Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury.
This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and α-smooth muscle actin (α-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+) and PECAM-1(+) cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic-ischemic brain injury.


[Awareness of illness in patients with schizophrenia: theoretical insights and a proposal for treatment].
The percentage of persons with schizophrenia who have only a limited insight into their illness is rather large (50–80%); this has a negative impact on specific outcomes. Up till now there has not been a universal model that can explain this limited insight. Furthermore, there is a lack of treatment options and interventions likely to improve patients' insight into their illness. To provide an overview of the literature on insight of patients into their illness and suggest a model for treatment. In this essay we review the literature dealing with the insight of patients with schizophrenia and thereafter we discuss the correlates of insight (illness variables as well as outcomes), theoretical models of insight and current treatment of options. On the basis of the literature we propose a new theoretical model which incorporates factors from earlier models and which aims to improve patients' insight into their illness. Using the preconditions for insight specified in our models (namely, sensitivity to stigma, seeing the illness in perspective, mental flexibility and self-reflection) we have developed a new treatment (reflex) for improving the insight of persons with schizophrenia. The treatment will be evaluated in the course of the next two years at eight centres in the Netherlands providing treatment for persons with schizophrenia; the evaluation should tell us whether the proposed treatment is effective in increasing patient's insight into their illness.


Molecular correlates of experimental cerebral malaria detectable in whole blood.
Cerebral malaria (CM) is a primary cause of deaths caused by Plasmodium falciparum in young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using the Plasmodium berghei ANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, β-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathione S-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation in P. falciparum-infected young African children as diagnostic markers of CM.


[Liposuction as a treatment for Launois Bensaude disease].
Launois Bensaude disease is a widespread symmetrical lipomatosis with a head-neck-trunk predominance. Its pathogeny is unknown and its treatment, basically surgical, is aggressive, difficult and even exasperating as a result of the large amount of noticed relapses.


N-of-1 Trials in Pediatric Oncology: From a Population-Based Approach to Personalized Medicine-A Review.
Pediatric oncology is a critical area where the more efficient development of new treatments is urgently needed. The speed of approval of new drugs is still limited by regulatory requirements and a lack of innovative designs appropriate for trials in children. Childhood cancers meet the criteria of rare diseases. Personalized medicine brings it even closer to the horizon of individual cases. Thus, not all the traditional research tools, such as large-scale RCTs, are always suitable or even applicable, mainly due to limited sample sizes. Small samples and traditional versus subject-specific evidence are both distinctive issues in personalized pediatric oncology. Modern analytical approaches and adaptations of the paradigms of evidence are warranted. We have reviewed innovative trial designs and analytical methods developed for small populations, together with individualized approaches, given their applicability to pediatric oncology. We discuss traditional population-based and individualized perspectives of inferences and evidence, and explain the possibilities of using various methods in pediatric personalized oncology. We find that specific derivatives of the original N-of-1 trial design adapted for pediatric personalized oncology may represent an optimal analytical tool for this area of medicine. We conclude that no particular N-of-1 strategy can provide a solution. Rather, a whole range of approaches is needed to satisfy the new inferential and analytical paradigms of modern medicine. We reveal a new view of cancer as continuum model and discuss the "evidence puzzle".


A disciplined approach to implementation of evidence-based practices decreases ICU and hospital length of stay in traumatically injured patients.
Evidence-based medicine has gained wide acceptance in practice of medicine since the 1990s. The objective of our study was to demonstrate the effect of evidence-based critical care practices on ICU and hospital length of stay in mechanically ventilated trauma patients. Retrospective cohort using historic controls. During 2004, several different evidence-based practices were implemented, including low tidal volume ventilation, protocol driven trauma resuscitation, and a sepsis bundle. Outcomes in critically ill, mechanically ventilated patients who were ≥ 18 y old were compared between a historic control group (2000-2003) and the study group after implementation (2005-2008). Patients were identified using the institutional trauma registry (NATIONAL TRACS). Gender, age, ISS, mechanism of injury, and mortality were also examined to identify trends in epidemiology. From 2000 to 2003. there were 6920 trauma admissions and during 2005-2008 there were 8911 (increase of 28.8%). These included 217 and 337 (increase of 55.3%) admissions to the ICU of mechanically ventilated patients, respectively. The mean age was 43.9 y versus 45.9 y (P = 0.258). Males were 66.4% versus 71.8% (P = 0.610). The mean ISS was 29 versus 27 (P = 0.25). Blunt mechanism was 87% versus 89% (P = 0.913). Mortality rate was 36.4% versus 36.5% (P = 0.944). The mean number of ICU days and hospital days decreased from 7.6 versus 5.5 (P = 0.02) and 13.2 versus 9.7 (P = 0.03), respectively. The application of evidence-based critical care practices decreases length of ICU and hospital stay, but not mortality, in critically ill, mechanically ventilated trauma patients. Our trauma volume, including critically ill patients, increased during the study periods.


Hematopoietic stem cell transplantation for follicular lymphoma: optimal timing and indication.
The definitive management of advanced follicular lymphoma (FL) remains controversial due to various treatment options, including watchful waiting, single-agent or combination chemotherapy, monoclonal antibody, and radioimmunotherapy. These options can provide prolonged progression-free survival. However, they cannot cure advanced FL. Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the sole curative therapy for FL. Allo-SCT has had a major impact with the use of reduced-intensity conditioning regimens because of its lower associated nonrelapse mortality compared with myeloablative regimens. Autologous SCT (auto-SCT) shows high response rates and extends progression-free survival in patients with chemosensitive relapse. In the rituximab era, however, associated comorbidities, risk of secondary cancers, and presence of refractory disease have become problematic in the auto-SCT population. On the basis of results from large-scale randomized trials, upfront auto-SCT is not recommended. Novel conditioning regimens including radioimmunotherapy followed by either auto-SCT or allo-SCT are likely to show efficacy even in chemorefractory disease. Consequently, the optimal timing for SCT remains a matter of opinion, except for patients in first remission. However, the outcomes of allo-SCT and auto-SCT keep on improving. Physicians should note that there is no therapy with a track record equivalent to that of SCT for relapsed or refractory FL.


Binding of anisotropic curvature-inducing proteins onto membrane tubes.
Bin/Amphiphysin/Rvs superfamily proteins and other curvature-inducing proteins have anisotropic shapes and anisotropically bend biomembranes. Here, we report how the anisotropic proteins bind the membrane tube and are orientationally ordered using mean-field theory including an orientation-dependent excluded volume. The proteins exhibit a second-order or first-order nematic transition with increasing protein density depending on the radius of the membrane tube. The tube curvatures for the maximum protein binding and orientational order are different and varied by the protein density and rigidity. As the external force along the tube axis increases, a first-order transition from a large tube radius with low protein density to a small radius with high density occurs once, and subsequently, the protein orientation tilts to the tube-axis direction. When an isotropic bending energy is used for the proteins with an elliptic shape, the force-dependence curves become symmetric and the first-order transition occurs twice. This theory quantitatively reproduces the results of meshless membrane simulation for short proteins, whereas deviations are seen for long proteins owing to the formation of protein clusters.


