Investigation of effects of anesthesia and age on aspiration in mice through LacZ gene transfer by recombinant E1-deleted adenovirus vectors.
To examine the role of disturbed upper airway reflexes in aspiration, we administered 20 microliters of the adenovirus (Ad) vector Ad-CMV-LacZ or 20 microliters of phosphate buffered saline (PBS) intranasally to C57 black mice. We investigated expression of the LacZ gene by this Ad vector in the nostrils of each mouse, with or without anesthesia. Under anesthesia, LacZ gene expression was detected in the lungs of every mouse given the Ad vector. However, no LacZ gene expression was found in the trachea or lungs of mice given the Ad vector without anesthesia. In mice given PBS or wild-type adenovirus transnasally during anesthesia, there was no LacZ gene expression in the nostrils, trachea, or lungs, suggesting that with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining, blue-stained cells indicated transferred LacZ gene expression. These results suggested that aspiration of intranasal solution into lower airways was caused by disturbed upper airway reflexes during anesthesia. This process can be analyzed by the distribution of LacZ gene expression in airways. We next examined the effect of age on anesthesia-induced aspiration. Twenty-six-mo-old mice exhibited more LacZ gene expression in their lungs than did 6-mo-old mice at a concentration of 0.5 to 4.0% halothane in 100% oxygen. This suggests that light anesthesia may depress upper airway reflexes and cause aspiration in older animals. This novel model of aspiration, generated with the Ad-CMV-LacZ vector, may be useful for elucidating the mechanism of development of aspiration pneumonia in relation to age-related impairment of upper airway reflexes.


Diagnosis and management of functional neurological disorder.
Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments. This represents a major step toward destigmatizing the disorder, which was often doubted and deemed untreatable. FND is prevalent, generally affecting young and middle aged adults, and can cause severe disability in some individuals. An early diagnosis, with subsequent access to evidence based rehabilitative and/or psychological treatments, can promote recovery-albeit not all patients respond to currently available treatments. This review presents the latest advances in the use of validated rule-in examination signs to guide diagnosis, and the range of therapeutic approaches available to care for patients with FND. The article focuses on the two most frequently identified subtypes of FND: motor (weakness and/or movement disorders) and seizure type symptoms. Twenty two studies on motor and 27 studies on seizure type symptoms report high specificities of clinical signs (64-100%), and individual signs are reviewed. Rehabilitative interventions (physical and occupational therapy) are treatments of choice for functional motor symptoms, while psychotherapy is an emerging evidence based treatment across FND subtypes. The literature to date highlights heterogeneity in responses to treatment, underscoring that more research is needed to individualize treatments and develop novel interventions.


Radiomics Based on Contrast-Enhanced CT for Recognizing c-Met-Positive Hepatocellular Carcinoma: a Noninvasive Approach to Predict the Outcome of Sorafenib Resistance.
The purpose of our project was to investigate the effectiveness of radiomic features based on contrast-enhanced computed tomography (CT) that can detect the expression of c-Met in hepatocellular carcinoma (HCC) and to validate its efficacy in predicting the outcome of sorafenib resistance. In total, 130 patients (median age, 60 years) with pathologically confirmed HCC who underwent contrast material-enhanced CT from October 2012 to July 2020 were randomly divided into a training set (n = 91) and a test set (n = 39). Radiomic features were extracted from arterial phase (AP), portal venous phase (VP) and delayed phase (DP) images of every participant's enhanced CT images. The entire group comprised 39 Met-positive and 91 Met-negative patients. The combined model, which included the clinical factors and the radiomic features, performed well in the training (area under the curve [AUC] = 0.878) and validation (AUC = 0.851) cohorts. The nomogram, which relied on the combined model, fits well in the calibration curves. Decision curve analysis (DCA) further confirmed that the clinical valuation of the nomogram achieved comparable accuracy in c-Met prediction. Among another 20 patients with HCC who had received sorafenib, the predicted high-risk group had shorter overall survival (OS) than the predicted low-risk group (p < 0.05). A multivariate model acquired from three phases (AP, VP and DP) of enhanced CT, HBV-DNA and γ glutamyl transpeptidase isoenzyme II (GGT-II) could be considered a satisfactory preoperative marker of the expression of c-Met in patients with HCC. This approach may help in overcoming sorafenib resistance in advanced HCC.


Aqueous humor lidocaine concentrations in topical and intracameral anesthesia.
To assess aqueous humor lidocaine concentrations in 2 common regimens of topical anesthesia and after intracameral injection of the anesthetic agent. University hospital eye clinic. Twenty patients having routine cataract surgery were randomized into 3 groups: 1 given 3 drops of lidocaine 4% before surgery; 1 given 6 drops; 1 given 3 drops plus an intracameral injection of 0.1 mL lidocaine 1%. Lidocaine concentration was measured in aqueous humor samples taken before surgery. With 3 drops, aqueous lidocaine concentration was 1.4 micrograms/mL +/- 0.5 (SD) and with 6 drops, 4.3 +/- 1.5 micrograms/mL (P = .0015). With an intracameral injection, it was 341.8 +/- 152.6 micrograms/mL. Measurable amounts of lidocaine entered the anterior chamber in topical anesthesia, and more entered when more drops were given. It is likely that concentrations in this range could anesthetize the iris, but they are far lower than concentrations after an intracameral injection.


A medium-density genotyping platform for cultivated strawberry using DArTag technology.
Genomic prediction in breeding populations containing hundreds to thousands of parents and seedlings is prohibitively expensive with current high-density genetic marker platforms designed for strawberry. We developed mid-density panels of molecular inversion probes (MIPs) to be deployed with the "DArTag" marker platform to provide a low-cost, high-throughput genotyping solution for strawberry genomic prediction. In total, 7742 target single nucleotide polymorphism (SNP) regions were used to generate MIP assays that were tested with a screening panel of 376 octoploid Fragaria accessions. We evaluated the performance of DArTag assays based on genotype segregation, amplicon coverage, and their ability to produce subgenome-specific amplicon alignments to the FaRR1 assembly and subsequent alignment-based variant calls with strong concordance to DArT's alignment-free, count-based genotype reports. We used a combination of marker performance metrics and physical distribution in the FaRR1 assembly to select 3K and 5K production panels for genotyping of large strawberry populations. We show that the 3K and 5K DArTag panels are able to target and amplify homologous alleles within subgenomic sequences with low-amplification bias between reference and alternate alleles, supporting accurate genotype calling while producing marker genotypes that can be treated as functionally diploid for quantitative genetic analysis. The 3K and 5K target SNPs show high levels of polymorphism in diverse F. × ananassa germplasm and UC Davis cultivars, with mean pairwise diversity (π) estimates of 0.40 and 0.32 and mean heterozygous genotype frequencies of 0.35 and 0.33, respectively.


Ultrasound pretreatment for enhanced biogas production from olive mill wastewater.
This study investigates applicability of low frequency ultrasound technology to olive mill wastewaters (OMWs) as a pretreatment step prior to anaerobic batch reactors to improve biogas production and methane yield. OMWs originating from three phase processes are characterized with high organic content and complex nature. The treatment of the wastewater is problematic and alternative treatment options should be investigated. In the first part of the study, OMW samples were subjected to ultrasound at a frequency of 20kHz with applied powers varying between 50 and 100W under temperature controlled conditions for different time periods in order to determine the most effective sonication conditions. The level of organic matter solubilization at ultrasound experiments was assessed by calculating the ratio of soluble chemical oxygen demand/total chemical oxygen demand (SCOD/TCOD). The results revealed that the optimum ultrasonic condition for diluted OMW is 20kHz, 0.4W/mL for 10min. The application of ultrasound to OMW increased SCOD/TCOD ratio from 0.59 to 0.79. Statistical analysis (Friedman's tests) show that ultrasound was significantly effective on diluted OMW (p<0.05) in terms of SCOD parameter, but not for raw OMW (p>0.05). For raw OMW, this increase has been found to be limited due to high concentration of suspended solids (SS). In the second part of the study, biogas and methane production rates of anaerobic batch reactor fed with the ultrasound pretreated OMW samples were compared with the results of control reactor fed with untreated OMW in order to determine the effect of sonication. A nonparametric statistical procedure, Mann-Whitney U test, was used to compare biogas and methane production from anaerobic batch reactors for control and ultrasound pretreated samples. Results showed that application of low frequency ultrasound to OMW significantly improved both biogas and methane production in anaerobic batch reactor fed with the wastewater (p<0.05). Anaerobic batch reactor fed with ultrasound pretreated diluted OMW produced approximately 20% more biogas and methane compared with the untreated one (control reactor). The overall results indicated that low frequency ultrasound pretreatment increased soluble COD in OMW and subsequently biogas production.


Association of Serum Magnesium on Mortality in Patients Admitted to the Intensive Cardiac Care Unit.
Although electrolyte disturbances may affect cardiac action potential, little is known about the association between serum magnesium and corrected QT (QTc) interval as well as clinical outcomes. A consecutive 8498 patients admitted to the Mayo Clinic Hospital-Rochester cardiac care unit (CCU) from January 1, 2004 through December 31, 2013 with 2 or more documented serum magnesium levels, were studied to test the hypothesis that serum magnesium levels are associated with in-hospital mortality, sudden cardiac death, and QTc interval. Patients were 67 ± 15 years; 62.2% were male. The primary diagnoses for CCU admissions were acute myocardial infarction (50.7%) and acute decompensated heart failure (42.5%), respectively. Patients with higher magnesium levels were older, more likely male, and had lower glomerular filtration rates. After multivariate analyses adjusted for clinical characteristics including kidney disease and serum potassium, admission serum magnesium levels were not associated with QTc interval or sudden cardiac death. However, the admission magnesium levels ≥2.4 mg/dL were independently associated with an increase in mortality when compared with the reference level (2.0 to <2.2 mg/dL), having an adjusted odds ratio of 1.80 and a 95% confidence interval of 1.25-2.59. The sensitivity analysis examining the association between postadmission magnesium and analysis that excluded patients with kidney failure and those with abnormal serum potassium yielded similar results. This retrospective study unexpectedly observed no association between serum magnesium levels and QTc interval or sudden cardiac death. However, serum magnesium ≥2.4 mg/dL was an independent predictor of increased hospital morality among CCU patients.


