Bisphosphonate therapy for metastatic bone disease: the pivotal role of nurses in patient education.
To describe the role of bisphosphonate therapy for metastatic bone disease and skeletal-related events associated with some of the most common malignancies, and to highlight the importance and untapped potential of nurses intervening in the education and treatment of patients with these issues. Contemporary evidence-based studies on the prevalence and impact on quality of life in metastatic bone disease and skeletal-related events, and all major clinical trials describing the efficacy of bisphosphonates for the treatment of metastatic bone disease. Metastatic bone disease is a common consequence of cancer that impairs patient quality of life. Bisphosphonate therapy is effective in preventing or delaying complications associated with metastatic bone disease. Bisphosphonate therapy can help preserve functional independence and improve the quality of life for many patients with cancer. Poor adherence to bisphosphonate therapy frequently is caused by patients not understanding how the drug works or why they need it. Premature discontinuation of bisphosphonate therapy leaves patients at risk for painful and debilitating skeletal-related events, which reduces their functional independence and impairs their activities of daily living. Nurses are uniquely positioned to educate patients and their caregivers about the need to begin or continue taking bisphosphonates for treatment of metastatic bone disease and associated skeletal-related events. Nurses often are the most appropriate healthcare providers for counseling patients with metastatic cancer about personal and family issues and for communicating the needs and concerns of patients to their physicians.


Association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases.
Infertility is a common manifestation of the polycystic ovary syndrome (PCOS), a condition characterized by chronic anovulation, hyperinsulinemia and hyperandrogenism. Hyperinsulinemia leads to increased ovarian androgen production, resulting in follicular atresia and anovulation. Metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS. We present three consecutive cases from our clinic that support this premise. Three patients were seen in the reproductive endocrinology clinic with documented PCOS, long-standing infertility and clinically diagnosed insulin resistance. The first patient had hyperandrogenic, insulin-resistant acanthosis nigricans syndrome and had been resistant to multiple courses of clomiphene citrate; the second exhibited hypertension, hyperlipidemia and glucose intolerance along with anovulation; and the third presented with poorly controlled type 2 diabetes and a desire to conceive. Each patient received metformin, which led to restoration of menstrual cyclicity and conception in all three cases. These three patients reflect the heterogeneous nature of PCOS, and treating their underlying insulin resistance with metformin resulted in pregnancy. These findings suggest that metformin may be a useful adjunct for treatment of infertility in patients with PCOS.


Incidence of anaphylaxis and subtypes of anaphylaxis in a general hospital emergency department.
The absence of large-scale international studies means that data on anaphylaxis in emergency departments in different geographic areas are still necessary. To determine the incidence of anaphylaxis and subtypes of anaphylaxis and their distribution by age group in the emergency department of Hospital Universitario Fundación Alcorcon, Alcorcon (Madrid), Spain. Our study was performed between 2004 and 2005. We used the definition of anaphylaxis established by the NIAID-FAAN Symposium. Patient information was collected from the electronic clinical records of the emergency department using alphanumeric strings to identify acute allergic illnesses. This strategy recovered 91.7% of all anaphylaxis episodes in a pilot study. We observed a crude cumulative incidence of 0.9 episodes of anaphylaxis per 1000 emergency episodes (95% confidence interval [CI], 0.8-1.1), and 0.8 episodes per 1000 people (95% CI, 0.7-0.9). Standardized cumulative incidence of anaphylaxis according to the Standardized European Population was 1.1 (95% CI, 0.9-1.2). On analyzing the 213 cases of anaphylaxis, we discovered that the main cause was food (28.6%), followed by drugs (28.2%), unknown causes (27.2%), Anisakis (10.8%), Hymenoptera venom (3.3%), exercise (2.4%), and latex (0.9%). Food-induced anaphylaxis was less frequent in all groups older than the 0-4 age group in both reference populations (people who attend the emergency department and the general population). The cumulative incidence of anaphylaxis in our emergency department is low. Anaphylaxis by foods is more frequent in the 0-4 year group than in the other age groups. Drugs and food are the most frequent causes of anaphylaxis in our emergency department.


Emotion theories and adolescent well-being: Results of an online intervention.
Individuals' theories about emotions-the beliefs about the nature of emotions and the ability to influence them-have been linked to well-being. However, their causal role is not clear. To address this issue, we delivered a randomized controlled intervention to 1,645 middle school students that targeted their theories of emotion through interactive online modules. Students were taught that they could modify their emotions, get better at modifying their emotions with practice, and use strategies to improve their well-being. One month later, we found that students assigned to the intervention condition (compared to an active control condition) reported more adaptive theories of emotion and greater emotional well-being in school, although well-being outside of school was unchanged. Secondary analyses showed that these effects were present regardless of students' race, gender, or grade level. These findings suggest that theories of emotion may be a promising target for improving adolescent well-being. (PsycINFO Database Record


Parental response and understanding towards febrile convulsion.
A questionnaire survey was conducted on parents of 58 patients admitted with febrile convulsion (FC) over a 4 month period to the University of Malaya Medical Centre, Kuala Lumpur to determine parental response towards febrile convulsion in their child and their understanding of home management of FC. The majority of parents (93%) were frightened or were in a panic state on witnessing FC in their child. Most (77.6%) of them were able to bring their child to medical attention within 30 minutes, with delays attributed to transport problems. Parental understanding on FC was deficient, particularly with regard to home management of acute seizures. The parents' main source of information was friends and relatives. Urgent intervention to counsel and allay fears of parents who have just witnessed an acute FC in their child is required. More effort must be made to educate parents about FC, with particular reference to home management of seizures.


Runx1 promotes murine erythroid progenitor proliferation and inhibits differentiation by preventing Pu.1 downregulation.
Pu.1 is an ETS family transcription factor (TF) that plays critical roles in erythroid progenitors by promoting proliferation and blocking terminal differentiation. However, the mechanisms controlling expression and down-regulation of Pu.1 during early erythropoiesis have not been defined. In this study, we identify the actions of Runx1 and Pu.1 itself at the Pu.1 gene Upstream Regulatory Element (URE) as major regulators of Pu.1 expression in Burst-Forming Unit erythrocytes (BFUe). During early erythropoiesis, Runx1 and Pu.1 levels decline, and chromatin accessibility at the URE is lost. Ectopic expression of Runx1 or Pu.1, both of which bind the URE, prevents Pu.1 down-regulation and blocks terminal erythroid differentiation, resulting in extensive ex vivo proliferation and immortalization of erythroid progenitors. Ectopic expression of Runx1 in BFUe lacking a URE fails to block terminal erythroid differentiation. Thus, Runx1, acting at the URE, and Pu.1 itself directly regulate Pu.1 levels in erythroid cells, and loss of both factors is critical for Pu.1 down-regulation during terminal differentiation. The molecular mechanism of URE inactivation in erythroid cells through loss of TF binding represents a distinct pattern of Pu.1 regulation from those described in other hematopoietic cell types such as T cells which down-regulate Pu.1 through active repression. The importance of down-regulation of Runx1 and Pu.1 in erythropoiesis is further supported by genome-wide analyses showing that their DNA-binding motifs are highly overrepresented in regions that lose chromatin accessibility during early erythroid development.


Ceruloplasmin, copper, selenium, iron, zinc, and manganese levels in normal and sulfite oxidase deficient rat plasma: effects of sulfite exposure.
A noticeable effect of sulfite treatment was observed on the plasma ceruloplasmin ferroxidase activity of rats with normal sulfite oxidase activity when compared to normal controls. The plasma levels of selenium, iron, and zinc were unaffected by sulfite in normal and sulfite oxidase (SOX)-deficient rats. While plasma level of Mn was decreasing, plasma Cu level increased in SOX-deficient rats. Treating SOX-deficient groups with sulfite did not alter plasma level of Mn but made plasma level of Cu back to its normal level. This is the first evidence that Cu and Mn status were affected in experimental sulfite oxidase deficiency induced by low molybdenum diet with tungsten addition deserving further research to determine the underlying mechanisms of these observations in experimental sulfite oxidase deficiency.


Male breast cancer: Specific biological characteristics and survival in a Portuguese cohort.
Male breast cancer (BC) represents an individual subtype of BC, with therapeutic procedures based on female BC therapy results. The present study evaluated the parameters currently used for the characterization and therapy of male BC, and their association with disease-free (DFS) and overall survival (OS), aiming to obtain a comprehensive basis to improve the personalized care of male BC. A total of 196 patients from March 1970 to March 2018 (mean follow-up, 84.9 months) were profiled, using clinicopathological review, molecular assessment [BRCA1/2, DNA repair associated (BRCA1/2) status, immunohistochemistry, fluorescence in situ hybridization and DNA flow cytometry] and Cox regression statistical analysis. The median age of patients was 66.5 years. At presentation, 39.2% of patients with invasive carcinomas were in anatomic stage (AS) I. Patients exhibited primarily invasive carcinomas of no special type, histological grade 2, estrogen receptor α-(ERα) and progesterone receptor (PR)-positive, receptor tyrosine kinase erbB-2-negative, high Ki-67, Luminal B-like and aneuploid tumors. A total of 13 of the 44 (29.5%) BRCA-evaluated patients exhibited BRCA2 mutations, significantly associated with family history (FH), bilaterality, high Ki-67 expression, absence of PR and Luminal B-like tumors. Bilaterality was associated with the occurrence of non-breast primary neoplasms (NBPN). The 5 and 10-year DFS rates, excluding patients with distant metastasis, NBPN and in situ carcinomas (n=145) were 65.9 and 58.2%, respectively, and the 5 and 10-year OS rates were 77.5 and 59.2%, respectively. In the univariate analysis, Luminal B-like subtype, BRCA2 mutations, high Ki-67 expression, and AS II and III were significantly associated with shorter DFS and OS. In addition, age >70 years was associated with low OS. In the multivariate analysis, FH, AS II and III, and Luminal B-like subtypes were associated with poorer OS. In conclusion, the data from the present study emphasize the high incidence of BRCA2 mutation in male BC, and its association with FH, bilaterality, high Ki-67 expression, negative PR expression and Luminal B-like subtypes, and with shorter DFS and OS in univariate analysis.


