[Immunotropic properties of exoglycan obtained from the marine micro-organism Vibrio alginolyticus].
Immune system modulating activity of exoglycane isolated from culture media of Vibrio alginolyticus (strain 945-80) was investigated. The substance demonstrated stimulating activity on the humoral and cell immune system, potentiated phagocyte activity of macrophage and neutrophils, increased survival index of the animals infected by Gram-positive and Gram-negative bacteria.


Detection of bone erosions in early rheumatoid arthritis: 3D ultrasonography versus computed tomography.
Three-dimensional (3D) volumetric ultrasonography (US) is an interesting tool that could improve the traditional approach to musculoskeletal US in rheumatology, due to its virtual operator independence and reduced examination time. The aim of this study was to investigate the performance of 3DUS in the detection of bone erosions in hand and wrist joints of early rheumatoid arthritis (ERA) patients, with computed tomography (CT) as the reference method. Twenty ERA patients without erosions on standard radiography of hands and wrists underwent 3DUS and CT evaluation of eleven joints: radiocarpal, intercarpal, ulnocarpal, second to fifth metacarpo-phalangeal (MCP), and second to fifth proximal interphalangeal (PIP) joints of dominant hand. Eleven (55.0%) patients were erosive with CT and ten of them were erosive also at 3DUS evaluation. In five patients, 3DUS identified cortical breaks that were not erosions at CT evaluation. Considering CT as the gold standard to identify erosive patients, the 3DUS sensitivity, specificity, PPV, and NPV were 0.9, 0.55, 0.71, and 0.83, respectively. A total of 32 erosions were detected with CT, 15 of them were also observed at the same sites with 3DUS, whereas 17 were not seen on 3DUS evaluation. The majority of these 3DUS false-negative erosions were in the wrist joints. Furthermore, 18 erosions recorded by 3DUS were false positive. The majority of these 3DUS false-positive erosions were located at PIP joints. This study underlines the limits of 3DUS in detecting individual bone erosion, mostly at the wrist, despite the good sensitivity in identifying erosive patients.


Heart Failure and Midrange Ejection Fraction: Implications of Recovered Ejection Fraction for Exercise Tolerance and Outcomes.
Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF<40%; n=620); HF with midrange ejection fraction and no recovered ejection fraction (LVEF was consistent between 40% and 55%; n=107); HF with recovered midrange ejection fraction (LVEF, 40%-55% but previous LVEF<40%; n=170); and HF with preserved LVEF (HFpEF; LVEF>55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.


Antibiotic in myrrh from Commiphora molmol preferentially kills nongrowing bacteria.
To demonstrate that myrrh oil preferentially kills nongrowing bacteria and causes no resistance development. Growth inhibition was determined on regular plates or plates without nutrients, which were later overlaid with soft agar containing nutrients to continue growth. Killing experiments were done in broth and in buffer without nutrients. Bacterial cells were inhibited preferentially in the absence of nutrients or when growth was halted by a bacteriostatic antibiotic. After five passages in myrrh oil, surviving colonies showed no resistance to the antibiotic. Myrrh oil has the potential to be a commercially viable antibiotic that kills persister cells and causes no resistance development. This is a rare example of an antibiotic that can preferentially kill nongrowing bacteria.


A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction.
A homeobox sequence has been used to isolate a new Xenopus cDNA, named XIHbox6. A short probe from this gene serves as an early marker of posterior neural differentiation in the Xenopus nervous system. The gene recognized by this cDNA sequence is first transcribed at the late gastrula stage and solely in the posterior neural cells. The gene is expressed when ectodermal and mesodermal tissues of an early gastrula are placed in contact, but not by either tissue cultured on its own. However, gene expression is most easily inducible in ectoderm from the dorsal region, i.e., in ectoderm normally destined to form neural structures. This establishes the principle, in contrast to previous belief, that the induction of the embryonic nervous system involves a predisposition of the ectoderm and does not depend entirely on an interaction with inducing mesoderm.


The immunoglobulin heavy chain switch: structural features of gamma 1 recombinant switch regions.
The immunoglobulin heavy chain isotype switch is mediated by a DNA rearrangement involving specific genomic segments referred to as switch regions. Switch regions are composed of tandemly repeated simple sequences. The role of the tandemly repeated structure of switch regions in the switch recombination process is not understood. We mapped eight recombination sites--six in the gamma 1 and two in the gamma 3 tandem arrays. In addition, we obtained molecular clones representing three of the six gamma 1 rearrangements, and determined the nucleotide sequences of the recombination sites in each. In general, the rearrangements are confined to the tandem repeat units, and are not clustered in a particular portion of either the gamma 3 or gamma 1 switch region. Nucleotide sequence analysis of one of the recombinant clones, gamma M35, reveals evidence for a successive switch event wherein a recombination between S mu and S gamma 3 was followed by recombination 57 bp downstream with S gamma 1. gamma 1 sequence data from the molecular clones we obtained, together with similar data from other investigators regarding the gamma 1, gamma 2b, and gamma 2a switch regions, reveals that recombinations tend to occur at homologous positions of the respective gamma-unit repeats, adjacent to the elements AGCT and GGGG found in each. This finding suggests that the cutting and religation step of the recombination process is mediated by a recombinase common to the four gamma-isotypes.


Laparoscopic Habib 4X: a bipolar radiofrequency device for bloodless laparoscopic liver resection.
In recent years the progress of laparoscopic procedures and the development of new and dedicated technologies have made laparoscopic hepatic surgery feasible and safe. In spite of this laparoscopic liver resection remains a surgical procedure of great challenge because of the risk of massive bleeding during liver transection and the complicated biliary and vascular anatomy in the liver. A new laparoscopic device is reported here to assist liver resection laparoscopically. The laparoscopic Habib 4X is a bipolar radiofrequency device consisting of a 2 x 2 array of needles arranged in a rectangle. It is introduced perpendicularly into the liver, along the intended transection line. It produces coagulative necrosis of the liver parenchyma sealing biliary radicals and blood vessels and enables bloodless transection of the liver parenchyma. Twenty-four Laparoscopic liver resections were performed with LH4X out of a total of 28 attempted resections over 12 months. Pringle manoeuvre was not used in any of the patients. None of the patients required intraoperative transfusion of red cells or blood products. Laparoscopic liver resection can be safely performed with laparoscopic Habib 4X with a significantly low risk of intraoperative bleeding or postoperative complications.


Therapeutic approaches to the modulation of apoptosis.
The appreciation of the role of apoptosis in the vast majority of diseases affecting humans has revolutionized the discovery and development of drugs targeting inflammation and oncology. Novel therapeutic approaches to modulate disease by regulating apoptosis are currently being tested in preclinical and clinical settings. Enthusiasm for some of these therapies is reflected in the fact that they have received U.S. Food and Drug Administration approval in record time. Approaches include the traditional use of small molecules to target specific players in the apoptosis cascade. They also include radical new approaches such as using antisense molecules to inhibit production of the Bcl-2 protein or antibodies that ligate either death receptors, such as TRAIL (tumour necrosis factor-related apoptosis-inducing ligand), or the MHC (HLA-DR), resulting in the initiation of apoptosis of target cells. Antibodies targeting cell-specific antigens are being used in conjunction with radioactive isotopes to deliver a more specific chemotherapy, particularly in the case of B-cell lymphomas. Other therapies target mitochondria, a key organelle in the apoptosis cascade. This diverse range of therapies includes photodynamic therapy, retinoic acid and arsenic trioxide, all of which induce apoptosis by generating reactive oxygen species. As our understanding of apoptosis increases, further opportunities will arise for tailor-made therapies that will result in improved clinical outcome without the devastating side effects of current interventions.


Virus-like particle vaccine conferred complete protection against a lethal influenza virus challenge.
We have previously demonstrated the formation and release of influenza virus-like particles (VLPs) from the surface of Sf9 cells infected with either a quadruple baculovirus recombinant that simultaneously expresses the influenza structural proteins hemagglutinin (HA), neuraminidase (NA), matrix 1 (M1), and matrix 2 (M2), or a combination of single recombinants that include the M1 protein. In this work, we present data on the immunogenicity and protective efficacy afforded by VLPs (formed by M1 and HA) after immunization of mice. VLP vaccine ( approximately 1 microg HA) were formulated with or without IL-12 as adjuvant and administered twice, at 2-week intervals, by either intranasal instillation or intramuscular injection. All VLP-vaccinated and influenza-immunized control mice demonstrated high antibody titers to the HA protein; however, intranasal instillation of VLPs elicited antibody titers that were higher than those induced by either intramuscular inoculation of VLPs or intranasal inoculation with two sub-lethal doses of the challenge influenza virus (control group). Antibody responses were enhanced when VLP vaccine was formulated with IL12 as adjuvant. All mice were challenged with 5 LD50 of a mouse-adapted influenza A/Hong Kong/68 (H3N2) virus. Intramuscular administration of VLP vaccine formulated with or without IL-12 afforded 100% protection against a lethal influenza virus challenge. Similarly, intranasal instillation of VLP vaccine alone protected 100% of the mice, whereas VLP formulated with IL-12 protected 90% of the vaccinated mice. Not only do these results suggest a novel approach to the development of VLP vaccines for diverse influenza virus strains, but also the creation of multivalent vaccines by decoration of the surface of the VLPs with antigens from other pathogens.