Bulbous gold-carbon nanodot hybrid nanoclusters for cancer therapy.
Assemblies of inorganic nanoparticles and carbon nanodots have emerged as promising candidates for hybrid materials in biomedical applications. In this work, the formation and properties of gold nanoparticles synthesized with the aid of carbon nanodots (CND) as reducing/stabilizing agents was investigated. Through careful modification of the reaction conditions, such as precursor concentrations and temperature, the size and shape of the particles can be controlled. In general, CNDs provide reductive sites at which gold seeds can be formed. As the gold nanoparticles grow, the CNDs form a polar solubilizing shell in the polar aqueous environment, yielding bulbous Au@pCND nanoclusters. In fact, charge-transfer interactions between the pCND shell and the Au core are implicit, as confirmed by steady state and time resolved absorption and fluorescence spectroscopies. Finally, this work demonstrated via in cell internalization tests that the size and the shape of the Au@pCND nanoclusters play a crucial role for the cancer cell toxicity. Also the Au@pCND prove to be good candidates as sensitizers in cancer radio-therapy.


Neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions.
In managing our way through interpersonal conflict, anger might be crucial in determining whether the dispute escalates to aggressive behaviors or resolves cooperatively. The Ultimatum Game (UG) is a social decision-making paradigm that provides a framework for studying interpersonal conflict over division of monetary resources. Unfair monetary UG-offers elicit anger and while accepting them engages regulatory processes, rejecting them is regarded as an aggressive retribution. Ventro-medial prefrontal-cortex (vmPFC) activity has been shown to relate to idiosyncratic tendencies in accepting unfair offers possibly through its role in emotion regulation. Nevertheless, standard UG paradigms lack fundamental aspects of real-life social interactions in which one reacts to other people in a response contingent fashion. To uncover the neural substrates underlying the tendency to accept anger-infused ultimatum offers during dynamic social interactions, we incorporated on-line verbal negotiations with an obnoxious partner in a repeated-UG during fMRI scanning. We hypothesized that vmPFC activity will differentiate between individuals with high or low monetary gains accumulated throughout the game and reflect a divergence in the associated emotional experience. We found that as individuals gained more money, they reported less anger but also more positive feelings and had slower sympathetic response. In addition, high-gain individuals had increased vmPFC activity, but also decreased brainstem activity, which possibly reflected the locus coeruleus. During the more angering unfair offers, these individuals had increased dorsal-posterior Insula (dpI) activity which functionally coupled to the medial-thalamus (mT). Finally, both vmPFC activity and dpI-mT connectivity contributed to increased gain, possibly by modulating the ongoing subjective emotional experience. These ecologically valid findings point towards a neural mechanism that might nurture pro-social interactions by modulating an individual's dynamic emotional experience.


[Splicing. 2. Splicing of mRNA in the cell nucleus].
The mosaic structure of genes is shown for three out of four known types of RNAs, namely transfer, ribosomal and messenger. At least three different splicing mechanisms are involved in maturation of transcripts of these genes, two of them had been described in the previous review. Well-developed effective in vitro splicing systems permit to provide a scheme for the nuclear pre-mRNA maturation processes which take place presumably in specific ribonucleoprotein complex particles. Alternative splicing character of these pre-mRNAs, yields in increased variety of the encoded proteins.


Erythrocyte flow and dynamic hematocrit in the renal papilla of the rat.
The microcirculation of the renal papilla was investigated in 32 vasa recta of Wistar rats. Using fluorescence microscopy in combination with a high-sensitivity television system we measured the velocity and flux of fluorescent-tagged erythrocytes in descending (DVR) and ascending vasa recta (AVR). After staining the plasma with fluorescent high molecular weight dextran we determined the diameters of DVR and AVR. Red cell flux (Qrbc) was determined from the ratio of the frequency of fluorescent-tagged red cells detected per unit time (fFITC) to the number of fluorescent-tagged red cells per nanoliter packed red cells (NFITC). From red cell velocity (Vrbc) and vessel diameter (D) we calculated the volume flow (Vapp). The dynamic hematocrit was directly derived as the ratio of Qrbc to Vapp. During antidiuresis Vrbc was 1.35 +/- 0.15 mm X s-1 (mean +/- SE) in DVR and 0.47 +/- 0.07 mm X s-1 in AVR. Qrbc in the same vessels averaged 3.26 +/- 0.9 and 1.72 +/- 0.35 nl X min-1, respectively. The diameter in DVR was 14.3 +/- 0.9 and in AVR 17.9 +/- 0.9 micron. From these values we calculated a dynamic hematocrit of 26 +/- 4 in DVR and 25 +/- 4% in AVR. The systemic hematocrit was 44 +/- 1%. The dynamic hematocrit in vasa recta represented 59 +/- 9 and 57 +/- 8% of the value in the systemic circulation, respectively.


Diagnosing causes of headache within the postpartum period.
Headache is one of the most common symptoms following delivery and the underlying cause may be benign or life threatening. Identification of the cause of headache in the postpartum period can be challenging and relies on a comprehensive history and thorough examination, with particular focus on the presence or absence of neurological signs, which may suggest a more serious diagnosis (Nelson-Piercy 2010 ). However, through clinical experience and research, we have noted that post-partum headache is significantly under-recognised and treated (Goldszmidt et al. 2005 ). To ensure a standardised approach to the management of patients presenting with postpartum headache, we sought to introduce a diagnostic tool for postpartum headache. This was a literature review combined with a postpartum headache case example that occurred within our institution in 2015. Risk factors and potential clinical failures from the case were noted and compared to the literature. Our case is a 28-year-old woman who developed a postpartum headache following spontaneous vaginal delivery. Of note, the patient had an epidural inserted in labour for analgesia. Initially, systemic and neurological examinations were normal and the patient was discharged home with simple analgesics and a diagnosis of tension-type headache. She represented with worsening headache, pyrexia and signs of meningism. Lumbar puncture confirmed a diagnosis of bacterial meningitis caused by Haemophilus influenzae. She was treated with IV ceftriaxone and discharged home without any long-term sequelae. In an attempt to improve recognition of post-partum headache, especially rare causes such as meningitis, NHS Tayside has chosen to adopt the PARTUM mneumonic (Lim et al. 2014 ). Pressure (blood pressure for pre-eclampsia/eclampsia) Anaesthetic (post-dural puncture headache) Reversible (vasoconstriction syndrome) Thrombosis (cerebral venous sinus thrombosis, ischaemic stroke) Use your brain (there are so many other causes of headache) Migraine (Lim et al. 2014 ). PARTUM was first devised in 2014 as part of a research paper published by the Journal Practical Neurology (Lim et al. 2014 ). The aim of the mnemonic is to allow the treating physician a basic list of postpartum headache causes to use as a working diagnosis (Lim et al. 2014 ). Research has shown that many postpartum headaches go undiagnosed and as a result are poorly treated, often returning following discharge from secondary care (Nelson-Piercy 2010 ). The hope is that the introduction of this adjuvant will allow clinicians to identify the cause of postpartum headaches earlier and will allow life threatening diagnoses to be quickly excluded.


A survey of grid knowledge and grid perception in the public sector.
Grids have been developed to enable computational or data intensive scientific applications and to share resources. Existing infrastructures can benefit other possible user groups. This qualitative survey focuses on the public sector with universities, governments and hospitals. Interviews were performed to collect information on the perception of Grids by decision makers, system administrators and high level users in the sector. Application scenarios and main barriers for Grid adoption are discussed based on the users' and institutional interests.


Ir/Zn Dual Catalysis: Enantioselective and Diastereodivergent α-Allylation of Unprotected α-Hydroxy Indanones.
A one-step enantioselective and diastereodivergent α-allylation of unprotected α-hydroxy indanones has been developed using an Ir/Zn dual catalyst system; no additional base is required. The cyclic tertiary α-hydroxyketones containing vicinal stereocenters can be synthesized with excellent enantioselectivity (up to >99% ee) and good diastereoselectivity (up to 12:1 dr). By a simple choice of the appropriate chiral metal catalyst combination, all four product stereoisomers could be obtained from the same starting materials and under identical conditions.


The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders.
An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.


Collision tumor in form of primary adenocarcinoma and neuroendocrine carcinoma of the duodenum.
Collision tumor is a rare phenomenon characterized by coexistence of completely distinct and independent tumors at the same body location. Collision tumors have been reported in different sites. However, they are extremely uncommon in the duodenum. We report the case of a 52-year old man with a collision tumor in the third portion of the duodenum with two distinct tumors of primary adenocarcinoma and neuroendocrine carcinoma, and both tumors coexisting within a single metastatic lymph node. Immunohistochemistry studies were performed to conclude that this was a case of collision cancer. To the best of our knowledge, this is the first collision tumor case reported to date at this location, and the first report of lymph node with a collision metastasis from a collision tumor. Such tumor is very rare and may thus provide diagnostic challenges. This report also provides a review of other cases on duodenal collision tumors.


[Tooth brushing in babies and toddlers].
The aim of this study was to investigate tooth brushing in toddlers and children younger than 4 years of age and the experiences of their parents. This study was performed in 3 towns in the middle of the Netherlands at the Office for Parent and Childcare. 99.4% of the children were brushed at least once a day during 0.5-1 minute. Tooth brushing is considered as a part of daily health care. Most children are cooperative and their parents enjoy brushing the teeth of their children. 17.5% of all parents experience problems with brushing teeth of their toddler or young child; 46% of them would like more information. But as the total number of children in a family increases, the parents' pleasure in brushing decreases. The Office for Parent and Childcare in the Netherlands has an important place in providing information on oral healthcare and especially tooth brushing for toddlers and children younger than 4 years of age. It would be useful to investigate how these healthcare workers get their dental information.


