Effect of green tea extract on enteric viruses and its application as natural sanitizer.
In this work, the effect of green tea extract (GTE) was assessed against murine norovirus (MNV) and hepatitis A virus (HAV) at different temperatures, exposure times and pH conditions. Initially, GTE at 0.5 and 5 mg/ml were individually mixed with each virus at 5 log TCID50/ml and incubated 2 h at 37 °C at different pHs (from 5.5 to 8.5). GTE affected both viruses depending on pH with higher reductions observed in alkaline conditions. Secondly, different concentrations of GTE (0.5 and 5 mg/ml) were mixed with viral suspensions and incubated for 2 or 16 h at 4, 25 and 37 °C at pH 7.2. A concentration-, temperature- and exposure time-dependent response was showed by GTE in suspension tests, where complete inactivation was achieved after overnight exposure at 37 °C for both viruses and also at 25 °C for HAV. In addition, antiviral effect of GTE proved efficient in the surface disinfection tests since 1.5 log reduction and complete inactivation were recorded for MNV and HAV on stainless steel and glass surfaces treated with 10 mg/ml GTE for 30 min, analyzed in accordance with ISO 13697:2001. GTE was also evaluated as a natural disinfectant of produce, showing 10 mg/ml GTE reduced MNV and HAV titers in lettuce and spinach by more than 1.5 log after 30 min treatment. The results show a potential of GTE as natural disinfectant able to limit enteric viral (cross-)contaminations conveyed by food and food-contact surfaces.


The short- and long-term risk of stroke after herpes zoster - a nationwide population-based cohort study.
Varicella zoster virus (VZV) is known to cause VZV vasculopathy, which may be associated with stroke. A recent study found an increased risk of stroke within one year of herpes zoster. We aimed to investigate the short and long-term effects of herpes zoster on the risk of stroke. Using Danish national registers, we constructed a cohort consisting of all Danish adults ≥18 years old between 1995 and 2008 (n = 4.6 million; person-years of follow-up = 52.9 million). Individual-level information on prescriptions for herpes zoster antiviral treatment and diagnoses of stroke was obtained from national registers. We compared the risk of stroke in persons who had received the specific dosage of acyclovir for herpes zoster with persons who had never received antiviral treatment by Poisson regression. During follow-up, 2.5% received treatment for herpes zoster and 5.0% were diagnosed with stroke. Individuals who had received medication had a 127% (95% CI 83-182%) increased risk the first two weeks, 17% (CI 9-24%) between two weeks and one year, and 5% (2-9%) after the first year. The increased risk was greatest in the youngest age group (<40). To control for healthcare-seeking behaviour, we conducted parallel analyses investigating the risk of selected fractures after herpes zoster and found no similar increased risks. This large nationwide cohort study found an increased risk of stroke after treatment for herpes zoster. Although the short-term risk was particularly high, we cannot rule out the possibility of a small but important long-term risk.


Specialization and despecialization in psychology: divergent processes in the three worlds.
This paper raises some fundamental questions about the consequences of specialization in the discipline of psychology, as well as the psychological consequences of specialization. Increasing specialization is taking place as a result of wide-ranging psychological and societal factors, rather than strictly scientific criteria. Among the consequences of increasing specialization are fragmentation in psychology, and microcosmic, rather than wholistic, models of behavior. Some third world psychologists trained in the first and second worlds are moving toward despecialization, in order to tackle major social problems that invariably require a wholistic approach. It is proposed that despecialization has potential benefits for all of psychology.


Effectiveness of narrative pedagogy in developing student nurses' advocacy role.
The literature and research on nursing ethics and advocacy has shown that generally very few nurses and other clinicians will speak up about an issue they have witnessed regarding a patient advocacy concern and that often advocacy in nursing is not learned until after students have graduated and begun working. To evaluate the effectiveness of narrative pedagogy on the development of advocacy in student nurses, as measured by the Protective Nursing Advocacy Scale. We tested the hypothesis that use of a narrative pedagogy assignment related to ethics would improve student nurse's perception of their advocacy role as measured by the Protective Nursing Advocacy Scale using a quasi-experimental nonrandomized study using a pre-test, intervention, post-test design. Data collection occurred during class time from October 2012 to December 2012. The Protective Nursing Advocacy Scale tool was administered to students in class to assess their baseline and was administered again at the completion of the educational intervention to assess whether narrative pedagogy was effective in developing the nursing student's perception of their role as a patient advocate. Students were informed that their participation was voluntary and that the data collected would be anonymous and confidential. The survey was not a graded assignment, and students did not receive any incentive to participate. The institutional review board of the college determined the study to be exempt from review. School of Nursing at a small liberal arts college in the Northeastern United States. A consecutive, nonprobability sample of 44 senior-level nursing students enrolled in their final nursing semester was utilized. Results indicated significant differences in student nurse's perception of their advocacy role related to environment and educational influences following an education intervention using an ethics digital story. Using the Protective Nursing Advocacy Scale, we were able to measure the effectiveness of narrative pedagogy on nursing student's perception of the nurse's advocacy role.


Hydrocarbons in the Meniscus: Effects on Conductive Atomic Force Microscopy.
It is commonly accepted that during conductive atomic force microscopy (CAFM) measurement in ambient, a liquid meniscus can form between the tip and the sample. Such a liquid bridge, normally assumed to be composed of water, is a major factor in analyzing and understanding CAFM results. Here, we show that the adsorption of adventitious hydrocarbons from the air to a surface can greatly affect CAFM data both in imaging mode and in local spectroscopy (current-voltage or I-V curves). We propose a model to explain the phenomena whereby hydrocarbon contaminates contribute to the composition of the liquid bridge between the tip and the sample.


Psychological issues and construction of the mother-child relationship in women with cancer during pregnancy: a perspective on current and future directions.
Cancer during pregnancy is a rare event. However, knowledge about treatment has progressed in recent years with improved maternal and neonatal outcomes. The number of women who decide to continue their pregnancy and undergo cancer treatment is increasing. Women face two critical events simultaneously; oncological illness and pregnancy, with different and conflicting emotions. In addition, the last trimester of gestation sets the ground for construction of the mother-child relationship, which is of great importance for the child's development. Studies have showed that maternal exposure to stressful events during pregnancy is linked to adverse outcomes in children. Although several authors consider cancer to be a 'critical life event', studies that address the psychosocial implications of cancer in expecting mothers are scarce. There are no studies addressing the possible negative impact of a cancer diagnosis during pregnancy on the mother-child relationship and on the child's development. It is important to emphasize the need for in-depth knowledge of the contributing psychological factors involved in order to provide holistic, individualised, and supportive care. An analysis of cognitive aspects, emotional processes, and maternal attachment in cases of cancer during pregnancy may contribute to the development of a model of care, both in an evolutionary and in a psycho-oncology context, with implications for clinical practice.


A retrospective observational study of benign anthracotic lymphadenitis and its association with PET avid lymph nodes in patients undergoing cancer evaluation.
Accurate staging of newly diagnosed or recurrent malignancy is essential for effective treatment. An important first step in staging involves the use of PET/CT to identify areas of FDG avidity. PET/CT however has limitations, including false positive FDG uptake from benign causes. In this paper we characterize an uncommon yet clinically important cause of false positive PET/CTs, that of benign anthracotic lymphadenitis (BAL). We examine the clinical, radiographic and histologic characteristics of BAL in patients referred for endobronchial ultrasound (EBUS) guided biopsies and discuss its context in relation to existing literature. We performed a retrospective observational case series of 20 patients who were referred for EBUS guided biopsies of PET positive mediastinal and hilar lymph nodes during the work-up or treatment of suspected malignancy. To be included, all patients received PET imaging as well as an EBUS guided biopsy of FDG avid lymph nodes which demonstrated anthracotic pigment as the only histologic abnormality. The key findings were that 90% of patients in this cohort were born outside of the US, 90% had bilateral FDG avid lymph nodes with an average standardized uptake value (SUV) of 7.9±2.2. Most patients, based on their history, had a likely exposure to biomass fuel or urban pollution. BAL may be an underrecognized cause for PET positive lymph nodes in patients undergoing work-up for malignancy. These findings support the importance of sampling mediastinal and hilar lymph nodes even when SUVs are highly suggestive of malignancy.


Maximum, minimum, and optimal mutation rates in dynamic environments.
We analyze the dynamics of the parallel mutation-selection quasispecies model with a changing environment. For an environment with the sharp-peak fitness function in which the most fit sequence changes by k spin flips every period T , we find analytical expressions for the minimum and maximum mutation rates for which a quasispecies can survive, valid in the limit of large sequence size. We find an asymptotic solution in which the quasispecies population changes periodically according to the periodic environmental change. In this state we compute the mutation rate that gives the optimal mean fitness over a period. We find that the optimal mutation rate per genome, k/T , is independent of genome size, a relationship which is observed across broad groups of real organisms.


Financial impact of two different ways of evaluating early virological response to peginterferon-alpha-2b plus ribavirin therapy in treatment-naive patients with chronic hepatitis C virus genotype 1.
Patients infected with chronic hepatitis C virus (HCV) genotype 1 are the least responsive to peginterferon (pegIFN) and ribavirin therapy. The monitoring of early virological response (EVR) is therefore an important tool for quickly identifying non-responders, permitting therapy discontinuation and avoiding adverse effects and costs. To analyse the financial impact, in treatment-naive patients infected with HCV genotype 1, of two different measurement techniques for evaluating the EVR during pegIFN-alpha-2b plus ribavirin therapy, and to compare the results of a 48-week standard course of therapy with pegIFN-alpha-2b plus ribavirin without measuring EVR. A budget impact model was constructed using a decision-tree analysis. EVR was defined as a >2 log decline in HCV RNA levels at week 12 either tested with two quantitative HCV RNA tests or undetectable HCV core antigen (HCV core Ag) protein levels at week 12 (one HCV core Ag test). Clinical data were taken from multicentre trials and costs from the published literature (euro, 2003 values). The analysis was carried out from the perspective of the Spanish healthcare system and therefore only direct costs were considered. The base-case scenario assumed that a potential study population of 18,504 people in Spain with chronic HCV genotype 1 would be eligible for treatment with pegIFN-alpha-2b plus ribavirin. In the base case, the most effective strategy was testing EVR by HCV core Ag. This resulted in 12,745 patients reaching a sustained virological response (SVR) at an overall cost of 243.98 million euro (19,142 euro per SVR). Conversely, quantitative HCV RNA testing resulted in 11,776 patients with an SVR at a cost of 232.73 million euro ( 19,763 euro per SVR). The incremental cost per successfully treated patient with HCV core Ag testing versus quantitative HCV RNA testing was 11,597 euro. One-way sensitivity analyses demonstrated that changes in the study parameters did not modify the outcomes, except when increasing the EVR or SVR of strategy 2 or when decreasing the EVR or SVR of strategy 3. This model suggests, with its underlying assumptions and data, that the assessment of EVR at week 12 by HCV core Ag testing in chronic HCV patients infected with genotype 1 permits identification of those patients expected to achieve an SVR with pegIFN-alpha-2b and ribavirin, resulting in a lower overall cost to the Spanish healthcare system than HCV RNA testing or no testing at all.


