRI in under two minutes: Feasibility and impact of resolution, k-space sampling patterns, and respiratory navigator gating on hemodynamic measurements.
To assess the performance of highly accelerated free-breathing aortic four-dimensional (4D) flow MRI acquired in under 2 minutes compared to conventional respiratory gated 4D flow. Eight k-t accelerated nongated 4D flow MRI (parallel MRI with extended and averaged generalized autocalibrating partially parallel acquisition kernels [PEAK GRAPPA], R = 5, TRes = 67.2 ms) using four ky -kz Cartesian sampling patterns (linear, center-out, out-center-out, random) and two spatial resolutions (SRes1 = 3.5 × 2.3 × 2.6 mm3 , SRes2 = 4.5 × 2.3 × 2.6 mm3 ) were compared in vitro (aortic coarctation flow phantom) and in 10 healthy volunteers, to conventional 4D flow (16 mm-navigator acceptance window; R = 2; TRes = 39.2 ms; SRes = 3.2 × 2.3 × 2.4 mm3 ). The best k-t accelerated approach was further assessed in 10 patients with aortic disease. The k-t accelerated in vitro aortic peak flow (Qmax), net flow (Qnet), and peak velocity (Vmax) were lower than conventional 4D flow indices by ≤4.7%, ≤ 11%, and ≤22%, respectively. In vivo k-t accelerated acquisitions were significantly shorter but showed a trend to lower image quality compared to conventional 4D flow. Hemodynamic indices for linear and out-center-out k-space samplings were in agreement with conventional 4D flow (Qmax ≤ 13%, Qnet ≤ 13%, Vmax ≤ 17%, P > 0.05). Aortic 4D flow MRI in under 2 minutes is feasible with moderate underestimation of flow indices. Differences in k-space sampling patterns suggest an opportunity to mitigate image artifacts by an optimal trade-off between scan time, acceleration, and k-space sampling. Magn Reson Med 79:195-207, 2018. © 2018 International Society for Magnetic Resonance in Medicine.


Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review.
Influenza is a common respiratory infection that may cause complications, including cardiovascular events. Influenza illness has been shown to double the risk of myocardial infarction, with the highest risk among patients with established cardiovascular disease. Vaccination against influenza has been associated with reductions in myocardial infarction, cerebrovascular disease, and death. To evaluate the evidence for influenza vaccination as a strategy to reduce cardiovascular events specifically in patients with established cardiovascular disease. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched with the terms "influenza vaccine" and "cardiovascular disease". Included in this review were randomized controlled trials (RCTs), nonrandomized studies, and meta-analyses that compared influenza vaccination against control in patients with established cardiovascular disease and that reported clinically meaningful cardiovascular outcomes (defined as cardiovascular death, myocardial infarction, and stroke). The search yielded 10 studies (3 nonrandomized studies, 5 RCTs, and 2 meta-analyses). The nonrandomized studies and the RCTs had inconsistent results with respect to cardiovascular death and adverse cardiovascular events. The 2 meta-analyses, which included the same 4 RCTs involving patients with established cardiovascular disease, showed that the influenza vaccine reduced cardiovascular death by about 50% relative to control. Vaccination also reduced major cardiovascular events by about 43%; the reduction was greater (54%) in the subgroup of patients with recent (≤ 1 year) acute coronary syndrome. However, these data are potentially confounded by small sample sizes, low event rates, and variable outcome reporting. There was also high clinical heterogeneity among the studies, which may not reflect contemporary practice. Given the limitations of these data, it is unclear whether the cardiovascular benefit with influenza vaccination in patients with cardiovascular disease is a true effect. Nevertheless, because of the potential benefit and the low risk of adverse events, the annual influenza vaccine should be recommended for all patients with established cardiovascular disease.


Analysis of acoustic impedance matching in dual-band ultrasound transducers.
Dual-frequency band probes are needed for ultrasound (US) reverberation suppression and are useful for image-guided US therapy. A challenge is to design transducer stacks that achieve high bandwidth and efficiency at both operating frequencies when the frequencies are widely separated with a frequency ratio ∼6:1-20:1. This paper studies the loading and backing conditions of transducers in such stacks. Three stack configurations are presented and analyzed using one-dimensional models. It is shown that a configuration with three layers of material separating the transducers is favorable, as it reduces high frequency ringing by ∼20 dB compared to other designs, and matches the low frequency (LF) transducer to the load at a lower frequency. In some cases, the LF load matching is governed by a simple mass-spring interaction in spite of having a complicated matching structure. The proposed design should yield improved performance of reverberation suppression algorithms. Its suitability for reduction of probe heating, also in single-band probes, should be investigated.


