Integration of bioconversion and downstream processing: starch hydrolysis in an aqueous two-phase system.
Integration of bioconversion and the first step(s) of down stream processing can be used as a means to increase the productivity of bioprocesses. This integration also gives the possibility to run the bioconversion in a continuous mode. We demonstrate the use of an aqueous two-phase system in combination with ultrafiltration to accomplish this. Conversion of native starch to glucose by alpha-amylase and glucoamylase was carried out in an aqueous two-phase system in connection with a membrane filtration unit. In this way, a continuous stream of glucose in buffer solution was obtained; the phase-forming polymers as well as the starch-degrading enzymes were recycled, and clogging of the ultrafiltration membrane was avoided. The process was carried out continuously in a mixer-settler reactor for a period of 8 days. The enzyme activities in the top and bottom phases and in the mixing chamber were monitored intermittently throughout the experiment. The optimum pH, temperature, and ionic strength for the activity of the enzyme mixture were determined. The settling time of phase systems containing varying amounts of PEG, crude dextran, and solid starch was studied. The activity and stability of enzyme mixtures was studied both in buffer medium and in the medium containing the polymers. The enzymes were found to be more active and stable in medium containing polymers than in the buffer solutions.


Direct energy recovery from primary and secondary sludges by supercritical water oxidation.
Supercritical water oxidation (SCWO) oxidizes organic and biological materials virtually completely to benign products without the need for stack gas scrubbing. Heavy metals are recovered as stabilized solid, along with the sand and clay that is present in the feed. The technology has been under development for twenty years. The major obstacle to commercialization has been developing reactors that are not clogged by inorganic solid deposits. That problem has been solved by using tubular reactors with fluid velocities that are high enough to keep solids in suspension. Recently, system designs have been created that reduce the cost of processing sewage sludges below that of incineration. At 10 wt- % dry solids, sludge can be oxidized with virtually complete recovery of the sludge heating value as hot water or high-pressure steam. Liquid carbon dioxide of high purity can be recovered from the gaseous effluent and excess oxygen can be recovered for recycle. The net effect is to reduce the stack to a harmless vent with minimal flow rate of a clean gas. Complete simulations have been developed using physical property models that accurately simulate the thermodynamic properties of sub- and supercritical water in mixtures with O2, N2, CO2, and organics. Capital and operating cost estimates are given for sewage sludge treatment, which are less costly than incineration. The scenario of direct recovery of energy from sludges has inherent benefits compared to other gasification or liquefaction options.


Leveraging data science to enhance suicide prevention research: a literature review.
The purpose of this research is to identify how data science is applied in suicide prevention literature, describe the current landscape of this literature and highlight areas where data science may be useful for future injury prevention research. We conducted a literature review of injury prevention and data science in April 2020 and January 2021 in three databases. For the included 99 articles, we extracted the following: (1) author(s) and year; (2) title; (3) study approach (4) reason for applying data science method; (5) data science method type; (6) study description; (7) data source and (8) focus on a disproportionately affected population. Results showed the literature on data science and suicide more than doubled from 2019 to 2020, with articles with individual-level approaches more prevalent than population-level approaches. Most population-level articles applied data science methods to describe (n=10) outcomes, while most individual-level articles identified risk factors (n=27). Machine learning was the most common data science method applied in the studies (n=48). A wide array of data sources was used for suicide research, with most articles (n=45) using social media and web-based behaviour data. Eleven studies demonstrated the value of applying data science to suicide prevention literature for disproportionately affected groups. Data science techniques proved to be effective tools in describing suicidal thoughts or behaviour, identifying individual risk factors and predicting outcomes. Future research should focus on identifying how data science can be applied in other injury-related topics.


Implementing Artificial Intelligence for Emergency Radiology Impacts Physicians' Knowledge and Perception: A Prospective Pre- and Post-Analysis.
The aim of this study was to evaluate the impact of implementing an artificial intelligence (AI) solution for emergency radiology into clinical routine on physicians' perception and knowledge. A prospective interventional survey was performed pre-implementation and 3 months post-implementation of an AI algorithm for fracture detection on radiographs in late 2022. Radiologists and traumatologists were asked about their knowledge and perception of AI on a 7-point Likert scale (-3, "strongly disagree"; +3, "strongly agree"). Self-generated identification codes allowed matching the same individuals pre-intervention and post-intervention, and using Wilcoxon signed rank test for paired data. A total of 47/71 matched participants completed both surveys (66% follow-up rate) and were eligible for analysis (34 radiologists [72%], 13 traumatologists [28%], 15 women [32%]; mean age, 34.8 ± 7.8 years). Postintervention, there was an increase that AI "reduced missed findings" (1.28 [pre] vs 1.94 [post], P = 0.003) and made readers "safer" (1.21 vs 1.64, P = 0.048), but not "faster" (0.98 vs 1.21, P = 0.261). There was a rising disagreement that AI could "replace the radiological report" (-2.04 vs -2.34, P = 0.038), as well as an increase in self-reported knowledge about "clinical AI," its "chances," and its "risks" (0.40 vs 1.00, 1.21 vs 1.70, and 0.96 vs 1.34; all P's ≤ 0.028). Radiologists used AI results more frequently than traumatologists (P < 0.001) and rated benefits higher (all P's ≤ 0.038), whereas senior physicians were less likely to use AI or endorse its benefits (negative correlation with age, -0.35 to 0.30; all P's ≤ 0.046). Implementing AI for emergency radiology into clinical routine has an educative aspect and underlines the concept of AI as a "second reader," to support and not replace physicians.


The Chemokine Receptor CCR7 Uses Distinct Signaling Modules With Biased Functionality to Regulate Dendritic Cells.
Chemotaxis is a molecular mechanism that confers leukocytes the ability to detect gradients of chemoattractants. Chemokine receptors are well-known regulators of chemotaxis in leukocytes; however, they can regulate several other activities in these cells. This information has been often neglected, probably due to the paramount role of chemotaxis in the immune system and in biology. Therefore, the experimental data available on the mechanisms used by chemokine receptors to regulate other functions of leukocytes is sparse. The results obtained in the study of the chemokine receptor CCR7 in dendritic cells (DCs) provide interesting information on this issue. CCR7 guides the DCs from the peripheral tissues to the lymph nodes, where these cells control T cell activation. CCR7 can regulate DC chemotaxis, survival, migratory speed, cytoarchitecture, and endocytosis. Biochemical and functional analyses show: first, that CCR7 uses in DCs the PI3K/Akt pathway to control survival, the MAPK pathway to control chemotaxis, and the RhoA pathways to regulate actin dynamics, which in turn controls migratory speed, cytoarchitecture, and endocytosis; second, that these three signaling pathways behave as modules with a high degree of independence; and third, that although each one of these routes can regulate several functions in different settings, CCR7 promotes in DCs a functional bias in each pathway. The data uncover an interesting mechanism used by CCR7 to regulate the DCs, entailing multifunctional signaling pathways organized in modules with biased functionality. A similar mechanism could be used by other chemoattractant receptors to regulate the functions of leukocytes.


Mechanisms involved in the functional divergence of duplicated GroEL chaperonins in Myxococcus xanthus DK1622.
The gene encoding the GroEL chaperonin is duplicated in nearly 30% of bacterial genomes; and although duplicated groEL genes have been comprehensively determined to have distinct physiological functions in different species, the mechanisms involved have not been characterized to date. Myxococcus xanthus DK1622 has two copies of the groEL gene, each of which can be deleted without affecting cell viability; however, the deletion of either gene does result in distinct defects in the cellular heat-shock response, predation, and development. In this study, we show that, from the expression levels of different groELs, the distinct functions of groEL1 and groEL2 in predation and development are probably the result of the substrate selectivity of the paralogous GroEL chaperonins, whereas the lethal effect of heat shock due to the deletion of groEL1 is caused by a decrease in the total groEL expression level. Following a bioinformatics analysis of the composition characteristics of GroELs from different bacteria, we performed region-swapping assays in M. xanthus, demonstrating that the differences in the apical and the C-terminal equatorial regions determine the substrate specificity of the two GroELs. Site-directed mutagenesis experiments indicated that the GGM repeat sequence at the C-terminus of GroEL1 plays an important role in functional divergence. Divergent functions of duplicated GroELs, which have similar patterns of variation in different bacterial species, have thus evolved mainly via alteration of the apical and the C-terminal equatorial regions. We identified the specific substrates of strain DK1622's GroEL1 and GroEL2 using immunoprecipitation and mass spectrometry techniques. Although 68 proteins bound to both GroEL1 and GroEL2, 83 and 46 proteins bound exclusively to GroEL1 or GroEL2, respectively. The GroEL-specific substrates exhibited distinct molecular sizes and secondary structures, providing an encouraging indication for GroEL evolution for functional divergence.


The cerebellar norepinephrine system: inhibition, modulation, and gating.
A series of studies has been conducted to determine the mode of action on the cerebellar cortical circuitry of the norepinephrine (NE)-containing afferents from the locus coeruleus. NE has been known to exert an "inhibitory" action on the background firing observed in Purkinje cells, due presumably to a shift in conductances favoring hyperpolarization. An additional independent action at low threshold appears to be an enhancement of GABA, the inhibitory transmitter of cerebellar interneurons. Recent whole-cell patch-clamp studies on isolated Purkinje cells indicate that exposure to NE increases the chloride current caused by transient pulses of GABA applied iontophoretically. NE applied to Purkinje cells in the parafloccular lobule during stimulation by moving visual patterns revealed the capacity either to "gate" signals initially not expressed, or to amplify the gain of phasic excitations. The control of emergent circuit functions may be the functional consequence of the multiple modulatory functions of NE.


