Detection of Nitric Oxide from Living Cells Using Polymeric Zinc Organic Framework-Derived Zinc Oxide Composite with Conducting Polymer.
Sensitive and selective detection of nitric oxide (NO) in the human body is crucial since it has the vital roles in the physiological and pathological processes. This study reports a new type of electrochemical NO biosensor based on zinc-dithiooxamide framework derived porous ZnO nanoparticles and polyterthiophene-rGO composite. By taking advantage of the synergetic effect between ZnO and poly(TTBA-rGO) (TTBA = 3'-(p-benzoic acid)-2,2':5',2″-terthiophene, rGO = reduced graphene oxide) nanocomposite layer, the poly(TTBA-rGO)/ZnO sensor probe displays excellent electrocatalytic activity and explores to detect NO released from normal and cancer cell lines. The ZnO is immobilized on a composite layer of poly(TTBA-rGO). The highly porous ZnO offers a high electrolyte accessible surface area and high ion-electron transport rates that efficiently catalyze the NO reduction reaction. Amperometry with the modified electrode displays highly sensitive response and wide dynamic range of 0.019-76 × 10-6 m with the detection limit of 7.7 ± 0.43 × 10-9 m. The sensor probe is demonstrated to detect NO released from living cells by drug stimulation. The proposed sensor provides a powerful platform for the low detection limit that is feasible for real-time analysis of NO in a biological system.


Profiling of soil volatile organic compounds after long-term application of inorganic, organic and organic-inorganic mixed fertilizers and their effect on plant growth.
The complexity of soil processes involved in the production, consumption and accumulation of volatile organic compounds (VOCs) makes hard to access the overall dynamics of VOCs in the soil. In this study, the field soil, applied with inorganic (CF), organic (OF) and inorganic-organic mixed (CFOF) fertilizers for ten years was evaluated for the emission of VOCs at different temperature and moisture levels. We identified 30-50 soil emitted VOCs representing the most common soil VOCs groups by using the solid-phase microextraction (SPME) fiber and gas chromatography-mass spectroscopy. The highest total emission of VOCs was found in OF treatment, but it was non-significantly different with CF treatment. The emission of VOCs was significantly increased with the decrease in moisture contents and increase in the temperature of the soil. Among different fertilizer treatments, the emission of VOCs was significantly higher in OF treatment at 5% moisture, and in CF and OF treatments at 35°C. Further, the VOCs emitted from soil treated with CFOF showed the highest increase in plant growth while CF and OF treatments showed similar results. The VOCs were also extracted from the soil using methanol to better understand the dynamics of VOCs. The abundance of VOCs extracted from the soil was 44-61%, while the richness was 65-70% higher than the VOCs emitted from the soil in different treatments. Taken together the results of emitted and extracted VOCs from the soil, we conclude that the fertilizers are able to discriminate among the VOC patterns of soil. In addition, most of the VOCs are retained in the soil and the emission of VOCs from soil depends on the type of VOCs, soil properties and environmental conditions; however, more research is required to find out better soil VOCs analysis methods.


Rhein Ameliorates Cognitive Impairment in an APP/PS1 Transgenic Mouse Model of Alzheimer's Disease by Relieving Oxidative Stress through Activating the SIRT1/PGC-1α Pathway.
Mitochondrial oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recently, antioxidant therapy has been considered an effective strategy for the treatment of AD. Our previous work discovered that rhein relieved mitochondrial oxidative stress in β-amyloid (Aβ) oligomer-induced primary neurons by improving the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha- (PGC-1α-) regulated mitochondrial biogenesis. While encouraging results have been provided, mechanisms underlying the beneficial effect of rhein on AD are yet to be elucidated in vivo. In this study, we evaluated the therapeutic effect of rhein on an APP/PS1 transgenic (APP/PS1) mouse model of AD and explored its antioxidant mechanisms. As a result, rhein significantly reduced Aβ burden and neuroinflammation and eventually ameliorated cognitive impairment in APP/PS1 mice. Moreover, rhein reversed oxidative stress in the brain of APP/PS1 mice and protected neurons from oxidative stress-associated apoptosis. Further study revealed that rhein promoted mitochondrial biogenesis against oxidative stress by upregulating SIRT1 and its downstream PGC-1α as well as nuclear respiratory factor 1. Improved mitochondrial biogenesis not only increased the activity of superoxide dismutase to scavenge excess reactive oxygen species (ROS) but also repaired mitochondria by mitochondrial fusion to inhibit the production of ROS from the electron transport chain. Notably, the exposure of rhein in the brain analyzed by tissue distribution study indicated that rhein could permeate into the brain to exert its therapeutic effects. In conclusion, these findings drive rhein to serve as a promising therapeutic antioxidant for the treatment of AD. Our research highlights the therapeutic efficacy for AD through regulating mitochondrial biogenesis via the SIRT1/PGC-1α pathway.


Two cases of frontotemporal dementia with predominant temporal lobe atrophy.
Frontotemporal dementia (FTD) is a subtype of frontotemporal lobar degeneration, which also includes semantic dementia (SD) and progressive non-fluent aphasia. Frontotemporal dementia is characterized by changes in personality and behavioral abnormalities, generally associated with predominant frontal lobe atrophy. Conversely, SD is typically characterized by Gogi (word meaning) aphasia based on semantic memory impairment and is associated with predominant temporal lobe atrophy. However, in the present cases, we diagnosed FTD on the basis of clinical symptoms, such as disinhibition, indifference, and stereotypy, without semantic memory impairment, even though neuroimaging showed predominant temporal lobe atrophy. We suggest that clinical symptoms are the most important cues for an accurate clinical diagnosis and there is no exclusive relationship between the syndrome and atrophy of the temporal lobes.


Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, protects against gastric ischemia-reperfusion damage in rats: role of oxygen free radicals generation.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a nuclear hormone receptor super family that has recently been implicated in atherosclerosis, inflammation, cancer, infertility, and demyelination. Oxidative stress, neutrophil infiltration, proinflammatory cytokines, and the exhibition of luminal acid play a role in the pathogenesis of gastric injury induced by ischemia-reperfusion. Rosiglitazone, a specific PPAR-gamma ligand, has been shown to have antiinflammatory activity, but its effects on experimental ischemia-reperfusion gastric injury remain unknown. We have investigated the effects of the rosiglitazone on gastric injury caused by ischemia following reperfusion in rats. Tumour necrosis factor-alpha (TNF-alpha) levels and changes in enzymatic activities of myeloperoxidase, as a marker of neutrophils infiltration, xanthine oxidase, superoxide dismutase, and glutathione peroxidase, were determined. Histological analysis of the lesions was also carried out. Pretreatment with 1 or 4 mg/kg of rosiglitazone ameliorated the gastric damage induced by clamping the celiac artery for 30 min followed by 60 min of reperfusion. It significantly (P<0.05) reduced the index of neutrophil infiltration and the levels of the cytokine. Rosiglitazone did not revert the reduced glutathione peroxidase activity but enhanced significantly (P<0.01) the decreased xanthine oxidase and superoxide dismutase activities in gastric mucosa of ischemic rats. In conclusion, rosiglitazone reduces the damage in ischemia-reperfusion gastric injury and alleviates the inflammatory response and the oxidative events.


Utility of initial prehospital end-tidal carbon dioxide measurements to predict poor outcomes in adult asthmatic patients.
To determine if an initial (before treatment) prehospital end-tidal carbon dioxide (EtCO2) measurement in adult, non-chronic obstructive pulmonary disease (COPD), asthmatic patients predicts patient outcomes. This is a retrospective chart review of EtCO2 assessment data in a convenience sample of adult, asthmatic patients transported via advanced life support (ALS) units to a large, urban, academic hospital. Initial EtCO2 measurements were obtained routinely on all respiratory distress patients in the field, and emergency department physicians were unaware of the results. Data were analyzed using descriptive statistics, including percentages, means, and 95% confidence intervals (CI). We reviewed data for prehospital initial EtCO2 measurements on 299 unique asthma patients (repeat visits by same patient were not included). Mean (SD) age was 43.1 years (12.5) and 142 (47.5%) were male. The mean EtCO2 measurement was 38.8 mmHg (SD ± 9.5; CI: 37.7-39.9; range: 14-82). Examination of initial EtCO2 measurements by deciles revealed that extreme values, in the lowest (14-28 mmHg) and highest (50-82 mmHg) deciles, experienced more markers of poor outcome than less extreme measurements. Patients were thus dichotomized by extreme (n = 59) or nonextreme (n = 240) EtCO2 measurements. More extreme patients were ultimately intubated (30.5 vs. 5.8%; p < 0.001; positive predictive value (ppv) = 30.5% ), and/or admitted to the intensive care unit (ICU) (28.8 vs. 6.7%; p <0.001; ppv = 28.8%), and/or died (5.1 vs. 0%; p = 0.007 [Fisher's exact test]; ppv = 5.1%), than nonextreme patients, respectively. Extreme (both low and high) prehospital initial EtCO2 measurements may be associated with markers of poor patient outcomes. Future work will prospectively determine whether the addition of this information improves early recognition of severe asthma episodes beyond clinical assessment.


Viral infections in the intensive care unit.
Serious viral infections requiring intensive care generally occur in immunocompromised patients and in those patients with underlying cardiopulmonary disease. However, occasional cases may occur in normal hosts. This article reviews the serious viral diseases that are commonly encountered in the adult ICU, including viral pneumonia, encephalitis, and hepatitis, and focuses on diagnostic techniques and management principles. A separate section is devoted to cytomegalovirus infection, given the prominent role that this virus plays in the immunocompromised host receiving intensive care.


