Assessing the Potential for Interaction in Insecticidal Activity Between MON 87751 × MON 87701 Produced by Conventional Breeding.
Pyramiding (combining) of plant incorporated protectants (PIPs) with insecticidal activity in genetically engineered crops is a strategy used to improve efficacy as well as delay potential resistance for a specific group of targets. In some countries, a regulatory risk assessment is required for breeding "stacks" expressing multiple PIPs and these countries may require an assessment of potential interaction among the PIPs. This study evaluated whether combining soybean events MON 87551 and MON 87701 results in a toxicological interaction that effects a species that is controlled by each event. MON 87751 coexpresses the Cry1A.105 and Cry2Ab2 proteins and MON 87701 expresses the Cry1Ac protein. EC50 values for MON 87751 and MON 87701 were comparable in diet-incorporation bioassays using corn earworm (Lepidoptera: Noctuidae, Helicoverpa zea) and the observed combined activity of the stack was consistent with predictions of additivity (i.e., no interaction). Under the concentration and response addition models, predicted and observed median effect levels differed by <10%. These results demonstrate independent action at the median effect level between the insecticidal activity of MON 87751 and MON 87701. Taken together, no interaction between these PIPs and acceptable margins of safety for the individual proteins to nontarget organisms, it is appropriate to bridge back to the risk assessments for the individual products that demonstrated environmental safety of stack products containing both MON 87751 and MON 87701.


Male and Female Hypogonadism.
Hypogonadism is a clinical syndrome that results in hormone deficiency in men and women. Primary hypogonadism is caused by gonadal (testicular or ovarian) failure. Secondary hypogonadism is the result of a dysfunction within the hypothalamus and/or pituitary. Diagnosis of hypogonadism requires a comprehensive health history, evaluation of the signs and symptoms, complete physical examination, as well as laboratory and diagnostic testing for both sexes. Hormone replacement is the hallmark of hypogonadism treatment. Restoring and/or maintaining quality of life is a major consideration in the management of patients with hypogonadism.


Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol.
The combination of high levels of beta2-microglobulin (beta2-m) and chromosome 13 deletion allows identification of a high-risk subgroup of patients with de novo multiple myeloma (MM). In this population of patients, we have evaluated the impact of a murine anti-interleukin 6 (anti-IL-6) monoclonal antibody (BE-8) as part of the second conditioning regimen in a multicenter prospective randomized trial of tandem autologous stem cell transplantation (ASCT). Conditioning for the first ASCT was accomplished with melphalan 200 mg/m2 and for the second one with melphalan 220 mg/m2 plus dexamethasone with or without BE-8 infusion. This trial included 219 patients, of whom 166 were randomized, 85 without BE-8 (arm A) and 81 with BE-8 (arm B). The median overall survival (OS) and event-free survival (EFS) times of the whole group of patients were 41 and 30 months, respectively. Response rates, OS, and EFS were not different between the 2 arms of the trial. OS at 54 months was 46% in arm A and 51% in arm B (P = .90); median EFS was 35 months in arm A and 31 in arm B (P = .39). In high-risk patients the dose intensity of melphalan at 420 mg/m2 led to encouraging results, but the addition of anti-IL-6 monoclonal antibody to the second conditioning regimen did not improve either OS nor EFS.


A national child mental health literacy initiative is needed to reduce childhood mental health disorders.
Half of all lifetime mental health disorders emerge in childhood, so intervening in the childhood years is critical to prevent chronic trajectories of mental health disorders. The prevalence of child mental health disorders is not decreasing despite the increased availability of evidence-based interventions. One key reason for the high prevalence and low treatment uptake may be low levels of child mental health literacy in the general community. Mental health literacy refers to knowledge and beliefs about mental health disorders that aid in their recognition, prevention and management. There is emerging evidence of poor recognition of child mental health problems in the community and low levels of parental knowledge about how to seek help, along with high levels of stigmatising attitudes. Although Australia has been a world leader in research and practice in improving mental health literacy for adolescent and adult mental health disorders, particularly depression and anxiety, mental health literacy for childhood disorders has been largely overlooked. In order to improve knowledge of child mental health disorders, reduce stigma, improve appropriate help-seeking and impact on the prevalence of child mental health disorders, we argue that a national initiative focussing on increasing mental health literacy for childhood disorders is urgently needed.


Managing hypertension in athletes and physically active patients.
Athletes and other physically active patients should be screened for hypertension and given appropriate therapy if needed. Mild hypertension should be treated with non-pharmacologic measures for six months. If blood pressure control is adequate, lifestyle modifications are continued. If control is inadequate, low-dose therapy with an angiotensin-converting enzyme inhibitor or a calcium channel blocker may be started. A thiazide diuretic may be used as first-line treatment for hypertension in casually active patients; however, diuretic therapy is less desirable in high-intensity or endurance athletes because of the risk of hypovolemia or hypokalemia. If beta blockade is needed, a combined alpha-beta blocker may be the best choice. When the target blood pressure is achieved, long-term follow-up care and management should be emphasized. If excellent control is maintained for six to 12 months, medication may be reduced or withdrawn in a small number of patients. If the target blood pressure is not achieved, the medication dosage may be adjusted, or a second medication, usually a diuretic, may be added. Physicians need to be aware of the effects of various medications on exercise tolerance and the rules for participation established by sports regulatory bodies (Am Fam Physician 2002;66:457-8).


The Influence of Cultural Communication on the Psychological Health of University Students in the Environment of Big Data.
With the progress of information technology and Internet technology, many new media communication technologies are also progressing, and university students are at the forefront of the development of the Internet and the application of cultural communication. Therefore, the impact of modern cultural communication on college students is the most obvious. Time culture communication relies on time communication media, which affects university students' psychological cognition, experience, and mental health level. University students are the high-risk group of mental health problems. At present, most college students are mentally healthy. However, a considerable number of students' mental health is not optimistic. Therefore, paying attention to the impact of culture on college students' mental health plays an important role in the healthy growth of college students. However, a considerable number of students' psychological health is not optimistic. Therefore, paying attention to the impact of culture on university students' psychological health plays an important role in the healthy growth of university students. In this article, 300 university students were randomly selected as the subjects of this study. SCL-90 test and related factors were used to investigate, covering 9 factors. Five common classification algorithms were trained with training sets and evaluated through verification sets. The classifier with the best effect was selected as our algorithm; it is used to discern students with psychological health problems in the test set. The experipsychological results show that precision reaches 0.68, recall reaches 0.56, and F1 measure reaches 0.67. Based on the influencing factors of university students' psychological health, through the analysis of random samples, based on family environment, school environment, community environment, information culture environment, and other factors, this article puts forward strategies to create a warm and progressive family environment, a friendly and positive campus environment, a democratic and scientific community education environment, and a civilized and fair legal environment, so as to properly solve the psychological health problems of university students.


A subset of human limbal epithelial cells with greater nucleus-to-cytoplasm ratio expressing high levels of p63 possesses slow-cycling property.
The purpose of this study was to evaluate the subset of limbal epithelial cells with greater nucleus-to-cytoplasm (N/C) ratio expressing high levels of p63 for their slow-cycling property, a characteristic feature of stem cells (SCs). Limbal and peripheral corneal explant cultures were pulse labeled with 5-5-bromo-2'-deoxyuridine (BrdU) for 5 days, followed by a period of 3-week chase. Cultured explants were cryosectioned and stained for BrdU. The epithelial cells in the outgrowth and those remaining on the explant were isolated and subjected to cytospin and double immunostaining for BrdU and p63, followed by identification of label-retaining cells (LRCs) and quantification of p63 expression using confocal microscopy. A distinct population of small cells with large N/C ratio expressing high levels of p63 retained the BrdU label after 21-day chase. Further, this population of LRCs, negative for the differentiation marker K3, was observed in the epithelial outgrowth of limbal but not in that of peripheral cornea. LRCs were seen to migrate along the cut edge of limbal explants in culture and were also observed as clusters of small cells in the outgrowth, which contained cells with the ability to form holoclone colonies. These results demonstrate that the small cells with large N/C ratio and high levels of p63 have BrdU label retaining slow-cycling property, thus confirming that these 2 parameters in combination may serve as a precise marker for identification and quantification of ex vivo-expanded limbal SCs. This method would be useful to standardize the optimal culture conditions that can maintain and expand SCs for therapeutic applications.


A novel cinnamide YLT26 induces breast cancer cells apoptosis via ROS-mitochondrial apoptotic pathway in vitro and inhibits lung metastasis in vivo.
Breast cancer is the leading cause of cancer death among women worldwide and metastasis is the major cause of treatment failure. Thus, new treatment options for breast cancer, especially, drugs which could prevent metastasis, are pressingly needed. In the present study, we designed and synthesized a novel cinnamide derivative, (E)-N-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (YLT26), which displayed potent inhibitory effects on breast cancer cells. The cell viability, apoptosis-inducing effect and reactive oxygen species (ROS) production were examined in 4T1 cells following treatment with YLT26. Meanwhile, apoptosis-related proteins levels were determined by western blotting. Finally, we evaluated the effects of YLT26 on breast tumor growth, lung metastases in vivo and the infiltration of myeloid-derived suppressor cells (MDSCs) in lung tissue. Our results showed that the proliferation inhibitory effects of YLT26 were correlated with its apoptosis-inducing effect. Exposure to YLT26 induced mitochondrial transmembrane potential (∆Ψm) change, activated caspase-9, and downregulated the Bcl-2 expression, as well as enhanced ROS accumulation in 4T1 cells. Moreover, YLT26 significantly inhibited tumor growth without obvious side effects in the 4T1 tumor-bearing mice model. Immunohistochemistry analyze revealed YLT26 also induced apoptosis in vivo. More importantly, YLT26 also significantly inhibited lung metastases, which may be associated with the reduction of MDSCs. The present study suggested that YLT26 could inhibit breast cancer cells proliferation via ROS-mitochondrial apoptotic pathway, delay breast tumor progression, and suppress lung metastases by impacting on the immunologic microenvironment in vivo. © 2015 S. Karger AG, Basel.