[A Case of Retroperitoneal Leiomyosarcoma Treated with Repeated Surgical Resection].
A 55-year-old male revealed with a 5 cm-diameter mass in the lower abdomen on ultrasonography incidentally. Computed tomography showed a mass of 7 cm in size on the left side of the bladder. A malignant tumor was suspected, and surgically excised for purpose of diagnosis and treatment. Pathological examination confirmed retroperitoneal leiomyosarcoma, and the resection margins were negative. Follow-up computed tomography scan was performed every 3 months. Repeated resections were performed for twice recurrences within a year after surgery. A year after the first surgery, lung metastasis was detected and chemotherapy was started. Although retroperitoneal leiomyosarcoma is considered to have a poor prognosis, the present case had relatively good prognosis. This may be due to early detection and repeated surgical resection.


Impact of Electrodes on Recombination in Bulk Heterojunction Organic Solar Cells.
In recent years, the efficiency of organic solar cells (OSCs) has increased to more than 13%, although different barriers are on the way for reaching higher efficiencies. One crucial barrier is the recombination of charge carriers, which can either occur as the bulk recombination of photogenerated charges or the recombination of photogenerated charges and electrodic induced charges (EICs). This work studies the impact of EICs on the recombination lifetime in OSCs. To this end, the net recombination lifetime of photogenerated charge carriers in the presence of EICs is measured by means of conventional and newly developed transient photovoltage techniques. Moreover, a new approach has been introduced to exclusively measure the bulk recombination lifetime, i.e., in the absence of EICs; this approach was conducted by depositing transparent insulating layers on both sides of the OSC active layer. An examination of these approaches on OSCs with different active layer materials, thicknesses, and varying light intensities determined that the EICs can only reduce the recombination lifetime of the photogenerated charges in OSCs with very weak recombination strength. This work supports that for OSCs with highly reduced recombination strength, eliminating the recombination of photogenerated charges and EICs is critical for achieving better performance. Therefore, the use of a proper blocking layer suppresses EIC recombination in systems with very weak recombination.


[Effects of oxidative stress on ventricular remodeling after myocardial infarction in rats].
To investigate the effects of oxidative stress on ventricular remodeling after acute myocardial infarction (AMI) in rats. AMI was induced in 20 SD rats by ligation of the anterior descending coronary artery, and another 12 rats without the ligation served as the sham-operated group. Six weeks after the operation, the heart mass index (HMI), left ventricular mass index (LVMI), right ventricular mass index (RVMI), the indexes of heart function, cardiac myocyte apoptosis index, collagen content and collagen I/III ratio and the indexes of oxidative stress were measured. After AMI, HMI, LVMI and RVMI increased significantly (P<0.05), the heart function deteriorated significantly (P<0.01), and the cardiac myocyte apoptosis index in the non-infarct area, collagen content and collagen I/III ratio in the infarct and non-infarct areas were all significantly increased (P<0.05 or 0.01). Myocardial superoxide dismutase (SOD) activity was significantly lowered after AMI, which resulted in significantly increased myocardial malondialdehyde (MDA) level and decreased ratio of SOD/MDA (P<0.05). Correlations were found between the indexes of oxidative stress in myocardium, those of the heart function and those pertaining to ventricular remodeling after AMI. Oxidative stress may be involved in ventricular remodeling after AMI, and antioxidants can be an option for treatment of ventricular remodeling.


Rapid detection and quantitation of ketamine and norketamine in urine and oral fluid by wooden-tip electrospray ionization mass spectrometry.
Drug analysis is an indispensable task in controlling drug abuse, which is a serious problem worldwide nowadays. In this study, we report a simple and rapid approach for detection and quantitation of drugs-of-abuse in urine and oral fluid by wooden-tip electrospray ionization mass spectrometry (WT-ESI-MS). We demonstrated that ketamine, one of the most common abused drugs, and its major metabolite, norketamine, in raw urine and oral fluid could be readily detected and quantified by WT-ESI-MS with only little sample preparation and no chromatographic separation, and the analytical performances, including the linear range, accuracy, precision, LOD and LOQ, were well acceptable for analysis of real samples.


Dietary Intervention during 9 Months with a Hypocaloric Diet, Interaction of the Genetic Variant of Adiponectin Gene rs822393 with Metabolic Parameters.
rs822393 (-4522C/T) genetic variant is associated with hypoadiponectinemia and other metabolic parameters. The aim of our investigation was to analyze the effects of a hypocaloric diet with Mediterranean dietary pattern during 9 months according to genetic variant rs822393 of ADIPOQ gene. A sample of 269 obese patients was enrolled. Anthropometric and serum parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR), glucose, C reactive protein, and adipokines) were determined, at basal time and after 3 and 9 months. All patients were genotyped in the rs822393. The genotype distribution was as follow; 176 patients (65.4%) CC, 83 patients CT (30.9%), and 10 patients TT (3.7%). After dietary intervention, the following parameters improved in non-T allele carriers; BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin levels, HOMA-IR, leptin, total cholesterol, and LDL-cholesterol improved significantly. HDL-cholesterol (delta: 5.7 ± 1.1 mg/dl vs. 1.0 ± 0.8 mg/dl; p = 0.01), serum adiponectin (delta: 14.4 ± 2.0 ng/dl vs. 7.1 ± 3.1 ng/dl; p = 0.02), and adiponectin/leptin ratio (delta: 0.54 ± 0.1 vs. 0.22 ± 0.09 ng/dl; p = 0.03). Basal and postintervention HDL cholesterol, adiponectin levels, and adiponectin/leptin levels were lower in T-allele carriers than non-T Allele carriers. T allele carriers showed lower levels of HDL-cholesterol, adiponectin, and adiponectin/leptin ratio than non-T allele carriers. A medium-term hypocaloric diet with a Mediterranean partner increased adiponectin levels, ratio adiponectin/leptin, and HDL-cholesterol in non-T allele carriers.


Proactive approaches for mold-free interior environments.
Interior design education and practice can contribute to the prevention of mold growth in indoor environments. The authors provide an overview of current thinking within the interior design educational and professional communities regarding proactive approaches to achieving mold-free building interiors, including identification of current best practices for the prevention of mold problems in buildings. They also discuss the development of certification programs. A review of recent literature points to the need for interior designers to be educated to specify the use of ecologically sound materials that support the health of building occupants. The authors present trade-offs between best practices for designing mold-free indoor environments (including considerations of cost, maintenance, and operation) and occupant comfort, health, and well-being.


Diltiazem Does Not Prevent Postoperative Atrial Fibrillation After Thoracoscopic Lobectomy.
Thoracoscopic lobectomy is associated with lower rates of adverse events compared to thoracotomy. Despite this, postoperative atrial fibrillation (POAF) occurs in at least 10% of patients. Our objective is to determine if prophylaxis with diltiazem significantly reduced POAF events. Patients without prior history of atrial fibrillation who underwent thoracoscopic lobectomy from 2007 to 2016 at one institution were analyzed in a retrospective cohort study utilizing a prospective database. Patients treated from 2007 to 2012 received no prophylaxis. Patients treated after 2012 received diltiazem postoperatively. All patients were monitored with continuous telemetry postoperatively. Multivariate direct logistic regression was performed to determine independent predictors of POAF. We report adjusted odds ratios and accompanying 95% confidence intervals, with P < 0.05 denoting statistical significance. The final regression model included 416 patients (52 with POAF, 364 without). In univariate analysis, the variables of body mass index and history of congestive heart failure, diabetes, or hypertension, and prophylaxis status did not meet inclusion criteria. Age, gender, history of stroke or transient ischemic attack, and vascular disease were included. Only ages 65 to 74 (P = 0.03) and ≥75 (P = 0.02), compared to <65, were statistically significant predictors of POAF. Adjusted odds ratios of ages 65 to 74 and ≥75 were 2.88 and 2.62, respectively. Diltiazem prophylaxis did not significantly reduce POAF incidence following thoracoscopic lobectomy. Further study is warranted since POAF remains an unwanted source of morbidity and cost for lobectomy patients.


Asking "Meaning Questions" in Evidence-Based Reviews and the Utility of Qualitative Findings in Practice.
Evidence-based practice (EBP) systematic reviews are mostly conducted using etiology, diagnosis, therapy, prevention, and prognosis question format. "Meaning" or qualitative questions are very rarely used. The purpose of this article is to discuss qualitative findings' contribution to EBP through asking "meaning questions" in conducting systematic reviews and the utilization of the results to practice. Two EBP systematic review exemplars using meaning questions including the relevance and utilization of qualitative findings in health care decision-making, practice, and policy are presented. There is a need to instill an evidence-based mindset into systematic reviews that balance scientific knowledge gained through empirical research and evidence from qualitative studies. This is turn will increase awareness among clinicians and decision makers on the different ways in which qualitative evidence can be used and applied in practice.


Activity-dependent increases in [Ca2+]i contribute to digital-analog plasticity at a molluscan synapse.
In a type of short-term plasticity that is observed in a number of systems, synaptic transmission is potentiated by depolarizing changes in the membrane potential of the presynaptic neuron before spike initiation. This digital-analog form of plasticity is graded. The more depolarized the neuron, the greater the increase in the efficacy of synaptic transmission. In a number of systems, including the system presently under investigation, this type of modulation is calcium dependent, and its graded nature is presumably a consequence of a direct relationship between the intracellular calcium concentration ([Ca2+]i) and the effect on synaptic transmission. It is therefore of interest to identify factors that determine the magnitude of this type of calcium signal. We studied a synapse in Aplysia and demonstrate that there can be a contribution from currents activated during spiking. When neurons spike, there are localized increases in [Ca2+]i that directly trigger neurotransmitter release. Additionally, spiking can lead to global increases in [Ca2+]i that are reminiscent of those induced by subthreshold depolarization. We demonstrate that these spike-induced increases in [Ca2+]i result from the activation of a current not activated by subthreshold depolarization. Importantly, they decay with a relatively slow time constant. Consequently, with repeated spiking, even at a low frequency, they readily summate to become larger than increases in [Ca2+]i induced by subthreshold depolarization alone. When this occurs, global increases in [Ca2+]i induced by spiking play the predominant role in determining the efficacy of synaptic transmission.NEW & NOTEWORTHY We demonstrate that spiking can induce global increases in the intracellular calcium concentration ([Ca2+]i) that decay with a relatively long time constant. Consequently, summation of the calcium signal occurs even at low firing frequencies. As a result there is significant, persistent potentiation of synaptic transmission.