Chitin/chitosan transformation by thermo-mechano-chemical treatment including characterization by enzymatic depolymerization.
Chitosan, the deacetylated derivative of chitin, was until recently produced by hydrolysis in 50% (w/v) NaOH. Application of thermo-mechano-chemical technology to chitin deacetylation was evaluated as an alternative method of chitosan production. This process consists of a cascade reactor unit operating under reduced alkaline conditions of 10% (w/v) NaOH. Prior mercerization of chitin at 4 degrees C for 24 h was required for high deacetylation yields. Sudden decompression of the aqueous alkaline suspension of mercerized chitin resulted in near complete deacetylation of chitin. Reactor residence time was 90 s at 230 degrees C prior to decompression. The chitosan produced was characterized by elemental analysis, (13)C-NMR and enzymatic depolymerization. Enzymatic determination of the degree of acetylation of chitin/chitosan mixtures was also investigated. Relative chitinase and/or chitosanase digestibilities were shown to be strongly dependent on chitin deacetylation. Based on enzymatic digestibilities, the alkaline aqueous high shear process does not appear to produce significant secondary products. Correlation of chitosanase digestibility with percentage of deacetylation provides a simple biological assay to study chitosan composition.


An epistemology for clinical medicine: an argument for reflection on the ends of medical practice and ways of knowing with implications for the selection and training of physician.
Today physicians and scientists have a detailed understanding of human biology and have developed diagnostic and therapeutic tools that were unimaginable a century ago. Yet physicians have provided care and counsel for more than 3000 years. Some, such as Hippocrates and Osler, remain exemplars of the excellent physician. They did not have our scientific knowledge or tools, but they knew something important and performed some task of great value to their patients. What did they know and what did they do? This article explores the questions every ill patient asks, the timeless nature of patient as person, and the forms of non-factual knowing (described as know-how, know-what, know-who, and know-how-it-feels) that are essential to patient care. From this, it is suggested that the combination of understanding, insight, and judgment used for practical action, what Aristotle called "phronesis," is the core competency of excellent physicians which has remained unchanged across the centuries.


Light-triggered nitric oxide release and structure transformation of peptide for enhanced intratumoral retention and sensitized photodynamic therapy.
Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects. Unfortunately, nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements. In this work, we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide (NO) release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy (PDT). The designed nanoparticle is self-assembled from a chimeric peptide monomer, TPP-RRRKLVFFK-Ce6, which contains a photosensitive moiety (chlorin e6, Ce6), a β-sheet-forming peptide domain (Lys-Leu-Val-Phe-Phe, KLVFF), an oligoarginine domain (RRR) as NO donor and a triphenylphosphonium (TPP) moiety for targeting mitochondria. When irradiated by light, the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod, enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation. More importantly, the conversion of generated NO and reactive oxygen species (ROS) in a light-responsive way to peroxynitrite anions (ONOO-) with higher cytotoxicity enables NO to sensitize PDT in cancer treatment. Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently. The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.


Structure of a pre-catalytic spliceosome.
Intron removal requires assembly of the spliceosome on precursor mRNA (pre-mRNA) and extensive remodelling to form the spliceosome's catalytic centre. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae pre-catalytic B complex spliceosome at near-atomic resolution. The mobile U2 small nuclear ribonucleoprotein particle (snRNP) associates with U4/U6.U5 tri-snRNP through the U2/U6 helix II and an interface between U4/U6 di-snRNP and the U2 snRNP SF3b-containing domain, which also transiently contacts the helicase Brr2. The 3' region of the U2 snRNP is flexibly attached to the SF3b-containing domain and protrudes over the concave surface of tri-snRNP, where the U1 snRNP may reside before its release from the pre-mRNA 5' splice site. The U6 ACAGAGA sequence forms a hairpin that weakly tethers the 5' splice site. The B complex proteins Prp38, Snu23 and Spp381 bind the Prp8 N-terminal domain and stabilize U6 ACAGAGA stem-pre-mRNA and Brr2-U4 small nuclear RNA interactions. These results provide important insights into the events leading to active site formation.