Human exposure from pulsed magnetic field therapy mats: a numerical case study with three commercial products.
A previous study found that incident magnetic field exposure from pulsed magnetic field therapy (PMFT) mats can exceed ICNIRP 1998 reference levels. Due to the popularity of PMFT mats for private therapeutic use, regulators need to know if the products are compliant with the basic restrictions and how overexposure can be determined. This case study's objective was to test if such products are intrinsically compliant with ICNIRP 1998 and ICNIRP 2010 basic restrictions by evaluating three different commercially-available PMFT products. In the first step, experimentally validated numerical models of these mats were developed. As a second step, the induced fields were evaluated in high-resolution anatomical models of the IT'IS Virtual Population for various lying positions and compared to the safety guidelines. As expected, a strong influence of exposure on the PMFT design, anatomy, lying position and body orientation was found. The maximum exposure of one PMFT exceeds 3.1 times the basic restrictions of ICNIRP 1998 for the central nervous system tissues and 1.36 times the limit of ICNIRP 2010 for the peripheral tissues. Body loops can significantly increase the electric fields close to the skin, e.g., when the hand and thigh are in contact during mat use. In conclusion, PMFT products are not intrinsically compliant with ICNIRP 1998 and ICNIRP 2010 basic restrictions and therefore require special considerations.


Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics.
Information theoretic approaches can be used to quantify information transfer via cell signaling networks. In this study, we do so for gonadotropin-releasing hormone (GnRH) activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells (NFAT) in large numbers of individual fixed LβT2 and HeLa cells. Information transfer, measured by mutual information between GnRH and ERK or NFAT, was <1 bit (despite 3-bit system inputs). It was increased by sensing both ERK and NFAT, but the increase was <50%. In live cells, information transfer via GnRH receptors to NFAT was also <1 bit and was increased by consideration of response trajectory, but the increase was <10%. GnRH secretion is pulsatile, so we explored information gained by sensing a second pulse, developing a model of GnRH signaling to NFAT with variability introduced by allowing effectors to fluctuate. Simulations revealed that when cell-cell variability reflects rapidly fluctuating effector levels, additional information is gained by sensing two GnRH pulses, but where it is due to slowly fluctuating effectors, responses in one pulse are predictive of those in another, so little information is gained from sensing both. Wet laboratory experiments revealed that the latter scenario holds true for GnRH signaling; within the timescale of our experiments (1 to 2 hours), cell-cell variability in the NFAT pathway remains relatively constant, so trajectories are reproducible from pulse to pulse. Accordingly, joint sensing, sensing of response trajectories, and sensing of repeated pulses can all increase information transfer via GnRH receptors, but in each case the increase is small.


SOX4 cooperates with neurogenin 3 to regulate endocrine pancreas formation in mouse models.
The sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) family of transcription factors is essential for normal organismal development. Despite the longstanding knowledge that many SOX family members are expressed during pancreas development, a role for many of these factors in the establishment of insulin-producing beta cell fate remains to be determined. The aim of this study is to elucidate the role of SOX4 during beta cell development. We used pancreas and endocrine progenitor mouse knockouts of Sox4 to uncover the roles of SOX4 during pancreas development. Lineage tracing and in vitro models were used to determine how SOX4 regulates beta cell formation and understand the fate of Sox4-null endocrine lineage cells. This study demonstrates a progenitor cell-autonomous role for SOX4 in regulating the genesis of beta cells and shows that it is required at multiple stages of the process. SOX4 deletion in the multipotent pancreatic progenitors resulted in impaired endocrine progenitor cell differentiation. Deletion of SOX4 later in the Neurog3-expressing cells also caused reductions in beta cells. Lineage studies showed loss of Sox4 in endocrine progenitors resulted in a block in terminal islet cell differentiation that was attributed to reduction in the production of key beta cell specification factors. These results demonstrate that SOX4 is essential for normal endocrine pancreas development both concomitant with, and downstream of, the endocrine fate decision. In conclusion, these studies position Sox4 temporally in the endocrine differentiation programme and provide a new target for improving in vitro differentiation of glucose-responsive pancreatic beta cells.


[Overlap syndrome--asthma and chronic obstructive pulmonary disease].
Asthma and chronic obstructive pulmonary disease (COPD) as separate diseases are considered for a long time. Now this concept needs to be re-evaluated because in many clinical situations both diseases may coexist, or one condition may evolve into the other. Especially in older patients with obstructive disease an overlapping diagnosis of asthma and COPD may be observed. Epidemiological data show that overlap syndrome is recognized by the coexistence of incompletely reversible airway obstruction and features of airway remodeling. The analysis of clinical symptoms indicates that the risk factors are the same in asthma and COPD, and a role of inflammatory process in the small airways may be a key point to understand the pathology of overlap syndrome. Studying these events may bring new insights into the treatment of obstructive diseases of the respiratory tract.


Dietary Habits and Lifestyle During Coronavirus Pandemic Lockdown: Experience From Lebanon.
This study aimed to examine the impact of quarantine on eating habits and lifestyle behaviors among the Lebanese adult population. A cross-sectional study was conducted using an online questionnaire designed on Google Forms between 3 June and 28 June 2020. The survey questions were adapted from the Short Food Frequency Questionnaire, the International Physical Activity Questionnaire Short Form, and the second version of the Copenhagen Psychosocial Questionnaire. A total of 2,507 adults completed the questionnaire. During the lockdown, 32.8% claimed weight gain, 44.7% did not eat fruits daily, 35.3% did not eat vegetables on daily basis, and 72.9% reported drinking less than eight cups of water per day. Moreover, there was a significant increase in the number of meals consumed per day, consumption of homemade meals, sedentary time, stress, and sleeping disturbances during the pandemic compared to before the pandemic (all p < 0.001). However, there was a significant decrease in physical activity engagement, sleep quality, and energy level during the lockdown compared to before the pandemic (all p < 0.001). The study highlights that the COVID-19 lockdown was associated with unfavorable changes in dietary habits and lifestyle behaviors in Lebanon. Sleep and mental health were also negatively impacted by the pandemic.


Intraindividual Fluctuations in Sleep Predict Subsequent Goal Setting in Adolescents.
The purpose of this study was to investigate within- and between-person associations between sleep and subsequent goal setting in adolescents. We conducted an intensive repeated measures longitudinal study to assess intra- and inter-individual associations between sleep and goal setting and potential moderators of such associations. Thirty-nine seventh through 12th graders reported on their sleep quality and propensity to set goals in their daily lives several times per week for approximately four months. We used a combination of multilevel modeling with time-varying covariates and centering techniques to partition within- and between-person variance. We found significant and positive associations between sleep and goal setting within individuals, but no such associations between individuals. That is, students were more likely to set goals for their work after getting a good night's sleep relative to their own average sleep quality, but getting good sleep on average relative to other individuals showed no association with average goal setting. These relationships were not moderated by participant age, gender, or sociodemographic status as indexed by maternal education. Differences in average sleep between adolescents matters less for their propensity to set goals than whether they experienced better- or worse-than-usual sleep the previous night given their own average. This finding represents the first evidence documenting effects of sleep on goal setting, which is an important psychological precursor to many youth behavioral and achievement outcomes. Our findings highlight the individuality of sleep needs and point to new directions for sleep-related practice and policy aimed at youth.


Diet in the etiology of inflammatory bowel disease.
The two predominant forms of inflammatory bowel disease (IBD) namely Crohn's disease (CD) and ulcerative colitis (UC) can have a significant impact on patients' quality of life and incur major costs in terms of time off work and for therapies. The precise aetiology of IBD is unknown, but is probably due to a combination of: genetic, immunological and environmental factors. The role for the latter is strongly supported by rises in the incidence of IBD in the 20th century, and emergence of both CD and UC in countries in the East. Dietary changes over time and according to region may be the environmental factor explaining these incidence patterns.


Changes in the Mental Health of Children and Adolescents during the COVID-19 Lockdown: Associated Factors and Life Conditions.
This study investigated the psychological impact of the coronavirus disease 2019 (COVID-19) among youth by analyzing their emotional/behavioral problems before and during the long-lasting lockdown in Spain. For that purpose, 699 parents with children aged 6-17 and 552 adolescents aged 12-17, who completed the parent and adolescent version of the Strengths and Difficulties Questionnaire at the beginning of 2019, responded to a survey from 26 May to 15 June 2020 that assessed psychological well-being and life conditions during quarantine (i.e., sociodemographic characteristics, situation before the lockdown, physical environment and accompaniment during the lockdown, COVID-related variables). According to both parent- and self-reports, children and youth experienced a significant worsening in emotional symptoms, conduct problems, hyperactivity/inattention, peer problems, and total difficulties subscales. Findings also suggested that impairment was mainly associated with variables related to the child's situation prior to home quarantine, the quality and quantity of the child's social networks during the lockdown, the daily routines the child followed, the concerns the child had about health, and the presence of economic and learning problems caused by the COVID-19. Thus, the present investigation emphasizes the need for carefully monitoring the mental health of younger people, provides guidance for the development of interventions that mitigate some of the psychological difficulties faced in a situation of confinement, and highlights the importance of paying special attention to high-risk groups.