MGT-SM: A Method for Constructing Cellular Signal Transduction Networks.
A cellular signal transduction network is an important means to describe biological responses to environmental stimuli and exchange of biological signals. Constructing the cellular signal transduction network provides an important basis for the study of the biological activities, the mechanism of the diseases, drug targets and so on. The statistical approaches to network inference are popular in literature. Granger test has been used as an effective method for causality inference. Compared with bivariate granger tests, multivariate granger tests reduce the indirect causality and were used widely for the construction of cellular signal transduction networks. A multivariate Granger test requires that the number of time points in the time-series data is more than the number of nodes involved in the network. However, there are many real datasets with a few time points which are much less than the number of nodes in the network. In this study, we propose a new multivariate Granger test-based framework to construct cellular signal transduction network, called MGT-SM. Our MGT-SM uses SVD to compute the coefficient matrix from gene expression data and adopts Monte Carlo simulation to estimate the significance of directed edges in the constructed networks. We apply the proposed MGT-SM to Yeast Synthetic Network and MDA-MB-468, and evaluate its performance in terms of the recall and the AUC. The results show that MGT-SM achieves better results, compared with other popular methods (CGC2SPR, PGC, and DBN).


MicroRNA-206 is associated with invasion and metastasis of lung cancer.
MicroRNAs are novel small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and cancer development and progression. The present study aims to explore the function of miR-206 in the proliferation, apoptosis, motility, and invasion of nonsmall cell lung cancer. Using real-time PCR, we detected the miR-206 expression of normal lung tissues, tumor tissues, human normal bronchial epithelial cell line, and six lung cancer cell lines (LCCLs). Then, we evaluated the role of miR-206 in cell proliferation, apoptosis, and invasion using Cell Counting Kit-8 assay, Annexin-V/FITC assay, wound healing, and Transwell assay in LCCLs. As a result, miR-206 expression level was lower in high metastasis tumors and 95D than low metastasis tumors and normal lung tissues as well as other LCCLs. After miR-206 was upregulated in LCCLs, cell proliferation was notably attenuated and apoptosis was significantly increased. Furthermore, overexpression of miR-206 inhibited migration and invasion of lung cancer cells. In conclusion, our data suggest that expression level of miR-206 was inversely correlated with metastatic potential of lung cancer.


Complete mitochondrial genome of an enigmatic dragonfly, Epiophlebia superstes (Odonata, Epiophlebiidae).
This study reported the 15,435 bp-long complete mitochondrial genome of the relict Epiophlebia superstes (Odonata, Epiophlebiidae), an enigmatic dragonfly of the paraphyletic 'Anisozygoptera' possessing characteristics similar to members of both extant odonate suborders, the Zygoptera and the Anisoptera. This mitogenome comprises the common set of 37 genes and an A + T-rich control region, and has a gene arrangement identical to those of all available odonates. The genome contains three non-coding inter-genic spacers (s1-s3), which occurs in all of other known odonates, but it lacks the inter-genic spacer s5 typically found in the Anisoptera. This result suggests that E. superstes possesses a mitogenmic organization more closely related to that of the Zygoptera than that of the Anizoptera.


Patients' perspectives on pain.
Nociceptive and neuropathic pain (NP) are common consequences following spinal cord injury (SCI), with large impact on sleep, mood, work, and quality of life. NP affects 40% to 50% of individuals with SCI and is sometimes considered the major problem following SCI. Current treatment recommendations for SCI-NP primarily focus on pharmacological strategies suggesting the use of anticonvulsant and antidepressant drugs, followed by tramadol and opioid medications. Unfortunately, these are only partly successful in relieving pain. Qualitative studies report that individuals with SCI-related long-lasting pain seek alternatives to medication due to the limited efficacy, unwanted side effects, and perceived risk of dependency. They spend time and money searching for additional treatments. Many have learned coping strategies on their own, including various forms of warmth, relaxation, massage, stretching, distraction, and physical activity. Studies indicate that many individuals with SCI are dissatisfied with their pain management and with the information given to them about their pain, and they want to know more about causes and strategies to manage pain. They express a desire to improve communication with their physicians and learn about reliable alternative sources for obtaining information about their pain and pain management. The discrepancy between treatment algorithms and patient expectations is significant. Clinicians will benefit from hearing the patient´s voice.


A model to assess acute and delayed lung toxicity of oxaliplatin during in vivo lung perfusion.
To determine the dose-limiting toxicity of oxaliplatin chemotherapy delivered by in vivo lung perfusion (IVLP). To allow assessment of subacute toxicities, we aimed to develop a 72-hour porcine IVLP survival model. In total, 12 Yorkshire male pigs were used. Left lung IVLP was performed for 3 hours. At 72 hours postoperatively, computed tomography imaging of the lungs was performed before the pigs were killed. Lung physiology, airway dynamics, gross appearance, and histology were assessed before and during IVLP, at reperfusion, and when the pigs were euthanized. An accelerated titration dose-escalation study design was employed whereby oxaliplatin doses were sequentially doubled provided no clinically significant toxicity was observed, defined as an arterial partial pressure of oxygen to fraction of inspired oxygen ratio <300 mm Hg or severe acute lung injury on biopsy. After an initial training phase, no mortality or adverse events related to the procedure were observed. There was no lung injury observed at the time of IVLP for any case. At sacrifice, clinically significant lung injury was observed at 80 mg/L oxaliplatin, with an arterial partial pressure of oxygen to fraction of inspired oxygen ratio of 112 mm Hg. Mild and subclinical lung injury was observed at 40 mg/L, with this dose being repeated to confirm safety. A stable and reproducible porcine 3-day IVLP survival model was established that will allow toxicity assessment of agents delivered by IVLP. Oxaliplatin delivered by IVLP showed delayed-onset toxicity that was not apparent at the time of reperfusion, with a maximal-tolerated dose of 40 mg/L. This information will inform initiation of a clinical trial examining IVLP delivery of oxaliplatin at our institution.


Drug therapy of hypercholesterolemia.
The rationale for drug treatment of patients with hypercholesterolemia is that sustained reductions in the plasma concentrations of atherogenic lipoproteins will retard the development of atherosclerosis. Drug therapy should be initiated only after the exclusion of secondary factors and after an adequate trial of dietary therapy has failed to lower plasma cholesterol to a satisfactory level. The bile-acid sequestrants (cholestyramine and colestipol), nicotinic acid, and lovastatin are the most effective drugs for use in patients with primary hypercholesterolemia; these agents reduce total and LDL cholesterol concentrations by 15-35%. For patients with high concentrations of LDL cholesterol who concurrently have hypertriglyceridemia, nicotinic acid is the drug of choice, and bile-acid sequestrants are contraindicated. Combined therapy with drugs that have different mechanisms of action can be effectively utilized in the treatment of patients with severe hypercholesterolemia; combinations involving lovastatin, nicotinic acid, and bile-acid sequestrants are the most effective.


Suicidality in Huntington's Disease: A Qualitative Study on Coping Styles and Support Strategies.
Huntington's disease (HD) mutation carriers are at increased risk of suicidal ideation, suicide attempts, and completed suicide. However, research is lacking on coping strategies and treatment options that can be offered to suicidal HD mutation carriers. This study explores how individuals with pre-motor or motor symptomatic HD cope with suicidality, how their partners support them, and their ideas and wishes regarding how relatives and healthcare professionals can help them in coping with suicidality. This qualitative study included 11 HD mutation carriers who experienced suicidal ideation or attempted suicide and 3 of their partners. They participated in a focus group discussion or an individual in-depth interview. Two independent researchers fragmented the transcribed interviews, coded these fragments, grouped them under themes, and structured the data. HD study participants used four main strategies to cope with suicidality, including talking about suicidality, employing self-management activities, using medication, and discussing end-of-life wishes. Partners, relatives, and healthcare professionals can support suicidal HD mutation carriers in each of those four strategies. Despite the absence of a turnkey solution for suicidality in HD, healthcare professionals can play an important role in supporting suicidal HD mutation carriers by providing an opportunity to talk about suicidality, providing psychoeducation on self-management, prescribing medication, and discussing end-of-life wishes. Future HD-specific intervention studies could investigate the effect of combining these treatment strategies into one holistic approach.


Differentially expressed seed aging responsive heat shock protein OsHSP18.2 implicates in seed vigor, longevity and improves germination and seedling establishment under abiotic stress.
Small heat shock proteins (sHSPs) are a diverse group of proteins and are highly abundant in plant species. Although majority of these sHSPs were shown to express specifically in seed, their potential function in seed physiology remains to be fully explored. Our proteomic analysis revealed that OsHSP18.2, a class II cytosolic HSP is an aging responsive protein as its abundance significantly increased after artificial aging in rice seeds. OsHSP18.2 transcript was found to markedly increase at the late maturation stage being highly abundant in dry seeds and sharply decreased after germination. Our biochemical study clearly demonstrated that OsHSP18.2 forms homooligomeric complex and is dodecameric in nature and functions as a molecular chaperone. OsHSP18.2 displayed chaperone activity as it was effective in preventing thermal inactivation of Citrate Synthase. Further, to analyze the function of this protein in seed physiology, seed specific Arabidopsis overexpression lines for OsHSP18.2 were generated. Our subsequent functional analysis clearly demonstrated that OsHSP18.2 has ability to improve seed vigor and longevity by reducing deleterious ROS accumulation in seeds. In addition, transformed Arabidopsis seeds also displayed better performance in germination and cotyledon emergence under adverse conditions. Collectively, our work demonstrates that OsHSP18.2 is an aging responsive protein which functions as a molecular chaperone and possibly protect and stabilize the cellular proteins from irreversible damage particularly during maturation drying, desiccation and aging in seeds by restricting ROS accumulation and thereby improves seed vigor, longevity and seedling establishment.


