[Magnesium and vitamin B2 status of children with bronchial asthma and obesity].
Insufficiency or deficiency of some micronutrients may be additional modifying factors that influence the pathogenesis of the disease and the effectiveness of standard pharmacotherapy. The aim of the study - to evaluate the level of magnesium and vitamin B2 in blood serum of patients with bronchial asthma and obesity in order to develop methods for individual correction of deficiency. Material and methods. The study included 51 children aged 12-17 years. The first group included 23 patients (12 girls and 11 boys) with asthma with comorbidities (obesity), and the second group consisted of 28 children (10 girls and 18 boys) with obesity. The concentration of magnesium in blood serum was determined by a colorimetric method without deproteinization, and vitamin B2 - by an immunological microbiological method. Results and discussion. When analyzing the concentration of magnesium in blood serum of the examined children, it was found that in patients with bronchial asthma and obesity, a reduced content of this mineral was observed in 15 (65.2%) patients. The average magnesium concentration was 0.66±0.02 mmol/l at a rate of 0.7-1.2 mmol/l. A statistically significant decrease in the magnesium level in children suffering from asthma and obesity was noted, compared with the level in children with obesity (0.66 [0.57; 0.73] vs 0.71 [0.67; 0.73] mmol/l, р<0.05). Low serum magnesium levels in obese patients were detected more rarely (р<0.05) - only in 6 (21.4%) children, mostly in patients with grade III obesity. The remaining 22 (78.6%) children had magnesium level within the normal range. Patients with low serum magnesium levels showed increased irritability, sleep disturbance, loss of memory and concentration. Vitamin B2 levels in all examined children were within the normal range (137-370 ng/ml). Conclusion. The results indicate a decrease in the concentration of magnesium and normal levels of vitamin B2 in serum in patients with bronchial asthma and obesity. Low serum magnesium levels were observed in children with low bronchial asthma control. To increase the effectiveness of therapy and control the symptoms of bronchial asthma, especially when combined with obesity, correction of the accompanying magnesium deficiency is necessary.


The alarmin HMGB-1 influences healing outcomes in fetal skin wounds.
In mice, cutaneous wounds generated early in development (embryonic day 15, E15) heal scarlessly, while wounds generated late in gestation (embryonic day 18, E18) heal with scar formation. Even though both types of wounds are generated in the same sterile uterine environment, scarless fetal wounds heal without inflammation, but a strong inflammatory response is observed in scar-forming fetal wounds. We hypothesized that altered release of alarmins, endogenous molecules that trigger inflammation in response to damage, may be responsible for the age-related changes in inflammation and healing outcomes in fetal skin. The purpose of this study was to determine whether the alarmin high-mobility group box-1 (HMGB-1) is involved in fetal wound repair. Immunohistochemical analysis showed that in unwounded skin, E18 keratinocytes expressed higher levels of HMGB-1 compared with E15 keratinocytes. After injury, HMGB-1 was released to a greater extent from keratinocytes at the margin of scar-forming E18 wounds, compared with scarless E15 wounds. Furthermore, instead of healing scarlessly, E15 wounds healed with scars when treated with HMGB-1. HMGB-1-injected wounds also had more fibroblasts, blood vessels, and macrophages compared with control wounds. Together, these data suggest that extracellular HMGB-1 levels influence the quality of healing in cutaneous wounds.


Academic Mentorship Builds a Pathology Community.
Since academic mentorship focuses on developing and supporting the next generation of pathologists as well as the existing faculty, it plays a vital role in creating a successful academic pathology department whose faculty deliver quality teaching, research, and clinical care. The central feature is the mentor-mentee relationship which is built on mutual respect, transparency, and a genuine interest from the mentor in the success of the mentee. This relationship is a platform for career development, academic guidance, informed professional choices, and problem solving. Departments of pathology must embrace a culture of effective mentorship so that trainees and faculty members are well mentored. Mentorship should become an academic activity that is valued and rewarded. Departments should create and support formal educational programs that train mentors in mentorship. Effective models of formal mentorship need to be created and evaluated in order to strengthen academic pathology. A successful mentorship culture will provide for a sustainable community of academic pathologists that transmits their best practices to the next generation.


Breaking the taboo: an interpretative phenomenological analysis of healthcare professionals' experience of caring for palliative patients with disgusting symptoms.
Disgusting symptoms are common in healthcare settings. Previous research has identified that healthcare professionals systematically avoid contact with patients with disgusting symptoms, potentially compromising patient care. Furthermore, research has highlighted disgust in healthcare professionals as a possible contributory factor to dehumanisation and abuse of patients. Given that healthcare professionals often feel that disgust is unprofessional, they may also feel unable to express or process disgust in their work, potentially impacting their emotional health, and contributing to burning out. Given the ubiquity of disgust in palliative care, we investigated how palliative healthcare professionals' experience and cope with disgust in their work, and how they are supported in doing so. We interviewed six palliative healthcare professionals and analysed their transcripts using Interpretative Phenomenological Analysis, from which four themes are discussed. Three key findings emerged. Firstly, participants were uncomfortable talking about disgust at work, reducing their access to support for disgust. Secondly, participants often neglected their own emotional needs, and as a result, sometimes become emotionally entangled with patients. Finally, participants were at risk of reducing vital socio-emotional support for patients with disgusting symptoms. Based on our analysis, we suggest interventions to counteract these effects.


[Stage Ⅳ Gastric Cancer with Long Term Survival by Conversion Surgery-A Case Report].
A 78-year-old man presenting with a chief complaint of discomfort was found to have advanced gastric cancer invading pancreatic body, and with the metastasis of paraaortic lymph node(No. 16). After 3 courses of the S-1 plus oxaliplatin regimen, CT scan showed the disappearance of invasion to pancreatic body, and the No. 16 lymph node. Then total gastrectomy(D2+No. 19+No. 16a1+No. 16a2), Roux-en-Y reconstruction and cholecystectomy were undergoing. Histological assessment for treatment response showed Grade 1a, and we finally diagnosed gastric cancer: MU, Post, type 2, 30×20 mm, tub1>por1, ypT3, ypN1, ycM0, ypStage ⅡB. The postoperative course was uneventful, and the patient was discharged from the hospital on postoperative day 19. S-1 as adjuvant chemotherapy was performed for 12 months, and no recurrence was recognized for 5 years and 9 months after operation.


Design of a compact and high sensitive refractive index sensor base on metal-insulator-metal plasmonic Bragg grating.
A nanometric and high sensitive refractive index sensor based on the metal-insulator-metal plasmonic Bragg grating is proposed. The wavelength encoded sensing characteristics of the refractive index sensor were investigated by analyzing its transmission spectrum. The numerical results show that a good linear relationship between the Bragg wavelength and the refractive index of the sensing material can be obtained, which is in accordance with the analytical results very well. A high refractive index sensitivity of 1,488 nm/RIU around Bragg resonance wavelength of 1,550 nm was obtained. Besides, the simulation results show that the sensitivity is depended on the Bragg resonance wavelength and the longer the Bragg resonance wavelength, the higher sensitivity can be obtained. Furthermore, the figure of merit of the refractive index sensor can be greatly increased by introducing a nano-cavity in the proposed plasmonic Bragg grating structure. This work pave the way for high sensitive nanometric refractive index sensor design and application.


Thiamine responsive anaemia: a study of two further cases.
A brother and sister of Pakistani origin suffered from sensorineural deafness, diabetes mellitus and a macrocytic anaemia. Their bone marrows showed megaloblastic erythropoiesis and contained many ringed sideroblasts. Electron microscope studies of the bone marrow revealed (1) iron-laden mitochondria in many erythroblasts, (2) non-specific abnormalities indicative of dyserythropoiesis in some erythroblasts, and (3) evidence of ineffective erythropoiesis. The deoxyuridine suppression test indicated that the megaloblastic changes were not caused by an impairment of the methylation of deoxyuridylate. Studies of nucleic acid synthesis in the bone marrow cells showed that the rate of incorporation of [3H]thymidine into DNA was increased and that the rates of incorporation of [14C]glycine and [14C]adenine into both DNA and RNA were essentially within the normal range. The anaemia did not respond to therapy with hydroxocobalamin, folic acid or pyridoxine but responded to 25 mg thiamine, daily, by mouth. In one of the cases a post-thiamine marrow aspirate showed a considerable improvement in both the megaloblastic and sideroblastic changes.


How does perceived respect affect innovative behavior? The role of thriving at work and spiritual leadership.
Many enterprises use innovation to deal with the rapidly changing business environment and gain market competitiveness. How to internally motivate employees, especially the new generation of employees (e.g., employees born after 1980), to take initiative to innovate is receiving great interest from both academic and practical perspectives. Based on the broaden-and-build theory, this study presents a moderated mediation model of the impact of perceived respect on innovative behavior. SPSS and Mplus were used to analyze the data from 506 leader-employee pairs. The results show that perceived respect had a significant positive influence on innovative behavior through the effect of thriving at work, and the moderating effect of spiritual leadership was significant. When the effect of spiritual leadership was strong, the effect of perceived respect on innovative behavior through the effect of thriving at work was enhanced. This study reveals the dynamic mechanisms of improving employees' innovative behavior, providing theoretical and practical ideas for promoting enterprises' sustainable and innovative development.


Current perspectives in assessment: the assessment of performance at work.
Traditional assessment has improved significantly over the past 50 years. A number of new testing methods are now in place, the computer is improving both the fidelity and efficiency of examinations, and the psychometric principles on which assessment rests are more sophisticated than ever. There is growing interest in quality improvement and there are increasing demands for public accountability. This has shifted the focus of testing from education to work. The purpose of this paper is to describe the assessment of work. In contrast to traditional assessment, there are no 'methods' for the evaluation of work because the content and difficulty of the examination are not controlled in any fashion. Instead it is a matter of identifying the basis for the judgements (outcomes, process, or volume), deciding how the data will be gathered (practice records, administrative databases, diaries/logs, or observation), and avoiding threats to validity and reliability (patient mix, patient complexity, attribution, and numbers of patients). Overall, the assessment of doctors' performance at work is in its infancy and much research and development is needed. Nonetheless, it is being used increasingly in programmes of continuous quality improvement and accountability. It is critical that refinements occur quickly to ensure that patients receive the highest quality of care and that doctors are treated fairly and provided with the information they need to guide their professional development.