Principles of cryopreservation by vitrification.
Vitrification is an alternative approach to cryopreservation that enables hydrated living cells to be cooled to cryogenic temperatures in the absence of ice. Vitrification simplifies and frequently improves cryopreservation because it eliminates mechanical injury from ice, eliminates the need to find optimal cooling and warming rates, eliminates the importance of differing optimal cooling and warming rates for cells in mixed cell type populations, eliminates the need to find a frequently imperfect compromise between solution effects injury and intracellular ice formation, and enables cooling to be rapid enough to "outrun" chilling injury, but it complicates the osmotic effects of adding and removing cryoprotective agents and introduces a greater risk of cryoprotectant toxicity during the addition and removal of cryoprotectants. Fortunately, a large number of remedies for the latter problem have been discovered over the past 30+ years, and the former problem can in most cases be eliminated or adequately controlled by careful attention to technique. Vitrification is therefore beginning to realize its potential for enabling the superior and convenient cryopreservation of most types of biological systems (including molecules, cells, tissues, organs, and even some whole organisms), and vitrification is even beginning to be recognized as a successful strategy of nature for surviving harsh environmental conditions. However, many investigators who employ vitrification or what they incorrectly imagine to be vitrification have only a rudimentary understanding of the basic principles of this relatively new and emerging approach to cryopreservation, and this often limits the practical results that can be achieved. A better understanding may therefore help to improve present results while pointing the way to new strategies that may be yet more successful in the future. To assist this understanding, this chapter describes the basic principles of vitrification and indicates the broad potential biological relevance of vitrification.


Decreased expression of humanized Fat-1 in porcine fetal fibroblasts following deletion of PGK-neomycin resistance.
The neomycin-resistance (neo(r)) gene is widely used as a selectable marker in eukaryotic expression vectors; however, its expression often affects that of target genes. Cre recombinase recognizes LoxP sites, leading to site-specific recombination and deletion of DNA and RNA between two LoxP sites. In the present study, a humanized Fat-1 gene (hFat-1) was generated by DNA Works and used to construct a pC-PGK-neo(r)-hfat-1 expression vector, in which PGK-neo(r) was flanked by two LoxP sites. The pC-PGK-neo(r)-hfat-1 plasmids were transfected into porcine fetal fibroblasts using liposomes, and three transgenic cell lines were obtained by culturing with 400 μg/mL G418 for 7 days. Next, these cell lines were transfected with a Cre recombinase expression plasmid, which contains a puromycin resistance gene, in order to delete neo(r), which was integrated into the genome. hFat-1-neo(r) negative cells were obtained following puromycin selection. Real-time quantitative polymerase chain reaction data indicated that neomycin-resistant cells had higher hFat-1 expression than neomycin-sensitive cells. High performance gas chromatography data suggested that the n-6/n-3 ratio was significantly lower in transfected cells than in wild-type cells. The n-6/n-3 ratio in Cre-treated hFat-1-transfected cells was higher than that in untreated cells, suggesting that deletion of PGK-neo(r) decreased hFat-1 expression.


Substitution of a highly conserved histidine in the Escherichia coli heat shock transcription factor, sigma32, affects promoter utilization in vitro and leads to overexpression of the biofilm-associated flu protein in vivo.
The heat shock sigma factor (sigma(32) in Escherichia coli) directs the bacterial RNA polymerase to promoters of a specific sequence to form a stable complex, competent to initiate transcription of genes whose products mitigate the effects of exposure of the cell to high temperatures. The histidine at position 107 of sigma(32) is at the homologous position of a tryptophan residue at position 433 of the main sigma factor of E. coli, sigma(70). This tryptophan is essential for the strand separation step leading to the formation of the initiation-competent RNA polymerase-promoter complex. The heat shock sigma factors of all gammaproteobacteria sequenced have a histidine at this position, while in the alpha- and deltaproteobacteria, it is a tryptophan. In vitro the alanine-for-histidine substitution at position 107 (H107A) destabilizes complexes between the GroE promoter and RNA polymerase containing sigma(32), implying that H107 plays a role in formation or maintenance of the strand-separated complex. In vivo, the H107A substitution in sigma(32) impedes recovery from heat shock (exposure to 42 degrees C), and it also leads to overexpression at lower temperatures (30 degrees C) of the Flu protein, which is associated with biofilm formation.


[Value of a blood pressure profile in evaluating 2 antihypertensive agents].
Bopindolol (Sandoz) in single daily doses of 1 and 2 mg was compared with atenolol (ICI) in single daily doses of 50 and 100 mg in respect of antihypertensive effect in a population of 33 patients divided by random allocation into 4 groups and treated for 12 months. Statistical analysis of the more than 4000 blood pressure readings obtained with a noninvasive ambulatory blood pressure recorder indicates equivalence of efficacy between bopindolol 1 mg, bopindolol 2 mg and atenolol 100 mg, with atenolol 50 mg less effective. Bopindolol's long duration of effect was reflected in lower morning values and in the absence of hypotension in the circadian profile.


A family/systems approach to illness-maintaining behaviors in chronically ill adolescents.
A distressingly significant number of chronic, seriously ill adolescents demonstrate poor medical management of their illnesses through "illness-maintaining behaviors." These behaviors are defined in this article as any action that compromises chronically ill adolescents' care and prevents them from functioning optimally. Current conceptualizations of illness-maintaining behaviors offer explanations that view these behaviors as individually focused, using either psychodynamic or behavioral models. This article, however, presents a family systems model of illness-maintaining behaviors. A therapeutic framework leading to specific intervention strategies is also developed.


Rare portal hypertension caused by Abernethy malformation (Type IIC): A case report.
Abernethy malformation is a rare congenital vascular malformation with a portosystemic shunt that may clinically manifest as cholestasis, dyspnea, or hepatic encephalopathy, among other conditions. Early diagnosis and classification are very important to further guide treatment. Typically, patients with congenital portosystemic shunts have no characteristics of portal hypertension. Herein, we report an 18-year-old female with prominent portal hypertension that manifested mainly as rupture and bleeding of esophageal varices. Imaging showed a thin main portal vein, no portal vein branches in the liver, and bleeding of the esophageal and gastric varices caused by the collateral circulation upwards from the proximal main portal vein. Patients with Abernethy malformation type I are usually treated with liver transplantation, and patients with type II are treated with shunt occlusion, surgery, or transcatheter coiling. Our patient was treated with endoscopic surgery combined with drug therapy and had no portal hypertension and good hepatic function for 24 mo of follow-up. This case report describes our experience in the diagnosis and treatment of an 18-year-old female with Abernethy malformation type IIC and portal hypertension. This condition was initially diagnosed as cirrhosis combined with portal hypertension. The patient was ultimately diagnosed using liver histology and subsequent imaging, and the treatment was highly effective. To publish this case report, written informed consent was obtained from the patient, including the attached imaging data. Abernethy malformation type IIC may develop portal hypertension, and traditional nonselective beta-blockers combined with endoscopic treatment can achieve high efficacy.


Local health department partnerships with faith-based organizations.
Collaboration between public health and faith communities is encouraged by national and state policies. The study in this article examined the prevalence, characteristics, and effectiveness of partnerships between faith-based organizations and local health departments in Wisconsin. Data were collected from local health departments using a 2-stage, cross-sectional survey. A subset analysis of partnerships that included faith-based organizations was conducted using descriptive, bivariate, and 2-level logit regression methods, with partnerships nested in health departments. Twenty-four percent of local health department partnerships included faith-based organizations (n = 224). Community assessment was the most commonly reported partnership focus. Partnerships that included faith-based organizations were more likely to include many partners and have few partners contributing financially. Partnerships that include faith-based organizations are no more likely to be effective than those that do not. Predictors of local health department/faith-based organizations effectiveness included having a budget and longer time in existence. Local health departments engage faith-based organizations in partnership strategies when addressing issues that require broad community attention. Partnership effectiveness is enhanced by existence of a budget and sufficient time for development.


Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors.
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr kinase that comprises two complexes, termed mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTORC1 phosphorylates S6K1 at Thr 389, whereas mTORC2 phosphorylates AKT at Ser 473 to promote cell growth. As the mTOR name implies it is the target of natural product called rapamycin, a clinically approved drug used to treat human disease. Short-term rapamycin treatment inhibits the kinase activity of mTORC1 but not mTORC2. However, the ATP-competitive catalytic mTOR inhibitor Torin1 was identified to inhibit the kinase activity of both mTORC1 and mTORC2. Here, we report that H89 (N-(2-(4-bromocinnamylamino) ethyl)-5-isoquinolinesulfonamide), a well-characterized ATP-mimetic kinase inhibitor, renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors across multiple cell lines. Moreover, H89 prevented the dephosphorylation of AKT and S6K1 under nutrient depleted conditions. PKA and other known H89-targeted kinases do not alter the phosphorylation status of S6K1 and AKT. Pharmacological inhibition of some phosphatases also enhanced S6K1 and AKT phosphorylation. These findings suggest a new target for H89 by which it sustains the phosphorylation status of S6K1 and AKT, resulting in mTOR signaling.