Tissue Identification of Intervertebral Disc Anatomy Using Forward-oriented Ultrasound Endoscopic System: A Feasibility Study.
Minimally invasive surgery is widely used for spine surgery, however the commonly used optical endoscopes cannot identity tissues under surface. In this study, a forward-oriented ultrasound endoscopic system was proposed to detect and identity different types of tissues for surgical approaches. A total of 150 ultrasound image data were collected from 6 types of intervertebral disc tissue using a custom-developed endoscopic probe. The gray-level co-occurrence matrix (GLCM) properties including energy (angular second moment, ASM), contrast, entropy, and homogeneity (inverse difference moment, IDM) were calculated on the acquired ultrasound images, and the single-parameter and combined parameter were applied for tissue classification. The classification accuracies of fibrous ring, nerve roots and bone were 100%, and the overall accuracy for all tissues was 73.33%. The results indicated that the combined parameter method provided more accurate classification output. It demonstrated that the proposed endoscopic ultrasonography system had the potential of identifying different tissues under surface during the endoscopic spine surgery.Clinical Relevance-This study establishes that the forward-oriented ultrasound endoscopic system was feasible to identify different types of tissues under surface during the endoscopic spine surgery.


Recruiting middle school students into nursing.
The purpose of this literature review is to illustrate the importance of initiating nursing recruitment during the middle school years. Data sources included citations from the years 1989 to 2006. The study focused on middle school students 9 to 13 years of age in Grades 6 to 8. One survey compared middle school students' perceptions of an ideal career and a career in nursing. Other studies discussed interventions such as nursing camps, recruitment videos, presentations, and handouts. After the intervention, the studies found statistically significant increases in the desire of middle school students to consider or make nursing their career choice. One strategy for addressing future nursing shortages might be the implementation of recruitment efforts targeting middle school students.


[Investigation of the impact of pterygium on ocular optic system aberration. Communication 2. New approaches to reducing aberrations during surgical treatment for pterygium].
The authors made a detailed comparative analysis of the aberration pattern of the cornea as a result of surgical treatment for pterygium, by applying various technologies. Forty-four patients (55 eyes) with primary Stages II to IV pterygium were examined. According to the surgical techniques, the patients were divided into 2 groups: (1) those in whom pterygium was surgically removed, followed by abrasive microsurgery and plastic repair with an autoconjunctiva (29 eyes) (a control group); (2) those who had undergone surgical pterygium removal, abrasive microsurgery, and plastic repair with an autoconjunctiva, followed by phototherapeutic eximer laser keratoablation (26 eyes). The study has revealed that phototherapeutic eximer laser ablation of the cornea after surgical excision and abrasive treatment of the corneal bed in Stages II to IV pterygium causes a considerable reduction in the level of aberrations of higher orders. The expedience of phototherapeutic keratoablation as part of multimodality treatment for Stages III and IV pterygium, which has been shown by the aberration analysis, is only one of the first steps in evaluating the efficiency of this technology of surgical treatment for pterygium. Studies involving an integrated clinicofunctional and ophthalmoergonomic assessment of this treatment technology should be continued, which makes it possible to evaluate the clinical efficiency of this procedure and to define a place of the presented technology in the surgical treatment of pterygium.


Learning About End-of-Life Care in Nursing-A Global Classroom Educational Innovation.
Teaching nursing students how to provide patient-centered end-of-life care is important and challenging. As traditional face-to-face classroom teaching is increasingly supplanted by digital technology, this provides opportunities for developing new forms of end-of-life care education. The aim of this article is to examine how a global classroom was developed using online technology to enhance nursing students' learning of end-of-life care in England and the United States. The PDSA (Plan-Do-Study-Act) quality improvement approach was used to guide the design and delivery of this curriculum innovation. The global classroom enhanced the educational experience for students. Teaching needs to be inclusive, focused, and engaging; the virtual platform must be stable and support individual learning, and learning needs to be collaborative and authentic. These findings can be used to inform the integration of similar approaches to end-of-life care education in other health care professional preparation programs. [J Nurs Educ. 2017;56(11):688-691.].


Smoking, nicotine dependence, and motives to quit in Asian American versus Caucasian college students.
Few smoking cessation programs are designed for college students, a unique population that may categorically differ from adolescents and adults, and thus may have different motivations to quit than the general adult population. Understanding college student motives may lead to better cessation interventions tailored to this population. Motivation to quit may differ, however, between racial groups. The current study is a secondary analysis examining primary motives in college student smokers, and differences between Asian American and Caucasian students in smoking frequency, nicotine dependence, and motives to quit. Participants (N = 97) listed personal motives to quit cigarette smoking, which were then coded into categories: health, personal relationships (e.g., friends, family, romantic partners), self-view (e.g., "addicted" or "not in control"), image in society, impact on others or the environment (e.g., second-hand smoke, pollution), and drain on personal resources (e.g., money, time). Mean number of motives were highest in the category of health, followed by personal relationships, drain on resources, self-view, image, and impact. Asian American students listed significantly fewer motives in the categories of health, self-view and image, and significantly more in the category of personal relationships than Caucasian students. Nicotine dependence was significantly higher for Asian American students. However, frequency of smoking did not differ between groups. Results may inform customization of smoking cessation programs for college students and address relevant culturally specific factors of different racial groups.


Genetic influences in gastro-oesophageal reflux disease: a twin study.
A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD. To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins. A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year. Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19-81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20-82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% v 26%; p<0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32-55%) of the variance in liability to GORD is due to additive genetic factors. There is a substantial genetic contribution to the aetiology of GORD.


Rollover effects in gatekeeper programs: cushioning the impact of restricted choice.
Public and private medical care plans that restrict the beneficiary's choice of providers have experienced rapid growth in the past decade as a means to contain costs and coordinate care. Such plans have been criticized for engendering beneficiary dissatisfaction and potentially impeding access to necessary care. Some of the objections to primary care "gatekeeping" may be diminished by recruiting the physician who served previously as the beneficiary's "usual source of care" to assume the role of formal gatekeeper. This study examines how persons whose gatekeepers were their regular source of care before plan implementation differed in their use and satisfaction from persons required to change their regular source of care. Our findings indicate that satisfaction was significantly higher among individuals who experienced no change in usual source of care. These individuals also tended to be less likely to use the emergency department as a source of care. Although the data are from Medicaid managed care programs, the findings may also be applicable to private sector point-of-service plans that adopt the primary care gatekeeper model.


Over-expression of Stat5b confers protection against diabetes in the non-obese diabetic (NOD) mice via up-regulation of CD4(+)CD25(+) regulatory T cells.
The signal transducers and activators of transcription (STAT) family of proteins play a critical role in cytokine signaling required for fine tuning of immune regulation. Previous reports showed that a mutation (L327M) in the Stat5b protein leads to aberrant cytokine signaling in the NOD mice. To further elaborate the role of Stat5b in diabetes, we established a NOD transgenic mouse that over-expresses the wild type Stat5b gene. The incidences of spontaneous diabetes as well as cyclophosphamide-induced diabetes were significantly reduced and delayed in the Stat5b transgenic NOD mice compared to their littermate controls. The total cell numbers of CD4(+) T cells and especially CD8(+) T cells in the spleen and pancreatic lymph node were increased in the Stat5b transgenic NOD mice. Consistent with these findings, CD4(+) and CD8(+) T cells from the Stat5b transgenic NOD mice showed a higher proliferation capacity and up-regulation of multiple cytokines including IL-2, IFN-γ, TNF-α and IL-10 as well as anti-apoptotic gene Bcl-xl. Furthermore, the number and proportion of CD4(+)CD25(+) regulatory T cells were significantly increased in transgenic mice although in vitro suppression ability of the regulatory T-cells was not affected by the transgene. Our results suggest that Stat5b confers protection against diabetes in the NOD mice by regulating the numbers and function of multiple immune cell types, especially by up-regulating CD4(+)CD25(+) regulatory T cells.


HriGFP Novel Flourescent Protein: Expression and Applications.
Biosensors based on microbial cells have been developed to monitor environmental pollutants. These biosensors serve as inexpensive and convenient alternatives to the conventional lab based instrumental analysis of environmental pollutants. Small monomeric naturally occurring fluorescent proteins (fp) can be exploited by converting them as small biosensing devices for biomedical and environmental applications. Moreover, they can withstand exposure to denaturants, high temperature, and a wide pH range variation. The current study employs newly identified novel fluorescent protein HriGFP from Hydnophora rigida to detect environmental contaminants like heavy metals and organo-phosphorous (pesticide) compounds such as methyl parathion. The HriGFP was initially tested or its expression in bacterial systems (Gram positive and Gram negative) and later on for its biosensing capability in E coli (BL21DE3) for detection of heavy metals and methyl parathion was evaluated. Our results indicated the discrete and stable expression of HriGFP and a profound fluorescent quenching were observed in the presence of heavy metals (Hg, Cu, As) and methyl parathion. Structural analysis revealed heavy metal ions binding to HriGFP via amino acid residues. In-silico-analysis further revealed strong interaction via hydrogen bonds between methyl parathion phosphate oxygen atoms and the amino group of Arg119 of HriGFP. This study implies that HriGFP can act as a biosensor for detecting harmful carcinogenic pesticide like methyl parathion in water resources in the vicinity of heavily pesticide impregnated agricultural lands and heavy metal contaminated water bodies around industrial areas.