Measurements of fast fluctuations of viscoelastic properties with the quartz crystal microbalance.
The quartz crystal microbalance (QCM) was used to study the variability of acoustic properties of living cells on the sub-second time scale. A confluent cell layer of rat cardiac myocytes was grown onto the electrode of quartz crystal resonator. The cell layer performed periodic, synchronous contractions at a rate of about 1.5 Hz. In order to monitor these rather fast changes in the state of the cells, the QCM was operated in a "fast mode", which allows sampling of the shift of the resonance frequency and energy dissipation with a rate of up to 100 Hz. The contractions were clearly reflected in periodic variations of the resonance frequency and the bandwidth. The rate of the contractions, in particular, could be easily detected in this way. Building on the rate of contraction, the setup can be used to monitor the response of the cell layer to heart stimulating drugs like isoproterenol. Depending on the concentration of isoproterenol, the beat rate was found to increase by up to a factor of two.


Chronic Inflammation in Chronic Kidney Disease.
Chronic kidney disease (CKD) is an increasingly prevalent disease that affects approximately 10-12% of the global population. Therefore, it is considered a public health priority. Persistent and systemic low-grade chronic inflammation (CI) is an important part of the poor prognosis in CKD, especially for patients with advanced disease. For example, CI worsens anemia and promotes atherosclerosis. Therefore, CI deserves our attention. The formation of CI in CKD involves many aspects. Among them, the decline in the glomerular filtration rate leads to the influence of substances or inflammatory cytokines that should be cleared in time. In addition, oxidative stress, the gut and the gut microbiota are also influencing factors. In this review, we highlight the mechanisms involved in the development of CI in CKD.


Sociodemographic Determinants of COVID-19 Vaccine Hesitancy, Fear of Infection, and Protection Self-Efficacy.
Arkansas COVID-19 vaccine uptake has been lower than the national average. This study examined associations between sociodemographic factors and COVID-19 vaccine hesitancy, fear of infection, and protection self-efficacy. Adults either residing, having employment, or receiving health care in Arkansas (n = 754) participated in an online survey between October 30, 2020 and January 16, 2021. Participants were recruited in both rural and urban areas from 6 Arkansas primary care clinics. Survey questions addressed sociodemographic factors, COVID-19 infection fear, protection self-efficacy, and COVID-19 vaccine attitudes. Bivariate and multivariable logistic regression models were used to assess associations between dependent variables and respondents' sociodemographic characteristics, COVID-19 infection fear, and COVID-19 protection self-efficacy. About 38% of participants reported COVID-19 vaccine hesitancy. Age, sex, race, and education were significantly associated with COVID-19 and general vaccine attitudes. Odds of COVID-19 vaccine hesitancy decreased as age increased (OR = 0.98; P < .01). Women had higher odds of COVID-19 vaccine hesitancy than men (OR = 1.52; P < .05). Respondents with a high school diploma and below and respondents with some college or a technical degree had greater odds of COVID-19 vaccine hesitancy (OR = 2.58; P < .001; and OR = 1.97; P < .01, respectively) compared to respondents with a 4-year college degree. Black/African American respondents had greater odds of COVID-19 vaccine hesitancy compared to White respondents (OR = 3.08; P < .001). No significant difference was observed among rural and urban respondents regarding COVID-19 vaccine hesitancy; however, respondents in rural areas were more likely to report low general vaccine trust compared to those in urban areas (OR = 1.87; P < .01). Respondents reporting no fear (OR = 5.51; P < .001) and very little fear (OR = 1.95; P < .05) of COVID-19 had greater odds of COVID-19 vaccine hesitancy compared to respondents who feared COVID-19 infection to a great extent. COVID-19 vaccine hesitancy and general trust in vaccines differ significantly among age, sex, race, and education. These trust and hesitancy patterns are challenges for achieving population immunity and follow similar patterns of vulnerability to COVID-19. Vaccination programs and interventions must consider these differences in COVID-19 vaccine hesitancy and general vaccine trust to alleviate COVID-19 disparities. Findings make a significant contribution in evaluating vaccine hesitancy among a large, diverse sample from a rural state.


[Association between ovarian stimulation regime and protein metabolism of patients undergoing IVF/ICSI therapy].
The aim of this study was to determine the relationship between the ovarian stimulation protocol (with HMG or FSH) after down-regulation with GnRH anologa and protein (total protein and albumin) as well as bilirubin and urea in serum. Furthermore, it was intended to find out the effect of these parameters on IVF/ICSI outcome. 50 patients were included in this study. All patients underwent controlled ovarian hyperstimulation for assisted reproduction therapy either with FSH (Gonal-F) or HMG (Menogon). Ovulation induction was induced by human chorionic gonadotrophine (HCG, Predalon) 10 000 IU i. m. The protein concentration (total protein, albumin) as well as bilirubin and urea concentrations were determined before down-regulation with GnRHa, at the beginning of ovarian stimulation with FSH or HMG, on the day of ovulation induction with HCG, during oocyte retrieval and fourteen days after embryo transfer. The age, body mass index and etiology of infertility showed no significant difference between patients stimulated with HMG or FSH. Total protein and albumin concentration decreased significantly (p=0.001) from 77.45 +/- 5.90 g/L and 47.02 +/- 3.41 g/L to 74.60 +/- 4.6 g/L and 45.04 +/- 2.39 g/L, respectively at the time of oocyte retrieval. Whereas, no significant change with bilirubin and urea concentration was observed. However, the mean concentration of total protein, albumin, bilirubin of patients who become pregnant was higher of those who did not. In conclusion, this study shows that total protein and albumin concentration in plasma decreased during the follicular phase significantly with the application of exogenous gonadotrophins and steroid hormones in comparison to the value before down-regulation. The mean value of total protein, albumin, bilirubin of patients who become pregnant was higher (but not significant) of those who did not. However, the high individual variation in the present results shows that these parameters are not useful as a predictor of IVF/ICSI outcome.


"Search-and-capture" of microtubules through plus-end-binding proteins (+TIPs).
The generation of a polarized microtubule organization is critically important for proper cellular functions, such as cell division, differentiation and migration. Microtubules themselves are highly dynamic structures, and this dynamic property is temporally and spatially regulated within cells, especially at their plus ends. To explain how microtubules set up and make contacts with cellular structures, a "search-and-capture" mechanism has been proposed, in which the microtubule plus ends dynamically search for and capture specific sites, such as mitotic kinetochores and cell cortex. To date, several classes of proteins have been shown to be associated with microtubule plus ends in a wide range of organisms from fungi to humans and to play critical roles in the "search-and-capture" mechanism. In this review, we overview our current understanding of the "plus-end-binding proteins" (+TIPs), including APC (adenomatous polyposis coli) tumor suppressor protein, cytoplasmic linker proteins (CLIPs), CLIP-associating proteins (CLASPs), cytoplasmic dynein/dynactin, and EB1, an APC-interacting protein.


Chili pepper fruits: content and pattern of capsaicinoids in single fruits of different ages.
The content of capsaicinoids differs widely in fruits of an individual plant. This is shown for Capsicum annuum var. Cayenne and var. DeArbol and Capsicum frutescens var. Hot Siberian, respectively. Three age groups, (i) very young, (ii) medium age, and (iii) older fruits, were studied. A consistent dependence on the node position on the plant for fruit weight and capsaicinoid content of the individual fruits was not observed. These traits do not develop concomitantly and are influenced differently by environmental factors. Therefore, the expression as capsaicinoid content per fruit leads to a different conclusion than a comparison of concentration values (mg/kg). This is exemplified for C. frutescens var. Hot Siberian grown in two consecutive years with fruits of lower fruit weight but the same capsaicinoid accumulation in the second year. Higher values for pungency (expressed as mg/kg) would have been the result from the analysis of bulked material. The fatty acid pattern of capsaicinoids is uniform for all fruits from one plant, irrespective of the large variation of total capsaicinoid content.


The Cox-Maze IV procedure for atrial fibrillation is equally efficacious in patients with rheumatic and degenerative mitral valve disease.
To determine whether the etiology of mitral valve disease (MVD), due to either rheumatic or degenerative pathology, influences long-term outcomes after the Cox-Maze IV procedure (CMPIV). Between February 2001 and July 2015, 245 patients received a CMIV and concomitant mitral valve procedure. Patients were separated into 2 cohorts based on their etiology of MVD, degenerative (n = 153) and rheumatic (n = 92). Patients were followed prospectively (mean follow-up: 41 ± 37 months) for recurrent atrial tachyarrhythmias (ATAs). Perioperative variables and long-term freedom from ATAs on and off antiarrhythmic drugs (AADs) were analyzed retrospectively. The 2 groups differed in that patients with rheumatic MVD were younger, more likely female, had a larger preoperative left atrial diameter, a longer duration of atrial fibrillation (AF), a greater percentage of longstanding persistent AF, and worse New York Heart Association functional class (P ≤ .001). Although there was no difference in operative mortality or overall major complications between the groups, the median length of stay in the intensive care unit was longer in the rheumatic cohort. Freedom from recurrent ATAs through 5 years was similar between the 2 cohorts. Predictors of recurrence included failure to use a box-lesion (P = .012), the duration of preoperative AF (P = .001), and early occurrence of ATAs (P = .015). The long-term efficacy of the CMPIV in restoring sinus rhythm was similar in patients with either rheumatic or degenerative mitral valve disease. Despite representing a sicker patient population with a longer duration of preoperative AF, patients with rheumatic MVD equally benefit from the CMPIV.