The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats.
While lipid emulsion may reverse the systemic toxicity of bupivacaine, the pharmacokinetics and tissue distribution of bupivacaine after lipid emulsion infusion are not clear. In this study, we assessed the influence of lipid emulsion administration on the pharmacokinetics and tissue distribution of bupivacaine. Rats in the lipid group were administered IV bupivacaine at the rate of 2 mg·kg(-1)·min(-1) for 4 minutes, and then were treated with an infusion of 30% lipid emulsion at the rate of 3 mL·kg(-1)·min(-1) for 5 minutes; saline was substituted in the control group (n = 6 for pharmacokinetics). We then randomly assigned 100 rats into the lipid group and control group (n = 50 for distribution). The toxicity model and treatment were the same as the pharmacokinetic portion. Plasma and tissues including brain, heart, liver, spleen, lung, kidney, omentum, and muscle were collected. The plasma concentration and tissue content of bupivacaine were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the pharmacokinetics of bupivacaine. All data are shown as mean ± SD. After treatment with the lipid emulsion, t1/2β of bupivacaine in the lipid group was significantly shorter (110 ± 25 minutes vs 199 ± 38 minutes, P = 0.001), the clearance was higher (14 ± 4 mL·mg(-1)·kg(-1) vs 9 ± 4 mL·mg(-1)·kg(-1), P = 0.038), and the t1/2α was longer than that of the control group (4 ± 1 minutes vs 2 ± 1 minutes, P = 0.014); the K12 in the lipid group was less than that of the control group (0.13 ± 0.04 vs 0.32 ± 0.13, P = 0.011). In the lipid group, the bupivacaine content in heart, brain, lung, kidney, and spleen was lower than that in the control group, but higher in the liver at 20, 30, and 45 minutes. The lipid sink phenomenon was observed in this study. The use of a lipid emulsion accelerated the elimination of bupivacaine.


Comparison of Plasma Trace Elements Between 2 Captive Humboldt Penguin (Spheniscus humboldti) Populations.
Environmental pollutants and their effect on wildlife health play an important role in the conservation of endangered species and can be clinically relevant in captive animals too. Data on relevant concentrations of trace elements in captive birds with no known exposures are rare. For this study, silver, arsenic, gold, barium, cadmium, cobalt, chromium, copper, iron, mercury, magnesium, manganese, molybdenum, thallium, selenium, and zinc were measured by inductively coupled plasma mass spectrometry in lithium heparinized plasma samples from 18 Humboldt penguins at 2 zoological collections in Germany. The results showed that the plasma concentrations of silver, arsenic, gold, cadmium, cobalt, chromium, mercury, and selenium differed significantly (P ≤ 0.05) between the 2 penguin collections. The results indicate that the location of the birds has a strong influence on the plasma trace element concentrations. Well water used in the enclosures was suspected to be associated with these significant differences. Trace elemental concentrations in feed (eg, marine fish) and contamination from enclosure construction materials may also play a role. This study could provide a basis for further comparative, biomonitoring, toxicity, and reference interval studies.


DNA repair and evolutionary considerations. A search for a general principle in nuclear biology with use of radiation as a probe.
Three types of DNA repair are known: photoenzymatic repair, excision repair, and tolerance repair (the ability to generate damage-free copies of DNA, which could be not exact copies, from damaged DNA templates). Photoenzymatic repair involves the most simple molecular mechanisms and is the most specific (effective only for pyrimidine dimers) and the most widely distributed among present living organisms, followed by excision repair and then by tolerance repair in order of increasing complexity. It is proposed that these repair systems also evolved in this order after the primordial life was created by solar UV light. Current but fragmentary evidence concerning the molecular and genetic bases of the three types of repair tends to support the idea that the increase in DNA-content needed for the evolution of higher forms from the prokaryotes may have been accompanied by the inherent threat of fragility of the giant DNA molecules, so that the higher forms now possess a greatly increased tolerance capacity. Probably the increase is approximately proportional to their DNA content compared with that of prokaryotes. It is shown theoretically that photoenzymatic and excision repair alone cannot deal with the inherent fragility of giant DNA. The development of tolerance-repair capacity, however, inevitably enhances probability of errors in the repair of DNA damage, leading to the accumulation of misrepair events such as mutation, chromosomal aberration and cancer. It is proposed that DNA repair and misreplication repair are responsible for preventing living organisms from regressing to the randomness-dominated world of the non-living. Living organisms would have evolved slowly along zigzag lines between error and repair of DNA.


Estimation of plasma and urinary hemoglobin by a rate spectrophotometric method.
A method is described for estimating plasma and urinary hemoglobin concentrations as low as 3 mg/L. The assay measures at 528 nm the rate of peroxidation of chlorpromazine by hemoglobin and is not affected by ascorbate and bilirubin concentrations up to 500 mumol/L. Results by this method (mean +/- SD: 54.4 +/- 41.6 mg/L; n = 19) correlated well with those by a scanning spectrophotometric method (52.5 +/- 41.6 mg/L; r = 0.96) and a Coulter Instrument method (r = 0.99; Coulter method: 125 +/- 15 g/L; rate method: 122 +/- 15 g/L; n = 10, r = 0.99). The correlation for assays of 20 plasma samples by our method and a tetramethylbenzidine method was also good (r = 0.95) though the latter gave lower results (31.1 +/- 31.6 mg/L) than the chlorpromazine method (50.9 +/- 41.1 mg/L). The chlorpromazine rate method gave an intra- and interday CV of 7.9% and 9.7%, respectively, at a hemoglobin concentration of 31 mg/L.


[Disease modifying therapies in multiple sclerosis].
The purpose of this section is to introduce the clinical utility of several disease-modifying agents including natalizumab and immunosuppressive treatments that are currently available in Japan, and glatiramer acetate that will be probably available in Japan within a few years. Immunosuppressive therapy has been used to treat multiple sclerosis(MS) for over 30 years based on the hypothesis that MS is a T cell-mediated autoimmune disease. The most commonly used immunosuppressive agents in MS are azathioprine, cyclophosphamide, methotrexate, and mitoxantrone. Like the interferons and glatiramer acetate, immunosuppressive drugs are most efficacious in stages of MS that have an inflammatory component as evidenced by relapses and/or gadolinium-enhancing lesions on MRI or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the CNS. There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. It is appropriate to consider glatiramer acetate for treatment in any patient who has relapsing remitting MS (RRMS), and glatiramer acetate may be helpful in patients with progressive disease. Because of the possibility that natalizumab therapy may be responsible for the increased risk of primary progressive leukoencephalopathy (PML), it is recommended that natalizumab be reserved for use in selected patients with relapsing remitting disease who have failed other therapies either through continued disease activity or medication intolerance, or who have a particularly aggressive initial disease course.


Species traits predict assemblage dynamics at ephemeral resource patches created by carrion.
Carrion is an ephemeral and spatially patchy resource that supports a diverse subset of species linked to nutrient cycling and the decomposition process. A number of studies have separately documented changes in the diversity of plants, arthropods and vertebrates at individual carcasses, but there are few studies that have examined how functional traits of different groups of organisms underpin their responses to carrion patches. We used a carrion addition experiment to compare changes in composition and functional traits of insect and plant assemblages at carcasses compared with control sites. We found that significant changes in insect assemblage evenness and heterogeneity was associated with species' dispersal traits, and that plant assemblage responses to subsequent soil nitrogen changes was most apparent among graminoids and exotic species. Beetles at carcasses were twice as large as their counterparts at control sites during the first week of carrion decomposition, and also had higher wing loadings. Plants with high specific leaf area responded faster to the carcass addition, and twice as many species recolonised the centre of carcasses in exotic-dominated grassland compared with carcasses in native-dominated grassland. These results provide an example of how traits of opportunist species enable them to exploit patchy and dynamic resources. This increases our understanding of how carcasses can drive biodiversity dynamics, and has implications for the way carrion might be managed in ecosystems, such as appropriate consideration of spatial and temporal continuity in carrion resources to promote heterogeneity in nutrient cycling and species diversity within landscapes.


Neural ensemble coding in inferior temporal cortex.
1. Isolated, single-neuron extracellular potentials were recorded sequentially in area TE of the inferior temporal cortex (IT) of two macaque monkeys (n = 58 and n = 41 neurons). Data were obtained while the animals were performing a paired-associate task. The task utilized five stimuli and eight stimulus pairings (4 correct and 4 incorrect). Data were evaluated as average spike rate during experimental epochs of 100 or 400 ms. Single-unit and population characteristics were measured using a form of linear discriminant analysis and information theoretic measures. To evaluate the significance of covariance on population code measures, additional data consisting of simultaneous recordings from < or = 8 isolated neurons (n = 37) were obtained from a third macaque monkey that was passively viewing visual stimuli. 2. On average, 43% of IT neurons were activated by any of the stimuli used (60% if those inhibited also are included). Yet the neurons were rather unique in the relative magnitude of their responses to each stimulus in the test set. These results suggest that information may be represented in IT by the pattern of activity across neurons and that the representation is not sparsely coded. It is further suggested that the representation scheme may have similarities to DNA or computer codes wherein a coding element is not a local parametric descriptor. This is a departure from the V1 representation, which appears to be both local and parametric. It is also different from theories of IT representation that suggest a constructive basis set or "alphabet". From this view, determination of stimulus discrimination capacity in IT should be evaluated by measures of population activity patterns. 3. Evaluation of small groups of simultaneously recorded neurons obtained during a fixation task suggests that little information about visual stimuli is conveyed by covariance of activity in IT when a 100-ms time scale is used as in this study. This finding is consistent with a prior report, by Gochin et al., which used a 1-ms time scale and failed to find neural activity coherence or oscillations dependent on stimuli. 4. Population-stimulus-discrimination capacity measures were influenced by the number of neurons and to some extent the number and type of stimuli. 5. Information conveyed by individual neurons (mutual information) averaged 0.26 bits. The distribution of information values was unimodal and is therefore more consistent with a distributed than a local coding scheme.(ABSTRACT TRUNCATED AT 400 WORDS)


