Residential Immersive Life Skills Programs: A Catalyst for Facilitating Emotional Literacy Development for Youth with Disabilities.
Residential Immersive life skills (RILS) programs are unique programs for youth with disabilities. These programs enable youth to develop adaptive behaviors required to navigate adulthood. This study explored the emergence of emotional literacy development for youth who attended RILS programs. This study draws on twenty-five qualitative interviews that were conducted with nine youth who attended RILS programs. Data were analyzed using thematic analysis, aligned to a phenomenological approach. The themes reflecting emotional literacy development in youth were: (1) Enhanced intrapersonal development; (2) Shifts in emotional regulation and emotional responses; (3) Realized potential and self-actualization. The opportunities and experiences offered in the RILS programs have the potential to facilitate emotional literacy development in youth with disabilities. The findings contribute towards the research evidence on the importance of emotional literacy development in young people with disabilities and the development and mobilization of evidence-based life skills programs.


Effects of Galvanic vestibular stimulation on cognitive function.
Although imaging studies suggest activation of cortical areas by vestibular input, there is little evidence of an adverse effect of non-veridical vestibular input on cognitive function. To test the hypothesis that degraded vestibular afferent input adversely affects cognition, we compared performance on a cognitive test battery in a group undergoing suprathreshold bilateral bipolar Galvanic vestibular stimulation (GVS) with a control group receiving no GVS or subthreshold stimulation. The battery consisted of six cognitive tests as follows: reaction time, dual tasking, Stroop, mental rotation, perspective-taking and matching-to-sample, as well as a simple visuomotor (manual tracking) task. Subjects performed the test battery before, during and after suprathreshold GVS exposure or subthreshold stimulation. Suprathreshold GVS significantly increased error rate for the match-to-sample and perspective-taking tasks relative to the subthreshold group, demonstrating a negative effect of non-veridical vestibular input in these specific cognitive tasks. Reaction time, dual tasking, mental rotation and manual tracking were unaffected by GVS exposure. The adverse effect of suprathreshold GVS on perspective taking but not mental rotation is consistent with imaging studies, which have demonstrated that egocentric mental transformations (perspective taking) occur primarily in cortical areas that receive vestibular input (the parietal-temporal junction and superior parietal lobule), whereas object-based transformations (mental rotation) occur in the frontoparietal region. The increased error rate during the match-to-sample task is likely due to interference with hippocampal processing related to spatial memory, as suggested by imaging studies on vestibular patients.


[Correction of immunodeficiency status caused by herbicide 2,4-D in experiment].
A possibility to correct the immunodeficiency state, caused by herbicide 2.4-D (20 mg/kg of weight daily during 5 days), by using immunomodulators Levamisole (perorally), Tactivinum (hypodermically) and Spleninum (hepodermically) in reactions Graft-versus-Host (GH), Antibody-Forming Cells (AFG) and phagocytic activity of peritoneal macrophages in vivo and in vitro etc, was studied in experiments with 360 mice of lines CBA and F1 (CBAxC57B1/6) weighing 18 to 22 g. It was established that Levamisole (2.5 mg/kg per body weight, for 1 to 3 days) and Tactivinum (0.2 mkg/mouse, for 1 to 3 days) had an immunocorrecting effect in poisoning by 2.4-D. Spleninum (10 mcl/mouse) corrected mainly the humoral chain in the immune response with the AFG recovery to the level observed in intact animals (controls). The data on the influence produced by the immunomodulators on the phagocytic activity in vitro correlated with such data obtained in vivo.


So you want to be ... a medical oncologist.
We are all influenced in our choice of career by senior doctors that we come into contact with as medical students or junior doctors. I had such an influential encounter as a student at Barts. Professor Gordon Hamilton-Fairley was a new breed in a fledgling specialty which was burgeoning in the USA as a result of dramatic advances in the treatment of patients with haematological malignancies, especially Hodgkin's disease. His appeared to be a rather maverick world, the treatments could not be found in any textbook and patients were scattered the length and breadth of the hospital.


[Profile of the neurotic personality and its prevention in adulthood].
The neurotic personality creates numerous problems of behaviour in the infant and youth population. Given that this profile is not described in the manuals of psychopathology, we offer our criteria for its detection and treatment. One is dealing with patients who live anchored in an infantile egocentricity, intolerant in face of frustrations and highly dissatisfied. These basic symptoms are complemented by some that we describe in our questionnaire: Q-2-O ("QUESTIONARI 2, d'Osona") which might help in evaluating their intensity: anxiety, psychomotor restlessness, dysthymia, indiscipline, aggressiveness and laziness. This maturational stagnation is accompanied by the certitude that they cannot change, because "that's how they are". With a highly vigilant super-ego, they can achieve a perfect socio-school adaptation, while at home their tyranny makes them unbearable. We suggest a genetic based aetiology, but there is much in this disorder that is learned. That is where we focus its treatment. It is necessary to correct this behaviour before adult life is reached.


Effects of yearling, juvenile and adult survival on reef manta ray (Manta alfredi) demography.
The trade in manta ray gill plates has considerably increased over the last two decades. The resulting increases in ray mortality, in addition to mortality caused by by-catch, has caused many ray populations to decrease in size. The aim of this study was to ascertain how yearling and juvenile growth and survival, and adult survival and reproduction affect reef manta ray (Manta alfredi) population change, to increase our understanding of manta ray demography and thereby improve conservation research and measures for these fish. We developed a population projection model for reef manta rays, and used published life history data on yearling and juvenile growth and adult reproduction to parameterise the model. Because little is known about reef manta ray yearling and juvenile survival, we conducted our analyses using a range of plausible survival rate values for yearlings, juveniles and adults. The model accurately captured observed variation in population growth rate, lifetime reproductive success and cohort generation time in different reef manta ray populations. Our demographic analyses revealed a range of population consequences in response to variation in demographic rates. For example, an increase in yearling or adult survival rates always elicited greater responses in population growth rate, lifetime reproductive success and cohort generation time than the same increase in juvenile survival rate. The population growth rate increased linearly, but lifetime reproductive success and cohort generation time increased at an accelerating rate with increasing yearling or adult survival rates. Hence, even a small increase in survival rate could increase lifetime reproductive success by one pup, and cohort generation time by several years. Elasticity analyses revealed that, depending on survival rate values of all life stages, the population growth rate is either most sensitive to changes in the rate with which juveniles survive but stay juveniles (i.e., do not mature into adults) or to changes in adult survival rate. However, when assessing these results against estimates on population growth and adult survival rates for populations off the coasts of Mozambique and Japan, we found that the population growth rate is predicted to be always most sensitive to changes in the adult survival rate. It is important to gain an in-depth understanding of reef manta ray life histories, particularly of yearling and adult survival rates, as these can influence reef manta ray population dynamics in a variety of ways. For declining populations in particular, it is crucial to know which life stage should be targeted for their conservation. For one such declining population off the coast of Mozambique, adult annual survival rate has the greatest effect on population growth, and by increasing adult survival by protecting adult aggregation sites, this population's decline could be halted or even reversed.


Maternal dietary protein restriction and excess affects offspring gene expression and methylation of non-SMC subunits of condensin I in liver and skeletal muscle.
Recent evidence indicates that maternal nutrition during pregnancy influences gene expression in offspring through epigenetic alterations. In the present study we evaluated the effect of protein excess and deficiency during porcine pregnancy on offspring hepatic and skeletal muscular expression patterns of key genes of methionine metabolism (DNMT1, DNMT3a, DNMT3b, BHMT, MAT2B and AHCYL1), condensin I subunit genes (NCAPD2, NCAPG and NCAPH), important for chromosome condensation and segregation, global DNA methylation and gene-specific DNA methylation. German Landrace sows were randomly assigned to control (CO), high protein (HP) and low protein (LP) diet groups. Tissue samples of offspring were collected from fetal (dpc95), newborn (dpn1), weanling (dpn28) and finisher pigs (dpn188). Gene expression of DNMT1, DNMT3a and DNMT3b was influenced by both HP and LP diets, indicating an involvement of DNA methylation in fetal programming by maternal protein supply. Moreover, hepatic global methylation was significantly affected by protein restriction at dpc95 (p = 0.004) and by protein excess at dpn188 (p = 0.034). Gene expression in fetal liver was significantly different between CO and LP for NCAPD2 (p = 0.0005), NCAPG (p = 0.0009) and NCAPH (p < 0.0001). In skeletal muscle, LP fetuses had significantly altered gene expression of NCAPD2 (p = 0.020) and NCAPH (p = 0.001), compared with CO. Furthermore, NCAPG was differentially methylated among LP, HP and CO; indeed, a significant positive correlation was detected with transcript amount in fetal pigs (r = 0.47, p = 0.002). These data demonstrate that both restriction and excess dietary protein during pregnancy alters the offspring's epigenetic marks and influences gene expression.