The impact of periventricular white matter lesions in patients with bipolar disorder type I.
White matter hyperintensities (WMHs) are one the most common neuroimaging findings in patients with bipolar disorder (BD). It has been suggested that WMHs are associated with impaired insight in schizophrenia and schizoaffective patients; however, the relationship between insight and WMHs in BD type I has not been directly investigated. Patients with BD-I (148) were recruited and underwent brain magnetic resonance imaging (MRI). Affective symptoms were assessed using Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS17); the presence of impaired insight was based on the corresponding items of YMRS and HDRS17. Multiple punctate periventricular WMHs (PWMHs) and deep WMHs (DWMHs) were observed in 49.3% and 39.9% of the cases, respectively. Subjects with lower insight for mania had significantly more PWMHs (54.6% vs 22.2%; p < 0.05) when compared to BD-I patients with higher insight for mania. The presence of PWMHs was independently associated with lower insight for mania: patients who denied illness according to the YMRS were 4 times more likely to have PWMHs (95% CI: 1.21/13.42) than other patients. Impaired insight in BD-I is associated with periventricular WMHs. The early identification of BD-I subjects with PWMHs and impaired insight may be crucial for clinicians.


Comparison of human stromelysin and collagenase by cloning and sequence analysis.
A comparison of the cDNA-derived amino acid sequences of human stromelysin and collagenase with the N-terminal sequences of purified enzymes reveals that these metalloproteinases are highly conserved and that they are secreted as proenzymes. A putative zinc-binding site was identified by its homology with the zinc-chelating sequence of thermolysin. These sequences permitted the identification of: transin, a protein induced in rat fibroblasts either exposed to growth factors or transformed by oncogenic viruses, as the rat homologue of stromelysin, and XHF1, a protein induced in human fibroblasts after treatment with tumourigenic agents, as collagenase.


Protein context shapes the specificity of SH3 domain-mediated interactions in vivo.
Protein-protein interactions (PPIs) between modular binding domains and their target peptide motifs are thought to largely depend on the intrinsic binding specificities of the domains. The large family of SRC Homology 3 (SH3) domains contribute to cellular processes via their ability to support such PPIs. While the intrinsic binding specificities of SH3 domains have been studied in vitro, whether each domain is necessary and sufficient to define PPI specificity in vivo is largely unknown. Here, by combining deletion, mutation, swapping and shuffling of SH3 domains and measurements of their impact on protein interactions in yeast, we find that most SH3s do not dictate PPI specificity independently from their host protein in vivo. We show that the identity of the host protein and the position of the SH3 domains within their host are critical for PPI specificity, for cellular functions and for key biophysical processes such as phase separation. Our work demonstrates the importance of the interplay between a modular PPI domain such as SH3 and its host protein in establishing specificity to wire PPI networks. These findings will aid understanding how protein networks are rewired during evolution and in the context of mutation-driven diseases such as cancer.


Enhanced shift and scale tolerance for rotation invariant polar matching with dual-tree wavelets.
Polar matching is a recently developed shift and rotation invariant object detection method that is based upon dual-tree complex wavelet transforms or equivalent multiscale directional filterbanks. It can be used to facilitate both keypoint matching, neighborhood search detection, or detection and tracking with particle filters. The theory is extended here to incorporate an allowance for local spatial and dilation perturbations. With experiments, we demonstrate that the robustness of the polar matching method is strengthened at modest computational cost.


Hemorrhage after pancreatoduodenectomy.
The authors reviewed the hemorrhagic complications of patients who underwent pancreatoduodenectomies between 1972 and 1996. Although recent studies have demonstrated a reduction in the mortality of pancreatic resection, morbidity is still high. Bleeding is a close second to anastomotic dehiscence in the list of dangerous postoperative complications. The medical records from a prospective data bank of 559 patients who underwent pancreatic resection at the Surgical Clinic of Mannheim (Heidelberg University) were analyzed in regard to postoperative hemorrhagic complications. Differences were evaluated with the Fisher exact test. The overall mortality rate was 2.7%. Postoperative bleeding occurred in 42 patients (7.5%), with 6 episodes ending fatally (14.3%). Erosive bleeding after pancreatic leak was noted in 11 patients (26.2%), 4 of whom died. Gastrointestinal hemorrhage occurred in 22 patients, and operative field hemorrhage was present in 20 cases. Relaparotomy was necessary in 29 patients. An angiography with interventional embolization for recurrent bleeding was performed in three patients. Seven hemorrhages (4.6%) occurred after pancreatectomy for chronic pancreatitis and 35 episodes of bleeding (8.6%) were encountered after pancreatectomy for malignant disease. Obstructive jaundice was present in 359 patients (63.9%). In this group of patients, 32 (8.9%) postoperative hemorrhages occurred. Preoperative biliary drainage did not influence the type and mortality rate of postoperative hemorrhage in jaundiced patients. The prevention of these bleeding complications depends in the first place on meticulous hemostatic technique. Preoperative biliary drainage does not lower postoperative bleeding complications in jaundiced patients. Continuous, close observation of the patient in the postoperative period, so as to detect complications in time, and expeditious hemostasis are paramount.


Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study.
The Multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p less than 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients.


Degradation of individual chromosomes in recA mutants of Escherichia coli.
Rapidly growing wild-type Escherichia coli cells contain two, four, or eight fully replicated chromosomes after treatment with rifampin, reflecting that all replication origins are initiated simultaneously. Cells with defects in the timing of the initiation of replication may contain three, five, six, or seven fully replicated chromosomes after such treatment. This phenotype, termed the asynchrony phenotype, is also seen in recombination-deficient recA mutants. It is shown here that for recA strains, the phenotype can be explained by a selective and complete degradation of individual chromosomes. The selective degradation is largely recD dependent and is thus carried out by the RecBCD exonuclease.


Vegetables and fruit, as a source of bioactive substances, and impact on memory and cognitive function of elderly.
The phenomenon of population aging is not only associated with an increase in the number and proportion of older people in society, but also with an increase in the incidence of cognitive impairment. This can impair the functioning of the elderly in everyday life, work and social life participation and impair their quality of life. Hence, it is important to identify the protective factors. Neurodegenerative changes are closely linked to inflammatory processes and oxidative stress. Diet is of great importance, with particular attention being paid to the adequate intake of fruits and vegetables, due to their proven health benefits. This may be correlated to the protective effect of the bioactive substances that are present in fruits and vegetables, in particular flavonoids and carotenoids. The elderly who consume 5 servings a day of fruits and vegetables have a higher antioxidant capacity of blood serum, while the risk of chronic diseases, including neurodegenerative and mortality rates are lower. The analysis included the results of 16 published epidemiological studies, including people aged 65+. Their results are discussed in 4 fields of the effects on cognitive function (1) fruit and vegetable intake; (2) flavonoids intake; (3) carotenoid nutritional status; (4) mechanism of action of plant bioactive substances. It has been found that the positive effects of consumption of fruits and vegetables may be associated with cognitive functions in the three possible areas, ie.: (1) improvement in cognitive testing; (2) delaying or preventing age-related deterioration of cognitive decline; (3) reducing the risk of neurodegenerative diseases.


Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) causes progressive lung scarring and high mortality. Reliable and accurate prognostic biomarkers are urgently needed. To identify and validate circulating protein biomarkers of IPF survival. High-throughput proteomic data were generated using prospectively collected plasma samples from patients with IPF from the Pulmonary Fibrosis Foundation Patient Registry (discovery cohort) and the Universities of California-Davis, Chicago, and Virginia (validation cohort). Proteins associated with three-year transplant-free survival (TFS) were identified using multivariable Cox proportional hazards regression. Those associated with TFS after adjustment for false discovery in the discovery cohort were advanced for testing in the validation cohort, with proteins maintaining TFS association with consistent effect direction considered validated. After combining cohorts, functional analyses were performed, and machine learning used to derive a proteomic signature of TFS. Of 2921 proteins tested in the discovery cohort (n=871), 231 were associated with differential TFS. Of these, 140 maintained TFS association with consistent effect direction in the validation cohort (n=355). After combining cohorts, validated proteins with strongest TFS association were latent-transforming growth factor beta-binding protein 2 (HR 2.43, 95% CI 2.09-2.82), collagen alpha-1(XXIV) chain (HR 2.21; 95% CI 1.86-2.39) and keratin 19 (HR 1.60; 95% CI 1.47-1.74). In decision curve analysis, a proteomic signature of TFS outperformed a similarly derived clinical prediction model. In largest proteomic investigation of IPF outcomes performed to date, we identified and validated 140 protein biomarkers of TFS. These results shed important light on potential drivers of IPF progression.


Stress and coping among children of alcoholic parents through the young adult transition.
The transition to young adulthood is both a time when risky health behaviors such as substance misuse peak and a time of opportunity for growth and development through the acquisition of adult roles. In this transition, coping styles include responses to the stressors and opportunities associated with the emergence of adulthood. The extent to which such coping styles are skillfully employed in part determines adjustment into adulthood. The current study used a high-risk, longitudinal design to examine the development of coping styles over adolescence, continuity in these coping styles from adolescence to adulthood, the impact of coping on adult stress and substance misuse, the ability of coping to buffer effects of stress on substance use, and differences in coping between at-risk youth (i.e., children of alcoholics [COAs]) and their peers. A sample of 340 adolescents completed four assessments over ages 11-23. We used latent trajectory models to examine interindividual and intraindividual change in coping over time. Evidence for both change and continuity in the development of coping from adolescence to adulthood was found, although adolescent coping had limited impact on stress and substance use in adulthood. Support was also found for complex stress-buffering and stress-exacerbating effects of coping on the relations between major life events and adult drug use and between stress associated with the new roles of adulthood and heavy alcohol use. Implications of these findings for development and adjustment in the transition to adulthood are discussed.