Health promotion in motion: improving quality of life for persons with neurogenic bladder and bowel using assistive technology.
The neurogenic bladder and bowel lead to many complications in individuals with spinal cord injury (SCI). Management of these neurological complications is a multidimensional challenge for persons with SCI and their caregivers, and can affect the person medically, economically, socially, and personally. This may result in social isolation, poor self-image, and overall decreased quality of life (QOL). When facing this challenge, nurses working with persons with SCI must expand their practice to include more than traditional preventive care. A newly available technique for promoting health with a neurogenic bladder and bowel is the VOCARE Bladder and Bowel Control System. Sixteen persons with SCI who received this system were interviewed by telephone and asked for their recollections of health and QOL pre-operatively in relation to bladder and bowel care and to rate changes in their QOL post-implant. Post-operatively, the recipients reported improved health, a decrease in costs of management of their neurogenic bladder and bowel, increased independence leading to less social isolation, increased sense of control, increased feelings of self-worth, and overall improvement in QOL. These outcomes illustrate the global impact that can be made on the lives of persons with SCI by health services that go beyond prevention of complications and into the realm of health promotion.


Cytoskeletal network of intermediate filament proteins in the adult human vestibular labyrinth.
The cytoskeleton of adult human vestibular hair cells lacks intermediate filament (IF) proteins, whereas in fetal material immunoreactivity for cytokeratin (cks; a subclass of IFs) occurs in both types of hair cells. The shift in the cytoskeletal composition can be hypothesized to their onset of physiological function. Since the IFs are extremely rigid intracellular structures, they provide considerable mechanical stability. The entire cytoplasm of all supporting cells in the epithelial lining of all five vestibular organs is filled with cks. In this way most vestibular hair cells become compartmentalized, each with a rigid shell surrounding it. The distinct delineation of IF proteins in adult tissues, in contrast to fetal inner ear organs in which often a rather general cytoplasmic expression occurs, probably reflects their anatomical basis for their function.


Cutaneous epithelioid angioleiomyoma.
We describe an unusual dermal neoplasm with epithelioid morphology. A 44-year-old man presented with a solitary, tender, 4-mm nodule on the leg. Excisional biopsy showed several well-circumscribed dermal epithelioid tumor nodules, prominent vascularity, and smooth muscle differentiation. We suggest the term cutaneous epithelioid angioleiomyoma for this neoplasm. In a review of the literature, we found reports of two similar cases and a recent report describing five cutaneous epithelioid leiomyosarcomas. Cutaneous epithelioid angioleiomyoma represents a rare variant of dermal smooth muscle tumor and could represent the benign counterpart to the recently described epithelioid leiomyosarcoma of the skin.


Polycystic Ovary Syndrome May Be an Autoimmune Disorder.
Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine disorder affecting females. It is a common cause of menstrual irregularities and infertility during reproductive age. Genetic and hormonal factors play crucial role in the pathogenesis of PCOS. Low level of progesterone in PCOS causes overstimulation of immune system that produces more estrogen which leads to various autoantibodies. Different autoantibodies have been documented in PCOS, for example, anti-nuclear (ANA), anti-thyroid, anti-spermatic, anti-SM, anti-histone, anti-carbonic anhydrase, anti-ovarian, and anti-islet cell antibodies. There is an association between PCOS and autoimmune diseases such as ANA and anti-TPO that have been documented in systemic lupus erythematosus and Hashimoto thyroiditis, respectively, and it is suspected that there are autoantibodies that might affect the long term clinical management of these patients. Therefore fluctuating levels of autoantibodies in different PCOS patients give us the way to open new chapter for future research on molecular level. This may lead to discovery of better treatment options for PCOS in near future.


Recombinant soluble interleukin-4 (IL-4) receptor acts as an antagonist of IL-4 in murine cutaneous Leishmaniasis.
This study was performed to evaluate the soluble interleukin-4 receptor (sIL-4R) as a potential antagonist of interleukin-4 (IL-4) in an infectious disease. It is shown that antigen-triggered proliferation and cytokine secretion of Leishmania major-specific, cloned Th2 cells in vitro can be inhibited dose dependently by recombinant murine, but not control human, sIL-4R. In vivo, we found that endogenous synthesis of IL-4 mRNA is upregulated during the first week of infection, while an increase of IL-4R mRNA occurred later after infection of BALB/c mice with L. major. To interfere successfully with the IL-4 ligand-receptor interaction, we therefore chose to treat infected BALB/c mice with recombinant sIL-4R during the onset (e.g., days 0 to 7) of the immune response. Treatment with murine, but not with human, sIL-4R during the first week of infection rendered BALB/c mice clinically resistant to L. major, led to a 7- to 12-fold reduction of the parasite load in spleen and lymph nodes at 7 weeks of infection, shifted the pattern of cytokines towards a Th1 type, and provided durable resistance against reinfection. Thus, it could be demonstrated that the balance among sIL-4R, membrane-bound IL-4R, and their ligand IL-4 can be modulated in vivo, thereby modifying the antiparasitic immune response. These results suggest a therapeutic value of sIL-4R in diseases in which neutralization of IL-4 is desirable.


Advances in deubiquitinating enzymes in lung adenocarcinoma.
The process of ubiquitination and deubiquitination is widely present in the human body's protein reactions and plays versatile roles in multiple diseases. Deubiquitinating enzymes (DUBs) are significant regulators of this process, which cleave the ubiquitin (Ub) moiety from various substrates and maintain protein stability. Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer (NSCLC) and remains refractory to treatment. To elucidate the mechanism of LUAD and advance new therapeutic targets, we review the latest research progress on DUBs in LUAD. We summarize the biological capabilities of these DUBs and further highlight those DUBs that may serve as anticancer target candidates for precision treatment. We also discuss deubiquitinase inhibitors, which are expected to play a role in targeted LUAD therapy.


Injection and trapping of tunnel-ionized electrons into laser-produced wakes.
A method, which utilizes the large difference in ionization potentials between successive ionization states of trace atoms, for injecting electrons into a laser-driven wakefield is presented. Here a mixture of helium and trace amounts of nitrogen gas was used. Electrons from the K shell of nitrogen were tunnel ionized near the peak of the laser pulse and were injected into and trapped by the wake created by electrons from majority helium atoms and the L shell of nitrogen. The spectrum of the accelerated electrons, the threshold intensity at which trapping occurs, the forward transmitted laser spectrum, and the beam divergence are all consistent with this injection process. The experimental measurements are supported by theory and 3D OSIRIS simulations.


The effect of small hydrostatic pressure gradients on the rate of active sodium transport across isolated living frog-skin membranes.
1. The rate of active sodium transport across living isolated skins from Rana temporaria was measured when the skins were bulged inwards and outwards by small constant hydrostatic pressure gradients and by pushing them mechanically in the absence of such gradients. The effect of pressure gradients in the absence of bulging was also studied.2. An apparatus was designed to circulate Ringer solution to each side of the skin at constant temperature, flow and pressure. The pressures were controlled to within 0.5 mm H(2)O.3. It was found that bulging the skins in the absence of hydrostatic pressure gradients had no effect on sodium transport but that pressure gradients of less than 5 mm H(2)O had a marked effect, increasing transport when the pressure was higher on the outside of the skin, and decreasing it when the pressure was higher on the inside.4. It is concluded that increasing surface area does not influence sodium transport, whereas small hydrostatic pressure gradients have a marked effect.5. Possible causes for this phenomenon are discussed and its significance is considered with special reference to sodium reabsorption from the proximal tubule of the kidney.


Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone.
The reduced incidence of prostate cancer (PCa) in Asia countries has been attributed to high soy diets, and major soy isoflavones, in particular daidzein and genistein, are thought to be the source of the beneficial and anti-cancer effects of soy foods. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans, which is especially the concern for consumers taking regular soy isoflavone dietary supplements. The main objective of this study is thus to identify a soy isoflavone combination with lower levels of daidzein and genistein to be a more efficacious and safer chemo-preventive agent for PCa. The anticancer effects of daidzein and genistein, and their combinations on early-stage androgen-dependent PCa cells (LNCaP) and bone metastatic LNCaP-derivative PCa cells (C4-2B) were compared. Cells were treated with varying concentrations of daidzein, genistein (25-200 μM) or their combinations (25 or 50 μM) and cell proliferation, apoptosis, cell cycles and cellular uptakes of the isoflavones were measured after 48 h. Daidzein and genistein showed a synergistic effect on inhibiting cell proliferation and inducing apoptosis of both PCa cells. Twenty-five μM daidzein/50 μM genistein and 50 μM daidzein/50 μM genistein significantly increased the apoptotic effects on C4-2B cells although they did not show any effect when used individually. Except 50 μM daidzein/50 μM genistein, all other combinations had no impacts on cell cycles. For treatment with soy isoflavone combination, genistein was always better taken up than daidzein by both LNCaP and C4-2B cells.