Twelve Tips for COVID-19 friendly learning design in medical education.
This article was migrated. The article was marked as recommended. The COVID-19 pandemic has caused educational institutions around the world to close their doors and move their teaching and learning into the online space. For many medical educators, who usually rely on face-to-face and blended instruction, this presents a challenge. By rethinking learning design, medical educators can ensure a smooth transition of their subjects into the online space. However, because of the immersive nature of medical education, not all teaching and learning activities can be delivered online. This paper outlines twelve tips using evidence-based educational practices and a student-centred approach. The twelve tips presented and discussed in this paper can help medical educators to transition to online learning and maintain the integrity of their subjects. They can also promote student self-regulation, help develop graduate attributes, and generally enhance learning experiences during pandemic social distancing. Finally, these tips can be used to rethink medical education in the post-pandemic era.


Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia.
Patients with relapsed acute myeloid leukemia (AML) have limited therapeutic options. Vesicular stomatitis virus (VSV)-interferon β (IFNβ)-sodium iodide symporter (NIS) is an oncolytic VSV encoding IFNβ and the NIS reporter. Syngeneic AML C1498 tumors responded to IV therapy with VSV-murine IFNβ (mIFNβ)-NIS in a dose-dependent manner. Imaging for NIS expression showed robust virus infection within the tumors. Virus infection did not increase programmed death ligand 1 (PD-L1) on tumor cells. Combining VSV-mIFNβ-NIS with anti-PD-L1 antibody (Ab) therapy enhanced antitumor activity compared with treatment with virus alone or Ab alone; this enhancement was not significant at higher VSV-mIFNβ-NIS doses. Systemic VSV therapy reduced systemic C1498-green fluorescent protein (GFP) tumor burden in the blood, bone marrow, spleen, and liver of mice with AML. Combination VSV-mIFNβ-NIS and anti-PD-L1 Ab therapy significantly enhanced the survival of these mice with no evidence of toxicity, compared with isotype control, anti-PD-L1, or virus alone. There was an increase in tumor-infiltrating CD4 and CD8 cells. Single-agent VSV-mIFNβ-NIS virotherapy induced both VSV-specific and GFP-specific CD8 T cells as determined by IFN-γ enzyme-linked immunospot, pentamer, and intracellular IFN-γ staining assays. Both of these responses were further enhanced by addition of anti-PD-L1 Ab. Depletion of CD8 or natural killer cells, but not CD4 cells, resulted in loss of antitumor activity in the VSV/anti-PD-L1 group. Clinical samples from chronic myelomonocytic leukemia and acute myelomonocytic leukemia appear to be especially susceptible to VSV. Overall, our studies show that oncolytic virotherapy combined with immune checkpoint blockade is a promising approach to AML therapy.


Online processing of native and non-native phonemic contrasts in early bilinguals.
There is considerable debate about whether bilinguals can distinguish L2 phonemic contrasts as efficiently as first language speakers can. To test this issue, a group of highly proficient Spanish-dominant Catalan-Spanish bilinguals (who had been exposed to Catalan between the ages of 3 and 4, but who, previous to this age, had been exposed only to Spanish) and another group of Catalan-dominant bilinguals (who had been exposed to Catalan from birth) were compared in a gating task. We developed a variation of the gating procedure that included a two-alternative forced choice test after each fragment was played. The differences between the two alternatives consisted of phonemic contrasts existing in Catalan but not in Spanish. Four contrasts were tested: two vocalic contrasts [symbols: see text] and two consonantal contrasts [symbols: see text]. The results showed that Spanish-dominant bilinguals, even the subset who were able to make correct identifications at the last gate, systematically performed worse than the group of Catalan-dominant bilinguals, needing longer portions of the signal to be able to correctly identify the stimuli. We argue that these results support the hypothesis that L1 shapes the perceptual system at early stages of development in such a way that it will determine the perception of non-native phonemic contrasts, even if there is extensive and early exposure to L2.


In vitro activities of novel oxapenems, alone and in combination with ceftazidime, against gram-positive and gram-negative organisms.
Four novel oxapenem compounds (i.e., AM-112, AM-113, AM-114, and AM-115) were investigated for their beta-lactamase inhibitory activity against a panel of isolated class A, C, and D enzymes, which included expanded-spectrum beta-lactamase enzymes (ESBLs). The oxapenems were potent beta-lactamase inhibitors. Activity varied within the group, with AM-113 and AM-114 proving to be the most active compounds. The 50% inhibitory concentrations for these agents were up to 100,000-fold lower than that of clavulanic acid against class C and D enzymes. As a group, the oxapenems were more potent than clavulanic acid against enzymes from all classes. The ability of these compounds to protect ceftazidime from hydrolysis by beta-lactamase-producing strains was evaluated by MIC tests that combined ceftazidime and each oxapenem in a 1:1 or 2:1 ratio. The oxapenems markedly reduced the MICs for ceftazidime against class C hyperproducing strains and strains producing TEM- and SHV-derived ESBLs. There was little difference between the activity of 1:1 and 2:1 combinations of ceftazidime and oxapenem. The oxapenems failed to enhance the activity of ceftazidime against derepressed AmpC-producing Pseudomonas aeruginosa strains.


Role of nifedipine in treatment of hypertension.
The efficacy of nifedipine in the treatment of hypertension was assessed in 15 patients whose hypertension continued while being treated with atenolol 100 mg and bendrofluazide 5 mg daily. Nifedipine was added in doses of 10, 20, and 30 mg three times daily in a placebo controlled, double blind trial. One patient was withdrawn from the trial because of severe postural hypotension with the highest dose. Erect and supine blood pressure in the remaining 14 patients were significantly reduced by all doses of nifedipine. The drug was well tolerated but plasma potassium fell by 0.3 mmol(mEq)/1 during treatment (p less than 0.05). Nifedipine is thus effective in the treatment of hypertension but should probably be used in combination with a potassium sparing diuretic.


Cyanotic congenital heart disease the coronary arterial circulation.
The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.


Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha-chaconine, in the Syrian Golden hamster.
Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute intoxication, coma, and death when consumed in high amounts. These effects have been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha-chaconine, naturally present in all potatoes. The level of GAs in potato tubers has previously been shown to increase substantially as a result of improper handling and postharvest storage. A short-term study was performed to investigate the dose-response profile of alpha-solanine and alpha-chaconine alone or in combination, administered daily by oral gavage to Syrian Golden hamsters. Daily doses of 100 mg of alpha-solanine [kg body weight (BW)] (-1) induced death in two of four hamsters within 4 days, when administered by gavage to female Syrian hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha-chaconine combined in a ratio of 1:2.5, in doses of 75 or 100 mg (kg BW) (-1), induced death in one of four hamsters within the same period. Animals dosed with alpha-solanine alone or in combination with alpha-chaconine suffered from fluid-filled and dilated small intestines. The GA administration had no effect on acetyl cholinesterase (AChE) or butyryl cholinesterase (BuChE) activity in plasma or brain. Liquid chromatography-mass spectrometry-based metabolomics showed that there was a specific accumulation of alpha-chaconine in the liver tissues. In addition, metabolomics gave direct evidence of glycolytic metabolism of the GA with the beta 1, beta 2, and gamma-GAs detected in the urine and, to a lesser extent, the feces. Doses from 75 mg (kg BW) (-1) of alpha-chaconine, alpha-solanine, or the two compounds combined were potentially lethal within 4-5 days in the Syrian Golden hamster. However, the cause of death in these studies could not be established. No synergistic effects of alpha-solanine combined with alpha-chaconine were evident.