Driving the Crystallization of Zeolites.
The synthesis of zeolites with new structures and/or improved properties heavily relies on trial and error efforts that are not entirely blind, as the large empirical background accumulated for the last 7 decades can be, to some extent, rationalized and purposefully used to make new materials. The so-called structure-directing factors may be combined to promote (or frustrate) the crystallization of a particular structure. This personal account opens with the concept of geoinspiration, as suggested by Prof. Ruiz-Hitzky, and its application to zeolite synthesis. We then provide a concise overview of structure-direction in the synthesis of zeolites and detail examples, both new and from the literature, on how they can be combined to drive the crystallization towards (or away from) structures displaying particular features.


Nutritional determinants of worldwide diabetes: an econometric study of food markets and diabetes prevalence in 173 countries.
Ageing and urbanization leading to sedentary lifestyles have been the major explanations proposed for a dramatic rise in diabetes worldwide and have been the variables used to predict future diabetes rates. However, a transition to Western diets has been suggested as an alternative driver. We sought to determine what socio-economic and dietary factors are the most significant population-level contributors to diabetes prevalence rates internationally. Multivariate regression models were used to study how market sizes of major food products (sugars, cereals, vegetable oils, meats, total joules) corresponded to diabetes prevalence, incorporating lagged and cumulative effects. The underlying social determinants of food market sizes and diabetes prevalence rates were also studied, including ageing, income, urbanization, overweight prevalence and imports of foodstuffs. Data were obtained from 173 countries. Population-based survey recipients were the basis for diabetes prevalence and food market data. We found that increased income tends to increase overall food market size among low- and middle-income countries, but the level of food importation significantly shifts the content of markets such that a greater proportion of available joules is composed of sugar and related sweeteners. Sugar exposure statistically explained why urbanization and income have been correlated with diabetes rates. Current diabetes projection methods may estimate future diabetes rates poorly if they fail to incorporate the impact of nutritional factors. Imported sugars deserve further investigation as a potential population-level driver of global diabetes.


Emerging Methods to Objectively Assess Pruritus in Atopic Dermatitis.
Atopic dermatitis (AD) is an inflammatory skin disease with a chronic, relapsing course. Clinical features of AD vary by age, duration, and severity but can include papules, vesicles, erythema, exudate, xerosis, scaling, and lichenification. However, the most defining and universal symptom of AD is pruritus. Pruritus or itch, defined as an unpleasant urge to scratch, is problematic for many reasons, particularly its negative impact on quality of life. Despite the profoundly negative impact of pruritus on patients with AD, clinicians and researchers lack standardized and validated methods to objectively measure pruritus. The purpose of this review is to discuss emerging methods to assess pruritus in AD by describing objective patient-centered tools developed or enhanced over the last decade that can be utilized by clinicians and researchers alike. This review is based on a literature search in Medline, Embase, and Web of Science databases. The search was performed in February 2019. The keywords were used "pruritus," "itch," "atopic dermatitis," "eczema," "measurements," "tools," "instruments," "accelerometer," "wrist actigraphy," "smartwatch," "transducer," "vibration," "brain mapping," "magnetic resonance imaging," and "positron emission tomography." Only articles written in English were included, and no restrictions were set on study type. To focus on emerging methods, prioritization was given to results from the last decade (2009-2019). The search yielded 49 results in PubMed, 134 results in Embase, and 85 results in Web of Science. Each result was independently reviewed in a standardized manner by two of the authors (M.S., K.L.), and disagreements between reviewers were resolved by consensus. Relevant findings were categorized into the following sections: video surveillance, acoustic surveillance, wrist actigraphy, smart devices, vibration transducers, and neurological imaging. Examples are provided along with descriptions of how each technology works, instances of use in research or clinical practice, and as applicable, reports of validation studies and correlation with other methods. The variety of new and improved methods to evaluate pruritus in AD is welcomed by clinicians, researchers, and patients alike. Future directions include next-generation smart devices as well as exploring new territories, such as identifying biomarkers that correlate to itch and machine-learning programs to identify itch processing in the brain. As these efforts continue, it will be essential to remain patient-centered by developing techniques that minimize discomfort, respect privacy, and provide accurate data that can be used to better manage itch in AD.


Chemical probing of the tRNA--ribosome complex.
We probed the (Escherichia coli) tRNAPhe--ribosome interaction with the chemical reagents dimethyl sulfate and diethyl pyrocarbonate. This monitored the higher-order structure of the tRNA in this biological complex and identified critical sites in the tRNA molecule involved in binding to the ribosome. The methylation of the N-7 position of guanosine and the N-3 position of cytidine as well as diethyl pyrocarbonate attack on adenosines are sensitive to secondary and tertiary interactions. Here we identify specific bases in E. coli Phe-tRNAPhe affected by the interaction with the ribosome. The 70S ribosome protects the N-3 position of cytidine-74 and 75 in the 3'-terminal C-C-A, suggesting a strong, possibly base pairing, interaction between the ribosome and that universal sequence. The ribosome also induces strong reactivities at the N-7 positions of G-24 and G-46 in the central region of the tRNA molecule near the variable-loop domain as well as less significant reactivities at 11 other guanosines. Two of these, G-10 and G-44, are close to G-24 and G-46 in the center of the molecule; the others (guanosines 1, 5, 6, 18, 19, 63, 65, 69, and 71) are in the coaxial acceptor stem-T stem helix. All of the effects are ribosome induced and occur in the presence or absence of the messenger poly(U). Prior chemical modification of the anticodon bases as well as the two adjacent 3' purines and, less effectively, four purines in the anticodon stem prevent stable poly(U)-directed ribosome binding. Thus, we identify the 3' terminal C-C-A sequence, near the peptidyl transferase site, and the anticodon stem and loop of tRNAPhe as forming critical contacts with the ribosome. Other regions of the molecule become reactive on ribosome binding, but these do not suggest a significant conformational change being more likely due to a change of environment.


The acidity/basicity of metal-containing ionic liquids: insights from surface analysis and the Fukui function.
Metal-containing ionic liquids (ILs) have been recognized as potential solvents, catalysts, catalyst precursors and reagents for many organic processes. In this work, several quantum-chemical parameters, including the surface electrostatic potential (Vs,max and Vs,min), the lowest surface average local ionization energy (I̅s,min), and the electrostatic potential at the position of an atom (EPnuc), were adopted to understand the acidity/basicity of metal-containing ILs. Chlorometallate-based ILs show stronger acidity than conventional ILs, because of the increased electron-deficiency of the imidazole ring upon the incorporation of metal chloride. For the ILs with the Ag-coordinated cations, the acidity tends to attenuate while the basicity becomes stronger, as compared to traditional ILs. In addition, the regional Fukui function was also used to assess the molecular distribution of the Lewis acidity/basicity of the ILs under study. Overall, the introduction of metals into either the cations or the anions influences the acidity/basicity of ILs to a large degree, which would be beneficial for their certain applications, such as catalysis and extraction. We hope that the results presented here will assist in the development of novel metal-containing ILs with desirable properties.


A GTPase chimera illustrates an uncoupled nucleotide affinity and release rate, providing insight into the activation mechanism.
The release of GDP from GTPases signals the initiation of a GTPase cycle, where the association of GTP triggers conformational changes promoting binding of downstream effector molecules. Studies have implicated the nucleotide-binding G5 loop to be involved in the GDP release mechanism. For example, biophysical studies on both the eukaryotic Gα proteins and the GTPase domain (NFeoB) of prokaryotic FeoB proteins have revealed conformational changes in the G5 loop that accompany nucleotide binding and release. However, it is unclear whether this conformational change in the G5 loop is a prerequisite for GDP release, or, alternatively, the movement is a consequence of release. To gain additional insight into the sequence of events leading to GDP release, we have created a chimeric protein comprised of Escherichia coli NFeoB and the G5 loop from the human Giα1 protein. The protein chimera retains GTPase activity at a similar level to wild-type NFeoB, and structural analyses of the nucleotide-free and GDP-bound proteins show that the G5 loop adopts conformations analogous to that of the human nucleotide-bound Giα1 protein in both states. Interestingly, isothermal titration calorimetry and stopped-flow kinetic analyses reveal uncoupled nucleotide affinity and release rates, supporting a model where G5 loop movement promotes nucleotide release.


Effects of tertatolol on the responsiveness of isolated femoral, mesenteric, and renal resistance arteries to adrenergic stimuli.
We evaluated effects of the beta-adrenoceptor antagonist tertatolol on responses of resistance arteries to isoproterenol and phenylephrine and compared them with those of propranolol. The experiments were performed in femoral, mesenteric, and renal resistance arteries that had been isolated from adult Wistar-Kyoto rats, chemically sympathectomized and mounted for recording of contractile reactivity in vitro. In renal resistance arteries that had been pretreated with phenoxybenzamine, isoproterenol did not affect contractile responses to potassium. Under these conditions, isoproterenol induced relaxation in mesenteric resistance arteries. Low concentrations of both SR-tertatolol and SR-propranolol shifted concentration-response curves for isoproterenol to the right. Affinity for competitive beta-adrenergic antagonism did not differ between both agents. Unlike SR-propranolol, SR-tertatolol reduced maximal relaxing responses to isoproterenol. As compared with R-tertatolol, S-tertatolol was 100 times less potent as a competitive beta-adrenergic antagonist and failed to affect maximal relaxing responses to isoproterenol. In femoral, mesenteric, and renal resistance arteries preconstricted by phenylephrine, concentrations of SR-tertatolol greater than 1 microM induced relaxation. This relaxing effect did not differ between SR-tertatolol and SR-propranolol or between S-tertatolol and R-tertatolol. These data indicate that in resistance arteries tertatolol is a stereoselective beta-adrenoceptor antagonist that exhibits both a competitive and a noncompetitive mechanism of action. In addition, high concentrations of tertatolol relax resistance arterial smooth muscle. This effect was neither stereoselective nor selective for the renal vascular bed and was also observed with propranolol.