Expanding the knowledge translation metaphor.
Knowledge translation (KT) is a buzzword in modern medical science. However, there has been little theoretical reflection on translation as a process of meaning production in KT. In this paper, we argue that KT will benefit from the incorporation of a more theoretical notion of translation as an entangled material, textual and cultural process. We discuss and challenge fundamental assumptions in KT, drawing on theories of translation from the human sciences. We show that the current construal of KT as separate from and secondary to the original scientific message is close to the now deeply compromised literary view of translation as the simple act of copying the original. Inspired by recent theories of translation, we claim that KT can be more adequately understood in terms of a 'double supplement' - on the one hand, KT offers new approaches to the communication of scientific knowledge to different groups in the healthcare system with the aim of supplementing a lack of knowledge among clinicians (and patients). On the other, it demonstrates that a textual and cultural supplement, namely a concern with target audiences (clinicians and patients), is inevitable in the creation of an 'autonomous' science. Hence, the division between science and its translation is unproductive and impossible to maintain. We discuss some possible implications of our suggested shift in concept by drawing on pharmaceutical interventions for the prevention of HIV as a case. We argue that such interventions are based on a supplementary and paradoxical relation to the target audiences, both presupposing and denying their existence. More sophisticated theories of translation can lay the foundation for an expanded model of KT that incorporates a more adequate and reflective description of the interdependency of scientific, cultural, textual and material practices.


Application of an Asthma Screening Questionnaire in Children with Sickle Cell Disease.
Objective: Asthma in sickle cell disease (SCD) patients is associated with elevated morbidity and mortality. Early detection and initiation of treatment may therefore lead to improved outcome. Utility of an asthma screening questionnaire to identify obstructive airway disease and physician diagnosed asthma in children with SCD at an outpatient setting as an effective, easy-to-administer screening tool has not previously been evaluated in this population. Methods: A previously validated asthma screening questionnaire and spirometry were prospectively administered to 41 SCD children at a routine clinic visit. Results: Prevalence of obstructive airway was 51.2% (n = 21) and physician diagnosis of asthma 33.3% (n = 13). Sensitivity (40%) and specificity (75%) of the questionnaire was poor in detecting obstructive airway disease, but sensitivity (77%), specificity (100%), positive predictive value (100%), and negative predictive value (90%) were high in detecting physician diagnosis of asthma. Conclusion: An asthma screening questionnaire could be a useful tool in identifying at-risk SCD children who may benefit from further management.


Binding of ATP to brain glutamate decarboxylase as studied by affinity chromatography.
The interactions of two forms of porcine brain glutamate decarboxylase (beta-GAD and gamma-GAD) with the effector ATP were studied by affinity chromatography. A third form, alpha-GAD, was only slightly retarded by the affinity matrix and was eluted in the buffer wash. The interaction of GAD with the ATP affinity matrix was qualitatively similar to its interaction with free ATP as reported in previous kinetic studies. The rank order of adenine nucleotides as eluting agents and affinity ligands was ATP greater than ADP greater than AMP. GAD was also eluted by its cofactor, pyridoxal 5'-phosphate, and this was enhanced by 1 mM Pi. In contrast, a high concentration (140 mM) of Pi by itself was required to elute the enzyme. GAD remained active while bound to the affinity column and was eluted in the holoenzyme form by ATP, indicating that the affinity ligand did not bind in the active site and did not displace catalytically active cofactor from the enzyme.


Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.
The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.


PAMAM dendrimers and model membranes: differential scanning calorimetry studies.
Dendrimers attract much attention as potential drug and gene carriers for intracellular delivery. From this point of view, it is crucial to extend our knowledge about their interactions with membranes. The influence of polyamidoamine (PAMAM) dendrimers on the thermotropic behavior of DPPC multilamellar vesicles and DMPC small unilamellar vesicles was examined by differential scanning calorimetry. We used three types of PAMAM dendrimers to determine how a dendrimer structure determines interactions with liposomes. We show that the strength of interactions depends on both the dendrimers' structure and degree of hydrophobicity. A model for the interaction of each type of dendrimer with liposomes was proposed.


Performance Analysis of Segmentation and Classification of CT-Scanned Ovarian Tumours Using U-Net and Deep Convolutional Neural Networks.
Difficulty in detecting tumours in early stages is the major cause of mortalities in patients, despite the advancements in treatment and research regarding ovarian cancer. Deep learning algorithms were applied to serve the purpose as a diagnostic tool and applied to CT scan images of the ovarian region. The images went through a series of pre-processing techniques and, further, the tumour was segmented using the UNet model. The instances were then classified into two categories-benign and malignant tumours. Classification was performed using deep learning models like CNN, ResNet, DenseNet, Inception-ResNet, VGG16 and Xception, along with machine learning models such as Random Forest, Gradient Boosting, AdaBoosting and XGBoosting. DenseNet 121 emerges as the best model on this dataset after applying optimization on the machine learning models by obtaining an accuracy of 95.7%. The current work demonstrates the comparison of multiple CNN architectures with common machine learning algorithms, with and without optimization techniques applied.


Rapid Improvement Following Receipt of Infliximab in Steroid-refractory Durvalumab-Associated Grade 3 Pneumonitis.
Immune checkpoint inhibitors (ICIs) are important novel agents used in advanced non-small cell lung cancer (NSCLC) standard regimens; however, their use increases the risk of immune-related adverse effects (IRAEs). The incidence of IRAE pneumonitis is well documented in ICI use. Corticosteroids continue to be the mainstay of treatment for IRAEs. Here we report one of the first cases of using infliximab to treat durvalumab-associated pneumonitis.


Interaction of gum arabic with fatty acid studied using electron paramagnetic resonance.
Electron paramagnetic resonance (EPR) is here used to study the interaction between gum arabic and a fatty acid. The EPR spectra of 5-doxyl stearic acid (5-DSA), a spin-labeled fatty acid analog, displayed increasingly anisotropic line features upon addition of gum arabic, indicating a strong immobilization of the nitroxyl moiety when the fatty acid is bound to gum arabic. To understand the nature of the interaction, EPR measurements were carried out at different pHs and using two fractions of gum arabic separated by hydrophobic interaction chromatography (HIC). 5-DSA bound favorably to the hydrophobic fraction, which contains mainly glycoprotein, and a small amount of high molecular weight arabinogalactan protein (AGP). Binding occurred to a less extent to the hydrophilic fraction, which contains essentially arabinogalactan (AG). Such a hydrophobic binding mechanism is further supported by a sharp drop in the binding when pH is raised above the pK(a) value of 5-DSA (approximately pH 5). This is because the ionization of carboxylic groups would lead to increased polarity and hydrophilicity of the fatty acid. A secondary effect involving the formation of ionic hydrogen bonds between carboxylic groups in fatty acid and lysine residues in gum arabic might also contribute. This is consistent with the reduction in binding ability when the pH was elevated above the pK(a) value of lysine residue (approximately pH 10). The biological significance of these findings is considered.


Ophthalmic manifestations of MEPAN syndrome.
Mitochondrial enoyl CoA reductase protein-associated neurodegeneration (MEPAN) syndrome is an ultra-rare autosomal recessive disorder caused by loss-of-function mutations in the MECR gene. The syndrome is characterized by dystonia in early childhood, basal ganglia signal abnormalities on MRI, and subsequent optic atrophy, with relative sparing of cognition. We characterize the ophthalmic manifestations observed in a patient with MEPAN syndrome, as a detailed account of ocular findings has not been published to date. Case study of a patient with genetically confirmed MEPAN syndrome, with full ophthalmic evaluation including slit-lamp exam, sensorimotor exam, fundus photography, retinal ocular coherence tomography (OCT), electroretinography, visual evoked potentials, and visual field testing. The patient exhibited decreased visual acuity of 20/150 in both eyes with moderate dyschromatopsia on pseudoisochromatic plate testing, while peripheral vision was largely intact on Goldmann visual field testing. Fundus exam revealed bilateral optic atrophy with pallor most pronounced temporally, corresponding to OCT findings of diffuse retinal nerve fiber layer thinning most prominent in the papillomacular bundle region and severe ganglion cell layer thinning in the maculae. She also displayed a high frequency horizontal end-gaze nystagmus and symmetric bilateral external ophthalmoplegia. The pattern of bilateral optic atrophy in our patient with MEPAN syndrome shows predilection for the papillomacular bundle, similar to that seen in other mitochondrial disorders with optic neuropathy, such as Leber Hereditary Optic Neuropathy and Dominant Optic Atrophy. Our patient's external ophthalmoplegia is another neuro-ophthalmic finding that may be seen in patients with heritable mitochondrial disease, either as an isolated ocular phenotype or within a constellation of systemic manifestations.


The dalhousie family therapy training program: our 6-year experience.
Training in family therapy for general psychiatry residents during their child rotation is either not taught or the objectives not well described in psychiatric curricula. Based on the combined experience of 4 family therapists over a 6 year period with 56 students (psychiatry, social work, psychology), we describe our experience with training general psychiatry residents in an introduction to an interdisciplinary family therapy, systemic-reflective course during their child psychiatry rotation. The model was based on experiential training, where both trainees and supervisors could build skills as they reflect on their process as learners and teachers. Residents' ratings at the end of rotation indicated extremely high satisfaction with the course. We advocate that an experiential interdisciplinary course serving as an introduction to family assessment and systemic/reflective principles are valuable skills that have lasting value to general psychiatry residents.