Dietary induction of mulberry heart disease and hepatosis dietetica in pigs. I. Nutritional aspects.
Two trials were conducted, involving 48 Yorkshire specific pathogen-free pigs, three to four weeks old, to investigate diets which would result in a high incidence of deaths from mulberry heart disease and hepatosis dietetica in pigs. Diets based on ground corn with torula yeast resulted in a high incidence of death. Protein supplements of dried skim milk or soybean meal with corn did not induce a high incidence of death. Diets supplemented with torula yeast had the lowest selenium concentration and highest (alpha-)tocopherol concentration of the diets investigated and resulted in lower liver selenium concentrations. A higher frequency of hepatosis dietetica, mulberry heart disease, skeletal muscle degeneration and exudative diathesis was observed in pigs fed the low level selenium diets containing torula yeast.


Cognitive, clinical, and functional characteristics of verbally superior schizophrenia patients.
The existence of small numbers of schizophrenia patients with superior ability in specific cognitive domains is implied by meta-analytic evidence as well as by occasional empirical reports. The authors identified 25 patients with superior (i.e., > or =90th percentile) ability on the Vocabulary subtest of the Wechsler Adult Intelligence Scale 3rd edition (Wechsler, 1997). These cognitively advantaged patients were compared with 22 healthy participants performing at the superior level and with 126 schizophrenia patients and 50 healthy participants scoring below the superior range. Verbally superior schizophrenia patients and verbally superior healthy participants had similar cognitive profiles and life skills performance, but diverged markedly in terms of independent "real-world" functioning. Verbally superior patients significantly outperformed more typical patients in other aspects of cognitive performance, life skills, and support requirements. However, severity of positive and negative symptoms was equivalent in the patient groups. Detailed biobehavioral study of cognitively exceptional patients may offer new insights into mechanisms mediating psychotic disorders.


Road safety situation of electric bike riders: A cross-sectional study in courier and take-out food delivery population.
Almost all courier and take-out food delivery riders in China use electric bikes as the main transport mode. This study aims to understand their riding behaviors and road traffic injury information of this population. A cross-sectional field study focused on this population was conducted, including roadside observation and face-to-face retrospective street intercept interviews. Six hundred target delivery riders were observed and 480 were interviewed. The rate of overspeeding was 91.3%, and windshield use during winter was 91.2%. Traffic violation behaviors observed included riding in the motor vehicle lane (32.8%), not waiting behind the white line at a red light (23.3%), and using cell phone when riding (21.2%). Helmet use was significantly more common during the day (73.0%) than at night (64.7%; P = .028). About 46.5% of respondents rode an e-bike more than 8 h per day. In addition, 76.5% of interviewees had been involved in a traffic crash at least once. About 13.9% of crashes happened in motor vehicle lanes and 8.2% on sidewalks. Logistic regression analysis indicated that compared with uninjured riders, injured riders showed significantly greater odds ratios of unsafe behaviors for running red lights (odds ratio [OR] = 1.75) and protective factors for wearing a helmet (OR = 0.56). The courier and take-out food delivery population is a vulnerable occupational group and road traffic injuries related to e-bike use require more attention.


False Immunosuppressant Measurement by LC-MS/MS Method Due to Radiopaque Agents.
Although liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is preferred as a reliable method, some molecules in the blood matrix may lead to false positive or false negative results. False positive or negative results show the direction of the deviation rate from the target value. The aim of this study was to investigate the effect of seven different radiopaque agents on four immunosuppressant drugs. Every agent coded with RM1 to RM7 was added to control materials containing tacrolimus, everolimus, sirolimus, and cyclosporine A drugs. Measurements were performed using an LC-MS/MS instrument. Bias values were calculated to detect the deviation rates. All RMs led to false negative results in the tacrolimus and cyclosporine A levels at a rate of -19.77% (95% CI, -27.16 to 12.52) to -44.45% (95% CI, -49.20 to -39.69). The smallest deviations were seen in the everolimus levels with the administration of RM6 (gadodiamide) and in the sirolimus levels with RM1 (gadobutrol) at the rates of 4.04% (95% CI, -11.36 to -3.17) and 2.11% (95% CI, -7.18 to 7.11), respectively. The most affected drug by RM4 (gadopentetate dimeglumine salt) was sirolimus at the rate of 114.01% (95% CI, 97.31 - 130.76). RM5 (gadodiamide) interfered cyclosporine A at the most. The highest deviations were observed with the administration of RM3 (iohexol) in the everolimus and sirolimus levels at the rates of 153.72% (95% CI, 142.44 to 164.78) and 171.41% (95% CI, 157.91 to 184.97), respectively. Radiopaque agents interfered the measurement of immunosuppressant drugs. Especially, everolimus and sirolimus levels were affected due to using iohexol. The choice of gadodiamide or ioversol is important to reduce the risk of interference for everolimus measurement. The blood samples should be obtained for measurement of drug levels before contrast-enhanced imaging.


The recent development of carbon-based nanoparticles as a novel approach to skin tissue care and management - A review.
Since the skin is the first barrier of the body's defense against pathogens, delays in the healing process are affected by infections. Therefore, applying advanced substitute assistance improves the patient's quality of life. Carbon-based nanomaterials show better capabilities than conventional methods for managing skin wound infections. Due to their physicochemical properties such as small size, large surface area, great surface-to-volume ratio, and excellent ability to communicate with the cells and tissue, carbon-based nanoparticles have been considered in regenerative medicine. moreover, the carbon nano family offers attractive potential in wound healing via the improvement of angiogenesis and antibacterial compared to traditional approaches become one of the particular research interests in the field of skin tissue engineering. This review emphasizes the wound-healing process and the role of carbon-based nanoparticles in wound care management interaction with tissue engineering technology.