Induction of the 70 kDa heat shock protein stress response inhibits autophagy: possible consequences for pregnancy outcome.
The induction of heat shock protein synthesis and activation of autophagy are intracellular processes stimulated under adverse conditions. We evaluated the relationship between intracellular concentrations of the inducible 70 kDa heat shock protein (hsp70) and autophagy induction in human peripheral blood mononuclear cells (PBMCs) following exposure to sera from pregnant and non-pregnant women. Autophagy was induced in PBMCs by incubation for 48 h with sera from 42 pregnant women at mid-gestation and 45 non-pregnant women. Intracellular concentrations of hsp70 and p62 were measured by ELISA. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration in the cytoplasm is inversely proportional to the extent of autophagy induction (high p62 = low autophagy). The p62 concentration was highly correlated with the hsp70 level utilizing sera from both pregnant (Spearman r = 0.4731, p = 0.0015) and non-pregnant (Spearman r = 0.6214, p < 0.0001) women. Median p62 (7.4 ng/ml versus 2.7 ng/ml, p < 0.0001) and hsp70 (7.0 ng/ml versus 3.5 ng/ml, p = 0.0022) levels were higher when PBMCS were incubated with sera from pregnant women. The extent of autophagy in PBMCs is inversely proportional to the intracellular hsp70 concentration and sera from pregnant women induces hsp70 and inhibits autophagy to a greater extent than does sera from non-pregnant women. A stress response that induces hsp70 has the potential to interfere with autophagy-related events.


An unusual isolated anterior mediastinal lesion.
Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.


Treatment of vertigo due to acute unilateral vestibular loss with a fixed combination of cinnarizine and dimenhydrinate: a double-blind, randomized, parallel-group clinical study.
Acute unilateral vestibular loss is a balance disorder that is accompanied by vertigo symptoms and concomitant vegetative symptoms, including nausea and vomiting. Patients are frequently confined to bed rest but may continue to experience vertigo symptoms. A well-established antivertiginous therapy consisting of cinnarizine and dimenhydrinate at low doses may offer rapid relief of acute vertigo symptoms due to acute vestibular loss, without inhibiting physiological compensation processes. The purpose of this study was to compare the clinical efficacy and tolerability of a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg versus monotherapy with its respective components in the treatment of acute vertigo symptoms due to acute unilateral vestibular loss. In this prospective, single-center, randomized, double-blind, parallel-group clinical study, 50 patients with acute vestibular vertigo were randomly assigned to receive 4 weeks of treatment (1 tablet 3 times daily) with a fixed combination of 20 mg cinnarizine and 40 mg dimenhydrinate, 20 mg cinnarizine alone, or 40 mg dimenhydrinate alone. All patients received a 15% mannitol infusion as standard therapy during the first 6 days of treatment. Efficacy was determined by the patients' assessments of vertigo symptoms after 1 and 4 weeks of treatment using a verbal rating scale (vertigo score) and by vestibulo-ocular and vestibulospinal tests. The primary efficacy criterion was defined as the relief of vertigo symptoms after 1 week of treatment. After 1 week of treatment, the fixed combination was significantly more effective than 20 mg cinnarizine (P < 0.001) and 40 mg dimenhydrinate (P < 0.01). After 4 weeks, the fixed combination was still significantly more effective than cinnarizine in reducing vertigo symptoms (P < 0.01) and significantly more effective than dimenhydrinate in improving the patients' balance while standing (P < 0.05). The tolerability of the fixed combination was rated good or very good by 100% of the patients (cinnarizine alone, 82.4%; dimenhydrinate alone, 94.4%). No serious adverse events occurred. Four patients in the fixed combination and the cinnarizine groups, and 6 patients in the dimenhydrinate group reported nonserious adverse events. The results of this study suggest a distinct benefit in using a fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg versus the respective monotherapies in this population of patients with acute vestibular vertigo.


[Models for intervention in autism spectrum disorders: Denver and SCERTS].
Given the increased prevalence of diagnoses of autism in recent years, the growing amount of research on models with which to work with people with autism spectrum disorders (ASD) has led to the development of different techniques and methods enabling better results to be obtained. As a result, it has become possible to help improve many of the symptoms that prevent people with this diagnosis and their families from leading a normal life. To review two intervention models specifically designed for working with persons with ASD. The review first examines an early intervention model, the Early Start Denver Model, which consists in a checklist for children with ASD aged from 12 to 48 months, based on their progress. The SCERTS model is also reviewed. Unlike the Denver, this model presents goals that must be worked on throughout the entire lifespan of those with ASD. In the absence of further results from scientific evidence-based practice regarding the two models reviewed here, it can be concluded that there is no single standardised model and that children with difficulties in joint attention and imitation need to be referred at an early stage, as well as working together with the families. Thus, to perform a correct intervention it is necessary to take into account evidence-based practice and for the therapist to have a deep knowledge, respect and understanding of children with ASD and of their families.


Mining and analysing spatio-temporal patterns of gene expression in an integrative database framework.
Mining patterns of gene expression provides a crucial approach in discovering knowledge such as finding genetic networks that underpin the embryonic development. Analysis of mining results and evaluation of their relevance in the domain remains a major concern. In this paper we describe our explorative studies in support of solutions to facilitate the analysis and interpretation of mining results. In our particular case we describe a solution that is found in the extension of the Gene Expression Management System (GEMS), i.e. an integrative framework for spatio-temporal organization of gene expression patterns of zebrafish to a framework supporting data mining, data analysis and patterns interpretation As a proof of principle, the GEMS has been equipped with data mining functionality suitable for spatio-temporal tracking, thereby generating added value to the submission of data for data mining and analysis. The analysis of the genetic networks is based on the availability of domain ontologies which dynamically provides meaning to the discovered patterns of gene expression data. Combination of data mining with the already presently available capabilities of GEMS will significantly augment current data processing and functional analysis strategies.


Dual-Reactivity trans-Cyclooctenol Probes for Sulfenylation in Live Cells Enable Temporal Control via Bioorthogonal Quenching.
Sulfenylation (RSH → RSOH) is a post-translational protein modification associated with cellular mechanisms for signal transduction and the regulation of reactive oxygen species. Protein sulfenic acids are challenging to identify and study due to their electrophilic and transient nature. Described here are sulfenic acid modifying trans-cycloocten-5-ol (SAM-TCO) probes for labeling sulfenic acid functionality in live cells. These probes enable a new mode of capturing sulfenic acids via transannular thioetherification, whereas "ordinary" trans-cyclooctenes react only slowly with sulfenic acids. SAM-TCOs combine with sulfenic acid forms of a model peptide and proteins to form stable adducts. Analogously, SAM-TCO with the selenenic acid form of a model protein leads to a selenoetherification product. Control experiments illustrate the need for the transannulation process coupled with the activated trans-cycloalkene functionality. Bioorthogonal quenching of excess unreacted SAM-TCOs with tetrazines in live cells provides both temporal control and a means of preventing artifacts caused by cellular-lysis. A SAM-TCO biotin conjugate was used to label protein sulfenic acids in live cells, and subsequent quenching by tetrazine prevented further labeling even under harshly oxidizing conditions. A cell-based proteomic study validates the ability of SAM-TCO probes to identify and quantify known sulfenic acid redox proteins as well as targets not captured by dimedone-based probes.


Iron overload facilitates neonatal hypoxic-ischemic brain damage via SLC7A11-mediated ferroptosis.
Oxidative damage and cell death are involved in the pathogenesis of hypoxic-ischemic brain damage (HIBD). Ferroptosis is a newly identified mode of cell death that results from the oxidative damage induced by excessive iron. In HIBD, iron accumulates in brain tissues due to the massive destruction of red blood cells and increased permeability of the blood brain barrier vasculature, which can trigger ferroptosis. Ferroptosis is implicated in various diseases involving neuronal injury; however, the roles of iron and ferroptosis in HIBD have not been identified. In the present study, we investigated the role of iron overload in neuronal ferroptosis both in HIBD rat models and in oxygen- and glucose-deprived (OGD) SH-SY5Y cells. We observed that iron deposition in the cerebral cortex was significantly increased in HIBD rats. Features of ferroptosis such as shrunken mitochondria, increased MDA (malondialdehyde) levels, and reduced solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression were observed in the cerebral cortex of HIBD rats. Administration of an iron chelator in HIBD rats upregulated SLC7A11 expression and alleviated neuronal ferroptosis in cerebral cortex tissue. Additionally, overexpression of SLC7A11 in SH-SY5Y cells increased cell viability and attenuated OGD-induced ferroptosis. Our results demonstrate that iron overload induces neuronal ferroptosis by inhibiting SLC7A11 expression in HIBD. Inhibition of neuronal ferroptosis may be a promising strategy to alleviate brain damage in HIBD.


Structural basis for sequence-dependent DNA cleavage by nonspecific endonucleases.
Nonspecific endonucleases hydrolyze DNA without sequence specificity but with sequence preference, however the structural basis for cleavage preference remains elusive. We show here that the nonspecific endonuclease ColE7 cleaves DNA with a preference for making nicks after (at 3'O-side) thymine bases but the periplasmic nuclease Vvn cleaves DNA more evenly with little sequence preference. The crystal structure of the 'preferred complex' of the nuclease domain of ColE7 bound to an 18 bp DNA with a thymine before the scissile phosphate had a more distorted DNA phosphate backbone than the backbones in the non-preferred complexes, so that the scissile phosphate was compositionally closer to the endonuclease active site resulting in more efficient DNA cleavage. On the other hand, in the crystal structure of Vvn in complex with a 16 bp DNA, the DNA phosphate backbone was similar and not distorted in comparison with that of a previously reported complex of Vvn with a different DNA sequence. Taken together these results suggest a general structural basis for the sequence-dependent DNA cleavage catalyzed by nonspecific endonucleases, indicating that nonspecific nucleases could induce DNA to deform to distinctive levels depending on the local sequence leading to different cleavage rates along the DNA chain.


Bacterial hydrogen sulfide drives cryptic redox chemistry in gut microbial communities.
Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H2S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H2S accumulation in vivo. Cryptic H2S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.