Factors Associated with Surgical Treatment in Postpartum Women with Mastitis or Breast Abscess: A Retrospective Cohort Study.
Objective: The aim of this study was to identify factors associated with requiring surgical treatment for mastitis or breast abscess in postpartum mothers. Materials and Methods: This was a retrospective cohort study using the Japan Medical Data Center Claims Database. Information on pairs of infants born between April 2012 and December 2016 and their mothers were extracted. Data regarding the baseline characteristics, medical history, medical practice, and prescription drugs of mothers and their infants were collected. Multivariable logistic regression analysis was used to examine factors associated with undergoing surgical treatment. Results: The data of 69,363 eligible mothers were analyzed. The proportion of mothers who were diagnosed with mastitis or breast abscess within 1 year after childbirth was 10.8% (7,516/69,363). There were 114 mothers who underwent surgical treatment within 1 year after childbirth. This was 0.2% of all mothers and 1.5% of those diagnosed with mastitis or breast abscess. Surgical treatment was significantly associated with mothers having their first child (adjusted odds ratio [AOR], 2.58; 95% confidence interval [CI], 1.63-4.07) compared to those with a second or later child; it was also significantly associated with the diagnosis of breast abscess (AOR, 10.38; 95% CI, 5.28-20.40). Conclusions: This was the first report of the prevalence of mastitis or breast abscess and the requirement for surgical treatment among postpartum mothers in Japan. A first diagnosis of breast abscess and having a first child were associated with requiring surgical treatment. Health care professionals providing postpartum care should be aware of these factors.


Association of TLR4-T399I polymorphism with chronic obstructive pulmonary disease in smokers.
Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.


Integrating space with place in health research: a multilevel spatial investigation using child mortality in 1880 Newark, New Jersey.
Research on neighborhoods and health increasingly acknowledges the need to conceptualize, measure, and model spatial features of social and physical environments. When ignoring underlying spatial dynamics, we run the risk of biased statistical inference and misleading results. In this article, we propose an integrated multilevel spatial approach for Poisson models of discrete responses. In an empirical example of child mortality in 1880 Newark, New Jersey, we compare this multilevel spatial approach with the more typical aspatial multilevel approach. Results indicate that spatially defined egocentric neighborhoods, or distance-based measures, outperform administrative areal units, such as census units. In addition, although results do not vary by specific definitions of egocentric neighborhoods, they are sensitive to geographic scale and modeling strategy. Overall, our findings confirm that adopting a spatial multilevel approach enhances our ability to disentangle the effect of space from that of place, pointing to the need for more careful spatial thinking in population research on neighborhoods and health.


Compensation for effects of linear motion in MR imaging.
Various compensation methods for different types of motion during MR image acquisition have been proposed. Presented here is a postprocessing scheme for eliminating artifacts due to linear, intra-slice motion of known velocity. The data for each phase encoding or "view" acquired from a moving object are shown to differ from those which would be measured from the stationary object by a phase factor which depends on the object's displacement from a reference point. This derivation is then used to propose a correction scheme for linear motion in which all phase encodings measured at different positions of the moving object are collapsed onto the same reference position. After subsequent reconstruction, the object appears perfectly "focused." By selection of different reference positions, the method permits positioning of the compensated object as desired within the field of view of the image. This property allows the method to be extended to create sequences of corrected images with smooth object motion between frames of the sequence. The basic correction scheme and its variations were tested experimentally in phantom studies with velocities as large as 8 cm/s.


Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO.
In aerobic cells, urate is oxidized to 5-hydroxyisourate by two distinct enzymes: a coenzyme-independent urate oxidase (EC 220.127.116.11) found in eukaryotes and bacteria like Bacillus subtilis and a prokaryotic flavoprotein urate hydroxylase (HpxO) originally found in some Klebsiella species. More cases of analogous or non-homologous isofunctional enzymes (NISE) for urate catabolism have been hypothesized by inspecting bacterial genomes. Here, we used a functional complementation approach in which a candidate gene for urate oxidation is integrated by homologous recombination in the Acinetobacter baylyi ADP1 genome at the locus of its original hpxO gene. Catabolism of urate was restored in A. baylyi ADP1 expressing a FAD-dependent protein from Xanthomonas campestris, representing a new urate hydroxylase family that we called HpyO. This enzyme was kinetically characterized and compared with other HpxO enzymes. In contrast to the latter, HpyO is a typical Michaelian enzyme. This work provides the first experimental evidences for the function of HpyO in bacterial urate catabolism and establishes it as a NISE of HpxO.


Psychometric properties of the parent and teacher forms of the Japanese version of the Strengths and Difficulties Questionnaire.
This study examined the psychometric properties of the parent and teacher forms of the Japanese version of the Strengths and Difficulties Questionnaire (SDQ). Parents and teachers of 1487 elementary school children (759 boys and 728 girls aged 6-12 years) participated in this study. The results of confirmatory factor analyses of the parent and teacher versions of the SDQ supported the five-factor structure reported in previous studies. However, factor invariance across sex was not observed. The alpha coefficients for the subscales of the SDQs varied between 0.55 and 0.86, the same reliability measures that were also reported in previous studies. Moreover, analyses of variance showed significant differences on all of the subscales according to sex and teacher-parent ratings. The factor structure of the SDQ was generally supported, but more gender-segregated investigations of the factor structures are needed. Parents tended to give higher ratings on the difficulties and strengths of children compared to the teachers. Boys were rated higher than girls were on difficulties, while girls were rated higher than boys were on strengths.


Survivorship Care Plan Preferences and Utilization Among Asian American Breast Cancer Survivors.
The survivorship care plan (SCP) is an individualized document with cancer diagnosis, treatment, surveillance, and health promotion recommendations. This integrative review synthesizes the extant literature to understand preferences and utilization of SCPs among Asian American survivors. The CINAHL®, Embase®, PsycINFO®, and PubMed® databases were searched for articles about Asian American women with breast or cervical cancer and SCPs. Two independent reviewers evaluated 481 titles and abstracts according to inclusion and exclusion criteria. Of those 481 titles and abstracts, 14 articles were selected for inclusion. There was little evidence surrounding utilization of SCPs. Articles identified addressed only survivors of breast cancer, predominately of Southeast Asian descent. Asian American women with breast cancer reported preferences surrounding their survivorship needs. Barriers to delivery of the SCP were related to socioeconomic factors. There is a paucity of information guiding evidence-based delivery of SCPs in the vastly heterogenous population of Asian American survivors. More work is needed to provide high-quality care to these survivors.


Neuraxial opioid-induced pruritus: An update.
Pruritus is a troublesome side-effect of neuraxial (epidural and intrathecal) opioids. Sometimes it may be more unpleasant than pain itself. The prevention and treatment still remains a challenge. A variety of medications with different mechanisms of action have been used for the prevention and treatment of opioid-induced pruritus, with mixed results. The aim of this article is to review the current body of literature and summarize the current understanding of the mechanisms and the pharmacological therapies available to manage opioid-induced pruritus. The literature source of this review was obtained via PubMed, Medline and Cochrane Database of Systematic Reviews until 2012. The search results were limited to the randomized controlled trials, systemic reviews and non-systemic reviews.


Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells.
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables such as broccoli. The ability of SFN to inhibit histone deacetylase (HDAC) enzymes may be one mechanism by which it acts as a chemoprevention agent. The ability of a chemopreventive agent to specifically cause cytotoxicity in cancer and not normal cells is an important factor in determining its safety and clinical relevance. We characterized the effects of SFN in normal (PrEC), benign hyperplasia (BPH1) and cancerous (LnCap and PC3) prostate epithelial cells. We observed that 15 μM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells. SFN treatment also selectively decreased HDAC activity, and Class I and II HDAC proteins, increased acetylated histone H3 at the promoter for P21, induced p21 expression and increased tubulin acetylation in prostate cancer cells. HDAC6 over-expression was able to reverse SFN-induced cyotoxicity. In PrEC cells, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. The differences in sensitivity to SFN in PrEC and PC3 are likely not due to differences in SFN metabolism or differences in phase 2 enzyme induction. SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.


[Application of automated quantitative cytometry in diagnosis of lung cancer].
The paper deals with evaluation of the literature data and our experience with automated quantitative cytometric examination of sputum for diagnosis of lung cancer and, in particular, early one. This novel procedure uses measurement of quantitative indices which characterise tumors-induced alterations. The LungSign computerized system was employed to scan cellular nuclei. The results were evaluated by linear discriminative analysis with the aid of ROC-curves and underlying areas. The procedures were run in 248 cases and its sensitivity was significantly higher that of a standard cytological one (36.6% and 13.3%, respectively; p = 0.033), albeit a slight decrease in specificity (93.7% and 100%, respectively; p = 0.003). Automated quantitative cytometric indices varied significantly in cohorts of patients with confirmed (-0.275871) and false (-1.24990) diagnosis of lung cancer (p = 0.0001).