Giant and Tunable Out-of-Plane Spin Polarization of Topological Antimonene.
Topological insulators are bulk insulators with metallic and fully spin-polarized surface states displaying Dirac-like band dispersion. Due to spin-momentum locking, these topological surface states (TSSs) have a predominant in-plane spin polarization in the bulk fundamental gap. Here, we show by spin-resolved photoemission spectroscopy that the TSS of a topological insulator interfaced with an antimonene bilayer exhibits nearly full out-of-plane spin polarization within the substrate gap. We connect this phenomenon to a symmetry-protected band crossing of the spin-polarized surface states. The nearly full out-of-plane spin polarization of the TSS occurs along a continuous path in the energy-momentum space, and the spin polarization within the gap can be reversibly tuned from nearly full out-of-plane to nearly full in-plane by electron doping. These findings pave the way to advanced spintronics applications that exploit the giant out-of-plane spin polarization of TSSs.


Sleep Apnea and Hypertension: Are There Sex Differences? The Vitoria Sleep Cohort.
Evidence from longitudinal studies has reported contradictory results regarding the association between OSA and hypertension. In a previous analysis of the Vitoria Sleep Cohort, the relationship between OSA and the risk of developing hypertension was evaluated and no independent association after adjustment for confounding factors was found. In the present study, a post hoc analysis to assess the association between OSA and incident stage 2 hypertension (systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg) was made on the basis of sex differences. A prospective study was performed over 7.5 ± 0.8 years on a middle-aged general population, which included 1,155 normotensive subjects (43.7% men) who completed the follow-up. BP measurements (at baseline and follow-up) and polygraphy at baseline were performed. Logistic regression models were used to determine the association between the respiratory disturbance index (RDI) and stage 2 hypertension and a recursive partitioning method was used to determine the variables related to the incidence of stage 2 hypertension. The RDI was divided into subgroups (0-2.9, 3-6.9, 7-13.9, and ≥ 14), using the first subgroup as reference. For men, an RDI ≥ 14 was associated with a significantly increased OR for stage 2 hypertension (OR, 2.54 [95% CI, 1.09-5.95], P = .032). This association was not statistically significant among women (P = .371). The results suggest an association between moderate and severe OSA, and the incidence of more severe forms of hypertension occurring in men but not in women. However, because this is a community-based study, the women's population characteristics may differ from women usually seen in sleep-disorders clinics.


New ultrasound grading system for cesarean scar pregnancy and its implications for management strategies: An observational cohort study.
A cesarean section pregnancy (CSP) indicated the gestational sac (GS) implanted in the previous cesarean scar. The clinical manifestations of CSP present a wide range of variations, and the optimal management is yet to be defined. We retrospectively enrolled 109 patients with the diagnosis of CSP from our department and categorized them into four grades based on the ultrasound presentation. Grade I CSP indicated the GS embedded in less than one-half thickness of the lower anterior corpus; and grade II CSP represented the GS extended to more than one-half thickness of overlying myometrium. Grade III CSP implied the GS bulged out of the cesarean scar; and grade IV CSP denoted that GS became an amorphous tumor with rich vascularity at the cesarean scar. Seventy-eight women received surgery, and the complication rate was 14.1% (11/78). Linear regression analysis demonstrated a significant association between the invasiveness of the surgery and their ultrasound gradings. The mainstream operation for grade I CSP was transcervical resection, while the majority of grade III and IV patients required hysterotomy or hysterectomy. Another 31 women received chemotherapy with methotrexate as their initial treatment. The success rate for chemotherapy was 61.3%; the remaining patients required further surgery due to persistent CSP or heavy bleeding during or after chemotherapy. Fifteen patients (48.3%) receiving chemotherapy suffered from complications (mostly bleeding). Among them, 7 (22.6%) patients experienced bleeding of more than 1,000 mL, and 9 (29.0%) of these 31 patients required blood transfusions. Our novel ultrasound grading system for CSP may help to communicate between physicians, and determine the optimal surgical strategy. Chemotherapy with methotrexate for CSP is not satisfactory and is associated with a higher rate of complications.


Nano-sized zeolites as modulators of thiacloprid toxicity on Chironomus riparius.
This study investigated whether zeolites of different size (Y30 (nano-sized) and H-Beta(OH)-III (forming large aggregates/agglomerates composed of 50 nm small primary particles)) exerted acute toxicity on larvae of the non-biting midge, Chironomus riparius, and whether such zeolites are able to modulate the toxicity of a common insecticide, thiacloprid, by means of adsorption of a dissolved toxicant. We conducted acute toxicity tests with fourth instar larvae of C. riparius. In these tests, larvae were exposed to zeolites or thiacloprid solely, or to mixtures of both compounds. The mixtures comprised 1.0 µg/L thiacloprid in addition to low (5.2 mg/L), medium (18.2 mg/L), and high (391.7 mg/L) zeolite concentrations, resulting in different adsorption rates of thiacloprid. As biological endpoints, changes in mortality rates and in behavior were monitored every 24 h over a total investigation period of 96 h. Furthermore, we conducted chemical analyses of thiacloprid in the medium and the larvae and located the zeolite particles within the larvae by LA-ICP-MS imaging techniques. Our results demonstrate that both types of zeolites did not exert acute toxicity when applied as single-substances, but led to reduced acute toxicity of thiacloprid when applied together with thiacloprid. These results are in line with the sorption properties of zeolites indicating reduced bioavailability of thiacloprid, although our data indicate that thiacloprid can desorb from zeolites to some extent. While freely dissolved (i.e., non-sorbed) fraction of thiacloprid was a good parameter to roughly estimate toxic effects, it did not correlate with measured internal thiacloprid concentrations. Moreover, it was shown that both zeolite types were ingested by the larvae, but no indication for cellular uptake of them was found.


Pretreatment with alum or powdered activated carbon reduces bacterial predation-associated irreversible fouling of membranes.
This study evaluated the co-application of bacterial predation by Bdellovibrio bacteriovorus and either alum coagulation or powdered activated carbon adsorption to reduce fouling caused by Escherichia coli rich feed solutions in dead-end microfiltration tests. The flux increased when the samples were predated upon or treated with 100 ppm alum or PAC, but co-treatment with alum and predation gave the best flux results. The total membrane resistance caused by the predated sample was reduced six-fold when treated with 100 ppm PAC, from 11.8 to 1.98 × 10(11) m(-1), while irreversible fouling (Rp) was 2.7-fold lower. Treatment with 100 ppm alum reduced the total resistance 14.9-fold (11.8 to 0.79 × 10(11) m(-1)) while the Rp decreased 4.25-fold. SEM imaging confirmed this, with less obvious fouling of the membrane after the combined process. This study illustrates that the combination of bacterial predation and the subsequent removal of debris using coagulation or adsorption mitigates membrane biofouling and improves membrane performance.


Bariatric surgery in patients with inflammatory bowel disease: an accessible path? Report of a case series and review of the literature.
Morbid obesity is an emerging problem in the inflammatory bowel disease [IBD] population. Bariatric and IBD surgeries share technical difficulties and elevated morbidity. However, nothing is known about the possibility of performing bariatric surgery in patients with a definite diagnosis of IBD. The aim of this study was to evaluate safety and efficacy of restrictive bariatric surgical procedures in IBD patients. Six patients with morbid obesity and IBD were operated on with restrictive bariatric surgery and concomitant or deferred IBD surgery. We compared BMI, excess weight loss, and perioperative complications of restrictive bariatric surgery in IBD with a control group of 95 bariatric patients. We also evaluated clinical, biochemical, pharmacological, and endoscopic characteristics before and after surgery in IBD patients. Perioperative results, in terms of BMI, excess weight loss, and complications after restrictive bariatric surgery, were comparable between obese IBD and control patients. IBD patients experienced a significant postoperative reduction in BMI, CRP levels, WCC, and systolic blood pressure and a significant increment in hemoglobin levels. None of the patients reported signs of malabsorption. All the patients except one were able to discontinue steroids, were in endoscopic remission at 1 year, and were in clinical remission at the latest follow-up visit. Two patients halved azathioprine dosage. One patient had a postoperative clinical recurrence treated with adalimumab. Bariatric surgery seems to be safe and effective in IBD patients. Concomitant ileocolic resection does not increase perioperative complications. Relationship between IBD and obesity remains unclear, but weight loss could be useful in the pharmacological control of IBD.


Religious and Spiritual Growth Goals: A Forgotten Outcome.
Religious and spiritual (R/S) growth goals have been forgotten among self-improvement goals. We used social cognitive theory, useful in other domains of self-improvement, to study R/S goals. Data from 350 adults (Mage = 40.5, SD = 14.6) were used to examine the relations among age, gender, social interactions, and commitment to R/S goals and physical activity goals. Results of the path analysis, X2 (DF = 2, N = 350) = 9.91, p < .01, showed similar contributions of positive social interactions to persistence on both goals. Differences between the two outcomes included a direct effect of age (β = .18), dissatisfaction with negative social interactions (β = .12), and satisfaction with positive social exchanges (β = .15) on persistence on R/S goals. Only positive social exchanges (β = .31) related to physical activity goals. The results are discussed in terms of the feasibility of applying goal-striving frameworks to the examination of R/S growth goals.


