Worniu, a Snail family zinc-finger protein, is required for brain development in Drosophila.
The Snail family of zinc-finger transcriptional repressors is essential for morphogenetic cell movements, mesoderm formation, and neurogenesis during embryonic development. These proteins also control cell cycle, cell death, and cancer progression. In Drosophila, three members of this protein family, Snail, Escargot, and Worniu, have essential but redundant functions in asymmetric cell division of neuroblasts. In addition, Snail is critical for early mesoderm formation and Escargot is required for maintaining diploidy in wing imaginal disc cells. In this report, we demonstrate that Worniu plays a role in brain development. We show that alleles of the l(2)35Da complementation group are mutants of worniu. The developing larvae of these mutant alleles fail to shorten their brainstems. The brain phenotype, as well as the lethality, of these mutants can be rescued by worniu transgenes. Moreover, RNAi experiments targeting the worniu transcript show the same nonshortening phenotype in larval brains. worniu is expressed in the neuroblasts of brain hemispheres and ventral ganglions. The results suggest that the loss of Worniu function within the neuroblasts ultimately causes the larval brainstem to fail to go through shortening during development.


Highly Stable Artificial Cells from Galactopyranose-Derived Single-Chain Amphiphiles.
Single-chain amphiphiles (SCAs) that self-assemble into large vesicular structures are attractive components of synthetic cells because of the simplicity of bilayer formation and increased membrane permeability. However, SCAs commonly used for vesicle formation suffer from restricted working pH ranges, instability to divalent cations, and the inhibition of biocatalysts. Construction of more robust biocompatible membranes from SCAs would have significant benefits. We describe the formation of highly stable vesicles from alkyl galactopyranose thioesters. The compatibility of these uncharged SCAs with biomolecules makes possible the encapsulation of functional enzymes and nucleic acids during the vesicle generation process, enabling membrane protein reconstitution and compartmentalized nucleic acid amplification, even when charged precursors are supplied externally.


Biogenesis of inner membrane proteins in Escherichia coli.
The inner membrane proteome of the model organism Escherichia coli is composed of inner membrane proteins, lipoproteins and peripherally attached soluble proteins. Our knowledge of the biogenesis of inner membrane proteins is rapidly increasing. This is in particular true for the early steps of biogenesis - protein targeting to and insertion into the membrane. However, our knowledge of inner membrane protein folding and quality control is still fragmentary. Furthering our knowledge in these areas will bring us closer to understand the biogenesis of individual inner membrane proteins in the context of the biogenesis of the inner membrane proteome of Escherichia coli as a whole. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.


Dynamics of the Extended String-Like Interaction of TFIIE with the p62 Subunit of TFIIH.
General transcription factor II E (TFIIE) contains an acid-rich region (residues 378-393) in its α-subunit, comprising 13 acidic and two hydrophobic (Phe387 and Val390) residues. Upon binding to the p62 subunit of TFIIH, the acidic region adopts an extended string-like structure on the basic groove of the pleckstrin homology domain (PHD) of p62, and inserts Phe387 and Val390 into two shallow pockets in the groove. Here, we have examined the dynamics of this interaction by NMR and molecular dynamics (MD) simulations. Although alanine substitution of Phe387 and/or Val390 greatly reduced binding to PHD, the binding mode of the mutants was similar to that of the wild-type, as judged by the chemical-shift changes of the PHD. NMR relaxation dispersion profiles of the interaction exhibited large amplitudes for residues in the C-terminal half-string in the acidic region (Phe387, Glu388, Val390, Ala391, and Asp392), indicating a two-site binding mode: one corresponding to the final complex structure, and one to an off-pathway minor complex. To probe the off-pathway complex structure, an atomically detailed free-energy landscape of the binding mode was computed by all-atom multicanonical MD. The most thermodynamically stable cluster corresponded to the final complex structure. One of the next stable clusters was the off-pathway structure cluster, showing the reversed orientation of the C-terminal half-string on the PHD groove, as compared with the final structure. MD calculations elucidated that the C-terminal half-acidic-string forms encounter complexes mainly around the positive groove region with nearly two different orientations of the string, parallel and antiparallel to the final structure. Interestingly, the most encountered complexes exhibit a parallel-like orientation, suggesting that the string has a tendency to bind around the groove in the proper orientation with the aid of Phe387 and/or Val390 to proceed smoothly to the final complex structure.


Thrombus resolution and right ventricular functional recovery using ultrasound-accelerated thrombolysis in acute massive and submassive pulmonary embolism.
This study aims to evaluate the efficacy and safety of ultrasound-accelerated catheter-directed thrombolysis (UACDT) in the treatment of massive and submassive pulmonary embolism (PE). We conducted a prospective, observational cohort study of consequtive patients with massive or submassive PE treated with low-dose UACDT using EKOS EkoSonic® system at single center from May 2014 until April 2015. Overall, thirty-eight patients (median age, 64.5 years) were included. The primary safety outcomes were change in right ventricular (RV) to left ventricular (LV) diameter ratio within 24 hours of procedure initiation, at 1- and 6-month follow-up and major bleeding within 96 hours of the procedure initiation. BNP, troponin and D-dimer levels were also measured. The ultrasound-accelerated thrombolytic catheters were bilaterally placed in 25 (65.8%) patients. The median tissue plasminogen activator (tPA) dose for all patients in our study was 21.0 mg and the median infusion time was 15 hours. Measurements before and after treatment showed a decrease in pulmonary artery pressure. The median value of RV/LV diameter ratio decreased from 0.9 (0.7-1.1) at baseline to 0.7 (0-0.97) at 6-month follow-up (P=0.001) and pulmonary artery pressure from 61.4 ±16.7 to 37.2±9.1 mmHg (P=0.001). The median BNP level at baseline was 169 (29-721) pg/mL and 45.5 (0-328) pg/mL at 6 month follow-up (P=0.001). Of 38 patients with PE, one had intracranial hemorrage, one gastrointestinal bleeding and two developed puncture site bleeding. This prospective study provides alternative treatment option and an addition to the treatment algorithm for the management of pulmonary embolism.


Congenital muscular dystrophy in Arab children.
The congenital muscular dystrophies are autosomal recessive disorders with different clinical phenotypes, the spectrum of which varies between different ethnic communities. We report our findings in 21 Arab children with congenital muscular dystrophy. All 21 cases were of the pure type, with normal mental status, except 1 case with perinatal hypoxic-ischemic insult. Fourteen were laminin alpha2 (merosin) deficient, and six were laminin alpha2 positive; laminin alpha2 status was not determined in one patient. None of the laminin alpha2-deficient patients achieved independent ambulation, whereas three of the laminin alpha2-positive patients were able to walk. The elevated levels of serum creatine kinase did not differentiate the two groups and tended to decrease after the age of 5 years. Radiologic evaluation demonstrated an abnormal central white-matter signal in 11 of 13 laminin alpha2-deficient and in 1 of 5 laminin alpha2-positive patients; none had evidence of brain dysplasia. Nerve conduction velocities were normal in 5 of 5 laminin alpha2-positive patients, whereas in the laminin alpha2-deficient patients, it was slow in 9 of 11 for the motor nerves and normal in 8 of 9 for the sensory nerve. Two of the laminin alpha2-positive patients had pseudohypertrophy of the calves, and two of the laminin alpha2-deficient ones had seizures. The patient in whom the laminin alpha2 status was not determined had a severe course, an abnormal central white-matter signal, and epilepsy and resembled more the laminin alpha2-deficient group.


Application of the Theory of Planned Behavior to Predict Nutrition Students' Intention to Work with Older Adults.
As Registered Dietitian Nutritionists play an important role in providing nutrition care plans for successful aging, it is important to identify factors influencing nutrition students' intention to work with older adults. A cross-sectional study was conducted to identify significant predictors of nutrition students' intention to work with older adults by utilizing the Theory of Planned Behavior (TPB). A total of 183 students, majoring in Nutrition at a large Southern University, completed a questionnaire examining validated TPB constructs. Structural Equation Modeling with maximum likelihood was used to analyze the data. The structural model provided a good fit to the data (x2 = 44.95, df = 38, p < 0.01; RMSEA = 0.03, CFI = 0.99; TLI = 0.99. Attitude (γ = 0.49, p < 0.001) and subjective norm (γ = 0.39, p < 0.001) emerged as significant predictors of nutrition students' intention to work with older adults. Findings highlight the importance of providing dietetics curricula that provide opportunities for students to develop positive attitudes toward working with older adults. Dietetic educators should present themselves as positive role models in working with older adults, as the educators influence students' intention to work with this population.


Modification of fatty acid composition in tomato (Lycopersicon esculentum) by expression of a borage delta6-desaturase.
The improvement of nutritional quality is one potential application for the genetic modification of plants. One possible target for such manipulation is the modification of fatty acid metabolism. In this work, expression of a borage delta6-desaturase cDNA in tomato (Lycopersicon esculentum L.) has been shown to produce gamma-linolenic acid (GLA; 18:83 delta6,9,12) and octadecatetraenoic acid (OTA; 18:4 delta6,9,12,15) in transgenic leaf and fruit tissue. This genetic modification has also, unexpectedly, resulted in a reduction in the percentage of linoleic acid (LA 18:2 delta9,12) and a concomitant increase in the percentage of alpha-linolenic acid (ALA; 18:3 delta9,12,15) in fruit tissue. These changes in fatty acid composition are thought to be beneficial for human health.


Cathepsin L-like protease from Xenopus embryos that is stimulated by nucleoside phosphates and nucleic acids.
An acid thiol protease that was activated at an early stage of embryogenesis was purified from Xenopus embryos. The N-terminal amino acid sequence (16 residues) of the heavy chain of the enzyme was similar to that of cathepsin L. The proteolytic activity of the protease was enhanced by ATP. Other nucleoside triphosphates, AMP and nucleic acids also enhanced the proteolytic activity. The possible mechanism and biological significance of the activation of the protease in Xenopus embryos are discussed.