Effects of El Niño-driven changes in wind patterns on North Pacific albatrosses.
Changes to patterns of wind and ocean currents are tightly linked to climate change and have important implications for cost of travel and energy budgets in marine vertebrates. We evaluated how El Niño-Southern Oscillation (ENSO)-driven wind patterns affected breeding Laysan and black-footed albatross across a decade of study. Owing to latitudinal variation in wind patterns, wind speed differed between habitat used during incubation and brooding; during La Niña conditions, wind speeds were lower in incubating Laysan (though not black-footed) albatross habitat, but higher in habitats used by brooding albatrosses. Incubating Laysan albatrosses benefited from increased wind speeds during El Niño conditions, showing increased travel speeds and mass gained during foraging trips. However, brooding albatrosses did not benefit from stronger winds during La Niña conditions, instead experiencing stronger cumulative headwinds and a smaller proportion of trips in tailwinds. Increased travel costs during brooding may contribute to the lower reproductive success observed in La Niña conditions. Furthermore, benefits of stronger winds in incubating habitat may explain the higher reproductive success of Laysan albatross during El Niño conditions. Our findings highlight the importance of considering habitat accessibility and cost of travel when evaluating the impacts of climate-driven habitat change on marine predators.


Three-dimensional nanostructures formed by single step, two-photon exposures through elastomeric penrose quasicrystal phase masks.
We describe the fabrication of unusual classes of three-dimensional (3D) nanostructures using single step, two-photon exposures of photopolymers through elastomeric phase masks with 5-fold, Penrose quasicrystalline layouts. Confocal imaging, computational studies, and 3D reconstructions reveal the essential aspects of the flow of light through these quasicrystal masks. The resulting nanostructures show interesting features, including quasicrystalline layouts in planes parallel to the sample surfaces, with completely aperiodic variations through their depths, consistent with the optics. Spectroscopic measurements of transmission and reflection provide additional insights.


Therapeutic options in systemic AL amyloidosis.
Systemic amyloid light chain (AL) amyloidosis is a severe disease with unfavourable prognosis. Since the late 1970s different therapeutic modalities in AL amyloidosis have been investigated, trying to prolong survival. This review deals with the therapeutic modalities in AL amyloidosis to date, and highlights future perspectives.


FiTAc-seq: fixed-tissue ChIP-seq for H3K27ac profiling and super-enhancer analysis of FFPE tissues.
Fixed-tissue ChIP-seq for H3K27 acetylation (H3K27ac) profiling (FiTAc-seq) is an epigenetic method for profiling active enhancers and promoters in formalin-fixed, paraffin-embedded (FFPE) tissues. We previously developed a modified ChIP-seq protocol (FiT-seq) for chromatin profiling in FFPE. FiT-seq produces high-quality chromatin profiles particularly for methylated histone marks but is not optimized for H3K27ac profiling. FiTAc-seq is a modified protocol that replaces the proteinase K digestion applied in FiT-seq with extended heating at 65 °C in a higher concentration of detergent and a minimized sonication step, to produce robust genome-wide H3K27ac maps from clinical samples. FiTAc-seq generates high-quality enhancer landscapes and super-enhancer (SE) annotation in numerous archived FFPE samples from distinct tumor types. This approach will be of great interest for both basic and clinical researchers. The entire protocol from FFPE blocks to sequence-ready library can be accomplished within 4 d.


Expression and localization of the vascular endothelial growth factor and changes of microvessel density during hair follicle development of Liaoning cashmere goats.
Vascular endothelial growth factors (VEGFs) play important roles in neovascularization, tissue development, and angiogenesis. In this study, changes in VEGF expression patterns and microvessel density (MVD), and their correlations, were investigated during hair follicle development in epidermal appendages of Liaoning cashmere goats. Polyclonal antibodies to VEGF and microvessels were used for monthly immunohistochemical examinations of normal skin specimens from adult female goats for one year. VEGF was expressed in the hair bulb of primary and secondary hair follicles, the outer and inner root sheaths, sebaceous glands (ductal and secretory portions), eccrine sweat glands (ductal and secretory portions), and the epidermis. Abundant expression of VEGF was observed in the follicular basement membrane zone surrounding the bulb matrix and in ductal and secretory portions of eccrine sweat glands. The change in VEGFs in primary hair follicles showed a bimodal pattern, with the first peak observed from March to May, and the second in August. Maximal expression in secondary hair follicles occurred in May and August. Therefore, VEGF expression in primary and secondary hair follicles is synchronized throughout the year, and is correlated to hair development. In the later telogen and anagen phases, VEGF expression was higher in the secondary, compared to the primary, hair follicle. Changes in MVD also showed a bimodal pattern with peaks in May and August. VEGF expression and MVD showed moderate and strongly positive correlation in the primary and secondary hair follicles, respectively. Therefore, MVD and VEGF are closely related to the processes involved in hair cycle regulation.


Multilevel analysis of temperature dependent near-infrared spectra.
Quantitative spectra-temperature relationship (QSTR) between near-infrared (NIR) spectra and temperature has been used for quantitative determination of the compositions in mixtures. In this work, QSTR is studied using multilevel simultaneous component analysis (MSCA) and the spectral data of the samples with different concentrations measured at different temperatures. MSCA model contains a between-individual model describing the differences between the individuals and a within-individual model capturing the differences within the data of all the individuals. NIR spectra of five different compositions (water-ethanol-isopropanol) measured at seven temperatures were analyzed. A between-temperature model describing the effect of temperature and a within-temperature model describing the variation of concentration were obtained, from which QSTR model is established and quantitative analysis is achieved. Furthermore, the difference between the between-temperature or within-temperature models of different mixtures is used to study the composition of the solvent.


68Ga- and 211At-Labeled RGD Peptides for Radiotheranostics with Multiradionuclides.
Probes for radiotheranostics could be produced by introducing radionuclides with similar chemical characteristics into the same precursors. We recently developed an 211At-labeled RGD peptide and a corresponding radioiodine-labeled RGD peptide. Both labeled peptides accumulated in large quantities in the tumor with similar biodistribution, demonstrating their usefulness for radiotheranostics. In this study, we hypothesized that probes for radiotheranostics combined with multiradionuclides, such as 68Ga and 211At, have useful clinical applications. New radiolabeled RGD peptide probes were synthesized via a molecular design approach, with two labeling sites for metal and halogen. These probes were evaluated in biodistribution experiments using tumor-bearing mice. [67Ga]Ga-DOTA-c[RGDf(4-I)K] ([67Ga]4), Ga-DOTA-[125I]c[RGDf(4-I)K] ([125I]4), and Ga-DOTA-[211At]c[RGDf(4-At)K] ([211At]7) showed similar biodistribution, with high and equivalent accumulation in tumors. These results indicate the usefulness of these probes in radiotheranostics with multiradionuclides, such as a radiometal and a radiohalogen, and they could contribute to a personalized medicine regimen.


Distribution of Facial Exposure to Non-melanoma Biologically Effective UV Irradiance Changes by Rotation Angles.
To show the distribution of facial exposure to non-melanoma biologically effective UV irradiance changes by rotation angles. This study selected the cheek, nose, and forehead as representative facial sites for UV irradiance measurements, which were performed using a rotating manikin and a spectroradiometer. The measured UV irradiance was weighted using action spectra to calculate the biologically effective UV irradiances that cause non-melanoma (UVBEnon-mel) skin cancer. The biologically effective UV radiant exposure (HBEnon-mel) was calculated by summing the UVBEnon-mel data collected over the exposure period. This study revealed the following: (1) the maximum cheek, nose and forehead exposure UVA and UVB irradiance times and solar elevation angles (SEA) differed from those of the ambient UV irradiance and were influenced by the rotation angles; (2) the UV irradiance exposure increased in the following order: cheek < nose < forehead; (3) the distribution of UVBEnon-mel irradiance differed from that of unweighted UV radiation (UVR) and was influenced by the rotation angles and exposure times; and (4) the maximum percentage decreases in the UVBEnon-mel radiant exposure for the cheek, nose and forehead from 0°to 180°were 48.41%, 69.48% and 71.71%, respectively. Rotation angles relative to the sun influence the face's exposure to non-melanoma biologically effective UV.


Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans.
Piwi-interacting RNAs (piRNAs) constitute a class of small RNAs that bind PIWI proteins and are essential to repress transposable elements in the animal germline, thereby promoting genome stability and maintaining fertility. C. elegans piRNAs (21U RNAs) are transcribed individually from minigenes as precursors that require 5' and 3' processing. This process depends on the PETISCO complex, consisting of four proteins: IFE-3, TOFU-6, PID-3, and ERH-2. We used biochemical and structural biology approaches to characterize the PETISCO architecture and its interaction with RNA, together with its effector proteins TOST-1 and PID-1. These two proteins define different PETISCO functions: PID-1 governs 21U processing, whereas TOST-1 links PETISCO to an unknown process essential for early embryogenesis. Here, we show that PETISCO forms an octameric assembly with each subunit present in two copies. Determination of structures of the TOFU-6/PID-3 and PID-3/ERH-2 subcomplexes, supported by in vivo studies of subunit interaction mutants, allows us to propose a model for the formation of the TOFU-6/PID-3/ERH-2 core complex and its functionality in germ cells and early embryos. Using NMR spectroscopy, we demonstrate that TOST-1 and PID-1 bind to a common surface on ERH-2, located opposite its PID-3 binding site, explaining how PETISCO can mediate different cellular roles.