Outcomes of One straight-line flow with and without pedal arch in patients with critical limb ischemia.
This study aimed to compare the outcomes of revascularization strategies for patients with critical limb ischemia (CLI) whereby single vessel run off to the foot was established with or without flow into a patent pedal arch. We retrospectively analyzed data from 312 consecutive patients with CLI who underwent endovascular therapy (EVT) between December 2009 and February 2011. Below-the-knee angiography identified one vessel run off in 137 patients (44%), and we aimed to compare the outcomes between those patients where revascularization resulted in one-straight-line flow into a patent pedal arch (76 limbs, Group A) versus those who attained one straight-line flow to the distal end of a tibial vessel without flow into a patent pedal arch (61 limbs, Group B). The study endpoints were amputation free survival rate, limb salvage rate and wound healing rate at 12 months after EVT. Amputation free survival rate differed significantly between groups (88.2% in group A vs. 65.6% in group B, P = 0.01). Limb salvage rate also differed between groups (98.4% vs.89.3%, P = 0.03). Wound healing rate showed a trend towards difference between the two groups (89.4% vs. 80.6% P = 0.11). Among patients with CLI where only one vessel runoff can be established to the foot, direct flow into a patent pedal arch is essential to improve their clinical outcomes. © 2015 Wiley Periodicals, Inc.


Comparison of a mouse and a novel human scFv-SNAP-auristatin F drug conjugate with potent activity against EGFR-overexpressing human solid tumor cells.
Antibody-drug conjugates (ADCs) can deliver toxins to specific targets such as tumor cells. They have shown promise in preclinical/clinical development but feature stoichiometrically undefined chemical linkages, and those based on full-size antibodies achieve only limited tumor penetration. SNAP-tag technology can overcome these challenges by conjugating benzylguanine-modified toxins to single-chain fragment variables (scFvs) with 1:1 stoichiometry while preserving antigen binding. Two (human and mouse) scFv-SNAP fusion proteins recognizing the epidermal growth factor receptor (EGFR) were expressed in HEK 293T cells. The purified fusion proteins were conjugated to auristatin F (AURIF). Binding activity was confirmed by flow cytometry/immunohistochemistry, and cytotoxic activity was confirmed by cell viability/apoptosis and cell cycle arrest assays, and a novel microtubule dynamics disassembly assay was performed. Both ADCs bound specifically to their target cells in vitro and ex vivo, indicating that the binding activity of the scFv-SNAP fusions was unaffected by conjugation to AURIF. Cytotoxic assays confirmed that the ADCs induced apoptosis and cell cycle arrest at nanomolar concentrations and microtubule disassembly. The SNAP-tag technology provides a platform for the development of novel ADCs with defined conjugation sites and stoichiometry. We achieved the stable and efficient linkage of AURIF to human or murine scFvs using the SNAP-tag technology, offering a strategy to improve the development of personalized medicines.


The role of receptor subtype diversity in the CNS.
The molecular characterization of neuroreceptors and voltage-gated ion channels has revealed that receptor subtype heterogeneity is a common feature of chemical and electrical signal reception. The use of distinct genes encoding receptor subtypes is a favoured mechanism for generation of this diversity. We propose that the significance of the multiplicity and diversity of signal reception proteins is to increase the information-handling capacity of neurons. This may contribute to neural plasticity.


Poxvirus host range genes.
As a family of viruses, poxviruses collectively exhibit a broad host range and most of the individual members are capable of replicating in a wide array of cell types from various host species, at least in vitro. At the cellular level, poxvirus tropism is dependent not upon specific cell surface receptors, but rather upon: (1) the ability of the cell to provide intracellular complementing factors needed for productive virus replication, and (2) the ability of the specific virus to successfully manipulate intracellular signaling networks that regulate cellular antiviral processes downstream of virus entry. The large genomic coding capacity of poxviruses enables the virus to express a unique collection of viral proteins that function as host range factors, which specifically target and manipulate host signaling pathways to establish optimal cellular conditions for viral replication. Functionally, the known host range factors from poxviruses have been associated with manipulation of a diverse array of cellular targets, which includes cellular kinases and phosphatases, apoptosis, and various antiviral pathways. To date, only a small number of poxvirus host range genes have been identified and studied, and only a handful of these have been functionally characterized. For this reason, poxvirus host range factors represent a potential gold mine for the discovery of novel pathogen-host protein interactions. This review summarizes our current understanding of the mechanisms by which the known poxvirus host range genes, and their encoded factors, expand tropism through the manipulation of host cell intracellular signaling pathways.


Cation segregation in Nb16W18O94 using high angle annular dark field scanning transmission electron microscopy and image processing.
We report the characterization of the complex oxide Nb16W18O94 using high angle annular dark field imaging at 200 kV in a scanning transmission electron microscope. The results of this study suggest that the W and Nb cations are not uniformly distributed among the cation columns projected along [001] but that there is preferential segregation of the heavier species to certain column sites. In order to analyse the experimental data obtained, an image processing methodology has been developed which may also find application in locating specific motifs within a generally distorted image field.


Serum creatine kinase and alkaline phosphatase in experimental small bowel infarction.
Serum creatine phosphokinase (CK) and alkaline phosphatase (ALP) rise after mesenteric infarction; it is not known which one rises earlier or which one has the greater elevation. This experiment compared and contrasted the elevations in both these enzyme systems after acute small bowel infarction. Isoenzymes of both systems were analyzed to determine if any qualitative changes occurred. After baseline blood samples had been drawn, 10 dogs had midline laparotomies under general anesthesia. Each was assigned to one of two groups according to a randomized block design. Controls (CON) were closed after exploration (N = 5). The infarction (INF) group had ligation and division of the arteries to the jejunum and ileum (N = 5). Blood samples were obtained from both groups at 3, 6, 9, 12, 24, and 27 hr after surgery. Sera were analyzed for total CK and ALP activity by automated spectrophotometry. Isoenzymes were determined by agarose gel electrophoresis. Serum CK rose faster and to a higher level than ALP after small bowel infarction (470 +/- 181 vs 196 + 28 IU/liter). CK-BB was a better marker of small bowel necrosis than was intestinal ALP. The elevation of both CK and ALP by 12 hr after infarction may be a diagnostic aid if similar changes occur in humans.


Thyroid circadian timing: roles in physiology and thyroid malignancies.
The circadian clock represents an anticipatory mechanism, well preserved in evolution. It has a critical impact on most aspects of the physiology of light-sensitive organisms. These rhythmic processes are governed by environmental cues (fluctuations in light intensity and temperature), an internal circadian timing system, and interactions between this timekeeping system and environmental signals. Endocrine body rhythms, including hypothalamic-pituitary-thyroid (HPT) axis rhythms, are tightly regulated by the circadian system. Although the circadian profiles of thyroid-releasing hormone (TRH), thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) in blood have been well described, relatively few studies have analyzed molecular mechanisms governing the circadian regulation of HPT axis function. In this review, we will discuss the latest findings in the area of complex regulation of thyroid gland function by the circadian oscillator. We will also highlight the molecular makeup of the human thyroid oscillator as well as the potential link between thyroid malignant transformation and alterations in the clockwork.


Acylation of subtilisin A by aryl esters: contribution to rate limitation by a physical step preceding general acid-base catalysis.
The specificity ratios kc/Km = k for subtilisin A catalyzed hydrolysis of five aryl esters of N-(methoxycarbonyl)-L-Phe (McPhe) were determined at pH 7.03 and its pD equivalent. The ratios are independent of the electronic properties of the leaving group substituent. Kinetic solvent isotope effects, Dk, increase from about 0.9 to 1.3 as leaving group ability decreases from p-nitrophenolate to p-methoxyphenolate. The k of N-(methoxycarbonyl)-L-phenylalanine p-nitrophenyl ester (NPE) with native enzyme exhibits a strong temperature dependence; delta H* = 87 +/- 3 kJ mol-1 and delta S* = 148 +/- 14 J K-1 mol-1 at 25 degrees C (H2O). The Dk with this substrate is 1.36 at 13.6 degrees C, declines to 0.89 at 25 degrees C, and then increases to 1.04 at 39.4 degrees C. Above neutral pH(D), with McPhe NPE as substrate, the dependence of k is for the dissociated form of a single base of pKapp = 7.38 +/- 0.03 in H2O and 7.67 +/- 0.03 in D2O. The pKapp values are apparently those of the uncomplexed native protein. By contrast, k of 3-phenylpropanoic acid (Prop) p-nitrophenyl ester exhibits a weaker temperature dependence; delta H* = 20 kJ mol-1 and delta S* = -90 J K-1 mol-1 (H2O) at 25 degrees C. The Dk are larger than those for McPhe NPE, decreasing from 1.99 at 20.5 degrees C to 1.74 at 46.1 degrees C. These results, combined with those of previous studies, are consistent with limitation of k by at least two processes.(ABSTRACT TRUNCATED AT 250 WORDS)


Experimental data required to support second medical use claims.
The timing of filing a new patent application always requires a judgment call to be made between securing the earliest filing date and waiting to collect enough data to ensure the claims are fully supported and enabled across their scope. In addition, it is important to ensure that the application is drafted in such a way that it is suitable for filing in various jurisdictions. The case law we have considered for the sufficiency/enablement of second medical use claims in Europe, the USA and Australia makes it clear that experimental results should be included in the application at filing, and that the results must demonstrate that the claimed pharmaceutical product could be reasonably expected to treat the claimed indication.


Does Hsp60 Provide a Link between Mitochondrial Stress and Inflammation in Diabetes Mellitus?
The focus of this review is to summarise the known relationships between the expression of heat shock protein 60 (Hsp60) and its association with the pathogenesis of Type 1 and Type 2 diabetes mellitus. Hsp60 is a mitochondrial stress protein that is induced by mitochondrial impairment. It is known to be secreted from a number of cell types and circulating levels have been documented in both Types 1 and 2 diabetes mellitus patients. The biological significance of extracellular Hsp60, however, remains to be established. We will examine the links between Hsp60 and cellular anti- and proinflammatory processes and specifically address how Hsp60 appears to affect immune inflammation by at least two different mechanisms: as a ligand for innate immune receptors and as an antigen recognised by adaptive immune receptors. We will also look at the role of Hsp60 during immune cell activation in atherosclerosis, a significant risk factor during the pathogenesis of diabetes mellitus.