Combination treatment with TRA-8 anti death receptor 5 antibody and CPT-11 induces tumor regression in an orthotopic model of pancreatic cancer.
Evaluate the response of human pancreatic cancer cell lines and orthotopic tumors to TRA-8, an agonistic antibody to death receptor 5, in combination with irinotecan (CPT-11). MIA PaCa-2 and S2VP10 cells were treated with TRA-8 and/or CPT 11. Cell viability was determined by ATP assay. JC-1 mitochondrial depolarization and Annexin V assays confirmed cell death by apoptosis. Immunoblotting was used to evaluate protein changes. MIA PaCa-2 cells were injected into the pancreas of severe combined immunodeficient mice. Mice underwent abdominal ultrasound to quantitate tumor size before and after treatment with twice weekly injections of 200 microg TRA-8 and/or 25 mg/kg CPT-11 for one or two treatment cycles, each lasting 2 weeks. MIA PaCa-2 cells were more sensitive to TRA-8 and showed additive cytotoxicity, whereas S2VP10 cells showed synergistic cytotoxicity when treated with TRA-8 and CPT-11. Cell death occurred via apoptosis with increased cleavage of caspase-3, caspase-8, and caspase-9 and proapoptotic proteins Bid and poly(ADP)ribose polymerase after combination treatment compared with either agent alone. XIAP and Bcl-XL inhibitors of apoptosis were down-regulated. After a single cycle of in vivo combination therapy, tumor sizes had diminished significantly (P<0.001) at 8 days posttreatment compared with no treatment, CPT-11, and TRA-8; and there was a 50-day increase in survival with combination treatment over untreated controls (P=0.0002), 30 days over TRA-8, and a 36-day increase over CPT-11 monotherapy (P=0.0003). With two cycles of TRA-8/CPT-11 treatment, mean survival time increased significantly (P<0.001) to 169 days versus untreated controls, TRA-8 or CPT-11 (76, 121, or 108 days, respectively). Combination TRA-8 and CPT-11 therapy produced enhanced cytotoxicity and survival in the MIA PaCa-2 orthotopic model of pancreatic cancer.


Cortical Strut Graft for Enigmatic Thigh Pain in Uncemented Total Hip Replacement.
Aims Enigmatic thigh pain in uncemented femoral components of a total hip replacement can be severe and disabling. Treatment can be conservative or surgical with cortical strut graft or revision of the femoral stem. Cortical strut grafting may offer good results with reduced morbidity. The aim of this study was to report the functional and radiographic outcomes of four patients with enigmatic thigh pain treated with cortical strut allograft. Materials and Methods Between 2016 and 2018, four women underwent cortical strut allografting at two centres. All patients had an uncemented, proximally porous S-ROM femoral implant (DePuy, Warsaw, In, USA). All other causes of anterolateral thigh pain were excluded. The mean age was 36.7 years (range: 29-51 years). Patients were followed up for a minimum of 14 months (range: 14-38 months). The University of California, Los Angles (UCLA) activity score, pain scores, complications, and radiographs at six weeks, three months, six months, nine months and one year were recorded. Results Mean UCLA activity scores increased from 3.2 (range: 2-4) to 6.2 (range: 6-7) post-operatively. Radiologically, all four patients had complete osseointegration of their strut grafts. Pain scores decreased at six weeks and at six months. One deep venous thrombosis occurred. One patient experienced recurrence of anterolateral thigh pain 26 months post-strut graft, which resolved with protected weight-bearing and analgesia for three months. Conclusions In uncemented femoral prostheses, cortical strut grafting to treat enigmatic thigh pain can reduce symptoms and increase activity without the need to revise a well-fixed femoral stem. We add to the growing body of evidence that this can be a successful surgical technique.


Circular RNA circUBXN7 represses cell growth and invasion by sponging miR-1247-3p to enhance B4GALT3 expression in bladder cancer.
Circular RNAs (circRNAs) have recently been confirmed to participate in different pathological processes, including cancer progression. However, the role and precise mechanism of action of the majority of circRNAs have not been elucidated in bladder cancer (BC). Here, we identified a novel circular RNA, termed circUBXN7, which was significantly downregulated in BC tissues compared with matched nontumor tissues. Importantly, we found that decreased circUBXN7 expression was associated with pathological stage, grade and poor prognosis of BC patients. Functional experiments showed that circUBXN7 overexpression dramatically inhibited proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Mechanistically, circUBXN7 could directly bind to miR-1247-3p and reverse the oncogenic effects induced by miR-1247-3p. Furthermore, B4GALT3 was predicted and confirmed to be a target of miR-1247-3p. Rescue experiments demonstrated that circUBXN7 abrogated miR-1247-3p-mediated inhibition of B4GALT3 expression. Finally, silencing of B4GALT3 promoted proliferation and invasion of BC cells; and partially abolished the tumor suppressive effects caused by circUBXN7. Taken together, our study revealed that circUBXN7 serves as a competitive endogenous RNA of miR-1247-3p to elevate B4GALT3 expression, consequently inhibiting cell viability and invasion in BC. The circUBXN7-miR-1247-3p-B4GALT3 regulatory network may provide a new perspective for gene-based treatment strategies for BC.


[Preoperative risk factors of portal venous thrombosis after splenectomy and gastric pericardial devascularization for portal hypertension].
To investigate the preoperative risk factors of portal venous thrombosis (PVT) after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension. Clinical data was collected for 127 patients who underwent splenectomy and gastric pericardial devascularization for portal hypertension at our hospital between January 2010 and December 2012.The patient data were analyzed retrospectively according to patient status of presence or absence of PVT postoperatively.The preoperative risk factors of PVT were statistically analyzed. There were no significant differences between the postoperative PVT-positive and-negative groups in regards to sex, age, receipt of emergency surgery, presence of ascites, admission to hospital for upper gastrointestinal bleeding, grade of esophageal-gastric varices, Child-Pugh classification, spleen vein diameter, liver function (as determined by levels of alanine aminotransferase, total bilirubin, direct bilirubin, albumin, globulin, cholinesterase, and gamma-glutamyltransferase), renal function (as determined by creatinine level), and coagulation function (as determined by prothrombin time, prothrombin activity degree, activated partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, and antithrombin III).However, there were significant differences between the groups for the parameters of postoperative PVT presence, upper gastric bleeding history, aspartate aminotransferase level, and blood urea nitrogen level (all P less than 0.05).Portal vein diameter and history of upper gastric bleeding were both identified as independent risk factors for PVT (P less than 0.05).Incidence of postoperative PVT was higher in patients who had portal vein diameter > 13.15 mm (cutoff value of 13.75 mm) and in patients who had a history of upper gastric bleeding. Portal vein diameter and history of upper gastric bleeding were independent risk factors for PVT occurrence after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension.


Molecular organization of the nanoscale surface structures of the dragonfly Hemianax papuensis wing epicuticle.
The molecular organization of the epicuticle (the outermost layer) of insect wings is vital in the formation of the nanoscale surface patterns that are responsible for bestowing remarkable functional properties. Using a combination of spectroscopic and chromatographic techniques, including Synchrotron-sourced Fourier-transform infrared microspectroscopy (FTIR), x-ray photoelectron spectroscopy (XPS) depth profiling and gas chromatography-mass spectrometry (GCMS), we have identified the chemical components that constitute the nanoscale structures on the surface of the wings of the dragonfly, Hemianax papuensis. The major components were identified to be fatty acids, predominantly hexadecanoic acid and octadecanoic acid, and n-alkanes with even numbered carbon chains ranging from C14 to C30. The data obtained from XPS depth profiling, in conjunction with that obtained from GCMS analyses, enabled the location of particular classes of compounds to different regions within the epicuticle. Hexadecanoic acid was found to be a major component of the outer region of the epicuticle, which forms the surface nanostructures, and was also detected in deeper layers along with octadecanoic acid. Aliphatic compounds were detected throughout the epicuticle, and these appeared to form a third discrete layer that was separate from both the inner and outer epicuticles, which has never previously been reported.


Reaction Gas Ratio Effect on the Growth of a Diamond Film Using Microwave Plasma-Enhanced Chemical Vapor Deposition.
In this study, diamond films were prepared using the microwave plasma-enhanced chemical vapor deposition (PECVD) system, which included a DC bias system to enhance the nucleation of the films. The films were synthesized on Si wafers with different ratios of methane (CH4) and hydrogen (H2) gases. We have studied the effects of the CH4-to-H2 ratio on the structural and optical properties of diamond films. The thickness and surface profile of the films were characterized via field emission scanning electron microscopy (FE-SEM). Raman was used to investigate the structural properties of the diamond films. The refractive indexes as functions of the CH4-to-H2 ratio were measured using an ellipsometer. The FE-SEM analysis showed that the 3 and 5 sccm CH4 created diamond films. The Raman analysis indicated that a nanocrystalline diamond film was formed at 3 sccm; a general diamond film, at 5 sccm; and films similar to the a-C:H film, at 7 sccm. The ellipsometer measurement showed that the refractive index of the synthesized diamond film was around 2.42 at 3 sccm. This value decreased as the CH4 volume increased.


The Association of Life Stress with Subsequent Brain and Cognitive Reserve in Middle-Aged Women.
Cognitive and brain reserve refer to individual differences that allow some people to better withstand brain pathology than others. Although early life stress has been recognized as a risk factor for low reserve in late life, no research yet has studied this across midlife. To examine the associations of life stress with brain and cognitive reserve in midlife. We included 1,232 middle-aged women who participated in the ORACLE Study between 2002-2006). Life stress was calculated as the shared variance of four cumulative stress domains, created from items measured between pregnancy and 10 years after childbirth. Brain reserve was defined as healthy-appearing brain volume measured with MRI; cognitive reserve as better cognitive functioning than expected based on age, education, and brain MRI measures, using structural equation modelling. More life stress was associated with lower brain (standardized adjusted difference: -0.18 [95% CI 0.25,-0.12]) and cognitive reserve (-0.19 [-0.28,-0.10]). Although, effect sizes were typically smaller, cumulative stress domains were also associated with brain reserve (life events: -0.10 [-0.16,-0.04]; contextual stress: -0.13 [-0.19,-0.07]; parenting-related stress: -0.13[-0.19,-0.07]; interpersonal stress: -0.10 [-0.16,-0.04]) and cognitive reserve (life events: -0.18 [-0.25,-0.11]; contextual stress: -0.15 [-0.10,-0.02]; parenting-related stress: -0.10 [-0.18,-0.03]; interpersonal stress not significant). Women who experience more life stress in midlife were found to have lower reserve. Effects were primarily driven by shared variance across cumulative stress domains, suggesting that focusing on single domains may underestimate effects. The effect of life stress on lower reserve may make women with stress more prone to neurodegenerative disease later in life than women without stress.