Advocating for Training in End-Of-Life Conversations With Seriously Ill Patients During Residency.
According to section IV.B.1.e of common residency program requirements from the Accreditation Council for Graduate Medical Education (ACGME), "[r]esidents must learn to communicate with patients and families to partner with them to assess their care goals, including, when appropriate, end-of-care [EOL] goals". EOL conversations are frequently appropriate for patients suffering from serious, life-threatening diseases (ie, terminal illness) or otherwise chronic health conditions with poor disease trajectories. These conversations are often followed with services and care from palliative medicine or hospice specialists depending on patients' projected prognoses (ie, 6 months or less). The focus of this patient-centered care, then, is on relieving patient and caregiver suffering, establishing clear treatment goals, and managing the physical, psychosocial, and spiritual burdens of disease. Although palliative medicine and hospice care have been shown to reduce health care costs and improve the overall care of patients who require these services, recent literature still suggests a gap in training programs being able to provide effective, educational strategies to their trainees regarding the appropriate and competent delivery of EOL conversations. Herein, this commentary will provide a discussion on what EOL is, palliative vs hospice care indications, and address current literature regarding EOL exposure within training programs while offering our personal insight and advocacy on the manner.


Expression of CD29 on lymphoma cells and/or CD36 on microvascular endothels correlates with high serum LDH level in diffuse large B-cell lymphomas (DLBCLs) and is frequent in de novo CD5-positive DLBCLs.
Our previous study demonstrated that CD29 and CD36 mRNAs were overexpressed in de novo CD5-positive diffuse large B-cell lymphomas (CD5+ DLBCLs) compared with CD5-negative (CD5-) DLBCLs. CD29 was expressed on lymphoma cells, and CD36 on microvascular endothels. In the present study, we analyzed the clinicopathological significance of CD29 and microvascular CD36 (mvCD36) expression in many cases of DLBCLs. CD29 and CD36 expression was examined by immunohistochemistry on frozen sections of 159 specimens, consisting of 120 cases of CD5-DLBCL, 14 cases of de novo CD5+ DLBCL, 11 cases of follicular lymphoma, 8 cases of mantle cell lymphoma, and 6 cases of reactive lymphoid hyperplasia. Three cases of CD5- intravascular large B-cell lymphomas (IVLs) with hepatic intrasinusoidal infiltration were also examined. CD29+ and/or mvCD36+ DLBCL cases had significantly higher serum LDH levels compared with CD29- mvCD36- DLBCL cases. The number of CD29+ and mvCD36+ cases, and the number of CD29+ or mvCD36+ cases, were significantly higher in de novo CD5+ DLBCLs than in CD5- DLBCLs. The frequencies of CD29 and mvCD36 expression were low in follicular lymphomas, and mvCD36 was negative in reactive lymphoid hyperplasias. Liver biopsies of three IVL cases showed that CD29 was positive on lymphoma cells, and, that CD36 was expressed on hepatic sinusoids. The present study supports the notion that CD29 and/or mvCD36 expression manifests the aggressive feature of a subset of DLBCLs because of its correlation with high serum LDH levels. Furthermore, CD29 and mvCD36 expression should be evaluated in relation to the intravascular growth pattern of lymphoma cells.


Unexpectedly high yield carbon nanotube synthesis from low-activity carbon feedstocks at high concentrations.
We report a new direction for highly efficient carbon nanotube (CNT) synthesis where, in place of conventional highly reactive carbon feedstocks at low concentrations, highly stable carbon feedstocks at high concentrations were shown to produce superior yields. We found that a saturated hydrocarbon that is considered to possess a low reactivity, delivered at high concentrations, could achieve an extremely high growth yield (2.5 times that when using ethylene). This result stems from the unique behavior where the CNT yield linearly increased with carbon concentration, in contrast to more reactive carbon feedstocks, where the yield peaks. We propose that the mechanisms for the growth kinetics for high- and low-reactivity carbon feedstocks are fundamentally different, where the latter benefits from a longer catalyst lifetime because of a relatively low production rate of carbon impurities.


Ethical issues in transfusion medicine: the safety of blood and hematopoietic stem cell donation.
Blood and hematopoietic stem cell donors present special challenges to the transfusion medicine and hematology services. The autologous donor has a personal, vested interest in the donation, but the allogeneic donor is usually donating for altruistic reasons. Our ethical obligation and duty to donors requires that the donor be fully informed of any risks and benefits associated with the donation process. This duty is even more imperative as donors are increasingly exposed to a variety of medications to optimize the production and collection of hematopoietic cells. Transfusion medicine professionals must work to safeguard the health of the donor. The establishment of a national donor registry to collect and analyze short-term and long-term safety data is recommended.


Impact of single amino acid substitution on the structure and function of TANK-binding kinase-1.
Tank-binding kinase 1 (TBK1) is a serine/threonine protein kinase involved in various signaling pathways and subsequently regulates cell proliferation, apoptosis, autophagy, antiviral and antitumor immunity. Dysfunction of TBK1 can cause many complex diseases, including autoimmunity, neurodegeneration, and cancer. This dysfunction of TBK1 may result from single amino acid substitutions and subsequent structural alterations. This study analyzed the effect of substituting amino acids on TBK1 structure, function, and subsequent disease using advanced computational methods and various tools. In the initial assessment, a total of 467 mutations were found to be deleterious. After that, in detailed structural and sequential analyses, 13 mutations were found to be pathogenic. Finally, based on the functional importance, two variants (K38D and S172A) of the TBK1 kinase domain were selected and studied in detail by utilizing all-atom molecular dynamics (MD) simulation for 200 ns. MD simulation, including correlation matrix and principal component analysis, helps to get deeper insights into the TBK1 structure at the atomic level. We observed a substantial change in variants' conformation, which may be possible for structural alteration and subsequent TBK1 dysfunction. However, substitution S172A shows a significant conformational change in TBK1 structure as compared to K38D. Thus, this study provides a structural basis to understand the effect of mutations on the kinase domain of TBK1 and its function associated with disease progression.


[Current status of congenital myasthenic syndromes].
Since Engel reported the first case of congenital myasthenia in 1977 and the first pathogenic gene was found in 1995, knowledge about congenital myasthenic syndromes has continued to grow. Over the years, the pathogenic basis, its clinical features, the phenotype-genotype correlations that have been established and its therapeutic management have all been described. In this group of diseases the safety margin of neuromuscular transmission is altered by different mechanisms: in the synthesis or storage of acetylcholine quanta in the synaptic vesicles, in the calcium-mediated release of acetylcholine in the nerve terminal or in the efficiency of the quantum released to generate a post-synaptic depolarisation. Increased knowledge about them has enabled a number of different therapeutic strategies to be established. In this review the main updates on these syndromes are reported, including: the genes described as classifying 50% of cases, their current classification based on the localisation of the proteins that alter neuromuscular transmission, including a new group of congenital myasthenias, glycosylation disorders, the main key diagnoses and the therapeutic management of this group of under-diagnosed patients.


[Attitudes toward disabilities and mental illness in work settings: a review].
The aim of the present work is to analyse employers' and employees' attitudes towards the job integration of people with mental illness or disability and to highlight the socio-demographic and organizational characteristic that are more significantly associated with such attitudes. We performed PsycINFO, AskERIC and Medline searches for studies published from 1961 to 2002, with key words such as attitudes, stigma, schizophrenia, mental illness, disability, employers, employees, co-workers and supported employment. Our review of the literature showed that the possibility for people with severe mental illness or disability to enter job market is limited by the discriminating attitudes of employers. The socio-demographic and organizational characteristics, which are more significantly associated with employers' more positive attitudes, are: dimension of the company, previous positive contact with people with disability and employers' high educational level. Such information could be useful to identify and, perhaps, select those companies, which can be predicted as more likely to accept people with mental disorders as part of their work force; they could also be used to train job applicants to improve their social skills. Finally such information could be used to plan specific programs to modify attitudes of employees and employers.


Shame and Defectiveness Beliefs in Treatment Seeking Patients With Body Dysmorphic Disorder.
Shame is a distressing emotion experienced when individuals judge themselves in a broadly negative and critical manner. Clinical descriptions of body dysmorphic disorder (BDD) emphasize the centrality of shame, yet research on shame in BDD remains scarce. This study is the largest investigation of shame in clinically diagnosed individuals with BDD, and it is the first to examine whether shame changes with treatment. Eighty-three adults with BDD were treated with 14 weeks of open-label escitalopram. Shame was measured using the Young Schema Questionnaire-Short Form. Shame was significantly higher in individuals with BDD than in previously reported healthy control and psychiatric outpatient samples. Shame was significantly, moderately correlated with greater suicidal thoughts and hopelessness and marginally significantly correlated with greater BDD severity. Shame decreased significantly with treatment. Reductions in shame with escitalopram were significantly associated with reductions in suicidal thoughts and hopelessness, even when accounting for reductions in BDD and depression severity.


Genetic control of the root system in rice under normal and drought stress conditions by genome-wide association study.
A variety of adverse conditions including drought stress severely affect rice production. Root system plays a critical role in drought avoidance, which is one of the major mechanisms of drought resistance. In this study, we adopted genome-wide association study (GWAS) to dissect the genetic basis controlling various root traits by using a natural population consisting of 529 representative rice accessions. A total of 413 suggestive associations, containing 143 significant associations, were identified for 21 root traits, such as maximum root length, root volume, and root dry weight under normal and drought stress conditions at the maturation stage. More than 80 percent of the suggestive loci were located in the region of reported QTLs for root traits, while about 20 percent of suggestive loci were novel loci detected in this study. Besides, 11 reported root-related genes, including DRO1, WOX11, and OsPID, were found to co-locate with the association loci. We further proved that the association results can facilitate the efficient identification of causal genes for root traits by the two case studies of Nal1 and OsJAZ1. These loci and their candidate causal genes provide an important basis for the genetic improvement of root traits and drought resistance.