Physiologic tailoring of treatment in resistant hypertension.
Resistant hypertension is a major opportunity for prevention of cardiovascular disease. Despite widespread dissemination of consensus guidelines, most patients are uncontrolled with approaches that assume that all patients are the same. Causes of resistant hypertension include 1) non-compliance 2) consumption of substances that aggravate hypertension (such as salt, alcohol, nonsteroidal anti-inflammatory drugs, licorice, decongestants) and 3) secondary hypertension. Selecting the appropriate therapy for a patient depends on finding the cause of the hypertension. Once rare causes have been eliminated (such as pheochromocytoma, licorice, adult coarctation of the aorta), the cause will usually be found by intelligent interpretation (in the light of medications then being taken) of plasma renin and aldosterone.If stimulated renin is low and the aldosterone is high, the problem is primary aldosteronism, and the best treatment is usually aldosterone antagonists (spironolactone or eplerenone; high-dose amiloride for men where eplerenone is not available). If the renin is high, with secondary hyperaldosteronism, the best treatment is angiotensin receptor blockers or aliskiren. If the renin and aldosterone are both low the problem is over-activity of renal sodium channels and the treatment is amiloride. This approach is particularly important in patients of African origin, who are more likely to have low-renin hypertension.


Variability of multisystemic features in myotonic dystrophy type 1--lessons from Serbian registry.
Myotonic dystrophy type 1 (DM1) is a rare disease. Creating registry for such a disease is of outstanding importance since it provides us with a full spectrum of the disorder. To assess variability of different multisystemic features in a large cohort of patients with DM1. Data from the Serbian registry for myotonic dystrophies were used in the study. Final number of included DM1 subjects was 275. Registry included 53.8% of male patients. Age at enrollment was 47.2 ± 9.9 years, mean disease duration 20.4 ± 9.9 years, and mean CTG repeats number 598.3 ± 269.8.Progression of muscle weakness was pretty slow, slower in proximal than distal muscles, and slower in arms than in legs. Severe ECG abnormality was found in 25.0% of patients and pacemaker was implanted in 9.5%. Lens opacities were observed in 83.5% of DM1 patients and 35.3% had ocular hypotony. Metabolic disturbances were very common, while 19.5% of patients had hypokalemia and 37.8% hypochloremia. Sterility was found in 20.5% of males and 4.1% of females. Cholelithiasis was found in 36.4% of patients and constipation in 29.9%. We defined the most common characteristics of our DM1 patients and observed some treatable symptoms that have been neglected previously. Certain findings deserve further investigations in terms of their causes and consequences. Besides this, presented data analysis directs us to make further improvements of the registry.


Polymorphisms in NLRP1 Gene Are Associated with Type 1 Diabetes.
The aim of this study was to clarify the association of two single-nucleotide polymorphisms (SNPs) (rs11651270 and rs2670660) in the NLRP1 (NLR family pyrin domain containing 1) gene with type 1 diabetes (T1D) in the Chinese Han population. We hypothesize that mutations in the NLRP1 gene may affect the susceptibility to T1D. A case control study was designed, and participants fulfilling the diagnostic criteria of classical T1D as well as nondiabetic controls were enrolled in the study. The polymorphisms rs11651270 and rs2670660 were genotyped by polymerase chain reaction (PCR) and Sanger sequencing. Chi-squared test and logistic regression analysis were performed to compare the distributions of the allele and genotype between cases and controls. Kruskal-Wallis one-way ANOVA was used to compare the characteristics of different genotypes in participants with T1D. A total of 510 participants with classical T1D as well as 531 nondiabetic controls were enrolled in the study. The two groups were matched in sex (p = 0.418). The age (p < 0.001) and BMI (p < 0.001) were significantly lower in cases compared to controls. Significantly higher values were observed for fasting plasma glucose (FPG) (p < 0.001) and 2 h postprandial plasma glucose (PPG) (p < 0.001) in individuals with T1D. Regarding the allelic model, the minor allele C of rs11651270 was significantly associated with lower risk of T1D compared with the T allele (OR = 0.714, 95% CI = 0.579-0.882). Both rs11651270 and rs2670660 polymorphisms were associated with T1D in the Chinese Han population under a dominant model (OR = 0.648, 95% CI = 0.503-0.834 and OR = 0.716, 95% CI = 0.549-0.934, respectively) and an overdominant model (OR = 0.663, 95% CI = 0.511-0.860 and OR = 0.711, 95% CI = 0.541-0.935, respectively). Additionally, the polymorphism rs11651270 was also related to T1D in an additive model (OR = 0.719, 95% CI = 0.583-0.887). Most importantly, when we analyzed the clinical characteristics of T1D individuals with different genotypes, we found that the age of onset with the TT genotype at rs11651270 was younger than those with the other two genotypes (p = 0.001). SNPs in the NLRP1 gene were associated with T1D, as well as the age of onset in the Chinese Han T1D individuals. Our study indicated that the NLRP1 gene might play a pivotal role in the etiopathogenesis of T1D and could be applied to genetic screening of T1D in the Chinese Han population.


Diabetes mellitus: an independent predictor of duration of prostaglandin labor induction.
The objective of this study is to analyze the association of diabetes mellitus with progress and outcomes of prostaglandin (PG) labor induction using a retrievable vaginal insert. This is a secondary analysis of data collected during the Misoprostol Vaginal Insert Trial (Miso-Obs-004), a multicenter, double-blind, randomized controlled trial of women undergoing induction of labor with PGs. The duration, characteristics and outcomes of labor were compared in women with and without diabetes. Multivariable regression analysis was performed on all outcomes of interest, adjusting for differences in baseline characteristics. There were 122 women with diabetes within the sample of 1275 women who delivered during their first admission. The time to reach active labor was significantly prolonged among women with diabetes compared with those without (22.0±13.0 vs 18.5±11.1, P=0.008) as was the time to delivery (30.2±15.0 vs 26.0±12.6, P=0.004). Fewer women with diabetes delivered within 36 h (adjusted odds ratio: 0.41, 95% confidence interval: 0.26 to 0.66, P=0.0003) and 48 h (adjusted odds ratio: 0.36, 95% confidence interval: 0.19 to 0.71, P=0.004). These relationships were significant after a multivariate regression analysis of baseline characteristics that adjusted for age, race, parity, body mass index, baseline modified Bishop Score, gestational age at induction and treatment group allocation. After PG labor induction, women with diabetes took longer to reach active labor and to deliver. We emphasize that this result comes from a secondary analysis and needs confirmation with additional studies.


Factors Associated with Level of Physical Activity After Minor Stroke.
To explore factors from the acute phase, and after three and 12 months, associated with level of self-reported physical activity 12 months after a minor ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 in persons 70 years or younger. In this longitudinal cohort study patients were recruited consecutively from two stroke units. Activity level were measured with three sets of questions addressing the average number of frequency (times exercising each week), the average intensity, and duration (the average time), and a sum score was constructed. The association between physical activity 12 months after stroke and sociodemographic factors, NIHSS, body mass index, balance, and neuropsychiatric symptoms were explored using multiple linear regression. This study included 101 patients, with mean age (SD) 55.5 (11.4) years, NIHSS median (Q1, Q3) 0.0 (0.0, 1.0), and 20 % were female. Multiple linear regression analyses showed sick leave status at stroke onset, balance at three and 12 months, and anxiety, depression, apathy, and fatigue at 12 months to be factors associated with physical activity at 12 months after stroke. We found that pre-stroke sick leave, post-stroke balance, and neuropsychiatric symptoms were associated with the level of physical activity one year after minor stroke. This might be of importance when giving information about physical activity and deciding about post-stroke follow-up.


Job satisfaction and professional development of health information administration faculty.
To provide seamless care for patients while the health care industry undergoes changes, an integrated health information system must be developed. This effort affects the roles and responsibilities of practitioners and educators in health information administration (HIA). The changes may affect job satisfaction of HIA educators as they prepare entry-level practitioners for emerging roles. A national survey of HIA faculty's job satisfaction used the JDI/JIG scales and a researcher-developed instrument. The survey asked what job, institutional, and individual factors were significantly related to overall job satisfaction, whether there is a relationship between organizational fit and overall job satisfaction, and whether HIA faculty were pursuing terminal degrees, and what incentives and impediments they found to do so. Response rate was 78%. These faculty were very satisfied with their jobs. Work, pay, supervision, and co-workers were significantly related to overall job satisfaction, with work and supervision accounting for 47% of the variance. Doctorally prepared faculty valued research more than did others, and tended to be in institutions perceived to value research. Although 79% reported that their institutions encouraged them to pursue advanced degrees, only 23.6% were pursuing doctorates. These findings may be useful in recruiting HIA practitioners into academia as well as for accreditation purposes.


Comparison of imo and Humphrey field analyzer perimeters in glaucomatous eyes.
To compare the imo perimeter, a new portable head-mounted perimeter unit that enables both eyes to be examined quickly and simultaneously, with the Humphrey field analyzer (HFA) perimeter to investigate correlations and their diagnostic ability in glaucomatous eyes. The performance of the equipment in 128 glaucomatous eyes and 40 normal eyes were tested. We investigated the correlations of mean deviation, pattern standard deviation, visual field index, and the sensitivity. Measurements of mean deviation (r=0.886, P<0.001), pattern standard deviation (r=0.814, P<0.001), and visual field index (r=0.871, P<0.001) in both perimeters were strongly and positively correlated. The sensitivities in the imo perimeter were 80.5% for mean deviation, 81.2% for pattern standard deviation, and 80.5% in visual field index; those in the HFA were 63.3% for mean deviation, 74.5% for pattern standard deviation, and 80.5% for visual field index. Both perimeters demonstrated high diagnostic ability. The parameters by the imo and HFA in glaucomatous eyes show strong positive correlations with favorable sensitivity, specificity, and diagnostic ability. However, the difference between imo and HFA results increases with the increase in visual field disturbance.