Color flow Doppler sonography in the diagnosis of vesicoureteric reflux.
We describe an alternative technique using color flow Doppler sonography (CFDS) for detection of vesicoureteric reflux (VUR). Twenty-one children, ages 2-16 years, were investigated for VUR using voiding cystourethrography (VCU) and CFDS. Forty-two ureterovesical junctions were studied and a total of 27 were found to be refluxing at VCU. Five of these 21 patients were operated for VUR and they were also reevaluated 3 and 6 months after the operation. With good diuresis ureteric jets could easily be detected with CFDS and if there was a reflux of urine into the ureter this could also be displayed. Afterwards, the patient was asked to urinate and if reflux into the ureter was detected, particular attention was paid to the detection of ureteral and pelvicalyceal dilatation by conventional gray-scale sonography. Taking VCU as the gold standard, CFDS revealed reflux in all cases except 1. There were 3 patients who had only one-sided reflux at VCU and bilateral reflux at CFDS examination (false-positive: 20%). Correlation of CFDS and VCU was 90, 100 and 75% in low grade, grade III and grade IV reflux, respectively. The results of CFDS correlated well with the results of VCU during the follow-up of 5 patients who had antireflux operations. As a conclusion, CFDS could be used as an adjunct to standard ultrasonography for detection of VUR.


Genetic polymorphism and TH1/TH2 orientation.
It is likely that besides developmental and environmental factors, genetic factors also play an important role in Th1/Th2 orientation and susceptibility to related disorders. Thus, for each genetic factor involved one would expect an opposite pattern of susceptibility towards Th1- and Th2-associated diseases. We report a comparative analysis of the pattern of association of four genetic polymorphisms with bronchial asthma (Th2 disease) and Crohn's disease (CD; Th1 disease). The study population included 291 Roman children with bronchial asthma and 72 adult Romans with CD, and haptoglobin, adenosine deaminase (ADA), acid phosphatase locus 1 (ACP1) and MN phenotypes were determined. Compared with controls from the same population, the pattern of phenotype association observed in bronchial asthma is exactly opposite to that observed in CD. The analysis of pairwise gametic type distribution for ACP1, ADA and MN polymorphisms has shown that the pattern of differences between bronchial asthma and controls is opposite to that observed between CD and controls. The pattern of differences between bronchial asthma versus CD is compatible with the hypothesis that some of the genetic systems considered contribute to Th1/Th2 orientation.


LINC01535 Attenuates ccRCC Progression through Regulation of the miR-146b-5p/TRIM2 Axis and Inactivation of the PI3K/Akt Pathway.
lncRNAs, a group of eukaryotic cell genome-encoded transcripts, have been demonstrated to exert a notable impact on tumorigenesis. LINC01535, belonging to the lncRNA family, was reported to have an aberrant expression in certain types of cancers and thus affect cancer progression. Nevertheless, the expression pattern and potential roles of LINC01535 in clear cell renal cell carcinoma (ccRCC) remain to be elucidated. Here, LINC01535 expression was detected in ccRCC by RT-qPCR, cell proliferation by CCK-8 assays, and invasion by transwell assays. Besides, effects of LINC01535 on in vivo tumor growth were investigated by xenograft tumor models. The miR-146b-5p/LINC01535/TRIM2 interaction was evaluated via luciferase reporter assays. This study showed downregulation of LINC01535 in ccRCC. Moreover, LINC01535 upregulation attenuated in vitro ccRCC development and hindered in vivo tumor growth. Furthermore, LINC01535 sponged miR-146b-5p which had a negative correlation with LINC01535, and TRIM2 was a direct target of miR-146b-5p and mediated by LINC01535. Mechanically, LINC01535/miR-146b-5p/TRIM2 axis affected ccRCC progression by mediating the PI3K/Akt signaling. All in all, our observations suggest the LINC01535/miR-146b-5p/TRIM2 axis as a crucial role in ccRCC.


A new approach using intraoperative ultrasound imaging for the localization and removal of multiple foreign bodies in the neck.
An innovative method of using ultrasound imaging intraoperatively is reported. Multiple radiopaque and radiolucent foreign bodies within soft tissues were localized in theatre using high resolution ultrasonography. Depth of injury and vessel status were also ultrasonically assessed. Surgical removal of all foreign bodies was aided by intraoperative ultrasound guidance. In addition, this new approach of using intraoperative ultrasonography was pivotal in confirming the removal of all foreign bodies from the wound at the time of the operation.


Palladium-catalyzed cross-coupling reactions in one-pot multicatalytic processes.
Palladium-catalyzed cross-coupling reactions have been investigated in multicatalytic processes to synthesize disubstituted alkenes and alkanes from carbonyl derivatives. The use of copper-catalyzed methylenation reactions is the key starting reaction to produce terminal alkenes which are not isolated, but submitted to further structure elongation. Not only is the isolation of the alkene intermediate unnecessary, but also the copper catalyst is a beneficial cocatalyst in the palladium-catalyzed cross-coupling reactions. The desired products are thus typically obtained in higher yields using this one-pot approach. We have used these processes to synthesize hydroxylated (E)-stilbenoids, which are known chemopreventive and chemotherapeutic agents, odorant-substituted indanes, and non-natural amino acids, such as homophenylalanine.


Interferon-gamma and tumor necrosis factor-alpha levels in sera and whey of cattle with naturally occurring coliform mastitis.
Concentrations of interferon-gamma (lFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in serum and whey samples from cattle with naturally occurring coliform mastitis for two weeks after onset using bovine INF-gamma and TNF-alpha-specific ELISA. In serum and whey samples from healthy cows. IFN-gamma was almost undetectable and TNF-alpha was detected at low levels. At the onset of illness, INF-gamma in sera and whey and TNF-alpha in whey from the mastitic cows were significantly higher than their respective values in healthy cows. Concentrations of IFN-gamma and TNF-alpha in whey from mastitic cattle decreased significantly as the cows recovered.


Copolymers including L-histidine and hydrophobic moiety for preparation of nonbiofouling surface.
A new type of copolymer composed of l-histidine (ampholyte) and n-butyl methacrylate (hydrophobic moiety) was developed for the preparation of nonbiofouling surfaces. The copolymer adsorbed onto resin surfaces and made the surface very hydrophilic. The hydrophilization effect was higher than that of bovine serum albumin (BSA). When polystyrene surfaces were coated with the copolymer, both the nonspecific adsorption of protein and the adhesion of cells were significantly reduced in comparison with BSA coating. The newly synthesized polymer is a new and useful candidate for the preparation of nonbiofouling surfaces.


Awareness and training need of biomedical waste management among undergraduate students, Andhra Pradesh.
Total 463 undergraduate students (216 males & 247 females) of ASRAM medical college of Andlira Pradesh were surveyed regarding awareness about biomedical waste management. Most of the students have heard about biomedical waste. Some of them were aware that it causes health hazards. But knowledge about category of wastes, duration of waste storage, responsibility of waste, type of bags used for collection, identification of Biohazard symbol was poor. Awareness of Biomedical waste. management and Handling rule 1998 was also poor. There were gaps in various aspects of Biomedical waste management among medical students. Appropriate training or inclusion of a topic in undergraduate medical curriculum can fulfill this.


Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis.
Naproxen strongly inhibits platelet aggregation. To examine the risk of acute thromboembolic cardiovascular events (TCEs) (myocardial infarction, sudden death, and stroke) with current naproxen use among patients with rheumatoid arthritis. We studied patients aged 40 to 79 years with rheumatoid arthritis in the British General Practice Research Database, excluding those with a prior TCE and potentially confounding conditions. We matched up to 4 controls by sex, age, and site of medical practice to cases with first incident TCEs. The case diagnosis date was designated as the index date for each case and his or her controls. We categorized naproxen according to the most recent prescription prior to the index date as being current (< or =30 days), past (> 30 days but < 365 days), or none (> or =365 days before index date). Using conditional logistic regression, we conducted a matched case-control analysis with adjustment for potential confounders. We identified 809 cases. Current naproxen use was more common among controls (5.7%) than cases (3.2%). Adjusting for calendar year of treatment start, systemic corticosteroid use, diabetes, and comorbidity, we found that the odds ratio (95% confidence interval) for current naproxen use was 0.61 (0.39-0.94) while that for past use was 0.87 (0.65-1.16). Secondary and sensitivity analyses supported these results. In this case-control study, patients with rheumatoid arthritis and a current prescription for naproxen had a reduced risk of acute major TCEs relative to those with no naproxen prescription in the past year. These results are consistent with the ability of naproxen to inhibit platelet aggregation.


Mitochondrial Calcium Transporters Mediate Sensitivity to Noise-Induced Losses of Hair Cells and Cochlear Synapses.
Mitochondria modulate cellular calcium homeostasis by the combined action of the mitochondrial calcium uniporter (MCU), a selective calcium entry channel, and the sodium calcium exchanger (NCLX), which extrudes calcium from mitochondria. In this study, we investigated MCU and NCLX in noise-induced hearing loss (NIHL) using adult CBA/J mice and noise-induced alterations of inner hair cell (IHC) synapses in MCU knockout mice. Following noise exposure, immunoreactivity of MCU increased in cochlear sensory hair cells of the basal turn, while immunoreactivity of NCLX decreased in a time- and exposure-dependent manner. Inhibition of MCU activity via MCU siRNA pretreatment or the specific pharmacological inhibitor Ru360 attenuated noise-induced loss of sensory hair cells and synaptic ribbons, wave I amplitudes, and NIHL in CBA/J mice. This protection was afforded, at least in part, through reduced cleavage of caspase 9 (CC9). Furthermore, MCU knockout mice on a hybrid genetic CD1 and C57/B6 background showed resistance to noise-induced seizures compared to wild-type littermates. Owing to the CD1 background, MCU knockouts and littermates suffer genetic high frequency hearing loss, but their IHCs remain intact. Noise-induced loss of IHC synaptic connections and reduction of auditory brainstem response (ABR) wave I amplitude were recovered in MCU knockout mice. These results suggest that cellular calcium influx during noise exposure leads to mitochondrial calcium overload via MCU and NCLX. Mitochondrial calcium overload, in turn, initiates cell death pathways and subsequent loss of hair cells and synaptic connections, resulting in NIHL.