Endoscopic Preoperative Tattooing and Marking in the Gastrointestinal Tract: A Systematic Review of Alternative Methods.
Background: An accurate and reliable localization of endoluminal gastrointestinal (GI) lesions is crucial, particularly during minimally invasive surgery. As an extreme consequence, a misdetected GI lesion can lead to the resection of the wrong segment, especially in colorectal surgery. A preoperative endoscopic marking is recommended in case of GI lesions, which are expected to be difficult to detect from the serosal side. In clinical practice, three preoperative endoscopic marking methods are currently used: India ink, SPOT™, and endoclips with intraoperative fluoroscopy. All of them have substantial limitations. This has encouraged research on alternative solutions. Methods: In the current systematic review, animal and clinical studies about alternative preoperative endoscopic marking methods of GI lesions were analyzed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: Thirty studies were found using PubMed/MEDLINE, EMBASE/Ovid, and the Cochrane Library for the qualitative analysis. Conclusion: Although several smart solutions have been proposed and tested successfully, all of them seem to have a substantial drawback related either to scarce stability on the marking site or potential spreading on the bowel wall or diffusion into the surgical planes.


Great value BVA In Practice CPD for 2017.
BVA has 16 CPD courses coming up for the second half of the year. They are aimed at vets working in general and mixed practice. Zoe Davies, marketing manager, outlines some of the highlights.


Developmental expression of the cellular prion protein in elongating axons.
PrPc, a sialoglycoprotein present in the normal adult hamster brain, is particularly abundant in plastic brain regions but little is known about the level of expression and the localization of the protein during development. Western blot analysis of whole brain homogenates with mab3F4 show very low levels of the three main molecular weight forms of the protein at birth, in contrast to the strong and wide expression of mRNA transcripts. The PrPc levels increase sharply through P14 and are diminished somewhat in the adult. Regional analysis showed that in structures with ongoing growth or plasticity such as the olfactory bulb and hippocampus, PrPc remains high in the adult, while in areas where structural and functional relationships stabilize during development, such as the cortex and the thalamus, PrPc levels decline after the third postnatal week. In the neonate brain PrPc was prominent along fiber tracts similar to markers of axon elongation and in vitro experiments showed that the protein was present on the surface of elongating axons. PrPc is then localized to the synaptic neuropil in close spatio-temporal association with synapse formation. The localization of PrPc on elongating axons suggests a role for the protein in axon growth. In addition, the relative abundance of the protein in developing axon pathways and during synaptogenesis may provide a basis for the age-dependent susceptibility to transmissible spongiform encephalopathies.


Spontaneous tumor-specific humoral and cellular immune responses to NY-ESO-1 in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common cancer around the world. Although several therapeutic approaches for treatment of HCC are available, survival rates for HCC patients are still very poor because of inefficient treatment options. For HCC, as well as other tumors, antigen-specific immunotherapy remains a viable approach that is dependent on the definition of tumor-associated antigens. NY-ESO-1, a member of the cancer testis antigen family, is one possible candidate for a tumor-specific antigen in HCC. The aim of this study was to show the relevance of NY-ESO-1 in hepatocellular carcinoma. Sera samples from 189 HCC patients were analyzed for NY-ESO-1-specific antibodies. Forty-nine HCC patients were screened for NY-ESO-1 mRNA expression in HCC tissue. Selected patients were followed for up to 3 years to correlate their immune response with their clinical course of events. NY-ESO-1-specific CD4+ and CD8+ T-cell responses from NY-ESO-1 seropositive patients were analyzed and a NY-ESO-1+ specific cytotoxic T-cell line was generated. Twelve of 49 analyzed tumor samples expressed NY-ESO-1 mRNA and 23 of 189 patients showed NY-ESO-1-specific antibody responses. These humoral immune responses were accompanied by NY-ESO-1-specific functional CD4+ and CD8+ T-cell responses. Finally, NY-ESO-1 humoral responses were dependent on the presence of NY-ESO-1-expressing tumors. This is the first report of a spontaneous immune response in HCC patients to a known tumor-specific antigen, NY-ESO-1 protein. Our data favor the possibility of immunotherapeutic strategies for the treatment of HCC.


Ultralight Interconnected Graphene-Amorphous Carbon Hierarchical Foam with Mechanical Resiliency for High Sensitivity and Durable Strain Sensors.
Ultralight graphene-amorphous carbon (AC) hierarchical foam (G-ACHF) was synthesized by chemical vapor deposition at 1065 °C, close to the melting point of copper. The high temperature leads to the hierarchical structure with an inner layer of graphene and an outer layer of AC. The inner graphene layer with high conductivity and integrity provides high sensitivity. The outer AC layer helps to enhance its durability and mechanical resiliency. The hierarchical structure recovers without damaging the structural integrity after a large strain of 90%. The electrical resistance of G-ACHF remains stable after 200 cycles of compression to a strain level of 50%. The fluctuation of the resistance value remains within ±3%, showing its stability in sensing performance. The pressure sensitivity of G-ACHF reaches as high as ∼11.47 Pa-1. Finite element simulation reveals that the stress borne by the key position of G-ACHF is 47% lower than that of graphene foam without the AC layer, proving that the AC layer can disperse the stress effectively. With a very low density of 1.17 × 10-3 g cm-1, the reversibly compressible G-ACHF strain sensor material exhibits its promising application potential in lightweight and wearable devices.


Improved Application of Carbon Nanotube Atomic Force Microscopy Probes Using PeakForce Tapping Mode.
In this work PeakForce tapping (PFT) imaging was demonstrated with carbon nanotube atomic force microscopy (CNT-AFM) probes; this imaging mode shows great promise for providing simple, stable imaging with CNT-AFM probes, which can be difficult to apply. The PFT mode is used with CNT-AFM probes to demonstrate high resolution imaging on samples with features in the nanometre range, including a Nioprobe calibration sample and gold nanoparticles on silicon, in order to demonstrate the modes imaging effectiveness, and to also aid in determining the diameter of very thin CNT-AFM probes. In addition to stable operation, the PFT mode is shown to eliminate "ringing" artefacts that often affect CNT-AFM probes in tapping mode near steep vertical step edges. This will allow for the characterization of high aspect ratio structures using CNT-AFM probes, an exercise which has previously been challenging with the standard tapping mode.


A comparison of serial quantitative serum and urine tests in early pregnancy.
Serial urinary beta human chorionic gonadotropin (beta-hCG) immunoassay was performed on 60 patients during early pregnancy. Results were expressed as tube dilutions positive and were compared with quantitative serum beta human chorionic gonadotropin radioimmunoassay (beta-hCG-RIA) values. The parallel rise of human chorionic gonadotropin (hCG) measured by serum beta-hCG-RIA and a macroflocculation beta-specific urinary immunoassay in early pregnancy was confirmed. The ability of each to predict abortion prior to the onset of patient symptoms or clinical signs of disturbed gestation was quantitated. Results were expressed for each method according to standard regression lines or doubling time for individuals. Utilizing either statistical method, urinary testing was as accurate as serum testing for the prediction of normal pregnancy (about 90% for each). Serum testing was 78% correct in predicting abortion; urinary testing was 63% accurate.


Effect of the nanowire diameter on the linearity of the response of GaN-based heterostructured nanowire photodetectors.
Nanowire photodetectors are investigated because of their compatibility with flexible electronics, or for the implementation of on-chip optical interconnects. Such devices are characterized by ultrahigh photocurrent gain, but their photoresponse scales sublinearly with the optical power. Here, we present a study of single-nanowire photodetectors displaying a linear response to ultraviolet illumination. Their structure consists of a GaN nanowire incorporating an AlN/GaN/AlN heterostructure, which generates an internal electric field. The activity of the heterostructure is confirmed by the rectifying behavior of the current-voltage characteristics in the dark, as well as by the asymmetry of the photoresponse in magnitude and linearity. Under reverse bias (negative bias on the GaN cap segment), the detectors behave linearly with the impinging optical power when the nanowire diameter is below a certain threshold (≈80 nm), which corresponds to the total depletion of the nanowire stem due to the Fermi level pinning at the sidewalls. In the case of nanowires that are only partially depleted, their nonlinearity is explained by a nonlinear variation of the diameter of their central conducting channel under illumination.


Trans-translation in Helicobacter pylori: essentiality of ribosome rescue and requirement of protein tagging for stress resistance and competence.
The ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans. We investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori. We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics.


Pulmonary manifestations of lymphoma: A pictorial essay.
Lymphomatous involvement of the lungs manifests in an infinite number of ways. Often there is a considerable overlap of the patterns of manifestations which comes as a diagnostic challenge to the radiologist. We retrospectively reviewed the pulmonary manifestations of biopsy proven cases of primary or secondary non-Hodgkin's lymphoma or Hodgkin's lymphoma. The patterns of lung involvement were then classified into broad categories which included large masses, mass like consolidation, nodules with or without cavitation, ground glass and lymphangitis/ perilymphatic pattern. This article illustrates the spectrum of CT manifestations of lung involvement in non-Hodgkin's lymphoma as well as Hodgkin's lymphoma.


Activated, Pro-Inflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice.
Delayed-type hypersensitivity arthritis (DTHA) is a recently established experimental model of rheumatoid arthritis (RA) in mice with pharmacological values. Despite an indispensable role of CD4+ T cells in inducing DTHA, a potential role for CD4+ T cell subsets is lacking. Here we have quantified CD4+ subsets during DTHA development and found that levels of activated, pro-inflammatory Th1, Th17, and memory CD4+ T cells in draining lymph nodes were increased with differential dynamic patterns after DTHA induction. Moreover, according to B-cell depletion experiments, it has been suggested that this cell type is not involved in DTHA. We show that DTHA is associated with increased levels of B cells in draining lymph nodes accompanied by increased levels of circulating IgG. Finally, using the anti-rheumatoid agents, methotrexate (MTX) and the anti-inflammatory drug dexamethasone (DEX), we show that MTX and DEX differentially suppressed DTHA-induced paw swelling and inflammation. The effects of MTX and DEX coincided with differential regulation of levels of Th1, Th17, and memory T cells as well as B cells. Our results implicate Th1, Th17, and memory T cells, together with activated B cells, to be involved and required for DTHA-induced paw swelling and inflammation.