The bovine leukemia virus X region encodes a trans-activator of its long terminal repeat.
We constructed a fusion plasmid, pMX-I, by which the major open reading frame, X-I, of the bovine leukemia virus (BLV) X gene was expressed under control of the mouse metallothionein promoter. pMX-I was cotransfected into CV1 monkey kidney cells together with another construct containing the BLV long terminal repeat (LTR) linked to the chloramphenicol acetyltransferase (CAT) structural gene. The result of assay of CAT synthesis suggests that the X-I product functions as a trans-acting activation factor of the BLV LTR.


Characterizing and correcting camera noise in back-illuminated sCMOS cameras.
With promising properties of fast imaging speed, large field-of-view, relative low cost and many others, back-illuminated sCMOS cameras have been receiving intensive attention for low light level imaging in the past several years. However, due to the pixel-to-pixel difference of camera noise (called noise non-uniformity) in sCMOS cameras, researchers may hesitate to use them in some application fields, and sometimes wonder whether they should optimize the noise non-uniformity of their sCMOS cameras before using them in a specific application scenario. In this paper, we systematically characterize the impact of different types of sCMOS noise on image quality and perform corrections to these types of sCMOS noise using three representative algorithms (PURE, NCS and MLEsCMOS). We verify that it is possible to use appropriate correction methods to push the non-uniformity of major types of camera noise, including readout noise, offset, and photon response, to a satisfactory level for conventional microscopy and single molecule localization microscopy. We further find out that, after these corrections, global read noise becomes a major concern that limits the imaging performance of back-illuminated sCMOS cameras. We believe this study provides new insights into the understanding of camera noise in back-illuminated sCMOS cameras, and also provides useful information for future development of this promising camera technology.


Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study.
The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.


CD8+ T Cells Protect During Vein Graft Disease Development.
Aims: Vein grafts are frequently used conduits for arterial reconstruction in patients with cardiovascular disease. Unfortunately, vein graft disease (VGD) causes diminished patency rates. Innate immune system components are known to contribute to VGD. However, the role of T cells has yet to be established. The purpose of this study was to investigate the role of T cells and T cell activation pathways via the T cell receptor (TCR), co-stimulation and bystander effect in VGD. Methods and results: Here, we show upon vein graft surgery in mice depleted of CD4+ T cells or CD8+ T cells, that CD8+ T cells are locally activated and have a major protective role for vein graft patency. In presence of CD8+ T cells vein grafts appear patent while CD8+ T cell depletion results in occluded vein grafts with increases apoptosis. Importantly, the protective effect of CD8+ T cells in VGD development was TCR and co-stimulation independent. This was demonstrated in vein grafts of OT-I mice, CD70-/-, CD80/86-/-, and CD70/80/86-/- mice compared to C57BL/6 mice. Interestingly, cytokines including IL-15, IL-18, IL-33, and TNF are up-regulated in vein grafts. These cytokines are co-operatively capable to activate CD8+ T cells in a bystander-mediated fashion, in contrast to CD4+ T cells. Conclusions: T cells are modulators of VGD with a specific protective role of CD8+ T cells, which are locally activated in vein grafts. CD8+ T cells may protect against occlusive lesions by providing survival signals, and concert their protection independent of TCR and co-stimulation signaling.


Relation of the pdxB-usg-truA-dedA Operon and the truA Gene to the Intracellular Survival of Salmonella enterica Serovar Typhimurium.
Salmonella is the genus of Gram-negative, facultative intracellular pathogens that have the ability to infect large numbers of animal or human hosts. The S. enterica usg gene is associated with intracellular survival based on ortholog screening and identification. In this study, the λ-Red recombination system was used to construct gene deletion strains and to investigate whether the identified operon was related to intracellular survival. The pdxB-usg-truA-dedA operon enhanced the intracellular survival of S. enterica by resisting the oxidative environment and the usg and truA gene expression was induced by H₂O₂. Moreover, the genes in this operon (except for dedA) contributed to virulence in mice. These findings indicate that the pdxB-usg-truA-dedA operon functions in resistance to oxidative environments during intracellular survival and is required for in vivo S. enterica virulence. This study provides insight toward a better understand of the characteristics of intracellular pathogens and explores the gene modules involved in their intracellular survival.


A non-intrusive voltage measurement scheme based on MEMS electric field sensors: Theoretical analysis and experimental verification of AC power lines.
A non-interference AC voltage measurement system based on a resonant electric field microsensor is proposed. The equivalent circuit of the proposed system is established, which shows that the frequency response function is only related to the capacitances of the system structure in the kHz low-frequency range. Furthermore, the sensitivity analysis and experiments demonstrate that the amplitude sensitivity is independent of the frequency of an unknown AC voltage. Therefore, this technique is very suitable for measuring arbitrary waveform voltage. A functional prototype was developed and tested to acquire AC power-line voltages. The prototype responded well to the transient waveform of the AC input signal, yet with a phase delay of 177.24°. The output of the system was linear in the range of 0-1000 Vrms at 50-Hz and the linearity was 0.54%, whereas the maximum relative deviation of the rms voltage measurements above 10 V was -0.83%. Finally, the shielding ability of the system against interference and noise was verified through the AC interference voltage measurement.


Targeting success in heart failure: evidence-based management.
Heart failure (HF) is a common condition in primary care with 1% of the population self-reporting this condition. Mortality is substantial, approaching 40% to 50% over 5 years. Heart failure is a complex syndrome in which abnormal heart function results in, or increases the subsequent risk of, clinical symptoms and signs of low cardiac output or pulmonary or systemic congestion.¹ This article will present some practical tips for managing HF.²


Ecophysiological analysis reveals distinct environmental preferences in closely related Baltic Sea picocyanobacteria.
Cluster 5 picocyanobacteria significantly contribute to primary productivity in aquatic ecosystems. Estuarine populations are highly diverse and consist of many co-occurring strains, but their physiology remains largely understudied. In this study, we characterized 17 novel estuarine picocyanobacterial strains. Phylogenetic analysis of the 16S rRNA and pigment genes (cpcB and cpeBA) uncovered multiple estuarine and freshwater-related clusters and pigment types. Assays with five representative strains (three phycocyanin rich and two phycoerythrin rich) under temperature (10-30°C), light (10-190 μmol photons m-2 s-1 ), and salinity (2-14 PSU) gradients revealed distinct growth optima and tolerance, indicating that genetic variability was accompanied by physiological diversity. Adaptability to environmental conditions was associated with differential pigment content and photosynthetic performance. Amplicon sequence variants at a coastal and an offshore station linked population dynamics with phylogenetic clusters, supporting that strains isolated in this study represent key ecotypes within the Baltic Sea picocyanobacterial community. The functional diversity found within strains with the same pigment type suggests that understanding estuarine picocyanobacterial ecology requires analysis beyond the phycocyanin and phycoerythrin divide. This new knowledge of the environmental preferences in estuarine picocyanobacteria is important for understanding and evaluating productivity in current and future ecosystems.


ART failure: oocyte contributions to unsuccessful fertilization.
The complexity of fertilization failure during assisted reproductive technologies (ART) is often under-appreciated, as this failure can occur at any number of essential mechanistic and cellular events. Importantly, successful fertilization is heavily dependent upon inherent qualities of the oocytes, and thus reliant upon fidelity of oocyte maturation. Pubmed and medline were searched up to April 2008 for papers on oocyte fertilization and its mechanistic components. References to clinical/human studies were selected wherever possible. Successful oocyte maturation cannot simply be determined via visual assessment of polar body extrusion, but rather entails coordination of numerous cytoplasmic processes not readily observed. Proper regulation of intra-oocyte signaling cascades is crucial for sufficient production and storage of carbohydrates and proteins, successful relocation of organelles and regulation of metabolic pathways required for an apparently mature metaphase II oocyte to complete subsequent fertilization events; such as cumulus penetration, sperm/oocyte binding, fusion, oocyte activation, sperm processing and pronuclear (PN) formation. Regulation of oocyte maturation begins during oocyte growth and is intimately connected with events influencing folliculogenesis. Therefore, the oocyte is subject to a multitude of potential effector impacting fertilization potential and developmental competence long before encountering the artificial environment of the IVF laboratory. Although meticulous care and continued research is essential for future improvement, failure to fertilize and properly form PN following clinical ART is likely to be dependent on historical events in oocyte maturation, not easily explained or prevented through simple modification of contemporary laboratory protocols.


Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives.
Hematopoietic cell transplantation is a potentially lifesaving procedure for patients with hematological malignancies who are refractory to conventional chemotherapy and/or irradiation treatment. Umbilical cord blood (CB) transplantation, as a hematopoietic stem and progenitor cell (HSPC) source, has several advantages over bone marrow transplantation with respect to matching and prompt availability for transplantation. Additionally, CB has some inherent features, such as rapid expansion of T cells, lower prevalence of graft-versus-host disease and higher graft versus tumor efficacy that make this HSPC cell source more favorable over other HSPC sources. Areas covered: This review summarizes the current CB and CB derived T cell applications aiming to better disease control for hematological malignancies and discusses future directions to more effective therapies. Expert commentary: CB transplantation could be used as a platform to extract cord blood derived T cells for ex vivo expansion and/or gene modification to improve cellular immunotherapies. In addition, combining cord blood gene-engineered T cell products with vaccination strategies, such as cord blood derived dendritic cell based vaccines, may provide synergistic immunotherapies with enhanced anti-tumor effects.