Assessments of Algal Toxicity and PBT Behaviour of Pesticides with No Eco-toxicological Data: Predictive Ability of QSA/(T)R Models.
In the present study, the effect of eight pesticides with no ecotoxicological data on the growth rate of Chlorella vulgaris was measured. The selected pesticides are acetochlor, acetamiprid, boscalid diphenamid, gibberellic acid, ioxynil, diclofop and 2,4,5-T. The algal toxicity (IC50 ) of boscalid could not be determined within its solubility limit. Acetamiprid, diphenamid and gibberellic acid revealed IC50 values>100 mg/L. Among the others, the order of 96-h IC50 of pesticides was found as acetochlor>ioxynil>diclofop>2,4,5-T. The IC50 values were also predicted by using four Quantitative Structure-Activity/(Toxicity) Relationship (QSA/(T)R) models selected from the literature. The predictions of the models provided by QSARINS-Chem module of QSARINS as well as those obtained in our previous studies were compared with the results of experimental algal toxicity tests that were performed in our laboratory. The QSTR model generated for the toxicity of diverse chemicals to freshwater algae was able to correctly predict the toxicity order of the pesticides tested in the present study, confirming the utility of the QSA/(T)R approach. Additionally, Persistence, Bioaccumulation and Toxicity (PBT) Index model provided via the software QSARINS was employed and boscalid and diclofop were found to be PBT chemicals based on the PBT model. The present study will be very helpful when a more holistic approach applied to understand the fate of these chemicals in the environment.


Trends in the Epidemiology and Outcomes of Pneumocystis Pneumonia among Human Immunodeficiency Virus (HIV) Hospitalizations.
Introduction: Pneumocystis Pneumonia (PCP) is a common opportunistic infection among people living with the human immunodeficiency virus (HIV). This study's objective was to assess temporal trends in PCP epidemiology among hospitalized patients with HIV/AIDS in the US and to compare data for hospitalizations with HIV with PCP to those without PCP. Methods: The national inpatient sample (NIS) data were analyzed from 2002−2014. The discharge coding identified hospitalized patients with HIV or AIDS and with or without PCP. Results: We identified 3,011,725 hospitalizations with HIV/AIDS during the study period; PCP was present in 5% of the patients with a diagnosis of HIV. The rates of PCP progressively declined from 6.7% in 2002 to 3.5 % in 2014 (p < 0.001). Overall mortality in patients with HIV was 3.3% and was significantly higher in those with PCP than without PCP (9.9% vs. 2.9%; p < 0.001). After adjusting for demographics and other comorbidities, PCP had higher odds of hospital mortality 3.082 (OR 3.082; 95% CI, 3.007 to 3.159; p < 0.001). Conclusion: From 2002 to 2014, the rate of PCP in HIV patients has decreased significantly in the United States but is associated with substantially higher mortality.


Imaging Review of Hockey-Related Upper Extremity Injuries.
Ice hockey is a fast-paced contact sport with a high incidence of injuries. Upper extremity injury is one of the most common regions of the body to be injured in hockey. This imaging review will equip the radiologist with a knowledge of the more common and severe upper extremity injuries that occur in this sport.


Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression.
Treatment of primary monocytes with soluble HIV-Tat protein is associated with increased monocyte metalloproteinase-9 (MMP-9) expression and enhanced beta 2 integrin expression that increases monocyte/endothelial adhesion. These alterations require greater than 12 h of HIV-Tat treatment, suggesting the involvement of intermediate factors. Thus, we have examined the role of cytokines in the HIV-Tat-induced alteration of monocyte function. Treatment of monocytes with HIV-Tat rapidly up-regulated the production of IL-1 beta, IL-6, IL-8, and TNF-alpha, but not IL-3, granulocyte-macrophage CSF, basic fibroblast growth factor, or macrophage-inflammatory protein-1 alpha, and was associated with up-regulation of the corresponding cytokine mRNA. Inclusion of neutralizing anti-cytokine Abs to IL-1 beta or TNF-alpha during the HIV-Tat pretreatment period significantly inhibited the HIV-Tat-induced increase in MMP-9 production, monocyte/endothelial adhesion, and monocyte-dependent endothelial damage. In contrast, neutralizing Abs against IL-6 and IL-8 had no effect. The effects of HIV-Tat treatment, namely MMP-9 production, enhanced monocyte/endothelial cell adhesion, and monocyte-dependent endothelial damage, were mimicked by treating the monocytes with IL-1 beta or TNF-alpha, but not with IL-6 or IL-8. Therefore, the mechanism by which HIV-Tat activates monocyte function is dependent on HIV-Tat-induced production of cytokines (IL-1 beta and TNF-alpha).


Development of a medical robot system for minimally invasive surgery.
Robot-assisted systems have been widely used in minimally invasive surgery (MIS) practice, and with them the precision and accuracy of surgical procedures can be significantly improved. Promoting the development of robot technology in MIS will improve robot performance and help in tackling problems from complex surgical procedures. A medical robot system with a new mechanism for MIS was proposed to achieve a two-dimensional (2D) remote centre of motion (RCM). An improved surgical instrument was designed to enhance manipulability and eliminate the coupling motion between the wrist and the grippers. The control subsystem adopted a master-slave control mode, upon which a new method with error compensation of repetitive feedback can be based for the inverse kinematics solution. A unique solution with less computation and higher satisfactory accuracy was also obtained. Tremor filtration and trajectory planning were also addressed with regard to the smoothness of the surgical instrument movement. The robot system was tested on pigs weighing 30-45 kg. The experimental results show that the robot can successfully complete a cholecystectomy and meet the demands of MIS. The results of the animal experiments were excellent, indicating a promising clinical application of the robot with high manipulability.


Use of a molybdenum(VI) complex as artificial protease in protein photocleavage.
In this study, a molybdenum(VI) peroxo α-amino acid complex, MoO(O2)2(α-leucine) (H2O), was prepared and used as an artificial protease for site-specific cleavage of porcine pepsin, a model protein. Cleavage of pepsin by MoO(O2)2(α-leucine) (H2O) was achieved under photochemical conditions at room temperature and pH 7.0. The reaction was activated by irradiation of the MoO(O2)2(α-leucine) (H2O)-protein mixture by UV light (320 and 340nm) for up to 30min. No cleavage was observed in the absence of MoO(O2)2(α-leucine) (H2O) or the light. The photocleavage yield increased with irradiation time. The cleaved fragments were sequencable, and the cleavage site was assigned to Leu(112)-Tyr(113). The cleavage reaction was quenched by ethanol. Therefore, hydroxyl radicals may be involved in the reaction and responsible for the cleavage of the protein. This is the first demonstration of the successful photocleavage of proteins by a molybdenum complex. This observation can provide a new approach for the photochemical footprinting of metal binding sites on proteins.


Antibiotic prophylaxis in surgery of the intervertebral disc. A comparison between gentamicin and cefuroxime.
Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis.


Antitumor activity of polysaccharides isolated from Patrinia heterophylla.
The research investigated the effect of Patrinia heterophylla Bunge (Valerianaceae) polysaccharides (PHB-P1) on U14-bearing mice. The tumor weight of mice treated with PHB-P1 (30, 60 mg/kg body weight) was significantly lower than that of the control group, a decrease of serum lactate dehydrogenase (LDH) activity was observed, and the serum alkaline phosphatase (AKP) level was increased slightly. The number of apoptotic tumor cells was significantly increased in the mice by treatment of PHB-P1 (30, 60 mg/kgbw). Cell cycle analysis showed the accumulation of tumor cells in the G2/M phase and a relative decrease of the S phase. By the immunohistochemical analysis, PHB-P1 (30, 60 mg/kgbw) might up-regulate the expression of p53 and Bax, and significantly inhibited the expression of Bcl-2 in tumor tissues. In conclusion, PHB-P1 could inhibit tumor growth and induce tumor cell apoptosis.


Surgical outcomes after total colectomy with ileorectal anastomosis in patients with medically intractable slow transit constipation.
The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation. A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner's constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients' postoperative satisfaction scores were collected using a 4-point scale. The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner's scores were collected from 33 patients (89.1%), and the mean preoperative Wexner's score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%). A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation.


A giant nerve net with multi-effector synapses underlying epithelial adhesive strips in the mouth of Beroë (Ctenophora).
We present ultrastructural evidence for the first known example of a giant nerve net in the phylum Ctenophora. The giant fibre system in Beroë underlies paired strips of adherent epithelial cells that run inside the lips. Interlocking actin-lined cell junctions between opposing adhesive strips keep Beroë's large mouth closed while the ctenophore searches for prey. The giant neurons, up to 6-8 microns in diameter, form a continuous lattice-like plexus rich in vesicles, microtubules, and 'presynaptic triads'. A novel feature is that individual giant axons make synaptic contacts with more than one type of effector, i.e. longitudinal muscle fibres and epithelial adhesive cells. Contact of prey with sensory receptors on the lips of Beroë induces rapid disappearance of the actin-lined adhesive cell junctions, and muscular opening of the mouth to ingest prey. Electron microscopy of food-opened mouths shows local thickening of longitudinal muscles and widening of the basal ends of epithelial cells in the adhesive strip, correlated with retraction of the adhesive epithelium into the mesoglea. Addition of 1% Triton X-100 to formaldehyde fixative in the absence of prey also elicits regional thickening of longitudinal muscles at the location of the adhesive strips (visualized by rhodamine-phalloidin staining). The giant neuron system may serve as a final common pathway to rapidly signal disassembly of actin-based junctions between adhesive cells as well as contractions of longitudinal muscles underlying the adhesive strips, thereby enabling Beroë to open its mouth rapidly to engulf prey.


How Should Lived Experience of Racism Count in Medical School Admissions?
There are fewer Black men in US medical schools today than in 1970. This and other kinds of ongoing inequity express the systemic racism Black Americans face in health care. Increasing Black physician representation in medicine is key to motivating health equity, so many colleges and universities have developed programs to recruit and retain students with minoritized identities. This article suggests how Black medical school applicants' lived experiences of racism can contribute prominently to building medicine's capacity to promote healing and health equity.