[Treatment of arterial hypoxemia in early period of traumatic disease].
Issues of arterial hypoxemia treatment in early period of traumatic disease, taking into account modern approaches, adopted in surgery of injuries and anesthesy-resuscitation. It is recommended to use the method proposed for the arterial oxygen content enhancing in an acute respiratory insufficiency of various genesis, including the cases of progressive posttraumatic disease.


Short-term risk of falling after cochlear implantation.
Cochlear implantation is a highly effective intervention for hearing loss, but insertion of an implant into the cochlea is often accompanied by loss of residual hearing function. Sometimes, postoperative testing also shows loss of function in the semicircular canals or otolith organs. The effect of this loss on equilibrium, particularly in the short term following surgery, and the risk of falling due to this loss is unknown. We prospectively measured balance in 16 consecutive adult cochlear implant patients before and 2 weeks after surgery. Subjects stood on a foam pad with eyes closed, feet together and arms at the side. The length of time over which this posture could be maintained was recorded up to a maximum value of 30 s indicating normal performance. Ten of 16 subjects reached a maximal time on preoperative testing. Nine of 16 subjects lost balance function after surgery. Four of the 10 subjects with normal preoperative balance function lost function. Subjects older than the age of 60 were more likely to lose balance function than younger subjects. We used previously published values relating balance performance on foam to risk of falling to calculate the fall risk among our subjects. The relative risk of falling increased after surgery by more than threefold in some patients. Imbalance after cochlear implantation may be much more common, particularly in the short term, than previously appreciated. This imbalance is accompanied by an increased risk of falling in many patients. Careful preoperative counseling before implantation and postoperative therapeutic intervention to improve comfort and reduce the chance of falling may be warranted, particularly in patients at a risk for injuries from falls (level of evidence: 2b).


A Low-Cost Audio Prescription Labeling System Using RFID for Thai Visually-Impaired People.
This research aims to develop a low-cost audio prescription labeling (APL) system for visually-impaired people by using the RFID system. The developed APL system includes the APL machine and APL software. The APL machine is for visually-impaired people while APL software allows caregivers to record all important information into the APL machine. The main objective of the development of the APL machine is to reduce costs and size by designing all of the electronic devices to fit into one print circuit board. Also, it is designed so that it is easy to use and can become an electronic aid for daily living. The developed APL software is based on Java and MySQL, both of which can operate on various operating platforms and are easy to develop as commercial software. The developed APL system was first evaluated by 5 experts. The APL system was also evaluated by 50 actual visually-impaired people (30 elders and 20 blind individuals) and 20 caregivers, pharmacists and nurses. After using the APL system, evaluations were carried out, and it can be concluded from the evaluation results that this proposed APL system can be effectively used for helping visually-impaired people in terms of self-medication.


Insufficient restoration of lumbar lordosis and FBI index following pedicle subtraction osteotomy is an indicator of likely mechanical complication.
Pedicle subtraction osteotomies (PSO) enable correction of spinal deformities but remain difficult and are associated with high complication rates. This study aimed to prospectively review different post-operative complications and mechanical problems in patients who underwent PSO as treatment for sagittal imbalance as sequelae of degenerative disc disease or previous spinal fusion. This was a descriptive prospective single center study of 63 patients who underwent sagittal imbalance correction by PSO. Radiographic analysis of pre- and post-operative pelvic and spinal parameters was completed based on EOS images following 3D modeling. Global and sub-group analyses were completed based on the Roussouly classification. A systematic analysis of post-operative complications was conducted during hospital stay and at follow-up visits. Complications included 15 cases (20.2%) of bilateral leg pain, with transient neurological deficit in 6 cases (9.5%), and 9 cases (12.5%) of early surgical site infections. Intra-operative complications included five tears of the dura mater and two cases of excessive blood loss (>5,000 mL). Two mortalities occurred from major intracerebral bleeds in the early post-operative period. Mechanical complications were principally non-union (9 cases) and junctional kyphosis (3 cases). All 19 post-operative complications (28.1%) were revised at an average of 2 years following surgery. All mechanical complications were found in the patients who had insufficient imbalance correction and this was mainly associated with high PI (>60°) or a moderate PI (45-60º) combined with excess FBI pre-operatively that remained >10° post-operatively. Infection and neurologic complications following PSO are relatively common, and frequently reported in the literature. The principal cause of mechanical complications, such as non-union or junctional kyphosis, was insufficient sagittal correction, characterized by post-operative FBI >10°. The risks of insufficient correction are greater in patients with higher pelvic incidence and those patients who required very high correction.


Sirtuin-6 preserves R-spondin-1 expression and increases resistance of intestinal epithelium to injury in mice.
Sirtuin-6 (Sirt6) is a critical epigenetic regulator, but its function in the gut is unknown. Here, we studied the role of intestinal epithelial Sirt6 in colitis-associated intestinal epithelial injury. We found that Sirt6, which is predominantly expressed in epithelial cells in intestinal crypts, is decreased in colitis in both mice and humans. Colitis-derived inflammatory mediators including interferon-γ and reactive oxygen species strongly inhibited Sirt6 protein expression in young adult mouse colonocyte (YAMC) cells. The susceptibility of the cells to injurious insults was increased after knockdown of Sirt6 expression. In contrast, YAMC cells with Sirt6 overexpression exhibited more resistance to injurious insult. Furthermore, intestinal epithelial-specific Sirt6 (Sirt6IEC-KO) knockout mice exhibited greater susceptibility to dextran sulfate sodium (DSS)-induced colitis. RNA sequencing transcriptome analysis revealed that inflammatory mediators such as tumor necrosis factor (TNF)-α suppressed expression of R-spondin-1 (Rspo1, a critical growth factor for intestinal epithelial cells) in Sirt6-silenced YAMC cells in vitro. In addition, lipopolysaccharide was found to inhibit colonic Rspo1 expression in Sirt6IEC-KO mice but not their control littermates. Furthermore, Sirt6IEC-KO mice with DSS-induced colitis also exhibited in a significant decrease in Rspo1 expression in colons. In vitro, knockdown of Rspo1 attenuated the effect of ectopic expression of Sirt6 on protection of YAMC cells against cell death challenges. In conclusion, Sirt6 plays an important role in protecting intestinal epithelial cells against inflammatory injury in a mechanism associated with preserving Rspo1 levels in the cells.


Monitoring and characterization of diamondback moth (Lepidoptera: Plutellidae) resistance to spinosad.
Fourteen populations of the diamondback moth, Plutella xylostella (L.), were collected from fields of crucifer vegetables in the United States, Mexico, and Thailand in 1999 and 2000 for susceptibility tests with spinosad. Most populations were susceptible to spinosad and similar to earlier baseline values, but populations from Thailand and Hawaii showed high levels of tolerance. A statewide survey in Hawaii in 2000 and 2001 indicated resistance problems on several islands. One colony collected in October 2000 from Pearl City, HI, was subjected to further selection pressure, using spinosad in the laboratory, and then was used as the resistant strain (Pearl-Sel) for other tests. Spray tests using the recommended field rates of spinosad on potted broccoli plants in the greenhouse confirmed that field control failures due to resistance were possible in the areas of these collections. Analysis of probit lines from F1 reciprocal crosses between the Pearl-Sel and S strain indicated that resistance to spinosad was inherited autosomally and was incompletely recessive. A direct test of monogenic inheritance based on the F1 x Pearl-Sel backcrosses suggested that resistance to spinosad was probably controlled by one locus. The synergists S,S,S-tributyl phosphorotrithioate and piperonyl butoxide did not enhance the toxicity of spinosad to the resistant colony, indicating metabolic mediated detoxification was probably not responsible for the spinosad resistance. Two field colonies in Hawaii that were resistant to spinosad were not cross-resistant to emamectin benzoate or indoxacarb. Resistance developed in Hawaii due to the continuous cultivation of crucifers in which as many as 50 applications of spinosad per year may have been made to a common population of P. xylostella in sequential plantings, although each grower might have used the labeled restrictions for resistance management. Resistance management strategies will need to address such cropping and pest management practices.


V1 mechanisms and some figure-ground and border effects.
V1 neurons have been observed to respond more strongly to figure than background regions. Within a figure region, the responses are usually stronger near figure boundaries (the border effect), than further inside the boundaries. Sometimes the medial axes of the figures (e.g., the vertical midline of a vertical figure strip) induce secondary, intermediate, response peaks (the medial axis effect). Related is the physiologically elusive "cross-orientation facilitation", the observation that a cell's response to a grating patch can be facilitated by an orthogonally oriented grating in the surround. Higher center feedbacks have been suggested to cause these figure-ground effects. It has been shown, using a V1 model, that the causes could be intra-cortical interactions within V1 that serve pre-attentive visual segmentation, particularly, object boundary detection. Furthermore, whereas the border effect is robust, the figure-ground effects in the interior of a figure, in particular, the medial axis effect, are by-products of the border effect and are predicted to diminish to zero for larger figures. This model prediction (of the figure size dependence) was subsequently confirmed physiologically, and supported by findings that the response modulations by texture surround do not depend on feedbacks from V2. In addition, the model explains the "cross-orientation facilitation" as caused by a dis-inhibition, to the cell responding to the center of the central grating, by the background grating. Furthermore, the elusiveness of this phenomena was accounted for by the insight that it depends critically on the size of the figure grating. The model is applied to understand some figure-ground effects and segmentation in psychophysics: in particular, that contrast discrimination threshold is lower within and at the center of a closed contour than that in the background, and that a very briefly presented vernier target can perceptually shine through a subsequently presented large grating centered at the same location.