Antitumor effect of polysaccharide coated liposomal adriamycin on AH66 hepatoma in nude mice.
Drug delivery systems play a crucial role in cancer chemotherapy, not only in the achievement of sufficient tumoricidal effect but also in minimizing systemic side effects. We investigated the effect of liposomal adriamycin with tumor recognition molecule, 1-aminolactose (1-AL), on AH66 hepatoma transplanted into nude mice. Adriamycin (ADM) was encapsulated in liposome coating with cholesterol pullulan (CHP) to increase the stability in the blood stream. 1-AL was assembled to the outer layer of CHP-coated liposomal ADM as a tumor recognition molecule. In an in vivo therapeutic study. 1-AL/CHP-coated liposomal ADM restrained tumor growth more when compared with CHP-coated liposomal ADM. Thus, 1-AL/CHP-coated liposome seems to be a carrier of ADM to tumor cells.


Quantitative evaluation of the morphology of the inner surface of composite restorations.
The aim of the present study was to develop a method for quantitative evaluation of the morphology of inner surfaces of composite resin restorations. Twelve restorations made in vivo using the acid etch technique were examined in a scanning electron microscope at a magnification of x 2000. 2500 predetermined areas (6300 micron2 each) on the inner surfaces of the fillings were scored from 0 to 3 with respect to the impression of their rendering of morphologic details from the etched cavity walls. Based on all the scorings and parts of the scorings, estimates for the enamel and for the dentin relief on each of the fillings were calculated. The statistical comparison of these estimates that approximately 50 areas per filling might be scored to attain an objective and reliable quantitation of the surface morphology.


Public views regarding the responsibility of patients, clinicians, and institutions to participate in research in the United States.
The need for more and better evidence to inform clinical decision making among all stakeholders has fueled calls for creating learning healthcare systems. The successful realization of a learning healthcare system seems to assume that various parties have a responsibility to participate in learning activities, including research. The objective of this study was to determine whether members of the general public perceive an ethical responsibility to participate in pragmatic clinical research that would be inherent to a learning health system. A total of 2994 English-speaking adults completed a nationally representative online survey. About two-thirds of respondents were relatively neutral regarding a responsibility for themselves and others to participate in research; the remainder felt that they and others did not have a responsibility to participate in research. Efforts to justify and develop a robust learning health system in an ethically acceptable fashion need to take these findings into account.


Structural Polymorphism as the Result of Kinetically Controlled Self-Assembly.
Traditionally, the goal of self-assembly and supramolecular chemistry is to engineer an equilibrium structure with a desired geometry and functionality; this is achieved through careful choice of molecular monomers, growth conditions, and substrate. Supramolecular assemblies produced under nonequilibrium conditions, in contrast, can form metastable structures with conformations quite different from those accessible in equilibrium self-assembly. The study of nonequilibrium growth of clusters potentially impacts the study of nucleation in atmospheric aerosols, nucleation in organic crystallization, and mesoscale organization for systems ranging from biological molecules to molecular electronics. In our experiments, we prepare surface monolayers of small organic and organometallic molecules through direct injection of a solution onto a substrate in high vacuum. During this process, the rapid evaporation of small solution droplets in high vacuum can lead to nonequilibrium growth conditions. The resulting structures are then characterized by scanning tunneling microscopy. Among the features observed in these experiments are cyclic, hydrogen-bonded pentamers. For carboxylic acids, the two-molecule ring dimer is the common binding motif. Large, cyclic hydrogen-bonded systems are uncommon, especially so for rings with five members. Despite this, pentagonal clusters appear to be a general phenomenon for systems containing adjacent strong and weak hydrogen-bonding elements on five-member aromatic rings. Regular pentamers have been observed as metastable structures for ferrocenecarboxylic acid, indole-2-carboxylic acid, and isatin (1-H-indole-2,3-dione). Electronic structure calculations confirm the relative stability of these structures with respect to the dimer or catemer conformations which are observed in the solid-state crystal structures. For ferrocenecarboxylic acid, cyclic pentamers undergo further self-assembly, resulting in long-range order in conjunction with local 5-fold rotational symmetry. This system is the first reported self-assembled molecular quasicrystal, and it remains the only example of a hydrogen-bonded quasicrystal. This supramolecular structure forms as a result of the cocrystallization of hydrogen-bonded cyclic pentamers with intercalated molecular dimers. The shared bonding to a single dimer is responsible for locking the adjacent pentamers in specific distances and orientations, which produces the quasicrystal. Careful analysis of experimental data provides evidence that, in some cases, metastable clusters are formed in solution and then subsequently adsorb on the surface. This is a unusual mechanism for supramolecular assembly, and it has important implications for understanding questions in crystal growth, namely: what the initial stages of crystal growth are as molecules are first precipitating from solution; what role the solvent plays in determining crystal structure; and whether solvent-mediated clustering is important in the broader phenomenon of solid-state polymorphism.


Hepatitis B virus and host cell membrane antigens on a primary hepatocellular carcinoma cell line.
We have defined some membrane antigens of the cultured hepatocellular carcinoma cell line PLC/PRF/5, which contains the integrated genome of hepatitis B virus. Using fluoresceinated antibodies, we identified HLA Class 1 glycoprotein and HB surface antigen on the membrane. Only in a minority of cells was physical association of these antigens demonstrated by co-capping. The presence of a "division" antigen was indicated by reactivity of the cells with the murine monoclonal antibody OKT9.


Evolving concepts of laryngeal paralysis.
Accepted concepts of the pathophysiology and treatment of laryngeal paralysis have changed over the years. It has long been observed that symptoms of laryngeal paralysis vary greatly, both between patients and over time. There have been various theories to explain these differences. This article reviews how these ideas have changed over time as research has produced new information. Currently, the most popular view is that the laryngeal nerve regenerates after injury, albeit incompletely and inconsistently, and that variations in symptoms and laryngeal posture can be accounted for by muscle activity.


Nutrition intervention to decrease symptoms in patients with advanced heart failure.
For a majority of patients with advanced heart failure, there is a need for complementary, non-pharmacologic interventions that could be easily implemented by health care providers to provide palliative care. Three major pathologic pathways underlying heart failure symptoms have been identified: fluid overload, inflammation, and oxidative stress. Prior research has demonstrated that three nutrients-sodium, omega-3 fatty acids, and lycopene-can alter these pathologic pathways. Therefore, the purposes of this study are to test the effects of a 6-month nutrition intervention of dietary sodium reduction combined with supplementation of lycopene and omega-3 fatty acids on heart failure symptoms, health-related quality of life, and time to heart failure rehospitalization or all-cause death. The aims of this double blind-placebo controlled study are (1) to determine the effects of a 6-month nutrition intervention on symptom burden (edema, shortness of air, and fatigue) and health-related quality of life at 3 and 6 months, and time to heart failure rehospitalization or all-cause death over 12 months from baseline; (2) compare dietary sodium intake, inflammation, and markers of oxidative stress between the nutrition intervention group and a placebo group at 3 and 6 months; and (3) compare body weight, serum lycopene, and erythrocyte omega-3 index between the nutrition intervention group and a placebo group at 3 and 6 months. A total of 175 patients with advanced heart failure will be randomized to either the nutrition intervention or placebo group.


Validation of the social communication questionnaire in a population cohort of children with autism spectrum disorders.
To examine the properties of the Social Communication Questionnaire (SCQ) in a population cohort of children with autism spectrum disorders (ASDs) and in the general population. SCQ data were collected from three samples: the Special Needs and Autism Project (SNAP) cohort of 9- to 10-year-old children with special educational needs with and without ASD and two similar but separate age groups of children from the general population (n = 411 and n= 247). Diagnostic assessments were completed on a stratified subsample (n = 255) of the special educational needs group. A sample-weighting procedure enabled us to estimate characteristics of the SCQ in the total ASD population. Diagnostic status of cases in the general population samples were extracted from child health records. The SCQ showed strong discrimination between ASD and non-ASD cases (sensitivity 0.88, specificity 0.72) and between autism and nonautism cases (sensitivity 0.90, specificity 0.86). Findings were not affected by child IQ or parental education. In the general population samples between 4% and 5% of children scored above the ASD cutoff including 1.5% who scored above the autism cutoff. Although many of these high-scoring children had an ASD diagnosis, almost all(approximately 90%) of them had a diagnosed neurodevelopmental disorder. This study confirms the utility of the SCQ as a first-level screen for ASD in at-risk samples of school-age children.


[Outcome assessment in lumbar spine surgery: the patient's perspective].
At present, there is an increasing interest in evaluating the outcome of lumbar spinal surgery from the patient's perspective. For this purpose, numerous self-report questionnaires for patients have been developed during last two decades. Recently, a core set of five domains has been recommended by an international panel of experts in order to assess patients with back pain: pain intensity and frequency, back specific function, general health status, work status and patient satisfaction. Also, several specific questionnaires to measure these domains, such as the Oswestry Disability Index, the Roland-Morris Disability Questionnaire, or the Short-Form 36, have been selected. In this paper, information about elementary features, properties and interpretation of these questionnaires, as well as recommendations of the international panel, are provided. Some adaptations to these statements for use in our country are suggested. In the discussion advantages, disadvantages and controversies related to the employment of questionnaires, and the need of further research on this field, are emphasized.


Inferring population structure and genetic diversity of broad range of wild diploid alfalfa (Medicago sativa L.) accessions using SSR markers.
Diversity analyses in alfalfa have mainly evaluated genetic relationships of cultivated germplasm, with little known about variation in diploid germplasm in the M. sativa-falcata complex. A collection of 374 individual genotypes derived from 120 unimproved diploid accessions from the National Plant Germplasm System, including M. sativa subsp. caerulea, falcata, and hemicycla, were evaluated with 89 polymorphic SSR loci in order to estimate genetic diversity, infer the genetic bases of current morphology-based taxonomy, and determine population structure. Diploid alfalfa is highly variable. A model-based clustering analysis of the genomic data identified two clearly discrete subpopulations, corresponding to the morphologically defined subspecies falcata and caerulea, with evidence of the hybrid nature of the subspecies hemicycla based on genome composition. Two distinct subpopulations exist within each subsp. caerulea and subsp. falcata. The distinction of caerulea was based on geographical distribution. The two falcata groups were separated based on ecogeography. The results show that taxonomic relationships based on morphology are reflected in the genetic marker data with some exceptions, and that clear distinctions among subspecies are evident at the diploid level. This research provides a baseline from which to systematically evaluate variability in tetraploid alfalfa and serves as a starting point for exploring diploid alfalfa for genetic and breeding experiments.