[Diagnosis and surgical treatment of intraparenchymal sylvian fissure meningioma].
To describe the characteristics of patients diagnosed with intraparenchymal sylvian meningioma at our department. A retrospective review was performed over 5 patients with intraparenchymal sylvian fissure meningioma confirmed by histopathology and receiving treatment at our department during January 1997 to September 2008. The mean age was 19.4 years old and there were 3 males and 2 females. On CT scanning, intraparenchymal sylvian meningioma was iso- or slightly hyper-dense masses. On MR imaging, tumors showed iso- or hypo- intense signal on T1WI and hyperintense signal on T2WI. After contrast enhancement, T1-weighted images revealed well-demarcated enhancing masses and intimately associated with the middle cerebral artery and its branches in the sylvian fissure. All the patients underwent craniotomy. As a rare disease with radiographic characteristics similar to those of general meningiomas, intraparenchymal sylvian fissure meningioma does not adhere to the dura matter but adhere to or even encase the middle cerebral artery and its branches in the sylvian fissure. All of the above have differential values. During the surgical procedures, a proper handling of tumor and encompassed main trunk of middle cerebral artery and its branches is crucial to patient prognosis.


Effects of the home environment on school-aged children's sleep.
Examine the relationship between the sleep behavior of elementary school-aged children and characteristics of the home environment. Cross-sectional analysis of children participating in a cohort study. Cleveland Children's Sleep and Health Study, an ethnically mixed, urban, community-based cohort. Four hundred forty-nine children (50% girls, 46% African-American) aged 8 to 11 years. Sleep and health data were obtained from a child-completed 7-day sleep journal and caregiver-completed health and sleep questionnaire. Home-environment predictors were Middle-Childhood Home Observation for Measurement of the Environment (MC-HOME) total score and Encouragement of Maturity and Physical Environment subscale scores. Sleep outcomes were mean nightly sleep duration, night-to-night variation in sleep duration, and bedtime of 11 PM or later. Adjusted analyses showed that higher Encouragement of Maturity subscale scores were associated with longer sleep duration (P < .05) and decreased odds of a bedtime at 11 PM or later (odds ratio = .74, 95% confidence interval, .58-.95). In girls, higher Encouragement of Maturity scores were also associated with decreased nightly variation in mean sleep duration (P < .001). Increases in total MC-HOME score were associated with increased mean sleep duration among African-American children only (P < .05). Collectively, results indicate that a parenting style encouraging social maturity in children is linked to healthier sleep patterns.


Renaissance of Bernal's random close packing and hypercritical line in the theory of liquids.
We review the scientific history of random close packing (RCP) of equal spheres, advocated by J D Bernal as a more plausible alternative to the non-ideal gas or imperfect crystal as a structural model of simple liquids. After decades of neglect, computer experiments are revealing a central role for RCP in the theory of liquids. These demonstrate that the RCP amorphous state of hard spheres can be well defined, is reproducible, and has the thermodynamic status of a metastable ground state. Further evidence from simulations of square-well model liquids indicates an extended role of RCP as an amorphous ground state that terminates a supercooled liquid coexistence line, suggesting likewise for real liquids. A phase diagram involving percolation boundaries has been proposed in which there is no merging of liquid and gas phases, and no critical singularity as assumed by van der Waals. Rather, the liquid phase continuously spans all temperatures, but above a critical dividing line on the Gibbs density surface, it is bounded by a percolation transition and separated from the gas phase by a colloidal supercritical mesophase. The colloidal-like inversion in the mesophase as it changes from gas-in-liquid to liquid-in-gas can be identified with the hypercritical line of Bernal. We therefore argue that the statistical theory of simple liquids should start from the RCP reference state rather than the ideal gas. Future experimental priorities are to (i) find evidence for an amorphous ground state in real supercooled liquids, (ii) explore the microscopic structures of the supercritical mesophase, and (iii) determine how these change from gas to liquid, especially across Bernal's hypercritical line. The theoretical priority is a statistical geometrical theory of RCP. Only then might we explain the coincident values of the RCP packing fraction with Buffon's constant, and the RCP residual entropy with Boltzmann's ideal gas constant.


A Linear Discriminant Analysis Model Based on the Changes of 7 Proteins in Plasma Predicts Response to Anlotinib Therapy in Advanced Non-Small Cell Lung Cancer Patients.
Anlotinib is a multi-targeted tyrosine kinase inhibitor mainly targeting angiogenesis signaling. The predictive marker of anlotinib's efficacy remains elusive. This study was designed to explore the predictive marker of anlotinib in non-small cell lung cancer (NSCLC). We prospectively enrolled 52 advanced NSCLC patients who underwent at least one line of targeted therapy or chemotherapy between August 2018 and March 2020. Patients were divided into durable responders (DR) and non-durable responders (NDR) based on the median progression-free survival (PFS, 176 days). The Olink Immuno-Oncology panel (92 proteins) was used to explore the predictive protein biomarkers in plasma samples before treatment (baseline) and on the first treatment evaluation (paired). At baseline, the response to anlotinib was not significantly associated with age, gender, smoke history, histology, oligo-metastases, EGFR mutations, and other clinical characteristics. The results of PFS-related protein biomarkers at baseline were all not satisfying. Then we assessed the changes of 92 proteins levels in plasma on the first treatment evaluation. We obtained a Linear discriminant analysis (LDA) model based on 7 proteins, with an accuracy of 100% in the original data and an accuracy of 89.2% in cross validation. The 7 proteins were CD70, MIC-A/B, LAG3, CAIX, PDCD1, MMP12, and PD-L2. Multivariate Cox analysis further showed that the changes of CD70 (HR 25.48; 95% CI, 4.90-132.41, P=0.000) and MIC-A/B (HR 15.04; 95% CI, 3.81-59.36, P=0.000) in plasma were the most significant prognostic factors for PFS. We reported herein a LDA model based on the changes of 7 proteins levels in plasma before and after treatment, which could predict anlotinib responders among advanced NSCLC patients with an accuracy of 100%. Further studies are warranted to verify the prediction performance of the LDA model.


In-stent Anchoring Facilitating Side-branch Balloon Delivery for Final Kissing: A Prospective, Single-center Registry Study.
Recrossing the compromised side branch (SB) with a balloon is sometimes technically challenging. The aim of this study was to evaluate whether in-stent anchoring (ISA) is safe and effective to facilitate SB balloon delivery for final kissing. One hundred and fifty-nine consecutive patients were included (166 bifurcation lesions) in this prospective, single-center registry. ISA was used as a bailout method after unsuccessful SB crossing using conventional techniques, including low-profile balloons. Technique success was defined as SB balloon delivery and final kissing. Kissing-balloon delivery was successfully performed with conventional strategies in 149 of 166 lesions (89.8%). In the remaining 17 lesions (10.2%), recrossing of the main vessel stent strut was not successful; therefore, ISA was attempted. The balloon successfully crossed the stent struts, and final kissing was achieved in 15 of 17 lesions (88.2%). Total final kissing was achieved in 164 of 166 lesions (98.8%), with success rates of 100% in the single-stent group and 97.6% in the two-stent group. Two cases without balloon delivery had complex bifurcation lesions with severe calcification. There was no vessel dissection in the anchoring zone. ISA is safe and effective for recrossing stent struts when conventional low-profile balloons have failed. However, large-scale trials are warranted for further evaluation.


A rapidly self-healing supramolecular polymer hydrogel with photostimulated room-temperature phosphorescence responsiveness.
Development of self-healing and photostimulated luminescent supramolecular polymeric materials is important for artificial soft materials. A supramolecular polymeric hydrogel is reported based on the host-guest recognition between a β-cyclodextrin (β-CD) host polymer (poly-β-CD) and an α-bromonaphthalene (α-BrNp) polymer (poly-BrNp) without any additional gelator, which can self-heal within only about one minute under ambient atmosphere without any additive. This supramolecular polymer system can be excited to engender room-temperature phosphorescence (RTP) signals based on the fact that the inclusion of β-CD macrocycle with α-BrNp moiety is able to induce RTP emission (CD-RTP). The RTP signal can be adjusted reversibly by competitive complexation of β-CD with azobenzene moiety under specific irradiation by introducing another azobenzene guest polymer (poly-Azo).


Terminal diols as efficient substrates for transglycosylational activity of NAD glycohydrolase.
Linear terminal alkane-diols have been shown to function as more efficient substrates of the transglycosylational activity of NAD+ glycohydrolase (NADase) than the corresponding respective 1-alkanols. A series of eight alkane-diols from ethane-1,2- to nonane-1,9-diols underwent an O-ADP-ribosylation in the incubation reaction with NAD/NADase to provide the corresponding ribosylated products. The structural properties of these products were characterized by 1H NMR and MS spectrometries. No substantial double ADP-ribosylation of the two hydroxy functions was observed which was initially expected in the diols of higher carbon number.


Differentially expressed genes of virulent and nonvirulent Entamoeba histolytica strains identified by suppression subtractive hybridization.
Entamoeba histolytica is a parasite which presents capacity to degrade tissues and therefore has a pathogenic behavior. As this behavior is not shown by all strains, there have been several studies investigating molecular basis of the cytotoxicity process. Using the suppression subtractive hybridization (SSH) technique, differential gene expressions of two E. histolytica strains, one virulent (EGG) and one nonvirulent (452), have been analyzed with the purpose of isolating genes which may be involved with amoebic virulence. Nine cDNA fragments presenting high homology with E. histolytica previously sequenced genes were subtracted. Of these, four genes were confirmed by RT-PCR. Two coding for hypothetical proteins, one for a cysteine-rich protein, expressed only in the virulent strain, EGG and another one, coding for grainin 2 protein, exclusive from 452 strain. This study provided new insight into the proteins differences in the virulent and nonvirulent E. histolytica strains. We believe that further studies with these proteins may prove association of them with tissue damage, providing new perceptions to improve treatment or diagnosis of the invasive disease.