Soft Matter in Lipid-Protein Interactions.
Membrane lipids and cellular water (soft matter) are becoming increasingly recognized as key determinants of protein structure and function. Their influences can be ascribed to modulation of the bilayer properties or to specific binding and allosteric regulation of protein activity. In this review, we first consider hydrophobic matching of the intramembranous proteolipid boundary to explain the conformational changes and oligomeric states of proteins within the bilayer. Alternatively, membranes can be viewed as complex fluids, whose properties are linked to key biological functions. Critical behavior and nonideal mixing of the lipids have been proposed to explain how raft-like microstructures involving cholesterol affect membrane protein activity. Furthermore, the persistence length for lipid-protein interactions suggests the curvature force field of the membrane comes into play. A flexible surface model describes how curvature and hydrophobic forces lead to the emergence of new protein functional states within the membrane lipid bilayer.


Electronic transitions in [Re6S8X6](4-) (X = Cl, Br, I): results from time-dependent density functional theory and solid-state calculations.
Relativistic time-dependent density functional theory (TDDFT) calculations were performed on the excited states of the [Re6S8X6](4-) (X = Cl, Br, I) series. For all members of the series, the lowest excited states in the spectra do not correspond to a ligand-to-metal (or ligand-to-cluster) excitation but rather a cluster-cluster transition from the HOMO e(g) to antibonding t(1u) orbitals with only a modest admixture of Re-X sigma* character. These results lead to a re-evaluation of the role of the axial ligand in these compounds. The calculated excitation energies reproduce the experimental absorption and emission spectra. This work also confirms previous TDDFT calculations on the emission energies. Results for discrete cluster ions are compared with those obtained from calculations in the solid state in Cs4[Re6S8X6].CsX (X = Cl, Br) and Cs4[Re6S8I6].2CsI. Significant differences are seen in the relatively higher energies of the antibonding t(1u) orbital in the solid-state case, and an inversion in the orbital character of the two allowed absorptions is calculated. The e(g) (HOMO)-to-a(2g) (LUMO) orbital energy differences corresponding to the emission transition are quite comparable for the solid state and discrete cluster calculations, and both overestimate the observed emission energy by the same margin.


Dendritic Spine Dynamics after Peripheral Nerve Injury: An Intravital Structural Study.
Neuropathic pain is an intractable medical condition with few or no options for effective treatment. Emerging evidence shows a strong structure-function relationship between dendritic spine dysgenesis and the presence of neuropathic pain. Postmortem tissue analyses can only imply dynamic structural changes associated with injury-induced pain. Here, we profiled the in vivo dynamics of dendritic spines over time on the same superficial dorsal horn (lamina II) neurons before and after peripheral nerve injury-induced pain. We used a two-photon, whole-animal imaging paradigm that permitted repeat imaging of the same dendritic branches of these neurons in C57/Bl6 Thy1-YFP male mice. Our study demonstrates, for the first time, the ongoing, steady-state changes in dendritic spine dynamics in the dorsal horn associated with peripheral nerve injury and pain. Ultimately, the relationship between altered dendritic spine dynamics and neuropathic pain may serve as a structure-based opportunity to investigate mechanisms of pain following injury and disease.SIGNIFICANCE STATEMENT This work is important because it demonstrates for the first time: (1) the powerful utility of intravital study of dendritic spine dynamics in the superficial dorsal horn; (2) that nerve injury-induced pain triggers changes in dendritic spine steady-state behavior in the spinal cord dorsal horn; and (3) this work opens the door to further investigations in vivo of spinal cord dendritic spine dynamics in the context of injury and disease.


Kugel's Artery as a Rare Intracoronary Collateralization Does Not Effectively Guarantee the Presence of Viable Hibernating Myocardium.
In this note, it was aimed to describe a 66-year-old patient for ischemia evaluation following the episodes of chest discomfort using dipyridamole stress-rest myocardial perfusion single-photon emission computed tomography (SPECT). Invasive coronary angiography demonstrated a total occlusion of the right coronary artery (RCA) and prominent RCA intracoronary collateral (Kugel's artery) associated with nonviable, infarcted myocardium in the inferior wall of left ventricular LV on myocardial perfusion SPECT. Thus, recanalization of RCA was not performed in our patient. It is concluded that performing complementary imaging modalities for assessing myocardial perfusion like SPECT for the prediction of viability to sole reliance on angiographic data in decision making for revascularization is encouraged.


Visual processing patterns of adults with traumatic brain injury when viewing image-based grids and visual scenes.
Many individuals with traumatic brain injury (TBI) rely on augmentative and alternative communication (AAC) supports to meet functional communication needs. The use of images to display message content may be advantageous for this population, given deficits in literacy, visual processing, and cognition. Grid and visual scene displays are two options for presenting images within AAC systems. Eye-tracking technology was utilized to evaluate the visual processing patterns of 13 adults with a history of TBI and 13 adults without TBI when interpreting themes depicted in grid and visual scene displays. Results indicated that differential processing and effort was required when interpreting the two display types. Both groups of participants required significantly more visual fixation time and exhibited patterns consistent with greater cognitive effort when identifying themes depicted in grids compared to visual scenes (i.e., greater numbers of short fixations). The participants with TBI were overall less efficient than those without TBI when identifying themes presented in both AAC display types. These results add to the growing body of evidence indicating that visual scenes may more effectively represent complex concepts than decontextualized, grid-based images for individuals with TBI. Additional clinical implications are discussed.


Long Noncoding RNAs and Human Liver Disease.
Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease.


Compas-Y: A mixed methods pilot evaluation of a mobile self-compassion training for people with newly diagnosed cancer.
Compas-Y is a compassionate mind training app that was co-designed to be fully adapted to mobile technology and to people with newly diagnosed cancer. This study aimed to evaluate the use, appreciation and impact of the app. Seventy-one people with cancer who created an app account were included (38% breast cancer, 72% diagnosed <4 months ago, 76% received chemotherapy). Participants had very high baseline scores of self-compassion. In a convergent mixed methods design, back-end log-data (n = 71), pre-post surveys (n = 34) and semi-structured interviews (n = 23) collected for >8 weeks and were concurrently analysed using joint displays. About half of the participants (45%) used 4 of the 6 modules. Compas-Y was highly appreciated, with all content considered relevant and a source of support. Experienced benefits related to improved mental health. Particularly, we found significant changes in anxiety, but not in depression or well-being. In the interviews, people reported experiencing more rest and more positive emotions due to using the app. Process benefits included significant reductions in self-criticism (inadequate self and self-blame), but not self-compassion. In the interviews, people reported improved self-compassion and less self-criticism, more self-awareness, recognition and support, and improved emotion regulation and coping. The surveys did not capture the full range of outcomes that participants reported in the interviews. Compas-Y is a highly appreciated mobile intervention that supported users in aspects of their mental health. Findings are discussed in terms of reach and adherence, app functionalities, co-design and tailoring of cancer-related and compassion-based eHealth.


Postoperative adjuvant therapy.
There is no proven significant benefit of adjuvant chemotherapy in colorectal cancer. Portal infusion of 5-FU in the immediate postoperative period has given some promising results but further trials of this treatment are necessary. Intraperitoneal administration should also be tested. All clinical studies of adjuvant chemotherapy must include control groups who do not receive adjuvant treatment.


Follicle ablation improves the ovarian response and the number of collected embryos in superovulated cows during the early stages of lactation.
A field study was designed to compare ovarian response and embryo yield in cows during early lactation when gonadotropin administration followed one of four treatments. In group 1A (n = 19) and 1B (n = 9), the estrouses were synchronized by two prostaglandin F2alpha (PG) injections given 11 days apart, and starting from day 9 of the synchronized cycle superovulation was conducted with eight decreasing dose of FSH. In group 1B, ablation of all follicles >3 mm was carried out on day 8. In group 2A and 2B (each n = 9), a progesterone plus oestradiol intravaginal device (PRID) was inserted for 11 days and gonadotropin administration started on day 9, while cows from group 2B had a follicle ablation on day 8. In all groups, two PG injections were given along with the sixth and the seventh dose of FSH, and the cows were twice inseminated 12 and 24 h after estrus detection. Embryos were collected on day 7. In cumulative results from aspirated and non-aspirated cows, follicular ablation significantly improved: the ovarian response (10 +/- 1.23 vs 6.69 +/- 0.60 corpora lutea per donor), the mean collected embryos (6.57 +/- 0.94 vs 2.46 +/- 0.53) and the mean transferable embryos (4.43 +/- 0.89 vs 2.18 +/- 0.47). Group 1B and 2B cows had better ovarian response than 1A (6.44 +/- 0.81, 12.25 +/- 4.11 and 9.44 +/- 0.93, for groups 1A, 1B and 2B, respectively, p < 0.05). Similarly, from groups 1B and 2B more (p < 0.05) embryos were collected in comparison with their respective group, while the mean transferable embryos from group 2B (5.22 +/- 1.13) was greater (p < 0.05) than that of group 1A (1.67 +/- 0.35), and tented to be greater than those of groups 2A (3.44 +/- 1.19, p = 0.062) and 1B (3.00 +/- 1.78, p = 0.066). The highest (p < 0.05) transferable embryo collection rate was recorded in group 2B (55.29%), followed by that of group 1B (41.33%). In summary, early in lactation, an acceptable number of transferable embryos can be collected from high producing dairy cows, when follicle ablation prior to superovulation is combined with progesterone and oestradiol administration.


Clinical and Genetic Study of Three Inherited Microdeletions of Chromosome 16p11.2.
Copy number variations (CNVs) in chromosome 16p11.2 are not rare. 16p11.2 microdeletion is among the most commonly known genetic etiologies of overweightness, autism spectrum disorder (ASD), and related neurodevelopmental disorders. We report the prenatal diagnosis and genetic counseling of three cases with inherited 16p11.2 microdeletions. In these families, mother/father and fetus have the same microdeletion. Following the use of molecular genetic techniques including array-based methods, the number of reported cases has rapidly increased. A combination of prenatal three-dimensional ultrasound, karyotype analysis, chromosomal microarray analysis (CMA), copy number variation sequencing (CNV-seq), whole-exome sequencing (WES), and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.