Treatment Guidelines for Atopic Dermatitis Since the Approval of Dupilumab: A Systematic Review and Quality Appraisal Using AGREE-II.
Since its approval for adults with moderate-to-severe atopic dermatitis (AD) in 2017, dupilumab has been incorporated into clinical practice guidelines (CPGs). However, recommendations differ internationally, and the quality assessment of their development is unclear. We aimed to systematically review and appraise the quality of CPGs for adult AD reported since 2017 and map the recommendations for dupilumab initiation relative to conventional systemic therapy (CST). A literature search was conducted in June 2020 in MEDLINE, EMBASE, SCOPUS, and CINAHL. Twelve CPGs were retrieved. Methodological quality was assessed using the validated Appraisal of Guidelines for Research & Evaluation II tool (AGREE-II). Recommendations were extracted and compared. AGREE-II median scores per domain of the CPGs were (%, r = range): scope/purpose, 78% (50-96); stakeholder involvement, 54% (28-85); rigor of development, 39% (21-63); clarity of presentation, 85% (69-100); applicability, 27% (6-51); and editorial independence, 76% (42-100). Neither met the threshold of 70% quality criteria for rigor of development nor the applicability domains. Three CPGs met the criteria for recommendation without modification. CPGs' approach to dupilumab initiation was as follows: second line, preferred over CST and nbUVB (n = 1/12 CPG); second line, equivalent to CST or nbUVB (n = 3/12 CPGs); third line, after nbUVB or CST (n = 5/12 CPGs); and fourth line after nbUVB and CST (n = 2/12). No consensus was reached for n = 1/12 CPG. Dupilumab is now incorporated into CPGs for adult AD. These CPGs exhibited good quality in scope/purpose, clarity, and editorial independence domains. However, none met AGREE-II criteria for methodological rigor/applicability. Gaps were found in mechanisms for updates, facilitators/barriers, resource implications, and stakeholder involvement. Only n = 3/12 CPGs met quality criteria for recommendation without modifications. Of these, two favored a conservative sequential approach for the initiation of dupilumab relative to CST, while one did not reach consensus. Our findings highlight divergent recommendations AD treatment, underlining a need to incorporate quality criteria into future guideline development.


Calcium-sensing receptor and associated diseases.
The calcium-sensing receptor (CASR) is expressed in parathyroid hormone (PTH)-secreting cells of the parathyroid gland and cells lining the renal tubule. The activated CASR modulates intracellular signaling pathways altering PTH secretion and renal cation and water handling. Inherited abnormalities of the CASR gene give rise to a variety of disorders of mineral ion homeostasis. Heterozygous loss-of-function mutations cause familial (benign) hypocalciuric hypercalcemia (FHH) in which the lifelong mild hypercalcemia is generally asymptomatic. Homozygous inactivating mutations give rise to neonatal severe hyperparathyroidism (NSHPT) with extreme hypercalcemia and marked skeletal changes. Heterozygous activating mutations of the CASR cause autosomal dominant hypocalcemia (ADH) that may be asymptomatic or present with seizures in the neonatal period or childhood or later in life. Phenocopies of FHH or ADH are due to circulating CASR inactivating or activating autoantibodies, respectively. The CASR is the target of small molecule allosteric modifiers, either activators, calcimimetics, or inhibitors, calcilytics.


Copper-Catalyzed Vinylogous Aerobic Oxidation of Unsaturated Compounds with Air.
A mild and operationally simple copper-catalyzed vinylogous aerobic oxidation of β,γ- and α,β-unsaturated esters is described. This method features good yields, broad substrate scope, excellent chemo- and regioselectivity, and good functional group tolerance. This method is additionally capable of oxidizing β,γ- and α,β-unsaturated aldehydes, ketones, amides, nitriles, and sulfones. Furthermore, the present catalytic system is suitable for bisvinylogous and trisvinylogous oxidation. Tetramethylguanidine (TMG) was found to be crucial in its role as a base, but we also speculate that it serves as a ligand to copper(II) triflate to produce the active copper(II) catalyst. Mechanistic experiments conducted suggest a plausible reaction pathway via an allylcopper(II) species. Finally, the breadth of scope and power of this methodology are demonstrated through its application to complex natural product substrates.


MOF-Templated Assembly Approach for Fe3 C Nanoparticles Encapsulated in Bamboo-Like N-Doped CNTs: Highly Efficient Oxygen Reduction under Acidic and Basic Conditions.
Developing high-performance non-precious metal catalysts (NPMCs) for the oxygen-reduction reaction (ORR) is of critical importance for sustainable energy conversion. We report a novel NPMC consisting of iron carbide (Fe3 C) nanoparticles encapsulated in N-doped bamboo-like carbon nanotubes (b-NCNTs), synthesized by a new metal-organic framework (MOF)-templated assembly approach. The electrocatalyst exhibits excellent ORR activity in 0.1 m KOH (0.89 V at -1 mA cm-2 ) and in 0.5 m H2 SO4 (0.73 V at -1 mA cm-2 ) with a hydrogen peroxide yield of below 1 % in both electrolytes. Due to encapsulation of the Fe3 C nanoparticles inside porous b-NCNTs, the reported NPMC retains its high ORR activity after around 70 hours in both alkaline and acidic media.


Sparse Codebook Model of Local Structures for Retrieval of Focal Liver Lesions Using Multiphase Medical Images.
Characterization and individual trait analysis of the focal liver lesions (FLL) is a challenging task in medical image processing and clinical site. The character analysis of a unconfirmed FLL case would be expected to benefit greatly from the accumulated FLL cases with experts' analysis, which can be achieved by content-based medical image retrieval (CBMIR). CBMIR mainly includes discriminated feature extraction and similarity calculation procedures. Bag-of-Visual-Words (BoVW) (codebook-based model) has been proven to be effective for different classification and retrieval tasks. This study investigates an improved codebook model for the fined-grained medical image representation with the following three advantages: (1) instead of SIFT, we exploit the local patch (structure) as the local descriptor, which can retain all detailed information and is more suitable for the fine-grained medical image applications; (2) in order to more accurately approximate any local descriptor in coding procedure, the sparse coding method, instead of K-means algorithm, is employed for codebook learning and coded vector calculation; (3) we evaluate retrieval performance of focal liver lesions (FLL) using multiphase computed tomography (CT) scans, in which the proposed codebook model is separately learned for each phase. The effectiveness of the proposed method is confirmed by our experiments on FLL retrieval.


MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review).
Lung adenocarcinoma (LUAD) poses a significant global health burden owing to its high incidence rate and unfavorable prognosis, driven by frequent recurrence and drug resistance. Understanding the biological mechanisms underlying LUAD is imperative to developing advanced therapeutic strategies. Recent research has highlighted the role of dysregulated microRNAs (miRNAs) in LUAD progression through diverse signaling pathways, including the Wnt and AKT pathways. Of particular interest is the novel pathological mechanism involving the interaction between competing endogenous RNAs (ceRNAs) and miRNAs. This review critically analyzed the impact of aberrant miRNA expression on LUAD development, shedding light on the associated signaling pathways. It also highlighted the emerging significance of ceRNA‑miRNA interactions in LUAD pathogenesis. Elucidating the intricate regulatory networks involving miRNAs and ceRNAs presents a promising avenue for the development of potential therapeutic interventions and diagnostic biomarkers in LUAD. Further research in this area is essential to advance precision medicine approaches and improve patient outcomes.


[Hyperventilation syndrome in a very old woman].
A 92-year-old woman was admitted to our hospital due to hypertension, nausea, pain in the anterior part of the chest, epigastralgia, and tachypnea. During the initial examination of the patient in the emergency ward, she was very excited, howled, and both her hands were numb. Arterial blood gas analysis revealed a marked alkalemia (pH greater than 7.55) and hypocapnia (Pco2 24.1 mmHg). After paper bag re-breathing, the pH and Pco2 were within normal limits. Because there was no lesion in the lungs or the brain that would account for hyperventilation and convulsions, the attack was considered to be a manifestation of hyperventilation syndrome should be carefully considered in the differential diagnosis of disturbance of consciousness even in elderly patients.


Predictive factors of operative or nonoperative management of blunt hepatic trauma.
Nonoperative management (NOM) has revolutionized the care of blunt hepatic trauma patients. The aim of the present study was to identify and evaluate the predictors of NOM of these patients. The Trauma Registry data of 55 consecutive adult patients admitted with blunt hepatic trauma over a 4-year period was reviewed. Patients were divided into immediately operated (OP-group) and selected for NOM (NOM-group). Factors analyzed were: demographics, injury mechanism, initial vital signs, liver injury grade, concomitant injuries, and total injury severity scoring systems. Concomitant abdominal trauma, high Injury Severity Score (ISS), low International Classification of Diseases 9(th) revision Injury Severity Score (ICISS), and low probability of survival (Ps) were predictors for operative management. Compared to NOM-patients (66%, N=36), OP-patients (34%, N=19) suffered more frequently concomitant abdominal injuries (84.2% vs 47.2%, P=0.004) and were more severely totally injured as expressed by higher ISS (25 vs 20, P=0.01), lower ICISS (0.51 vs 0.74, P=0.003), and lower Ps (0.81 vs 0.98, P=0.005). NOM resulted in lower intensive care unit admission and mortality rates (47.2% vs 78.9%, P=0.002 and 2.7% vs 15.8%, P=0.03, respectively). NOM-success rate was 92%. NOM of blunt hepatic trauma is safe and efficient. Concomitant abdominal trauma, ISS, ICISS, and Ps are predictors for operative or nonoperative management.