Improved glucose tolerance after high-load strength training in patients undergoing dialysis.
The aim of this controlled study was to investigate the effect of high-load strength training on glucose tolerance in patients undergoing dialysis. 23 patients treated by dialysis underwent a 16-week control period followed by 16 weeks of strength training three times a week. Muscle fiber size, composition and capillary density were analyzed in biopsies obtained in the vastus lateralis muscle. Glucose tolerance and the insulin response were measured by a 2-hour oral glucose tolerance test. All outcome measures remained unchanged during the control period. After strength training the relative area of type 2X fibers was decreased. Muscle fiber size and capillary density remained unchanged. After the strength training, insulin concentrations were significantly lower in patients with impaired glucose tolerance or type 2 diabetes (n = 14) (fasting insulin from 68 ± 12 (46-96) to 54 ± 10 (37-77) pmol/l, p < 0.05, 2-hour insulin from 533 ± 104 (356-776) to 344 ± 68 (226-510) pmol/l, p < 0.05, total insulin area under the curve from 1,868 ± 334 (1,268-2,536) to 1,465 ± 222 (1,094-1,913), p < 0.05). Insulin concentrations were unchanged in patients with normal glucose tolerance (n = 9). The conducted strength training was associated with a significant improvement in glucose tolerance in patients with impaired glucose tolerance or type 2 diabetes undergoing dialysis. The effect was apparently not associated with muscle hypertrophy, whereas the muscle fiber type composition was changed.


Intrinsic Differences in Backbone Dynamics between Wild Type and DNA-Contact Mutants of the p53 DNA Binding Domain Revealed by Nuclear Magnetic Resonance Spectroscopy.
Mutations in p53's DNA binding domain (p53DBD) are associated with 50% of all cancers, making it an essential system to investigate and understand the genesis and progression of cancer. In this work, we studied the changes in the structure and dynamics of wild type p53DBD in comparison with two of its "hot-spot" DNA-contact mutants, R248Q and R273H, by analysis of backbone amide chemical shift perturbations and 15N spin relaxation measurements. The results of amide chemical shift changes indicated significantly more perturbations in the R273H mutant than in wild type and R248Q p53DBD. Analysis of 15N spin relaxation rates and the resulting nuclear magnetic resonance order parameters suggests that for most parts, the R248Q mutant exhibits limited conformational flexibility and is similar to the wild type protein. In contrast, R273H showed significant backbone dynamics extending up to its β-sandwich scaffold in addition to motions along the DNA binding interface. Furthermore, comparison of rotational correlation times between the mutants suggests that the R273H mutant, with a higher correlation time, forms an enlarged structural fold in comparison to the R248Q mutant and wild type p53DBD. Finally, we identify three regions in these proteins that show conformational flexibility to varying degrees, which suggests that the R273H mutant, in addition to being a DNA-contact mutation, exhibits properties of a conformational mutant.


From gRNA Identification to the Restoration of Dystrophin Expression: A Dystrophin Gene Correction Strategy for Duchenne Muscular Dystrophy Mutations Using the CRISPR-Induced Deletion Method.
The discovery of the CRISPR-Cas9 system raises hope for the treatment of many genetic disorders. We describe here an approach based on the use of a pair of single guide RNAs to form a hybrid exon that does not only restore the dystrophin gene reading frame but also results in the production of a dystrophin protein with an adequate structure of the central rod-domain, with a correct spectrin-like repeat. The therapeutic approach described here involved DMD patient cells having a deletion of exons 51-53 of the DMD gene.


Urodynamic Study Findings Prior to Myelomeningocele Repair in Neonates.
Myelomeningocele (MMC) is the most common cause of neurogenic bladder dysfunction in children. Neurogenic bladder dysfunction is developed before birth due to autonomous nervous system affected prenatally in patients with MMC. The aim of this study was to share urodynamic study findings before MMC repair and to discuss the correlation with neurological evaluation. We prospectively studied 37 patients who underwent surgery for MMC repair in our institution in the first 20 h of their lives between 2013 and 2016. All patients were evaluated by a neurosurgeon, neonatologist, and pediatric surgeon. Urodynamic study was performed in first 18h of life before MMC repair in all patients. Lesion level, occurrence of hydrocephalus, neurological functions, spinal deformities, and urodynamic study results were analyzed. The study included 18 female and 19 male patients. Overactive detrusor was detected in 22 patients, and hypoactive detrusor was detected in 5 patients. Overactive sphincter muscle was detected in 32 patients, and hypoactive sphincter was detected in 2 patients. Detrusor-sphincter dyssynergia was present in 34 patients. Detailed analysis of urodynamic study findings in larger patient groups may be important to understand the physiopathology of prenatal damage in patients with MMC.


How to Group Genes according to Expression Profiles?
The most commonly applied strategies for identifying genes with a common response profile are based on clustering algorithms. These methods have no explicit rules to define the appropriate number of groups of genes. Usually the number of clusters is decided on heuristic criteria or through the application of different methods proposed to assess the number of clusters in a data set. The purpose of this paper is to compare the performance of seven of these techniques, including traditional ones, and some recently proposed. All of them produce underestimations of the true number of clusters. However, within this limitation, the gDGC algorithm appears to be the best. It is the only one that explicitly states a rule for cutting a dendrogram on the basis of a testing hypothesis framework, allowing the user to calibrate the sensitivity, adjusting the significance level.


[Biological causes of depression in Systemic Lupus Erythematosus].
The high prevalence of depression in patients with systemic lupus erythematosus (SLE) may result from the psychosocial impact of this chronic disease as well as from a lesion of the central nervous system (CNS). Recently, the biological basis of depression in SLE has been confirmed, under the influence of several factors, which will be reviewed here. Published evidence points to the participation of biochemical and neurophysiological changes, induced by cytokines, in the development of neuropsychiatric symptoms. Through activation of the enzyme indoleamine 2,3-dioxygenase (IDO), the alteration of neurotransmitters' bioavailability, the modification of neuroplasticity and neurogenesis and the overstimulation of certain neural circuits, cytokines are capable of causing mood swings and depression. On the other hand, associated with the immune deregulation, the Hypothalamic-Pituitary-Adrenal (HPA) axis dysfunction correlates with neurophysiological changes involved in depression. Moreover, cerebro-reactive autoantibodies present in the cerebrospinal fluid (CSF), such as anti-N-methyl-D-aspartate(NMDA) and anti-ribosomal P, can cause significant damage to neurons in brain areas which are relevant to humor and behavior, potentially leading to depressive symptoms. In neuroanatomical terms, brain lesions in areas of the limbic system present in lupus patients, despite their unclear etiology, suggest impairment of cerebral achievement in emotional and behavioral functions. In summary, several biological changes are able to cause depression in SLE and their identification is essential to the management of the disease.


Antibacterial Activity of Bacillus inaquosorum Strain T1 against pirABVp -Bearing Vibrio parahaemolyticus: Genetic and Physiological Characterization.
Acute hepatopancreatic necrosis disease (AHPND) is caused by PirAB toxin-producing Vibrio parahaemolyticus and has devastated the global shrimp aquaculture industry. One approach for preventing the growth of AHPND-producing Vibrio spp. is through the application of beneficial bacteria capable of inhibiting these pathogens. In this study, we focused on the inhibitory activity of Bacillus inaquosorum strain T1, which hinders V. parahaemolyticus growth in coculture experiments in a density-dependent manner; inhibition was also observed using cell-free supernatants from T1 stationary-phase cultures. Using mariner-based transposon mutagenesis, 17 mutants having a complete or partial loss of inhibitory activity were identified. Of those displaying a total loss of activity, 13 had insertions within a 42.6-kb DNA region comprising 15 genes whose deduced products were homologous to nonribosomal polypeptide synthetases (NRPSs), polyketide synthases (PKSs), and related activities, which were mapped as one transcriptional unit. Mutants with partial activity contained insertions in spo0A and oppA, indicating stationary-phase control. The levels of expression of NRPS and PKS lacZ transcriptional fusions were negligible during growth and were the highest during early stationary phase. Inactivation of sigH resulted in a loss of inhibitor activity, indicating a role for σH in transcription. Disruption of abrB resulted in NRPS and PKS gene overexpression during growth as well as enhanced growth inhibition. Our characterization of the expression and control of an NRPS-PKS gene cluster in B. inaquosorum T1 provides an understanding of the factors involved in inhibitor production, enabling this strain's development for use as a tool against AHPND-causing Vibrio pathogens in shrimp aquaculture.IMPORTANCE The shrimp aquaculture industry has been significantly impacted by acute hepatopancreatic necrosis disease (AHPND), resulting in significant financial losses annually. AHPND is caused by strains of the bacterial pathogen Vibrio parahaemolyticus, and treatment of AHPND involves the use of antibiotics, which leads to a rise in the number of antibiotic-resistant strains. Alternative treatments include the application of beneficial microorganisms having inhibitory activities against pathogens causing AHPND. In this study, we examined the ability of Bacillus inaquosorum strain T1 to inhibit the growth of an AHPND-causing Vibrio strain, and we show that this activity involves a gene cluster associated with antibacterial compound production. We found that gene expression is under stationary-phase control and that enhanced activity occurs upon inactivation of a global transition state regulator. Our approach for understanding the factors involved in producing B. inaquosorum strain T1 inhibitory activity will allow for the development of this strain as a tool for AHPND prevention and treatment.


Cellular immune responses in seronegative sexual contacts of acute hepatitis C patients.
Acute hepatitis C virus (HCV) is typically defined as new viremia and antibody seroconversion. Rates and immunologic correlates of hepatitis C clearance have therefore been based on clearance of viremia only in individuals who initially had an antibody response. We sought to characterize the immunological correlates of clearance in patients with acute hepatitis C and their sexual contacts. We prospectively determined CD4(+) and CD8(+) cytotoxic T-lymphocyte responses in index patients with acute HCV and their sexual contacts who developed acute infection, either with or without spontaneous clearance, as well as those contacts who never developed viremia. Responses were measured using proliferation and ELISpot assays for CD4(+) and CD8(+) responses. We demonstrate in this prospective study that cellular immune responses can develop in exposed but persistently aviremic and antibody-negative individuals as well as those individuals with spontaneous clearance of acute HCV. These findings lend further credence to the importance of cellular immune responses in recovery from HCV and suggest that low exposure to HCV may lead to development of HCV-specific immune responses without ongoing HCV replication. This finding has important implications for HCV vaccine and therapeutic development.