Pierre Bourdieu: Expanding the scope of nursing research and practice.
Bourdieu is an important thinker within the sociological tradition and has a philosophically sophisticated approach to theoretical knowledge and research practice. In this paper, we examine the implication of his work for nursing and the health sciences more broadly. We argue that his work is best described as a reflexive realist who provides a space for a nonpositivist approach to knowledge that does not fall into the trap of idealism or relativism. We emphasize that Bourdieu was not an abstract theorist, but only utilized theories to understand and explain the social world in all its empirical complexity. Theory is emphasized over method without denying the importance of method. We then provide a brief overview of some of his key concepts: habitus, field and capital. His work is a scientifically astute practice that has an emancipatory purpose, with particular resonance to the problems of nursing as a social practice. Some have criticized Bourdieu for undermining agency and we briefly address this issue, but argue that his conceptual framework helps us to understand what endures in social practice and why change is often problematic. In short, this paper argues that Bourdieu's work is a fruitful resource for critiquing existing nursing approaches that are preoccupied with agency over structure.


Slipped capital femoral epiphysis. The prevalence of late contralateral slip.
We evaluated the prevalence of slipped capital femoral epiphysis in the contralateral hip of 169 children who had been managed with pinning in situ and thirty who had been managed with immobilization in a spica cast. Only children who had initially been seen with a unilateral slip and had been followed for a minimum of two years or until skeletal maturity were included in the study. The average duration of follow-up was 3.6 years (range, 0.5 to 9.5 years) for the group that had been managed with a cast and 2.8 years (range, 1.0 to 8.3 years) for the group that had been managed operatively. In sixty-one (36 per cent) of the 169 patients who had had operative treatment and two (7 per cent) of the thirty who had been managed with a spica cast, a slip subsequently developed in the contralateral hip; this difference was significant (p = 0.001). On the basis of these findings, we recommend that closer attention be paid to the potential development of a slip in the contralateral hip after pinning.


Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow.
Our guiding hypothesis is that ecto-enzymatic conversion of extracellular ATP to adenosine activates A(1) adenosine receptors, reducing resistance to aqueous humor outflow and intraocular pressure. The initial step in this purinergic regulation is ATP release from outflow-pathway cells by mechanisms unknown. We measured similar ATP release from human explant-derived primary trabecular meshwork (TM) cells (HTM) and a human TM cell line (TM5). Responses to 21 inhibitors indicated that pannexin-1 (PX1) and connexin (Cx) hemichannels and P2X(7) receptors (P2RX(7) ) were comparably important in modulating ATP release induced by hypotonic swelling, whereas vesicular release was insignificant. Consistent with prior studies of PX1 activity in certain other cells, ATP release was lowered by the reducing agent dithiothreitol. Overexpressing PX1 in HEK293T cells promoted, while partial knockdown (KD) in both HEK293T and TM5 cells inhibited hypotonicity-activated ATP release. Additionally, KD reduced the pharmacologically defined contribution of PX1 and enhanced those of Cx and P2RX(7) . ATP release was also triggered by raising intracellular Ca(2+) activity with ionomycin after a prolonged lag time and was unaffected by the PX1 blocker probenecid, but nearly abolished by P2RX(7) antagonists. We conclude that swelling-stimulated ATP release from human TM cells is physiologically mediated by PX1 and Cx hemichannels and P2X(7) receptors, but not by vesicular release. PX1 appears not to be stimulated by intracellular Ca(2+) in TM cells, but can be modulated by oxidation-reduction state. The P2RX(7) -dependent component of swelling-activated release may be mediated by PX1 hemichannels or reflect apoptotic magnification of ATP release, either through itself and/or hemichannels.


Automated identification of cell-type-specific genes in the mouse brain by image computing of expression patterns.
Differential gene expression patterns in cells of the mammalian brain result in the morphological, connectional, and functional diversity of cells. A wide variety of studies have shown that certain genes are expressed only in specific cell-types. Analysis of cell-type-specific gene expression patterns can provide insights into the relationship between genes, connectivity, brain regions, and cell-types. However, automated methods for identifying cell-type-specific genes are lacking to date. Here, we describe a set of computational methods for identifying cell-type-specific genes in the mouse brain by automated image computing of in situ hybridization (ISH) expression patterns. We applied invariant image feature descriptors to capture local gene expression information from cellular-resolution ISH images. We then built image-level representations by applying vector quantization on the image descriptors. We employed regularized learning methods for classifying genes specifically expressed in different brain cell-types. These methods can also rank image features based on their discriminative power. We used a data set of 2,872 genes from the Allen Brain Atlas in the experiments. Results showed that our methods are predictive of cell-type-specificity of genes. Our classifiers achieved AUC values of approximately 87% when the enrichment level is set to 20. In addition, we showed that the highly-ranked image features captured the relationship between cell-types. Overall, our results showed that automated image computing methods could potentially be used to identify cell-type-specific genes in the mouse brain.


Metabolic rate and muscle activation level when wearing state-of-the-art cold-weather protective clothing during level and inclined walking.
Use of cold-weather personal protective clothing (PPC) in cold climates is essential but can add metabolic cost to the wearer. This study measured the effect of wearing state-of-the-art PPC and personal protective equipment (PPE), with the possible effect of clothing layers and fit, on physiological responses including metabolic rate (MR) and muscle activation level. 19 male participants (80.2 ± 5.9 kg, 181.5 ± 5.1 cm) wore five different clothing ensembles during level (0°) and inclined (6°) walking. Compared to a base layer ensemble (388.7 ± 42.7 W/737.8 ± 57.9 W), wearing a 3-layer PPC ensemble (421.5 ± 44.7 W/811.7 ± 69.2 W) significantly increased MR, and adding PPE (458.3 ± 59.8 W/864.5 ± 71.2 W) further increased MR during level/inclined walking. Independent of the extra weight, adding a middle layer between base layer and outer clothing significantly increased MR during inclined walking only, and no effect of oversized outer clothing was measured.


[Enhancing the effectiveness of microbiological nutrient media through balancing their content by an experimental analytical method].
The possibility of successful use of the analitico-experimental method for the development and improvement of balanced microbiological growth media, economical in composition, has been shown. By this method a new variant of the semisynthetic medium for growing Bordetella pertussis vaccine strain has been obtained, thus making it possible to achieve a considerable increase in the yield of the biomass without decreasing the immunogenicity of the culture. The use of the balanced medium in the production of vaccines may alone give the overall economic effect totalling 11000 roubles per 10000 liters.


Development and validation of the ankle fracture outcome of rehabilitation measure (A-FORM).
Delphi panel and cohort study. To develop and refine a condition-specific, patient-reported outcome measure, the Ankle Fracture Outcome of Rehabilitation Measure (A-FORM), and to examine its psychometric properties, including factor structure, reliability, and validity, by assessing item fit with the Rasch model. To our knowledge, there is no patient-reported outcome measure specific to ankle fracture with a robust content foundation. A 2-stage research design was implemented. First, a Delphi panel that included patients and health professionals developed the items and refined the item wording. Second, a cohort study (n = 45) with 2 assessment points was conducted to permit preliminary maximum-likelihood exploratory factor analysis and Rasch analysis. The Delphi panel reached consensus on 53 potential items that were carried forward to the cohort phase. From the 2 time points, 81 questionnaires were completed and analyzed; 38 potential items were eliminated on account of greater than 10% missing data, factor loadings, and uniqueness. The 15 unidimensional items retained in the scale demonstrated appropriate person and item reliability after (and before) removal of 1 item (anxious about footwear) that had a higher-than-ideal outfit statistic (1.75). The "anxious about footwear" item was retained in the instrument, but only the 14 items with acceptable infit and outfit statistics (range, 0.5-1.5) were included in the summary score. This investigation developed and refined the A-FORM (Version 1.0). The A-FORM items demonstrated favorable psychometric properties and are suitable for conversion to a single summary score. Further studies utilizing the A-FORM instrument are warranted. J Orthop Sports Phys Ther 2014;44(7):488-499. Epub 22 May 2014. doi:10.2519/jospt.2014.4980.


Endothelial dysfunction and circulating microparticles from patients with obstructive sleep apnea.
Endothelial dysfunction is involved in vascular complications of obstructive sleep apnea (OSA). In this study, circulating microparticles (MPs) from patients with OSA-induced nocturnal desaturations were characterized and their effects on endothelial function were evaluated. Two age-matched groups of patients undergoing polysomnography for OSA were compared: 35 desaturators with a 3% oxyhemoglobin desaturation index (ODI) > or = 10 events per hour of sleep and 27 nondesaturators with ODI <10 events per hour. MPs were characterized by flow cytometry and then either used to treat in vitro human endothelial cells or to study endothelial function in mice. Circulating MPs did not differ between groups, but MPs from granulocytes and activated leukocytes (CD62L(+)) were found at higher levels in desaturators. In vitro, MPs from desaturators reduced endothelial nitric oxide (NO) production by enhancing phosphorylation of endothelial NO synthase at the site of inhibition and expression of caveolin-1. CD62L(+) MPs positively correlated with ODI. Endothelial NO production negatively correlated with both CD62L(+) MPs and ODI. MPs from desaturators increased expression of endothelial adhesion molecules including E-selectin, ICAM-1 and ITGA5, and cyclooxygenase 2. Moreover, injection of MPs from desaturators into mice impaired endothelium-dependent relaxation in aorta and flow-induced dilation in small mesenteric arteries. This study demonstrates an association between endothelial dysfunction and increased circulating levels of CD62L(+) MPs. This may initiate atherogenic processes in patients with OSA and severe nighttime hypoxia.