Gonadoblastoma and Papillary Tubal Hyperplasia in Ovotesticular Disorder of Sexual Development.
Ovotesticular disorder of sexual development (DSD), formerly known as true hermaphroditism, is a rare form of DSD in which both testicular and ovarian tissues are present in the same individual either in a single gonad (ovotestis) or in opposite gonads with a testis and an ovary on each side. The diagnosis of ovotesticular DSD is based solely on the presence of ovarian and testicular tissue in the gonad and not on the characteristics of the internal and external genitalia, even if ambiguous. Herein, we report two patients with ovotesticular DSD-one presenting with ambiguous genitalia on the third day after birth and the other with short stature and primary amenorrhea in adolescence. Clinical and histopathological investigation revealed a sex-determining region on the Y chromosome (SRY)-positive 46,XX karyotype and bilateral ovotestes in case 1 and a 46,XY karyotype with hypergonadotropic hypogonadism and a streak gonad in one ovotestis with dysgerminoma, gonadoblastoma, and papillary tubal hyperplasia in the contralateral ovotestis in case 2. Laparoscopic examination and gonadal biopsy for histopathological diagnosis remain the cornerstones for a diagnosis of ovotesticular DSD. Moreover, SRY positivity in a 46,XX patient, a 46,XY karyotype, an intra-abdominal gonad, and the age of patient at the time of diagnosis are predictive risk factors for the development of gonadoblastoma and/or dysgerminoma in ovotesticular DSD.


Probability Statements Extraction with Constrained Conditional Random Fields.
This paper investigates how to extract probability statements from academic medical papers. In previous work we have explored traditional classification methods which led to numerous false negatives. This current work focuses on constraining classification output obtained from a Conditional Random Field (CRF) model to allow for domain knowledge constraints. Our experimental results indicate constraining leads to a significant improvement in performance.


Emergency coronary revascularization.
Emergency operations for restoration of coronary artery blood flow are an effective means for treatment of unstable anginal syndromes. The risk of such operations is minimized by preoperative stabilization with medical therapy. Mechanical circulatory assistance may be a useful adjunct in some patients, especially in the presence of left main coronary obstruction. Utilization of emergency revascularization for patients with evolving myocardial infarction may be beneficial in some patients, but this approach remains controversial at present. Emergency revascularization for cardiogenic shock improves chances for survival in selected patients, and it may be combined with valve replacement, infarct resection, or repair of ruptured myocardium in patients with adequate residual contractile tissue.


Diversification of a Novel α-Galactosyl Ceramide Hotspot Boosts the Adjuvant Properties in Parenteral and Mucosal Vaccines.
The development of potent adjuvants is an important step for improving the performance of subunit vaccines. CD1d agonists, such as the prototypical α-galactosyl ceramide (α-GalCer), are of special interest due to their ability to activate iNKT cells and trigger rapid dendritic cell maturation and B-cell activation. Herein, we introduce a novel derivatization hotspot at the α-GalCer skeleton, namely the N-substituent at the amide bond. The multicomponent diversification of this previously unexplored glycolipid chemotype space permitted the introduction of a variety of extra functionalities that can either potentiate the adjuvant properties or serve as handles for further conjugation to antigens toward the development of self-adjuvanting vaccines. This strategy led to the discovery of compounds eliciting enhanced antigen-specific T cell stimulation and a higher antibody response when delivered by either the parenteral or the mucosal route, as compared to a known potent CD1d agonist. Notably, various functionalized α-GalCer analogues showed a more potent adjuvant effect after intranasal immunization than a PEGylated α-GalCer analogue previously optimized for this purpose. Ultimately, this work could open multiple avenues of opportunity for the use of mucosal vaccines against microbial infections.


An acoustic sensor for monitoring airflow in pediatric tracheostomy patients.
Without proper monitoring, patients with artificial airways in the trachea are at high risk for complications or death. Despite routine maintenance of the tube, dislodged or copious mucus can obstruct the airway. Young children ( 3yrs) have difficulty tending to their own tubes and are particularly vulnerable to blockages. They require external respiratory sensors. In a hospital environment, ventilators, end-tidal CO2 monitors, thermistors, and other auxiliary equipment provide sufficient monitoring of respiration. However, outpatient monitoring methods, such as thoracic impedance and pulse oximetry, are indirect and prone to false positives. Desensitization of caregivers to frequent false alarms has been cited in medical literature as a contributing factor in cases of child death. Ultrasonic time-of-flight (TOF) is a technique used in specialized industrial applications to non-invasively measure liquid and gas flow. Two transducers are oriented at a diagonal across a flow channel. Velocity measurement is accomplished by detecting slight variations in transit time of contra-propagating acoustic signals with a directional component parallel to air flow. Due to the symmetry of acoustic pathway between sensors, velocity measurements are immune to partial fouling in the tube from mucus, saliva, and condensation. A first generation proof of concept prototype was constructed to evaluate the ultrasonic TOF technique for medical tracheostomy monitoring. After successful performance, a second generation prototype was designed with a smaller form factor and more advanced electronics. This prototype was tested and found to measure inspired volume with a root-mean-square error < 2% during initial trials.


Complete genome sequence and analysis of the multiresistant nosocomial pathogen Corynebacterium jeikeium K411, a lipid-requiring bacterium of the human skin flora.
Corynebacterium jeikeium is a "lipophilic" and multidrug-resistant bacterial species of the human skin flora that has been recognized with increasing frequency as a serious nosocomial pathogen. Here we report the genome sequence of the clinical isolate C. jeikeium K411, which was initially recovered from the axilla of a bone marrow transplant patient. The genome of C. jeikeium K411 consists of a circular chromosome of 2,462,499 bp and the 14,323-bp bacteriocin-producing plasmid pKW4. The chromosome of C. jeikeium K411 contains 2,104 predicted coding sequences, 52% of which were considered to be orthologous with genes in the Corynebacterium glutamicum, Corynebacterium efficiens, and Corynebacterium diphtheriae genomes. These genes apparently represent the chromosomal backbone that is conserved between the four corynebacteria. Among the genes that lack an ortholog in the known corynebacterial genomes, many are located close to transposable elements or revealed an atypical G+C content, indicating that horizontal gene transfer played an important role in the acquisition of genes involved in iron and manganese homeostasis, in multidrug resistance, in bacterium-host interaction, and in virulence. Metabolic analyses of the genome sequence indicated that the "lipophilic" phenotype of C. jeikeium most likely originates from the absence of fatty acid synthase and thus represents a fatty acid auxotrophy. Accordingly, both the complete gene repertoire and the deduced lifestyle of C. jeikeium K411 largely reflect the strict dependence of growth on the presence of exogenous fatty acids. The predicted virulence factors of C. jeikeium K411 are apparently involved in ensuring the availability of exogenous fatty acids by damaging the host tissue.


The evolving landscape of metastatic renal cell carcinoma.
The treatment paradigm in metastatic renal cell carcinoma (mRCC) has evolved over the last 5 years. There are now seven approved targeted therapies against the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. The use of targeted therapy, sequences, combinations, and investigational compounds will be discussed. Prognostic and predictive tools are detailed, although much work must be done to find predictive biomarkers in an effort to individualize therapy for patients.


A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons.
1. A long-lasting afterhyperpolarization (AHP) follows current-induced repetitive firing in hippocampal CA1 neurons studied in vitro. A 10-25% increase in membrane slope conductance occurs during the AHP, suggesting that it may be mediated by an increased conductance to either K+ or Cl-. 2. Intracellular Cl- iontophoresis does not alter the AHP but does attenuate the IPSP. In contrast Ba2+, a cation that can decrease K+ conductance, eliminates the AHP but not the IPSP. These findings suggest the AHP is produced by a long-lasting increased conductance to K+, and is distinct from the IPSP. 3. Mn2+, a Ca2+-channel blocker, eliminates the AHP. In comparison, the AHP persists in the presence of the Na+-channel blocker, tetrodotoxin (TTX), and appears to be temporally associated with TTX-resistant "Ca2+ spikes." It is concluded that AHP is probably activated by Ca2+ influx. 4. These observations indicate that the AHP may be produced by a Ca2+ activated K+ current. A balance between cellular depolarization produced by Ca2+ entry and repolarization generated by a Ca2+-activated K+ current appears to operate to control excitability in some mammalian cortical neurons as it does in molluscan neurons. Disruption of this balance by Ba2+ produces spontaneous membrane-potential oscillations and recurrent burst firing in hippocampal neurons. Increases in the magnitude and duration of Ca2+ depolarization and/or decreases in the Ca2+-activated, K+-mediated repolarization may be mechanisms that lead to spontaneous, epileptiform bursting in mammalian cortical neurons.


The emerging story of acute lymphoblastic leukemia among the Latin American population - biological and clinical implications.
Higher incidence rates and poor outcomes have been reported among Latin American patients (Latinos) with acute lymphoblastic leukemia (ALL). Distinct patterns in recent genomic studies allude to a predisposing genetic component. In this review, we critically examine the increasing amount of empirical information on the epidemiology, outcomes and genomics of Latinos with ALL. We discuss the immense diversity within the Latino community and varying definitions of what is considered Latino, which pose an epidemiological challenge. Environmental factors have been evaluated as possible predisposing factors in the development of ALL but studies have produced conflicting results. In this review we describe chromosomal abnormalities and the specific genomic landscape in Latinos with ALL and their association with unfavorable prognosis, focusing on the higher frequency of Philadelphia chromosome-Like ALL. Recent data suggest an association between polymorphisms that are commonly found in indigenous Americans and high rates of ALL. The review compares the distribution of ALL throughout the various countries in Latin America in an attempt to shed some epidemiological light on the genetic ancestry of ALL. We additionally identify areas where research is warranted in efforts toward the advent of novel targeted agents that are relevant in improving outcomes within the Latino community.