A germin-like protein gene (CchGLP) of Capsicum chinense Jacq. is induced during incompatible interactions and displays Mn-superoxide dismutase activity.
A germin-like gene (CchGLP) cloned from geminivirus-resistant pepper (Capsicum chinense Jacq. Line BG-3821) was characterized and the enzymatic activity of the expressed protein analyzed. The predicted protein consists of 203 amino acids, similar to other germin-like proteins. A highly conserved cupin domain and typical germin boxes, one of them containing three histidines and one glutamate, are also present in CchGLP. A signal peptide was predicted in the first 18 N-terminal amino acids, as well as one putative N-glycosylation site from residues 44-47. CchGLP was expressed in E. coli and the recombinant protein displayed manganese superoxide dismutase (Mn-SOD) activity. Molecular analysis showed that CchGLP is present in one copy in the C. chinense Jacq. genome and was induced in plants by ethylene (Et) and salicylic acid (SA) but not jasmonic acid (JA) applications in the absence of pathogens. Meanwhile, incompatible interactions with either Pepper golden mosaic virus (PepGMV) or Pepper huasteco yellow vein virus (PHYVV) caused local and systemic CchGLP induction in these geminivirus-resistant plants, but not in a susceptible accession. Compatible interactions with PHYVV, PepGMV and oomycete Phytophthora capsici did not induce CchGLP expression. Thus, these results indicate that CchGLP encodes a Mn-SOD, which is induced in the C. chinense geminivirus-resistant line BG-3821, likely using SA and Et signaling pathways during incompatible interactions with geminiviruses PepGMV and PHYVV.


Database Structure and Manipulation Capabilities of a Picture Database Management System (PICDMS).
The database structure and data manipulation capabilities of a generalized PICture Database Management System (PICDMS) are presented. They are based on a dynamic, stacked-image, logical database structure that uses gridded, rather than topological, data representation. A prototype PICDMS has been designed and implemented. A commercial version is being used as a generator of image processing programs. The system has novel capabilities for nonprogrammer users: it is able to 1) build multiple-variable databases from photographs and other two-dimensional data sources such as maps, drawings, etc., and 2) manipulate such data using simple logical commands. Physical organization and accessing strategies are outlined. A summary of the PICDMS data manipulation capabilities is presented and a subset of operations is illustrated with brief examples. A comprehensive example displays PICDMS capabilities and the programming advantages it possesses over other approaches.


The NHS visitor and migrant cost recovery programme - a threat to health?
In April 2014 the UK government launched the 'NHS Visitor and Migrant Cost Recovery Programme Implementation Plan' which set out a series of policy changes to recoup costs from 'chargeable' (largely non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced. There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP. We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13-1.66, p value 0.001). Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally.


Breast cancer risk and oral contraceptive use: results from a large case-control study.
The association between oral contraceptive use and breast cancer risk was examined using data from a case-control study of breast cancer in Long Island, New York. Cases were defined as female residents of Nassau and Suffolk Counties between the ages of 20 and 79, diagnosed with breast cancer between January 1, 1984 and December 31, 1986. Age- and county-matched controls were selected from driver's license files. Among all women under age 70 at diagnosis, there was no association between oral contraceptive use and breast cancer; there was, however, a positive association in the subgroup ages 20-49 (adjusted odds ratio = 1.68, 95% CI: 1.16-2.42). Risk increased with increasing duration of use, but did not differ between women who first used oral contraceptives before the first pregnancy and those who first used them later, or between women who first used oral contraceptives before age 25 and those who first used them at a later age. Risk also appeared to increase with number of years of use before the first pregnancy or before age 25, although numbers were small. History of benign breast disease did not influence risk. The association of breast cancer risk with oral contraceptive use appeared stronger in women from Suffolk County than Nassau County.


Influence of temperature and headgroup size on condensed-phase patterns in langmuir monolayers of some oxyethylenated nonionic surfactants.
The surface phase behavior in Langmuir monolayers of some oxyethylenated nonionic surfactants of the general formula C16En, with n = 1, 2, 3, and 4, at the air-water interface has been studied by film balance and Brewster angle microscopy (BAM) over a wide range of temperatures. The C16E4 monolayers cannot show any indicative features of phase transition because of strong dipolar as well as hydration-induced repulsive interactions between the bulky headgroups. On the other hand, the monolayers of C16E1, C16E2, and C16E3 show a sharp cusp point followed by a pronounced plateau region in their respective isotherms with subsequent formation of a variety of structures in the two-phase coexistence region between the liquid expanded (LE) and liquid condensed (LC) phases at different temperatures. As usually observed, the domains of C16E1, which bears only one ethylene oxide (EO) unit in the headgroup, are circular at lower temperatures while fractal at higher temperatures. On the other hand, those for C16E2 and C16E3 are initially found to be irregular structures, which attain increasingly compact shape with increasing temperature, and finally become circular when the subphase temperature is 26 and 15 degrees C for C16E2 and C16E3, respectively. It is concluded that a higher degree of dehydration around the headgroup region appreciably reduces the headgroup size, which imparts to the molecules an increase in hydrophobicity, thereby a closer molecular packing. Consequently, the line tension of the interface increases, showing compact structures at higher temperatures. Since C16E1 bears only one EO unit in its headgroup, the dehydration effect cannot appreciably raise its hydrophobicity to overcome the increases in thermal motion and chain flexibility of the molecules. Rather, increases in subphase temperature result in a decrease in the line tension of the interface, giving fractal structures at higher temperatures.


In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival.
Livers from controlled donation after circulatory death (DCD) donors suffer a higher incidence of nonfunction, poor function, and ischemic cholangiopathy. In situ normothermic regional perfusion (NRP) restores a blood supply to the abdominal organs after death using an extracorporeal circulation for a limited period before organ recovery. We undertook a retrospective analysis to evaluate whether NRP was associated with improved outcomes of livers from DCD donors. NRP was performed on 70 DCD donors from whom 43 livers were transplanted. These were compared with 187 non-NRP DCD donor livers transplanted at the same two UK centers in the same period. The use of NRP was associated with a reduction in early allograft dysfunction (12% for NRP vs. 32% for non-NRP livers, P = .0076), 30-day graft loss (2% NRP livers vs. 12% non-NRP livers, P = .0559), freedom from ischemic cholangiopathy (0% vs. 27% for non-NRP livers, P < .0001), and fewer anastomotic strictures (7% vs. 27% non-NRP, P = .0041). After adjusting for other factors in a multivariable analysis, NRP remained significantly associated with freedom from ischemic cholangiopathy (P < .0001). These data suggest that NRP during organ recovery from DCD donors leads to superior liver outcomes compared to conventional organ recovery.


Generation of idiotype-specific T cell help through network perturbation.
Different manipulations of BALB/c mice were used to generate idiotype-specific help: neonatally induced suppression of the T 15 idiotype and low-dose priming with anti-T15 antibody. The splenic foci culture system was used to study T15-idiotype-recognizing helper T cells under limiting-cell-dose conditions. These treatments induced T15 idiotype-specific help for B cells responding to TNP-T15. Normal or hemocyanin-primed BALB/c mice did not supply T15 idiotype-specific help. The helper cells were sensitive to anti-Thy-1.2 and complement treatment and can distinguish T15 from an idiotype-different, PC-binding myeloma protein, M167, and the TNP binding myeloma protein, M460. These data show that idiotype-specific T helper cells can be induced by at least two different manipulations of the idiotype network. These manipulations presumably do not act directly on the T15-recognizing T cells, but must involve complementary idiotypic circuits that stimulate anti-T15 specific T cells. Furthermore, this study demonstrates that the splenic-fragment culture technique provides a general method to investigate, at the single cell level, idiotypic T-B cell interactions induced by perturbations of the immune network.