High prevalence of an active human cytomegalovirus infection in patients with colonic diverticulitis.
Diverticulitis affects 10% of the western population and is characterized by microscopic inflammation of the colon. Increasing evidence suggests that human cytomegalovirus (HCMV) is an important pathogen in various inflammatory diseases. We hypothesized that HCMV contributes to the progression of diverticulitis, especially in immunocompromised patients in whom HCMV is a significant pathogen. To determine if HCMV is associated with diverticulitis and with an increased frequency of diverticulitis complications. We examined the prevalence of an active HCMV infection in 23 patients with diverticulitis. Serum samples were analyzed for the presence of HCMV-IgG and HCMV-IgM antibodies in 11 of these patients. Immunohistochemistry was used for detection of HCMV early antigens in intestinal paraffin tissue sections obtained from the diverticulitis patients. HCMV-early proteins could be detected in intestinal cells in 16/23 (69.6%) patients with diverticulitis. All of the 11 patients with serum samples were HCMV-IgG positive and 2 of these were also HCMV-IgM positive. Active HCMV infection is frequently associated with diverticulitis and could contribute to the inflammatory process characteristic of diverticulitis.


An overview of demographic analysis as a method for evaluating census coverage in the United States.
"Since the 1950 U.S. census, demographic methods based on the fundamental balancing equation of demography have played an important role in the evaluation of the census net undercount. Application of this set of methods, called demographic analysis, results in national estimates of the net undercount for age-race-sex groups. Although results of demographic analysis are readily available in Bureau of the Census publications, the procedures used to estimate each of the components of population change are less well-known. In this paper we review the historical foundation of demographic analysis, beginning with Coale's 1950 census evaluation project and concluding with the recent evaluation of the 1990 census. We examine each of the components of the method, how their estimation has changed over time, and how they were estimated for the 1990 census."


The effectiveness of inhaled Cannabis flower for the treatment of agitation/irritability, anxiety, and common stress.
An observational research design was used to evaluate which types of commonly labeled Cannabis flower product characteristics are associated with changes in momentary feelings of distress-related symptoms. We used data from 2306 patient-directed cannabis administration sessions among 670 people who used the real-time Cannabis effects recording software, Releaf App, between June 6, 2016, and February 23, 2019, for tracking the effects of Cannabis flower consumption. Fixed effects multivariable panel regression techniques were used to establish overall relief by symptom type and to determine which labeled product characteristics (e.g., subspecies/subtype, inhalation method, and major cannabinoid contents) showed the strongest correlation with changes in momentary feelings of agitation/irritability, anxiety, and stress, along with experienced side effects. In total, a decrease in symptom intensity levels was reported in 95.51% of Cannabis usage sessions, an increase in 2.32% of sessions, and no change in 2.16% of sessions. Fixed effects models showed, on average, respondents recorded a maximum symptom intensity reduction of 4.33 points for agitation/irritability (SE = 0.20, p < 0.01), 3.47 points for anxiety (SE = 0.13, p < 0.01), and 3.98 for stress (SE = 0.12, p < 0.01) on an 11-point visual analog scale. Fixed effects regressions showed that, controlling for time-invariant user characteristics, mid and high tetrahydrocannabinol (THC) levels were the primary independent predictor of increased symptom relief, and that when broken out by symptom type, this effect was only statistically significant for our largest sample of users, those reporting anxiety rather than agitation/irritability or stress. Cannabidiol (CBD) levels were generally not associated with changes in symptom intensity levels. In a minority of cannabis use sessions (< 13%), cannabis users reported anxiogenic-related negative side effects (e.g., feeling anxious, irritable, paranoid, rapid pulse, or restless), whereas in a majority of sessions (about 66%), users reported positive anxiolytic side effects (e.g., feeling chill, comfy, happy, optimistic, peaceful, or relaxed). The findings suggest the majority of patients in our sample experienced relief from distress-related symptoms following consumption of Cannabis flower, and that among product characteristics, higher THC levels were the strongest predictors of relief.


Unimanual SNARC Effect: Hand Matters.
A structural representation of the hand embedding information about the identity and relative position of fingers is necessary to counting routines. It may also support associations between numbers and allocentric spatial codes that predictably interact with other known numerical spatial representations, such as the mental number line (MNL). In this study, 48 Western participants whose typical counting routine proceeded from thumb-to-little on both hands performed magnitude and parity binary judgments. Response keys were pressed either with the right index and middle fingers or with the left index and middle fingers in separate blocks. 24 participants responded with either hands in prone posture (i.e., palm down) and 24 participants responded with either hands in supine (i.e., palm up) posture. When hands were in prone posture, the counting direction of the left hand conflicted with the direction of the left-right MNL, whereas the counting direction of the right hand was consistent with it. When hands were in supine posture, the opposite was true. If systematic associations existed between relative number magnitude and an allocentric spatial representation of the finger series within each hand, as predicted on the basis of counting habits, interactions would be expected between hand posture and a unimanual version of the spatial-numerical association of response codes (SNARC) effect. Data revealed that with hands in prone posture a unimanual SNARC effect was present for the right hand, and with hands in supine posture a unimanual SNARC effect was present for the left hand. We propose that a posture-invariant body structural representation of the finger series provides a relevant frame of reference, a within-hand directional vector, that is associated to simple number processing. Such frame of reference can significantly interact with stimulus-response correspondence effects, like the SNARC, that have been typically attributed to the mapping of numbers on a left-to-right mental line.


Predictive values of species' identifications from the Vitek Gram-Positive Identification Card using clinical isolates of coagulase-negative staphylococci.
The Gram-Positive Identification Card (GPI, bioMerieux Vitek) was compared to conventional tests for identification of 616 clinical isolates of coagulase-negative staphylococci. All tests were inoculated with subcultures from single isolated colonies. The predictive values of GPI species' identifications (the number of the system's correct calls divided by the total number of calls for each species) were 100% (12 of 12) for Staphylococcus capitis, 100% (79 of 79) for S saprophyticus, 98.4% (246 of 250) for S epidermidis and 96.0% (120 of 125) for S haemolyticus, but only 64.5% (69 of 107) for the other species analyzed. When an infrequently encountered Staphylococcus species is named using the GPI, the identification should be confirmed using additional tests.


The control of cell cycle in mouse primordial germ cells: old and new players.
The cell cycle of primordial germ cells (PGCs), the embryonic precursors of gametes, is characterized by a mitotic phase common to both sexes and a mitotic-meiotic switch in the female. In the present work, we will review the results obtained in the last decade by studies aimed to clarify intrinsic and extrinsic regulatory signals of such processes, with particular reference to mouse PGCs. Besides providing a better understanding of how the gamete population is established in mammals, information about the players controlling the PGC cycle will be useful to clarify other intriguing aspects of germ cell biology such as the origin of germ cell tumours and the mechanisms allowing the maintenance of totipotency in the germ line.


Implementation of flow cytometry in the diagnostic work-up of myelodysplastic syndromes in a multicenter approach: report from the Dutch Working Party on Flow Cytometry in MDS.
Flow cytometry (FC) is recognized as an important tool in the diagnosis of myelodysplastic syndromes (MDS) especially when standard criteria fail. A working group within the Dutch Society of Cytometry aimed to implement FC in the diagnostic work-up of MDS. Hereto, guidelines for data acquisition, analysis and interpretation were formulated. Based on discussions on analyses of list mode data files and fresh MDS bone marrow samples and recent literature, the guidelines were modified. Over the years (2005-2011), the concordance between the participating centers increased indicating that the proposed guidelines contributed to a more objective, standardized FC analysis, thereby ratifying the implementation of FC in MDS.


Patients' and health professionals' attitudes and perceptions towards the initiation of preventive drugs for primary prevention of cardiovascular disease: protocol for a systematic review of qualitative studies.
Lipid-lowering drugs and antihypertensive agents can be prescribed for the primary prevention of cardiovascular disease. In some cases, patients eligible for primary prevention of cardiovascular disease according to the European guidelines are not always started on preventive drugs. Existing research explores the attitudes of health professionals and patients towards cardiovascular preventive drugs but does not always differentiate between the attitudes towards drug initiation for primary or secondary prevention. We aim to systematically review qualitative studies assessing health professionals' and patients' attitudes and perceptions towards drug initiation for primary prevention of cardiovascular disease. MEDLINE, MEDLINE In Process, EMBASE, PsycINFO, CINAHL, Applied Social Sciences Index and Abstracts, Conference Proceedings Citation Index (Web of Science), Healthcare Management Information Consortium, and Open Grey will be searched without restrictions on date or language of publication. Searches will be limited to studies of qualitative design, standalone or in the context of a mixed-method design, focusing on cardiovascular drug initiation for primary prevention. The primary outcome is the attitudes of health professionals and patients towards drug initiation for primary prevention of cardiovascular disease. Two reviewers will independently carry out the study selection, data extraction and quality assessment. The Critical Appraisal Skills Programme Qualitative Research Checklist will be used to assess the quality of included studies. The findings will be analysed using Thomas and Harden's thematic synthesis approach. This systematic review does not require ethical approval as primary data will not be collected. The results of the study will be published in a peer-reviewed journal and presented at relevant conferences. CRD42018095346.


Sequential Proton-Coupled Electron Transfer Mediates Excited-State Deactivation of a Eumelanin Building Block.
Skin photoprotection is commonly believed to rely on the photochemistry of 5,6-dihydroxyindole (DHI)- and 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-based eumelanin building blocks. Attempts to elucidate the underlying excited-state relaxation mechanisms have been partly unsuccessful due to the marked instability to oxidation. We report a study of the excited-state deactivation of DHI using steady-state and time-resolved fluorescence accompanied by high-level quantum-chemistry calculations including solvent effects. Spectroscopic data show that deactivation of the lowest excited state of DHI in aqueous buffer proceeds on the 100 ps time scale and is 20 times faster than in methanol. Quantum-chemical calculations reveal that the excited-state decay mechanism is a sequential proton-coupled electron transfer, which involves the initial formation of a solvated electron from DHI, followed by the transfer of a proton to the solvent. This unexpected finding would prompt a revision of current notions about eumelanin photophysics and photobiology.