Design, synthesis and DNA interaction studies of new fluorescent platinum complex containing anti-HIV drug didanosine.
Forming coordination complexes with nucleoside analogues may be helpful in studying anti-tumour activity of them. Therefore, to improve the clinical efficacy of nucleoside analogue and design new ones, a new fluorescent platinum (Pt) complex with anti-human immunodeficiency virus drug didanosine (ddI); K[PtCl(OCH3)2(ddI)]; was synthesized and characterized. The ultraviolet-visible (UV-vis) spectroscopy, infrared, thermogravimetric analysis, mass assignments and elemental analysis confirmed the preparation of the complex. The molecular ion peaks seen at the positive mass spectrum of Pt complex confirm coordination of the drug to metal centre. The interaction of this complex with calf thymus DNA (ct-DNA) was studied using several spectroscopic techniques such as UV absorption, fluorescence spectroscopy and dynamic viscosity measurements. Hyperchromism of the band in the UV-vis spectra and the intrinsic binding constant (0.56 ± 0.25) × 104 M-1, decreasing in Hoechst-DNA fluorescence by adding Pt complex concentration and also relatively small changes in DNA viscosity indicated that this complex could interact as a groove-binder. According to the UV spectra and the fluorescence quenching of the complex in our case seems to be primarily caused by complex formation between the Pt complex and DNA. The thermodynamic parameters showed that hydrogen bond and van der Waals interactions play main roles in the binding of Pt complex to ct-DNA. The free energy values are negative, showing the spontaneity of the Pt complex-DNA binding. The docking simulation was performed and the results confirm a preference of groove site of synthesized complex on DNA helix. The knowledge gained from this study will be helpful to further understand the DNA binding mechanism and can also provide much fruitful information for designing a new type of anti-cancer drugs.Communicated by Ramaswamy H. Sarma.


Interferons in cancer immunoediting: sculpting metastasis and immunotherapy response.
Interferons (IFNs) are pleiotropic cytokines critical for regulation of epithelial cell functions and for immune system regulation. In cancer, IFNs contribute to tumor-intrinsic and -extrinsic mechanisms that determine the quality of antitumor immunity and response to immunotherapy. In this Review, we focus on the different types of tumor IFN sensitivity that determine dynamic tumor-immune interactions and their coevolution during cancer progression and metastasis. We extend the discussion to new evidence supporting immunotherapy-mediated immunoediting and the dual opposing roles of IFNs that lead to immune checkpoint blockade response or resistance. Understanding the intricate dynamic responses to IFN will lead to novel immunotherapeutic strategies to circumvent protumorigenic effects of IFN while exploiting IFN-mediated antitumor immunity.


IgG antibodies from patients with bullous pemphigoid bind to localized epitopes on synthetic peptides encoded by bullous pemphigoid antigen cDNA.
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized in part by the presence of tissue-bound and circulating antibodies specific for basement membrane zone proteins, the BP Ag. The purpose of the present study was to determine seroreactivity of patients with BP to six nonoverlapping synthetic peptides representing sequences in the carboxyl domain of the recently cloned 230-kDa BP Ag. Sera from 40 patients with BP, 57 normal subjects, and 18 patients with other autoimmune blistering skin diseases were examined in an ELISA for binding to six synthetic peptides varying between 17 and 19 amino acids in length. The binding of IgG from patients with BP to three synthetic peptides, P1-2, P1-1, and P3-1, was significantly different from that seen in the normal controls (p less than 0.001, Fisher's exact test). Affinity-purified anti-P1-2 antibody from a patient with BP bound in a characteristic linear band to the epidermal side of 1 M NaCl split skin and immunoprecipitated the native 230-kDa BP Ag. Serum IgG antibodies from a rabbit immunized with a BP fusion protein that contains the sequences for P1-1 and P1-2, bound on ELISA to P1-2 but not to P1-1. These data suggest that multiple epitopes on the 230-kDa BP Ag are recognized by circulating autoantibodies in patients with this disease, and that an epitope encoded within the synthetic peptide P1-2 is expressed on the native molecule and may be relevant in the generation of an immune response both in man and in an animal model.


Ruthenium nanoparticles on nano-level-controlled carbon supports as highly effective catalysts for arene hydrogenation.
The reaction of three types of carbon nanofibers (CNFs; platelet: CNF-P, tubular: CNF-T, herringbone: CNF-H) with [Ru3(CO)12] in toluene heated at reflux provided the corresponding CNF-supported ruthenium nanoparticles, Ru/CNFs (Ru content = 1.1-3.8 wt %). TEM studies of these Ru/CNFs revealed that size-controlled Ru nanoparticles (2-4 nm) exist on the CNFs, and that their location was dependent on the surface nanostructures of the CNFs: on the edge of the graphite layers (CNF-P), in the tubes and on the surface (CNF-T), and between the layers and on the edge (CNF-H). Among these Ru/CNFs, Ru/CNF-P showed excellent catalytic activity towards hydrogenation of toluene with high reproducibility; the reaction proceeded without leaching of the Ru species, and the catalyst was reusable. The total turnover number of the five recycling experiments for toluene hydrogenation reached over 180,000 (mol toluene) (mol Ru)(-1). Ru/CNF-P was also effective for the hydrogenation of functionalized benzene derivatives and pyridine. Hydrogenolysis of benzylic C-O and C-N bonds has not yet been observed. Use of poly(ethylene glycol)s (PEGs) as a solvent made possible the biphasic catalytic hydrogenation of toluene. After the reaction, the methylcyclohexane formed was separated by decantation without contamination of the ruthenium species and PEG. The insoluble PEG phase containing all of the Ru/CNF was recoverable and reusable as the catalyst without loss of activity.


Recruitment of DNA Repair MRN Complex by Intrinsically Disordered Protein Domain Fused to Cas9 Improves Efficiency of CRISPR-Mediated Genome Editing.
CRISPR/Cas9 is a powerful tool for genome editing in cells and organisms. Nevertheless, introducing directed templated changes by homology-directed repair (HDR) requires the cellular DNA repair machinery, such as the MRN complex (Mre11/Rad50/Nbs1). To improve the process, we tailored chimeric constructs of Cas9, in which SpCas9 was fused at its N- or C-terminus to a 126aa intrinsically disordered domain from HSV-1 alkaline nuclease (UL12) that recruits the MRN complex. The chimeric Cas9 constructs were two times more efficient in homology-directed editing of endogenous loci in tissue culture cells. This effect was dependent upon the MRN-recruiting activity of the domain and required lower amounts of the chimeric Cas9 in comparison with unmodified Cas9. The new constructs improved the yield of edited cells when making endogenous point mutations or inserting small tags encoded by oligonucleotide donor DNA (ssODN), and also with larger insertions encoded by plasmid DNA donor templates. Improved editing was achieved with both transfected plasmid-encoded Cas9 constructs as well as recombinant Cas9 protein transfected as ribonucleoprotein complexes. Our strategy was highly efficient in restoring a genetic defect in a cell line, exemplifying the possible implementation of our strategy in gene therapy. These constructs provide a simple approach to improve directed editing.


Cortisol levels in hair are altered in irritable bowel syndrome - A case control study in primary care.
Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls. In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints. The participants donated hair samples and completed questionnaires including a scale of self-reported perceived stress (PSS). 169 Rome III-fulfilling IBS patients and 316 non-IBS patients were available for final analyses. IBS patients had significantly lower HCC, median=16.3pg/mg, IQR=26.9pg/mg, compared to non-IBS patients, median=22.8pg/mg, IQR=29.1pg/mg. There was also a difference in the distribution of HCC quintiles between the two groups, with 30.2% IBS patients and 14.2% of non-IBS patients in the lowest quintile of HCC. PSS was higher among IBS patients with a mean (SD) total score of 25.3 (8.0) compared to controls 21.4, (7.5). Quintiles of HCC and PSS stayed significantly but very weakly related to IBS (B=-0.332, Std error=0.146, p<0.005) in multivariable analyses. This study suggests a possible suppression of the HPA-axis activity in a considerable portion of IBS patients.


High frequency dynamics in liquid nickel: An inelastic x-ray scattering study.
Owing to their large relatively thermal conductivity, peculiar, nonhydrodynamic features are expected to characterize the acousticlike excitations observed in liquid metals. We report here an experimental study of collective modes in molten nickel, a case of exceptional geophysical interest for its relevance in earth interior science. Our result shed light on previously reported contrasting evidences: In the explored energy-momentum region, no deviation from the generalized hydrodynamic picture describing nonconductive fluids is observed. Implications for high frequency transport properties in metallic fluids are discussed.


Towards improving the safety and diagnostic yield of stereotactic biopsy in a single centre.
Previously, we reported on our single centre results regarding the diagnostic yield of stereotactic needle biopsies of brain lesions. The yield then (1996-2006) was 89.4%. In the present study, we review and evaluate our experience with intraoperative frozen-section histopathologic diagnosis on-demand in order to improve the diagnostic yield. One hundred sixty-four consecutive frameless biopsy procedures in 160 patients (group 1, 2006-2010) were compared with the historic control group (group 2, n = 164 frameless biopsy procedures). Diagnostic yield, as well as demographics, morbidity and mortality, was compared. Statistical analysis was performed by Student's t, Mann-Whitney U, Chi-square test and backward logistic regression when appropriate. Demographics were comparable. In group 1, a non-diagnostic tissue specimen was obtained in 1.8%, compared to 11.0% in group 2 (p = 0.001). Also, both the operating time and the number of biopsies needed were decreased significantly. Procedure-related mortality decreased from 3.7% to 0.6% (p = 0.121). Multivariate analysis only proved operating time (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.000-1.025; p = 0.043), a right-sided lesion (OR, 3.183; 95% CI, 1.217-8.322; p = 0.018) and on-demand intraoperative histology (OR, 0.175; 95% CI, 0.050-0.618; p = 0.007) important factors predicting non-diagnostic biopsies. The importance of a reliable pathological diagnosis as obtained by biopsy must not be underestimated. We believe that when performing stereotactic biopsy for intracranial lesions, next to minimising morbidity, one should strive for as high a positive yield as possible. In the present single centre retrospective series, we have shown that using a standardised procedure and careful on-demand intraoperative frozen-section analysis can improve the diagnostic yield of stereotactic brain biopsy procedures as compared to a historical series.