The association of chronic spontaneous urticaria (CSU) with anxiety and depression: a nationwide cohort study.
Chronic spontaneous urticaria (CSU) is a dermatological disease associated with significant impairment of overall quality of life as well as psychological distress. Previous studies have demonstrated significant comorbidity between CSU and a wide range of mental illnesses. In this study we aimed to focus on the association between CSU and anxiety and depression, using an optimized matched controlled design. A nationwide matched control study was conducted using the Clalit Health Services (CHS) database. The study included 12,539 CSU patients and 60,510 age and sex matched controls. Three multiple logistic regression models were conducted to assess the association between CSU and anxiety and depression, while adjusting for age, sex, socioeconomic status (SES), diabetes, obesity, hypertension, and smoking status. A higher frequency of anxiety and depression was found in CSU patients compared to that in controls (anxiety frequency of 9.6% vs. 5.7%, p < 0.001; depression frequency of 11% vs 7.9%, p < 0.001, respectively) after adjustment for demographic and clinical factors. The association of CSU with anxiety was the strongest in the 18-29 age group, and in the high SES group, while the association of CSU with depression was the highest in the 50-69 age group, and in the low SES group. Chronic spontaneous urticaria is associated with anxiety and depression. In light of the clinical implications of a comorbid mental disorder, dermatologists should consider employing mental health screening procedures, especially for patients from specific risk groups.


How safe do teenagers behave on Facebook? An observational study.
The substantial use of social network sites by teenagers has raised concerns about privacy and security. Previous research about behavior on social network sites was mostly based on surveys and interviews. Observational research overcomes problems inherent to this research method, for example social desirability. However, existing observational research mostly focuses on public profiles of young adults. Therefore, the current observation-study includes 1050 public and non-public Facebook-profiles of teenagers (13-18) to investigate (1) what kind of information teenagers post on their profile, (2) to what extent they protect this information using privacy-settings and (3) how much risky information they have on their profile. It was found that young people mostly post pictures, interests and some basic personal information on their profile. Some of them manage their privacy-settings as such that this information is reserved for friends' eyes only, but a lot of information is accessible on the friends-of-friends' pages. Although general risk scores are rather low, more detailed analyses show that teenagers nevertheless post a significant amount of risky information. Moreover, older teenagers and girls post more (risky) information while there are no differences in applying privacy settings. We found no differences in the Facebook behavior of teenagers enrolled in different education forms. Implications of these results are discussed.


Acute effects of verbal feedback on upper-body performance in elite athletes.
Argus, CK, Gill, ND, Keogh, JWL, and Hopkins, WG. Acute effects of verbal feedback on upper-body performance in elite athletes. J Strength Cond Res 25(12): 3282-3287, 2011-Improved training quality has the potential to enhance training adaptations. Previous research suggests that receiving feedback improves single-effort maximal strength and power tasks, but whether quality of a training session with repeated efforts can be improved remains unclear. The purpose of this investigation was to determine the effects of verbal feedback on upper-body performance in a resistance training session consisting of multiple sets and repetitions in well-trained athletes. Nine elite rugby union athletes were assessed using the bench throw exercise on 4 separate occasions each separated by 7 days. Each athlete completed 2 sessions consisting of 3 sets of 4 repetitions of the bench throw with feedback provided after each repetition and 2 identical sessions where no feedback was provided after each repetition. When feedback was received, there was a small increase of 1.8% (90% confidence limits, ±2.7%) and 1.3% (±0.7%) in mean peak power and velocity when averaged over the 3 sets. When individual sets were compared, there was a tendency toward the improvements in mean peak power being greater in the second and third sets. These results indicate that providing verbal feedback produced acute improvements in upper-body power output of well-trained athletes. The benefits of feedback may be greatest in the latter sets of training and could improve training quality and result in greater long-term adaptation.


The human papillomavirus E6 oncogene dysregulates the cell cycle and contributes to cervical carcinogenesis through two independent activities.
Cervical cancer is a leading cause of death due to cancer among women worldwide. Using transgenic mice to dissect the contributions of the human papillomavirus (HPV) 16 E6 and E7 oncogenes in cervical cancer, E7 was identified previously to be the dominant oncogene. Specifically, when treated with exogenous estrogen for 6 months, E7 transgenic mice developed cancer throughout the reproductive tract, but E6 transgenic mice did not. E6 contributed to carcinogenesis of the reproductive tract, as E6/E7 double transgenic mice treated for 6 months with estrogen developed larger cancers than E7 transgenic mice. In the current study, we investigated whether the E6 oncogene alone could cooperate with estrogen to induce cervical cancer after an extended estrogen treatment period of 9 months. We found that the E6 oncogene synergizes with estrogen to induce cervical cancer after 9 months, indicating that E6 has a weaker but detectable oncogenic potential in the reproductive tract compared with the E7 oncogene. Using transgenic mice that express mutant forms of HPV16 E6, we determined that the interactions of E6 with cellular alpha-helix and PDZ partners correlate with its ability to induce cervical carcinogenesis. In analyzing the tumors arising in E6 transgenic mice, we learned that E6 induces expression of the E2F-responsive genes, Mcm7 and cyclin E, in the absence of the E7 oncogene. E6 also prevented the expression of p16 in tumors of the reproductive tract through a mechanism mediated by the interaction of E6 with alpha-helix partners.


Choose a path.
Managed care, organizational downsizing, and reengineering create two different paths for nurses to choose: one of opportunity and one of victimization. APNQ interviews author Jane Schweitzer and features excerpts from her book Tears and Rage: The Nursing Crisis in America.


Photophysical properties of three coordinated copper(i) complexes bearing 1,10-phenanthroline and a monodentate phosphine ligand.
We report the synthesis and photophysical properties of Cu(i) complexes with 1,10-phenanthroline (phen) and monodentate phosphine ligands. Single crystal X-ray structural analysis revealed that these have three-coordinated trigonal planar geometries. We also found that one of them, [Cu(phen)(Johnphos)]BF4 (Johnphos = 2-(di-tert-butylphosphino)biphenyl), is considerably emissive both in solution and solid states. The emission maximum wavelength of the emission of the complex is 580 nm, and the lifetime of the emission is 2 μs in solution. Moreover, we have systematically investigated the photophysical and redox properties of four-coordinate complexes [Cu(NN)(P)2]+ in addition to three-coordinate complexes [Cu(NN)(P)]+. Charge transfer transitions play a key role in the photophysics of these complexes.


Utility of retention prediction model for investigation of peptide separation selectivity in reversed-phase liquid chromatography: impact of concentration of trifluoroacetic acid, column temperature, gradient slope and type of stationary phase.
Peptide separation selectivity in reversed-phase liquid chromatography was investigated using a training set of 165 peptides with a total of 1698 amino acid residues. Gradient separation was performed at selected chromatographic conditions, varying column temperature, gradient slope, ion-pairing reagent concentration, and type of stationary phase. The retention times for each set of experiments were utilized to calculate the amino acid retention coefficients using a published prediction model (Rapid Commun. Mass Spectrom. 2007, 21, 2813-2821). The calculated retention coefficients reflect the contribution of each type of amino acid residue to peptide retention at a given chromatographic condition. For example, the concentration of ion-pairing reagent (trifluoroacetic acid) had the strongest impact on the retention of peptides containing an increasing number of basic (charged) amino acids, such as arginine, lysine, and histidine, while the retention coefficients of other amino acids are minimally affected. Increasing the separation temperature resulted in a moderate decrease of amino acid retention coefficients with the exception of isoleucine, leucine, valine, and proline. This finding suggests that these residues enhance peptide retention at elevated temperature. Amino acid residue retention coefficients were also helpful to understand the impact of sorbent pore size (130 vs 300 A) on peptide retention selectivity. In addition we investigated the selectivity differences of various reversed-phase chromatographic sorbents. The trends suggested by calculated retention coefficients were confirmed using a set of synthetic peptides with specifically designed sequences.


Internet use patterns and Internet addiction in children and adolescents with obesity.
There are no data regarding the Internet addiction (IA) rates and patterns in youth with obesity. This study aimed to explore the prevalence and patterns of IA in children and adolescents with obesity. The relationship between IA and body mass index (BMI) was also investigated. Study includes 437 children and adolescents with age ranging from 8 to 17 years: 268 with obesity and 169 with healthy controls. The Internet addiction scale (IAS) form was administered to all participants. The obesity group also completed a personal information form including Internet usage habits and goals. Linear regression analysis was utilized to assess the contributions of Internet use habits and goals to BMI in the obesity group and IAS scores to BMI in both groups. A total of 24.6% of the obese children and adolescents were diagnosed with IA according to IAS, while 11.2% of healthy peers had IA (p < 0.05). The mean IAS scores for the obesity group and the control group were 53.71 ± 25.04 and 43.42 ± 17.36, respectively (p < 0.05). The IAS scores (t = 3.105) and spending time more than 21 h week-1 on the Internet (t = 3.262) were significantly associated with increased BMI in the obesity group (p < 0.05). Other Internet habits and goals were not associated with BMI (p > 0.05). The IAS scores (t = 8.719) were also found to be associated with increased BMI in the control group (p < 0.05). The present study suggests that obese children and adolescents were found to have higher IA rates than their healthy peers, and the results indicate an association between IA and BMI.