[Effect of purified sewage on the composition of carcinogenic polycyclic aromatic hydrocarbons in the soil and vegetation].
Concentrations of benz(a)pyrene (BP) and 15 other polycyclic aromatic hydrocarbons (PAH) in soil with forage plants (lucerne) irrigated by biologically purified mixed domestic and industrial (coke-chemical) sewage from collection pond did not exceed those in control soil (irrigated by relatively clean fresh water) and were lower than in nonirrigated one, which is due, probably, to PAH oxidation by soil-proper microflora activated in humid soil polluted by PAH. BP content in control and experimental samples of lucerne coincide within +/- 25% limits.


Slc11a1 (formerly Nramp1) and susceptibility to canine visceral leishmaniasis.
Visceral leishmaniasis is the most important zoonosis in Europe and it is caused by Leishmania infantum, a protozoan intracellular parasite. Canine visceral leishmaniasis (CVL) is endemic in the Mediterranean basin, Middle East, and South America, and is emerging within non endemic areas such as the United Kingdom and North America. We have analyzed 24 polymorphisms in the canine Slc11a1 (formerly NRAMP1) gene: 19 new polymorphisms characterized by direct sequencing from 40 dogs of different breeds and five polymorphisms previously described. Data analysis in a case-control study including 164 dogs of 19 different breeds revealed that two of the 24 polymorphisms were associated with increased risk for CVL: one intronic single nucleotide polymorphism (SNP) (A4549G in intron 6: odds ratio (OR) = 6.78, P = 0.001) and one silent SNP in exon 8 (C4859T: OR = 13.44, P = 0.004). In silico analysis of the significant SNP revealed that SNP in the promoter region affect putative transcription binding sites and SNP C4859T in exon 8 disrupts a putative exonic splicing enhancer (ESE). These results corroborate that Slc11a1 polymorphisms are associated with increased risk for CVL.


Moderate anemia at diagnosis is an independent prognostic marker of the EUTOS, Sokal, and Hasford scores for survival and treatment response in chronic-phase, chronic myeloid leukemia patients with frontline imatinib.
This study aimed to examine the prognostic value of anemia for the diagnosis of chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib. One hundred and fifty-four CML-CP patients were enrolled. The influences of moderate anemia with hemoglobin (Hb) < 10 g/dl, four scoring systems, and the early molecular response at 3 months (BCR-ABL ≤10%; 3M-EMR) on the achievement of a deep molecular response (DMR, MR4.5), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) were compared. Moderate anemia was identified in 44 (28.6%) patients. These patients had more aggressive baseline features and higher risks, as assessed by scoring systems, and less favorable treatment responses vs those without anemia, including 3M-EMR (50.0% vs 69.1%), a complete cytogenetic response at 6 months (20.5% vs 50.9%), and a major molecular response at 12 months (22.5% vs 45.2%), with a median follow-up of 54.0 months. Furthermore, an Hb of 10 g/dl better distinguished DMR, EFS, PFS, and OS than the EUTOS, Sokal, and Hasford scores, and better predicted the responses and survivals in combination with 3M-EMR than 3M-EMR alone. This finding highlights the significance of anemia in CML-CP, and suggests that patients with anemia at diagnosis should be carefully monitored and might benefit from more potent TKIs if not achieving 3M-EMR.


Impact of feed intake in early gestation on maternal growth and litter size according to body reserves at weaning of young parity sows.
The effect of increasing the feed level (1.8, 2.5, and 3.2 kg/d) during early gestation in parity 1 (PO1) and parity 2 (PO2) sows on maternal growth and litter size was evaluated. A total of 361 sows were group-housed and fed a diet based on a corn-soybean meal (3.15 Mcal Metabolizable Energy (ME) per kg and 0.68% standardized ileal digestible lysine) from day 6 of gestation until day 30. Sows were weighed at weaning and on day 30 of gestation. Farrowing rate, number of total piglets born, piglets born alive, stillborn piglets, and mummified fetuses were recorded at farrowing. The effect of feed level on the total number of piglets born was also evaluated according to classes of body weight (BW), body condition score (BCS), backfat (BF), and caliper unit at weaning for each parity order. There was no evidence for significant effect of the interaction between feed level × parity on the variables related to maternal growth and reproductive performance (P ≥ 0.128). Greater feed levels linearly increased the gains in body condition (i.e., BW, BCS, BF, and caliper unit) between weaning and day 30 of gestation (P < 0.001). Farrowing rate was not influenced by the feed level (P ≥ 0.200) and parity (P ≥ 0.209). The number of total piglets born decreased linearly as the feed level increased (P = 0.041), whereas no evidences for differences were observed on piglets born alive among treatments (P ≥ 0.317), neither between parities (P ≥ 0.904). For PO1 sows, the total piglets born on BW classes (≤183 vs. >183 kg) and on classes of BF (≤11.5 vs. > 11.5 mm) were quadratically affected by the feed levels (P ≤ 0.041). In contrast, the number of total piglets born was marginally affected (linear; P ≤ 0.094) by the feed level in the different classes of BW, BCS, and caliper unit in PO2 sows. There was no evidence for differences for the interaction of feed level and classes of body condition (P ≥ 0.199) for PO2 sows. Similarly, no interactions between feed level and classes of BW, BCS, and BF at weaning were observed (P ≥ 0.233) for PO1 sows; however, the total piglets born were affected by an interaction between feed level and caliper unit class (P = 0.042). In conclusion, increased feed intake from day 6 of gestation until day 30 resulted in increased maternal BW gain but reduced the number of total piglets born. Furthermore, lighter and in a poor BCS PO1 sows at weaning produced fewer total born piglets with no benefits from greater amounts of feed.


Sphincteroplasty for anal incontinence.
Sphincteroplasty (SP) is the operation most frequently performed in patients suffering from moderate-to-severe anal incontinence (AI) who do not respond to conservative treatment. Other costly surgeries, such as artificial bowel sphincter (ABS) and electro-stimulated graciloplasty, have been more or less abandoned due to their high morbidity rate. Minimally invasive procedures are widely used, such as sacral neuromodulation and injection of bulking agents, but both are costly and the latter may cure only mild incontinence. The early outcome of SP is usually good if the sphincters are not markedly denervated, but its effect diminishes over time. SP is more often performed for post-traumatic than for idiopathic AI. It may also be associated to the Altemeier procedure, aimed at reducing the recurrence rate of rectal prolapse, and may be useful when AI is due either to injury to the sphincter, or to a narrowed rectum following the procedure for prolapse and haemorrhoids (PPH) and stapled transanal rectal resection (STARR). The outcome of SP is likely to be improved with biological meshes and post-operative pelvic floor rehabilitation. SP is more effective in males than in multiparous women, whose sphincters are often denervated, and its post-operative morbidity is low. In conclusion, SP, being both low-cost and safe, remains a good option in the treatment of selected patients with AI.