Neoadjuvant chemotherapy with low dose of pegylated liposomal doxorubicin plus weekly paclitaxel in operable and locally advanced breast cancer.
To determine the activity and safety of a schedule with a low dose of pegylated liposomal doxorubicin (PLD) and weekly paclitaxel in operable and locally advanced breast cancer patients. Thirty-five patients with histologically confirmed, operable, and locally advanced breast cancer entered the study. The median age was 59 years (range 31-74 years). The schedule was biweekly PLD at the dose of 15 mg/m for four administrations and weekly paclitaxel at the dose of 80 mg/m for eight administrations. All patients were evaluable for response and toxicity. Twenty-six patients responded (74%): three (8%) had a complete response and 23 (66%) had a partial response, seven (23%) remained stable, and one experienced progression (3%). Fifteen of 27 operable patients (55%) underwent conservative surgery. Three patients (9%) had a pathological complete response and the disappearance of infiltrating disease was documented in three other patients. The main toxicity was hand-foot syndrome (grade 3 in four patients; 11%). Other nonhematological grade 3 toxicities included stomatitis in three patients (8%) and liver toxicity in one patient (3%). Grade 3-4 neutropenia was documented in another three patients and dose reduction was necessary in two patients. The fourth administration of PLD was suspended in four patients for grade 2-3 hand-foot syndrome. No symptoms were related to impairment of cardiac function and no death related to toxicity occurred. The combination of biweekly PLD and weekly paclitaxel was active in operable and locally advanced breast cancer with a manageable safety profile.


Population frequency of the arylsulphatase A pseudo-deficiency allele.
The enzymatic diagnosis of metachromatic leukodystrophy is complicated by the frequent occurrence of the pseudo-deficiency of arylsulphatase A (ASA) enzyme activity. An A to G nucleotide transition in the first polyadenylation signal of the ASA gene results in the loss of its major mRNA species and a greatly reduced level of enzyme activity. This nucleotide change (nucleotide 1620 of the ASA cDNA) is the cause of ASA pseudo-deficiency and is closely linked to another A to G transition (nucleotide 1049), within the ASA gene, which changes Asn350 to serine but which does not affect ASA activity. The distribution of these 2 nucleotide changes has been investigated in 73 unrelated individuals from the Australian population. The two transitions were found together on 14 (9.6%) out of 146 chromosomes. The transition at nucleotide 1620 was not found alone; however, the other transition was found alone on 7 (4.8%) out of the 146 chromosomes. The carrier frequency of the ASA pseudo-deficiency mutation in Australia is thus estimated to be about 20%.


Papertronics: Marriage between Paper and Electronics Becoming a Real Scenario in Resource-Limited Settings.
Integrating electronic applications with paper, placed next to or below printed images or graphics, can further expand the possible uses of paper substrates. Consuming paper as a substrate in the field of electronics can lead to significant innovations toward papertronics applications as paper comprises various advantages like being disposable, inexpensive, biodegradable, easy to handle, simple to use, and easily available. All of these advantages will definitely spur the advancement of the electronics field, but unfortunately, putting electronics on paper is not an easy task because, compared to plastics, the paper surface is not just rough but also porous. For example, in the case of lateral flow assay testing the sensor response is delayed if the pore size of the paper is enormous. This might be a disadvantage for most electrical devices printed directly on paper. Still, some methods make it compatible when fit with a rough, absorbent surface of the paper. Building electronic devices on a standard paper substrate have sparked much interest because of its lightweight, environmental friendliness, minimal cost, and simple fabrication. A slew of improvements have been achieved in recent years to make paper electronics perform better in various applications, including transistors, batteries, and displays. In addition, flexible electronics have gained much interest in human-machine interaction and wireless sensing. This review briefly examines the origins and fabrication of paper electronics and then moves on to applications and exciting possible paths for paper-based electronics.


Growth-inhibitory effects of MOB2 on human hepatic carcinoma cell line SMMC-7721.
To investigate the growth-inhibiting and apoptosis-inducing effects of the gene MOB2 on human hepatic carcinoma cell line SMMC-7721. The full-length cDNA of the MOB2 gene was amplified from human umbilical vein endothelial cells. The correct full-length MOB2 cDNA was subcloned into the eukaryotic expression vector pEGFP-C1. After lipofection of the MOB2 gene into cancer cells, the levels of MOB2 protein in the cancer cells were detected by immunoblotting. To transfect the recombined plasmid vector pEGFP-CI-MOB2 into SMMC-7721 cells, the cells were cultured in Dulbecco's Modified Eagle's Medium with 10% fetal calf serum and glutamine, and then mixed with liposomes, Lipofectamine 2000 and the plasmid vector pEGFP-CI-MOB2. We observed the growth and proliferation of SMMC-7721 cells containing pEGFP-CI-MOB2 and analyzed their apoptosis and growth cycle phases by flow cytometry. We successfully transfected the recombined plasmid vector pEGFP-CI-MOB2 into SMMC-7721 cells and screened for a single clone cell containing MOB2. After transfection, MOB2 enhanced growth suppression, induced apoptosis, increased the ratio of G0/G1, significantly inhibited the advance of cell cycle phase, and arrested cells in G0/G1 phase. MOB2 overexpression induces apoptosis and inhibits the growth of human hepatic cancer cells, which may be useful in gene therapy for hepatic carcinoma.


Moderate-to-severe traumatic brain injury.
Managing patients with moderate-to-severe traumatic brain injury (TBI), particularly those with combat-related blast injury, is exceptionally challenging. Optimal care requires the coordinated efforts of numerous providers, contributing to an interdisciplinary team. Given the complexities of TBI and the variety of physiologic, physical, cognitive, behavioral, and emotional manifestations of the injury, a holistic approach to patient care is needed throughout the entire continuum of care. In this article, the authors provide an overview of how interdisciplinary care is provided from the acute to the chronic settings, and illustrate the important role that rehabilitation plays throughout the continuum of care in facilitating maximizing recovery, functional independence, and quality of life. Common conditions associated with TBI are illustrated through a case presentation of an individual with blast-related polytrauma and help to frame a more detailed discussion of subtopics including neurointensive care, posttraumatic seizures, venous thromboembolic disease prevention, spasticity management, vestibular disorders, endocrine dysfunction, and psychological trauma.


Real-time concentration monitoring in microfluidic system via plasmonic nanocrescent arrays.
In this work, on-chip bio/chemical sensor was reported based on localized surface plasmon resonance of nanocrescent patterns fabricated via electron beam lithography. The nanocrescent arrays with different dimensional features exhibited controllable plasmonic properties in accordance with the simulation results based on the finite-difference time-domain model. The highest refractive index sensitivity of the fabricated samples was achieved to be ~699.2 nm/RIU with a figure of merit of ~3.1 when the two opposite crescents own a gap of ~43.3 nm. Such obtained plasmonic sensor was further integrated into the microfluidic system which can simply control the specific analyte concentrations via tuning the flow rate ratios between two injecting microstreams. Our method has successfully demonstrated the capability of the nanocrescent patterns as on-chip plasmonic bio/chemical sensor for real-time monitoring of dynamic concentrations in the microchannel.


[PREFERENCES OF PARENTS FOR PEDIATRIC INPATIENT WARD PHYSICIAN'S ATTIRE].
The preferred attire for physicians has not been defined to date. In Israel, where casual attire is acceptable in most circumstances, patients' preferences have not yet been systematically evaluated. This is a cross-sectional study that was designed to evaluate parents' preferences for physicians' attire in a pediatric inpatient ward. A volunteer was dressed in four types of clothes sets: elegant attire, sportive attire, careless attire and scrubs - all of which were displayed, with or without a white coat. Parents were asked whether or not they felt the physician was an important component of the medical encounter; they were also asked to choose the picture of the doctor they preferred to care for their child. A total of 250 parents participated in the study; 68% of the parents believe that the physician's attire is an important component of the medical encounter; 41% of the parents preferred the doctor to wear scrubs with a white coat, 22% preferred scrubs without a white coat. Careless attire was the least preferred attire. The physicians' attire was important for most of the participants. We recommend that doctors in inpatient wards wear scrubs.


Magnitude and determinants of multimorbidity and health care utilization among patients attending public versus private primary care: a cross-sectional study from Odisha, India.
Multimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings. We undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits. The overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1-1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1-2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1-2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0-2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6-4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1-3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13-2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01-3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals. Our findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.


Odontogenic tumors: analysis of 706 cases.
From a total of 54,534 oral biopsy specimens, 706 (1.3%) odontogenic tumors were retrieved and reviewed. Odontomas comprised more than 65% of the odontogenic tumors, ameloblastomas about 10%, and the remaining six categories of odontogenic tumors accounted for approximately 25% of the lesions. The distribution by age, sex, and location of these tumors generally supported the data from other previously reported cases. A possible variant of the calcifying epithelial odontogenic tumor was described, and instances of two granular cell ameloblastic fibromas were reported. The myxomas as a group were characterized histologically more by residual bony trabeculae than by the presence of odontogenic rests. Because the clinical, histological, and behavioral features of the ameloblastic fibroma and ameloblastic fibro-odontoma were similar, these lesions were considered to be essentially the same. From limited follow-up information, the ameloblastoma was the only lesion that recurred. With the exception of one ameloblastoma found in the lung, no malignant odontogenic tumors were encountered.