A straightforward algorithm for the quantification of power Doppler signals.
To document a simple algorithm that quantifies power Doppler signals by computer-based statistical image analysis. Personal computer-based software was developed. Color pixels representing power Doppler signals were separated from the background gray pixels in power Doppler images converted in BMP format. To avoid misregistration during this segmentation, a threshold value is required to adequately distinguish between gray and color pixels. Equating the intensity of each color pixel to a Power Value (PV), a histogram of Power Values in power Doppler images was obtained. The software was designed to allow users to adjust two thresholds (Difference Threshold and Intensity Threshold) by observing the segmentation results in real time. The software calculates the following indexes within any region of interest as defined by the operator: mean PV, peak PV, standard deviation of PV, percentage power Doppler area, and integrated PV per unit area. Power Doppler signals can be objectively quantified using this straightforward algorithm. This simple and practical method can be applied to comparative or longitudinal studies upon vascularity or blood flow.


Outcomes of surgery in patients aged ≥90 years in the general surgical setting.
Introduction An increasing proportion of the population is living into their nineties and beyond. These high risk patients are now presenting more frequently to both elective and emergency surgical services. There is limited research looking at outcomes of general surgical procedures in nonagenarians and centenarians to guide surgeons assessing these cases. Methods A retrospective analysis was conducted of all patients aged ≥90 years undergoing elective and emergency general surgical procedures at a tertiary care facility between 2009 and 2015. Vascular, breast and endocrine procedures were excluded. Patient demographics and characteristics were collated. Primary outcomes were 30-day and 90-day mortality rates. The impact of ASA (American Society of Anesthesiologists) grade, operation severity and emergency presentation was assessed using multivariate analysis. Results Overall, 161 patients (58 elective, 103 emergency) were identified for inclusion in the study. The mean patient age was 92.8 years (range: 90-106 years). The 90-day mortality rates were 5.2% and 19.4% for elective and emergency procedures respectively (p=0.013). The median survival was 29 and 19 months respectively (p=0.001). Emergency and major gastrointestinal operations were associated with a significant increase in mortality. Patients undergoing emergency major colonic or upper gastrointestinal surgery had a 90-day mortality rate of 53.8%. Conclusions The risk for patients aged over 90 years having an elective procedure differs significantly in the short term from those having emergency surgery. In selected cases, elective surgery carries an acceptable mortality risk. Emergency surgery is associated with a significantly increased risk of death, particularly after major gastrointestinal resections.


Out-of-plane nesting driven spin spiral in ultrathin Fe/Cu(001) films.
Epitaxial ultrathin Fe films on fcc Cu(001) exhibit a spin spiral (SS), in contrast to the ferromagnetism of bulk bcc Fe. We study the in-plane (IP) and out-of-plane (OP) Fermi surfaces (FSs) of the SS in 8 monolayer Fe/Cu(001) films using energy-dependent soft-x-ray momentum-resolved photoemission spectroscopy. We show that the SS originates in nested regions confined to OP FSs, which are drastically modified compared to IP FSs. From precise reciprocal-space maps in successive zones, we obtain the associated real space compressive strain of 1.5+/-0.5% along c axis. An autocorrelation analysis quantifies the incommensurate ordering vector q=(2pi/a)(0,0, approximately 0.86), favoring a SS and consistent with magneto-optic Kerr effect experiments. The results reveal the importance of IP and OP FS mapping for ultrathin films.


Silencing of ATM expression by siRNA technique contributes to glioma stem cell radiosensitivity in vitro and in vivo.
Evidence has shown that both high expression of the ataxia-telangiectasia mutated (ATM) gene and glioma stem cells (GSCs) are responsible for radioresistance in glioma. Thus, we hypothesized that brain tumor radiosensitivity may be enhanced via silencing of the ATM gene in GSCs. In the present study we successfully induced GSCs from two cell lines and used CD133 and nestin to identify GSCs. A lentivirus was used to deliver siRNA-ATMPuro (A group) to GSCs prior to radiation, while siRNA-HKPuro (N group) and GSCs (C group) were used as negative and blank controls, respectively. RT-qPCR and western blotting were performed to verify the efficiency of the siRNA-ATM technique. The expression of the ATM gene and ATM protein were significantly downregulated post-transfection. Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that the A group demonstrated weak cell proliferation and lower survival fractions post-irradiation compared to the C/N groups. Flow cytometry was used to examine the percentage of cell apoptosis and G2 phase arrest, which were both higher in the A group than in the C/N groups. We found that the comet tail percentage evaluated by comet assay was higher in the A group than in the C/N groups. After radiation treatment, three radiosensitive genes [p53, proliferating cell nuclear antigen (PCNA), survivin] exhibited a decreasing tendency as determined by RT-qPCR. Mice underwent subcutaneous implantation, followed by radiation, and the resulting necrosis and hemorrhage were more obvious in the A group than in the N groups. In conclusion, silencing of ATM via the siRNA technique improved radiosensitivity of GSCs both in vitro and in vivo.


Outcomes of 1,639 hepatectomies for non-colorectal non-neuroendocrine liver metastases: a multicenter analysis.
Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear. Data regarding 1,639 hepatectomies performed between 2001 and 2010 for 1,539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed. The five most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 90% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1,465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the five frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type. Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor.


Influence of Block Copolymerization on the Antifreeze Protein Mimetic Ice Recrystallization Inhibition Activity of Poly(vinyl alcohol).
Antifreeze (glyco) proteins are produced by many cold-acclimatized species to enable them to survive subzero temperatures. These proteins have multiple macroscopic effects on ice crystal growth which makes them appealing for low-temperature applications-from cellular cryopreservation to food storage. Poly(vinyl alcohol) has remarkable ice recrystallization inhibition activity, but its mode of action is uncertain as is the extent at which it can be incorporated into other high-order structures. Here the synthesis and characterization of well-defined block copolymers containing poly(vinyl alcohol) and poly(vinylpyrrolidone) by RAFT/MADIX polymerization is reported, as new antifreeze protein mimetics. The effect of adding a large second hydrophilic block is studied across a range of compositions, and it is found to be a passive component in ice recrystallization inhibition assays, enabling retention of all activity. In the extreme case, a block copolymer with only 10% poly(vinyl alcohol) was found to retain all activity, where statistical copolymers of PVA lose all activity with very minor changes to composition. These findings present a new method to increase the complexity of antifreeze protein mimetic materials, while retaining activity, and also to help understand the underlying mechanisms of action.


Platelets stored at 4°C contribute to superior clot properties compared to current standard-of-care through fibrin-crosslinking.
Currently, platelets for transfusion are stored at room temperature (RT) for 5-7 days with gentle agitation, but this is less than optimal because of loss of function and risk of bacterial contamination. We have previously demonstrated that cold (4°C) storage is an attractive alternative because it preserves platelet metabolic reserves, in vitro responses to agonists of activation, aggregation and physiological inhibitors, as well as adhesion to thrombogenic surfaces better than RT storage. Recently, the US Food and Drug Administration clarified that apheresis platelets stored at 4°C for up to 72 h may be used for treating active haemorrhage. In this work, we tested the hypothesis that cold-stored platelets contribute to generating clots with superior mechanical properties compared to RT-stored platelets. Rheological studies demonstrate that the clots formed from platelets stored at 4°C for 5 days are significantly stiffer (higher elastic modulus) and stronger (higher critical stress) than those formed from RT-stored platelets. Morphological analysis shows that clot fibres from cold-stored platelets were denser, thinner, straighter and with more branch points or crosslinks than those from RT-stored platelets. Our results also show that the enhanced clot strength and packed structure is due to cold-induced plasma factor XIII binding to platelet surfaces, and the consequent increase in crosslinking.


The role of tissue and serum carcinoembryonic antigen in stages I to III of colorectal cancer-A retrospective cohort study.
Tissue carcinoembryonic antigen (t-CEA) and serum carcinoembryonic antigen (s-CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s-CEA and t-CEA in CRC. A total of 517 patients from January 2006 to December 2010 with stages I-III CRC were retrospectively examined, with 5-year postoperative follow-up and death as end-points. T-CEA expression, s-CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan-Meier method was used to analyze the 5-year disease-free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t-CEA and s-CEA expression. Tumor differentiation and the number of positive lymph node harvests were significantly different among the t-CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s-CEA and t-CEA expression had a significantly poorer prognosis than those with low s-CEA (P = 0.021) and t-CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t-CEA was an independent prognostic factor in CRC (P < 0.001), but s-CEA was not (P = 0.339). The 5-year disease-free survival rates among the t-CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s-CEA groups, this difference was observed only in stage III (P = 0.014). This study shows that postoperative t-CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s-CEA expression.


[Influence of molsidomine on exercise-ECG'S In coronary insufficiency (author's transl)].
Molsidomine was shown to have a strong pain-relieving action in 22 coronary patients investigated one hour after oral intake of 2 mg of the substance. During comparable maximal exercise load the ST interval lowering was reduced from an average of 0.22 mV to 0.09 mV (P less than 0.0005). At the termination of exercise it was still reduced from 0.23 mV to 0.12 mV (P less than 0.0005). At the same time the exercise tolerance increased from 570 to 717 Watt-minutes (P less than 0.0025). Pectanginal complaints were clearly reduced at the same exercise loads, 11 patients became symptom-free at the same load. Even when exercise loading was stopped at higher loads a decrease of the severity of angina pectoris could be shown. Seven patients became symptom-free at that stage. The heart rate was not influenced markedly at rest and during exercise. Systolic blood pressure was reduced from 135 mm Hg to 118 mm Hg (P less than 0.0005), and in comparable submaximal loads from 177 to 165 mm Hg (P less than 0.005).