Overview of artificial neural network models in the biomedical domain.
The aim of this paper is to provide an overview of artificial neural network (ANN) in biomedical domain and compare it with the logistic regression model. Artificial neural network models and logistic regression models were created and compared using a sample of a modified dataset adapted to the dataset from Framingham Heart Study. R statistical software package is used to create and compare the models. The results indicated that the ANN model is more accurate in classifying the dependent variable than the logistic regression model (84.4 % vs 82.9 %). This paper has shown the effect of artificial neural network models in classifying the survival status (event or non-event) (Tab. 2, Fig. 4, Ref. 29).


[The clinical application of retractorless surgery in patients with hypertensive basal ganglia hemorrhage].
Objective: To discuss the clinical feasibility and practical application of retractorless surgical for patients with hypertensive basal ganglia hemorrhage. Methods: A total of 84 patients underwentretractorless surgery in The First People's Hospital of Huzhou from Jun 2014 to Jun 2016 were retrospectively reviewed.There were 53 male and 31 female of the 84 patients. Their mean age were 58.7 years with range: 29-74 years.Glasgow coma scale score(GCS) at admissionwereas follow: GCS 4-5 points 10 cases(including 3 cases companied dilated pupils), GCS 6-8 points 25 cases, GCS 9-12 points 32 cases, and GCS 13-14 points 17 cases.The average volume of hematoma was 50.2 (30-100) mL.Complications related tosurgery and postoperative activities of daily living (ADL) scorewere analyzed. Results: 0f the 84 cases, there were 76 (90.5%) patientswhose intracranial hematoma were removed more than 90%. Postoperative bleeding was occurred in 6 cases (7.1%), all without secondary surgery. Cerebral infarctionwas occurred in 2 cases (2.4%), subcutaneous effusion associated with infectionwas occurred in 7 cases (8.3%). Postoperative follow-up of 58 cases, 85.3% recovered well. Conclusions: With the proficiency in microneurosurgery methods, retractorless surgery couldreduce the related postoperative complications, such as postoperative cerebral infarction.


Synthesis and hypoglycemic activity of phenacyltriphenylphosphoranes and phosphonium salts.
Phenacyl-riphenylphosphorane (1a) and several analogs substituted in the meta position of the phenacyl group lowered blood glucose levels in 48-hr fasted rats. The corresponding phosphonium salts had comparable hypoglycemic activity. Two compounds (1a and 1b) were also hypoglycemic in fed rats, but hypoglycemia could not be elicited in another species.


Diffuse conduction abnormalities in an adolescent with familial sinus node disease.
We report a case of familial sinus node disease with associated conduction abnormalities in the atrioventricular node and distal conduction system Spontaneous atrial pacemaker activity was absent though the atrium could be depolarized. The pacemaker activity of the heart resided in the atrioventricular junction. The AV node showed impaired automaticity and abnormal conduction properties which partially improved after vagal blockage.


Giant-cell reparative granuloma of the tibia.
Giant-cell reparative granuloma (GCRG) occurs in the jaw, temporal bone, and short tubular bones of the hands and feet. Although GCRG can affect long bones, only small numbers of such cases have been sporadically reported. This report describes a giant-cell reparative granuloma in the proximal tibia in a 60-year-old woman, describes features of GCRG in long bones and reviews the literature. A 60-year-old female patient was referred to us with complaints of moderately tender swelling of the right leg. Whole-body scintigraphic scanning was performed, which incidentally also disclosed a distal femoral lesion. The patient was admitted for surgery and incisional biopsies were performed on both lesions. Pathology analysis of the specimen from the tibia showed new bone lamellae encircled by osteoblasts and multinucleated giant cells which were more numerous in the haemorrhagic regions of the stroma; the latter displayed fibroblasts, histiocytes and inflammatory cells. The specimen from the femoral lesion showed typical features of a benign enchondroma. The patient was readmitted for surgery. The femoral enchondroma was curetted and the cavity was packed with bone graft. The tibial GCRG was treated with marginal resection, autogenous and allogenous bone grafting and intramedullary nailing. Follow-up examination after two years showed no clinical or radiological evidence of a recurrence. Although GCRG is uncommon, it should be considered whenever a lucent, expansile, and possibly destructive lesion of a long bone is encountered. It should be distinguished from true giant cell tumours occurring in the same locations because they have different biologic behaviours.