Degradation and utilization of xylans by the rumen anaerobe Prevotella bryantii (formerly P. ruminicola subsp. brevis) B(1)4.
Freshly harvested whole cells from cultures of P. bryantii B(1)4 grown with oat spelt xylan (OSX) as an energy source showed less than 25% of the enzyme activity against OSX, and less than 15% of the activity against birchwood xylan (BWX) and carboxymethylcellulose, that was detectable in sonicated cell preparations. This indicates that much of this hydrolytic activity is either periplasmic, membrane-associated or intracellular and may be concerned with the processing of transported oligosaccharides.P. bryantii B(1)4 cultures were able to utilise up to 45% and 51% of the total pentose present in OSX and BWX, respectively, after 24 h, but could utilize 84% of a water-soluble fraction of BWX. Analysis of the xylan left undegraded after incubation with P. bryantii showed that while xylose and arabinose were removed to a similar extent, uronic acids were utilized to a greater extent than xylose. Predigestion of xylans with two cloned xylanases from the cellulolytic rumen anaerobe Ruminococcus flavefaciens gave little increase in overall pentose utilization suggesting that external P. bryantii xylanases are as effective as the cloned R. flavefaciens enzymes in releasing products that can be utilised by P. bryantii cells. The xylanase system of P. bryantiiis able to efficiently utilise not only xylo-oligosaccharides but also larger water-soluble xylan fragments.


Reliability and Validity of the Greek Version of Patient Generated-Subjective Global Assessment in Cancer Patients.
The authors sought to determine the reliability and validity of psychometric properties of the Greek Patient-Generated Subjective Global Assessment (PG-SGA) in cancer patients attending a palliative care unit. The scale was translated into Greek. The study took place in an outpatient palliative care unit and 238 cancer patients completed the nutrition assessment. For treatment effect, the index was administered to 164 patients, whereas for the test of the instrument's robustness to 100 patients. Both assessments took place 15 days after the baseline assessment. Ninety-three patients were well-nourished, 104 were moderately malnourished, and 41 were severely malnourished. Reliability was assessed by the internal consistency and test-retest of the instrument. Validity was assessed with construct validity using the PG-SGA items, treatment effect, and criterion validity. Weight loss, physical examination, activities and function, and symptoms were predictors to the classification. Mean values in male patients classified as severely malnourished had the lowest values in all objective parameters except serum albumin, whereas severely malnourished female patients had the lowest values in all objective parameters except serum albumin and arm muscle circumference (AMC). Values of serum transferrin, AMC, and body mass index were significantly lower in patients classified as severely malnourished. The Greek PG-SGA is a psychometrically sound assessment in Greek cancer patients.


The Perspectives of Fieldwork Educators Regarding Level II Fieldwork Students.
ABSTRACT Ten occupational therapists employed in pediatric and adult rehabilitation settings participated in focus groups to discuss their perceptions of the benefits and drawbacks in working with occupational therapy students. Participants identified professional values, opportunities for continued professional development, recruitment of future employees, and pride in learning experiences available as incentives for working with students. Fieldwork educators who had supervised students lacking foundational communication, problem-solving, and clinical skills were cautious about accepting future Level II students. Time constraints and lack of preparation for the educator role were perceived as barriers to working with students. Fieldwork educators expected the academic institution to provide efficient support, including training for the educator role, information regarding the expectations of the academic program, and ongoing communication over the fieldwork experience. Strategies for strengthening the ties between academic programs and fieldwork sites were explored.


Association of subcortical structural shapes with fatigue in neuromyelitis optica spectrum disorder.
Although fatigue is a major symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), the underlying mechanism remains unclear. We explored the relationship between subcortical structures and fatigue severity to identify neural substrates of fatigue in NMOSD. Clinical characteristics with brain magnetic resonance imaging were evaluated in forty patients with NMOSD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) questionnaire (a higher score indicates less fatigue). We assessed the correlation between subcortical structures and fatigue severity using surface-based shape analysis. Most of the enrolled patients showed fatigue (72.5%; mean FACIT-fatigue score, 34.8 ± 10.8). The FACIT-fatigue score was negatively correlated with Expanded Disability Status Scale and Beck Depression Inventory scores (r = - 0.382, p = 0.016; r = - 0.578, p < 0.001). We observed that the right thalamus was the only extracted region for various threshold experiments. Further, patients with lower FACIT-fatigue scores (more fatigue) had decreased local shape volume in the right thalamus. Fatigue is common in patients with NMOSD, and atrophy in the right thalamus is strongly correlated with fatigue severity. The local shape volume of the right thalamus might serve as a biomarker of fatigue in NMOSD.


Somatostatin-immunoreactive neurons in the adult rabbit retina.
Somatostatin (SRIF) is a neuroactive peptide that is distributed throughout the nervous system, including the retina. This peptide has been localized to populations of amacrine cells in a variety of vertebrate species. In the rabbit retina, SRIF immunoreactivity is present in a sparse population of medium to large neurons (13.72 microns in diameter, or 147.84 mu 2) in the ganglion cell layer and in a small number of neurons in the inner nuclear layer. These cells display a preferential distribution to the inferior retina, with the highest density near the ventral and ventrolateral retinal margins (11.33 cells/mm2). SRIF-immunoreactive cells have two to five primary processes that arborize in the proximal inner plexiform layer (IPL). These give rise to a plexus of finer processes in the distal IPL. Occasional immunoreactive processes are also present in the outer plexiform layer. In the IPL, these laminar networks are present in all retinal regions. In addition, SRIF-immunoreactive cells often have a fine-caliber axonlike process that eminates from the soma or perisomal region. These processes travel for great distances across the retina in either the nerve fiber layer or in the distal IPL but are never seen to enter the optic nerve head. In addition, the number of SRIF-immunoreactive somata remains unchanged following transection of the optic nerve. Taken together, these data indicate that SRIF-immunoreactive neurons of the rabbit retina are displaced amacrine cells. Furthermore, the sparse distribution of SRIF-immunoreactive somata, the wide-ranging, asymmetric arborization of their cellular processes, and previous pharmacological studies suggest that these neurons mediate a broad modulatory role in retinal function.


Efficient neutralization of foot-and-mouth disease virus by monovalent antibody binding.
Neutralization of an aphthovirus by monovalent binding of an antibody is reported. Foot-and-mouth disease virus (FMDV) clone C-S8c1 was neutralized by monoclonal antibody (MAb) SD6, which was directed to a continuous epitope within a major antigenic site of the G-H loop of capsid protein VP1. On a molar basis, the Fab fragment was at most fivefold less active in neutralization than the intact antibody, and both blocked virus attachment to cells. Neither the antibody nor the Fab fragment caused aggregation of virions, as evidenced by sucrose gradient sedimentation studies of the antibody-virus complex formed at antibody to virion ratios of 1:50 to 1:10,000. The results of neutralization of infectivity and of ultracentrifugation are fully consistent with structural data based on X-ray crystallographic and cryoelectron microscopy studies, which showed monovalent interaction of the antibody with a critical receptor binding motif Arg-Gly-Asp. The conclusions of these neutralization studies are that (i) bivalent binding of antibody is not a requisite for strong neutralization of aphthoviruses and (ii) aggregation of viral particles, which has been proposed to be the dominant neutralization mechanism of antibodies that bind monovalently to virions, is not necessary for the neutralization of FMDV C-S8c1 by MAb SD6.


The cell adhesion molecule M-cadherin is not essential for muscle development and regeneration.
M-cadherin is a classical calcium-dependent cell adhesion molecule that is highly expressed in developing skeletal muscle, satellite cells, and cerebellum. Based on its expression pattern and observations in cell culture, it has been postulated that M-cadherin may be important for the fusion of myoblasts to form myotubes, the correct localization and function of satellite cells during muscle regeneration, and the specialized architecture of adhering junctions in granule cells of cerebellar glomeruli. In order to investigate the potential roles of M-cadherin in vivo, we generated a null mutation in mice. Mutant mice were viable and fertile and showed no gross developmental defects. In particular, the skeletal musculature appeared essentially normal. Moreover, muscle lesions induced by necrosis were efficiently repaired in mutant mice, suggesting that satellite cells are present, can be activated, and are able to form new myofibers. This was also confirmed by normal growth and fusion potential of mutant satellite cells cultured in vitro. In the cerebellum of M-cadherin-lacking mutants, typical contactus adherens junctions were present and similar in size and numbers to the equivalent junctions in wild-type animals. However, the adhesion plaques in the cerebellum of these mutants appeared to contain elevated levels of N-cadherin compared to wild-type animals. Taken together, these observations suggest that M-cadherin in the mouse serves no absolutely required function during muscle development and regeneration and is not essential for the formation of specialized cell contacts in the cerebellum. It seems that N-cadherin or other cadherins can largely compensate for the lack of M-cadherin.


Mortality of population in China and Japan: a comparative analysis.
The author compares mortality in China and Japan from 1950 to 1985 and analyzes the differences between the two countries. Consideration is given to sex differences, regional differences, and trends in the major causes of death. The analysis shows "the gap between China and Japan in the health standards of the population [and also suggests] a course for [reducing] mortality of the Chinese population.... There is great potential...of reducing infant mortality, especially for female infants....Moreover, the further control of infectious diseases can still play a major role in raising the average life expectancy of the Chinese population in the years ahead."


Antigenic and genetic variation in human respiratory syncytial virus.
Human respiratory syncytial virus (HRSV) is a leading cause of serious pediatric respiratory disease worldwide. Natural infection provides only partial protection as repeat infections occur throughout life. A brief review of the extent of antigenic and genetic variation observed in HRSV clinical isolates is presented. Recent experimental research is reviewed, describing key factors that may explain the ability of HRSV to cause multiple infections in the same individual even in the presence of an existing immune response. It is well-appreciated that variability of the G protein, both between and within antigenic subgroups A and B, is partially responsible for repeat HRSV infections. A high level of nucleotide change resulting in amino acid change provides strong evidence for selective pressure for change in G sequences, thus new HRSV variants. Although little variation in gene-coding sequences is observed in the F protein (the second major protective antigen), new evidence of genetic variation has identified alteration of gene expression levels by selection of changes in the gene end termination signal that precedes the gene encoding the F protein. Due to obligatory sequential transcription, these changes affect downstream gene expression levels. These data suggest that modulation of F protein levels may provide a selective advantage in the presence of a preexisting immune response. Experimental data in HRSV demonstrate that variation exists not only in gene-coding sequences but also in the signals that control gene expression. Thus alteration in the expression of key proteins provides a second type of antigenic "variation." A better understanding of these differences is critical to the development of an effective vaccine.