Comparison of the iCare rebound tonometer and the Goldmann applanation tonometer.
Tonometry is a fundamental procedure in routine ophthalmologic examination. Although regarded as the reference standard, the Goldmann applanation tonometer (GAT) has its limitations. A new portable alternative to the GAT is the iCare rebound tonometer (RT). The aim of the present study was to compare the intraocular pressure (IOP) results obtained using the RT and GAT and then correlate the results with the central corneal thickness (CCT). Moreover, the tolerability and safety of the RT were evaluated. The IOP of 336 patients (672 eyes) was determined by the RT and GAT. The patients were divided into three groups (group A, 7-15 mmHg, n=74; group B, 16-22 mmHg, n=218; and group C, 23-50 mmHg, n=44), based on the GAT IOP readings. Pachymetry and slit lamp inspection were also performed. To establish an agreement between the devices, a Bland-Altman analysis and paired t-test were performed. The correlation between CCT and IOP readings obtained by the two devices were assessed using linear regression correlation analysis. The mean IOP values of the RT and the GAT were 18.30±5.10 and 18.52±4.46 mmHg, respectively. There were no significant differences between them (t=-1.31, P=0.19). The 95% confidence interval of the differences between the two devices was -5.80-6.24 mmHg. The RT readings are correlated well with those of GAT (r=0.806, P=0.001). However, the RT measurements were significantly (t=-2.84, P=0.007) lower (-1.66±3.87 mmHg) than those obtained with GAT when GAT ≥23 mmHg. Both the RT (r=0.390, P=0.001) and the GAT (r=0.191, P=0.001) showed positive correlations with CCT. The IOP measurement with RT was well tolerated. None of the corneal epithelial defects was detected and all subjects denied discomfort. The RT is well tolerated and safe, and can be considered a reliable alternative to GAT for patients in a low to moderate IOP range. However, in patients with high IOP values, the measurements obtained with RT did not correlate well with those obtained by GAT. The RT readings are influenced more by CCT compared to GAT.


Search for viral nucleic acid sequences in the post mortem brains of patients with schizophrenia and individuals who have committed suicide.
Molecular hybridisation has been used to screen several areas of post mortem brain from 20 patients with schizophrenia, 23 individuals who were suspected of having committed suicide and 21 control cases, for viral nucleic acids. Cloned probes were able to detect picogram levels of viral DNA and to quantify herpes simplex type 1 DNA from encephalitic brain, but no sequences hybridising to cytomegalovirus, varicella zoster virus, herpes simplex type I or JC or BK papovaviruses were detected in any of the experimental samples. These findings are discussed with reference to the viral hypothesis of the aetiology of psychiatric disease.


The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity.
Both trait anger-in (managing anger through suppression) and anger-out (managing anger through direct expression) are related to pain responsiveness, but only anger-out effects involve opioid mechanisms. Preliminary work suggested that the effects of anger-out on postoperative analgesic requirements were moderated by the A118G single nucleotide polymorphism of the mu opioid receptor gene. This study further explored these potential genotypexphenotype interactions as they impact acute pain sensitivity. Genetic samples and measures of anger-in and anger-out were obtained in 87 subjects (from three studies) who participated in controlled laboratory acute pain tasks (ischemic, finger pressure, thermal). McGill Pain Questionnaire (MPQ) Sensory and Affective ratings for each pain task were standardized within studies, aggregated across pain tasks, and combined for analyses. Significant anger-outxA118G interactions were observed (p's<.05). Simple effects tests for both pain measures revealed that whereas anger-out was nonsignificantly hyperalgesic in subjects homozygous for the wild-type allele, anger-out was significantly hypoalgesic in those with the variant G allele (p's<.05). For the MPQ-Affective measure, this interaction arose both from low pain sensitivity in high anger-out subjects with the G allele and heightened pain sensitivity in low anger-out subjects with the G allele relative to responses in homozygous wild-type subjects. No genetic moderation was observed for anger-in, although significant main effects on MPQ-Affective ratings were noted (p<.005). Anger-in main effects were due to overlap with negative affect, but anger-outxA118G interactions were not, suggesting unique effects of expressive anger regulation. Results support opioid-related genotypexphenotype interactions involving trait anger-out.


Concentration profile distortion under ion beam mixing: an example of Levy flight.
In order to model the evolution of concentration profiles induced by ion beam mixing in thick layers, Monte Carlo simulations were performed to study in detail the transition probability controlling the evolution of this profile within the binary collision approximation. We demonstrate that this transition probability can be factorized in two distinct functions. The first one can be understood as a scale factor. The second one controls the dynamics of ion beam mixing which can be analyzed as a Levy flight. The power law form of the tail of this function closely linked to the cross section of a collision event is responsible for long tails of concentration profiles. We demonstrate that the Levy flight nature of ion beam mixing induces an enhancement of the evolution of the initial concentration profile.


Chest radiograph and functional radiology.
In the course of the years the concept of functional radiology has gradually been developed. It represents the integration of chest radiography with some basic concepts of respiratory pathophysiology. The correlation between the higher vascularization at the bases of lung as compared to the apex with the gravitation factor was the initial reference. From this data, combined with physiologic parameters, over the years, relatively simple but diagnostically significant semeiotic findings were achieved. The different combinations of acquired "morphofunctional" signs allow the differential diagnosis in a number of organic and hemodynamic alterations, adding to conventional "morphologic" radiology. New contributions to the functional radiology of the lung might come from procedures as high resolution computed tomography (HRCT) which with the dynamic study supplies morphologic and densitometric information to be correlated with changes in pulmonary flow and ventilation/perfusion ratio.


Non-Noble-Metal Nanoparticle Supported on Metal-Organic Framework as an Efficient and Durable Catalyst for Promoting H2 Production from Ammonia Borane under Visible Light Irradiation.
In this work, we propose a straightforward method to enhance the catalytic activity of AB dehydrogenation by using non-noble-metal nanoparticle supported on chromium-based metal-organic framework (MIL-101). It was demonstrated to be effective for hydrogen generation from ammonia borane under assistance of visible light irradiation as a noble-metal-free catalyst. The catalytic activity of metal nanoparticles supported on MIL-101 under visible light irradiation is remarkably higher than that without light irradiation. The TOFs of Cu/MIL-101, Co/MIL-101, and Ni/MIL-101 are 1693, 1571, and 3238 h(-1), respectively. The enhanced activity of catalysts can be primarily attributed to the cooperative promoting effects from both non-noble-metal nanoparticles and photoactive metal-organic framework in activating the ammonia borane molecule and strong ability in the photocatalytic production of hydroxyl radicals, superoxide anions, and electron-rich non-noble-metal nanoparticle. This work sheds light on the exploration of active non-noble metals supported on photoactive porous materials for achieving high catalytic activity of various redox reactions under visible light irradiation.


Improving Knowledge, Attitudes, and Skills of Medical Clinicians and Trainees in Clinical Medical Ethics.
Purpose: There is limited data in the medical literature evaluating knowledge, attitudes, and skill in clinical medical ethics for clinicians or medical trainees. Our study aimed to evaluate baseline clinician knowledge, attitudes, and skills regarding clinical medical ethics and to implement and evaluate a curriculum designed with the intent to improve these measures. Method: Internal medicine residents, palliative fellows, medical and pre-medical students, social workers, advanced practice providers, and chaplains were surveyed at a large urban academic center to determine their baseline knowledge, attitudes, and skills regarding clinical medical ethics (64% response rate, n = 93/145). A one-hour discussion-based curriculum on clinical medical ethics topics was implemented, followed by another survey; χ2 and McNemar tests were used to compare pre- and post-surveys to evaluate the curriculum. Results: Baseline knowledge of all respondents (n = 93) in the four principles of bioethics (54%-89%), determining an alternate decision-maker (5%-50%), decision-making capacity (14%-71%), and in-hospital cardiac arrest survival (19%-77%) significantly increased (P < .0001) post-curriculum, as did baseline self-reported attitudes towards clinicians making medical recommendations to patients (27%-60%) and having had adequate education on code status discussions (42%-77%). Self-reported skills in determining an alternate decision-maker (40%-89%) and assessing decision-making capacity (40%-72%) also significantly increased post curriculum (P < .01 and P < .05). Conclusion: Implementation of a curriculum in medical ethics improved baseline knowledge, attitudes and self-reported skills of medical providers and trainees in clinical medical ethics.


Reproducibility and discriminability of brain patterns of semantic categories enhanced by congruent audiovisual stimuli.
One of the central questions in cognitive neuroscience is the precise neural representation, or brain pattern, associated with a semantic category. In this study, we explored the influence of audiovisual stimuli on the brain patterns of concepts or semantic categories through a functional magnetic resonance imaging (fMRI) experiment. We used a pattern search method to extract brain patterns corresponding to two semantic categories: "old people" and "young people." These brain patterns were elicited by semantically congruent audiovisual, semantically incongruent audiovisual, unimodal visual, and unimodal auditory stimuli belonging to the two semantic categories. We calculated the reproducibility index, which measures the similarity of the patterns within the same category. We also decoded the semantic categories from these brain patterns. The decoding accuracy reflects the discriminability of the brain patterns between two categories. The results showed that both the reproducibility index of brain patterns and the decoding accuracy were significantly higher for semantically congruent audiovisual stimuli than for unimodal visual and unimodal auditory stimuli, while the semantically incongruent stimuli did not elicit brain patterns with significantly higher reproducibility index or decoding accuracy. Thus, the semantically congruent audiovisual stimuli enhanced the within-class reproducibility of brain patterns and the between-class discriminability of brain patterns, and facilitate neural representations of semantic categories or concepts. Furthermore, we analyzed the brain activity in superior temporal sulcus and middle temporal gyrus (STS/MTG). The strength of the fMRI signal and the reproducibility index were enhanced by the semantically congruent audiovisual stimuli. Our results support the use of the reproducibility index as a potential tool to supplement the fMRI signal amplitude for evaluating multimodal integration.