Reduced gastric emptying and mesenteric blood flow in IDDM with cardiac autonomic neuropathy.
Our objective was to investigate the relationship between gastric emptying and mesenteric blood flow in type 1 diabetic patients with (CAN+) and without (CAN-) cardiac autonomic neuropathy. CAN was determined by a series of cardiovascular reflex tests and power spectral analysis of heart rate variations (HRV) using a computerized system. We calculated from these data a score for cardiac autonomic neuropathy with a maximum of 7 points (1 point for abnormal value of: CV of HRV at supine rest, CV of HRV during deep breathing, Valsalva ratio, lying-to-standing ratio, PSA of HRV in the low frequency band, PSA of HRV in the mid frequency band, blood pressure response to standing). Patients were considered to have CAN if at least 3 of the 7 parameters were found to be abnormal (CAN score > or = 3). The resulting groups (CAN-, n = 14 vs. CAN+, n = 16) were well matched with respect to age (53 +/- 11 vs. 51 +/- 12 years), BMI (27.2 +/- 3.3 vs. 25.9 +/- 3.6 kg/m2), duration of diabetes (162 +/- 157 vs. 158 +/- 100 months), fasting blood glucose (6.9 +/- 2.6 vs. 6.8 +/- 2.4 mmol/l) and HbA1c (7.2 +/- 1.5 vs. 7.3 +/- 2.0%). Gastric emptying was determined by real-time ultrasonography (antral planimetry) during 60 min after a semiliquid test meal (Fresubin diabetes 300 ml, 53% carbohydrate, 32% lipid, 15% protein) and the blood flow of the superior mesenteric artery was measured by Doppler ultrasound technique. Type I diabetic patients with CAN had a significantly higher CAN score than those without CAN (6.1 +/- 0.4 vs. 1.3 +/- 0.7). Mean preprandial (before ingestion of the test meal) as well as postprandial (immediately after ingestion of test meal) antral areas of CAN+ (5.2 +/- 2.0v/10.9 +/- 2.8 cm2) and CAN- (5.1 +/- 1.5/10.8 +/- 2.2 cm2) were comparable. CAN+ had significantly slower decrease of postprandial antral areas at 15, 30, 45 and 60 min after ingestion of test meal (-1.7 +/- 0.4/-8.3 +/- 1.2/-9.5 +/- 0.9/-19.5 +/- 2.0 delta % compared to postprandial value) compared to CAN- (-8.9 +/- 1.8/-22.5 +/- 2.6/-29.1 +/- 2.9/-35.5 +/- 2.9 delta %). The increase in mesenteric blood flow at 15, 30 and 45 min after the meal was significantly reduced in CAN+ compared to CAN- patients. Significantly negative correlations were found between the CAN score and the decrease of antral area as well as between CAN score and the increase of diastolic mesenteric blood flow and significantly positive correlations between the decrease of antral area and the increase of diastolic mesenteric blood flow. In conclusion, type 1 diabetic patients with cardiac autonomic neuropathy showed delayed gastric emptying and diminished mesenteric blood flow during 60 min after ingestion of a semiliquid test meal.


Evaluating risk communication about fish consumption advisories: efficacy of a brochure versus a classroom lesson in Spanish and English.
Presentation format can influence the way target audiences understand risk-related information. Brochures or fish fact sheets are the methods traditionally used by state agencies to inform the public about fish consumption advisories and the risks from consuming fish. This study examines the efficacy of presenting information about the risks from consuming contaminated fish and shellfish in two different formats: a brochure and classroom presentation. The two instruments were developed and tested in Spanish and English, reflecting the local ethnic composition in the Newark Bay Complex. The instruments were tested on women of child-bearing age at the Women, Infants, and Children Center in Elizabeth, New Jersey. Detailed diagrams were used in both presentations, including contaminated fish species, fish preparation methods, and food chain bioaccumulation and transmission to the fetus. There were few language-related differences in the efficacy of the classroom lesson, and the main ideas were understood by both groups. Where there were significant differences in understanding about the risks from consuming fish or crabs from the contaminated waters of Newark Bay, in all cases the women exposed to the classroom lesson had a better understanding than those who read the brochure. Ninety-six percent of the women who heard the lesson understood that it was unsafe to eat fish from the port, compared to 72% of those reading the brochure. Both formats succeeded in imparting information to most women about the area under advisories, the fish species under advisories, and transmission of toxins to the fetus. Information on fish preparation was recalled less clearly, partly because women were asked to relate methods to reduce the risk from consuming fish from 11 presented, and most recalled only two or three of the list. The advantages and disadvantages of conducting short classes to women of child-bearing age are discussed.


A Dynamically Stable Sulfide Electrolyte Architecture for High-Performance All-Solid-State Lithium Metal Batteries.
All-solid-state batteries employing sulfide solid electrolyte and Li metal anode are promising because of their high safety and energy densities. However, the interface between Li metal and sulfides suffers from catastrophic instability which stems the practical use. Here, a dynamically stable sulfide electrolyte architecture to construct the hierarchy of interface stability is reported. By rationally designing the multilayer structures of sulfide electrolytes, the dynamic decomposing-alloying process from MS4 (M = Ge or Sn) unit in sulfide interlayer can significantly prohibit Li dendrite penetration is revealed. The abundance of highly electronic insulating decompositions, such as Li2 S, at the sulfide interlayer interface helps to well constrain the dynamic decomposition process and preserve the long-term polarization stability is also highlighted. By using Li6 PS5 Cl||Li10 SnP2 S12 ||Li6 PS5 Cl electrolyte architecture, Li metal anode shows an unprecedented critical current density over 3 mA cm-2 and achieves the steady over-potential for ≈900 hours. Based upon the merits, the Li||LiNi0.8 Co0.1 Mn0.1 O2 battery delivers a remarkable 75.3% retention even after 600 cycles at 1 C (1C-0.95 mA cm-2 ) under a low stack pressure of 15 MPa.


p38MAPK plays a critical role in induction of a pro-inflammatory phenotype of retinal Müller cells following Zika virus infection.
Zika virus (ZIKV) infection has been associated with ocular abnormalities such as chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells and its potential contribution to retinal pathology is still very limited. Here we found that primary Müller cells, the principal glial cells in the retina, expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive to ZIKV infection. In addition, ZIKV-infected Müller cells exhibited a pro-inflammatory phenotype and produced many inflammatory and growth factors. While a number of inflammatory signaling pathways such as ERK, p38MAPK, NF-κB, JAK/STAT3 and endoplasmic reticulum stress were activated after ZIKV infection, inhibition of p38MAPK after ZIKV infection most effectively blocked ZIKV-induced inflammatory and growth molecules. In comparison to ZIKV, Dengue virus (DENV), another Flavivirus infected Müller cells more efficiently but induced much lower pro-inflammatory responses. These data suggest that Müller cells play an important role in ZIKV-induced ocular pathology by induction of inflammatory and growth factors in which the p38MAPK pathway has a central role. Blocking p38MAPK may provide a novel approach to control ZIKV-induced ocular inflammation.


Mechanical strain increases PDGF-B and PDGF beta receptor expression in vascular smooth muscle cells.
Cyclic mechanical strain causes proliferation of vascular smooth muscle cells, mediated in part by platelet-derived growth factor (PDGF). We examined the effect of cyclic strain on expression of PDGF-B and the PDGF beta receptor. Neonatal rat vascular smooth muscle cells were exposed to 1 hertz cyclic strain on silicone elastomer plates. PDGF-B mRNA increased after 6 h of strain. In cells transfected with a PDGF-B promoter chloramphenicol acetyl transferase construct (psisCAT 6A), activity increased by 12-fold following 12 h of strain. Two neutralizing antibodies to the PDGF beta receptor both reduced strain-induced [(3)H]thymidine incorporation by 50%. Expression of the PDGF beta receptor protein increased 1.8-fold following 24 h of strain. During strain, PDGF beta receptor expression was not significantly altered by neutralizing antibodies to PDGF-B. Thus, both PDGF-B and the PDGF beta receptor are induced by cyclic mechanical strain and both contribute to cell proliferation in response to strain.


Modelling repressor proteins docking to DNA.
The docking of repressor proteins to DNA starting from the unbound protein and model-built DNA coordinates is modeled computationally. The approach was evaluated on eight repressor/DNA complexes that employed different modes for protein/ DNA recognition. The global search is based on a protein-protein docking algorithm that evaluates shape and electrostatic complementarity, which was modified to consider the importance of electrostatic features in DNA-protein recognition. Complexes were then ranked by an empirical score for the observed amino acid /nucleotide pairings (i.e., protein-DNA pair potentials) derived from a database of 20 protein/ DNA complexes. A good prediction had at least 65% of the correct contacts modeled. This approach was able to identify a good solution at rank four or better for three out of the eight complexes. Predicted complexes were filtered by a distance constraint based on experimental data defining the DNA footprint. This improved coverage to four out of eight complexes having a good model at rank four or better. The additional use of amino acid mutagenesis and phylogenetic data defining residues on the repressor resulted in between 2 and 27 models that would have to be examined to find a good solution for seven of the eight test systems. This study shows that starting with unbound coordinates one can predict three-dimensional models for protein/DNA complexes that do not involve gross conformational changes on association.


[Infections in patients with rheumatoid arthritis receiving anti-cytokine therapy: biological mechanisms and clinical aspects].
Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the same cytokines. Reduction in the production and/or activities of proinflammatory cytokines in rheumatoid arthritis remains a therapeutic objective for many patients. The tumour necrosis factor-alpha (TNF-alpha) blockers infliximab, etanercept and adalimumab and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are effective in patients with active rheumatoid arthritis. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. At this time, treating physicians must weigh carefully the benefits of biologics against their safety, particularly in patients at risk of infection.