Relationships between mood state, time estimation, and selected movement speed.
We investigated whether different aspects of mood state influence sense of time estimation and movement speed. Mood states were measured on the Multiple Mood Scale for 142 female undergraduate students, who were then asked to estimate the interval of time elapsed between the words "start" and "stop" spoken by a tester. Next, the same subjects were told to draw circles inside 1-cm squares printed on an A4 size sheet of paper in succession at their freely elected comfortable speed. Scores on Concentration (r=-.22, p<.01) and Being Startled (r=-.26, p<.01) each correlated significantly and negatively with time estimation, while scores on Boredom (r =.17, p <.05) had a significant positive correlation with movement speed. These results suggest that different aspects of mood state have some association with time estimation and selected movement speed. Values account for small common variance.


Overexpression of HDAC6, but not HDAC3 and HDAC4 in the penumbra after photothrombotic stroke in the rat cerebral cortex and the neuroprotective effects of α-phenyl tropolone, HPOB, and sodium valproate.
Epigenetic processes play important roles in brain responses to ischemic injury. We studied effects of photothrombotic stroke (PTS, a model of ischemic stroke) on the intracellular level and cellular localization of histone deacetylases HDAC3, HDAC4 and HDAC6 in the rat brain cortex, and tested the potential neuroprotector ability of their inhibitors. The background level of HDAC3, HDAC4 and HDAC6 in the rat cerebral cortex was relatively low. HDAC3 localized in the nuclei of some neurons and few astrocytes. HDAC4 was found in the neuronal cytoplasm. After PTS, their levels in penumbra did not change, but HDAC4 appeared in the nuclei of some cells. Its level in the cytoplasmic, but not nuclear fraction of penumbra decreased at 24, but not 4 h after PTS. HDAC6 was upregulated in neurons and astrocytes in the PTS-induced penumbra, especially in the nuclear fraction. Unlike HDAC3 and HDAC4, HDAC6 co-localized with TUNEL-positive apoptotic cells. Inhibitory analysis confirmed the involvement of HDAC6, but not HDAC3 and HDAC4 in neurodegeneration. HDAC6 inhibitor HPOB, HDAC2/8 inhibitor α-phenyl tropolone, and non-specific histone deacetylase inhibitor sodium valproate, but not HDAC3 inhibitor BRD3308, or HDAC4 inhibitor LMK235, decreased PTS-induced infarction volume in the mouse brain, reduced apoptosis, and recovered the motor behavior. HPOB also restored PTS-impaired acetylation of α-tubulin. α-phenyl tropolone restored acetylation of histone H4 in penumbra cells. These results suggest that histone deacetylases HDAC6 and HDAC2 are the possible molecular targets for anti-ischemic therapy, and their inhibitors α-phenyl tropolone, HBOP and sodium valproate can be considered as promising neuroprotectors.


Viability of Lactobacillus rhamnosus R0011 in an apple-based fruit juice under simulated storage conditions at the consumer level.
Lactobacillus rhamnosus R0011 was inoculated in an apple-pear-raspberry juice blend at 4.5 x 10(9) CFU/250 mL portion, and viability was followed during storage in conditions simulating consumer use. Study parameters were age of the juice (2 or 4 wk), sampling size (one to three 250-mL portions), incubation temperature (between 2 and 7 degrees C), and atmosphere (aerobic compared with anaerobic). Dependent variables were pH, dissolved oxygen (DO) level, and viable count. The DO level in the unopened PETE commercial bottles decreased from 10% to 3% over a 5-wk storage period at 7 degrees C. In shaken and opened bottles, DO increased to 15% during the 1st week of storage, irrespective of sampling size. However, agitation of bottles having more that 250 mL of headspace initially increased DO readings to 30% of maximum, but the DO level subsequently dropped to 15% during the 1-wk storage period between samplings. The presence of L. rhamnosus R0011 did not affect the DO data. The pH varied between 3.6 and 3.9, and was not influenced by L. rhamnosus R0011. However, the pH increased on average by 0.1 unit following multiple agitations and samplings. When the juices remained unopened in the PETE bottles, the viable population gradually dropped by 75% over 5 wk of storage at 7 degrees C, while in opened bottles reduction were only between 20% and 40%. Viability losses under anaerobic conditions were twice as high at 7 degrees C than at 4 degrees C. Data show that consumers can expect good viability of L. rhamnosus R0011 over a few weeks of storage in a refrigerator, even if the bottles have been opened and cells are exposed to oxygen.


Mechanism of stimulation of natural killer-cell cytotoxicity by interferon and an interferon-inducer in the rat.
The interferon-induced Newcastle disease virus (NDV) was shown to augment cytotoxicity attributable to natural killer (NK) cells in all of the major lymphoid organs of W/Fu rats except the thymus. The levels of interferon isolated from the spleen following NDV inoculation correlated with the increase in splenic cytotoxicity from the same spleen. Spleen-derived interferon was shown to augment splenic cytotoxicity following intravenous inoculation, and to augment spleen cell cytotoxicity in vitro. Three major peaks of interferon type I were found in spleen homogenates corresponding to mol. wt of greater than 100,000, 29-33,000 and 19-23,000. All these fractions stimulated spleen cell cytotoxicity when tested in vitro. The rapid drop in splenic cytotoxicity 24 hr after NDV inoculation was associated with a rapid fall in interferon levels in vivo. The need for the continued presence of interferon for the stimulation of cytotoxicity was demonstrated when spleen cells pretreated with interferon for 4 hr in vitro lost their augmented cytotoxicity upon culturing for a further 20 hr in the absence of interferon. Although splenic cytotoxicity returned to control levels within 24 hr of a single 10(7.3) EID50 dose of NDV, repeated doses of NDV maintained augmented cytotoxicity over a longer period. Spleen cells either taken from rats injected with NDV or pretreated in vitro with interferon showed a two-fold increase in the number of cytotoxic cells bound to W/FuG-1 target cells, with no change in the target binding-cell numbers. However, only the cells pretreated with interferon showed an increase in lytic efficiency.


Cis-dioxo-bis [3-methoxy-2,2-dimethylpropanediamine] Molybdenum/Surfactant-Modified Electrode for Simultaneous Sensing of Ascorbic Acid and Dopamine.
In this work, the carbon paste electrode (CPE) was modified using the cis-dioxo-bis[3-methoxy-2,2-dimethylpropanediamine] molybdenum(VI) complex and 1-octanaminium,N,N,N-trioctyl bromide. Using the modified electrode, the best separation of anodic peaks for ascorbic acid and dopamine was obtained in solutions with pH 5.0 and the linear range for ascorbic acid is acquired in the range from 3.0 × 10-6 to 6.0 × 10-3 M and for dopamine from 2.0 × 10-6 to 1.0 × 10-2 M. The limits of detection (S/N = 3) were 4 × 10-7 M and 5 × 10-7 M for dopamine and ascorbic acid, respectively. Surface regeneration and the very easy preparation of the modified CPE together with the very good peak resolution and sub-micromolar detection limits designate the prepared carbon paste electrode appropriate for simultaneous voltammetric determination of dopamine and ascorbic acid.


Effectiveness of time-limited psychotherapy for minor psychiatric disorders: randomised controlled trial evaluating immediate v. long-term effects.
Psychotherapy research rarely has studied outcome in the longer term. To evaluate the effectiveness of brief group dynamic psychotherapy (BGDP) intervention in patients with minor psychiatric disorders compared with the usual clinical management shortly after treatment termination and to investigate whether intervention would show a differential effect at 2-year follow-up. Patients were allocated randomly to an experimental or control group. The General Health Questionnaire (GHQ) was used as a primary outcome measure. Based on improvement in the GHQ, at termination of treatment the BGDP group showed a significant improvement in 23 out of 42 (54.8%) compared with 11 out of 41 (26.8%) in the clinical management group. The difference in the total improvement rate is 28% (95% C18-48) (chi(2)=6.7; d.f.=1; P=0.009). In contrast, no differential follow-up effects were found between the BGDP and clinical management groups. Psychotherapy appears to have beneficial effects at termination of treatment but the changes attained were not stable.


Electrical activity of superior colliculus associated with eye movements in alert cats.
Eye movement potentials (EMPs) were recorded from the superior colliculus (SC) of awake cats. When cats moved the eyes in front of a patterned or diffuse field, the EMP appeared as a sequence of the three components; EMP1, EMP2 and EMP3. The EMP1-EMP2-complex occurred while the eyes were moving and it had a wave form similar to that of the flash-evoked response. The EMP3 was seen 30-50 msec after the end of eye movement. In dark only the EMP3 was observed; its delay after the end of eye movement was as large as 70 msec. By placing electrodes at various depths of SC, the EMP was found to originate in the superficial layers. In immobilized, encéphale isolé cats, placed in dark or made blind by enucleation, the followings were observed; 1) Passive movements of the eye did not give rise to any significant electrical activity of SC. 2) Spontaneous mass activity of the oculomotor nucleus, that would result in eye movements if the cats were not paralysed, was followed by sharp wave activity of SC and this was the same after the visual cortex had been ablated bilaterally. From these findings it is concluded for the EMPs of awake cats that the EMP1-EMP2-complex is a response to retinal impulses caused by movements of images, whereas the EMP3 is due to an extraretinal factor such as the corollary mechanism. Besides the EMPs as described above, some activity was found to occur about 150 msec before the onset of eye movement. This EMP, called early EMP, seemed to appear when it was followed by eye movements with relatively high speeds.


Covalent immobilization of recombinant fusion proteins with hAGT for single molecule force spectroscopy.
A genetically modified form of the human DNA repair protein O(6)-alkylguanine-DNA-alkyltransferase (hAGT) was used to immobilize different recombinant hAGT fusion proteins covalently and selectively on gold and glass surfaces. Fusion proteins of hAGT with Glutathione S-Transferase and with tandem repeats of Titin Ig-domains, were produced and anchored via amino-polyethylene glycol benzylguanine. Anchoring was characterized and quantified with surface plasmon resonance, atomic force microscope and fluorescence measurements. Individual fusion proteins were unfolded by single molecule force spectroscopy corroborating the selectivity of the covalent attachment.