Diacylglycerol kinase α establishes T cell polarity by shaping diacylglycerol accumulation at the immunological synapse.
Polarization of the T cell microtubule-organizing center (MTOC) to the immunological synapse between the T cell and an antigen-presenting cell (APC) maintains the specificity of T cell effector responses by enabling directional secretion toward the APC. The reorientation of the MTOC is guided by a sharp gradient of the second messenger diacylglycerol (DAG), which is centered at the immunological synapse. We used a single-cell photoactivation approach to demonstrate that diacylglycerol kinase α (DGK-α), which catalyzes the conversion of DAG to phosphatidic acid, determined T cell polarity by limiting the diffusion of DAG. DGK-α-deficient T cells exhibited enlarged accumulations of DAG at the immunological synapse, as well as impaired reorientation of the MTOC. In contrast, T cells lacking the related isoform DGK-ζ did not display polarization defects. We also found that DGK-α localized preferentially to the periphery of the immunological synapse, suggesting that it constrained the area over which DAG accumulated. Phosphoinositide 3-kinase activity was required for the peripheral localization pattern of DGK-α, which suggests a link between DAG and phosphatidylinositol signaling during T cell activation. These results reveal a previously unappreciated function of DGK-α and provide insight into the mechanisms that determine lymphocyte polarity.


Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination.
Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves. Blockade Ab avidity to the GI.1 vaccine component peaked at day 35 (7 days after dose 2). Avidities to heterotypic genogroup I VLPs were not sustained at day 35 after vaccination or GI.1 infection, as measured from archived sera. Only secretor-positive participants maintained high avidity blockade Ab to GI.1 at day 180. Avidity to the GII.4c vaccine component peaked at day 7, remained elevated through day 180, and was not secretor dependent. Avidity to an immunologically novel GII.4 strain VLP correlated with preexisting Ab titer to an ancestral strain Epitope A. Host genetics and pre-exposure history shape norovirus vaccine Ab responses, including blockade Ab avidity. Avidity of potentially neutralizing Ab may be an important metric for evaluating vaccine responses to highly penetrant viruses with cross-reactive serotypes.


[Effect of the ts 15 mutation of transcription termination factor rho on expression of the uridine phosphorylase gene of Escherichia coli].
The expression of nucleoside-catabolizing genes was studied in two isogenic strains, SA1030(rho+) and AD1600(rho ts 15). The deo-enzymes activities do not differ markedly in these two strains, though when cells were grown on glycerol medium the deo-enzymes level appeared to be higher than on glucose medium. The synthesis of uridine phosphorylase in AD1600 strain was found to be constitutive. It was found also that the cytR regulation system was not altered in AD1600 strain and a wild-type allele of udp gene was present in the genome of AD1600 strain. A conclusion is made that constitutive synthesis of uridine phosphorylase is due to the presence of rho ts 15 mutation in the genome of the strain AD1600.


Muslim women's experiences of maternity services in the UK: qualitative systematic review and thematic synthesis.
This review aimed to identify and synthesise evidence of Muslim women's experiences of maternity services in the UK. A systematic review and thematic synthesis of qualitative evidence, unrestricted by type of publication was conducted. Muslim women who had accessed maternity services in the UK, regardless of obstetric or medical history were included. Databases were searched from 2001 to 2019 and screened for inclusion using pre-determined criteria. The Critical Appraisal Skills Programme Qualitative Research Checklist was used to assess study quality and findings were synthesised using thematic synthesis, as described by Thomas and Harden. Six studies were included. The following five themes were identified: Islamic practices and Individualised care; Talk, Teach and Translate; Injustice, Inequity and Intolerance; If Allah wills; and, 'It's not all that bad'. Synthesis highlighted the significance of Islam in shaping many of the women's decision-making relating to antenatal screening and medication, which was contrasted with healthcare professionals' limited awareness of the importance of Islam for motherhood. The majority of women experienced poor maternity care which at times indicated stereotypical and discriminatory behaviour. Education for healthcare professionals is warranted, to enhance the quality and cultural competency in providing appropriate care that acknowledges and meets Muslim women's needs.


Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension.
Systemic oxygenation is improved by inhaled nitric oxide therapy in some newborns with respiratory failure and pulmonary hypertension. Our results with inhaled nitric oxide were reviewed to determine factors associated with an acute improvement in systemic oxygenation. Newborns with oxygenation indices of 25 to 40 were prospectively randomized to receive conventional therapy with or without 20 ppm inhaled nitric oxide. All newborns with oxygenation indices greater than 40 were treated with inhaled nitric oxide. Hemodynamic, blood gas, and Doppler ultrasound measurements were performed before and after 30 to 60 minutes of observation or therapy. The severity of lung disease was classified by the chest radiograph as: (1) normal or focal disease; (2) moderate diffuse disease-diffuse lung disease with well-defined heart borders; or (3) severe diffuse disease-diffuse lung opacification with indistinct heart borders. Heart rate, blood pressure, and ductal diameters did not change. Blood gases and ductal shunting acutely improved only in patients treated with inhaled nitric oxide. Patients with normal lung fields or focal disease had the greatest degree of improvement in systemic oxygenation. Changes in oxygenation were not influenced by gestational age, baseline blood gases, the proportion of right-to-left ductal shunting, prior treatment with a surfactant, or the use of conventional or high-frequency jet ventilation. Collectively, blood gases and ductal shunting did not improve with inhaled nitric oxide in patients with lung hypoplasia or severe diffuse lung disease. Sustained improvement in oxygenation occurred in 87% of patients with oxygenation indices greater than 40 in whom oxygenation indices less than 40 acutely developed after exposure to nitric oxide, whereas 90% of patients in whom oxygenation indices less than 40 did not acutely develop were treated with extracorporeal membrane oxygenation or ultimately died. Inhaled nitric oxide acutely improves systemic oxygenation in many newborns with respiratory failure and pulmonary hypertension. The diagnosis and chest radiograph are helpful in identifying patients who will have favorable acute responses to therapy. In patients with severe hypoxemia, the need for invasive support with extracorporeal membrane oxygenation may be determined by an acute trial of inhaled nitric oxide.


Immunoglobulin G deficiency in United kingdom children with invasive pneumococcal disease.
This study aimed to determine whether nonprotective, convalescent pneumococcal serotype-specific immunoglobulin G (IgG) concentrations in children with invasive pneumococcal disease (IPD) might be associated with an underlying IgG deficiency. The first 200 convalescent blood samples from children with IPD that were submitted for pneumococcal antibody testing also had total serum IgG concentrations measured. Pneumococcal IgG testing was performed for 12 serotypes (1, 3, 5, 7, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F); serotype-specific pneumococcal IgG concentrations <0.35 μg/mL were considered nonprotective. IgG deficiency was defined as total serum IgG ≥2 standard deviations below the mean for age. Nineteen of 172 children (11.0%) with sufficient serum had IgG deficiency although serum IgG concentrations were only marginally below the lower limit for age and all 19 had IgG concentrations >2.0 g/L. IgG deficiency was associated with younger age at disease (median, 5.2 [interquartile range, 2.3-13.5] vs. 12.5 [7.4-17.0] months; P = 0.005) and nonprotective convalescent antibody concentrations against the infecting serotype (10/13 [77%] vs. 51/105 [49%]; P = 0.05). There was a correlation between IgG deficiency and the number of serotypes against which children had nonprotective pneumococcal antibody concentrations, particularly among vaccinated cases (P < 0.05). Vaccine failure was also twice as common among those with IgG deficiency (3/19 [16%] vs. 11/53 [7%], P = 0.20), although this association was not statistically significant. Three children with IgG deficiency who were retested 3 to 5 months later had normal serum IgG concentrations. Although 11% of children with IPD had IgG deficiency, total serum IgG concentrations were reassuringly only marginally below the reference range and were within the normal range in those who were retested, suggesting a transient deficiency rather than a serious underlying primary immunodeficiency.


[Changes in ventricular depolarization and repolarization in 116 cases of surgically treated interauricular communication].
The postoperative changes of ventricular depolarization and repolarization were studied in 116 cases of atrial septal defect 3 to 8 years after surgical treatment. High fidelity multiple unipolar registries as well as the vectorcardiographic curves in three planes were obtained. Before surgery there were 101 RBBB (87.07% of this series). Of 22 minor degree RBBB, 17 (77.27%) showed no changes, 2 (9.09%) became distal blocks and 3 (13.64%) became intermediate degree RBBB. Of 77 preoperative intermediate degree RBBB, 20 (25.97%) diminished to a minor degree, 1 (1.3%) became a distal block and 2 (2.6%) augmented to an advanced degree. Fifteen distal right blocks (12.93% of the total of cases) persisted postoperatively. Signs of right ventricular enlargement disappeared in all the cases. The right Q-Tc, previously prolonged in 38 cases (32.76% of this series), was normal after surgery. Peaked or negative interpolated T waves disappeared in right precordial and transitional leads. The electrocardiographic features of ventricular repolarization seem to reflect hemodynamic improvement better than those of depolarization. The electrocardiogram permits classification of the disturbances of right ventricular conduction, while the vectorcardiogram shows variations in dimensions of the right ventricle.