Efficacy of whole body vibration exercise in older people: a systematic review.
The aim of this study was to perform a systematic review of the literature on whole body vibration programs in older population and a meta-analysis of randomized controlled clinical trials. A search was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL and PsychINFO databases. We included randomized controlled trials evaluating the efficacy and safety of whole body vibration training in older populations compared to conventional exercise or control groups that assessed balance, muscle strength, falls, bone mineral density and adverse events. Sixteen trials met the inclusion criteria. Comparing the vibration and the control group, we found that vibration significantly improved knee muscle isometric strength (18.30 Nm, 95% CI 7.95-28.65), muscle power (10.44 W, 95% CI 2.85-18.03) and balance control (Tinetti test: 4.5 points, 95% CI 0.95-8.11). Comparison with a conventional exercise showed that the only significant difference was bone mineral density in the femoral neck (0.04 g/cm(-2), 95% CI 0.02-0.07). There were no serious complications in most of studies. Whole body vibration training may improve strength, power and balance in comparison with a control group, although these effects are not apparent when compared with a group that does conventional exercise.


Idiosyncratic drug hepatotoxicity revisited: new insights from mechanistic toxicology.
Drug-induced hepatotoxicity is a serious problem and has repeatedly led to the withdrawal of a drug after successful launching. Although reactive metabolites (which are predictable) are often involved, genetic or acquired host factors (which are unpredictable) can increase the penetrance and expressivity of the potential hepatotoxicity in a small subset of patients. The molecular mechanisms underlying liver injury are largely unknown. Evidence suggests, however, that there are four major modes of action: covalent modification of target proteins and oxidoreductive stress; immune-mediated reactions; interference with hepatobiliary export; and mitochondrial injury. A better prediction will include new animal models, new biomarkers, and genomics/transcriptomics analysis.


The reliability and validity of willingness to pay surveys for reproductive health pricing decisions in developing countries.
This paper examines the reliability, theoretical and predictive validity of willingness to pay (WTP) surveys for setting prices for reproductive health services in developing countries. Four country applications were conducted; the surveys used similar elicitation methods (a series of three closed-ended questions to cover the range of target prices, followed by a single open ended question to elicit maximum WTP) and samples of current or potential users of family planning, gynecology, and prenatal care services. In all four applications, respondents were able to understand WTP questions and responded with high levels of internal consistency. Evidence supporting theoretical validity was also found in all surveys. Higher income and more highly motivated users had higher WTP than lower income and less motivated users. Predictive validity was assessed in one study. Services utilization predicted by a WTP survey was compared with actual post-price increase utilization. Adding WTP to information already possessed by program managers resulted in a threefold increase in ability to predict utilization change as a result of a price increase, and in nearly half of cases predicted percent change in utilization was within 10% of observed change. WTP surveys when used for reproductive services price setting appear reliable and valid, and improve a program manager's ability to predict client responses to price changes.


High telomerase activity in granulocytes from clonal polycythemia vera and essential thrombocythemia.
Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic myeloproliferative disorders that share the involvement of a multipotent progenitor cell and dominance of the transformed clone over normal hematopoiesis. On the other hand, the heterogeneity of these diseases with respect to clonal development from a common progenitor has been well established. To identify useful prognostic indicators, we analyzed telomerase activity (TA), a known marker of neoplastic proliferation, in granulocytes (PMNs) and mononuclear cells (MNCs) from 22 female patients with ET and PV. Clonality status was determined by investigation of X chromosome inactivation patterns (XCIPs). We found a statistically significant positive correlation between high TA and monoclonal pattern of XCIP. Therefore, our data suggest that the use of multiple tumor markers may contribute to a better understanding of the deregulated physiology of these disorders and provide useful prognostic factors.


Selenium radiography versus storage phosphor and conventional radiography in the detection of simulated chest lesions.
To compare selenium detectors with three conventional and digital detector systems for the detection of simulated pulmonary lesions. Templates containing nodules, linear structures, and micronodular opacities were superimposed over an anthropomorphic chest phantom. The authors compared lesion detection with use of storage phosphor radiography (250 speed), selenium radiography (250 speed) with an antiscatter grid, selenium radiography (450 speed) without an antiscatter grid, an asymmetric screen-film system (400 speed), and a conventional screen-film system (250 speed). Detection performance of 10 radiologists was compared by using a multireader-multicase receiver operating characteristic analysis of variance. For the detection of nodules, no statistically significant differences between imaging modes were seen. For the detection of micronodules and linear lesions, both selenium techniques were superior to all other modes (P < .05). In addition, the asymmetric screen-film radiographs were inferior (P < .05) to the conventional screen-film radiographs and to storage phosphor radiographs for the detection of micronodules. The selenium detector improves detection of simulated fine linear and low-contrast micronodular details and appears to be superior to other detector systems for chest radiography.


A X-linked nonsense APOO/MIC26 variant causes a lethal mitochondrial disease with progeria-like phenotypes.
APOO/MIC26 is a subunit of the MICOS complex required for mitochondrial cristae morphology and function. Here, we report a novel variant of the APOO/MIC26 gene that causes a severe mitochondrial disease with overall progeria-like phenotypes in two patients. Both patients developed partial agenesis of the corpus callosum, bilateral congenital cataract, hypothyroidism, and severe immune deficiencies. The patients died at an early age of 12 or 18 months. Exome sequencing revealed a mutation (NM_024122.5): c.532G>T (p.E178*) in the APOO/MIC26 gene that causes a nonsense mutation leading to the loss of 20 C-terminal amino acids. This mutation resulted in a highly unstable and degradation prone MIC26 protein, yet the remaining minute amounts of mutant MIC26 correctly localized to mitochondria and interacted physically with other MICOS subunits. MIC26 KO cells expressing MIC26 harboring the respective APOO/MIC26 mutation showed mitochondria with perturbed cristae architecture and fragmented morphology resembling MIC26 KO cells. We conclude that the novel mutation found in the APOO/MIC26 gene is a loss-of-function mutation impairing mitochondrial morphology and cristae morphogenesis.


Lateral release associated with MPFL reconstruction in patients with acute patellar dislocation.
Medial patellofemoral ligament (MPFL) injury occurs in the majority of the cases of acute patellar dislocation. The role of concomitant lateral retinaculum release with MPFL reconstruction is not clearly understood. Even though the lateral retinaculum plays a role in both medial and lateral patellofemoral joint stability in MPFL intact knees, studies have shown mixed clinical outcomes following its release during MPFL reconstruction surgery. Better understanding of the biomechanical effects of the release of the lateral retinaculum during MPFL reconstruction is warranted. We hypothesize that performing a lateral release concurrent with MPFL reconstruction will disrupt the patellofemoral joint biomechanics and result in lateral patellar instability. A previously developed and validated finite element (FE) model of the patellofemoral joint was used to understand the effect of lateral retinaculum release following MPFL reconstruction. Contact pressure (CP), contact area (CA) and lateral patellar displacement were recorded. abstract. FE modeling and analysis demonstrated that lateral retinacular release following MPFL reconstruction with tibial tuberosity-tibial groove distance (TT-TG) of 12 mm resulted in a 39% decrease in CP, 44% decrease in CA and a 20% increase in lateral patellar displacement when compared to a knee with an intact MPFL. In addition, there was a 45% decrease in CP, 44% decrease in CA and a 21% increase in lateral displacement when compared to a knee that only had an MPFL reconstruction. This FE-based analysis exhibits that concomitant lateral retinaculum release with MPFL reconstruction results in decreased PF CA, CP and increased lateral patellar displacement with increased knee flexion, which may increase the risk of patellar instability.


Nefazodone and venlafaxine: two new agents for the treatment of depression.
Nefazodone and venlafaxine are two new antidepressants with pharmacologic actions and side-effect profiles that differ from those of the selective serotonin reuptake inhibitors (SSRIs). In addition to inhibition of serotonin reuptake, nefazodone exhibits 5-HT2 antagonism. Venlafaxine inhibits the reuptake of both norepinephrine and serotonin. Both appear to be effective and well tolerated in the treatment of major depressive disorder. Nefazodone differs from the SSRIs in that it does not cause sexual dysfunction or sleep impairment. Venlafaxine differs from the SSRIs because of its effects augmenting norepinephrine, as well as its demonstrated efficacy in the treatment of severely depressed, melancholic patients. Both drugs appear to hold significant promise as effective and well-tolerated medications for the treatment of major depression in the primary care setting.


Biosynthesis and metabolism of 2-iodohexadecanal in cultured dog thyroid cells.
2-Iodohexadecanal (2-IHDA) is a major thyroid iodolipid. It mimics the main regulatory effects of iodide on thyroid metabolism: inhibition of H2O2 production and of adenylyl cyclase. The biosynthesis of 2-IHDA and its metabolism have been investigated in cultured dog thyroid cells maintained in a differentiated state by forskolin. Incubation of these cells with [9,10-3H]hexadecan-1-ol or [9,10-3H]palmitic acid labeled several phospholipids, but [9, 10-3H]hexadecan-1-ol was selectively incorporated into plasmenylethanolamine. In the presence of an exogenous H2O2 generating system (glucose oxidase), iodide induced the production of [9,10-3H]2-IHDA from [9,10-3H]hexadecan-1-ol-labeled cells but not from [9,10-3H]palmitic acid-labeled cells. 2-IHDA was also generated during the lactoperoxidase-catalyzed iodination of brain and heart plasmalogens, and of ethyl hexadec-1-enyl ether, a synthetic vinyl ether-containing compound. Taken together, these results show that thyroid 2-IHDA is derived from plasmenylethanolamine via an attack of reactive iodine on the vinyl ether group. 2-Iodohexadecan-1-ol (2-IHDO) was also detected in these studies; it was formed later than 2-IHDA, and thyroid cells converted exogenous 2-IHDA into 2-IHDO in a time-dependent way. The ratio of 2-IHDO/2-IHDA increased with H2O2 production and decreased as a function of iodide concentration. An aldehyde-reducing activity was detected in subcellular fractions of the horse thyroid. No formation of 2-iodohexadecanoic acid could be detected. Reduction into the biologically inactive 2-IHDO is thus a major metabolic pathway of 2-IHDA in dog thyrocytes.