Ketogenic diet attenuates neuroinflammation and induces conversion of M1 microglia to M2 in an EAE model of multiple sclerosis by regulating the NF-κB/NLRP3 pathway and inhibiting HDAC3 and P2X7R activation.
Multiple sclerosis (MS) is an autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS); severe symptoms lead MS patients to use complementary treatments. Ketogenic diet (KD) shows wide neuroprotective effects, but the precise mechanisms underlying the therapeutic activity of KD in MS are unclear. The present study established a continuous 24 days experimental autoimmune encephalomyelitis (EAE) mouse model with or without KD. The changes in motor function, pathological hallmarks of EAE, the status of microglia, neuroinflammatory response and intracellular signaling pathways in mice were detected by the rotarod test, histological analysis, real-time PCR (RT-PCR) and western blotting. Our results showed that KD could prevent motor deficiency, reduce clinical scores, inhibit demyelination, improve pathological lesions and suppress microglial activation in the spinal cord of EAE mice. Meanwhile, KD shifted microglial polarization toward the protective M2 phenotype and modified the inflammatory milieu by downregulating the production of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, as well as upregulating the release of anti-inflammatory cytokines such as TGF-β. Furthermore, KD decreased the expression levels of CCL2, CCR2, CCL3, CCR1, CCR5, CXCL10 and CXCR3 in the spinal cord and spleen with reduced monocyte/macrophage infiltration in the CNS. In addition, KD inhibits NLRP3 activation in the microglia, as revealed by the significantly decreased co-expression of NLRP3+ and Iba-1+ in the KD + EAE group. Further studies demonstrated that KD suppresses inflammatory response and M1 microglial polarization by inhibiting the TLR4/MyD88/NF-κB/NLRP3 pathway, the JAK1/STAT1 pathway, HDAC3 and P2X7R activation, as well as up-regulation of JAK3/STAT6.


Effect of acid type on kinetics and mechanism of dental enamel demineralization.
The influence of acid type (pKa effects) of weak organic acid buffers on dissolution kinetics of dental enamel was critically examined for rigorous testing of the behavioral validity of the physical model of Patel et al. (1987). Quantitative evaluation of this model indicated that monitoring initial dissolution rates was a viable approach to critical testing of the model. Initial dissolution rates were determined in 0.1 mol/L acetate (pKa = 4.77), benzoate (pKa = 4.20), and salicylate (pKa = 2.98) buffers (pH = 4.50, mu = 0.50), with ground bovine enamel blocks of known surface area mounted in a rotating disk apparatus. The Levich theory was used to study dependence of dissolution rates on stirring rates in these buffers. The experimental data were analyzed by the physical model which includes pKa effects, complexation of the buffer anion with the other ions, surface kinetics, simultaneous diffusion and equilibrium of all species in enamel pores, diffusion layer thickness, and bulk solution composition. The KIAP (formula: see text) governing the dissolution reaction and the surface resistance factor were deduced from the model. Dissolution kinetics was also followed in these buffers in the presence of calcium or phosphate common ions. In effect, by conducting both the stirring rate studies and common ion experiments, we derived the driving force function independently by these two techniques. The results obtained in this study were consistent with the model, indicating that pKa effects on the dissolution of dental enamel can be accounted for quantitatively by the model, and it was found that weak acids do not influence either the apparent solubility or the surface reaction process of bovine dental enamel.


Differences in colorectal cancer surveillance epidemiology and screening in the WHO European Region.
The aim of this study was to describe the Colorectal Cancer (CRC) burden and prevention actions in 53 countries of the World Health Organization (WHO) European Region (ER). Multiple correspondence analysis was applied to examine the association among the following variables: Measures of occurrence; type of screening programme; existence of cancer registries; data quality and; and gross national income (GNI) level. The study demonstrated clear differences according to GNI: low-middle income (LMI) countries show low mortality rates and unorganized screening programme; upper-middle income (UMI) countries show no test offered, incomplete or absent data mortality, and low quality of the method used to estimate incidence and mortality rates; high income (HI) countries show high mortality rates, test offered (FOBT and colonoscopy), the existence of a national registry, screening population-based, insurance of payment policy, and high quality of the method used to estimate incidence and mortality rates. HI countries reflect a strong interest in epidemiological monitoring and produce accurate indicators of disease occurrence. On the other hand, surveillance strategies need to be improved in UMI and LMI countries: As national vital statistics are unavailable, partial or inaccurate, the coverage and completeness of the mortality data are frequently poor, there is a less efficient general organization. In conclusion, it is important to underline that the resources available (as measured by GNI) appear to be major factors in the Colorectal Cancer Surveillance Epidemiology and Screening in the WHO European Region.


Gross factors in treatment of nonhealing corneal ulcers and recurrent erosions.
Epidermal growth factor (EGF) is known to promote corneal epithelial wound healing in experimental scrape and keratectomy models. We studied its efficacy in treating alkali-burned epithelial ulceration. EGF induced hyperplasia and cell proliferation to resurface the denuded and denatured corneal stroma, but it did not prevent recurrent erosions. A combination of EGF with fibronectin (Fn) was noted to enhance epithelial defect closure after alkali burns of the cornea and was seen to prevent recurrent erosions. Histopathologic examination of these corneas revealed marked leukocytic infiltration of the alkali-burned corneal stroma. To find ways to retard this inflammatory response, we studied the role of topical steroids and their efficacy when used with EGF, Fn, and laminin (Ln) in the management of alkali-burned corneas. Use of steroids decreased the incidence of recurrent erosions and corneal perforations. Histologically, steroids markedly decreased the leukocytic infiltration of stromal tissue, thereby retarding the collagenolysis. Topical steroids used with EGF and fibronectin were seen to promote epithelial wound closure and to prevent recurrent erosions in alkali-burned corneas. Combinations of EGF, fibronectin, and steroids may have a place in the treatment of clinical corneal alkali burns.


Narrowband reflective generation of higher-order optical vortices in Bragg spun optical fibers.
We have studied theoretically reflecting and transmitting properties of Bragg multihelicoidal spun fibers, in which refractive index distribution features l helical branches and possesses an l-fold symmetry in the transverse cross section. It is shown that for a special choice of the profile function modulation, such fibers in certain spectral ranges have the property to change the topological charge of the incoming Gaussian beam in the reflected field by l units. This property could be used for narrowband generation of optical vortices (OVs) from Gaussian beams and for changing the topological charge of incoming OVs.


Interindividual variability in expression and activity of human beta-glucuronidase in liver and kidney: consequences for drug metabolism.
Glucuronidation of drugs represents a major pathway of human drug metabolism. Numerous studies show that the glucuronides formed can accumulate during chronic therapy and/or have direct pharmacological activity. In both cases, cleavage of the glucuronide by human beta-glucuronidase (beta-Gluc) would release the parent compound, thereby modifying drug disposition. Variability in expression of beta-Gluc could therefore be a confounding factor for interindividual variability in drug disposition both in the setting of accumulating glucuronides or for the use of glucuronides as prodrugs, such as the nontoxic glucuronide-spacer derivative of doxorubicin (Dox-S-G). We therefore investigated expression and function of beta-Gluc in human liver (n = 30) and human kidney (n = 18). Cleavage of the model compound 4-methylumbelliferyl-beta-D-glucuronide (MUG) revealed a wide range of activities in liver (0.32-1.85 mumol/mg/h, mean value 0.87 +/- 0.34 mumol/mg/h) and kidney (0.07-1.00 mumol/mg/h, mean 0.39 +/- 0.21 mumol/mg/h), which followed a log normal distribution. Variable enzyme activity was closely correlated to enzyme expression as assessed by Western blotting (r = 0.80, P < .001 and r = 0.71, P < .05 for liver and kidney, respectively). Glycyrrhizin (Ki = 470 and 570 microM), estradiol 3-glucuronide (Ki = 0.9 and 1.2 mM) and paracetamol glucuronide (Ki = 1.6 and 2 mM) were found to inhibit beta-Gluc activity competitively in liver and kidney, respectively. Enzyme kinetics were investigated in detail for MUG and Dox-S-G. Whereas MUG followed monophasic Michaelis-Menten kinetics in liver (K(m) = 1.32 +/- 0.25 mM, Vmax = 1201 +/- 462 nmol/mg/h, n = 3) and kidney (K(m) = 1.04 +/- 0.05 mM, Vmax = 521 +/- 267 nmol/mg/h, n = 3), cleavage of Dox-S-G was best described by the Hill equation, which indicated a cooperative substrate binding pattern of Dox-S-G. In summary, beta-Gluc function shows wide interindividual variability in human liver and kidney that is due to different steady-state levels of the enzyme. Moreover, enzyme kinetics are substrate-dependent, with Dox-S-G showing a cooperative binding. These data indicate the possibility of wide interindividual variability in beta-Gluc-mediated cleavage of drug glucuronides in the human.


Probing the impact of chromatin conformation on genome editing tools.
Transcription activator-like effector nucleases (TALENs) and RNA-guided nucleases derived from clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 systems have become ubiquitous genome editing tools. Despite this, the impact that distinct high-order chromatin conformations have on these sequence-specific designer nucleases is, presently, ill-defined. The same applies to the relative performance of TALENs and CRISPR/Cas9 nucleases at isogenic target sequences subjected to different epigenetic modifications. Here, to address these gaps in our knowledge, we have implemented quantitative cellular systems based on genetic reporters in which the euchromatic and heterochromatic statuses of designer nuclease target sites are stringently controlled by small-molecule drug availability. By using these systems, we demonstrate that TALENs and CRISPR/Cas9 nucleases are both significantly affected by the high-order epigenetic context of their target sequences. In addition, this outcome could also be ascertained for S. pyogenes CRISPR/Cas9 complexes harbouring Cas9 variants whose DNA cleaving specificities are superior to that of the wild-type Cas9 protein. Thus, the herein investigated cellular models will serve as valuable functional readouts for screening and assessing the role of chromatin on designer nucleases based on different platforms or with different architectures or compositions.