Structural and functional properties, chaperone activity and posttranslational modifications of alpha-crystallin and its related subunits in the crystalline lens: N-acetylcarnosine, carnosine and carcinine act as alpha- crystallin/small heat shock protein enhancers in prevention and dissolution of cataract in ocular drug delivery formulations of novel therapeutic agents.
Cataract is a leading cause of blindness worldwide and is responsible for ∼40-80% of the estimated 45 million cases of blindness that occur across the globe. In addition to providing refractive properties to the lens for focusing the image, it is believed that the molecular chaperone function of α-crystallin is essential in preventing the light scattering due to aggregation of other proteins and thus in the maintenance of lens transparency and thereby prevention of cataract. By now, it is fairly acknowledged that chaperoning ability of α-crystallin is instrumental in the maintenance of crystalline lens transparency, and decreased chaperone-like activity of α-crystallin is associated with various types and stages of cataract. A better pharmacological targeting of safeguarding the α-crystallin chaperone activity may aid the development of therapeutic strategies that could evade the need for cataract surgery and revive lens transparency of the cataractous lenses. This article originally summarizes the significance of modulation and enhancing of α-crystallin chaperone activity with imidazole-containing dipeptides N-acetylcarnosine, carnosine and carcinine in consequence to prevent, delay or dissolve the human cataract. A growing evidence and discussion of recent patents are presented in this study that demonstrate the ability of N-acetylcarnosine (lubricant eye drops) or carcinine (lubricant eye drops) (universal antioxidant and deglycation agent) resistant to enzymatic hydrolysis with carnosinase to act as pharmacological chaperones, to decrease oxidative stress and ameliorate oxidative and excessive glycation stress-related eye disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for age-related cataracts, age-related macular degeneration (AMD) and ocular complications of diabetes (OCD). The therapeutic strategies are highlighted in the study for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human age-related eye disease, such as cataracts and advanced glycation tissue proteins - engineered systems.


Lipid alterations in LLC-PK1 cells exposed to mercuric chloride.
We have studied the effects of HgCl2 on the lipids of LLC-PK1 (pig kidney) epithelial cells. Our results show that treatment of cells with HgCl2 caused a rapid accumulation of unesterified fatty acids (particularly arachidonic acid) and lysophospholipids. A 27-fold increase in unesterified arachidonic acid and a 17-fold increase in lysophosphatidylethanolamine (LPE) was accompanied by a 26% decline in the mass of phosphatidylethanolamine as determined by gas chromatography and lipid phosphorus assay. Similar changes were seen following HgCl2 treatment of cells whose lipids were labelled with 14C stearic acid, 3H arachidonic acid, or 14C acetate, but the radiolabelling techniques also identified an increased content of label in lysophosphatidylcholine (LPC) and a corresponding decrease in phosphatidylcholine. These alterations were accompanied by the formation of blebs on the plasma membrane and irreversible injury as indicated by electron microscopy. The possible role of unesterified fatty acids in the pathogenesis of injury was studied by adding fatty acids to the cells. The addition of unsaturated fatty acids (oleic, linoleic, or arachidonic acids) to the cells caused plasma membrane blebbing and loss of viability. Similarly, the addition of LPC or LPE to the cells resulted in cell death; however, plasma membrane blebbing did not result.


Comparison of ruminant anthelmintics, using multiple dose administration.
Eleven ruminant anthelmintics were administered to lambs over a 30-day period, using medicated feeds or multiple oral doses. Fenbendazole and its sulfinyl analog, oxfendazole, were effective (greater than 90%) in the control of clinical parasitism at feeding levels of 5 mg/kg of feed. Parbendazole and albendazole were effective at daily oral dose levels of 1 mg/kg of body weight and at feeding dose levels of 10 mg/kg of feed, respectively. Levamisole, mebendazole, and oxibendazole were ineffective in controlling intense natural parasitic infections of sheep at daily oral dose levels equal to or less than 1 mg/kg of body weight and/or a feeding level equal to or less than 10 mg/kg of feed.


[Experiences in the epidemiological surveillance of foodborne pathogens by pulsed field gel electrophoresis (PFGE) in Peru].
Foodborne diseases and other enteric infections often occur as outbreaks and cause morbidity and mortality all over the world. In Perú, they represent a serious public health problem, and are caused by a great variety of infectious agents. For epidemiological research, a wide array of typification methods are used. One of the most important tools for the molecular subtyping of bacterial pathogens is the Pulsed Field Gel Electrophoresis (PFGE), which is a highly precise method that allows the discrimination between different bacterial isolates which are epidemiologically related. The Instituto Nacional de Salud del Perú (INS) is part of the WHO Global Foodborne Infections Network (WHO-GFN) and of the PulseNet Latin American and Caribbean Net (PN-AL & C), with whom it shares the genetic profiles of the isolated pathogenic strains, so that it is possible to compare de genotypes of similar strains found in different countries and to identify the occurrence of epidemic outbreaks in the region, strengthening the regional system of epidemiological surveillance and generating a rapid, coordinated response between the countries. We present the two last years experience including the advances in the use of these strategic tools that have allowed us to characterize genotype patterns implicated in foodborne diseases from isolates recovered in the laboratory network of Peru.


Single-centre experience of radiation exposure in acute surgical patients: assessment of therapeutic impact and future recommendations.
Radiological investigations have become a key adjunct in patient management and consequently radiation exposure to patients is increasing. The study objectives were to examine the use of radiological investigations in the management of acute surgical patients and to assess whether a guideline-based radiation exposure risk/benefit analysis can aid in the choice of radiological investigation used. A prospective observational study was completed over a 12-week period from April to July 2008 for all acute surgical admissions. Data recorded included demographics, clinical presentation, differential diagnosis, investigations, surgical interventions, and final clinical outcome. The use of radiological investigative modalities as an adjunct to clinical assessment was then evaluated against The Royal College of Radiologists (RCR) guidelines. A total of 380 acute surgical admissions (M = 174, F = 185, children = 21) were assessed during the study period. Seven hundred thirty-four radiological investigations were performed with a mean of 1.93 investigations per patient. Based on the RCR guidelines, 680 (92.6%) radiological investigations were warranted and included 142 CT scans (19.3%), 129 chest X-rays (17.6%), and 85 abdominal X-rays (11.6%). Clinically, radiological imaging complemented surgical management in 326 patients (85.8%) and the management plan remained unchanged for the remaining 54 patients (14.2%). This accounted for an average radiation dose of 4.18 millisievert (mSv) per patient or 626 days of background radiation exposure. CT imaging was responsible for the majority of the radiation exposure, with a total of 1310 mSv (82.6%) of the total radiation exposure being attributed to CT imaging in 20.8% of acute admissions. Subgroup analysis demonstrated that 92.8% of the CT scans performed were appropriate. Radiation exposure was generally low for the majority of acute surgical admissions. However, it is recommended that CT imaging requests be evaluated carefully, particularly for patients with clinically confirmed pathologies and in younger women.


[Australian Refined Diagnosis Related Groups. Formal and inherent problems of grouping with the example of stroke care].
With the Health Reform 2000, the Australian Refined Diagnosis Related Groups (AR-DRG), Version 4.1 have been chosen as the basis for the future German costing system for hospitals. With regard to Stroke Severity (Barthel Index [BI]) we investigated to what extent the grouping according to AR-DRGs can reproduce healthcare expenditures for such patients. Options to adapt and optimize the system are discussed. 632 patients who had suffered a cerebrovascular accident and were discharged from conservative acute care in 1999, were classified according to the AR-DRGs. For the grouping we alternatively used data from the current hospital information system and a stroke database for quality assurance. The results were also compared with the clinical profiles for the public hospital sector of the corresponding DRGs in Australia (1997-98). On average 0.99 additional diagnoses per case were documented in the hospital information system, compared to 3.65 in the stroke database. In the stroke database 177 cases (36.8%) were assigned to the DRG with the highest cost weight. 53.7% of these patients suffered a serious stroke (BI < 30). Grouping on the basis of hospital information system data led only to 14 cases (2.8%) assigned to the DRG with the highest cost weight. Type and extent of additional diagnoses are crucial for the grouping process. From a clinical and economic point of view, measures of disability and impairment should be assigned to the grouping process to improve homogeneity under both aspects. Scores can also serve for determining reliable outcome parameters. For the development of an outcome related reimbursement system, procedures must be included in the definition of medical DRGs. In future, DRGs, which cover overlapping healthcare sectors, should be developed for patients with poststroke rehabilitation.


A Comparative Study of Pituitary Volume Variations in MRI in Acute Onset of Psychiatric Conditions.
The growing belief that endocrine abnormalities may underlie many mental conditions has led to increased use of imaging and hormonal assays in patients attending to psychiatric OPDs. People who are in an acute phase of a psychiatric disorder show Hypothalamic Pituitary Adrenal (HPA) axis hyperactivity, but the precise underlying central mechanisms are unclear. To assess the pituitary gland volume variations in patients presenting with new onset acute psychiatric illness in comparison with age and gender matched controls by using MRI. The study included 50 patients, with symptoms of acute psychiatric illness presenting within one month of onset of illness and 50 age and gender matched healthy controls. Both patients and controls were made to undergo MRI of the Brain. A 0.9 mm slices of entire brain were obtained by 3 dimensional T1 weighted sequence. Pituitary gland was traced in all sagittal slices. Anterior pituitary and posterior pituitary bright spot were measured separately in each slice. Volume of the pituitary (in cubic centimetre- cm3) was calculated by summing areas. Significance of variations in pituitary gland volumes was compared between the cases and controls using Analysis of Covariance (ANOVA). There were significantly larger pituitary gland volumes in the cases than the controls, irrespective of psychiatric diagnosis (ANOVA, f=15.56; p=0.0002). Pituitary volumes in cases were 15.36% (0.73 cm3) higher than in controls. There is a strong likelihood of HPA axis overactivity during initial phase of all mental disorders along with increased pituitary gland volumes. Further studies including hormonal assays and correlation with imaging are likely to provide further insight into neuroanatomical and pathological basis of psychiatric disorders.