The membrane protein MiRP3 regulates Kv4.2 channels in a KChIP-dependent manner.
MiRP3, the single-span membrane protein encoded by KCNE4, is localized by immunofluorescence microscopy to the transverse tubules of murine cardiac myocytes. MiRP3 is found to co-localize with Kv4.2 subunits that contribute to cardiac transient outward potassium currents (I(to)). Whole-cell, voltage-clamp recordings of human MiRP3 and Kv4.2 expressed in a clonal cell line (tsA201) reveal MiRP3 to modulate Kv4.2 current activation, inactivation and recovery from inactivation. MiRP3 shifts the half-maximal voltage for activation (V(1/2)) approximately 20 mV and slows time to peak approximately 100%. In addition, MiRP3 slows inactivation approximately 100%, speeds recovery from inactivation approximately 30%, and enhances restored currents so they 'overshoot' baseline levels. The cytoplasmic accessory subunit KChIP2 also assembles with Kv4.2 in tsA201 cells to increase peak current, shift V(1/2) approximately 5 mV, slow time to peak approximately 10%, slow inactivation approximately 100%, and speed recovery from inactivation approximately 250% without overshoot. Simultaneous expression of all three subunits yields a biophysical profile unlike either accessory subunit alone, abolishes MiRP3-induced overshoot, and allows biochemical isolation of the ternary complex. Thus, regional heterogeneity in cardiac expression of MiRP3, Kv4.2 and KChIP2 in health and disease may establish the local attributes and magnitude of cardiac I(to).


TP53 drives invasion through expression of its Δ133p53β variant.
TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.


[Vitality and inner resources as relevant components of psychological well-being].
Vitality and inner resources as relevant components of psychological well-being. The multidimensional model of well-being, created by Carol Ryff, proposes the following dimensions to study psychological well-being (PSWB): self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth. One of the main criticisms aimed at this proposal is that it is based on excessive ethnocentrism in the operationalization of the PSWB construct linked to contemporary individual societies. Because of this, the first aim of this study was to extend the PSWB model with two dimensions: inner resources and vitality. Through a cross-validation approach, exploratory and confirmatory factor analyses were performed. The results showed better psychometric data in reliability and validity for the scales of the extended model of PSWB. To examine the PSWB construct in depth, we conducted a second study to analyze the relationship between the extended version of PSWB and subjective well-being models, and their predictive capacity of positive and negative human functioning, i.e., self-esteem and depression. Results showed complementation and compensation effects from both models that denote their close connection and singularity.


Cervical thymic cyst.
Thymic derivatives should be included in the differential diagnosis of cystic masses in the neck. A classification of thymic cysts is proposed: namely, true mixed or false. A thymic cyst may contain cholesterol crystals in the luminal fluid, cholesterol clefts, granulomas and lymphocytic follicles as well as Hassall corpuscles in the wall. Treatment consists of simple excision of the cyst and its tract. The thirty-fifth case of cervical thymic cyst in the English Literature is reported.


Analysis of the Arabidopsis superman allelic series and the interactions with other genes demonstrate developmental robustness and joint specification of male-female boundary, flower meristem termination and carpel compartmentalization.
SUPERMAN is a cadastral gene controlling the sexual boundary in the flower. The gene's functions and role in flower development and evolution have remained elusive. The analysis of a contrasting SUP allelic series (for which the names superman, superwoman and supersex have been coined) makes it possible to distinguish early vs. late regulatory processes at the flower meristem centre to which SUP is an important contributor. Their understanding is essential in further addressing evolutionary questions linking bisexuality and flower meristem homeostasis. Inter-allelic comparisons were carried out and SUP interactions with other boundary factors and flower meristem patterning and homeostasis regulators (such as CLV, WUS, PAN, CUC, KNU, AG, AP3/PI, CRC and SPT) have been evaluated at genetic, molecular, morphological and histological levels. Early SUP functions include mechanisms of male-female (sexual) boundary specification, flower mersitem termination and control of stamen number. A SUP-dependent flower meristem termination pathway is identified and analysed. Late SUP functions play a role in organ morphogenesis by controlling intra-whorl organ separation and carpel medial region formation. By integrating early and late SUP functions, and by analyzing in one single experiment a series of SUP genetic interactions, the concept of meristematic 'transference' (cascade) - a regulatory bridging process redundantly and sequentially co-ordinating the triggering and completion of flower meristem termination, and carpel margin meristem and placenta patterning - is proposed. Taken together, the results strongly support the view that SUP(-type) function(s) have been instrumental in resolving male/female gradients into sharp male and female identities (whorls, organs) and in enforcing flower homeostasis during evolution. This has probably been achieved by incorporating the meristem patterning system of the floral axis into the female/carpel programme.


Signatures of founder effects, admixture, and selection in the Ashkenazi Jewish population.
The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate, yet it is still unclear how population bottlenecks, admixture, or positive selection contribute to its genetic structure. Here we analyzed a large AJ cohort and found higher linkage disequilibrium (LD) and identity-by-descent relative to Europeans, as expected for an isolate. However, paradoxically we also found higher genetic diversity, a sign of an older or more admixed population but not of a long-term isolate. Recent reports have reaffirmed that the AJ population has a common Middle Eastern origin with other Jewish Diaspora populations, but also suggest that the AJ population, compared with other Jews, has had the most European admixture. Our analysis indeed revealed higher European admixture than predicted from previous Y-chromosome analyses. Moreover, we also show that admixture directly correlates with high LD, suggesting that admixture has increased both genetic diversity and LD in the AJ population. Additionally, we applied extended haplotype tests to determine whether positive selection can account for the level of AJ-prevalent diseases. We identified genomic regions under selection that account for lactose and alcohol tolerance, and although we found evidence for positive selection at some AJ-prevalent disease loci, the higher incidence of the majority of these diseases is likely the result of genetic drift following a bottleneck. Thus, the AJ population shows evidence of past founding events; however, admixture and selection have also strongly influenced its current genetic makeup.


Hydrologic conditions describe West Nile virus risk in Colorado.
We examine the relationship between hydrologic variability and the incidence of human disease associated with West Nile virus (WNV; family Flaviviridae, genus Flavivirus) infection (hereafter termed "human WN cases") in Colorado from 2002 to 2007. We find that local hydrologic conditions, as simulated by the Mosaic hydrology model, are associated with differences in human WN cases. In Colorado's eastern plains, wetter spring conditions and drier summer conditions predict human WN cases. In Colorado's western mountains, drier spring and summer conditions weakly predict human WN cases. These findings support two working hypotheses: (1) wet spring conditions increase the abundance of Culex tarsalis vectors in the plains, and (2) dry summer conditions, and respondent irrigational practices during such droughts, favor Cx. pipiens and Cx. tarsalis abundance throughout Colorado. Both of these processes potentially increase the local vector-to-host ratio, favoring WNV amplification among competent avian hosts and bridging to humans.


Nanoparticles-Based Treatment for Bone Metastasis.
Bone is the principal site of metastasis for many carcinomas, including prostate. Once bone metastases are established, the chances of survival dramatically drop. Bone metastases place patients at increased risk of skeletal-related events, including pathologic fractures, bone pain and hypercalcemia. Indeed, skeletal metastases represent the prevalent cause of morbidity and mortality for many tumors. They are the result of interactions among tumour cells, bone marrow environment and bone cells (vicious cycle). In the last few years many efforts were undertaken to identify new therapeutic approaches for bone metastasis. Current therapies target the several players of bone vicious cycle. However many adverse effects are associated with these treatments. This review will focus on the new emerging sector of nanomedicine, that could be important to identify more specific and safe treatments for bone metastasis.


A new probe for the diagnosis of myotonic muscular dystrophy.
Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM gene region, chromosome 19 libraries were constructed and screened for restriction fragment length polymorphisms tightly linked to DM. A genomic clone, LDR152 (D19S19), was isolated that is tightly linked to DM; recombination fraction = 0.0 (95% confidence limits 0.0-0.03); lod score, 15.4.


Translation of ODC mRNA and polyamine transport are suppressed in ras-transformed CREF cells by depleting translation initiation factor 4E.
Rapid tumor growth and metastasis require increased polyamine metabolism, which is coordinately regulated by ornithine decarboxylase (ODC) and the polyamine transporter. Both activities are stimulated by ras signalling and are dependent upon protein biosynthesis. T24ras oncogene expression in rat embryo fibroblasts (CREFT24) induces cellular transformation and malignancy, in part, by stimulating the rate-limiting translation initiation factor, eIF-4E. CREFT24 expressing antisense RNA to eIF-4E (AS4E) have markedly decreased tumor growth rates and metastatic capacity, without altered monolayer growth rates. Herein, we demonstrate that in AS4E, ODC is translationally suppressed resulting in decreased ODC activity. Additionally, exogenous polyamine uptake is suppressed in AS4E cells indicating that AS4E can neither generate nor import the polyamines necessary to support rapid tumor growth. These data provide evidence that eIF-4E is the link between ras-induced malignancy and increased polyamine metabolism and support the hypothesis that eIF-4E plays a pivotal role in mediating ras-induced malignancy.


Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture.
Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture. However, their mechanisms of action may vary, as demonstrated by (1) differences in the morphological changes produced by these compounds; (2) varied responses to these drugs with respect to toxicity kinetics; and (3) respective rates of cell proliferation, DNA synthesis, and mitotic index. We studied the effects of acetaminophen on relative cell number further. Evidence is presented that acetaminophen induced cell death by an apoptotic mechanism after a brief burst of mitosis in which cell numbers increased transiently, followed by a reduction in cell number and an increase in DNA fragmentation, as evidenced by terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using cultures of adult human brain and embryonic rat brain, we demonstrated that glioma cells were several-fold more sensitive to acetaminophen than normal brain cells in culture. Finally, subtoxic doses of acetaminophen increased the sensitivity of the human glioma cells in culture to ionizing radiation. Taken together, these results suggest that acetaminophen may prove to be a useful therapeutic agent in the treatment of human brain tumors.