Evidence supporting the importance of terrestrial carbon in a large-river food web.
Algal carbon has been increasingly recognized as the primary carbon source supporting large-river food webs; however, many of the studies that support this contention have focused on lotic main channels during low-flow periods. The flow variability and habitat-heterogeneity characteristic of these systems has the potential to significantly influence food web structure and must be integrated into models of large-river webs. We used stable-isotope analysis and IsoSource software to model terrestrial and algal sources of organic carbon supporting consumer taxa in the main channel and oxbow lakes of the Brazos River, Texas, USA, during a period of frequent hydrologic connectivity between these habitat types. Standardized sampling was conducted monthly to collect production sources and consumer species used in isotopic analysis. Predictability of hydrologic connections between habitat types was based on the previous 30 years of flow data. IsoSource mixing models identified terrestrial C3 macrophytes (riparian origin) as the primary carbon source supporting virtually all consumers in the main channel and most consumers in oxbow lakes. Small-bodied consumers (<100 mm) in oxbow lakes assimilated large fractions of algal carbon whereas this pattern was not apparent in the main channel. Estimates of detritivore trophic positions based on delta15N values indicated that terrestrial material was likely assimilated via invertebrates rather than directly from detritus. High flows in the river channel influenced algal standing stock, and differences in the importance of terrestrial and algal production sources among consumers in channel vs. oxbow habitats were associated with patterns of flooding. The importance of terrestrial material contradicts the findings of recent studies of large-river food webs that have emphasized the importance of algal carbon and indicates that there can be significant spatial, temporal, and taxonomic variation in carbon sources supporting consumers in large rivers.


Demodex folliculorum in a nipple imprint.
Demodex mites were found in a nipple imprint. Their morphologic features in this cytologic preparation have been described and illustrated. These mites are common parasites of human skin and are apparently of little or no pathologic significance.


Eye-movements and ongoing task processing.
This study tests the relation between eye-movements and thought processing. Subjects were given specific modality tasks (visual, gustatory, kinesthetic) and assessed on whether they responded with distinct eye-movements. Some subjects' eye-movements reflected ongoing thought processing. Instead of a universal pattern, as suggested by the neurolinguistic programming hypothesis, this study yielded subject-specific idiosyncratic eye-movements across all modalities. Included is a discussion of the neurolinguistic programming hypothesis regarding eye-movements and its implications for the eye-movement desensitization and reprocessing theory.


The boundary-expressed EPIDERMAL PATTERNING FACTOR-LIKE2 gene encoding a signaling peptide promotes cotyledon growth during Arabidopsis thaliana embryogenesis.
The shoot organ boundaries have important roles in plant growth and morphogenesis. It has been reported that a gene encoding a cysteine-rich secreted peptide of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family, EPFL2, is expressed in the boundary domain between the two cotyledon primordia of Arabidopsis thaliana embryo. However, its developmental functions remain unknown. This study aimed to analyze the role of EPFL2 during embryogenesis. We found that cotyledon growth was reduced in its loss-of-function mutants, and this phenotype was associated with the reduction of auxin response peaks at the tips of the primordia. The reduced cotyledon size of the mutant embryo recovered in germinating seedlings, indicating the presence of a factor that acted redundantly with EPFL2 to promote cotyledon growth in late embryogenesis. Our analysis suggests that the boundary domain between the cotyledon primordia acts as a signaling center that organizes auxin response peaks and promotes cotyledon growth.


Effect of calcium concentration and inhibitors on the responses of platelets stimulated with collagen: contrast between human and rabbit platelets.
1. Variations in the concentration of Ca2+ [Ca2+] in the suspending medium have different effects on the responses of human and rabbit platelets to collagen. 2. When rabbit platelets are stimulated with a low concentration of collagen (0.5 micrograms/ml), aggregation, release of granule contents, and formation of thromboxane are maximal when the suspending medium contains [Ca2+] in the physiological range (0.5-2.0 mM), and very slight in a medium with no added Ca2+. 3. In contrast, human platelets respond most strongly when the suspending medium contains no added Ca2+ [( Ca2+] approx. 20 microM); this is attributable to the enhanced formation of thromboxane A2 (TXA2) upon close platelet-to-platelet contact in this medium. 4. When TXA2 formation is blocked by inhibition of cyclo-oxygenase with aspirin or indomethacin, rabbit platelet aggregation and release in response to 1.25-10 micrograms/ml collagen is also maximal at [Ca2+] of 0.5-2.0 mM and least at 20 microM; human platelets do not aggregate and the extent of release is relatively independent of [Ca2+]. 5. In 1 mM [Ca2+], use of apyrase and/or ketanserin with rabbit platelets in which TXA2 formation is blocked shows that released ADP and serotonin make large contributions to aggregation and release in response to high concentrations of collagen; human platelet aggregation is largely dependent on TXA2. 6. Use of fura-2-loaded platelets shows that the collagen-induced rise in cytosolic [Ca2+] is only slightly inhibited by aspirin or indomethacin in rabbit platelets, but almost completely inhibited in human platelets. 7. Responses of rabbit platelets to collagen are less dependent on TXA2 than those of human platelets. Released ADP and serotonin make major contributions to the responses of rabbit platelets to collagen.


Diet-Induced Obesity Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma via CX3CL1/CX3CR1 Axis.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, and the patients are generally diagnosed with distant metastasis. Liver is one of the preferred organs of distant metastasis, and liver metastasis is the leading cause of death in PDAC. Diet-induced obesity (DIO) is a risk factor for PDAC, and it remains unclear whether and how DIO contributes to liver metastasis of PDAC. In our study, we found that DIO significantly promoted PDAC liver metastasis compared with normal diet (ND) in intrasplenic injection mouse model. RNA-seq analysis for liver metastasis nodules showed that the various chemokines and several chemokine receptors were altered between ND and DIO samples. The expression levels of CX3CL1 and CX3CR1 were significantly upregulated in DIO-induced liver metastasis of PDAC compared to ND. Increased CX3CL1 promoted the recruitment of CX3CR1-expressing pancreatic tumor cells. Taken together, our data demonstrated that DIO promoted PDAC liver metastasis via CX3CL1/CX3CR1 axis.


Hidradenitis suppurativa: A clinician's tool for early diagnosis and treatment.
To enhance the clinician's knowledge of the diagnosis and treatment of hidradenitis suppurativa (HS). This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to: 1. Assess and diagnose the pathophysiology and prevalence of HS. 2. Interpret the diagnostic process for HS. 3. Evaluate treatment options for HS.


Osteoporotic compression fracture of spine treated with posterior instrumentation and transpedicular bone grafting.
A series of 11 patients with osteoporotic compression fracture of the spine who underwent posterior instrumentation and transpedicular bone drafting in Siriraj Hospital Bangkok was analysed retrospectively. The indications for surgery were neurological deficit, kyphotic deformity and intractable pain. The mean follow up period was 10.1 months (range, 2.1 - 25.5 months). On follow up, all patients indicated recovery from pain. Most patients (7/11) regained one Frankel grade and one patient who was Frankel grade D preoperatively remained grade D postoperatively. Daily functionality improved in nine patients, but two patients still required aid for walking and standing. There was no pedicle screw loosening, pull-out or implant breakage as of the last date of follow up. Adjacent vertebrae also did not show any fracture or reduction in height. We conclude that this operative method is acceptable for osteoporotic fracture of the spine, although a longer period of follow up is needed to further evaluate its efficacy.


Derivatization using dimethylamine for tandem mass spectrometric structure analysis of enzymatically and acidically depolymerized methyl cellulose.
Structure analysis of partially depolymerized methyl cellulose was performed by nanoelectrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) and by matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS). Dimethylamine (DMA) was used for the first time as a reducing end derivatization reagent for oligosaccharides. This is an attractive reagent since it could be easily removed from the reaction mixture. Most important it also introduces a basic functional group that increased the sensitivity in both MALDI and nano-ESI. Depolymerization was made in two ways: one by the cellulose selective endoglucanase 5A from Bacillus agaradhaerens (Ba Cel5A) and the other by trifluoroacetic acid. The DMA derivatives formed both protonated and sodiated molecules in nano-ESI and MALDI. Tandem MS of protonated molecules yielded predominantly Y fragments from which the distribution of the substituents in the oligomers could be measured. Fragments obtained in tandem MS of sodiated molecules provided information regarding the positions of the substituents within the anhydroglucose units (AGUs). It was found that Ba Cel5A could cleave glucosidic bonds also if the AGU on the reducing side of the bond was fully methylated. The combination of DMA derivatization and tandem MS was demonstrated as a tool for the characterization of endoglucanase selectivity.


Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli.
Strains of uropathogenic Escherichia coli (UPEC) can invade terminally differentiated superficial bladder epithelial cells and subsequently multiply, forming large biofilm-like inclusions referred to as pods. In contrast, within immature bladder cells UPEC enter a more quiescent state and often fail to replicate appreciably. As immature bladder epithelial cells undergo terminal differentiation the actin cytoskeleton is radically diminished, a phenomenon that we reasoned could influence the intracellular fate of UPEC. Here we show that UPEC within undifferentiated bladder cells is trafficked into acidic compartments having key features of late endosomes and lysosomes. These UPEC-containing vacuoles are often enmeshed within a network of actin filaments, the disruption of which stimulates intravacuolar growth and efflux of UPEC in cell culture-based studies. In this in vitro model system, release of UPEC into the host cytosol further stimulates intracellular bacterial growth and the rapid development of pod-like inclusions. These inclusions, as well as those observed using an in vivo mouse model, develop in association with cytokeratin intermediate filaments that may act as scaffolding for intracellular biofilm formation. Our data suggest an aetiological basis for recurrent urinary tract infections, linking bladder cell differentiation and the accompanying redistribution of actin microfilaments with the resurgence of UPEC from quiescent intravacuolar reservoirs within the bladder epithelium.


Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer.
This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triple-negative metastatic breast cancer.