Natural variations at the Stay-Green gene promoter control lifespan and yield in rice cultivars.
Increased grain yield will be critical to meet the growing demand for food, and could be achieved by delaying crop senescence. Here, via quantitative trait locus (QTL) mapping, we uncover the genetic basis underlying distinct life cycles and senescence patterns of two rice subspecies, indica and japonica. Promoter variations in the Stay-Green (OsSGR) gene encoding the chlorophyll-degrading Mg++-dechelatase were found to trigger higher and earlier induction of OsSGR in indica, which accelerated senescence of indica rice cultivars. The indica-type promoter is present in a progenitor subspecies O. nivara and thus was acquired early during the evolution of rapid cycling trait in rice subspecies. Japonica OsSGR alleles introgressed into indica-type cultivars in Korean rice fields lead to delayed senescence, with increased grain yield and enhanced photosynthetic competence. Taken together, these data establish that naturally occurring OsSGR promoter and related lifespan variations can be exploited in breeding programs to augment rice yield.


Speech pathology interventions in patients with neuromuscular diseases: a systematic review.
A systematic review was conducted to summarize and evaluate the literature on the effectiveness of speech pathology interventions in adults with neuromuscular diseases. Databases searched included the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, PsycINFO and PubMed. A total of 1,772 articles were independently screened on title and abstract by 2 reviewers. No randomized controlled trials or clinical controlled trials were found. Four other designs were included. Only one study on oculopharyngeal muscle dystrophy (OPMD) appeared to have sufficient methodological quality. There is evidence indicating that correction of head position in patients with OPMD improves swallowing efficiency (level III evidence). Despite 1,772 studies, there is only evidence of level III regarding the effectiveness of speech pathology interventions in patients with OPMD. Recommendations for future research are given.


Treatment of symptomatic neuroendocrine tumor syndromes: recent advances and controversies.
Neuroendocrine tumors(NETs), once thought rare, are increasing in frequency in most countries and receiving increasing-attention. NETs present two-treatment problems. A proportion is aggressive and a proportion has a functional, hormone-excess-state(F-NET), each of which must be treated. Recently, there have been many advances, well-covered in reviews/consensus papers on imaging-NETs; new, novel anti-tumor treatments and understanding their pathogenesis. However, little attention has been paid to advances in the treatment of the hormone-excess-state. These advances are usually reported in case-series, and case-reports with few large studies. In this paper these advances are reviewed. Areas covered: Advances in the last 5-years are concentrated on, but a review of literature from the last 10-years was performed. PubMed and other databases (Cochrane, etc.) were searched for F-NET-syndromes including carcinoid-syndrome, as well as meeting-abstracts on NETs. All advances that controlled hormone-excess-states or facilitated-control were covered. These include new medical-therapies [serotonin-synthesis inhibitors(telotristat), Pasireotide, new agents for treating ACTHomas], increased dosing with conventional therapies (octreotide-LAR, Lanreotide-Autogel), mTor inhibitors(everolimus), Tyrosine-kinase inhibitors(sunitinib),cytoreductive surgery, liver-directed therapies (embolization, chemoembolization, radioembolization, RFA), peptide radio-receptor-therapy(PRRT) and 131I-MIBG, ablation of primary F-NETs. Expert opinion: Although many of the newer therapies controlling the hormone-excess-states in F-NETs are reported in relatively few patients, all the approaches show promise. Their description also generates some controversies/unresolved areas,such as the order of these new treatments, their longterm-efficacy, and effectiveness of combinations which may require large,controlled studies.


Biosensing in a microelectrofluidic system using optical whispering-gallery mode spectroscopy.
Label-free detection of biomolecules using an optical whispering-gallery mode sensor in a microelectrofluidic channel is simulated. Negatively charged bovine serum albumin is considered as the model protein analyte. The analyte transport in aqueous solution is controlled by an externally applied electrical field. The finite element method is employed for solving the equations of the charged species transport, the Poisson equation of electric potential, the equations of conservation of momentum and energy, and the Helmholtz equations of electromagnetic waves. The adsorption process of the protein molecules on the microsensor head surface is monitored by the resonance frequency shifts. Frequency shift caused by temperature variation due to Joule heating is analyzed and found to be negligible. The induced shifts behave in a manner similar to Langmuir-like adsorption kinetics; but the time constant increases due to the presence of the external electrical field. A correlation of the frequency shift, the analyte feed concentration in the solution, and the applied voltage gradient is obtained, in which an excellent linear relationship between the frequency shift and the analyte concentration is revealed. The applied voltage gradient enhances significantly the analyte concentration in the vicinity of the sensor surface; thus, the sensor sensitivity which has a power function of the voltage gradient with exponent 2.85 in the controlled voltage range. Simulated detection of extremely low protein concentration to the pico-molar level is carried out.


A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70(-) and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70(+) and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70(-)) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease.


A conservative approach to quadricepsplasty: description of a modified surgical technique and a report of three cases.
Various techniques have been described for the treatment of soft tissue extension contracture of the knee. Some involve large exposures, and others can result in a permanent extensor lag. We describe a technique with limited exposure, avoiding transverse incisions in the rectus femoris. Through a midline incision, the extensor expansion is exposed. The rectus femoris is separated from the vastus medialis, lateralis, and intermedius to form a strap-like structure. Vastus intermedius is separated from the patella. If firm, careful manipulation of the knee is unsuccessful, the incisions are extended distally along both sides of the patella and patellar tendon, releasing the extensor mechanism from any underlying heterotopic bone, and further manipulation of the knee is performed. Postoperatively, a rehabilitation program is begun. A good outcome following this technique is described in 3 knees presenting with severe restriction of knee flexion. There were no wound complications and no residual extensor lag.


Levels of Intra-specific AFLP Diversity in Tuber-Bearing Potato Species with Different Breeding Systems and Ploidy Levels.
DNA-based marker analysis of plant genebank material has become a useful tool in the evaluation of levels of genetic diversity and for the informed use and maintenance of germplasm. In this study, we quantify levels of amplified fragment length polymorphism (AFLP) in representative accessions of wild and cultivated potato species of differing geographic origin, ploidy, and breeding system. We generated 449 polymorphic AFLP fragments in 619 plants, representing multiple plants (16-23) from 17 accessions of 14 potato taxa as well as single plants sampled from available accessions (from 3 to 56) of the same 14 taxa. Intra-accession diversities were compared to those of a synthetic 'taxon-wide' population comprising a single individual from a variable number of available accessions of each sampled taxon. Results confirm the expected considerably lower levels of polymorphism within accessions of self-compatible as compared to self-incompatible taxa. We observed broadly similar levels of 'taxon-wide' polymorphism among self-compatible and self-incompatible species, with self-compatible taxa showing only slightly lower rates of polymorphism. The most diverse accessions were the two cultivated potato accessions examined, the least diverse being the Mexican allohexaploids Solanum demissum and S. iopetalum. Generally allopolyploid self-compatible accessions exhibited lower levels of diversity. Some purported self-incompatible accessions showed relatively low levels of marker diversity, similar to the more diverse self-compatible material surveyed. Our data indicate that for self-compatible species a single plant is highly representative of a genebank accession. The situation for self-incompatible taxa is less clear, and sampling strategies used will depend on the type of investigation. These results have important implications for those seeking novel trait variation (e.g., disease resistance) in gene banks as well as for the selection of individuals for genomics studies. We also show that AFLPs, despite having been largely replaced by other marker types, is highly suitable for the evaluation of within and between accession diversity in genebanks.


[Echocardiography in diagnosis of pediatric pulmonary artery sling].
To evaluate the application of echocardiography in diagnosis of pediatric pulmonary artery sling. Twenty-five children diagnosed as pulmonary artery sling in the Children's Hospital, Zhejiang University School of Medicine from July 2012 to August 2017, and 50 healthy children(control group) were enrolled in the study. Echocardiography was performed in all subjects. The origins of the left pulmonary artery(LPA) and right pulmonary artery(RPA) were observed; the internal diameters of LPA, RPA and main pulmonary artery(MPA) were measured; and the ratios of LPA/MPA and RPA/MPA were calculated. The value of RPA/MPA and LPA/MPA in diagnosing pulmonary artery sling was evaluated by ROC curve. Echocardiography showed that the internal diameters of RPA were increased in all patients; while the LPA and blood flow signals in common pulmonary arterial bifurcation were not found in 24 cases, in whom the MPA was directly extended to the RPA, and the LPA was from the massive RPA. The ultrasound of one special case showed that there was no distinct bifurcation of MPA; the MPA walked to the right and then to the left with no change in the internal diameter. There were significant differences in RPA/MPA(0.50±0.05 vs. 0.71±0.15, t=7.06, P<0.01) and LPA/MPA(0.52±0.05 vs. 0.39±0.09, t=6.94, P<0.01) between controls and the patients. ROC curve analysis showed that the AUC of RPA/MPA and LPA/MPA in diagnosis of pulmonary artery sling were 0.90 and 0.89, respectively. When taking 0.60 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of RPA/MPA in diagnosis of pulmonary artery sling were 79%, 100%, 100%, 91% and 93%, respectively. When taking 0.43 as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LPA/MPA in diagnosis of pulmonary artery sling were 71%, 96%, 89%, 87% and 88%, respectively. s Echocardiography can effectively diagnose pediatric pulmonary artery sling. The RPA/MPA ratio of 0.60 and the LPA/MPA ratio of 0.43 can be used as cutoff values for diagnosis.