COVID-19: an opportunity of systematic integration for Chagas disease. Example of a community-based approach within the Bolivian population in Barcelona.
As a Neglected Tropical Disease associated with Latin America, Chagas Disease (CD) is little known in non-endemic territories of the Americas, Europe and Western Pacific, making its control challenging, with limited detection rates, healthcare access and consequent epidemiological silence. This is reinforced by its biomedical characteristics-it is usually asymptomatic-and the fact that it mostly affects people with low social and financial resources. Because CD is mainly a chronic infection, which principally causes a cardiomyopathy and can also cause a prothrombotic status, it increases the risk of contracting severe COVID-19. In order to get an accurate picture of CD and COVID-19 overlapping and co-infection, this operational research draws on community-based experience and participative-action-research components. It was conducted during the Bolivian elections in Barcelona on a representative sample of that community. The results show that 55% of the people interviewed had already undergone a previous T. cruzi infection screening-among which 81% were diagnosed in Catalonia and 19% in Bolivia. The prevalence of T. cruzi infection was 18.3% (with 3.3% of discordant results), the SARS-CoV-2 22.3% and the coinfection rate, 6%. The benefits of an integrated approach for COVID-19 and CD were shown, since it only took an average of 25% of additional time per patient and undoubtedly empowered the patients about the co-infection, its detection and care. Finally, the rapid diagnostic test used for COVID-19 showed a sensitivity of 89.5%. This research addresses CD and its co-infection, through an innovative way, an opportunity of systematic integration, during the COVID-19 pandemic.


A comparison of views regarding the use of de-identified data.
Data sharing of large genomic databases and biorepositories provides researchers adequately powered samples to advance the goals of precision medicine. Data sharing may also introduce, however, participant privacy concerns including possible reidentification. This study compares views of research participants, genetic researchers, and institutional review board (IRB) professionals regarding concerns about the use of de-identified data. An online survey was completed by cancer patients, their relatives, and controls from the Northwest Cancer Genetics Registry (n = 450) querying views about potential harms with the use of de-identified data. This was compared to our previous online national survey of human genetic researchers (n = 351) and IRB professionals (n = 208). Researchers were less likely to feel that participants would be personally identified or harmed from a study involving de-identified data or feel that a federal agency might compel researchers to disclose information about research participants. Compared to genetic researchers, IRB professionals and participants were significantly more likely to express that personal identification or harm was likely or that researchers might be forced to disclose information by a federal agency. An understanding of the differences in views regarding possible harm from the use of de-identified data between these three important stakeholder groups is necessary to move forward with genomic research.


Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity.
Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory properties compared with resident tissue ATMs. Using a dye (PKH26) to pulse label ATMs in vivo, we purified macrophages recruited to white adipose tissue during a high-fat diet. Comparison of gene expression in recruited and resident ATMs using real-time RT-PCR and cDNA microarrays showed that recruited ATMs overexpress genes important in macrophage migration and phagocytosis, including interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and C-C chemokine receptor 2 (CCR2). Many of these genes were not induced in ATMs from high-fat diet-fed CCR2 knockout mice, supporting the importance of CCR2 in regulating recruitment of inflammatory ATMs during obesity. Additionally, expression of Apoe was decreased, whereas genes important in lipid metabolism, such as Pparg, Adfp, Srepf1, and Apob48r, were increased in the recruited macrophages. In agreement with this, ATMs from obese mice had increased lipid content compared with those from lean mice. These studies demonstrate that recruited ATMs in obese animals represent a subclass of macrophages with unique properties.


Gilles de la Tourette's syndrome in twins: clinical and neurochemical data.
A pair of identical twins (probability of monozygosity by genetic marking = 99.99%) with Gilles de la Tourette's syndrome (GTS) were studied clinically and neurochemically. The two boys were distinguished within the family by dramatic differences in their behavior and tics. Twin 1 had severe motor tics, loud vocalizations, coprolalia, and school behavior problems, whereas twin 2 was only mildly affected. Neither boy had ever been treated with medication for his tic disorder. Lumbar puncture was performed on each after a night of bed rest. In spite of the marked clinical differences between the two boys, the major indices of dopamine and serotonin turnover in the cerebrospinal fluid were equivalent. Homovanillic acid levels were 65 and 60 ng/ml, respectively, and 5-hydroxyindoleacetic acid levels were 36 and 39 ng/ml. Observation of these twins suggests that the phenotypic expression of GTS relates to more factors than inheritance. Neurochemical metabolites of dopamine and serotonin did not reflect the comparative clinical severity of GTS in these boys.


Spiritual well-being, religiosity, hope, depression, and other mood states in elderly people coping with cancer.
To determine the relationships among spiritual well-being, religiosity, hope, depression, and other mood states in elderly people coping with cancer and if differences in hope, depression, and other mood states exist between those elderly with high and low intrinsic religiosity and spiritual well-being. Descriptive correlational and descriptive comparison. Acute care units of two hospitals located in the midwestern United States. 100 elderly people with diagnosis of cancer and a mean age of 73 years. Thirty-three of the subjects were male, and 67 were female. Sixty-two percent had either lung, breast, or colon cancer. Each subject was administered an intrinsic and extrinsic religiosity index, a spiritual well-being scale, a geriatric depression scale, the Miller hope scale, and the Profile of Mood States scale. Spiritual well-being, religiosity, hope, depression, and mood. A consistent positive correlation was found among intrinsic religiosity, spiritual well-being, hope, and other positive mood states. A consistent negative correlation among intrinsic religiosity, depression, and other negative mood states existed. Analysis of variance indicated that significantly higher levels of hope and positive moods existed in elderly patients with high levels of intrinsic religiosity and spiritual well-being. Intrinsic religiosity and spiritual well-being are associated with hope and positive mood states in elderly people coping with cancer. Nurses must assess and support intrinsic religiosity and promote spiritual well-being in elderly people coping with cancer.


Endothelin type A receptor (ETA) expression is regulated by HOXA10 in human endometrial stromal cells.
Endothelin type A receptor (ET(A)) is a member of the superfamily of G protein-coupled receptors. Our laboratory conducted a microarray screen that identified ET(A) as target of HOXA10 transcriptional control in endometrium. Here, we confirm HOXA10-regulated ET(A) expression in endometrium. Endometrial biopsies were obtained from fertile reproductive-age individuals, and first trimester decidual samples were obtained at the time of elective termination. Immunohistochemistry (IHC) was used to identify ET(A) protein in endometrium as well as first trimester decidua. ET(A) was expressed in endometrial stromal cells throughout the menstrual cycle. ET(A) was also highly expressed in first trimester decidual cells. The regulatory relationship between HOXA10 and ET(A) was established by transient transfection analysis. The human endometrial stromal cell line (HESC) and the human endometrial epithelial cell line (Ishikawa) were transfected with pcDNA/HOXA10, HOXA10 small interfering RNA (siRNA), or respective controls. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to determine expression levels of HOXA10 and ET(A) in each group. ET(A) gene expression increased 9-fold (P < .05) after pcDNA/HOXA10 transfection of HESC. ET(A) was not regulated by HOXA10 in Ishikawa cells. We conclude that ET(A) is expressed in normal endometrium and decidua. Expression of this receptor is regulated by an essential mediator of endometrial receptivity, HOXA10. ET(A) may enhance the proliferative potential of endometrial cells in a manner similar to that seen in vascular smooth muscle cells. ET( A) likely acts as a molecular mechanism by which HOXA10 promotes stromal cell growth and prostaglandin production in both the implantation window and decidua.


A Microfluidic Strategy for Controllable Generation of Water-in-Water Droplets as Biocompatible Microcarriers.
Droplet microfluidics has been widely applied in functional microparticles fabricating, tissue engineering, and drug screening due to its high throughput and great controllability. However, most of the current droplet microfluidics are dependent on water-in-oil (W/O) systems, which involve organic reagents, thus limiting their broader biological applications. In this work, a new microfluidic strategy is described for controllable and high-throughput generation of monodispersed water-in-water (W/W) droplets. Solutions of polyethylene glycol and dextran are used as continuous and dispersed phases, respectively, without any organic reagents or surfactants. The size of W/W droplets can be precisely adjusted by changing the flow rate of dispersed and continuous phases and the valve switch cycle. In addition, uniform cell-laden microgels are fabricated by introducing the alginate component and rat pancreatic islet (β-TC6) cell suspension to the dispersed phase. The encapsulated islet cells retain high viability and the function of insulin secretion after cultivation for 7 days. The high-throughput droplet microfluidic system with high biocompatibility is stable, controllable, and flexible, which can boost various chemical and biological applications, such as bio-oriented microparticles synthesizing, microcarriers fabricating, tissue engineering, etc.


Proteolysis of truncated hemolysin A yields a stable dimerization interface.
Wild-type and variant forms of HpmA265 (truncated hemolysin A) from Proteus mirabilis reveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structure via the implementation of on-edge main-chain hydrogen bonds donated by residues 243-263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formed via main-chain hydrogen bonds donated by residues 203-215 of adjacent monomers, and a previously unobserved tetramer is formed. In addition, an eight-stranded antiparallel β-sheet is formed from the flap regions of crystallographically related monomers in the high-salt structures. This new interface is possible owing to additional proteolysis of these variants after Tyr240. The interface formed in the high-salt crystal forms of hemolysin A variants may mimic the on-edge β-strand positioning used in template-assisted hemolytic activity.