Phosphate acquisition genes in Prochlorococcus ecotypes: evidence for genome-wide adaptation.
The cyanobacterium Prochlorococcus is the numerically dominant phototroph in the oligotrophic oceans. This group consists of multiple ecotypes that are physiologically and phylogenetically distinct and occur in different abundances along environmental gradients. Here we examine adaptations to phosphate (P) limitation among ecotypes. First, we used DNA microarrays to identify genes involved in the P-starvation response in two strains belonging to different ecotypes, MED4 (high-light-adapted) and MIT9313 (low-light-adapted). Most of the up-regulated genes under P starvation were unique to one strain. In MIT9313, many ribosomal genes were down-regulated, suggesting a general stress response in this strain. We also observed major differences in regulation. The P-starvation-induced genes comprise two clusters on the chromosome, the first containing the P master regulator phoB and most known P-acquisition genes and the second, absent in MIT9313, containing genes of unknown function. We examined the organization of the phoB gene cluster in 11 Prochlorococcus strains belonging to diverse ecotypes and found high variability in gene content that was not congruent with rRNA phylogeny. We hypothesize that this genome variability is related to differences in P availability in the oceans from which the strains were isolated. Analysis of a metagenomic library from the Sargasso Sea supports this hypothesis; most Prochlorococcus cells in this low-P environment contain the P-acquisition genes seen in MED4, although a number of previously undescribed gene combinations were observed.


Effects of outcomes and random arbitration on emotions in a competitive gambling task.
Research on self-serving biases in judgments and decision-making suggests that individuals first evaluate the outcomes they get, and then the procedures by which these outcomes were obtained. Evidence also suggests that the appraisal of the former (outcome favorability) can bias the appraisal of the latter (procedural fairness). We investigated the nature of the emotions that are elicited by these appraisals by using a new paradigm in which participants performed a choice task between pairs of competing gambles against a virtual opponent. Conflicts (when the participant selected the same gamble as his virtual opponent) were resolved by a neutral arbitrator who either confirmed the participant's choice ("pro-self") or attributed his gamble to the virtual opponent ("pro-competitor"). Trials in which the participant and his virtual opponent selected different gambles ("no-conflict") served as a control condition. In order to validate this new task, emotional reactions to the outcomes of the gambles were measured using self-reports, skin conductance responses, and facial electromyography (zygomaticus, corrugator, and frontalis). In no-conflict trials, effects of counterfactual thinking and social comparison resulted in (i) increased happiness as well as SCR and zygomaticus activity for wins compared to losses (valence effect) and for high compared to low gains (magnitude effect), and (ii) increased anger, regret, disappointment, and envy for losses compared to wins (valence effect). More importantly, compared to no-conflict trials and to pro-self awards with similar outcomes, pro-competitor awards increased subjective reports of anger for unfavorable outcomes, and increased happiness and guilt for favorable outcomes. Although the outcomes were independent from the arbitrators' decisions, and both the arbitrators' decisions and the outcomes were kept equally likely, individuals tended to attribute their outcomes to unfair arbitrators, reacting emotionally, especially when the modification of their initial choice for a gamble led to a negative outcome.


Molecular characterization of an autolytic amidase of Listeria monocytogenes EGD.
The gene encoding a 102 kDa autolysin has been cloned from an expression library of Listeria monocytogenes EGD genomic DNA, using a direct screening protocol. The encoded protein has two domains, an N-terminal enzymic domain showing a high level of homology to the amidase domain of the major autolysin (atl) of Staphylococcus aureus, and a C-terminal, putative cell-wall-binding domain containing four imperfect direct repeats. In order to examine the role of the enzyme, the autolysin-encoding gene was insertionally inactivated by site-specific integration of a temperature sensitive plasmid. The enzyme accounts for 66% of the total lytic enzyme activity when L. monocytogenes walls are used as substrate and several of the major autolytic bands are missing on renaturing gels when compared to the wild-type. The enzyme does not appear to be directly involved in cell separation but has a role in motility. Characterization of the recombinant enzyme expressed in Escherichia coli has revealed it to be an amidase and to be able to hydrolyse a range of peptidoglycan substrates.


Accurate convolution/superposition for multi-resolution dose calculation using cumulative tabulated kernels.
Convolution/superposition (C/S) is regarded as the standard dose calculation method in most modern radiotherapy treatment planning systems. Different implementations of C/S could result in significantly different dose distributions. This paper addresses two major implementation issues associated with collapsed cone C/S: one is how to utilize the tabulated kernels instead of analytical parametrizations and the other is how to deal with voxel size effects. Three methods that utilize the tabulated kernels are presented in this paper. These methods differ in the effective kernels used: the differential kernel (DK), the cumulative kernel (CK) or the cumulative-cumulative kernel (CCK). They result in slightly different computation times but significantly different voxel size effects. Both simulated and real multi-resolution dose calculations are presented. For simulation tests, we use arbitrary kernels and various voxel sizes with a homogeneous phantom, and assume forward energy transportation only. Simulations with voxel size up to 1 cm show that the CCK algorithm has errors within 0.1% of the maximum gold standard dose. Real dose calculations use a heterogeneous slab phantom, both the 'broad' (5 x 5 cm2) and the 'narrow' (1.2 x 1.2 cm2) tomotherapy beams. Various voxel sizes (0.5 mm, 1 mm, 2 mm, 4 mm and 8 mm) are used for dose calculations. The results show that all three algorithms have negligible difference (0.1%) for the dose calculation in the fine resolution (0.5 mm voxels). But differences become significant when the voxel size increases. As for the DK or CK algorithm in the broad (narrow) beam dose calculation, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 10% (7%) of the maximum dose. As for the broad (narrow) beam dose calculation using the CCK algorithm, the dose differences between the 0.5 mm voxels and the voxels up to 8 mm (4 mm) are around 1% of the maximum dose. Among all three methods, the CCK algorithm is demonstrated to be the most accurate one for multi-resolution dose calculations.


Oxygen deficient α-Fe2O3 photoelectrodes: a balance between enhanced electrical properties and trap-mediated losses.
Intrinsic doping of hematite through the inclusion of oxygen vacancies (VO) is being increasingly explored as a simple, low temperature route to preparing active water splitting α-Fe2O3-x photoelectrodes. Whilst it is widely accepted that the introduction of VO leads to improved conductivities, little else is verified regarding the actual mechanism of enhancement. Here we employ transient absorption (TA) spectroscopy to build a comprehensive kinetic model for water oxidation on α-Fe2O3-x . In contrast to previous suggestions, the primary effect of introducing VO is to block very slow (ms) surface hole - bulk electron recombination pathways. In light of our mechanistic research we are also able to identify and address a cause of the high photocurrent onset potential, a common issue with this class of electrodes. Atomic layer deposition (ALD) of Al2O3 is found to be particularly effective with α-Fe2O3-x , leading to the photocurrent onset potential shifting by ca. 200 mV. Significantly TA measurements on these ALD passivated electrodes also provide important insights into the role of passivating layers, that are relevant to the wider development of α-Fe2O3 photoelectrodes.