Randomised trial of personalised computer based information for patients with schizophrenia.
To compare use, effect, and cost of personalised computer education with community psychiatric nurse education for patients with schizophrenia. Randomised trial of three interventions. Modelling of costs of alternatives. 112 patients with schizophrenia in contact with community services; 67 completed the intervention. Three interventions of five educational sessions: (a) computer intervention combining information from patient's medical record with general information about schizophrenia; (b) sessions with a community psychiatric nurse; (c) "combination" (first and last sessions with nurse and remainder with computer). Patients' attendance, opinions, change in knowledge, and psychological state; costs of interventions and patients' use of NHS community services; modelling of costs for these three, and alternative, interventions. Rates of completion of intervention did not differ significantly (71% for combination intervention, 61% for computer only, 46% for nurse only). Computer sessions were shorter than sessions with nurse (14 minutes v 60 minutes). More patients given nurse based education thought the information relevant. Of 20 patients in combination group, 13 preferred the sessions with the nurse and seven preferred the computer. There were no significant differences between groups in psychological outcomes. Because of the need to transport patients to the computer for their sessions, there was no difference between interventions in costs, but computer sessions combined with other patient contacts would be substantially cheaper. The computer based patient education offered no advantage over sessions with a community psychiatric nurse. Investigation of computer use combined with other health service contacts would be worth while.


Effect of smoking on the clinical progression of HIV-1 infection.
Cigarette smoking as a risk factor in progression of HIV-1 disease was investigated in the Multicenter AIDS Cohort Study of homosexual men. Longitudinal data for T-cell subsets, HIV-related clinical symptoms, smoking behavior, and AIDS medication use were collected semiannually from 2,499 HIV-1-seropositive men for up to 9 years. Survival methods, including Kaplan-Meier analysis and multivariate Cox regression models, were used to assess the effect of cigarette smoking on development of Pneumocystis carinii pneumonia (PCP), AIDS, death, and self-reported oral thrush. After adjustment for CD4+ lymphocyte count and use of antiretroviral and anti-PCP medications, smoking was not significantly associated with progression to PCP, AIDS, or death in either the HIV-seroprevalent or-seroincident cohort members. Among men who had baseline CD4+ cell counts > 200/microliter, smoking was associated with a 40% increase in the hazard of oral thrush (p < or = 0.01). These data indicate that cigarette smoking does not have a major effect on the progression of HIV-1 infection to AIDS or death but may affect the incidence of oral thrush.


The application and relevance of ex vivo culture systems for assessment of IBD treatment in murine models of colitis.
The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Galphai2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Galphai2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1beta, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.


Immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken homologous integrin beta3.
The breaking of immune tolerance against angiogenesis-associated molecules should be a useful approach for cancer therapy by active immunity. We used chicken integrin beta3 as a model antigen to explore the feasibility of immunogene therapy of the tumors with a vaccine based on a single xenogeneic homologous gene, targeting the molecules associated with angiogenesis. To test this concept we constructed a plasmid DNA encoding the ligand-binding domain of chicken integrin beta3 (P-BD-C) and control vectors. We found that immunogene therapy of tumors with a vaccine based on the ligand-binding domain of chicken integrin beta3 (P-BD-C) was effective in both protective and therapeutic anti-tumor immunity in several tumor models in mice. Autoantibodies against integrin beta3 in sera of mice immunized with the ligand-binding domain of chicken integrin beta3 could be found by Western blot analysis and ELISA assay. The purified immunoglobulins were effective in the inhibition of endothelial cell proliferation in vitro, and in anti-tumor activity as well as in the inhibition of angiogenesis by adoptive transfer in vivo. The anti-tumor activity and the production of integrin beta3-specific autoantibodies (manifested by significantly elevated Ig G1 and Ig G2b) could be abrogated by the depletion of CD4+ T lymphocytes. These observations may provide a vaccine strategy for cancer therapy through the induction of the autoimmunity against the molecules associated with tumor growth in a cross-reaction with a single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.


Clinical characteristics of 134 convalescent patients with COVID-19 in Guizhou, China.
Previous studies have focused on the clinical characteristics of hospitalized patients with the novel 2019 coronavirus disease (COVID-19). Limited data are available for convalescent patients. This study aimed to evaluate the clinical characteristics of discharged COVID-19 patients. In this retrospective study, we extracted data for 134 convalescent patients with COVID-19 in Guizhou Provincial Staff Hospital from February 15 to March 31, 2020. Cases were analyzed on the basis of demographic, clinical, and laboratory data as well as radiological features. Of 134 convalescent patients with COVID-19, 19 (14.2%) were severe cases, while 115 (85.8%) were non-severe cases. The median patient age was 33 years (IQR, 21.8 to 46.3), and the cohort included 69 men and 65 women. Compared with non-severe cases, severe patients were older and had more chronic comorbidities, especially hypertension, diabetes, and thyroid disease (P < 0.05). Leukopenia was present in 32.1% of the convalescent patients and lymphocytopenia was present in 6.7%, both of which were more common in severe patients. 48 (35.8%) of discharged patients had elevated levels of alanine aminotransferase, which was more common in adults than in children (40.2% vs 13.6%, P = 0.018). A normal chest CT was found in 61 (45.5%) patients during rehabilitation. Severe patients had more ground-glass opacity, bilateral patchy shadowing, and fibrosis. No significant differences were observed in the positive rate of IgG and/or IgM antibodies between severe and non-severe patients. Leukopenia, lymphopenia, ground-glass opacity, and fibrosis are common in discharged severe COVID-19 patients, and liver injury is common in discharged adult patients. We suggest physicians develop follow-up treatment plans based on the different clinical characteristics of convalescent patients.


Impaired communication. A descriptive study.
This article presents data from a descriptive study, validating etiologies and defining characteristics for the nursing diagnosis of impaired communication. Implications for nursing research, practice, and education are discussed.


Comparison between monitored anesthesia care and general anesthesia in patients undergoing device closure of atrial septal defect.
Percutaneous atrial septal defect (ASD) device closure is usually performed under general anesthesia (GA) because it can ensure protection of the airway from the effects of insertion of the transesophageal echocardiogram probe insertion. However, recent studies have suggested that this procedure can be performed safely under deep sedation also. Thus, we compared the efficacy of using monitored anesthesia care (MAC) with deep sedation versus GA to perform this procedure and the post-procedural outcomes and incidence of complications associated with these two methods of anesthesia. We retrospectively analyzed cases involving 311 patients who underwent ASD device closures from January 2011 to December 2015. The demographics, laboratory values, echocardiographic findings, and intraoperative data of these patients were assessed. GA was induced with a continuous infusion of propofol and remifentanil using a target control infusion pump. MAC with deep sedation was performed by using a continuous infusion of dexmedetomidine and remifentanil. The primary outcome of the study was the overall complication rate that included the incidence of aspiration pneumonia, sore throat, dysphagia, vocal cord palsy, neurologic complication, device-related complications, and other minor complications during the procedure; and the secondary outcomes were the turnover time, procedure time, and duration of hospital stay. No significant differences were observed in the complication rate and length of the hospital stay between the MAC group and the GA group. However, the turnover time was significantly longer in the GA group than in the MAC group (56.2±13.3 vs. 51.0±15.4 min, P=0.004). MAC under deep sedation is an effective and safe anesthetic option comparable to GA for performing percutaneous ASD device closures.


Parallel genome-wide screens identify synthetic viable interactions between the BLM helicase complex and Fanconi anemia.
Maintenance of genome integrity via repair of DNA damage is a key biological process required to suppress diseases, including Fanconi anemia (FA). We generated loss-of-function human haploid cells for FA complementation group C (FANCC), a gene encoding a component of the FA core complex, and used genome-wide CRISPR libraries as well as insertional mutagenesis to identify synthetic viable (genetic suppressor) interactions for FA. Here we show that loss of the BLM helicase complex suppresses FANCC phenotypes and we confirm this interaction in cells deficient for FA complementation group I and D2 (FANCI and FANCD2) that function as part of the FA I-D2 complex, indicating that this interaction is not limited to the FA core complex, hence demonstrating that systematic genome-wide screening approaches can be used to reveal genetic viable interactions for DNA repair defects.


The Palliative Performance Scale Predicts Three- and Six-Month Survival in Older Adult Patients Admitted to the Hospital through the Emergency Department.
There is often little information on long-term prognosis available for Emergency Medicine physicians when decisions on admission, treatment, or consultations are being made for patients. There is a new focus to understand if palliative support should be offered in the emergency department (ED) and the Palliative Performance Scale (PPS), a screening tool used in other settings in palliative care, has been little used in the ED. The goal of this study was to assess the prognostic value of the PPS in predicting three- and six-month survival in patients admitted through the ED. A prospective cohort study. We evaluated 123 patients over the age of 55 years admitted through the ED of a tertiary care hospital in New England in November and December of 2013. Each patient's PPS score was evaluated initially in the ED, with follow-up assessments of PPS and survival at three and six months. Baseline PPS for the 123 patients was 72 ± 22. Information on 72 subjects (58.5%) at three months was 60 assessed and 12 deaths. Information on 47 subjects (38.2%) at six months was 26 assessed and 21 deaths (nine further deaths from three months). There were no significant differences in the demographics or PPS score in those evaluated and those lost to follow-up at three or six months. Patients with an initial PPS score of 30 or less had 14% survival at six months. In this small preliminary study, The PPS score may predict survival in patients admitted to the hospital through the ED. The ease of use holds promise that use of the PPS in the ED may help ED physicians predict survival and plan for better disposition, advocate for patient wishes, and initiate palliative care consultation.