Evaluation of the changes in hepatic apparent diffusion coefficient and hepatic fat fraction in healthy cats during body weight gain.
To determine the change in mean hepatic apparent diffusion coefficient (ADC) and hepatic fat fraction (HFF) during body weight gain in cats by use of MRI. 12 purpose-bred adult neutered male cats. The cats underwent general health and MRI examination at time 0 (before dietary intervention) and time 1 (after 40 weeks of being fed high-energy food ad libitum). Sequences included multiple-echo gradient-recalled echo MRI and diffusion-weighted MRI with 3 b values (0, 400, and 800 s/mm2). Variables (body weight and the HFF and ADC in selected regions of interest in the liver parenchyma) were compared between time points by Wilcoxon paired-sample tests. Relationships among variables were assessed with generalized mixed-effects models. Median body weight was 4.5 and 6.5 kg, mean ± SD HFF was 3.39 ± 0.89% and 5.37 ± 1.92%, and mean ± SD hepatic ADC was 1.21 ± 0.08 × 10-3 mm2/s and 1.01 ± 0.2 × 10-3 mm2/s at times 0 and 1, respectively. Significant differences between time points were found for body weight, HFF, and ADC. The HFF was positively associated with body weight and ADC was negatively associated with HFF. Similar to findings in people, cats had decreasing hepatic ADC as HFF increased. Protons associated with fat tissue in the liver may reduce diffusivity, resulting in a lower ADC than in liver with lower HFF. Longer studies and evaluation of cats with different nutritional states are necessary to further investigate these findings.


Immediate improvement of left ventricular mechanics following transcatheter aortic valve replacement.
Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). Transcatheter aortic valve replacement (TAVR) has become a widespread technique for patients with severe AS considered inoperable or high risk for traditional open-surgery. This procedure could have a positive impact in LV mechanics. The aim of this study was to evaluate the immediate effect of TAVR on LV function recovery, as assessed by myocardial deformation parameters. One-hundred twelve consecutive patients (81.4 ± 6.4 years, 50% female) from 10 centres in Europe with severe AS who successfully underwent TAVR with either a self-expanding CoreValve (Medtronic, Minneapolis, MN) or a mechanically expanded Lotus valve (Boston Scientific, Natick, MA) were enrolled in a prospective multi-center study. A complete echocardiographic examination was performed at baseline and immediately before discharge, including the assessment of LV strain using standard two-dimensional images. Echocardiographic examination with global longitudinal strain (GLS) quantification could be obtained in 92 patients, because of echocardiographic and logistic reasons. Between examinations, a modest statistically significant improvement in GLS could be seen (GLS% -15.00 ± 4.80 at baseline;-16.15 ± 4.97 at discharge, p = 0.028). In a stratified analysis, only women showed a significant improvement in GLS and a trend towards greater improvement in GLS according to severity of systolic dysfunction as measured by LV ejection fraction could be noted. Immediate improvement in GLS was appreciated after TAVR procedure. Whether this finding continues to be noted in a more prolonged follow-up and its clinical implications need to be assessed in further studies.


Molecular identification of a novel mammalian brain isoform of acyl-CoA:lysophospholipid acyltransferase with prominent ethanolamine lysophospholipid acylating activity, LPEAT2.
Acyl-CoA-dependent lysophospholipid acyltransferases play an important role in attaining the appropriate molecular species of phospholipids. A number of genes encoding these activities were recently identified. It has become clear that multiple genes can encode one enzymatic activity and that a given gene may encode multiple activities. Here we report the identification of a gene encoding a mammalian acyl-CoA-dependent lysophospholipid acyltransferase with prominent activity toward ethanolamine-containing lysophospholipids, which we termed acyl-CoA:lysophosphatidylethanolamine acyltransferase 2, LPEAT2 (previously annotated as AYTL3 or AGPAT7). LPEAT2 is predominantly expressed in brain, coinciding with an enrichment of phosphatidylethanolamine in this tissue. Ectopic expression of LPEAT2 in mammalian HEK293T cells led to a dramatic increase (up to 9-fold) in LPEAT activity when compared with cells transfected with empty vector or an unrelated acyltransferase. LPEAT2 also exhibited significant acyl-CoA-dependent acyltransferase activity toward 1-O-alkenyl-lysophosphatidylethanolamine, lysophosphatidylglycerol, 1-O-alkyl-lysophosphatidylcholine, lysophosphatidylserine, and lysophosphatidylcholine but lacked appreciable acylating activity toward glycerol 3-phosphate, lysophosphatidic acid, lysophosphatidylinositol, and diacylglycerol, demonstrating multiple but selective functions of LPEAT2 as an enzyme involved in phospholipid remodeling. LPEAT2 recognizes a broad range of medium and long chain fatty acyl-CoA, and its activity was not affected by Ca(2+). When overexpressed in mammalian cells, LPEAT2 is localized to the endoplasmic reticulum. siRNA-mediated knockdown of LPEAT2 in HEK293T cells significantly decreased LPEAT and 1-alkenyl-LPEAT activities but did not affect other lysophospholipid acylating activities. These findings identify LPEAT2 as an important enzyme in the biosynthesis of ethanolamine-containing phospholipids, especially in brain.


The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice.
Salmonella resides within host cells in a vacuole that it modifies through the action of virulence proteins called effectors. Here we examined the role of two related effectors, SopD and SopD2, in Salmonella pathogenesis. Salmonella enterica serovar Typhimurium (S. Typhimurium) mutants lacking either sopD or sopD2 were attenuated for replication in the spleens of infected mice when competed against wild-type bacteria in mixed infection experiments. A double mutant lacking both effector genes did not display an additive attenuation of virulence in these experiments. The double mutant also competed equally with both of the single mutants. Deletion of either effector impaired bacterial replication in mouse macrophages but not human epithelial cells. Deletion of sopD2 impaired Salmonella's ability to form tubular membrane filaments [Salmonella-induced filaments (Sifs)] in infected cells; the number of Sifs decreased, whereas the number of pseudo-Sifs (thought to be a precursor of Sifs) was increased. Transfection of HeLa cells with the effector SifA induced the formation of Sif-like tubules and these were observed in greater size and number after co-transfection of SifA with SopD2. In infected cells, SifA and SopD2 were localized both to Sifs and to pseudo-Sifs. In contrast, deletion of sopD had no effect on Sif formation. Our results indicate that both SopD and SopD2 contribute to virulence in mice and suggest a functional relationship between these two proteins during systemic infection of the host.


Cigarette smoking before and after an excise tax increase and an antismoking campaign--Massachusetts, 1990-1996.
In November 1992, residents of Massachusetts approved a ballot petition (Question 1) that increased the tax on each pack of cigarettes from $.26 to $.51 beginning January 1, 1993, and requested that the legislature spend the proceeds on tobacco control and health education. The Massachusetts Tobacco Control Program (MTCP), administered by the Massachusetts Department of Public Health (MDPH), was established in response to the approval of the petition. In October 1993, MTCP initiated a statewide mass-media antismoking campaign. In early 1994, the program began funding local boards of health and school health and other youth programs to promote policies to reduce public exposure to environmental tobacco smoke and to restrict youth access to cigarettes. Efforts also included support to health education programs, primary-care providers, and other services to help smokers quit. Through June 1996, MTCP expenditures totaled $116 million, including $43 million for the mass-media campaign. To assess the effects of the excise tax increase and the antismoking campaign on cigarette smoking in Massachusetts, CDC and MDPH analyzed data about the number of packs of cigarettes taxed per capita and the prevalence of cigarette smoking during the period preceding (1990-1992) and following (1993-1996) implementation of the ballot petition. This report summarizes the findings of the assessment and compares trends in cigarette consumption (i.e., purchases) in Massachusetts, in California (where a voter-mandated cigarette tax increase in January 1989 funded a statewide antismoking campaign that began in April 1990, and in the 48 remaining states and the District of Columbia combined. The findings suggest that the number of packs of cigarettes taxed per capita declined substantially in Massachusetts after implementation of the ballot petition.


Pharmacological analysis of intrinsic neuronal oscillations in rd10 retina.
In the widely used mouse model of retinal degeneration, rd1, the loss of photoreceptors leads to rhythmic electrical activity of around 10-16 Hz in the remaining retinal network. Recent studies suggest that this oscillation is formed within the electrically coupled network of AII amacrine cells and ON-bipolar cells. A second mouse model, rd10, displays a delayed onset and slower progression of degeneration, making this mouse strain a better model for human retinitis pigmentosa. In rd10, oscillations occur at a frequency of 3-7 Hz, raising the question whether oscillations have the same origin in the two mouse models. As rd10 is increasingly being used as a model to develop experimental therapies, it is important to understand the mechanisms underlying the spontaneous rhythmic activity. To study the properties of oscillations in rd10 retina we combined multi electrode recordings with pharmacological manipulation of the retinal network. Oscillations were abolished by blockers for ionotropic glutamate receptors and gap junctions. Frequency and amplitude of oscillations were modulated strongly by blockers of inhibitory receptors and to a lesser extent by blockers of HCN channels. In summary, although we found certain differences in the pharmacological modulation of rhythmic activity in rd10 compared to rd1, the overall pattern looked similar. This suggests that the generation of rhythmic activity may underlie similar mechanisms in rd1 and rd10 retina.