Signalling pathways in the brain: cellular transduction of mood stabilisation in the treatment of manic-depressive illness.
The long-term treatment of manic-depressive illness (MDI) likely involves the strategic regulation of signalling pathways and gene expression in critical neuronal circuits. Accumulated evidence has identified signalling pathways, in particular the family of protein kinase C (PKC) isozymes, as targets for the long-term action of lithium. Chronic lithium administration produces a reduction in the expression of PKC alpha and epsilon, as well as a major PKC substrate, MARCKS, which has been implicated in long-term neuroplastic events in the developing and adult brain. More recently, studies have demonstrated robust effects of lithium on another kinase system, GSK-3beta, and on neuroprotective/neurotrophic proteins in the brain. Given the key roles of these signalling cascades in the amplification and integration of signals in the central nervous system, these findings have clear implications not only for research into the neurobiology of MDI, but also for the future development of novel and innovative treatment strategies.


Randomised comparison of JUDkins vs. tiGEr catheter in coronary angiography via the right radial artery: the JUDGE study.
The aim of this study was to compare the performance of the Tiger-II with Judkins 3.5L/4R catheters in coronary angiography (CAG) via the transradial approach (TRA). Consecutive patients undergoing non-urgent CAG via the right TRA were randomised to either the Tiger-II (Terumo) or Judkins (3.5L/4R; Medtronic) 5 Fr catheters; 320 patients in each group were randomised. Catheter or access site change was required in 57 (17.8%) vs. 68 (21.3%) patients allocated to the Tiger-II and Judkins group, respectively (p=0.3). The study's primary endpoint of contrast volume (ml) used until completion of CAG was lower for Tiger-II vs. Judkins group: 66.8 (54.0-82.0) vs. 73.4 (60.0-94.1), p<0.001. Angiography, fluoroscopy time (min) and severe spasm rate were also significantly lower for Tiger-II vs. Judkins group: 5.52 (4.17-7.32) vs. 6.85 (5.15-9.63), p<0.00, 2.01 (1.32-3.13) vs. 2.24 (1.50-3.50), p=0.01 and 6 (2.8%) vs. 39 (12.2%), p<0.001, respectively. The Tiger-II catheter obtained better opacification grade for the right coronary artery (RCA): 4.0 (4.0-4.0) vs. 4.0 (3.0-4.0), p=0.02, but slightly compromised opacification of the left anterior descending (LAD) and left circumflex (LCX) arteries compared with the Judkins group: 3.75 (3.0-4.0) vs. 4.0 (3.5-4.0), p<0.001, and 3.78 (3.6-4.0) vs. 4.0 (3.6-4.0), p<0.001, respectively. The Tiger-II was found superior to the Judkins 3.5L/4R regarding contrast volume use, procedural and fluoroscopy time, spasm rate and RCA imaging, and inferior regarding LAD and LCX imaging.


[Tuberculous peritonitis in peritoneal dialysis].
We report a patient in Automatic Peritoneal Dialysis (APD) with tuberculous peritonitis by possible peritoneal infection due to the proximity between fallopian tube and the left ovary, a peritoneal liquid culture was constantly negative. The patient presented a bad clinic evolution. Her only medical history was hypercalcemia six months before developing a peritonitis and occasionally nausea and vomits To confirm the diagnosis it was needed a peritoneal biopsy by means of a laparoscopy with a removal of the peritoneal catheter and left anexectomy. Now, the patient is asintomatic in daily home hemodialysis.


Alpha-smooth muscle actin expression in tumor and stromal cells of benign and malignant human pigment cell tumors.
We examined the altered expression of alpha-smooth muscle actin (alpha-Sm) in human benign, pre-malignant, and malignant pigment cell tumors by immunohistochemical as well as biochemical (Western blot) analysis using anti-alpha-Sm monoclonal antibody (anti-alpha-Sm MoAb). The expression of alpha-Sm has been revealed immunohistochemically to be associated with mesodermal cells rather than with pigment cells. Western blot analysis using anti-alpha-Sm MoAb detected alpha-Sm expression as a 43-kD band in the extracts from normal papillary dermis, nevus cell nevus, and metastatic melanoma with stromal tissues, but not from primary melanoma with stromal tissues examined. The above findings of alpha-Sm expression by Western blot analysis were further characterized immunohistochemically in terms of the localization at the cellular level as follows. 1) In normal papillary dermis, pericytes encircling capillary vessels showed only positive staining with anti-alpha-Sm MoAb. 2) In nevus tissues, nevus cells were not shown to be positively stained, despite similar positivity of pericytes in normal papillary dermis. 3) In melanoma tissues, alpha-Sm expression of metastatic melanoma detected by Western blot analysis was found to be derived from fibroblasts with smooth-muscle differentiation (myofibroblasts), but not from melanoma cells. Such myofibroblastic stromal changes could not be found on primary melanoma tissue sections, which showed no reactivity in Western blot analysis. We conclude that the major sources of alpha-Sm in benign and pre-malignant pigment cell tumors are capillary pericytes, whereas alpha-Sm found in malignant melanoma tissue is primarily from melanoma-surrounding stromal fibroblasts that were changed to myofibroblasts by some cytokine factor(s), presumably secreted from melanoma cells.


Rate of progression and prognostic factors in Alzheimer's disease: a prospective study.
To study rate of progression and correlates of cognitive and functional/behavioral deterioration in Alzheimer patients. A 1-year multicenter prospective study. Outpatients and inpatients at geriatric institutions. Fifty-six patients with a clinical diagnosis of Alzheimer's disease according to DSM-III criteria of Primary Degenerative Dementia. Blessed Dementia Scale (BDS) and Blessed Information-Memory-Concentration test (BIMC) measured at baseline, third, sixth, and twelfth month. The mean annual (+/- SD) rate of progression of our sample was 3.5 (+/- 3.7) points on the BDS and 2.6 (+/- 4.9) on the BIMC, with a wide range of variability. The level of cognitive impairment (BIMC score) at baseline predicted functional and behavioral deterioration: the better the initial BIMC score, the less the rate of negative change of BDS (r = 0.37, P = 0.006). Furthermore, the younger the patients at the disease onset, the faster the progression of cognitive impairment (r = 0.48, P = 0.0003), with men having a slower rate of progression (P = 0.004) than women. The present study confirms previous findings showing a wide individual variability in rate of progression of cognitive and functional/behavioral impairment as assessed by BIMC and BDS. The cognitive profile may predict the clinical evolution better than the functional and behavioral status, with patients with an earlier onset and women having a faster deterioration.


Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3.
The febrile response is a complex physiological reaction to disease, including a cytokine-mediated increase in body temperature and the activation of inflammatory systems. Fever has beneficial roles in terms of disease prognosis, partly by suppressing the expression of inflammatory cytokines. However, the molecular mechanisms underlining the fever-mediated suppression of inflammatory gene expression have not been clarified. In this study, we showed that heat shock suppresses LPS-induced expression of IL-6, a major pyrogenic cytokine, in mouse embryonic fibroblasts and macrophages. Heat shock transcription factor 1 (HSF1) activated by heat shock induced the expression of activating transcription factor (ATF) 3, a negative regulator of IL-6, and ATF3 was necessary for heat-mediated suppression of IL-6, indicating a fever-mediated feedback loop consisting of HSF1 and ATF3. A comprehensive analysis of inflammatory gene expression revealed that heat pretreatment suppresses LPS-induced expression of most genes (86%), in part (67%) via ATF3. When HSF1-null and ATF3-null mice were injected with LPS, they expressed much higher levels of IL-6 than wild-type mice, resulting in an exaggerated febrile response. These results demonstrate a novel inhibitory pathway for inflammatory cytokines.


High-Performance PEDOT:PSS/Hexamethylene Diisocyanate-Functionalized Graphene Oxide Nanocomposites: Preparation and Properties.
Graphene oxide (GO) has emerged as an ideal filler to reinforce polymeric matrices owing to its large specific surface area, transparency, flexibility, and very high mechanical strength. Nonetheless, functionalization is required to improve its solubility in common solvents and expand its practical uses. In this work, hexamethylene diisocyanate (HDI)-functionalized GO (HDI-GO) has been used as filler of a conductive polymer matrix, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The nanocomposites have been prepared via a simple solution casting method, and have been characterized by scanning electron microscopy (SEM), UV⁻Vis and Raman spectroscopies, X-ray diffraction (XRD), thermogravimetric analysis (TGA), tensile tests, and four-point probe measurements to get information about how the HDI-GO functionalization degree (FD) and the HDI-GO concentration in the nanocomposite influence the final properties. SEM analysis showed a very homogenous dispersion of the HDI-GO nanosheets with the highest FD within the matrix, and the Raman spectra revealed the existence of very strong HDI-GO-PEDOT:PSS interactions. A gradual improvement in thermal stability was found with increasing HDI-GO concentration, with only a small loss in transparency. A reduction in the sheet resistance of PEDOT:PSS was found at low HDI-GO contents, whilst increasing moderately at the highest loading tested. The nanocomposites showed a good combination of stiffness, strength, ductility, and toughness. The optimum balance of properties was attained for samples incorporating 2 and 5 wt % HDI-GO with the highest FD. These solution-processed nanocomposites show considerably improved performance compared to conventional PEDOT:PSS nanocomposites filled with raw GO, and are highly suitable for applications in various fields, including flexible electronics, thermoelectric devices, and solar energy applications.