Cerebrovascular adaptation to prolonged halothane anesthesia is not related to cerebrospinal fluid pH.
The purpose of this study was to evaluate the time-dependent effects of steady-state halothane anesthesia on cerebrovascular variables and their relationship to cerebrospinal fluid (CSF) pH. Eight mongrel dogs underwent a 7-h anesthetic, receiving halothane (1.0% end-tidal), O2 (50%), and balance N2. Cerebral blood flow (CBF) was measured by injection of radioactively labeled microspheres. CSF was sampled from the cisterna magna and cerebral venous blood from the superior sagittal sinus. Measurements were made at 2 h postinduction and hourly for 5 h thereafter. Total CBF at 2 h postinduction was 148 +/- 36 ml X 100 g-1 X min-1 and showed a significant decay over the subsequent 5 h to 70 +/- 3 ml X 100 g-1 X min-1. Regional variations were noted, those areas with highest initial flows showing both a greater relative and absolute reduction in flow. Cerebral vascular resistance increased significantly (39%), as did mean arterial pressure (15%). CSF pH values remained constant throughout the experiment. Arterial blood acid-base physiology was also unchanged. Sagittal sinus PCO2 increased significantly from 43 +/- 4 to 49 +/- 3 mmHg while sagittal sinus pH decreased from 7.31 +/- 0.01 to 7.37 +/- 0.02, consistent with the normalization of CBF. Cerebral metabolic oxygen consumption did not change significantly. The authors conclude that time-dependent changes in cerebrovascular parameters under prolonged steady-state halothane anesthesia are not due to changes in CSF pH and thus brain extracellular acid-base chemistry.


PET111, a Saccharomyces cerevisiae nuclear gene required for translation of the mitochondrial mRNA encoding cytochrome c oxidase subunit II.
Mutations in the nuclear gene PET111 are recessive and specifically block accumulation of cytochrome c oxidase subunit II (coxII), the product of a mitochondrial gene. However, the coxII mRNA is present in pet111 mutants at a level approximately one-third that of wild type. The simplest explanation for this phenotype is that PET111 is required for translation of the coxII mRNA. The reduced steady-state level of this mRNA is probably a secondary effect, caused by increased degradation of the untranslated transcript. Mitochondrial suppressors of pet111, carried on rho-mtDNAs, bypass the requirement for PET111 in coxII translation. Three suppressors are fusions between the coxII structural gene and other mitochondrial genes, that encode chimeric proteins consisting of the N-terminal portions of other mitochondrially coded proteins fused to the coxII precursor protein. When present together with rho+ mtDNA in a heteroplasmic state, these suppressors allow coxII synthesis in pet111 mutants. Thus in wild type, the PET111 product, or something under its control, probably acts at a site coded in the proximal portion of the gene for coxII to promote translation of the mRNA. PET111 was isolated by molecular cloning and genetically mapped to a position approximately midway between rna1 and SUP8 on chromosome XIII.


A new method and device of aligning patient setup lasers in radiation therapy.
The aim of this study is to develop a new method to align the patient setup lasers in a radiation therapy treatment room and examine its validity and efficiency. The new laser alignment method is realized by a device composed of both a metallic base plate and a few acrylic transparent plates. Except one, every plate has either a crosshair line (CHL) or a single vertical line that is used for alignment. Two holders for radiochromic film insertion are prepared in the device to find a radiation isocenter. The right laser positions can be found optically by matching the shadows of all the CHLs in the gantry head and the device. The reproducibility, accuracy, and efficiency of laser alignment and the dependency on the position error of the light source were evaluated by comparing the means and the standard deviations of the measured laser positions. After the optical alignment of the lasers, the radiation isocenter was found by the gantry and collimator star shots, and then the lasers were translated parallel to the isocenter. In the laser position reproducibility test, the mean and standard deviation on the wall of treatment room were 32.3 ± 0.93 mm for the new method whereas they were 33.4 ± 1.49 mm for the conventional method. The mean alignment accuracy was 1.4 mm for the new method, and 2.1 mm for the conventional method on the walls. In the test of the dependency on the light source position error, the mean laser position was shifted just by a similar amount of the shift of the light source in the new method, but it was greatly magnified in the conventional method. In this study, a new laser alignment method was devised and evaluated successfully. The new method provided more accurate, more reproducible, and faster alignment of the lasers than the conventional method.


Epoxyazadiradione Purified from the Azadirachta indica Seed Induced Mitochondrial Apoptosis and Inhibition of NFκB Nuclear Translocation in Human Cervical Cancer Cells.
Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta indica) plant. In the present study, we have purified EAD from Neem seed and studied its anticancer potential in human cervical cancer (HeLa) cells. Cell proliferation inhibition studies indicated that the GI50 value of EAD is 7.5 ± 0.0092 μM in HeLa cells, whereas up to 50 μM concentrations EAD did not affect the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth of both HeLa and H9C2 cells with a GI50 value of 2.92 ± 1.192 and 4.22 ± 1.568 μM, respectively. Nuclear DNA fragmentation, cell membrane blebbing, phosphatidylserine translocation, upregulation of Bax, caspase 3 activity and poly (ADP ribose) polymerase cleavage and downregulation of BCl2 in HeLa cells on treatment with EAD indicated the apoptotic cell death. Increase in caspase 9 activity and release of active cytochrome c to the cytoplasm on treatment with EAD confirmed that the apoptosis was mediated through the mitochondrial pathway. Epoxyazadiradione also inhibited the nuclear translocation of nuclear factor κB in HeLa cells. Thus, our studies demonstrated EAD as a potent and safe chemotherapeutic agent when compared with the standard drug cisplatin that is toxic to both cancer and normal cells equally. Copyright © 2017 John Wiley & Sons, Ltd.


A clinical and experimental study of adult hereditary spherocytosis in the Chinese population.
Hereditary spherocytosis (HS) is often misdiagnosed due to lack of specific diagnostic methods. Our study summarized clinical characteristics and described the diagnostic workflow for mild and moderate HS in Chinese individuals, using data from 20 adults, 8 of whom presented a familial history for HS. We used scanning electron microscopy (SEM) to diagnose HS. We observed reduced eosin maleimide fluorescence activity (5.50 mean channel fluorescence (MCF) units) in the 10 cases of HS, which differed significantly when compared with 10 normal adults (15.50 units), iron deficiency anemia (15.50 MCF units), and megaloblastic anemia (12.00 MCF units) values (P < .05). Next generation sequencing results revealed that 9 out of 10 patients were found to have mutations in the spectrin alpha chain (SPTB), anchor protein (ANK1), and SLC4A1 genes. These mutations were not reported in the Human Gene Mutation Database (HGMD), 1000 human genome, ExAC, and dbSNP147 databases. Splenectomy proved to be beneficial in alleviating HS symptoms in 10 cases. It was found that for the diagnosis of HS, SEM and next generation gene sequencing method proved to be more ideal than red blood cell membrane protein analysis using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting.


Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33.
One of the contributors to atherogenesis is enzymatically modified LDL (eLDL). eLDL was detected in all stages of aortic valve sclerosis and was demonstrated to trigger the activation of p38 mitogen-activated protein kinase (p38 MAPK), which has been identified as a pro-inflammatory protein in atherosclerosis. In this study, we investigated the influence of eLDL on IL-6 and IL-33 induction, and also the impact of eLDL on calcification in aortic valve stenosis (AS). eLDL upregulated phosphate-induced calcification in valvular interstitial cells (VICs)/myofibroblasts isolated from diseased aortic valves, as demonstrated by alizarin red staining. Functional studies demonstrated activation of p38 MAPK as well as an altered gene expression of osteogenic genes known to be involved in vascular calcification. In parallel with the activation of p38 MAPK, eLDL also induced upregulation of the cytokines IL-6 and IL-33. The results suggest a pro-calcifying role of eLDL in AS via induction of IL-6 and IL-33.


The ethics of conducting a co-operative inquiry with vulnerable people.
Mental health services users have been calling for greater participation in clinical research. Participation in this context means research 'with' rather than 'on' groups of people. Conducting a co-operative inquiry involving the participation of vulnerable individuals as co-researchers, in particular those with a history of mental health problems, places an obligation on researchers to articulate and justify sound ethical procedures. The aim of this paper is to consider how the ethical issues encountered when conducting participative research with vulnerable people can be addressed in the implementation of a co-operative inquiry with users of mental health services. The study was based on personal reflection and a critical review of associated literature obtained from a database search using Boolean logic. The findings, presented under the headings of the four prima facie moral principles, suggest the need for researchers using participative approaches to demonstrate the humanistic attributes required for engaging and working with people over a period of time. These include building and maintaining trusting relationships, assessing competence to participate, managing interpersonal and group dynamics and making complex collaborative decisions about participants' continued participation in a study. When using a co-operative inquiry approach involving vulnerable individuals, researchers need to demonstrate clearly how a balance between autonomy and paternalism will be achieved, how risks will be anticipated and managed and how fairness will be maintained throughout all procedures. Researchers using participative approaches need to have developed a level of personal insight and self-awareness through access to supervision which focuses on sources of unintended manipulation and interpersonal dynamics that may arise at the inception of a study and throughout its course. Researchers and ethics committees have a shared responsibility to ensure that vulnerable people are appropriately engaged to maintain the advancement of user knowledge which informs nursing practice.


Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappaB and phosphatidylinositol 3-kinase/Akt pathway.
Ultraviolet (UV) radiation can cause inflammatory changes and may further contribute to skin carcinogenesis. Anthocyanins are known to be powerful antioxidants that help protect plants from UV damage. Recently, we isolated anthocyanins from black soybean [Glycine max (L.) Merr] seed coats. Thus, we investigated the protective effect of anthocyanins from black soybean seed coats on UVB radiation-induced inflammatory responses and the molecular mechanism responsible for regulation of apoptosis and inflammatory responses. Anthocyanins inhibited UVB-induced cylooxygenase-2 (COX-2) and PGE 2 production through a nuclear factor-kappaB-dependent pathway and regulation of the PI3 kinase/Akt pathway activated by UVB in a human keratinocyte cell line, HaCaT. Topical application of anthocyanins prior to UVB irradiation of hairless mice also inhibited induction of COX-2 and PGE 2. In conclusion, it is suggested that anthocyanins from the seed coat of black soybeans can be used as a useful drug to modulate oxidative disorders including UVB-induced inflammation.