Health-related Quality of Life Profile of Newly Diagnosed Patients With Myelodysplastic Syndromes by Age, Sex, and Risk Group: A Real-world Study by the GIMEMA.
Health-related quality of life (HRQoL) is an important goal of therapy for patients with myelodysplastic syndromes (MDS); however, little is known about HRQoL of these patients at clinical presentation. We report HRQoL profile of newly diagnosed patients with MDS across both the the International Prognostic Scoring System (IPSS) and IPSS-Revised (IPSS-R) classifications, stratified by sex and age group categories, aiming to also establish European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) reference values for these patients. Analysis was based on 927 patients with a median age of 73.3 years (interquartile range, 66.0-79.2), of whom 506 and 421 with lower- and higher-risk disease respectively, according to the IPSS classification. HRQoL was assessed with the EORTC QLQ-C30 and substantial differences by age groups and sex, between and within lower- and higher-risk disease categories were observed. For example, within higher-risk disease patients, the youngest group (ie, 30-59 years) tended to report clinically meaningful worse outcomes across various functional and symptom domains compared with older age groups. We also developed 2 regression models allowing for the prediction of EORTC QLQ-C30 reference scores for patients classified according to either the IPSS or the IPSS-R. Investigation of prevalence rates for clinically important problems and symptoms at diagnosis revealed a substantial burden of the disease with >50% of patients reporting clinically important problems with physical functioning and dyspnea in both lower- and higher-risk disease. Our findings may help to enhance the interpretation of HRQoL outcomes in future MDS studies and to better contextualize HRQoL data from routine practice settings.


Transient Fetal Tachycardia After Intravenous Diphenhydramine Administration.
Fetal tachycardia is attributable to a variety of etiologies, including an untreated maternal medical condition or an indicator of potential fetal compromise. Maternal medication administration may also affect the fetal heart rate. A 28-year-old nulliparous patient at 41 weeks of gestation was treated for pruritus with intravenous diphenhydramine after epidural administration of fentanyl. Within 14 minutes, the fetal heart rate increased from a baseline of 155 beats per minute (bpm) to more than 200 bpm while maintaining moderate variability. This was accompanied by an increase in uterine contractions occurring every 1.5 minutes. The fetal tachycardia lasted 51 minutes; several hours later, a healthy neonate was delivered. Diphenhydramine may produce transient fetal tachycardia as well as increased maternal uterine activity.


Autapse-induced multiple coherence resonance in single neurons and neuronal networks.
We study the effects of electrical and chemical autapse on the temporal coherence or firing regularity of single stochastic Hodgkin-Huxley neurons and scale-free neuronal networks. Also, we study the effects of chemical autapse on the occurrence of spatial synchronization in scale-free neuronal networks. Irrespective of the type of autapse, we observe autaptic time delay induced multiple coherence resonance for appropriately tuned autaptic conductance levels in single neurons. More precisely, we show that in the presence of an electrical autapse, there is an optimal intensity of channel noise inducing the multiple coherence resonance, whereas in the presence of chemical autapse the occurrence of multiple coherence resonance is less sensitive to the channel noise intensity. At the network level, we find autaptic time delay induced multiple coherence resonance and synchronization transitions, occurring at approximately the same delay lengths. We show that these two phenomena can arise only at a specific range of the coupling strength, and that they can be observed independently of the average degree of the network.


The Effect of a Muscle Weight-Bearing and Aerobic Exercise Program on the Body Composition, Muscular Strength, Biochemical Markers, and Bone Mass of Obese Patients Who Have Undergone Gastric Bypass Surgery.
The effect of an exercise program on the body composition, muscular strength (MS), biochemical markers, and bone mineral density (BMD) of individuals undergoing gastric bypass is unclear. We assessed lean mass (LM), MS, bone remodeling markers, and BMD before and after supervised weight-bearing and aerobic exercise training in obese patients who underwent Roux-en-Y gastric bypass (RYGB). This study included 37 obese patients (81.1% women, mean age 38.2 years, mean body mass index 42.4 ± 0.5 kg/m2). Whole body densitometry was used to evaluate pre- and postoperative BMD, total body fat, and LM. Serum calcium, parathyroid hormone, 25-hydroxyvitamin D, and bone remodeling markers were measured. MS was determined through the concentric 10 repetition maximum test. Postoperatively, participants were divided into two groups: the training group, who followed an exercise program (TG, n = 18), and the control group, who did not (CG, n = 19). After 1 year, the TG showed a lower decrease in total BMD and at the lumbar spine and right hip compared with the CG (p < 0.001). The TG had lower mass reduction and an increase in upper limb LM compared with the CG (both p < 0.05). There was no significant difference between groups in bone markers or calcium metabolism. MS was higher in the TG than the CG (p < 0.05). The supervised exercise program attenuated lumbar spine and right hip BMD loss and improved LM in the arms and overall MS but did not affect bone remodeling.


Child abuse: the nurse and prevention.
As professional practitioners, nurses can promote prevention by becoming knowledgeable about all aspects of the phenomenon of child abuse, by carefully scrutinizing their own beliefs and values, and by monitoring their own behavior. By careful use of the problem-solving approach in their practices they can effectively intervene in potentially problematic situations. As citizens who have more complete and accurate information than their lay counterparts, they can be vital resources. They can support movements and legislation that seek to establish methods for preventing child neglect and abuse, and where neither movements nor legislation exists, they can promote both. Finally, nurses can promote and participate in relevant research that will continue to identify causes and seek solutions.


Sequential Parenteral to Oral Clindamycin Dosing in Pediatric Musculoskeletal Infection: A Retrospective Review of 30 mg/kg/d Versus 40 mg/kg/d.
Children with musculoskeletal infection in methicillin-resistant Staphylococcus aureus (MRSA) prevalent communities are often treated with oral clindamycin. Current guidelines recommend approximately 40 mg/kg/d for MRSA infections. This study investigates the clinical practice of using 30 mg/kg/d of clindamycin as an alternative for outpatient dosing. Children with musculoskeletal infection treated with outpatient clindamycin from 2009 to 2014 were studied by retrospective review. The amount of clindamycin administered was determined from dose, interval and duration of outpatient treatment. Hospital readmission, surgeries and sequelae were assessed. Severity of illness was determined for children with osteomyelitis. The readmission rate of 25 children treated with 40 mg/kg/d was compared with that of 190 children treated with 30 mg/kg/d. The reason for readmission was evaluated to consider whether antibiotic dosing strategy was a potential factor. Among 215 children studied, the average outpatient duration of treatment was 32.8 days. There was no significant difference in the rate of readmission between dosing cohorts. Severity of illness scores (0-10 scale) was significantly higher among readmitted children with osteomyelitis (mean 9.8 ± 0.4) than among those with osteomyelitis who were not readmitted (mean 2.9 ± 3.2), P = 0.001. Sequelae were more common in the high-dose group and were noted in 3 children (12%) in that cohort compared with 6 children (3.2%) in the low-dose cohort (P > 0.05). Oral dosing of 30 mg/kg/d was effective for musculoskeletal infection in children in an MRSA prevalent community. Illness severity appeared to have greater impact on readmission and sequelae than did antibiotic dosing.


Stable Superwetting Meshes for On-Demand Separation of Immiscible Oil/Water Mixtures and Emulsions.
Oil-water separation is of great importance for the treatment of oily wastewater, including immiscible light/heavy oil-water mixtures, oil-in-water, or water-in-oil emulsions. Recently, interfacial materials (especially filtration membranes) with special wettability have been broadly developed to solve the environmental problems by virtue of their advantages in energy saving, high flux, and good selectivity. However, the given wetting property (superhydrophilicity or superhydrophobicity) and pore size and poor stability of filtration membranes limit their widespread applications, which is far from meeting a wide variety of oil-polluted water. Here polypyrrole-coated meshes with underwater superoleophobicity and underoil superhydrophobicity as well as controllable pore size were prepared by adopting cyclic voltammetry. It is found that the surface micro/nanohierarchical structures play a critical role in the formation of underwater superoleophobicity and underoil superhydrophobicity. HCl is advantageous to the construction of highly rough surface rather than H2SO4 and H3PO4. The obtained filtration membranes can be used for the on-demand separation of oil-water mixtures, showing outstanding stability in harsh conditions, such as high temperature (80 °C), low temperature (0 °C), salt (0.5 M NaCl), and acid (1 M HCl), except for alkali (1 M NaOH).


Analysing trends of Patient Safety Non-Technical Skills among postgraduate trainees through a modified survey tool.
To analyse practices of patient safety non-technical skills among postgraduate trainees to establish the utility of organised teaching programmes in this regard, and to determine the utilisation of different teaching modes. The multicentre, two-phase, cross-sectional study was conducted from February to August 2020 at 27 teaching hospitals across Pakistan which were part of the Patient Safety Friendly Hospital Initiative by the World Health Organisation. The Hospital Survey on Patient Safety Culture was modified with validated additional survey items before using it to gather relevant data. Data was analysed using SPSS 21. In the first phase, 42 additional survey items were developed with content validity ratio >0.66 and item content validity index >0.83. Cronbach's alpha of the modified survey tool was 0.790. The second phase comprised 388 postgraduate trainees; 199(51.3%) males and 189(48.7%) females. Of them, 134(34.5%) were in the third year of training, 215(55.4%) fourth, and 39(10.1%) in the final year. Highest positive response was found for learning Teamwork 216(55.7%) and the lowest for Situational Awareness 62(15.9%). Leadership had highest good practice responses (subscales range: 77.6% to 76.6%) and Communication had the lowest (subscales range: 16.5% to 74.2%). Agreement on Informal Learning mode was the highest 268(69.1%) and the lowest was for Simulator Learning 63(16.2%). Besides, 274(70.6%) and 281(72.4%) subjects agreed on the supportive role of supervisors and hospital administrations. The correlation of the studied variables with the year of training was significant only for Teamwork (p=0.02) and Medication Safety skills (p=0.01). Modified Hospital Survey on Patient Safety Culture could be used as a benchmark for evaluating patient safety teachings and practices. Significance of patient safety non-technical skills was established with limited evidence for the utility of organised teaching programmes.


Unilateral absence of the external carotid artery.
We report a patient with absence of the external carotid artery. The major external branches originate from the internal carotid artery which is really a common arterial trunk. The embryology and clinical significance of this rare vascular anomaly are discussed.


A comparative analysis of the rate of meiosis, chiasma frequency and terminalization in the Jerboas Allactaga and Jaculus (Rodentia: Dipodidae) in Egypt.
The rate of seven meiotic stages (zygotene-pachytene, diplotene-diakinesis, metaphase I, anaphase I, metaphase II, anaphase II, and quartet) was studied in the jerboas Jaculus jaculus jaculus, Jaculus orientalis, and Allactaga tetradactyla, chiasma frequency and terminalization being examined only in J. jaculus and J. orientalis, and compared with the previous data concerning A. tetradactyla. Significant differences in the rate of meiosis, frequency of bivalent types, and frequency of interstitial and distal or terminal chiasmata per genome length were observed between A. tetradactyla and the two congeneric species J. jaculus and J. orientalis. Differences of these parameters among individuals within each species are also discussed in detail.