Differential resistance among host and non-host species underlies the variable success of the hemi-parasitic plant Rhinanthus minor.
Rhinanthus minor is a root hemiparasitic plant that attacks a wide range of host species which are severely damaged by the parasite. Rhinanthus minor also attempts unsuccessfully to form connections to a range of non-hosts which in contrast are not damaged by the parasite; however, the underlying physiological basis of these differences is not fully understood. Biomass of host-parasite combinations was studied, and histology, electron microscopy and FT-IR microspectroscopy were used to determine the cellular-level interactions between Rhinanthus haustoria (the parasite's connective structure) and the roots of a range of potential host species. Two distinct defence responses were observed in the non-host forbs Plantago lanceolata and Leucanthemum vulgare. Firstly, L. vulgare was able to encapsulate the parasite's invading structures preventing it from gaining access to the stele. This was supported by FT-IR microspectroscopy, used to monitor lignification in response to Rhinanthus haustoria. Secondly, host cell fragmentation was observed at the interface between the parasite and P. lanceolata. Growth data confirmed the non-host status of the two forbs whilst, in contrast, grasses and a legume which were good hosts showed no evidence of defence at the host/parasite interface. Variable resistance to Rhinanthus is shown for the first time to be controlled by cellular-level resistance to haustoria by either cell fragmentation or lignification at the host/parasite interface.


IMPACT OF MOTOR ACTIVITY ON THE DYNAMICS OF INTELLECTUAL WORKING CAPACITY AND MENTAL COGNITIVE PROCESSES IN STUDENTS.
The aim: To study the impact of physical exercises of different intensity on the dynamics of intellectual working capacity and mental cognitive processes in students. Materials and methods: The research involved 293 students. The research was conducted in 2 stages. The 1st stage involved the study of the level of intellectual activity of students with sufficient (the experimental group, n = 76) and insufficient levels of their motor activity (the control group, n = 217). The 2nd stage provided for the determination of the dynamics of intellectual activity indicators in students (n = 76) before and after physical exercises of different intensity. Results: It was found that students with sufficient motor activity are characterized by significantly better indicators of intellectual working capacity and mental cognitive processes than students with insufficient motor activity. It was found that low-intensity physical exercises of a recreational nature had a more positive effect on intellectual working capacity in the course of training sessions. Conclusions: Organized motor activity and optimal physical exertion both during and after the end of intellectual functioning can directly affect the preser¬vation and improvement of students' intellectual working capacity.


An update on Fanconi anemia: Clinical, cytogenetic and molecular approaches (Review).
Fanconi anemia is a genetic syndrome clinically characterized by congenital malformations that affect several human systems, leads to progressive bone marrow failure and predisposes an individual to cancer, particularly in the urogenital area as well as the head and neck. It is commonly caused by the biallelic compromise of one of 22 genes involved in the FA/BRCA repair pathway in most cases. The diagnosis is based on clinical suspicion and confirmation using genetic analysis, where the chromosomal breakage test is considered the gold standard. Other diagnostic methods used include western blotting, multiplex ligation-dependent probe amplification and next-generation sequencing. This genetic condition has variable expressiveness, which makes early diagnosis difficult in certain cases. Although early diagnosis does not currently allow for improved cure rates for this condition, it does enable healthcare professionals to perform a specific systematic follow-up and, if indicated, a bone marrow transplantation that improves the mobility and mortality of affected individuals. The present review article is a theoretical revision of the pathophysiology, clinical manifestations and diagnosis methods intended for different specialists and general practitioners to improve the diagnosis of this condition.


[Efficiency of cycloferon and reamberin combination at the treatment of the patients with chronic sepsis].
The cytokine profile of blood (CPB) at the patients with chronic sepsis (CS) streptococcus or mixed (by a streptococcus and to staphylococcus etiology) was studied. To beginning of the treatment at intensifying of CS at the patients was detected the substantial increase of maintenance of proinflammatory (IL - 1β, IL - 2, IL - 6, TNF -α) cytokines (CК) in the blood serum at the moderate increase of antiinflammatory CK (IL-4). Thus, indexes, characterizing correlation pro- and antiinflammatory CК was rate, that testified to predominating of proinflammatory potencies of blood. Application in the complex treatment of the patients with CS combination of modern detoxic preparation reamberin and immunoactive preparation cycloferon promotes normalizations of CK maintenance in the blood and betweennesss by them. In a clinical plan the use of the reamberin and cycloferon combination provided acceleration of CS intensifying liquidation. Finding allow to consider pathogenetic reasonable and clinically perspective application of this preparations combination in treatment of the patients with CS.


Endothelial PI 3-kinase activity regulates lymphocyte diapedesis.
Lymphocyte recruitment to sites of inflammation involves a bidirectional series of cues between the endothelial cell (EC) and the leukocyte that culminate in lymphocyte migration into the tissue. Remodeling of the EC F-actin cytoskeleton has been observed after leukocyte adhesion, but the signals to the EC remain poorly defined. We studied the dependence of peripheral blood lymphocyte transendothelial migration (TEM) through an EC monolayer in vitro on EC phosphatidylinositol 3-kinase (PI 3-kinase) activity. Lymphocytes were perfused over cytokine-activated EC using a parallel-plate laminar flow chamber. Inhibition of EC PI 3-kinase activity using LY-294002 or wortmannin decreased lymphocyte TEM (48 +/- 6 or 34 +/- 7%, respectively, vs. control; mean +/- SE; P < 0.05). Similarly, EC knockdown of the p85alpha regulatory subunit of PI 3-kinase decreased lymphocyte transmigration. Treatment of EC with jasplakinolide to inhibit EC F-actin remodeling also decreased lymphocyte TEM to 24 +/- 10% vs. control (P < 0.05). EC PI 3-kinase inhibition did not change the strength of lymphocyte adhesion to the EC or formation of the EC "docking structure" after intercellular adhesion molecule-1 ligation, whereas this was inhibited by jasplakinolide treatment. A similar fraction of lymphocytes migrated on control or LY-294002-treated EC and localized to interendothelial junctions. However, lymphocytes failed to extend processes below the level of vascular endothelial (VE)-cadherin on LY-294002-treated EC. Together these observations indicate that EC PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier.


Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas.
Histological evidence suggests that insulin-producing beta (beta)-cells arise in utero from duct-like structures of the fetal exocrine pancreas, and genetic lineage tracing studies indicate that they are maintained in the adult by self-renewal. These studies have not addressed the origin of the new beta-cells that arise in large numbers shortly after birth, and contradictory lineage tracing results have been published regarding the differentiation potential of duct cells in this period. We established an independent approach to address this question directly. We generated mice in which duct and acinar cells, comprising the exocrine pancreas, can be genetically marked by virtue of their expressing the mucin gene Muc1. Using these mice, we performed time-specific lineage tracing to determine if these cells undergo endocrine transdifferentiation in vivo. We find that Muc1+ cells do give rise to beta-cells and other islet cells in utero, providing formal proof that mature islets arise from embryonic duct structures. From birth onwards, Muc1 lineage-labeled cells are confined to the exocrine compartment, with no detectable contribution to islet cells. These results argue against a significant contribution by exocrine transdifferentiation to the normal postnatal expansion and maintenance of beta-cell mass. Exocrine transdifferentiation has been proposed to occur during injury and regeneration, and our experimental model is suited to test this hypothesis in vivo.


Surgical Scales: Primary Closure versus Gastric Resection for Perforated Gastric Ulcer - A Surgical Debate.
Perforated gastric ulcer is one of the most life-threatening complications of peptic ulcer disease with high morbidity and mortality rates. The surgical strategy for gastric perforation in contrast with duodenal perforations often requires consilium and intraoperative debates. The subject of the debate is a 59-year-old male patient who presented with perforated giant gastric ulcer complicated by generalized peritonitis and severe sepsis. The debate is based on a systematized table dividing all factors into three groups and putting them on surgical scales. Pathology-related factors influencing the decision-making are size and site of perforation, local tissue inflammation, signs of malignancy, simultaneous complications of peptic ulcer, peritonitis, and sepsis. Besides these factors, patient- and healthcare-related factors should also be considered.


Pregnancy-associated polyuria in familial renal glycosuria.
A pregnant woman presented at gestational week 28 with loss of consciousness and profound polyuria. Further characterization revealed osmotic diuresis due to massive glycosuria without hyperglycemia. Glycosuria reduced substantially postpartum, from approximately 100 to approximately 30 g/1.73 m2 per day. DNA sequencing analysis of the SLC5A2 gene encoding the renal glucose transporter SGLT2 showed a homozygous frame-shift mutation (occurring after the glutamine at amino acid 168 and leading to premature termination of the protein at amino acid 186) diagnostic of familial renal glycosuria. Pregnant women with familial renal glycosuria can be at risk of profound polyuria during pregnancy due to the associated increase in glycosuria. These findings also have implications for the use of SGLT2 inhibitors in clinical practice.


Hylan GF-20 Viscosupplementation in the Treatment of Symptomatic Osteoarthritis of the Knee: Clinical Effect Survivorship at 5 Years.
Controversies remain surrounding the choice of hyaluronic acid products and patient selection. A study was conducted to report the long-term survivorship of intra-articular injection effect of high molecular weight hyaluronic preparation hylan GF-20 (Synvisc-One) for patients with symptomatic knee osteoarthritis. A retrospective observational analysis of a single therapeutic series was carried out. The analysis was conducted to determine therapeutic effect survivorship taking arthroplasty and any other surgical interventions as endpoint results. Seventy-seven consecutive patients (82 knees) were followed up for five years. At one-year follow-up, 71 knees (87%) responded to treatment and only 8 knees (10%) were offered arthroplasty due to persistence of symptoms. At five-year follow-up, 41 (50%) were still considered responders. During the study period, repeat injection was given in 9 knees (11%). Arthroplasty (either total or unicompartmental) was required in 26 (31%). Kaplan-Meier survivorship analysis of therapeutic effect demonstrated 67% survival at 5 years with arthroplasty as endpoint and 58% survival at 5 years with all secondary interventions as endpoint. This study demonstrates a significantly longer duration of clinical benefit of hylan GF-20 injection. Present results may suggest a notion of an ideal delay therapeutic strategy for patients not ready to receive an arthroplasty. Further studies will be required to help characterise these subsets of patients.