S2k guideline diagnosis, prevention, and therapy of hand eczema.
The consensus-based guideline "Diagnosis, prevention, and treatment of hand eczema (HE)" provides concrete instructions and recommendations for diagnosis, prevention, and therapy of HE based on an evidence- and consensus-based approach. The guideline was created based on the German guideline "Management von Handekzemen" from 2009 and the current guideline of the European Society of Contact Dermatitis (ESCD) "Guidelines for diagnosis, prevention, and treatment of hand eczema" from 2022. The general goal of the guideline is to provide dermatologists and allergologists in practice and clinics with an accepted, evidence-based decision-making tool for selecting and conducting suitable and sufficient therapy for patients with hand eczema. The guideline is based on two Cochrane reviews of therapeutic and preventive interventions for HE. The remaining chapters were mainly developed and consented based on non-systematic literature research by the expert group. The expert group consisted of members of allergological and occupational dermatological professional associations and working groups, a patient representative, and methodologists. The proposals for recommendations and key statements were consented by using a nominal group process during a consensus conference on September 15, 2022. The structured consensus-building process was professionally moderated. This guideline is valid until February 22, 2028.


Metabolic syndrome is directly associated with gamma glutamyl transpeptidase elevation in Japanese women.
This study aimed to determine whether metabolic syndrome is directly or indirectly, through fatty liver, associated with elevated gamma-glutamyl transpeptidase (GGT) levels in Japanese women. From 4 366 women who received their annual health check-up, 4 211 women were selected for analysis. All 4 211 women were negative for both hepatitis B surface antigen and antibody to hepatitis C virus. Clinical and biochemical variables were examined by using univariate and multivariate analysis. A raised GGT level (>68 IU/L) was seen in 258 (6.1%) of the 4 211 women. In univariate analysis, all variables examined (age, body mass index, blood pressure, hemoglobin concentration, fasting blood glucose, glycosylated hemoglobin A1c, cholesterol, triglyceride, and uric acid) were associated with the elevated GGT level, whereas in multivariate analysis, four variables (age > or =50 yr, hemoglobin > or =14 g/dL, triglyceride > or =150 mg/dL, and presence of diabetes) were significantly and independently associated with raised GGT level. Clinical variables predicting the presence of ultrasonographic evidence of fatty liver were also examined by multivariate analysis; four variables were associated with the presence of fatty liver: BMI > or =25 kg/m(2), hemoglobin > or =14 g/dL, triglyceride > or =150 mg/dL, and uric acid > or =7 mg/dL. There was no significant association between the raised GGT level and the presence of fatty liver. Hypertriglyceridemia was significantly and independently associated with both the raised GGT level and the presence of fatty liver. Metabolic syndrome seemed to be directly, not indirectly through fatty liver, associated with the raised GGT level in Japanese women.


The effect of an infertility diagnosis on treatment-related stresses.
The purpose of this study was to determine the effect of an infertility diagnosis on treatment-related stresses. One hundred infertile Chinese couples participated in this study. Three structured questionnaires were used to analyze the differences between husbands and wives. As a group wives appear to experience significantly more stress from infertility tests and treatment than their husbands, regardless of whether female infertility was present. Husbands with mixed or idiopathic infertility experienced less stress to infertility than husbands with only male infertility or female infertility. Wives with mixed or idiopathic infertility experienced less stress to infertility than wives with only a female infertility. Marital duration, time in treatment, and the number of AIH or IVF procedures were positively related to the wives' stress level, whereas only number of IVF procedures was positively related to the husbands' stress level. Interventions to enhance the infertility treatment experience are suggested.


Piceatannol enhances TRAIL-induced apoptosis in human leukemia THP-1 cells through Sp1- and ERK-dependent DR5 up-regulation.
Although piceatannol (PIC) is known to mediate anti-cancer, anti-inflammatory, and anti-oxidant activities, little is known about the mechanism of PIC in terms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. In this study, we examined whether combined treatment with PIC and TRAIL synergistically induces apoptosis in THP-1 leukemia cells. Results indicate that PIC substantially enhances TRAIL-induced cell death including DNA fragmentation and poly(ADP-ribose) polymerase cleavage. Consistent with TRAIL-induced apoptosis, PIC significantly increased the mRNA and protein expression levels of DR5, a death receptor of TRAIL. Further, PIC enhanced DR5 promoter activity via Sp1 activation. Interestingly, the DR5 chimera antibodies significantly suppressed PIC and TRAIL-mediated apoptosis. The inhibitor of ERK also decreased PIC and TRAIL-induced apoptosis by blocking DR5 expression. In conclusion, our results suggest that PIC sensitizes TRAIL-induced-apoptosis via Sp1- and ERK-dependent DR5 up-regulation.


Overcoming Individual Limitations Through Distributed Computation: Rational Information Accumulation in Multigenerational Populations.
Many of the computational problems people face are difficult to solve under the limited time and cognitive resources available to them. Overcoming these limitations through social interaction is one of the most distinctive features of human intelligence. In this paper, we show that information accumulation in multigenerational social networks can be produced by a form of distributed Bayesian inference that allows individuals to benefit from the experience of previous generations while expending little cognitive effort. In doing so, we provide a criterion for assessing the rationality of a population that extends traditional analyses of the rationality of individuals. We tested the predictions of this analysis in two highly controlled behavioral experiments where the social transmission structure closely matched the assumptions of our model. Participants made decisions on simple categorization tasks that relied on and contributed to accumulated knowledge. Success required these microsocieties to accumulate information distributed across people and time. Our findings illustrate how in certain settings, distributed computation at the group level can pool information and resources, allowing limited individuals to perform effectively on complex tasks.


The biomedical communications network.
The Biomedical Communications Network (BCN) is the embodiment of the plans of the National Library of Medicine to provide improved information, document, and education services to the health community. The BCN also will be the "core" public service network to ensure the most expeditious delivery of health information and education products to a selected public. As such, utilization of communications satellites as well as other more common forms of telecommunications are planned. The library component of the Network will provide decentralized library services to medical libraries, medical schools, hospitals, MEDLARS Centers, local medical centers and individual medical practitioners. These decentralized services will be provided through an information network with its hub at the Bethesda, Maryland site of the NLM. The NLM intends that the library services network be a controlled rather than a permissive system. This simply implies that participation and access to the services of the system will be determined by the NLM. Planning has already progressed to the point where services to be provided can be enumerated.


Image-guided 25-gauge needle biopsy for thoracic lesions: diagnostic feasibility and safety.
To report our experience regarding the feasibility and safety of 25-gauge needles for biopsy of thoracic lesions. Twenty-six patients with thoracic lesions, predominately pulmonary nodules, measuring 0.7-5.2 cm (mean, 1.6 cm) underwent biopsy with computed tomographic (n = 24), ultrasonographic (n = 1), or fluoroscopic (n = 1) guidance. Nineteen patients had severe chronic obstructive pulmonary disease (COPD), one had severe restrictive lung disease, and one had a coagulopathy; the other five patients had nonpulmonary primary tumors. Biopsy with an inner 25-gauge needle traversing an outer extrapleural coaxial cannula was performed in all patients. Cytologic quick staining was performed routinely to determine specimen adequacy and to establish a preliminary diagnosis. Complications, specimen adequacy, and need for larger specimens were evaluated. Adequate specimens (as determined by cytopathologists) were obtained in 24 (92%) of 26 patients, with a definitive diagnosis achieved in 23 (88%) patients during initial quick staining (17 malignant and six benign diagnoses). Two cases initially considered suspicious for malignancy were reclassified as benign (thymoma and histoplasmosis). At the request of cytopathologists, a larger needle was used to supplement the 25-gauge needle in six patients: In one patient, it provided further diagnostic information; in four, it did not; and in one, it confirmed non-Hodgkin lymphoma. Five patients developed a small pneumothorax (<10%) with use of the 25-gauge needle alone; one other patient, in whom larger needles were placed, received a radiologic chest catheter to evacuate the pneumothorax, thereby allowing the biopsy to continue. Image-guided 25-gauge needle biopsy is both feasible and safe.


Comparative study of the shear bond strength of various veneering materials on grade II commercially pure titanium.
To compare the shear bond strength of various veneering materials to grade II commercially pure titanium (CP-Ti). Thirty specimens of CP-Ti disc with 9 mm diameter and 10 mm height were divided into three experimental groups. Each group was bonded to heat-polymerized acrylic resin (Lucitone 199), porcelain (Triceram), and indirect composite (Sinfony) with 7 mm diameter and 2 mm height. For the control group (n=10), Lucitone 199 were applied on type IV gold alloy castings. All samples were thermocycled for 5000 cycles in 5-55℃ water. The maximum shear bond strength (MPa) was measured with a Universal Testing Machine. After the shear bond strength test, the failure mode was assessed with an optic microscope and a scanning electron microscope. Statistical analysis was carried out with a Kruskal-Wallis Test and Mann-Whitney Test. The mean shear bond strength and standard deviations for experimental groups were as follows: Ti-Lucitone 199 (12.11 ± 4.44 MPa); Ti-Triceram (11.09 ± 1.66 MPa); Ti-Sinfony (4.32 ± 0.64 MPa). All of these experimental groups showed lower shear bond strength than the control group (16.14 ± 1.89 MPa). However, there was no statistically significant difference between the Ti-Lucitone 199 group and the control group, and the Ti-Lucitone 199 group and the Ti-Triceram group. Most of the failure patterns in all experimental groups were adhesive failures. The shear bond strength of veneering materials such as heat-polymerized acrylic resin, porcelain, and indirect composite to CP-Ti was compatible to that of heatpolymerized acrylic resin to cast gold alloy.