Understanding the experiences of youth living with sickle cell disease: a photovoice pilot.
A Photovoice pilot was conducted with youth living with sickle cell disease (SCD), in order to further understand their lived experience and examine the acceptability, feasibility, and utility of this method in this population. SCD is an inherited genetic condition whose primary symptom is severe pain. Youth were able to reflect on their experiences with SCD using Photovoice and the adapted SHOWeD method. Parents and youth found Photovoice to be valuable for children and adolescents with SCD. Emerging themes included the impact of SCD, the importance of everyday activities and interests, and the importance of family and support.


Analysis and Purification of Mouse Intestinal Dendritic Cell and Macrophage Subsets by Flow Cytometry.
The unit presents a method for analysis of intestinal dendritic cell (DC) and macrophage subsets by flow cytometry in the single cell suspension prepared from the mouse small and large intestine (Basic Protocol). describes a strategy to enrich the hematopoietic cell fraction in the sample by Percoll gradient centrifugation, and describes preparation of single cell suspensions from specific tissue layers of the small intestine, such as the epithelium, villi mucosa, submucosa, and muscularis externa. Finally, Support Protocol explains how to purify specific intestinal DC and macrophage subsets by flow-cytometry-based cell sorting. © 2016 by John Wiley & Sons, Inc.


A longitudinal investigation of nutrition and dietary patterns in children of mothers with eating disorders.
To investigate dietary patterns and nutritional intake in children of mothers with eating disorders. Mothers (N = 9423) from a longitudinal general population birth cohort study, the Avon Longitudinal Study of Parents and Children, completed Food Frequency Questionnaires on their children at 3, 4, 7, and 9 years of age. Macronutrient intake was estimated, and dietary patterns were obtained using principal components analysis. Linear regression and mixed-effects models were used to assess dietary patterns and nutritional intake among children of women with lifetime anorexia nervosa (AN, n = 140), bulimia nervosa (BN, n = 170), or AN+BN (n = 71), compared with children of women without eating disorders (unexposed women, n = 9037). Children in the maternal AN and BN groups had higher scores on the "health conscious/vegetarian" dietary pattern compared with unexposed children. Less adherence to the "traditional" dietary pattern was observed in children of exposed mothers, with more pronounced differences in early childhood. Children of women with AN and BN had higher intake of energy and children of women with BN had higher intake of carbohydrates and starch and lower intake of fat, compared with children in the unexposed group. Maternal eating disorders are associated with altered offspring dietary patterns and macronutrient intake. Longitudinal changes in patterns of diet in children of women with eating disorders may increase the risk of weight gain or disordered eating later in life.


Remodeling of bone tissue around the distal part of Zweymüller stem.
The Zweymüller stem is well-known in Europe and widely used for total hip replacement since 1980. Few authors have noted the presence of increased bone density below the tip of the stem; however, the underlying mechanism is still unknown. The aim of this study was to reveal factors influencing bone remodeling around the tip of the Zweymüller stem. 102 consecutive patients (69 women and 33 men) who received a second generation Zweymüller type stem (123 prostheses) were included. Mean follow-up was 9.2 years (6 - 15 years). A Cortical Index (CI) was defined as the ratio between stem width and external cortical diameter in Gruen zones 3 and 5. Patients with a wide femoral canal and thin cortical bone (CI ≥0.4) demonstrated a positive correlation with the presence of increased bone density (IBD) below the stem (p<0.0001, r=0.6028). During follow-up, the mean Cortical Index decreased by 0.02 points and mean thickness of cortical bone in zone 3 and 5 increased by 2.0 millimeters. Cortical thickening was more pronounced in cases without IBD (1.5 vs. 2.4 mm, p=0.0172). 1. Thin cortical layers and a wide femoral canal (CI ≥0.4) can result in the presence of IBD below the stem. 2. IBDs probably appear due to mechanical stress transferred by the tip of stem to cancellous bone in Gruen zone 4. 3. Based on clinical symptoms, we conclude that the presence of IBD is not associated with increased aseptic loosening or stem instability.


Practical management of natural killer/T-cell lymphoma.
Natural killer (NK)/T-cell lymphoma is a distinct clinic-pathological entity in the WHO classification of lymphoid neoplasms. It is uncommon among all lymphomas but is more prevalent in Asian countries. The pathogenesis remains unknown despite its strong association with Epstein-Barr virus (EBV) infection. Conventional chemotherapeutic regimens such as CHOP do not appear to be effective and the prognosis is dismal especially in advanced-stage disease. The major objective of this review will focus on the practical management of patients with NK/T-cell lymphoma especially on the treatment using L-asparaginase-based regimen. Data on gene and micro-RNA expression profiling studies are also discussed which may impact the development of new drugs targeting specific oncogenic pathways. Gene expression profiling and other genetic studies have revealed distinct oncogenic signalling pathway activation and have identified potential targets for therapeutic intervention in NK/T-cell lymphoma. Quantitative measurement of EBV-DNA in cell-free plasma, rather than cellular EBV-DNA level predicts overall survival as shown by a recent prospective study. L-Asparaginase-based chemotherapeutic regimens such as SMILE and AspaMetDex have been demonstrated to be highly effective in the treatment of advanced-stage and relapsed/refractory disease. An accurate histopathological diagnosis and precise staging using PET computed tomography (PET-CT) scan are essential in the management of patients with NK/T-cell lymphoma. Recent prospective trials have demonstrated that L-asparaginase-based chemotherapeutic regimen is highly effective and improves outcome of patients with locally advanced as well as disseminated disease. The impact of haematopoietic stem cell transplantation remains to be defined.


Measurements of the distribution of time intervals between cell passages in flow cytometry as a method for the evaluation of sample preparation procedures.
It is expected that the time sequence of cells passing through the sensing region of a flow cytometer should follow the statistics of a Poisson process. Thus, measurement of time intervals between passages of fluorescent microspheres and cells stained with mithramycin demonstrated the negative exponential distribution characteristic of such a process. However, analysis of cells stained with fluorescein-iso-thiocyanate showed marked deviations from a negative exponential distribution of time intervals. The distribution had an additional component due to time intervals with mean value about 60 times shorter than the population mean, and in certain cases more than 50% of the cells were registered with such short time intervals. This percentage could, however, be reduced to acceptable levels by modifications of the sample preparation procedures. Measurement of the distribution of time intervals between cell passages is proposed as a method for the evaluation of possible improvements in sample preparation procedures.


Active Coping and Perceived Social Support Mediate the Relationship Between Physical Health and Resilience in Liver Transplant Candidates.
Without a transplant, end-stage liver disease is associated with significant morbidity and mortality. Transplant candidates endure physical and psychological stress while awaiting surgery, yet little is known about the relationship between physical health and psychological resilience during the wait-list period. This study examined predictors of psychological resilience and mediators of the relationship between physical health and psychological resilience in liver transplant candidates. Wait-listed candidates (N = 120) from a single Northeast transplant center completed assessments of physical functioning, coping, perceived social support, and resilience. Findings revealed that physical functioning, active coping, and perceived social support were positively associated with resilience; maladaptive coping was negatively associated with resilience. Perceived social support and active coping partially mediated the relationship between physical functioning and resilience. Transplant center care providers should promote active coping skills and reinforce the importance of effective social support networks. These interventions could increase psychological resilience among liver transplant candidates.


[Hospice - continuing care during patients life].
Palliative care is focused on enhancing quality of life for seriously ill. Hospice care is a comprehensive care provided by an interdisciplinary team for patients whose diseases cannot be cured and are approaching the end of life. To be eligible for admission to hospice care is required to be terminally ill with a life expectancy of 6 months or less. Currently, hospices are the main providers of specialized palliative care in the Czech Republic. This article is focused on the current state of palliative care and specifically on hospice care in the Czech Republic. This article should eliminate the myths associated with the hospice. It could also help physicians to better understand the role of hospice in delivering effective care for patients in the final stages of life.


Antigen-pulsed macrophage monolayers as specific immunoabsorbents: selective absorption of murine T cells committed to soluble protein antigen.
Antigen-pulsed macrophage (MO) monolayers in petri dishes were successfully employed as immunoabsorbents, for both the depletion and enrichment of T cells which proliferated upon exposure to soluble ovalbumin (OA). This procedure was shown not to deplete T cells reactive to a second antigen, and similarly MO monolayers pulsed with other antigens failed to deplete the T-cell preparation of OA-reactive cells. Employing brief incubation with trypsin/ethylenediamine tetracetic acid (EDTA), up to 2 X 10(6) OA-binding T cells could be recovered from each petri dish.


Patients' Preferences for Insulin Injection Devices.
In this issue, Pohlmeier et al report on a device assessment study in insulin-naïve patients with type 2 diabetes, to investigate the ease of use/learning and patient preference of the new prefilled U300 insulin glargine injection pen. Human factor studies are required by regulatory agencies and should ensure the proper use of the device in the context of the provided instructions. The patients found the device easy to learn/use and had a stable treatment satisfaction despite introduction of injection treatment. The lack of a control arm, the short duration, and the small sample size make it difficult to translate these results into clinical practice. It is encouraging to know, however, that the new pen is accepted by one of the intended patient populations.


Consequences of teenage pregnancy and motherhood.
In the past 15-20 years there has been a significant increase in sexual activity among teenagers as well as an increase in the rate of pregnancy. Teenage pregnancy has many social, psychological, economic and health consequences. Although there has been a significant increase in the use of abortion since the early 1970s among white teenagers, the majority of pregnant teenagers opt to carry their pregnancy to term and raise their child themselves. This review of the literature concerns itself with some of the variables associated with adolescent sexual behavior focusing on teenage pregnancy and the consequences of motherhood on child development. Suggestions are made for strategies that may be effective in ameliorating some of the problems as well as the research required for evaluating such strategies.