Psychosocial implications of pediatric surgical hospitalization.
The prevalence of childhood surgical illness and injury requiring hospitalization suggests the need for implementation of an applied intervention to decrease levels of anxiety in these patients. When psychological concerns are not addressed in the present moment, potential for long-term negative psychological effects occur. To respond to the psychosocial needs of pediatric surgical patients it is important to understand foundational stages of development. Age is not always directly correlated with developmental stage and attunement to this subtle differentiation is essential. Some medical facilities offer services to pediatric surgical patients that include education about upcoming procedures as well as medical play which offers the opportunity to express emotions correlated with the hospitalization experience. This approach is directive in nature and controls the process of making sense of the medical environment. An alternative is Child Centered Play Therapy (CCPT) which creates an outlet for any emotions the children choose to express. CCPT offers comprehensive mental health care through a developmentally-appropriate, undirected intervention carried out by a mental health therapist and has been shown to reduce perceived and actual psychological trauma, anxiety, and behavioral issues in children preparing for surgery.


POPULATION GENETICS OF A PARASITIC CHROMOSOME: EXPERIMENTAL ANALYSIS OF PSR IN SUBDIVIDED POPULATIONS.
Nasonia vitripennis is a parasitoid wasp that harbors several non-Mendelian sex-ratio distorters. These include MSR (Maternal Sex Ratio), a cytoplasmic element that causes nearly all-female families, and PSR (Paternal Sex Ratio), a supernumerary chromosome that causes all-male families. As in other hymenoptera, N. vitripennis has haplodiploid sex determination. Normally, unfertilized (haploid) eggs develop into males and fertilized (diploid) eggs develop into females. The PSR chromosome violates this normal pattern; it is inherited through sperm, but then causes destruction of the paternal chromosomes (except itself), thus converting diploid fertilized eggs (normally females) into haploid eggs that develop into PSR-bearing males. PSR is an extreme example of "parasitic" or "selfish" DNA. Because N. vitripennis has a highly subdivided population structure in nature, population-level selection may be important in determining the dynamics of PSR in natural populations. A theoretical analysis shows that subdivided population structure reduces PSR frequency, whereas high fertilization proportion (such as produced by the MSR element) increases PSR frequency. Population experiments using two deme sizes (3- and 12-foundress groups) and strains producing two fertilization proportions [wild-type (LabII)-57-67% female, and MSR (MI)-90-93% female] confirm these predictions. PSR achieved frequencies over 0.90 in 12-foundress group MSR populations in contrast to 0.20-0.40 in wild-type 12-foundress populations. PSR was selected against in wild-type populations composed of three-foundress groups. In MSR populations with three-foundress groups, presence of PSR selected against the MSR cytoplasmic element, eventually leading to low frequencies of both PSR and MSR. Complicated dynamics may occur when these two sex-ratio distorters are both present in highly subdivided populations. The existence of PSR in natural populations may depend on the presence of MSR. Results indicate that population subdivision could be important in determining the frequency of sex ratio distorters in N. vitripennis.


Modulation of working memory and of long- but not short-term memory by cholinergic mechanisms in the basolateral amygdala.
Male Wistar rats were exposed to one-trial step-down inhibitory avoidance training using a 0.5 mA footshock. Through bilaterally implanted indwelling cannulae, they received bilateral 0.5 microl infusions of saline, oxotremorine (0.06 or 0.3 microg) or scopolamine (0.25 or 2.0 microg) into the basolateral complex of the amygdaloid nucleus (BLA). Infusions were either 10 min before training (experiment 1) or 4 min after training (experiment 2). In experiment 1, the animals were tested three times: first for working memory (WM) 2 s after training, then for short-term memory (STM) 1.5 h later, and finally for long-term memory (LTM) 24 h later. Oxotremorine enhanced and scopolamine depressed WM and LTM while leaving STM unaffected. In experiment 2, the treatments were given after WM was presumably over. Again, oxotremorine again enhanced and scopolamine depressed LTM, and neither had any effect on STM. The results fit with the suggestion by Beninger and his co-workers that cholinergic synapses in the BLA regulate WM, generalize that finding to a different task, and show that this mechanism uses muscarinic receptors. In addition, they indicate that the well-known effects of intra-amygdala oxotremorine and scopolamine on LTM are independent of those that the drugs have on WM.


Do grazers respond to or control food quality? Cross-scale analysis of algivorous fish in littoral Lake Tanganyika.
Food quality determines the growth rate of primary consumers and ecosystem trophic efficiencies, but it is not clear whether variation in primary consumer densities control, or is controlled by, variation in food quality. We quantified variation in the density and condition of an abundant algae-eating cichlid, Tropheus brichardi, with respect to the quality and productivity of algal biofilms within and across rocky coastal sites in Lake Tanganyika, East Africa. Adjacent land use and sediment deposition in the littoral zone varied widely among sites. Tropheus brichardi maximized both caloric and phosphorus intake at the local scale by aggregating in shallow habitats: algivore density decreased with depth, tracking attached algae productivity (rETRMAX) remarkably well (r2 = 0.84, P = 0.00033). In contrast, algivore density was unrelated to among-site variation in algal productivity. Rather, there was significant increase in algal quality (r2 = 0.44, P = 0.011) and decrease in algal biomass (r2 = 0.53, P = 0.0068) with T. brichardi density across sites, consistent with strong top-down control of primary producers. The amount of inorganic sediment on rock surfaces was the strongest predictor of among-site variation in algivore density (r2 = 0.69, P = 0.00096), and algivore gut length increased with sedimentation (r2 = 0.36, P = 0.034). These patterns indicate extrinsic and top-down forcing of algal food quality and quantity across coastal landscapes, combined with adaptive habitat selection by fish at the local scale. Factors that degrade food quality by decreasing algal nutrient content or diluting the resource with indigestible material are likely to depress grazer densities, potentially dampening top-down control in high-light, low-nutrient aquatic ecosystems.


UBE3A and MCM6 synergistically regulate the proliferation and migration of lung adenocarcinoma cells.
Lung cancer is a leading cause of mortality worldwide and shows substantial clinical and biomolecular heterogeneity. Currently, specific therapeutic strategies are lacking, so effective drug targets are urgently needed. E6AP/UBE3A is a multifaceted ubiquitin ligase that controls various signaling pathways implicated in neurological diseases and various cancers; however, its role in lung cancer is incompletely understood. Here, MCM6 was identified as an interacting partner of E6AP using the yeast two-hybrid assay. MCM2 and MCM4 were then shown to interact with E6AP. E6AP knockout enhanced the ubiquitination of MCM2/4/6, suggesting that E6AP was not the E3 ubiquitin ligase for these three MCM proteins. Ablation of E6AP inhibited proliferation and migration, but had no significant effect on apoptosis in A549 and H1975 cells, and proliferation and migration inhibition was also observed in MCM6 knockdown cells. Furthermore, ablation of MCM6 and E6AP synergistically suppressed the proliferation and migration of A549 and H1975 cells. To verify the above findings in vivo, we established tumor models in nude mice and identified that the tumorigenicity of human lung adenocarcinoma (LUAD) cells was synergistically regulated by MCM6 and E6AP. Moreover, the expression levels of MCM6 and E6AP were higher in LUAD tissues than in adjacent tissues. Furthermore, the expression levels of MCM6 and E6AP were positively correlated in human LUAD samples. Thus, our study suggests that the interaction of E6AP and MCM proteins plays an important role in the progression of LUAD, which might offer potential therapeutic targets for cancer treatment.


Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas.
To investigate the clinicopathological characteristics of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expression in the tumour microenvironments of diffuse large B cell lymphoma (DLBCL). Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and PD-1. The expression of PD-L1 by tumour cells and/or tumour-infiltrating immune cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating PD-1(+) cells was assessed. PD-L1 expression in tumour cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B cell-like immunophenotype (16.7%) than germinal centre B cell-like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in tumour cells/macrophages showed similar clinicopathological characteristics. The quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with the level of PD-L1 expression in tumour cells (P = 0.042) or in tumour cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) cells was associated with prolonged progression-free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no prognostic significance. PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.


Hemostatic study before onset of disseminated intravascular coagulation.
Early diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre-DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre-DIC), in 237 patients with DIC, and in 50 patients without DIC or pre-DIC (non-DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), and FDP-D-dimer levels were significantly higher before the onset of DIC compared to the non-DIC patients. Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP-D-dimer might be useful for the diagnosis of a pre-DIC condition.


The Undertriage of Older Adults in the Emergency Department: A Review of Interventions.
The Research to Practice column is intended to improve the research critique skills of the advanced practice registered nurse and the emergency nurse and to assist with the translation of research into practice. A topic and a research study are selected for each column. A patient scenario is presented as a vehicle, in which to review and critique, the findings of the selected research study. In this column, we review the conclusions of A. Malinovska, L. Pitasch, N. Geigy, C. H. Nickel, and R. Bingisser (2019) from their article, titled "Modification of the Emergency Severity Index Improves Mortality Prediction in Older Patients."


Expression of cdc25 phosphatases in the germ cells of the rat testis.
cdc25A and cdc25C, which encode threonine/tyrosine phosphatases involved in cell cycle regulation, were found to be differentially localized in rat testicular germ cells during spermatogenesis. Northern blot analysis identified two cdc25A transcripts. A transcript of 3.8 kilobases (kb) was expressed in the early germ cells including spermatogonia, and a 3.3-kb transcript was highly expressed in spermatocytes and round spermatids. In situ hybridization showed that the levels of mRNA for cdc25A were highest in diplotene spermatocytes and round spermatids but were undetectable in Sertoli cells. Both transcripts for cdc25A increased with retinol treatment in the vitamin A-deficient testis. Immunolocalization showed that cdc25A protein was distributed in the cytoplasm of germ cells, whereas cdc25C was localized to the nucleus of late spermatocytes and round spermatids. Previous studies have identified two cdc25C transcripts of 2.1 kb and 1.9 kb, which were expressed in spermatocytes and round spermatids, respectively. These results suggest that cdc25A may function during mitosis of spermatogonia. Both cdc25A and cdc25C may function in the regulation of the meiotic cell cycle, although in different manners, as indicated by their subcellular localization.