Human lymphoblastoid interferon for the treatment of chronic hepatitis B. A randomized controlled trial.
The aim of this study was to demonstrate whether interferon alone could affect the course of chronic hepatitis B. A total of 66 patients have so far been randomly assigned to receive six months of interferon therapy or no therapy; three patients in the interferon group and two in the control group have withdrawn from the study. Loss of hepatitis B virus-DNA and hepatitis B e antigen was significantly higher in the patients receiving interferon than in the control group; a significant loss of hepatitis B surface antigen was observed only in patients who received interferon. The time to alanine aminotransferase normalization was significantly shorter in patients receiving interferon than in the control group. These data encourage the use of interferon in treatment of chronic hepatitis B.


Amplitude modulation thresholds in chinchillas with high-frequency hearing loss.
Estimates of auditory temporal resolution were obtained from normal chinchillas using sinusoidally amplitude modulated noise. Afterwards, the animals were exposed to noise whose bandwidth was progressively increased toward the low frequencies in octave steps. The first exposure was to an octave band of noise centered at 8 kHz. Three additional octave bands of noise were subsequently added to the original exposure in order to progressively increase the extent of the high-frequency hearing loss. The first exposure produced a temporary hearing loss of 50 to 60 dB near 8 kHz and elevated the amplitude modulation thresholds primarily at intermediate (128 Hz) modulation frequencies. Successive noise exposures extended the temporary hearing loss toward lower frequencies, but there was little further deterioration in the amplitude modulation function until the last exposure when the hearing loss spread to 1 kHz. The degradation in the amplitude modulation function observed after the last exposure, however, was due to a reduction in the sensation level of the test signal rather than to a decrease in the hearing bandwidth. The results of this study suggest that the high-frequency regions of the cochlea may be important for temporal resolution.


Combination of Urinary Neutrophil Gelatinase-associated Lipocalin, Kidney Injury Molecular-1, and Angiotensinogen for the Early Diagnosis and Mortality Prediction of Septic Acute Kidney Injury.
Acute kidney injury (AKI) is one of the most severe complications of sepsis. This study was conducted to analyze the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecular-1 (uKIM-1), and urinary angiotensinogen (uAGT) in the early diagnosis and mortality prediction of septic AKI. The prospective study enrolled 80 sepsis patients in the ICU and 100 healthy individuals and divided patients into an AKI group and a non-AKI group. uNGAL, uKIM-1, uAGT, serum creatinine/procalcitonin/C-reaction protein, and other indicators were determined, and clinical prediction scores were recorded. The sensitivity and specificity of uNGAL, uKIM-1, and uAGT in diagnosis and mortality prediction were analyzed by the receiver operator characteristic (ROC) curve and the area under the curve (AUC). uNGAL, uKIM-1, and uAGT levels were higher in sepsis patients than healthy controls, higher in AKI patients than non-AKI patients, and higher in AKI-2 and AKI-3 patients than AKI-1 patients. At 0 h after admission, the combined efficacy of three indicators in septic AKI diagnosis (ROC-AUC: 0.770; sensitivity: 82.5%; specificity: 70.0%) was better than a single indicator. At 24 h, uNGAL, uKIM-1, and uAGT levels were higher in sepsis non-survivals than survivals and higher in septic AKI non-survivals than septic AKI survivals. The combined efficacy of three indicators in the prediction of sepsis/septic AKI mortality (ROC-AUC: 0.828/0.847; sensitivity: 71.4%/100.0%; specificity: 82.7%/66.7%) was better than a single indicator. uNGAL, uKIM-1, and uAGT levels were increased in septic AKI, and their combination helped the early diagnosis and mortality prediction.


Protein-coding genes in B chromosomes of the grasshopper Eyprepocnemis plorans.
For many years, parasitic B chromosomes have been considered genetically inert elements. Here we show the presence of ten protein-coding genes in the B chromosome of the grasshopper Eyprepocnemis plorans. Four of these genes (CIP2A, GTPB6, KIF20A, and MTG1) were complete in the B chromosome whereas the six remaining (CKAP2, CAP-G, HYI, MYCB2, SLIT and TOP2A) were truncated. Five of these genes (CIP2A, CKAP2, CAP-G, KIF20A, and MYCB2) were significantly up-regulated in B-carrying individuals, as expected if they were actively transcribed from the B chromosome. This conclusion is supported by three truncated genes (CKAP2, CAP-G and MYCB2) which showed up-regulation only in the regions being present in the B chromosome. Our results indicate that B chromosomes are not so silenced as was hitherto believed. Interestingly, the five active genes in the B chromosome code for functions related with cell division, which is the main arena where B chromosome destiny is played. This suggests that B chromosome evolutionary success can lie on its gene content.


Sca13.
Spinocerebellar ataxia 13 (SCA13), initially described in a four-generation French family, has now also been characterized in a large Filipino pedigree. Ongoing investigations continue to identify additional SCA13 families and individuals. Recently, studies have shown that mutations in the voltage-gated potassium channel KCNC3 are causative for SCA13. Sequence analysis of KCNC3 revealed mutations 1554G-->A (R420H) in the Filipino and 1639C-->A (F448L) in the French pedigrees. Both mutations alter KCNC3 function in a Xenopus laevis oocyte expression system. KCNC3(R420H), located in the voltage sensor of the channel, has no detectable channel activity when expressed alone, and strong dominant negative effects when coexpressed with wild-type KCNC3. KCNC3(F448L) shifts the activation curve in the negative direction and causes an approximately sevenfold slowing of channel closure. These mutations are expected to change the output characteristics of fast-spiking cerebellar neurons, where KCNC channels confer capacity for high-frequency repetitive firing.


Conjugate gradient minimisation approach to generating holographic traps for ultracold atoms.
Direct minimisation of a cost function can in principle provide a versatile and highly controllable route to computational hologram generation. Here we show that the careful design of cost functions, combined with numerically efficient conjugate gradient minimisation, establishes a practical method for the generation of holograms for a wide range of target light distributions. This results in a guided optimisation process, with a crucial advantage illustrated by the ability to circumvent optical vortex formation during hologram calculation. We demonstrate the implementation of the conjugate gradient method for both discrete and continuous intensity distributions and discuss its applicability to optical trapping of ultracold atoms.


Alternating chirality in the monolayer H2TPP on Cu(110)-(2 × 1)O.
In this work, the structure of the tetraphenylporphyrin (H2TPP) monolayer grown on the oxygen passivated Cu(110)-(2 × 1)O surface has been investigated with LT-STM and elucidated by DFT-calculations. The monolayer is commensurate with all molecules occupying the same adsorption site, but there are two molecules per unit cell. The STM images suggest alternating chirality for the molecules within one unit cell which is supported by DFT total energy calculations for monolayers on the Cu-O substrate. STM simulations for alternating and single chirality monolayers have subtle differences which indicate that the experimentally observed surface is one containing molecules with alternating chirality, that is racemicity within the unit cell.


Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride.
Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 RA, and dexamethasone combination therapy is standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein we describe the physical and chemical stability of rolapitant injectable emulsion 166.5 mg in 92.5 mL (185 mg hydrochloride salt) admixed with palonosetron injection 0.25 mg in 5 mL (0.28 mg hydrochloride salt). Admixtures were prepared and stored in two types of container closures (110-mL Crystal Zenith plastic and glass bottles) and four types of intravenous administration sets (or intravenous tubing sets). Assessment of the physical and chemical stability was conducted on the admixtures in the ready-to-use container closure systems as supplied by the manufacturer, stored at room temperature (20°C to 25°C under fluorescent light), and evaluated at 0, 1, and 6 hours; 1 and 2 days; and under refrigeration (2°C to 8°C protected from light) after 1, 3, and 7 days. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20°C to 25°C initially, and then after 20 hours (total 27 hours) at 2°C to 8°C protected from light. Physical stability was assessed by visual examination of the container contents under normal room light, and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations and impurity levels with high-performance liquid chromatographic analysis. The results indicated that all samples were physically compatible throughout the duration of the study. The pH, turbidity, and particulate matter of the admixture stayed within narrow and acceptable ranges. Rolapitant admixed with palonosetron was chemically stable when admixed in glass and Crystal Zenith bottles for at least 48 hours at room temperature and for 7 days under refrigeration, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 hours at 2°C to 8°C. No loss of potency of any admixed components occurred in the samples stored at the two temperature ranges and time period studied.


Absence of Fyn and Src causes a reeler-like phenotype.
Nonreceptor protein tyrosine kinases of the Src family regulate the survival, proliferation, differentiation, and motility of many cell types, but their roles in brain development are unclear. Biochemical and in vitro experiments implicate Src and Fyn in the Reelin-dependent tyrosine phosphorylation of Dab1, which controls the positioning of radially migrating neurons in many brain regions. However, genetic evidence that either Src or Fyn mediates Reelin-dependent migrations in vivo has been lacking. Here, we report that, although Src is dispensable and although the absence of Fyn causes an intermediate phenotype, the combined absence of Src and Fyn almost abolishes tyrosine phosphorylation of Dab1 and causes defects in the fetal cortex and cerebellum very similar to those of dab1 mutants of the same age. Neurogenesis is not detectably affected, but the layering of neurons in the cortex is inverted, and the formation of the Purkinje plate is impaired. This implies that Src and Fyn are needed for Reelin-dependent events during brain development.