The involvement of metallothioneins in mitochondrial function and disease.
Mitochondrial oxidative phosphorylation deficiency is accompanied by various down-stream, adaptive responses which play a key role in the varied phenotypes observed when mitochondrial dysfunction occurs. These responses are often accompanied by the induction of genes involved in defense mechanisms against oxidative stress. Among these responses, metallothioneins (MTs) has been identified to be responsive to mitochondrial dysfunction. MTs, which are expressed in four different isoforms, are small, cysteine rich, metal binding proteins that have been associated with a protective effect in cells under numerous diseased and stressed states. Their diverse functionality and protective roles can be ascribed to their three basic abilities or primary functions which are metal homeostasis, heavy metal detoxification and free radical scavenging. The involvement of MTs with numerous cellular processes, organelles and cells has received much attention while notice of their involvement with the function of mitochondria has been lacking. It is believed that MTs promote the survival of mitochondrial dysfunctional cells by acting as highly efficient reducing elements against the damaging properties of reactive oxygen species (ROS) and by limiting apoptosis. In addition to their role in mitochondrial disease, convincing evidence exist, albeit with conflicting results, of its involvement in some key functions of the mitochondrion, including redox modulation, metal homeostasis and enzyme and transcription factor regulation.


Presynaptic dopaminergic function: implications for understanding treatment response in psychosis.
All current antipsychotic drugs block dopamine (DA) receptors, but the nature of the DA dysfunction in schizophrenia has not been clear. However, consistent evidence now shows that presynaptic dopaminergic function is altered in schizophrenia, specifically in terms of increased DA synthesis capacity, baseline synaptic DA levels, and DA release. Furthermore, presynaptic dopaminergic function is already elevated in prodromal patients who later developed the disorder. Currently available antipsychotics act on postsynaptic receptors, not targeting presynaptic DA abnormalities. This has implications for understanding response and developing new treatments. The lack of normalization of the abnormal presynaptic function could explain why discontinuation is likely to lead to relapse, because the major dopaminergic function persists, meaning that once treatment stops there is nothing to oppose the dysregulated dopamine function reinstating symptoms. Furthermore, it suggests that drugs that target presynaptic dopaminergic function may constitute new treatment possibilities for schizophrenic patients, in particular, for those in whom antipsychotics are poorly effective. In addition, the longitudinal changes with the onset of psychosis indicate the potential to target a defined dynamic neurochemical abnormality to prevent the onset of psychosis.


The Role of Daily Steps in the Treatment of Major Depressive Disorder: Secondary Analysis of a Randomized Controlled Trial of a 6-Month Internet-Based, Mindfulness-Based Cognitive Behavioral Therapy Intervention for Youth.
Current evidence supports physical activity (PA) as an adjunctive treatment for major depressive disorder (MDD). Few studies, however, have examined the relationship between objectively measured PA and MDD treatment outcomes using prospective data. This study is a secondary analysis of data from a 24-week internet-based, mindfulness-based cognitive behavioral therapy program for MDD. The purpose of this analysis was twofold: (1) to examine average daily step counts in relation to MDD symptom improvement, and whether pain moderated this relationship; and (2) to examine whether changes in step activity (ie, step trajectories) during treatment were associated with baseline symptoms and symptom improvement. Patients from the Centre for Addiction and Mental Health were part of a randomized controlled trial evaluating the effects of internet-based, mindfulness-based cognitive behavioral therapy for young adults (aged 18-30 years old) with MDD. Data from 20 participants who had completed the intervention were analyzed. PA, in the form of objectively measured steps, was measured using the Fitbit-HR Charge 2 (Fitbit Inc), and self-reported depression severity was measured with the Beck Depression Inventory-II (BDI-II). Linear regression analysis was used to test PA's relationship with depression improvement and the moderating effect of pain severity and pain interference. Growth curve and multivariable regression models were used to test longitudinal associations. Participants walked an average of 8269 steps per day, and each additional +1000-step difference between participants was significantly associated with a 2.66-point greater improvement (reduction) in BDI-II, controlling for anxiety, pain interference, and adherence to Fitbit monitoring (P=.02). Pain severity appeared to moderate (reduce) the positive effect of average daily steps on BDI-II improvement (P=.03). Higher baseline depression and anxiety symptoms predicted less positive step trajectories throughout treatment (Ps≤.001), and more positive step trajectories early in the trial predicted greater MDD improvement at the end of the trial (Ps<.04). However, step trajectories across the full duration of the trial did not significantly predict MDD improvement (Ps=.40). This study used objective measurements to demonstrate positive associations between PA and depression improvement in the context of cognitive behavioral treatment. Pain appeared to moderate this relationship, and baseline symptoms of anxiety and depression predicted PA trajectories. The findings inform future interventions for major depression. Future research with larger samples should consider additional moderators of PA-related treatment success and the extent to which outcomes are related to PA change in multimodal interventions. Clinical Trials.gov NCT03406052; https://www.clinicaltrials.gov/ct2/show/NCT03406052. RR2-10.2196/11591.


A cross sectional study of prevalence and correlates of current and past risks in schizophrenia.
The growing burden of chronic often untreated mental illness has increased the importance of risk assessment in people suffering from major mental disorders. The present study was undertaken to obtain prevalence of various risks and predictive factors for self-harm, violence and various other risks among randomly recruited schizophrenia subjects (N=270) on the basis of past history of their disorder. Using a rigorous translation, back translation and acceptability process, a specially constructed semi-structured assessment interview, based on a prior NHS Trust risk assessment interview along with the Diagnostic Interview for Genetic Studies (DIGS), detailed information was obtained for various risks. Risk of violence (historical) was reported among 65.55%, and risk of self-neglect among 53.33%, risk to others (47.41%), risk of coming to harm (24.07%), self-harm (22.59%), risk from others (11.85%), fire risk (2.96%). Risk of violence (historical) and risk to others was related to 'ever' having emotions related to harm and self-harm, 'current' emotions related to violence and poor compliance to treatment. Regular risk assessment is essential to assess emotions related to violence and non-adherence to treatment. Assessment of risk helps clinicians predict the risks involved in management and in timely intervention.


Health, income, and the preston curve: A long view.
Well-being is increasingly viewed as a multidimensional phenomenon, of which income is only one facet. In this paper I focus on another one, health, and look at its synthetic measure, life expectancy at birth, and its relationship with per capita income. International trends of life expectancy and per capita GDP differed during the past 150 years. Life expectancy gains depended on economic growth but also on the advancement in medical knowledge. The pace and breadth of the health transitions drove life expectancy aggregate tendencies and distribution. The new results confirm the relationship between life expectancy and per capita income and its outward shift over time as put forward by Samuel Preston. However, the association between nonlinearly transformed life expectancy and the log of per capita income does not flatten out over time, but becomes convex suggesting more than proportional increases in life expectancy at higher per capita income levels.


Agreement in electrocardiogram interpretation in patients with septic shock.
The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. Nine Canadian intensive care units. Adults with septic shock requiring at least 5 μg/min of norepinephrine for 6 hrs. Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved from fair to moderate (κ 0.52, p = .028) when unblinded to troponin. In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.


Nursing assessment of patients with non-acute wounds.
Accurate and thorough assessment of patients with wounds is essential in order to provide correct treatment. In relation to patients with open, non-acute wounds, the areas that need assessing include general health and specific underlying disease process, care being given and local wound environment. This article outlines specific details of the assessment process. It includes a breakdown of factors affecting healing, a discussion of the importance of diagnosis of cause, an outline of factors within care provision that may have a negative effect on healing, and areas relevant to the wound itself that should be assessed.


Does Bariatric Surgery Normalize Risks After Total Knee Arthroplasty? Administrative Medicare Data.
Patients with morbid obesity, defined as body mass index of greater than 40 kg/m2, are being referred for weight loss and bariatric surgery before being accepted for a total knee arthroplasty (TKA). Previous studies have identified the risks associated with doing a TKA in an individual with an increased body mass index. We now present data identifying the same risks in individuals who have undergone bariatric surgery before submitting to TKA. (1) Has the bariatric surgery improved the risk profile for the subsequent TKA? (2) Does the type of bariatric procedure matter? A retrospective cohort study was conducted of patients who underwent bariatric surgery followed by TKA using Medicare hospital claims data. A study was undertaken using the Current Procedure Terminology codes and International Classification of Diseases-9 and International Classification of Diseases-10 for bariatric surgery. These identified entries were then cross-referenced to individuals who later underwent TKA, identified by CPT 27447, between 2004 and 2016. Twelve different types of complications which occurred in the 90-day period after the TKA were analyzed. Postbariatric bypass surgery patients showed a markedly elevated risk in most complications examined. In each category, the type of previous gastric surgery had notable differences in the post-TKA complication profile. In the implant failure category, the data demonstrated an even greater risk after a gastric bypass. When postbariatric patients were compared with morbidly obese individuals who had not undergone bariatric surgery, the hazard ratios (HRs) were markedly elevated for death (HR 1.47/bypass), implant failure (HR 1.58/sleeve), and pneumonia (HR 1.68/bypass). (1) Submitting to bariatric surgery is not sufficient to normalize risks. (2) The type of previous bariatric procedure is associated with the type of complications encountered. (3) We were unable to attribute TKA to bariatric failures. (4) Health systems and health care providers should be cautious in withholding care for patients with morbid obesity.