Roles of internal cysteines in the function, localization, and reactivity of the TraV outer membrane lipoprotein encoded by the F plasmid.
We have examined the functional role of two internal cysteine residues of the F-plasmid TraV outer membrane lipoprotein. Each was mutated to a serine separately and together to yield three mutant traV genes: traV(C10S), traV(C18S), and traV(C10S/C18S). All three cysteine mutations complemented a traV mutant for DNA donor activity and for sensitivity to donor-specific bacteriophage; however, when measured by a transduction assay, the donor-specific DNA bacteriophage sensitivities of the traV(C18S) and, especially, traV(C10S/C18S) mutant strains were significantly less than those of the traV(+) and traV(C10S) strains. Thus, unlike the Agrobacterium tumefaciens T-plasmid-encoded VirB7 outer membrane lipoprotein, TraV does not require either internal cysteine to retain significant biological activity. By Western blot analysis, all three mutant TraV proteins were shown to accumulate in the outer membrane. However, by nonreducing gel electrophoresis, wild-type TraV and especially the TraV(C18S) mutant were shown to form mixed disulfides with numerous cell envelope proteins. This was not observed with the TraV(C10S) or TraV(C10S/C18S) proteins. Thus, it appears that TraV C10 is unusually reactive and that this reactivity is reduced by C18, perhaps by intramolecular oxidation. Finally, whereas the TraV(C10S) and TraV(C18S) proteins fractionated primarily with the outer membrane, as did the wild-type protein, the TraV(C10S/C18S) protein was found in osmotic shock fluid and inner membrane fractions as well as outer membrane fractions. Hence, at least one cysteine is required for the efficient localization of TraV to the outer membrane.


Disruption of Small GTPase Rab7 Exacerbates the Severity of Acute Pancreatitis in Experimental Mouse Models.
Although aberrations of intracellular vesicle transport systems towards lysosomes including autophagy and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7Δpan) mice. In Rab7Δpan pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected. In experimental models of acute pancreatitis, the histopathological severity, serum amylase concentration and intra-pancreatic trypsin activity were significantly higher in Rab7Δpan mice than in wild-type mice. Furthermore, the autophagy process was blocked in Rab7Δpan pancreas compared with wild-type mice. In addition, larger autophagic vacuoles that colocalize with early endosome antigen 1 (EEA1) but not with lysosomal-associated membrane protein (LAMP)-1 were much more frequently formed in Rab7Δpan pancreatic acinar cells. Accordingly, Rab7 deficiency exacerbates the severity of acute pancreatitis by impairing the autophagic and endocytic pathways toward lysosomes.


GSK-3β inhibitor, 9-ING-41, reduces cell viability and halts proliferation of B-cell lymphoma cell lines as a single agent and in combination with novel agents.
The complexities of GSK-3β function and interactions with PI3K/AKT/mTOR signaling, cell cycling, and apoptotic pathways are poorly understood in the context of lymphomagenesis and cancer therapeutics. In this study, we explored the anti-tumor effects of the GSK-3β inhibitor, 9-ING-41, in lymphoma cell lines as a single agent and in combination with novel agents comprising BCL-2 inhibitor (Venetoclax), CDK-9 inhibitor (BAY-1143572) and p110δ-PI3K inhibitor (Idelalisib). Treatment of Daudi, SUDHL-4, Karpas 422, KPUM-UH1, and TMD8 lymphoma cell lines with 1 μM 9-ING-41 reduced cell viability by 40-70% (p<0.05) and halted proliferation. Luminex analysis of apoptotic pathways revealed a significant increase in active caspase 3 in all lymphoma cell lines (p<0.001) except TMD8 cells. Co-treating SUDHL-4 and KPUM-UH1 lymphoma cells with 0.5 μM 9-ING-41 showed 8-and 2-fold reduction in IC50 values of Venetoclax, respectively. No significant benefit for this combination was seen in other lymphoma cells tested. The combination of BAY-1143572 with 0.5 μM 9-ING-41 showed an 8-fold reduction in the IC50 value of the former in SUDHL-4 lymphoma cells alone. No significant changes in IC50 values of Idelalisib were measured across all cell lines for the combination of 9-ING-41 and Idelalisib. Further, signaling analysis via Western blot in the double-hit lymphoma cell line, KPUM-UH1, suggests that phospho-c-MYC is modified with 9-ING-41 treatment. Altogether, our data show that 9-ING-41 results in increased apoptosis and decreased proliferation in aggressive B-cell lymphoma cells and enhances the antitumor effects of BCL-2 and CDK-9 antagonists.


[Dyspepsia of a nonulcerous nature in servicemen under conditions of ecological-occupational stress].
In the result of complex examination of servicemen with non-ulcer dyspepsia in the conditions of ecological-professional tension it was found out that clinical manifestations of this pathology were the following: existence of morphological substrate as erosive--acute or chronic--and follicular changes of gastroduodenal mucosa. As a rule the non-ulcer dyspepsia in patients with intact mucosa is accompanied by isolated motor-evacuative disorders of stomach and duodenum.


Striking Differences in Properties of Geometric Isomers of [Ir(tpy)(ppy)H](+): Experimental and Computational Studies of their Hydricities, Interaction with CO2, and Photochemistry.
We prepared two geometric isomers of [Ir(tpy)(ppy)H](+), previously proposed as a key intermediate in the photochemical reduction of CO2 to CO, and characterized their notably different ground- and excited-state interactions with CO2 and their hydricities using experimental and computational methods. Only one isomer, C-trans-[Ir(tpy)(ppy)H](+), reacts with CO2 to generate the formato complex in the ground state, consistent with its calculated hydricity. Under photocatalytic conditions in CH3CN/TEOA, a common reactive C-trans-[Ir(tpy)(ppy)](0) species, irrespective of the starting isomer or monodentate ligand (such as hydride or Cl), reacts with CO2 and produces CO with the same catalytic efficiency.


[Therapy of urinary tract infection from the internal medicine viewpoint].
Effective treatment of urinary tract infection is dependent on a precise case history and a thorough physical examination. Before using antibacterial compounds it is mandatory that the physiological defense mechanisms be actively supported by nonspecific actions. Depending on the environment where patients are being cared for (general practitioner--hospital), the antibacterial therapy should take into account bacteriological information on the sensitivity of the bacteria to antibacterial agents.


Molecular differences between two immunologically related spumaretroviruses: the human prototype HSRV and the chimpanzee isolate SFV6.
A comparative study at the genomic and protein level was performed between two immunologically related spumaretroviruses, the human HSRV and the simian SFV6. Cross immunoprecipitation analysis with specific polyclonal and monoclonal antisera indicates shared antigenic determinants. However, restriction analysis of the viral DNAs and thermal stability of the hybrids demonstrate that HSRV and SFV6 are two different isolates.


Effects of post-transfer annealing and substrate interactions on the photoluminescence of 2D/3D monolayer WS2/Ge heterostructures.
The ultraflat and dangling bond-free features of two-dimensional (2D) transition metal dichalcogenides (TMDs) endow them with great potential to be integrated with arbitrary three-dimensional (3D) substrates, forming mixed-dimensional 2D/3D heterostructures. As examples, 2D/3D heterostructures based on monolayer TMDs (e.g., WS2) and bulk germanium (Ge) have become emerging candidates for optoelectronic applications, such as ultrasensitive photodetectors that are capable of detecting broadband light from the mid-infrared (IR) to visible range. Currently, the study of WS2/Ge(100) heterostructures is in its infancy and it remains largely unexplored how sample preparation conditions and different substrates affect their photoluminescence (PL) and other optoelectronic properties. In this report, we investigated the PL quenching effect in monolayer WS2/Ge heterostructures prepared via a wet transfer process, and employed PL spectroscopy and atomic force microscopy (AFM) to demonstrate that post-transfer low-pressure annealing improves the interface quality and homogenizes the PL signal. We further studied and compared the temperature-dependent PL emissions of WS2/Ge with those of as-grown WS2 and WS2/graphene/Ge heterostructures. The results demonstrate that the integration of WS2 on Ge significantly quenches the PL intensity (from room temperature down to 80 K), and the PL quenching effect becomes even more prominent in WS2/graphene/Ge heterostructures, which is likely due to synergistic PL quenching effects induced by graphene and Ge. Density functional theory (DFT) and Heyd-Scuseria-Ernzerhof (HSE) hybrid functional calculations show that the interaction of WS2 and Ge is stronger than in adjacent layers of bulk WS2, thus changing the electronic band structure and making the direct band gap of monolayer WS2 less accessible. By understanding the impact of post-transfer annealing and substrate interactions on the optical properties of monolayer TMD/Ge heterostructures, this study contributes to the exploration of the processing-properties relationship and may guide the future design and fabrication of optoelectronic devices based on 2D/3D heterostructures of TMDs/Ge.


Expression of the immediate early gene c-fos in basal ganglia: induction by dopaminergic drugs.
Expression of the immediate early gene c-fos is increased in mammalian neurons by a number of stimuli and the usefulness of this gene as a marker of neuronal activation has been demonstrated in several systems. Directly-acting dopamine agonists of the D1-type (SKF 38393, CY 208-243) and indirectly-acting dopamine agonists (amphetamine, cocaine) all produce a rapid and transient increase in Fos protein levels in varying patterns in striatum and cerebral cortex. Directly-acting dopamine agonists only produce c-fos activation in denervated (supersensitive) striatum whereas cocaine and amphetamine activate c-fos in striatum in naive animals. Remarkably, D2 selective antagonists such as haloperidol, albeit in high doses, also activate c-fos expression. Activation of c-fos and other immediate early genes may play a part in the development of such long-term dopamine-related effects as dyskinetic movements and addiction.


Natriuretic peptide drug leads from snake venom.
Natriuretic peptides are body fluid volume modulators, termed natriuretic peptides due to a role in natriuresis and diuresis. The three mammalian NPs, atrial natriuretic peptide (ANP), brain or b-type natriuretic peptide (BNP) and c-type natriuretic peptide (CNP), have been extensively investigated for their use as therapeutic agents for the treatment of cardiovascular diseases. Although effective, short half-lives and renal side effects limit their use. In approximately 30 years of research, NPs have been discovered in many vertebrates including mammals, amphibians, reptiles and fish, with plants and, more recently, bacteria also being found to possess NPs. Reptiles have produced some of the more interesting NPs, with dendroaspis natriuretic peptide (DNP), which was isolated from the venom of the green mamba (Dendroaspis angusticeps), having greater potency and increased stability as compared to the mammalian family members, and taipan natriuretic peptide c (TNPc), which was isolated from the venom of the inland taipan (Oxyuranus microlepidotus) displaying similar activity to ANP and DNP at rat natriuretic peptide receptor A. Although promising, more research is required in this field to develop therapeutics that overcome receptor-mediated clearance, and potential toxicity issues. This review investigates the use of snake venom NPs as therapeutic drug leads.