Use of neuromuscular electrical stimulation and [corrected] dorsal wrist splint to improve the hand function of a child with spastic hemiparesis.
This case report describes a program for a child with spastic hemiparesis who had previously received physical therapy with neuromuscular electrical stimulation (NMES). After a year without physical therapy, he returned to continue to receive NMES to strengthen muscles, increase sensory awareness, and improve hand function. The child quickly regained his previous level of functioning and made additional progress. After 38 sessions, he still lacked adequate wrist stability for independent hand function. A dorsal wrist splint was used to stabilize the wrist while NMES facilitated muscle activity of the hand and wrist. While wearing the splint, the child could use his hand independently without adult interference or "assistance," thus allowing motor learning to occur. After 24 additional sessions (i.e., 9 months of using the splint), the child could use the hand for activities such as tying his shoelaces without the splint. No increase in spasticity was seen in spite of strengthening the spastic finger flexors.


Hepatic encephalopathy.
Hepatic encephalopathy is a severe complication of cirrhosis that is related to the effects of ammonia. Analysis of interorgan ammonia trafficking has identified an important role of skeletal muscle in ammonia removal and has highlighted the importance of the nutritional status. Ammonia causes neurotransmitter abnormalities and induces injury to astrocytes that is partially mediated by oxidative stress. These disturbances lead to astrocyte swelling and brain edema, which appear to be involved in the pathogenesis of neurological manifestations. Inflammatory mediators worsen brain disturbances. New methods for assessing hepatic encephalopathy include clinical scales, neuropsychological tests, imaging of portal-systemic circulation, and magnetic resonance of the brain. Reappraisal of current therapy indicates the need for performing placebo-controlled trials and the lack of evidence for administering diets with restricted protein content. Liver transplant should be considered in selected patients with hepatic encephalopathy. Future prospects include new drugs that decrease plasma ammonia, measures to reduce brain edema, and liver-support devices.


Treatment of alopecia areata with topical nitrogen mustard.
Eleven patients with severe alopecia areata (localized and totalis types) were treated with topically applied nitrogen mustard. Nine patients had terminal hair regrowth; in 7 of the 11 patients, it was cosmetically acceptable. Hair regrowth began approximately 1-2 months after the initiation of therapy. Two patients had an allergic contact dermatitis reaction to the mechloretamine solution; no systemic side effects were seen. During a follow-up period of 12 months, only two patients had a recurrence. These preliminary results indicate that topically applied nitrogen mustard has a significant effect in alopecia areata.


A comparative study of the effectiveness of an osteopathic primary care sports medicine led intervention on performance in men's collegiate lacrosse players.
Comprehensive sports medicine care goes beyond the treatment of injuries resulting from athletic activities. Ultimately, it is a competence that includes knowledge in physical therapy, training, nutrition, coaching, motivation, competition, mentoring, psychology, and spirituality that allows the physician and patient to collaborate on promoting the patient's health goals. The current literature demonstrates a lack of knowledge in the Osteopathic Primary Care Sports Medicine Model's effectiveness in performance. To determine whether a comprehensive osteopathic primary care sports medicine approach can improve performance and health outcomes in collegiate athletes. A randomized controlled trial commenced just prior to the start of the lacrosse season and concluded at the end of the season. All the New York Institute of Technology (NYIT) collegiate lacrosse players were educated first in a 1-day seminar of the core competencies, and all participants had access to ask questions on their own volition. Then they were randomized into two groups, either the experimental group receiving the direct osteopathic primary care sports medicine intervention (n=18) or the control group not having active intervention (n=19). Also, the overall team winning percentage for that season was computed and compared to that for the previous years and the following year. Participants were assessed before and after the intervention with the Patient Health Questionnaire (PHQ-9), the 36-Item Short Form Survey (SF-36), custom Osteopathic Primary Care Sports Medicine questionnaire, and body fat composition, and their changes were compared between the experimental group and the control group. Collected data were analyzed using the repeated-measures analysis of variance. Thirty-seven participants were enrolled in the study. After 14 participants were excluded due to being lost to follow-up, 23 athlete records were analyzed. The winning percentage of the team was highest during the year of the study period time than in the 3 previous years and the following year. The test group did not have any statistically significant change in the PHQ-9, SF-36, custom Osteopathic Primary Care Sports Medicine questionnaire, as well as in body fat composition. When used during a collegiate lacrosse season, this Osteopathic Primary Care Sports Medicine intervention did not significantly improve health outcomes. This preliminary study, despite its limitations in compliance and study population size, did demonstrate improvement in overall team performance when comparing the intervention sport season to other seasons but was not statistically significantly. Therefore, further studies are warranted to improve the understanding in this approach to athlete health outcomes and performance.


Epileptic nystagmus: electroclinical study of a case.
Epileptic nystagmus (EN) is a rare form of nystagmus that occurs only during epileptic seizures. We report a case in which EN was first noted in an 8 year-old boy. Neuro-imaging was normal. Sharp waves from the left occipital lobe characterised the interictal EEG. Ictal video-EEG showed the aspects of electric seizures during clinical manifestations e.g. nystagmus. Ambulatory EEG displayed numerous diurnal and nocturnal seizures, but exclusively in REM sleep. After two weeks of sodium valproate treatment, the seizures, EEG focus spikes and nystagmus, as well as the squint, disappeared. During a two-year follow-up the child had no further seizures, EEG was normal and the school performance was unaffected. This case has the main features of benign epilepsy, although there are unusual features such as epileptic nystagmus, permanent squint, reduction of EEG paroxysmal abnormalities during NREM, and the presence of seizures during REM sleep. The observation and the significance of EN are discussed with reference to the literature.


Non-consensual sex within pre-marital relationships: experiences of young women in India.
In India, little is known about the prevalence of non-consensual sex within pre-marital relationships and factors correlated with such experience, although a sizeable proportion of young people engage in pre-marital relationships. Drawing on qualitative and quantitative data from a representative study of youth in six Indian states, this paper examines the extent to which young women who had had pre-marital sex had experienced non-consensual sex, that is, sex by persuasion or force, and factors associated with it. Analysis is restricted to 821 young women who reported pre-marital sex. Of those who had had pre-marital sex, 33% reported that they were either persuaded (14%) or forced (19%) to engage in sex. Young women residing in urban areas and in communities reportedly characterised by physical fights among youth were more likely than their respective counterparts to have experienced sex by persuasion. Young women who had delayed sexual initiation and those who displayed self-efficacy were less likely than others to experience forced sex. Young women who had experienced geographic mobility in adolescence and who had witnessed parental violence were more likely than others to report forced sex. Finally, those in southern states were less likely than their northern counterparts to experience forced sex.


On the Illumination Influence for Object Learning on Robot Companions.
Most collaborative tasks require interaction with everyday objects (e.g., utensils while cooking). Thus, robots must perceive everyday objects in an effective and efficient way. This highlights the necessity of understanding environmental factors and their impact on visual perception, such as illumination changes throughout the day on robotic systems in the real world. In object recognition, two of these factors are changes due to illumination of the scene and differences in the sensors capturing it. In this paper, we will present data augmentations for object recognition that enhance a deep learning architecture. We will show how simple linear and non-linear illumination models and feature concatenation can be used to improve deep learning-based approaches. The aim of this work is to allow for more realistic Human-Robot Interaction scenarios with a small amount of training data in combination with incremental interactive object learning. This will benefit the interaction with the robot to maximize object learning for long-term and location-independent learning in unshaped environments. With our model-based analysis, we showed that changes in illumination affect recognition approaches that use Deep Convolutional Neural Network to encode features for object recognition. Using data augmentation, we were able to show that such a system can be modified toward a more robust recognition without retraining the network. Additionally, we have shown that using simple brightness change models can help to improve the recognition across all training set sizes.


The subacute hospital treatment of the borderline patient: III. Management of suicidal crisis by family intervention.
A family approach to suicidal crises in hospitalized borderline patients is described. The approach is aimed not only at the acute crises, but at the likelihood that repetitive, panic-inducing suicidal episodes provoke shame-producing over-regulation in the short run or exhaustion of support systems (family and treatment team) in the long run. An emergency family session with a hospitalized patient in acute suicidal crisis is presented. Subacute hospital treatment must respond to these crises mindful of long-term as well as acute risks. Subacute hospitalization allows for family intervention to buttress support systems for the long term task of caring for the suicidal borderline patient.


Kindling as a model for alcohol withdrawal syndromes.
Periodic brain stimulation, particularly in the limbic system, at stimulus intensities initially too low to produce any behavioural or EEG effects, progressively produces EEG changes, motor automatisms, and eventually convulsions, an effect called kindling. Data are presented and reviewed that suggest that the severity of alcohol withdrawal symptoms progressively increases over years of alcohol abuse in a stepwise fashion similar to the kindling process. The model is presented that the limbic system hyperirritability which accompanies each alcohol withdrawal serves over time to kindle increasingly widespread subcortical structures. These long-term changes in neuronal excitability might relate to the progression of alcohol withdrawal symptoms from tremor to seizures and delirium tremens, as well as the alcoholic personality changes between episodes of withdrawal.


Implementation science as a leadership capability to improve patient outcomes and value in healthcare.
When evidence thresholds are met, adopting healthcare innovations should add value, and this is forgone when evidence is not translated into practice. Activities that are not supported by evidence lead to ineffective or unnecessary care, or harm, poor outcomes, and low-value healthcare. This article provides an overview of implementation science, which is the scientific study of why implementation succeeds or fails. We draw parallels between the LEADS in a Caring Environment leadership framework and implementation science process models and frameworks. Taken together, the principles and practices in LEADS and the aims of implementation science are effectively quite similar and can be useful for healthcare management looking to optimize resources when implementing evidence-based practice and innovation into routine clinical care.