Reconstruction of irregularly-sampled volumetric data in efficient box spline spaces.
We present a variational framework for the reconstruction of irregularly-sampled volumetric data in, nontensor-product, spline spaces. Motivated by the sampling-theoretic advantages of body centered cubic (BCC) lattice, this paper examines the BCC lattice and its associated box spline spaces in a variational setting. We introduce a regularization scheme for box splines that allows us to utilize the BCC lattice in a variational reconstruction framework. We demonstrate that by choosing the BCC lattice over the commonly-used Cartesian lattice, as the shift-invariant representation, one can increase the quality of signal reconstruction. Moreover, the computational cost of the reconstruction process is reduced in the BCC framework due to the smaller bandwidth of the system matrix in the box spline space compared to the corresponding tensor-product B-spline space. The improvements in accuracy are quantified numerically and visualized in our experiments with synthetic as well as real biomedical datasets.


Stochastic soil water balance under seasonal climates.
The analysis of soil water partitioning in seasonally dry climates necessarily requires careful consideration of the periodic climatic forcing at the intra-annual timescale in addition to daily scale variabilities. Here, we introduce three new extensions to a stochastic soil moisture model which yields seasonal evolution of soil moisture and relevant hydrological fluxes. These approximations allow seasonal climatic forcings (e.g. rainfall and potential evapotranspiration) to be fully resolved, extending the analysis of soil water partitioning to account explicitly for the seasonal amplitude and the phase difference between the climatic forcings. The results provide accurate descriptions of probabilistic soil moisture dynamics under seasonal climates without requiring extensive numerical simulations. We also find that the transfer of soil moisture between the wet to the dry season is responsible for hysteresis in the hydrological response, showing asymmetrical trajectories in the mean soil moisture and in the transient Budyko's curves during the 'dry-down' versus the 'rewetting' phases of the year. Furthermore, in some dry climates where rainfall and potential evapotranspiration are in-phase, annual evapotranspiration can be shown to increase because of inter-seasonal soil moisture transfer, highlighting the importance of soil water storage in the seasonal context.


Lessons from the Trials for the Desirable Effects of Sodium Glucose Co-Transporter 2 Inhibitors on Diabetic Cardiovascular Events and Renal Dysfunction.
Recent large placebo-controlled trials of sodium glucose co-transporter 2 (SGLT2) inhibitors revealed desirable effects on heart failure (HF) and renal dysfunction; however, the mechanisms underlying these effects are unknown. The characteristic changes in the early stage of diabetic cardiomyopathy (DCM) are myocardial and interstitial fibrosis, resulting in diastolic and subsequent systolic dysfunction, which leads to clinical HF. Pericytes are considered to play crucial roles in myocardial and interstitial fibrosis. In both DCM and diabetic retinopathy (DR), microaneurysm formation and a decrease in capillaries occur, triggered by pericyte loss. Furthermore, tubulointerstitial fibrosis develops in early diabetic nephropathy (DN), in which pericytes and mesangial cells are thought to play important roles. Previous reports indicate that pericytes and mesangial cells play key roles in the pathogenesis of DCM, DR and DN. SGLT2 is reported to be functionally expressed in pericytes and mesangial cells, and excessive glucose and Na+ entry through SGLT2 causes cellular dysfunction in a diabetic state. Since SGLT2 inhibitors can attenuate the high glucose-induced dysfunction of pericytes and mesangial cells, the desirable effects of SGLT2 inhibitors on HF and renal dysfunction might be explained by their direct actions on these cells in the heart and kidney microvasculature.


Does varicocelectomy improve gonadal function in men with hypogonadism and infertility? Analysis of a prospective study.
Varicocele in infertile males is associated with Leydig cell dysfunction and hypogonadism. The effect of varicocelectomy on serum testosterone level is not yet established. We analysed 200 heterosexual infertile men diagnosed to have clinical varicocele they were divided into two groups: group 1 (100 men) had microsurgical varicocelectomy, and group 2 (100 patients) underwent assisted reproduction procedures. All participants had semen analysis, serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and total testosterone (TT), measured both at recruitment time and 6 months later. In group 1, the mean TT level increased significantly after varicocelectomy (1.644 ± 0.029 to 2.461 ± 0.0198 ng/dL, P < 0.0001) and testicular size correlated with the mean change in TT (P = 0.001). No similar change was found in group 2. Out of the 100 patients in group 1, 78 had postoperative normalization of TT unlike only 16 men in group 2.


Cross-layer cluster-based energy-efficient protocol for wireless sensor networks.
Recent developments in electronics and wireless communications have enabled the improvement of low-power and low-cost wireless sensors networks (WSNs). One of the most important challenges in WSNs is to increase the network lifetime due to the limited energy capacity of the network nodes. Another major challenge in WSNs is the hot spots that emerge as locations under heavy traffic load. Nodes in such areas quickly drain energy resources, leading to disconnection in network services. In such an environment, cross-layer cluster-based energy-efficient algorithms (CCBE) can prolong the network lifetime and energy efficiency. CCBE is based on clustering the nodes to different hexagonal structures. A hexagonal cluster consists of cluster members (CMs) and a cluster head (CH). The CHs are selected from the CMs based on nodes near the optimal CH distance and the residual energy of the nodes. Additionally, the optimal CH distance that links to optimal energy consumption is derived. To balance the energy consumption and the traffic load in the network, the CHs are rotated among all CMs. In WSNs, energy is mostly consumed during transmission and reception. Transmission collisions can further decrease the energy efficiency. These collisions can be avoided by using a contention-free protocol during the transmission period. Additionally, the CH allocates slots to the CMs based on their residual energy to increase sleep time. Furthermore, the energy consumption of CH can be further reduced by data aggregation. In this paper, we propose a data aggregation level based on the residual energy of CH and a cost-aware decision scheme for the fusion of data. Performance results show that the CCBE scheme performs better in terms of network lifetime, energy consumption and throughput compared to low-energy adaptive clustering hierarchy (LEACH) and hybrid energy-efficient distributed clustering (HEED).


Role of Cerebrospinal Fluid Biomarkers and (18)F-florbetapir PET Imaging in the Diagnosis of Primary Progressive Aphasia: A Retrospective Analysis.
The use of biomarkers has recently supported the association between Alzheimer disease (AD) pathology and the logopenic variant of primary progressive aphasia (PPA). We aim to investigate possible differences in cerebrospinal fluid (CSF) biomarker concentrations in the three PPA variants, and to assess any agreement between CSF biomarkers and (18)F-florbetapir PET. A group of 10 PPA were retrospectively enrolled. Patients with logopenic variant (lvPPA) showed different levels of Aβ1-42 and p-tau compared to nonfluent/agrammatic and semantic variants (nfv/svPPA). All nfv/svPPA patients had negative amyloid PET. Among the lvPPA group, a negative amyloid PET was found only in one patient, who was also the only one to display a normal CSF. Thus, this small cohort appeared to display an excellent agreement between CSF and (18)F-florbetapir PET and suggest that these examinations may have the same validity in detecting in vivo evidence of AD pathology in PPA clinical variants.


[Use of a point-scale assessment of patient status in the surgical treatment of craniocerebral injuries].
The indications and contraindications for surgical treatment in craniocerebral trauma (CCT) were based on estimation of the patient's condition in marks; the dynamics of changes of the results of the estimation in the pre- and postoperative periods were studied. A total of 375 patients with CCT were examined in different medical institutions according to a unified method. Neurosurgical interventions were carried out on 155 patients. All patients who underwent operation when their condition was rated below 15 marks died on the immediate postoperative days, whatever their age and whatever the time of the operation after the trauma. The probability of a favourable outcome increased to 40% in a condition rated 21-30 marks on the day of the operation and reached 69% when it was above 30 marks.


Agitation in the inpatient psychiatric setting: a review of clinical presentation, burden, and treatment.
Agitation among psychiatric inpatients (particularly those diagnosed with schizophrenia or bipolar disorder) is common and, unless recognized early and managed effectively, can rapidly escalate to potentially dangerous behaviors, including physical violence. Inpatient aggression and violence have substantial adverse psychological and physical consequences for both patients and providers, and they are costly to the healthcare system. In contrast to the commonly held view that inpatient violence occurs without warning or can be predicted by "static" risk factors, such as patient demographics or clinical characteristics, research indicates that violence is usually preceded by observable behaviors, especially non-violent agitation. When agitation is recognized, staff should employ nonpharmacological de-escalation strategies and, if the behavior continues, offer pharmacological treatment to calm patients rapidly. Given the poor therapeutic efficacy and potential for adverse events associated with physical restraint and seclusion, and the potential adverse sequelae of involuntary drug treatment, these interventions should be considered last resorts. Pharmacological agents used to treat agitation include benzodiazepines and first- and second-generation antipsychotic drugs. Although no currently available agent is ideal, recommendations for selecting among them are provided. There remains an unmet need for a non-invasive and rapidly acting agent that effectively calms without excessively sedating patients, addresses the patient's underlying psychiatric symptoms, and is reasonably safe and tolerable. A treatment with these characteristics could substantially reduce the clinical and economic burden of agitation in the inpatient psychiatric setting.


Psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders.
The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use. This cross-sectional study used Medicaid claims for calendar year 2001 from all 50 states and Washington, DC, to examine 60,641 children with an autism spectrum disorder diagnosis. Logistic regression with random effects was used to examine the child, county, and state factors associated with psychotropic medication use. Of the sample, 56% used at least 1 psychotropic medication, 20% of whom were prescribed > or = 3 medications concurrently. Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%). Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%). In adjusted analyses, male, older, and white children; those who were in foster care or in the Medicaid disability category; those who received additional psychiatric diagnoses; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs. Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications. Psychotropic medication use is common among even very young children with autism spectrum disorders. Factors unrelated to clinical presentation seem highly associated with prescribing practices. Given the limited evidence base, there is an urgent need to assess the risks, benefits, and costs of medication use and understand the local and national policies that affect medication use.


Transcriptional analysis of the putative glycosyltransferase gene (amv248) of the Amsacta moorei entomopoxvirus.
Amsacta moorei entomopoxvirus (AMEV), the most studied member of the genus Betaentomopoxvirus, was initially isolated from Red Hairy caterpillar larvae, Amsacta moorei. According to genome sequence and previous studies it was shown that amv248 encodes a putative glycosyltransferase that is the only conserved attachment protein in betaentomopoxviruses. Transcriptional analysis of the amv248 gene by RT-PCR and qPCR showed that transcription starts at 6h post infection (hpi). Also, transcription was not affected by a DNA replication inhibitor but was severely curtailed by a protein synthesis inhibitor. These results indicate that amv248 belongs to the intermediate class of gene expression. 5' and 3' untranslated regions analysis revealed that transcription initiates at position -126 relative to the translational start site, and ends between 50 and 83 bases after the stop codon. To narrow down the size and location of the gene's promoter, the upstream region as well as several different sized deletions thereof were generated and cloned upstream of a luciferase reporter gene. The constructs were used to measure the Firefly and Renilla luciferase activities in dual assays. The results showed that luciferase activity decreased when bases -198 to -235 of amv248 upstream region were missing. Sequence analysis among the intermediate gene promoters of AMEV showed that TTTAT(T/A)TT(T/A)2TTA is possibly a common motif, however, further investigations are needed to confirm this conclusion.


[A use of Magne-B6 in the treatment of anxiety-depressive states in patients with epilepsy].
Magne-B6 was used, together with anticonvulsive therapy, in the treatment of 25 patients with different forms of epilepsy. In all cases, psychiatric status of patients featured by depression, anxiety and some psychotic sighs. The drug was prescribed in the mean therapeutic dose during 28 days. Along with psychopathologic examination, a psychometric method, using self-rating scales for Zung anxiety and depression scale, SCL-90 and Global clinical impression (CGI) scale, was administered. Magne-B6 exerted a positive non-specific influence on patient's mental state, especially with regard to affective disorders. The positive effect of the drug emerged on 14th day of the treatment and achieved a statistically significant level to 28th day. The medication was more effective in asthenic and subdepressive syndromes, in encephalopathic syndrome the efficacy was lower. The drug was well tolerated and did not cause any side effects.


Impact of R&D expenditures on research publications, patents and high-tech exports among European countries.
This study aimed to compare the impact of Research&Development (R&D) expenditures on research publications, patents and high-tech exports among European countries. In this study, 47 European countries were included. The information regarding European countries, their per capita Gross Domestic Product (GDP), R&D spending, number of universities, indexed scientific journals, high technology exports and number of patents were collected. We recorded the total number of research documents in various science and social sciences subjects during the period 1996-2011. The main source for information was World Bank, Web of Science, Thomson Reuters and SCImago/Scopus. The mean GDP per capita for all the European countries is 23372.64 ± 3588.42 US$, yearly per capita spending on R&D 1.14 ± 0.13 US$, number of universities 48.17 ± 10.26, mean number of Institute of Scientific Information (ISI) indexed journal per country 90.72 ± 38.47, high technology exports 12.86 ± 1.59 and number of patent applications 61504.23 ± 22961.85. The mean of research documents published in various science and social science subjects among all the European countries during the period 1996-2011 is 213405.70 ± 56493.04. Spending on R&D, number of universities, indexed journals, high technology exports and number of patents have a positive correlation with number of published documents in various science and social science subjects. We found a positive correlation between patent application and high-tech exports. However, there was no association between GDP per capita and research outcomes. It is concluded that, the most important contributing factors towards a knowledge based economy are spending on R&D, number of universities, scientific indexed journals and research publications, which in turn give a boast to patents, high technology exports and ultimately GDP.


Impact of boarding pediatric psychiatric patients on a medical ward.
Psychiatric disorders account for an increasing number of pediatric hospitalizations. Due to lack of psychiatric beds, patients on involuntary psychiatric holds may be admitted to medical units. Our objectives were to evaluate the rate of admission of psychiatric patients to a medical unit, psychiatric care provided, and estimated cost of care. The study involved retrospective chart review of all patients on involuntary psychiatric holds presenting to 1 pediatric emergency department from July 2009 to December 2010. We determined the rate of admission to a medical unit, the rate of counseling or psychiatric medication administration, and the estimated cost of nonmedical admissions (boarding) of patients on the medical unit. A total of 555 (50.1%) of 1108 patients on involuntary psychiatric holds were admitted to the pediatric medical unit. The majority (523 [94.2%]) were admitted for boarding because no psychiatric bed was available. Thirty-two (6.1%) patients admitted for isolated psychiatric reasons had counseling documented, and 105 (20.1%) received psychiatric medications. Patients admitted to an affiliated psychiatric hospital were significantly more likely to receive counseling and medications. Psychiatric patients were boarded in medical beds for 1169 days at an estimated cost of $2 232 790 or $4269 per patient over the 18-month period. We found high admission rates of patients on involuntary psychiatric holds to a pediatric medical unit with little psychiatric treatment in 1 hospital. Further research in other centers is required to determine the extent of the issue. Future studies of longer term outcomes (including readmission rates and assessments of functioning) are needed.


Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs.
Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and anti-canine IgE, before and after a single oral administration of PEA at doses of 3, 10 and 30 mg/kg. A significant reduction in wheal area induced by both antigen and anti-canine IgE challenge was observed after PEA administration. No significant differences were observed between the two higher doses studied, suggesting that the 10 mg/kg dose had exerted the maximum inhibitory effect. When blood levels of PEA were compared with the effects at different times, an evident correlation was obtained. However, the anti-inflammatory effects of PEA were more long-lasting than their plasma concentrations. The intradermal injection of substance P did not reveal any skin reaction (wheal or erythema formation) at any of the concentrations tested. In conclusion, PEA might constitute a new therapeutic strategy for the treatment of allergic inflammatory skin diseases in companion animals.


Chemical Modification Alters Protein-Protein Interactions and Can Lead to Lower Protein Solubility.
The chemical modification of proteins is at the frontier of developments in biological imaging and biopharmaceutics. With the advent of more sensitive and higher resolution imaging techniques, researchers increasingly rely on the functionalization of proteins to enable these techniques to capture cellular processes. For biopharmaceutical therapies, chemically modified proteins, for example, antibody-drug conjugates (ADCs) offer the possibility of more tailored treatments for the disease with lower toxicities than traditional small molecule therapies. However, relatively little consideration is paid to how chemical modifications impact protein-protein interactions and solution stability. Using human γD-crystallin as a model, we demonstrate that chemical modification of the protein surface alters protein-protein interactions, which can result in lower solubility depending on the chemical nature of the modifier and the position on the protein where the modification is made. Understanding these effects is essential to ensure that modifying proteins effectively occurs with minimum self-association and that studies carried out using labeled proteins accurately reflect those of unmodified proteins.


A problem in measuring the Stroop facilitation and interference effects: implications for measuring performance change in general.
The Stroop facilitation and interference effects as observed in the Stroop color-naming task are typically measured as the difference in naming time between the congruent or the conflicting condition and the neutral condition. The measure assumes the regression function relating the congruent or conflicting naming time to neutral naming time is linear with a slope of one and a nonzero intercept. Instead, analysis showed that the regression function subserving the facilitation effect, in fact, had a slope of less than one with a zero intercept. Analysis also showed that the regression function subserving the interference effect had a zero intercept with a greater than one slope. These results suggest that the Stroop facilitation and interference effects are the consequence of a multiplicative process by which each stage of the naming process is reduced or increased by a constant proportion. Also the appropriate measure of the Stroop effect is the ratio of the congruent (for facilitation) or the conflicting (for interference) naming time over the neutral naming time.


Volume-of-interest imaging with dynamic fluence modulation using multiple aperture devices.
Volume-of-interest (VOI) imaging is a strategy in computed tomography (CT) that restricts x-ray fluence to particular anatomical targets via dynamic beam modulation. This permits dose reduction while retaining image quality within the VOI. VOI-CT implementation has been challenged, in part, by a lack of hardware solutions for tailoring the incident fluence to the patient and anatomical site, as well as difficulties involving interior tomography reconstruction of truncated projection data. We propose a general VOI-CT imaging framework using multiple aperture devices (MADs), an emerging beam filtration scheme based on two binary x-ray filters. Location of the VOI is prescribed using two scout views at anterior-posterior (AP) and lateral perspectives. Based on a calibration of achievable fluence field patterns, MAD motion trajectories were designed using an optimization objective that seeks to maximize the relative fluence in the VOI subject to minimum fluence constraints. A modified penalized-likelihood method is developed for reconstruction of heavily truncated data using the full-field scout views to help solve the interior tomography problem. Physical experiments were conducted to show the feasibility of noncentered and elliptical VOI in two applications-spine and lung imaging. Improved dose utilization and retained image quality are validated with respect to standard full-field protocols. We observe that the contrast-to-noise ratio (CNR) is 40% higher compared with low-dose full-field scans at the same dose. The total dose reduction is 50% for equivalent image quality (CNR) within the VOI.