Effects of wetting and anchoring on capillary phenomena in a confined liquid crystal.
A fluid of hard spherocylinders of length-to-breadth ratio L/D=5 confined between two identical planar, parallel walls--forming a pore of slit geometry--has been studied using a version of the Onsager density-functional theory. The walls impose an exclusion boundary condition over the particle's centers of mass, while at the same time favoring a particular anchoring at the walls, either parallel or perpendicular to the substrate. We observe the occurrence of a capillary transition, i.e., a phase transition associated with the formation of a nematic film inside the pore at a chemical potential different from micro(b)-the chemical potential at the bulk isotropic-nematic transition. This transition terminates at an Ising-type surface critical point. In line with previous studies based on the macroscopic Kelvin equation and the mesoscopic Landau-de Gennes approach, our microscopic model indicates that the capillary transition is greatly affected by the wetting and anchoring properties of the semi-infinite system, i.e., when the fluid is in contact with a single wall or, equivalently, the walls are at a very large distance. Specifically, in a situation where the walls are preferentially wetted by the nematic phase in the semi-infinite system, one has the standard scenario with the capillary transition taking place at chemical potentials less than micro(b) (capillary nematization transition or capillary ordering transition). By contrast, if the walls tend to orientationally disorder the fluid, the capillary transition may occur at chemical potentials larger than micro(b), in what may be called a capillary isotropization transition or capillary disordering transition. Moreover, the anchoring transition that occurs in the semi-infinite system may affect very decisively the confinement properties of the liquid crystal and the capillary transitions may become considerably more complicated.


Structural mutation analysis of PTEN and its genotype-phenotype correlations in endometriosis and cancer.
The phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene encodes a tumor suppressor phosphatase that has recently been found to be frequently mutated in patients with endometriosis, endometrial cancer and ovarian cancer. Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse-grained models of both wild-type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic-phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625-1643. © 2016 Wiley Periodicals, Inc.


[Mast cells and cells producing alpha-endorphin in the mucosa of the antral section of the stomach].
The distribution of mast cells, alpha-endorphine-producing cells (AER-cells) and argyrophilic cells in lamina propria of the antral mucosa was determined quantitatively in 13 normal men. The cells were detected by histochemical and immunohistochemical (PAP) methods. The form and site of AER-cells resembled those of mast cells and mucosal argyrophilic cells (in lamina propria). The authors assume that part of human gastric mucosal cells have argyrophilic properties and contain alpha-endorphine.


Glutamine synthetase of Mycobacterium tuberculosis: extracellular release and characterization of its enzymatic activity.
We have investigated the activity and extracellular release of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 220.127.116.11] of Mycobacterium tuberculosis. The purified, homogeneous M. tuberculosis glutamine synthetase appears to consist of 12 most likely identical subunits of M(r) 58,000, arranged in two superimpose hexagons. In the catalysis of L-glutamine, the enzyme has an apparent Km for L-glutamate of approximately 3 mM at the pH optimum of 7.5. M. tuberculosis releases a large proportion (approximately 30%) of its total measurable enzyme activity into the culture medium, a feature that is highly specific for pathogenic mycobacteria. Immunogold electron microscopy revealed that M. tuberculosis also releases the enzyme into its phagosome in infected human monocytes. Two potentially important roles for glutamine synthase in the pathogenesis of M. tuberculosis infection are (i) the synthesis of L-glutamine, a major component of the cell wall of pathogenic but not nonpathogenic mycobacteria, and (ii) the modulation of the ammonia level in the M. tuberculosis phagosome, which may in turn influence phagosomal pH and phagosomelysosome fusion.


Nurses' and Parents' Perceptions of Parental Guidance on Using Nonpharmacological Pain-Relieving Methods Among Neonates in the NICU.
Despite growing knowledge of parents' important role in their infants' pain management, the extent to which nurses in neonatal intensive care units (NICUs) provide guidance to parents on nonpharmacological methods is unclear. This study aimed to describe and compare the perceptions of parental guidance in using nonpharmacological pain-relieving methods among neonates in NICUs from the viewpoints of nurses and parents, and to examine the participants' demographics related to the guidance. A cross-sectional, descriptive, correlational study using questionnaire surveys was conducted. Eight NICUs of 5 university hospitals in Finland. A total of 427 participants, including 294 nurses and 178 parents. The participants indicated that the methods of touching and holding were the most commonly introduced strategies in infants' pain alleviation, as they were given as an alternative "nearly always/always" (nurses 91%, 87% and parents 61%, 58%, respectively). In contrast, music and breast-feeding were the less commonly introduced nonpharmacological methods (nurses 11%, 6% and parents 1%, 6%, respectively). A significant difference (p < .001) was found between the parents' and nurses' perceptions of parental guidance; nurses reported providing more guidance about all nonpharmacological methods compared with parents. In addition, many demographic factors of the nurses, the parents, and their infants were related to the parental guidance. Our findings indicate that parental guidance should not be based on nurses' evaluations of their activities without taking into account parents' perspectives. When counseling parents to use nonpharmacological methods, neonatal nurses should actively interact with families and discuss parents' individual needs.


Consumption of added sugars is decreasing in the United States.
The consumption of added sugars (caloric sweeteners) has been linked to obesity, diabetes, and heart disease. Little is known about recent consumption trends in the United States or how intakes compare with current guidelines. We examined trends in intakes of added sugars in the United States over the past decade. A cross-sectional study of US residents ≥2 y of age (n = 42,316) was conducted by using dietary data from NHANES 1999-2008 (five 2-y cycles) and data for added-sugar contents from the MyPyramid Equivalents Database. Mean intakes of added sugars (grams and percentage of total energy intake) were weighted to obtain national estimates over time across age, sex, and race-ethnic groups. Linear trends were tested by using Wald's F tests. Between 1999-2000 and 2007-2008, the absolute intake of added sugars decreased from a mean (95% CI) of 100.1 g/d (92.8, 107.3 g/d) to 76.7 g/d (71.6, 81.9 g/d); two-thirds of this decrease, from 37.4 g/d (32.6, 42.1 g/d) to 22.8 g/d (18.4, 27.3 g/d), resulted from decreased soda consumption (P-linear trend <0.001 for both). Energy drinks were the only source of added sugars to increase over the study period (P-linear trend = 0.003), although the peak consumption reached only 0.15 g/d (0.08, 0.22 g/d). The percentage of total energy from added sugars also decreased from 18.1% (16.9%, 19.3%) to 14.6% (13.7%, 15.5%) (P-linear trend <0.001). Although the consumption of added sugars in the United States decreased between 1999-2000 and 2007-2008, primarily because of a reduction in soda consumption, mean intakes continue to exceed recommended limits.


Comparison of Franseen and fork-tip needles for EUS-guided fine-needle biopsy of solid mass lesions: A systematic review and meta-analysis.
Franseen-tip and Fork-tip needles have been widely used in EUS guided fine-needle biopsy (FNB) of solid organs. There is conflicting data on the performance of these needles and unanswered questions on the ideal number of needle-passes and the requirement of an onsite cytopathologist (ROSE). We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (from inception through July 2018) to identify studies that reported on the use of Forktip and Franseen-tip needles in EUS-FNB of solid organs. The primary outcome was to estimate and compare the pooled rates of diagnostic-yield. A subgroup analysis compared the outcomes based on the number of needle-passes and the availability of ROSE. A total of 23 study-arms were available for analysis. The pooled rate of diagnostic yield with Fork-tip needle was 92.8% (95% CI 85.3 - 96.6, I2 = 73.1) and the pooled rate of diagnostic yield with Franseen-tip needle was 92.7% (95% CI 86.4 - 96.2, I2 = 88.4).


The birefringence of the human red cell ghosts.
The type of birefringence described by Mitchison, which extends some 0.5 micro in from the surface of the human red cell ghost in glycerol and which shows a maximum retardation of about 7 A, is only found in ghosts which are sufficiently well hemoglobinised to be seen with the ordinary microscope. Ghosts from which all hemoglobin has been lost are not visible with the ordinary microscope and are not birefringent, although they are clearly visible with phase contrast. About 90 per cent of the ghosts in glycerol preparations are of the latter type, the exact percentage being a function of time. Mitchison's measurements of birefringence, although reproducible, accordingly apply only to ghosts in which some hemoglobin still remains complexed with the lipoprotein layers of the red cell ultrastructure, and do not enable one to draw conclusions as to the thickness and orientation of the lipoprotein surface layers.


[Experiences with immunization against orthopox viruses of humans and animals using vaccine strain MVA].
Immunizations against orthopox virus infections require a replicating, but safe vaccinia virus. The strain MVA is well suited concerning this matter. Human beings and animals can be vaccinated without any risk. The virus propagated in cell culture is non-virulent and lost its contagiosity. Multiplication in vaccinated men and animals is limited and excretion does not happen. As known for other attenuated virus strains, there must be a minimal effective virus concentration in the vaccine, which is 10(7.5) TCID50 per ml for MVA. To achieve a solid basic immunity which endures for a minimal of one year, two parenteral applications of MVA at intervals of at least 3 weeks are necessary.


[Acute kidney injury-emergency or coincidence?].
An unifying definition of acute kidney injury as a precursor of acute renal failure has been published in march last year. Its remarkable mortality makes an early diagnosis an important goal. New biomarkers will be an important step to reach this goal in the near future. Depending on the underlying cause, therapeutic actions should be realized as soon as possible to diminish in-hospital mortality and chronic nephropathy. Intensive care units often are the first to test for new active substances.