Temporal dynamics and Leishmania infantum infection prevalence of Phlebotomus perniciosus (Diptera, Phlebotominae) in highly endemic areas of visceral leishmaniasis in Tunisia.
Phlebotomus perniciosus is one of the major vectors of Leishmania infantum in the Mediterranean basin. The aim of this work was (i) to provide information about abundance and temporal dynamics of this Larroussius species in a hot spot area of visceral leishmaniasis in Tunisia, (ii) to detect L. infantum DNA in wild caught female sandflies and (iii) to measure Phlebotomus perniciosus infection rate throughout the active season. Sandflies were collected monthly during one year using CDC miniature light-traps in house and in animal shelters. Male specimens were identified at species level according to morphological characters. Female specimens were conserved individually for molecular study. Leishmania infection was tested by kinetoplast DNA real-time PCR and ITS-1 PCR-sequencing. Subsequent sandfly species identification of infected specimens was done by mitochondrial cytochrome b sequencing. In one year period, overall 4,441 specimens (2230 males and 2211 females) were collected. Sandfly activity started in end-April and ended in early-November. Mean sandfly density in house was significantly lower than in animal shelters (51 ± 50 versus 504 ± 460 sandflies /CDC night, p<0.05). However, a higher proportion of females was found in house (58.4% versus 49.2%, p<0.001). Based on species identification of male specimens, Phlebotomus perniciosus was the dominant species (56% of the whole male sandfly fauna, p<0.0001). It showed two peaks of density in the active season, a sharp one in early May and a higher long lasting one from end-July to end-September. DNA was extracted from 190 female specimens randomly sampled and corresponding to 96 specimens from house and 94 from animal shelters. Twenty four female sandfly were infected by Leishmania infantum. All infected specimens were recognized as Phlebotomus perniciosus. Leishmania infantum infection rate in female sandflies was 2.3 fold higher in house than in animal shelters (17.7% versus 7.4%, p<0.05). In house, estimated number of infected specimens was the highest at the end of the active season. Abundance, dynamics of density and Leishmania infantum infection prevalence of Phlebotomus perniciosus in Tunisian hot spot of visceral leishmaniasis highlight the major role of this Phlebotominae species in L. infantum transmission.


Adsorption of Sodium Ions by Exopolysaccharides from Pseudomonas simiae MHR6 and Its Improvement of Na+/K+ Homeostasis in Maize under Salt Stress.
Exopolysaccharides (EPS) are macromolecular substances with environmentally beneficial properties. At present, some reports have focused on the effects of EPS on plants salt stress; however, few studies have carried out a deeper characterization of the EPS components involved in Na+ binding. We investigated the mechanism of Na+ adsorption by Pseudomonas simiae MHR6 EPS and the regulation of ion homeostasis in maize under salt stress. The results showed that NaCl at 6% significantly inhibited MHR6 growth but enhanced EPS secretion. The chemical composition of the EPS varied in response to an increased NaCl concentration, and the proportion of polysaccharides was consistently higher than that of proteins. The highest Na+ adsorption was observed for 6% NaCl. The FTIR, SEM, and EDX results further indicated that EPS effectively biosorbed Na+. Furthermore, adding EPS improved Na+/K+ homeostasis in maize under salt stress. These results suggest that MHR6 EPS has potential for future development and utilization as a plant growth biostimulant in saline-alkali land.


Defining a Cancer Dependency Map.
Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets.


Risk factors affecting oncological outcomes of surgical resections for middle and lower rectal cancer.
In our study, it was aimed to evaluate the factors affecting oncological outcomes in resections for rectal cancer. Between January 2010 and December 2014, patients with rectal tumors were analyzed retrospectively. Demographic and pathological data and oncological outcomes were analyzed as disease-free survival, overall survival, and local recurrence. A total of 158 patients' data were obtained. Median age was 60 (22-83). Fifty-three patients were older than 65 years of age (138). Ninety-five (60%) patients were males, and 63 (40%) were females. Eighty patients (50.4%) had middle rectal, and 78 (49.6) patients had lower rectal cancer. There was no effect of tumor localization on oncological outcomes. Univariate analyses revealed the effects of age (p= 0.003), operation type (p <0.001), nodal status (p <0.001), malignant lymph node ratio (p <0.001), stage of the disease (p <0.001), distal resection margin (p= 0.047), perineural invasion (p <0.001), lymphatic invasion (p <0.001), venous-vascular invasion (p= 0.025), local recurrence (p <0.001) and distant metastasis (p <0.001) on overall survival rates. Univariate analyses revealed the effects of nodal status (p= 0.007), malignant lymph node ratio (p= 0.005), stage of the disease (p= 0.008), perineural invasion (p= 0.004) and venous-vascular invasion (p <0.001) on disease-free survival rates. Univariate analyses revealed the effects of anastomotic leak (p= 0.015) and venous-vascular invasion (p= 0.001) on local recurrence rates. Older age, advanced nodal status, and distant metastasis were detected as independent risk factors for overall survival. Perineural and venous-vascular invasion were detected as independent risk factors for disease-free survival. Lastly, anastomotic leak and venous-vascular invasion were detected as independent risk factors for local recurrence.


Isomerization between 2-(2,4-dihydroxystyryl)-1-benzopyrylium and 7-hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium.
2-Phenyl-1-benzopyrylium (flavylium) and 2-styryl-1-benzopyrylium (styrylflavylium) cations establish in aqueous solution a series of equilibria defining chemical reaction networks responsive to several stimuli (pH, light, redox potential). Control over the mole fraction distribution of species by applying the appropiate stimuli defines a horizontal approach to supramolecular chemistry, in agreement with the customary bottom-up approach toward complex systems. In this work, we designed an asymmetric styrylchalcone able to cyclize in two different ways, producing two isomeric styrylflavylium cations whose chemical reaction networks are thus interconnected. The chemical reaction networks of 2-(2,4-dihydroxystyryl)-1-benzopyrylium (AH(+)) and 7-hydroxy-2-(4-hydroxystyryl)-1-benzopyrylium (AH(+)(iso)) comprise the usual species observed in flavylium-derived networks, in this case, the styryl derivatives of quinoidal bases, hemiketals, and chalcones. The thermodynamics and kinetics of the crossed networks were characterized by the use of UV-vis absorption and NMR spectroscopy as well as time-resolved pH jumps followed by stopped-flow. The two styrylflavylium cations are connected (isomerize) through two alternative intermediates, the asymmetric trans-styrylchalcone (Ct) and a spiropyran-type intermediate (SP). At pH = 1, AH(+) slowly evolves (k(obs) ≈ 10(-5) s(-1)) to a mixture containing 62% AH(+)(iso) through the Ct intermediate, while at pH = 5, the SP intermediate is involved. The observed rate constants for the conversion of the styrylflavylim cations into equilibrium mixtures containing essentially Ct follow a pH-dependent bell-shaped curve in both networks. While at pH = 1 in the dark, AH(+) evolves to an equilibrium mixture containing predominantly AH(+)(iso), irradiation at λ > 435 nm induces the opposite conversion.


Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases.
Conditional DNA excision between two LoxP sites can be achieved in the mouse using Cre-ER(T), a fusion protein between a mutated ligand binding domain of the human estrogen receptor (ER) and the Cre recombinase, the activity of which can be induced by 4-hydroxy-tamoxifen (OHT), but not natural ER ligands. We have recently characterized a new ligand-dependent recombinase, Cre-ER(T2), which was approximately 4-fold more efficiently induced by OHT than Cre-ER(T) in cultured cells. In order to compare the in vivo efficiency of these two ligand-inducible recombinases to generate temporally-controlled somatic mutations, we have engineered transgenic mice expressing a LoxP-flanked (floxed) transgene reporter and either Cre-ER(T) or Cre-ER(T2) under the control of the bovine keratin 5 promoter that is specifically active in the epidermis basal cell layer. No background recombinase activity could be detected, while recombination was induced in basal keratinocytes upon OHT administration. Interestingly, a dose-response study showed that Cre-ER(T2) was approximately 10-fold more sensitive to OHT induction than Cre-ER(T).


Proteomic analyses of transgenic LQT1 and LQT2 rabbit hearts elucidate an increase in expression and activity of energy producing enzymes.
Various biochemical and genomic mechanisms are considered to be a hallmark of metabolic remodeling in the stressed heart, including the hypertrophied and failing heart. In this study, we used quantitative proteomic 2-D Fluorescence Difference In-Gel Electrophoresis (2-D DIGE) in conjunction with mass spectrometry to demonstrate differential protein expression in the hearts of transgenic rabbit models of Long QT Syndrome 1 (LQT1) and Long QT Syndrome 2 (LQT2) as compared to littermate controls (LMC). The results of our proteomic analysis revealed upregulation of key metabolic enzymes involved in all pathways associated with ATP generation, including creatine kinase in both LQT1 and LQT2 rabbit hearts. Additionally, the expression of lamin-A protein was increased in both LQT1 and LQT2 rabbit hearts as was the expression of mitochondrial aldehyde dehydrogenase and desmoplakin in LQT1 and LQT 2 rabbit hearts, respectively. Results of the proteomic analysis also demonstrated down regulation in the expression of protein disulfide-isomerase A3 precuorsor and dynamin-like 120 kDa protein (mitochondrial) in LQT1, and of alpha-actinin 2 in LQT2 rabbit hearts. Up regulation of the expression of the enzymes associated with ATP generation was substantiated by the results of selective enzyme assays in LQT1 and LQT2 hearts, as compared to LMC, which revealed increases in the activities of glycogen phosphorylase (+50%, +65%, respectively), lactate dehydrogenase (+25%, +25%) pyruvate dehydrogenase (+31%, +22%), and succinate dehydrogenase (+32%, +60%). The activity of cytochrome c-oxidase, a marker for the mitochondrial function was also found to be significantly elevated (+80%) in LQT1 rabbit hearts as compared with LMC. Western blot analysis in LQT1 and LQT2 hearts compared to LMC revealed an increase in the expression of very-long chain-specific acyl-CoA dehydrogenase (+35%, +33%), a rate-limiting enzymes in β-oxidation of fatty acids. Collectively, our results demonstrate similar increases in the expression and activities of key ATP-generating enzymes in LQT1 and LQT2 rabbit hearts, suggesting an increased demand, and in turn, increased energy supply across the entire metabolic pathway by virtue of the upregulation of enzymes involved in energy generation.