A New Paired Associative Stimulation Protocol with High-Frequency Peripheral Component and High-Intensity 20 Hz Repetitive Transcranial Magnetic Stimulation-A Pilot Study.
Paired associative stimulation (PAS) is a stimulation technique combining transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) that can induce plastic changes in the human motor system. A PAS protocol consisting of a high-intensity single TMS pulse given at 100% of stimulator output (SO) and high-frequency 100-Hz PNS train, or "the high-PAS" was designed to promote corticomotoneuronal synapses. Such PAS, applied as a long-term intervention, has demonstrated therapeutic efficacy in spinal cord injury (SCI) patients. Adding a second TMS pulse, however, rendered this protocol inhibitory. The current study sought for more effective PAS parameters. Here, we added a third TMS pulse, i.e., a 20-Hz rTMS (three pulses at 96% SO) combined with high-frequency PNS (six pulses at 100 Hz). We examined the ability of the proposed stimulation paradigm to induce the potentiation of motor-evoked potentials (MEPs) in five human subjects and described the safety and tolerability of the new protocol in these subjects. In this study, rTMS alone was used as a control. In addition, we compared the efficacy of the new protocol in five subjects with two PAS protocols consisting of PNS trains of six pulses at 100 Hz combined with (a) single 100% SO TMS pulses (high-PAS) and (b) a 20-Hz rTMS at a lower intensity (three pulses at 120% RMT). The MEPs were measured immediately after, and 30 and 60 min after the stimulation. Although at 0 and 30 min there was no significant difference in the induced MEP potentiation between the new PAS protocol and the rTMS control, the MEP potentiation remained significantly higher at 60 min after the new PAS than after rTMS alone. At 60 min, the new protocol was also more effective than the two other PAS protocols. The new protocol caused strong involuntary twitches in three subjects and, therefore, its further characterization is needed before introducing it for clinical research. Additionally, its mechanism plausibly differs from PAS with high-frequency PNS that has been used in SCI patients.


Effects of exercise training on exercise capacity and quality of life in patients with a left ventricular assist device: a preliminary randomized controlled trial.
A paucity of studies has examined the effect of exercise training after left ventricular assist device (LVAD) implantation. Previous research has demonstrated that insertion of the LVAD alone improves exercise capacity and quality of life (QOL). This study investigated whether supervised exercise training results in a further improvement. This prospective, randomized controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis investigated the effect of exercise training on exercise capacity and QOL in 14 patients who underwent LVAD insertion as a bridge to heart transplantation. Exercise training consisted of 8 weeks of gym-based aerobic and strengthening exercises 3 times a week, with a progressive mobilization program, compared with the control group that completed mobilization alone. Exercise capacity was measured before and after the intervention using maximal cardiopulmonary exercise testing and 6-minute walk distance (6MWD). QOL was measured using the Short Form 36-item assessment. No adverse events were reported. There was a trend toward greater improvement in peak oxygen consumption (Vo(2)), 6MWD, and QOL in the exercise group (n = 7) compared with the control group (n = 7); however, no significant between-group difference was detected for improvements in peak Vo(2) [mean difference (exercise--control)] of 2.96 ml/kg/min (95% confidence interval, -1.04 to 6.97), 6MWD at 54 meters (-51 to 159 meters), and QOL scores over time (p > 0.05). Exercise training is feasible and safe in patients with a LVAD. Trends toward greater improvement in exercise capacity and QOL after exercise training warrant further investigation in a larger trial.


Preoperative Stereotactic Radiosurgery for Brain Metastases.
Stereotactic radiosurgery (SRS) is increasingly utilized to treat the resection cavity following resection of brain metastases and recent randomized trials have confirmed postoperative SRS as a standard of care. Postoperative SRS for resected brain metastases improves local control compared to observation, while also preserving neurocognitive function in comparison to whole brain radiation therapy (WBRT). However, even with surgery and SRS, rates of local recurrence at 1 year may be as high as 40%, especially for larger cavities, and there is also a known risk of leptomeningeal disease after surgery. Additional treatment strategies are needed to improve control while maintaining or decreasing the toxicity profile associated with treatment. Preoperative SRS is discussed here as one such approach. Preoperative SRS allows for contouring of an intact metastasis, as opposed to an irregularly shaped surgical cavity in the post-op setting. Delivering SRS prior to surgery may also allow for a "sterilizing" effect, with the potential to increase tumor control by decreasing intra-operative seeding of viable tumor cells beyond the treated cavity, and decreasing risk of leptomeningeal disease. Because there is no need to treat brain surrounding tumor in the preoperative setting, and since the majority of the high dose volume can then be resected at surgery, the rate of symptomatic radiation necrosis may also be reduced with preoperative SRS. In this mini review, we explore the potential benefits and risks of preoperative vs. postoperative SRS for brain metastases as well as the existing literature to date, including published outcomes with preoperative SRS.


Molecular analysis of the macrolide-lincosamide resistance gene region of a novel plasmid from Staphylococcus hyicus.
Resistance to macrolides and lincosamides in Staphylococcus hyicus has been shown to be encoded by a 4.0-kb plasmid designated pSES21. It differed distinctly in its restriction map from all other staphylococcal macrolide resistance plasmids reported so far. Southern blot hybridisation with gene probes specific for staphylococcal erm genes demonstrated that the macrolide resistance gene belonged to hybridisation class C. Analysis of the ermC gene revealed that the deduced amino-acid sequence of the pSES21-encoded ErmC methylase exhibited c. 93% identity with the ErmC methylase encoded by plasmid pE194. The ermC gene of pSES21 was expressed constitutively and sequence analysis of the regulatory region showed multiple base-pair insertions and substitutions in the translational attenuator. As a consequence of these mutations, the reading frame of the small regulatory peptide was destroyed and a novel pair of inverted repeated sequences was generated. Previous studies identified sequence deletions and sequence duplications in the ermC regulatory region as the basis for constitutive ermC gene expression. The multiple point mutations shown in the pSES21-encoded ermC translational attenuator represent a novel kind of structural alteration in this regulatory region and may explain constitutive ermC gene expression by pairing of the newly generated inverted repeated segments in the presence of a functionally deleted reading frame for the small regulatory peptide.


Renin-angiotensin system and myocardial collagen matrix: modulation of cardiac fibroblast function by angiotensin II type 1 receptor antagonism.
Left ventricular hypertrophy is an adaptive process to increased loading of the left ventricle. This condition becomes pathologic with impaired myocardial function if the various tissue compartments of the myocardium (myocyte, interstitial and vascular compartments) are inhomogeneously altered, particularly if myocardial fibrosis occurs. In arterial hypertension, myocardial fibrosis is known to occur in association with activated circulating or local renin-angiotensin systems and includes reactive perivascular and interstitial fibrosis in both the pressure-overloaded hypertrophied left ventricle and the normotensive non-hypertrophied right ventricle. Therefore, it appears that hemodynamics are not primarily responsible for the adverse myocardial collagen matrix remodeling in hypertensive heart disease. Accordingly, we studied the interaction between cultured adult rat cardiac fibroblasts, which express messenger (m)RNAs for types I and III collagens, the major fibrillar collagens in the heart, and angiotensin II (Ang II), the effector hormone of the renin-angiotensin system. Specifically, we sought to determine whether Ang II stimulates total collagen synthesis and the expression of type I collagen mRNA in cultured adult rat cardiac fibroblasts, and to investigate the effects of Ang II on intracellular Ca2+ levels. Adult rat cardiac fibroblasts were cultured in Dulbecco's Modified Eagle's Medium + 10% fetal calf serum and incubated for 24 h with Ang II with or without specific Ang II type 1 or type 2 receptor antagonists. Collagen synthesis was measured using a 3H-proline incorporation assay, and type I collagen mRNA was determined using reverse-transcriptase polymerase chain reaction. Intracellular Ca2+ transients were measured by fast fluorescence photometry using the fluorescent dye fura-2-acetoxymethylester. We found a 76% increase in type I collagen mRNA in cultured cardiac fibroblasts after a 24-h incubation with Ang II, and this was abolished by simultaneous incubation with the Ang II type 1 (AT1)-receptor antagonist candesartan. Likewise, total collagen synthesis was stimulated by Ang II in a dose-dependent manner, and this stimulation was also counteracted by candesartan. Additionally, incubation with Ang II resulted in a significant dose-dependent increase in intracellular Ca2+ transients which was also abolished by treatment with candesartan. Ang II stimulates collagen synthesis in cultured adult rat cardiac fibroblasts via AT1 receptors, most likely using Ca2+ as a second messenger. These findings suggest a direct interaction between Ang II and cardiac fibroblasts in mediating myocardial fibrosis in arterial hypertension, leading to pathologic left ventricular hypertrophy with initially impaired diastolic and ultimately reduced systolic function of the left ventricle. The AT1-receptor antagonist candesartan cilexetil, which is the prodrug of the active compound candesartan, may prove valuable in preventing or regressing myocardial fibrosis in hypertensive heart disease.