Modeling capsid self-assembly: design and analysis.
A series of simulations aimed at elucidating the self-assembly dynamics of spherical virus capsids is described. This little-understood phenomenon is a fascinating example of the complex processes that occur in the simplest of organisms. The fact that different viruses adopt similar structural forms is an indication of a common underlying design, motivating the use of simplified, low-resolution models in exploring the assembly process. Several versions of a molecular dynamics approach are described. Polyhedral shells of different sizes are involved, the assembly pathways are either irreversible or reversible and an explicit solvent is optionally included. Model design, simulation methodology and analysis techniques are discussed. The analysis focuses on the growth pathways and the nature of the intermediate states, properties that are hard to access experimentally. Among the key observations are that efficient growth proceeds by means of a cascade of highly reversible stages, and that while there are a large variety of possible partial assemblies, only a relatively small number of strongly bonded configurations are actually encountered.


Design and Implementation of a Professional Development Course Series.
Objective. To design and implement a longitudinal course series focused on professional development and professional identity formation in pharmacy students at Western New England University. Methods. A four-year, theme-based course series was designed to sequentially and longitudinally impart the values, attributes, and characteristics of a professional pharmacist. Requirements of the course include: goal planning and reflective assignments, submission of "Best Works," attendance at professional meetings, completion of service hours, annual completion of a Pharmacy Professionalism Instrument, attendance at Dean's Seminar, participation in roundtable discussions, and maintenance of an electronic portfolio. Though the Professional Development course series carries no credit, these courses are progression requirements and students are assessed on a pass/fail basis. Results. Course pass rates in the 2015-2016 academic year for all four classes were 99% to 100%, suggesting the majority of students take professional development seriously and are achieving the intended outcomes of the courses. Conclusion. A professional development course series was designed and implemented in the new Doctor of Pharmacy program at Western New England University to enhance the professional identity formation of students.


Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model.
Gene therapy represents an attractive approach for the treatment of eye diseases such as glaucoma. Ocular administration of viral vectors produces localized retinal gene expression with reduced risks of side effects reported with systemic administration of viral vectors. Recombinant adeno-associated viral (AAV) vectors have proven effective in producing long-term retinal gene expression, due to stable integration of DNA into the genome and lack of host immune response to the virus. Recently developed AAV constructs using the chicken beta-actin (CBA) promoter drive highly efficient transgene expression in retinal ganglion cells (RGCs), photoreceptors, and pigment epithelium. Rats were given unilateral intravitreal injections of AAV-CBA vector coding for human baculoviral IAP repeat-containing protein-4 (BIRC4), a potent caspase inhibitor. Ocular hypertension was induced in the same eye by sclerosis of aqueous humor outflow channels. After chronic exposure to elevated intraocular pressure, we performed optic nerve axon counts to determine the neuroprotective effects of retinal BIRC4 expression, and compared axon survival with vector and balanced salt solution control groups. Gene therapy delivering BIRC4 significantly promoted optic nerve axon survival in a chronic ocular hypertensive model of rat glaucoma. Blocking RGC apoptosis with caspase inhibitors represents a promising approach for treatment of human glaucoma.


An oxygen scavenging system for improvement of dye stability in single-molecule fluorescence experiments.
The application of single-molecule fluorescence techniques to complex biological systems places demands on the performance of single fluorophores. We present an enzymatic oxygen scavenging system for improved dye stability in single-molecule experiments. We compared the previously described protocatechuic acid/protocatechuate-3,4-dioxygenase system to the currently employed glucose oxidase/catalase system. Under standardized conditions, we observed lower dissolved oxygen concentrations with the protocatechuic acid/protocatechuate-3,4-dioxygenase system. Furthermore, we observed increased initial lifetimes of single Cy3, Cy5, and Alexa488 fluorophores. We further tested the effects of chemical additives in this system. We found that biological reducing agents increase both the frequency and duration of blinking events of Cy5, an effect that scales with reducing potential. We observed increased stability of Cy3 and Alexa488 in the presence of the antioxidants ascorbic acid and n-propyl gallate. This new O(2)-scavenging system should have wide application for single-molecule fluorescence experiments.


Interventional study to evaluate the impact of an alcohol-based hand gel in improving hand hygiene compliance.
To evaluate the effects of the introduction of an alcohol-based hand gel and multifaceted quality improvement (QI) interventions on hand hygiene (HH) compliance. Interventional, randomized cohort study with four study phases (baseline; limited intervention in two units; full intervention in three units; washout phase), performed in three intensive care units at a pediatric referral hospital. During 724 thirty-minute daytime monitoring sessions, a nonidentified observer witnessed 12,216 opportunities for HH and recorded compliance. Introduction of an alcohol-based hand gel; multifaceted QI interventions (educational program, opinion leaders, performance feedback). Baseline compliance decreased after the first 2 weeks of observation from 42.5% to 28.2% (presumably because of waning of a Hawthorne effect), further decreased to 23.3% in the limited intervention phase and increased to 35.1% after the introduction of a hand gel with QI support in all three units (P < 0.001). The rise in compliance persisted in the last phase (compliance, 37.2%); however, a gradual decline was observed during the final weeks. Except for the limited intervention phase, compliance achieved through standard handwashing and glove use remained stable around 20 and 10%, respectively, whereas compliance achieved through gel use increased to 8% (P < 0.001). After adjusting for confounding, implementation of the hand gel with QI support remained significantly associated with compliance (odds ratio, 1.6; 95% confidence interval, 1.4 to 1.8). In a final survey completed by 62 staff members, satisfaction with the hand gel was modest (45%). We noted a statistically significant, modest improvement in compliance after introduction of an alcohol-based hand gel with multifaceted QI support. When appropriately implemented, alcohol-based HH may be effective in improving compliance.


Spatial organization and function of RNA molecules within phase-separated condensates are controlled by Dnd1.
Germ granules, condensates of phase-separated RNA and protein, are organelles essential for germline development in different organisms The patterning of the granules and its relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that localization of RNA molecules to the periphery of the granules, where ribosomes are localized depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates' periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for posttranscriptional control, and its importance for preserving germ cell totipotency.


Photo methods for qualitative research in nursing: an ontological and epistemological perspective.
The use of photo research methods is influenced by underlying ontological and epistemological assumptions. Variant assumptions about reality and knowledge converge to conceive a relationship between the knower and what can be known. These assumptions provide the rationale for decided ways of engaging participants in the process of scientific inquiry. In this paper, we examine how perspectives of realism and relativism may shape epistemological understandings and influence type and use of photo methods in qualitative research. Based on deliberations about underlying ontological and epistemological assumptions and related strengths and challenges of photo methods, we assert that photo methods contribute to the development of knowledge that both matters to participants and informs nursing practice.


Dimensional Control in Contorted Aromatic Materials.
This Account details key developments in dimensional control of contorted aromatics for organic electronics. Coronene, perylene, pyrene, and [4]helicene, which are fragments of graphene, can be contorted using facile synthetic chemistry into large nanoribbons and nano-architectures. In comparing contorted or higher-dimensional graphene architectures to planar or lower-dimensional species, the materials properties are reliably enhanced for the contorted aromatics. Examples of enhanced properties include optical absorptivity, conductivity, device photoconversion efficiency, and solubility. These enhancements are exemplified in organic photovoltaics, photodetectors, field effect transistors, and perovskite solar cells. Described herein are key advances in dimensional control of contorted aromatics that have resulted in world record photoconversion efficiencies, photodetection capabilities matching inorganic state-of-the-art devices, and ∼5 nm long ultrathin soluble graphene nanoribbons.


[Familial Focal Segmental Glomerulosclerosis, a vademecum for clinical nephrologist].
The new genomic technologies (Next Generation Sequencing, NGS) are opening a new era in Genomic Medicine. This simple guide gives a state-of-the-art description of the genes that cause Focal Segmental Glomerulosclerosis and nephrotic syndrome.


Facile fabrication of ZnO nanowire memory device based on chemically-treated surface defects.
In this study, we demonstrate a transistor-type ZnO nanowire (NW) memory device based on the surface defect states of a rough ZnO NW, which is obtained by introducing facile H2O2 solution treatment. The surface defect states of the ZnO NW are validated by photoluminescence characterisation. A memory device based on the rough ZnO NW exhibits clearly separated bi-stable states (ON and OFF states). A significant current fluctuation does not exist during repetitive endurance cycling test. Stable memory retention characteristics are also achieved at a high temperature of 85 °C and at room temperature. The surface-treated ZnO NW device also exhibits dynamically well-responsive pulse switching under a sequential pulse test configuration, thereby indicating its potential practical memory applications. The simple chemical treatment strategy can be widely used for modulating the surface states of diverse low-dimensional materials.


Effect of gender and body mass index on pulmonary function tests in adolescents of tribal population of a north eastern state of India.
The present study was planned to assess the pulmonary function in tribal adolescents (age 12-16 yrs) of Tripura, a north eastern state of India, and to evaluate the effect of body mass index (BMI) on pulmonary functions of male and female subjects from tribal population. One hundred and seventeen male and seventy female subjects were selected for the study through a randomized method of sampling. Pulmonary function parameter recorded were forced vital capacity (FVC), forced expired volume in 1 second (FEV1), peak expiratory flow rate (PEFR) and maximal expiratory pressure (MEP). Values of all the pulmonary function parameters recorded in female subjects were found to be lower than the male subjects. FVC, FEV1, PEFR, MEP recorded in subjects from both the sexes correlated significantly with BMI. The results of the study provide basic data on pulmonary function parameters of tribal adolescents from Tripura.