Predictors of self-reported alcohol use and attitudes toward alcohol among 11-year-old British children with and without intellectual disability.
Reducing harmful levels of alcohol consumption among children is an important public health concern internationally and in many high income countries. Little is known about levels and predictors of alcohol use among children with intellectual disability (ID). Secondary analysis of child self-report data at age 11 years collected in the UK's Millennium Cohort Study. Children with ID were significantly more likely to: have used alcohol in the last 4 weeks; to have had five or more alcoholic drinks on one occasion; to have had five or more alcoholic drinks or been intoxicated on one occasion; to have more positive attitudes about the psychological and social benefits of drinking; and to have less negative attitudes about the social and physical costs of drinking. Potentially harmful levels of drinking (intoxication or 5+ alcoholic drinks on one occasion) among children with ID were associated with child smoking, having friends who use alcohol, reporting that drinking makes it easier to make friends, and reporting that drinking reduces worrying. Children with ID accounted for 9% of all children with potentially harmful levels of drinking. Public health interventions to reduce potentially harmful drinking among children in general must recognise that children with ID are a potentially high risk group and ensure that interventions are appropriately adjusted to take account of their particular needs and situation. Future research in this area is needed to untangle the causal pathways between attitudes toward alcohol and alcohol use among children with ID and the extent to which levels of alcohol use and predictors of alcohol use may be moderated by severity of ID.


Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.
The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals. Regulators of histone methylation have been associated with ageing in worms and flies, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complex-ASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2-extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylation-a mark associated with active chromatin-is detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.


Relationship of leptin concentration to gender, body mass index and age in Saudi adults.
Leptin concentrations are highly correlated with body fat storage and exhibit sexual dimorphism, with women having higher concentrations at every level of relative or absolute adiposity. To test whether or not this relation is consistent across the Saudi population. This study aims to investigate the effect of gender, obesity related parameters, and age on leptin levels from representative samples of Saudi women and men. This study was carried out at King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia during the year 2003. Fasting leptin concentrations were determined after an overnight fast in 122 healthy subjects (57 women, 65 men; age 20-75 years; body mass index [BMI] 16-56 kg/m2). The subjects were separated into female and male groups. To clarify the age and BMI-related changes in leptin levels, each gender was divided into 3 BMI groups (lean 15-24, overweight 25-30 and obese >30 kg/m2), and 3 age groups (younger 20-34, middle-aged 35-49 and older 50-75 years); and they were treated separately. Anthropometrics measurements (weight, height, waist, and hip circumferences), blood pressure, and fasting glucose levels were taken at the time of the collection. In the whole group, leptin levels were between 0.16-21.72 ng/ml, and females had higher leptin concentration (6.04 +/- 4.71 ng/ml versus 1.72 +/- 0.95 ng/ml, p<0.0001) than males. Gender differences remained clear when leptin concentrations were divided by BMI or age. In comparing the pattern of changes between the 2 genders, leptin levels were low in lean individuals and rose with increased BMI in both genders. Age-related change in leptin levels showed a tendency toward a non-significant reduction in older women and a significant (p=0.05) rise in older men. Correlation analysis between leptin and BMI were highly significant in female (r=0.64; p=0.0001) and male (r=0.49; p=0.0001) groups independent of age and sex. The findings were further explored using stepwise multiple linear regression analysis with leptin concentrations as the dependent variable and age, BMI, waist hip ratio (WHR), waist, and hip measurements as independent variables. The analysis demonstrated that the determinants of leptin concentrations were BMI and age (r=0.69; p=0.015) in women and BMI, age and WHR (r=0.61; p=0.01) in men. The present study demonstrates that there are gender-specific and age-dependent gender-specific differences in leptin concentrations in healthy Saudi individuals. However, this study indicates that there may be unknown variables that may also influence leptin levels in Saudi women and men.


Forecasting demand for maternal influenza immunization in low- and lower-middle-income countries.
Immunization of pregnant women against seasonal influenza remains limited in low- and lower-middle-income countries despite being recommended by the World Health Organization (WHO). The WHO/PATH Maternal Influenza Immunization Project was created to identify and address obstacles to delivering influenza vaccines to pregnant women in low resource setting. To gain a better understanding of potential demand from this target group, we developed a model simulating pregnant women populations eligible for vaccination during antenatal care (ANC) services in all low- and lower-middle-income countries. We assessed potential vaccine demand in the context of both seasonal and year-round vaccination strategies and identified the ways that immunization programs may be affected by availability gaps in supply linked to current vaccine production cycles and shelf life duration. Results of our analysis, which includes 54 eligible countries in 2015 for New Vaccine Support from Gavi, the Vaccine Alliance, suggest the demand for influenza vaccines could be 7.7 to 16.0 million doses in 2020, and 27.0 to 61.7 million doses by 2029. If current trends in production capacity and actual production of seasonal influenza vaccines were to continue, global vaccine supply would be sufficient to meet this additional demand-although a majority of countries would face implementation issues linked to timing of supply.


Effects of naproxcinod on blood pressure in patients with osteoarthritis.
Nonsteroidal anti-inflammatory drugs are associated with increases in blood pressure (BP), particularly in patients treated with antihypertensive therapy. Naproxcinod is a nitric oxide-donating cyclooxygenase inhibitor in development for osteoarthritis (OA). Thus, we characterized the effects of naproxcinod on BP in an integrated safety analysis of 3 pivotal trials of patients with OA of the hip or knee involving 2,734 patients. The changes from baseline in the systolic BP after 13 weeks of therapy with naproxcinod (375 and 750 mg), naproxen 500 mg (equipotent to naproxcinod 750 mg), or placebo twice daily were evaluated in all patients and in the subgroup taking renin-angiotensin system inhibitors. Heterogeneity testing showed no treatment-by-study interaction. The effects of naproxcinod 750 mg on the systolic BP was not different from placebo (mean change from baseline vs placebo -0.4 mm Hg, 95% confidence interval -1.6 to 0.8). Naproxen increased the systolic BP relative to placebo (mean change from baseline vs placebo +1.4 mm Hg, 95% confidence interval 0.1 to 2.7). In the renin-angiotensin system inhibitor-treated patients, the effect of naproxcinod 750 mg compared to naproxen 500 mg in the changes from baseline in the systolic BP was -4.3 mm Hg (95% confidence interval -8.5 to -0.0). In conclusion, naproxcinod had effects on BP similar to that of placebo in patients with OA. These results imply that naproxcinod would be less likely to alter systolic BP control in patients with OA than a conventional nonsteroidal anti-inflammatory drug, particularly in those treated with renin-angiotensin system inhibitor agents.


Evidence for the importance of genetic structuring to the structural and functional specialization of the Plasmodium falciparum var gene family.
The var gene family encodes Plasmodium falciparum erythrocyte membrane 1 (PfEMP1) proteins that act as virulence factors responsible for both antigenic variation and cytoadherence of infected erythrocytes. These proteins orchestrate infected erythrocyte sequestration from blood circulation and contribute to adhesion-based complications of P. falciparum malaria infections. For this study, we analysed the genetic organization and strain structure of var genes and present evidence for three separately evolving groups that have, in part, functionally diverged and differ between subtelomeric and central chromosomal locations. Our analyses suggest that a recombination hierarchy limits reassortment between groups and may explain why some var genes are unusually conserved between parasite strains. This recombination hierarchy, coupled with binding and immune selection, shapes the variant antigen repertoire and has structural, functional and evolutionary consequences for the PfEMP1 protein family that are directly relevant to malaria pathogenesis.


Effects of melatonin on peripheral nerve regeneration.
In the available literature, there are thousands of studies on peripheral nerve regeneration using many nerves of several animals at different ages with various types of lesions and different methods of evaluation at certain time of follow-up. Despite many experimental data and clinical observations, there is still no ideal treatment method enhancing peripheral nerve regeneration. In clinical practice, various types of surgical nerve repair techniques do not frequently result in complete recovery due to neuroma formation, lipid peroxidative damage, ischemia and other factors. Recently, a number of neuroscientists demonstrated that pineal neurohormone melatonin (MLT) has an effect on the morphologic features of the nerve tissue, suggesting its neuroprotective, free radical scavenging, antioxidative, and analgesic effects in degenerative diseases of peripheral nerves. At present, it is widely accepted that MLT has a useful effect on axon length and sprouting after traumatic events to peripheral nerves. Our studies using various experimental injury models clearly suggest positive effects of MLT on the number of axons, thickness of myelin sheath by inhibition of collagen accumulation and neuroma formation following traumatic events to peripheral nerves, myelination of developing peripheral nerve after intrauterine ethanol exposure. Nevertheless, further experimental and randomized controlled clinical studies are vital to identify the clinical use of MLT hormone. This is an overview of recent patents and current literature in terms of the effects of MLT on peripheral nerve regeneration based on a critical analysis of electrophysiological, biochemical and light and electron microscopic findings, in addition to functional observations.


Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2.
Lapatinib is active at the ATP-binding site of tyrosine kinases that are associated with the human epidermal growth factor receptor (Her-1 or ErbB1) and Her-2. It is conceivable that lapatinib may inhibit the function of ATP-binding cassette (ABC) transporters by binding to their ATP-binding sites. The aim of this study was to investigate the ability of lapatinib to reverse tumor multidrug resistance (MDR) due to overexpression of ABC subfamily B member 1 (ABCB1) and ABC subfamily G member 2 (ABCG2) transporters. Our results showed that lapatinib significantly enhanced the sensitivity to ABCB1 or ABCG2 substrates in cells expressing these transporters, although a small synergetic effect was observed in combining lapatinib and conventional chemotherapeutic agents in parental sensitive MCF-7 or S1 cells. Lapatinib alone, however, did not significantly alter the sensitivity of non-ABCB1 or non-ABCG2 substrates in sensitive and resistant cells. Additionally, lapatinib significantly increased the accumulation of doxorubicin or mitoxantrone in ABCB1- or ABCG2-overexpressing cells and inhibited the transport of methotrexate and E(2)17betaG by ABCG2. Furthermore, lapatinib stimulated the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. However, lapatinib did not affect the expression of these transporters at mRNA or protein levels. Importantly, lapatinib also strongly enhanced the effect of paclitaxel on the inhibition of growth of the ABCB1-overexpressing KBv200 cell xenografts in nude mice. Overall, we conclude that lapatinib reverses ABCB1- and ABCG2-mediated MDR by directly inhibiting their transport function. These findings may be useful for cancer combinational therapy with lapatinib in the clinic.


The effect of a nicotine patch on cigarette craving over the course of the day: results from two randomized clinical trials.
The objective of this analysis was to assess the efficacy of a 21 mg/24-h nicotine patch for the reduction of craving throughout the waking day, compared both to placebo, and to a 15 mg/16-h patch differing pharmacokinetic profile over the day. The primary end-point was craving during the evening hours, because previous research suggested that smoking relapse was particularly likely at that time. Data were drawn from two similar randomized clinical trials among nicotine-dependent smokers who were quitting smoking: Study 1 compared the 21 mg/24-h patch to a placebo patch, while Study 2 compared the 21 mg/24-h patch to a 15 mg/16-h nicotine patch. In both studies, subjects (Study 1: n = 102; Study 2: n = 244) were prompted by an electronic diary to rate their craving multiple times per day during a 1 week baseline period, and for up to 2 weeks after quitting. For analysis, the day was divided into five blocks: morning (up to 10:59 a.m.), mid-day (11:00 a.m.-1:59 p.m.), afternoon (2:00 p.m.-4:59 p.m.), evening (5:00 p.m.-8:59 p.m.), and late night (9:00 p.m. onwards). The individual craving ratings were divided into three intervals based on time since quitting: Days 1-3, 4-7, and 8-14. The 21 mg/24-h nicotine patch resulted in significantly lower craving during all post-quit intervals, at each time of day, both compared to placebo (Study 1), and compared to the 15 mg/16-h nicotine patch (Study 2). Study 2 saw a significant treatment by interval interaction: in later time intervals, the difference in craving experience between 24- and 16-h patch conditions shrunk--while remaining significantly different--as overall levels of craving experienced by subjects in the two groups dropped. Adverse events reported in both studies tended to be mild and transient, consistent with the well characterized adverse event profile of nicotine patches. Study 1 demonstrated that a 21 mg/24-h patch was effective in reducing craving throughout the day, including the evening period when relapse risk is heightened. A further study comparing the 21 mg/24-h patch to a 15 mg/16-h nicotine patch found that craving was significantly lower at all times of day for smokers using the 21 mg/24-h patch. The studies were limited in that craving was only monitored for the first 2 weeks of quitting (when craving is most prominent), and cannot elucidate the impact of patch use on craving outside of this time. Also, there was substantial attrition of the sample over time, partly due to relapse in all conditions.


Clinical outcome of en-block resection and reconstruction with nonvascularized fibular autograft for the treatment of giant cell tumor of distal radius.
Although giant cell tumor (GCT) is considered to be a primary benign bone tumor, its aggressive behavior makes its diagnosis and treatment, difficult and challenging. This is especially true in distal radius where GCT appears to be more aggressive and difficult to control locally. We report our clinical outcome of en-block resection and reconstruction with non-vascularized fibular autograft in 15 patients with distal radius GCT. We retrospectively reviewed 15 patients with GCT (Grade 2 and 3) of distal radius who were treated with en-block resection and non-vascularized fibular autograft. Five of 15 were recurrent GCT treated initially with extended curettage; local adjuvant therapy and filling the cavity with cement or bone graft. We followed the patients for mean 7.2 years post operation (range: 4-11 years). Patients were evaluated post operation with clinical examination, plain radiography of distal radius and chest X-ray and/or computed tomography scan. Furthermore pain, function, range of motion and grip strength of the affected limb were evaluated and mMayo wrist score was assessed. A total of 11 patients were women and 4 were men. Mean age of patients was 29 years (range: 19-48). We had no lung metastasis and bony recurrence occurred in one patient (6.6%). Nearly 53.3% of patients had excellent or good functional wrist score, 80% of the patients were free of pain or had only occasional pain and 80% of patients returned to work. Mean range of motion of the wrist was 77° of flexion-extension and mean grip strength was 70% of the normal hand. En-block resection of distal radius GCT and reconstruction with non-vascularized fibular autograft is an effective technique for treatment in local control of the tumor and preserving function of the limb.


Congenital granular cell lesion in newborn mandible.
Congenital granular cell lesion (CGCL) is a rare non-neoplastic lesion found in newborns also known as Neumann's tumor. This benign lesion occurs predominantly in females mostly as a single mass. The histogenesis and natural history of the lesion remains obscure. It arises from the mucosa of the gingiva, either from the maxillary or mandibular alveolar ridge. The lesion is more common in the maxillary alveolar ridge than the mandibular.The present report describes a case of congenital granular cell lesion in an eight-day-old female child who was born with a mass on the anterior mandibular alveolar ridge. The mass was protruding from her mouth and compromised feeding. A clinical diagnosis of teratoma was suggested. Histologically, cells of this lesion are identical to granular cell tumor (neuroectodermal type) and show intense diastase-resistant Periodic Acid Schiff positivity. Immunohistochemically, cells are positive for vimentin but negative for S-100 and desmin, thus suggesting that CGCL is possibly derived from primitive gingival mesenchymal cells rather than having schwannian origin.


Accumulation of irrigation fluid in the calf as a complication during high tibial osteotomy combined with simultaneous arthroscopic anterior cruciate ligament reconstruction.
Extravasation of irrigation fluid during arthroscopy is a well-known complication. We report a case of accumulation of fluid into the calf during open wedge high tibial osteotomy combined with simultaneous arthroscopic anterior cruciate ligament (ACL) reconstruction. The main cause for fluid extravasation was the drilling of the tibial tunnel, which allowed the fluid to cross the osteotomy gap and invade the flexor compartments. Although an elevation of the intracompartmental pressure was measured, there was no clinical evidence of compartment syndrome. A subcutaneous release of the flexor compartment of the leg was performed. The patient suffered no further sequelae. High tibial osteotomy combined with simultaneous arthroscopic ACL reconstruction has to be performed carefully, and potential complications must be detected immediately to prevent compartment syndrome.


Antibiotic innovation may contribute to slowing the dissemination of multiresistant Streptococcus pneumoniae: the example of ketolides.
Despite increasingly frequent bacterial resistance to antibiotics, antibacterial innovation is rare. Ketolides constitute one of the very few new antibiotic classes active against Streptococcus pneumoniae developed during the last 25 years. Their mechanism of action resembles that of macrolides, but they are unaffected by common resistance mechanisms. However, cross-resistance to ketolides has been observed in some macrolide-resistant strains. We examined how new antibiotic exposure may affect overall pneumococcal resistance patterns in the population. The aims of this study were to assess the potential dissemination of newly emerged resistances and to control the selection of strains already multiresistant to existing antimicrobials. We developed an age-structured population model for S. pneumoniae transmission in a human community exposed to heptavalent vaccine, and beta-lactams, macrolides and ketolides. The dynamics of intra-individual selection of resistant strains under antibiotic exposure and interindividual transmission were simulated, with antibiotic-specific resistance mechanisms defining the path to co-resistances and cross-resistances, and parameters concerning the French situation. Results of this simulation study suggest that new antibiotic consumption could markedly slow the diffusion of multiresistant strains. Wider use was associated with slower progression of multiresistance. When ketolides were prescribed to all ages, resistance to them reached 10% after >15 years, while it took >40 years when they were prescribed only to adults. In the scenario according to which new antibiotics totally replaced former antimicrobials, the beta-lactam resistance rate was limited at 70%. In a context of widespread vaccination and rational use of antibiotics, innovative antibiotic, prescribed to all age groups, may have an added impact on multiresistant-strain dissemination in the population.


pH-dependent behavior of surface-immobilized artificial leucine zipper proteins.
The coiled-coil protein motif occurs in over 200 proteins and has generated interest for a range of applications requiring surface immobilization of the constituent peptides. This paper describes an investigation of the environment-responsive behavior of a monolayer of surface-immobilized artificial proteins, which are known to assemble to form coiled-coil structures in bulk solution. An extended version of the quartz crystal microbalance (QCM-D) and surface plasmon resonance (SPR) are independently employed to characterize the adsorption of the proteins to a gold surface. The data suggest that the molecules arrange in a closely packed layer orientated perpendicular to the surface. QCM-D measurements are also employed to measure pH-induced changes in the resonant frequency (f) and the energy dissipation factor (D) of a gold-coated quartz crystal functionalized with the formed monolayer. Exposure of the protein monolayer to a pH 4.5 solution results in a shift of 43 Hz in f and a shift of -0.7 x 10(-6) in D as compared to pH 7.4. In contrast, increasing the pH to 11.2, results in f and D shifts of -17 Hz and 0.6 x 10(-6), respectively. The magnitude of the observed shifts suggests that the proteins form a rigid layer at low pH that can be hydrated to a fluid layer as the pH is increased. These observations correlate with spectroscopic changes that indicate a reduction in the helical content of the protein in bulk solutions of high pH.