In vitro antileishmanial activity of amphotericin B loaded in poly(epsilon-caprolactone) nanospheres.
The activity of formulations for amphotericin B (AmB) associated with poly(epsilon-caprolactone) nanospheres and coated with variable amounts of a non ionic surfactant poloxamer 188, was evaluated against AmB-susceptible (WT) and AmB-resistant (AmB(r)) strains of Leishmania donovani amastigotes in thioglycolate-elicited peritoneal macrophages. AmB-nanospheres were more actives than free AmB only against amastigotes of wild strain. The activity was not influenced by the concentration of poloxamer 188 used to stabilize the nanospheres in spite of this surfactant was previously reported to synergy with AmB on the membrane of the resistant parasite. Similarly, this improvement was not mediated through macrophage activation. In fact, these nanoparticle formulations appeared to inhibit both NO and TNF-alpha production induced by the free drug. Therefore, we suggest that the association of AmB with nanospheres may improve the capability of the drug to interact with ergosterol. This hypothesis appears to be supported by the fact that nanospheres did not show any improvement of the AmB activity against the resistant strain (characterized by the absence of ergosterol).


MiR-138-5p Inhibits the Proliferation of Gastric Cancer Cells by Targeting DEK.
Increasing evidence suggests that microRNAs (miRNAs) play critical roles in cancer progression. Therefore, investigating the function of miRNAs that are aberrantly expressed in gastric cancer (GC) and characterizing the involved underlying mechanism are essential for the treatment of gastric cancer. MiR-138-5p was found to be down-regulated in multiple cancers, which acted as a tumor suppressor in cancer progression; however, whether and how miR-138-5p regulates the malignant behaviors of GC has not been fully understood. The level of miR-138-5p in GC tissues and cell lines was detected by RT-qPCR. The effects of miR-138-5p on the growth of GC cells were evaluated by the in vitro Cell Counting Kit-8 (CCK-8) assay, cell apoptosis, cell cycle analysis, wound-healing assay, and in vivo xenograft mice model. The targets of miR-138-5p were predicted using the miRDB online tool, confirmed by luciferase report assay and Western blot. MiR-138-5p was frequently decreased in GC tissues and cell lines. Decreased expression of miR-138-5p was significantly associated with the lymph node metastasis of GC patients. Overexpression of miR-138-5p suppressed GC cell proliferation, migration, increased cell apoptosis as well as inhibited the tumor growth in vivo. DEK oncogene was predicted as a potential target of miR-138-5p. MiR-138-5p bound the 3'-UTR of DEK and inhibited the level of DEK in GC cells. Restoration of DEK abrogated miR-138-5p overexpression-mediated suppression of GC cell proliferation and cell cycle arrest. Our results demonstrated the anti-cancer role of miR-138-5p in GC by targeting DEK, which suggested miR-138-5p as a potential therapeutic target for the treatment of patient with GC.


Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya.
The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May-July 2002. Household surveys of cases and age-matched controls were conducted to collect information on household construction, exposure factors and socio-economic status. Household geographical location and altitude were determined using a hand-held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.


Cotton pedigree genome reveals restriction of cultivar-driven strategy in cotton breeding.
Many elite genes have been identified from the available cotton genomic data, providing various genetic resources for gene-driven breeding. However, backbone cultivar-driven breeding is the most widely applied strategy. Revealing the genetic basis of cultivar-driven strategy's restriction is crucial for transition of cotton breeding strategy. CRI12 is a backbone cultivar in cultivar-driven breeding. Here we sequence the pedigree of CRI12 using Nanopore long-read sequencing. We construct a graphical pedigree genome using the high-quality CRI12 genome and 13,138 structural variations within 20 different pedigree members. We find that low hereditary stability of elite segments in backbone cultivars is a drawback of cultivar-driven strategy. We also identify 623 functional segments in CRI12 for multiple agronomic traits in presence and absence variation-based genome-wide association study on three cohorts. We demonstrate that 25 deleterious segments are responsible for the geographical divergence of cotton in pathogen resistance. We also characterize an elite pathogen-resistant gene (GhKHCP) utilized in modern cotton breeding. In addition, we identify 386 pedigree fingerprint segments by comparing the segments of the CRI12 pedigree with those of a large cotton population. We characterize the genetic patterns of functional segments in the pedigree of CRI12 using graphical genome method, revealing restrictions of cultivar-driven strategies in cotton breeding. These findings provide theoretical support for transitioning from cultivar-driven to gene-driven strategy in cotton breeding.


Confidence and the stock market: an agent-based approach.
Using a behavioral finance approach we study the impact of behavioral bias. We construct an artificial market consisting of fundamentalists and chartists to model the decision-making process of various agents. The agents differ in their strategies for evaluating stock prices, and exhibit differing memory lengths and confidence levels. When we increase the heterogeneity of the strategies used by the agents, in particular the memory lengths, we observe excess volatility and kurtosis, in agreement with real market fluctuations--indicating that agents in real-world financial markets exhibit widely differing memory lengths. We incorporate the behavioral traits of adaptive confidence and observe a positive correlation between average confidence and return rate, indicating that market sentiment is an important driver in price fluctuations. The introduction of market confidence increases price volatility, reflecting the negative effect of irrationality in market behavior.


Orientation disruptor (ord): a recombination-defective and disjunction-defective meiotic mutant in Drosophila melanogaster.
The effects of a semidominant autosomal meiotic mutant, orientation disruptor (symbol: ord), located at 2-103.5 on the genetic map and in region 59B-D of the salivary map, have been examined genetically and cytologically. The results are as follows. (1) Crossing over in homozygous females is reduced to about seven percent of controls on all chromosomes, with the reduction greatest in distal regions. (2) Crossing over on different chromosomes is independent. (3) Reductional nondisjunction of any given chromosome is increased to about thirty percent of gametes from homozygous females. The probability of such nondisjunction is the same among exchange and nonexchange tetrads with the exception that a very proximal exchange tends to regularize segregation. (4) Equational nondisjunction of each chromosome is increased to about ten percent of gametes in homozygous females; this nondisjunction is independent of exchange. (5) The distributive pairing system is operative in homozygous females. (6) In homozygous males, reductional nondisjunction of each chromosome is increased to about ten percent, and equational nondisjunction to about twenty percent, of all gametes. (7) Cytologically, two distinct meiotic divisions occur in spermatocytes of homozygous males. The first division looks normal although occasional univalents are present at prophase I and a few lagging chromosomes are seen at anaphase I. However, sister chromatids of most chromosomes have precociously separated by metaphase II. Possible functions of the ord(+) gene are considered.


Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors.
The immunohistochemical demonstration of Enhancer of zeste homologue 2 (EZH2) proved to be a useful marker in several tumor types. It has been described to distinguish reliably hepatocellular carcinomas from liver adenomas and other benign hepatocellular lesions. However, no other types of malignant liver tumors were studied so far. To evaluate the diagnostic value of this protein in hepatic tumors we have investigated the presence of EZH2 by immunohistochemistry in hepatocellular carcinomas and other common hepatic tumors.EZH2 expression was examined in 44 hepatocellular carcinomas, 23 cholangiocarcinomas, 31 hepatoblastomas, 16 other childhood tumor types (rhabdomyosarcoma, neuroblastoma, Wilms' tumor and rhabdoid tumor), 17 metastatic liver tumors 24 hepatocellular adenomas, 15 high grade dysplastic nodules, 3 biliary cystadenomas, 3 biliary hamartomas and 3 Caroli's diseases. Most of the malignant liver tumors were positive for EZH2, but neither of the adenomas, cirrhotic/dysplastic nodules, reactive and hamartomatous biliary ductules stained positively. Our immunostainings confirm that EZH2 is a sensitive marker of hepatocellular carcinoma, but its specificity is very low, since almost all the investigated malignant liver tumors were positive regardless of their histogenesis. Based on these results EZH2 is a sensitive marker of malignancy in hepatic tumors. In routine surgical pathology EZH2 could be most helpful to diagnose cholangiocarcinomas, because as far as we know this is the first marker to distinguish transformed and reactive biliary structures. Although hepatoblastomas also express EZH2, the diagnostic significance of this observation seems to be quite limited whereas, the structurally similar, other blastic childhood tumors are also positive. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1173195902735693.


First detection of the equine herpesvirus 1 neuropathogenic variant in Brazil.
This report describes the first detection of an equine herpesvirus 1 (EHV-1) neuropathogenic variant (G2254/D752) in Brazil from a case of fatal equine herpesvirus myeloencephalopathy (EHM) in a mare. The results of nucleotide sequencing of the EHV-1 ORF30 gene showed that two other Brazilian EHV-1 isolates from EHM cases are representatives of the non-neuropathogenic variant (A2254/N752), suggesting that other unidentified factors are probably also involved in the neuropathogenicity of EHV-1 in horses. These findings will contribute to the epidemiological knowledge of EHV-1 infection in Brazil.


Experimentally induced autonomic neuropathy: beneficial effect of a systemic ACTH4-9 analogue on oculomotor nerve regeneration.
While the regenerating capacity of peripheral nerves has been the subject of intensive study, little is known about the regenerative capacity of the autonomic nervous system. Using an animal model, where the pupil diameter of the eye in the rat serves as a parameter of autonomic function, we studied whether systemic treatment with the neuropeptide Org 2766, a synthetic ACTH4-9, analogue, facilitates the functional recovery of parasympathetic nerve fibres after transection, and after a crush lesion of the oculomotor nerve. By simply photographing the rat's pupil under standardised conditions, we show that sectioning the oculomotor nerve leads to an immediate mydriasis, followed by spontaneous regeneration in 30 days. Systemic treatment with an ACTH4-9 analogue had no effect on the rate or quality of recovery. However, systemic treatment with an ACTH4-9 analogue after a crush lesion of the oculomotor nerve (spontaneous regeneration time 16 days) did enhance the speed of recovery of the parasympathetic nerve fibres in the oculomotor nerve, especially in the initial stages of regeneration. We conclude that the animal model used in this study is valuable for studying the regenerative capacity of the autonomic nervous system and the influence of neurotrophic peptides on autonomic neuropathies. Evidence is presented that synthetic ACTH4-9 analogue exerts beneficial neurotrophic effects, not only in peripheral sensorimotor neuropathies but also in autonomic neuropathies.


Dividing attention lowers children's but increases adults' false memories.
The present study examined the impact of divided attention on children's and adults' neutral and negative true and false memories in a standard Deese/Roediger-McDermott paradigm. Children (7- and 11-year-olds; n = 126) and adults (n = 52) received 5 neutral and 5 negative Deese/Roediger-McDermott word lists; half of each group also received a divided attention task. The results showed that divided attention affected children's and adults' false memory levels differently but did not alter true memory differently. Our results revealed a developmental shift in that divided attention lowered children's false memory rates but increased adults' false memory rates, regardless of the nature of the material (i.e., neutral or negative). Our study indicates that manipulations that target conscious processing (e.g., divided attention) result in marked qualitative and quantitative differences between children's and adults' false memories but not true memories.


Structural analysis of human 2'-O-ribose methyltransferases involved in mRNA cap structure formation.
The 5' cap of human messenger RNA contains 2'-O-methylation of the first and often second transcribed nucleotide that is important for its processing, translation and stability. Human enzymes that methylate these nucleotides, termed CMTr1 and CMTr2, respectively, have recently been identified. However, the structures of these enzymes and their mechanisms of action remain unknown. In the present study, we solve the crystal structures of the active CMTr1 catalytic domain in complex with a methyl group donor and a capped oligoribonucleotide, thereby revealing the mechanism of specific recognition of capped RNA. This mechanism differs significantly from viral enzymes, thus providing a framework for their specific targeting. Based on the crystal structure of CMTr1, a comparative model of the CMTr2 catalytic domain is generated. This model, together with mutational analysis, leads to the identification of residues involved in RNA and methyl group donor binding.


Cloning and characterization of the polyhydroxybutyrate depolymerase gene of Pseudomonas stutzeri and analysis of the function of substrate-binding domains.
The extracellular polyhydroxybutyrate (PHB) depolymerase gene (phaZPst) of Pseudomonas stutzeri was cloned and sequenced. phaZPst was composed of 1,728 bp encoding a protein of 576 amino acids. Analyses of the N-terminal amino acid sequence and the matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrum of the purified enzyme showed that the mature enzyme consisted of 538 amino acids with a deduced molecular mass of 57,506 Da. Analysis of the deduced amino acid sequence of the protein revealed a domain structure containing a catalytic domain, putative linker region, and two putative substrate-binding domains (SBDI and SBDII). The putative linker region was similar to the repeating units of the cadherin-like domain of chitinase A from Vibrio harveyi and chitinase B from Clostridium paraputrificum. The binding characteristics of SBDs to poly([R]-3-hydroxybutyrate) [P(3HB)] and chitin granules were characterized by using fusion proteins of SBDs with glutathione S-transferase (GST). These GST fusion proteins with SBDII and SBDI showed binding activity toward P(3HB) granules but did not bind on chitin granules. It has been suggested that the SBDs of the depolymerase interact specifically with the surface of P(3HB). In addition, a kinetic analysis for the enzymatic hydrolysis of 3-hydroxybutyrate oligomers of various sizes has suggested that the catalytic domain of the enzyme recognizes at least two monomeric units as substrates.


Investigation of the Reference Interval Values of Fasting Plasma Glucose, Blood Pressure, and Blood Lipids in the Longevity People Aged 90 Years Old and Above.
To our knowledge, the normal fasting plasma glucose (FPG), blood pressure (BP), and blood lipids (BL) interval values have not been well-established in the longevity population. This study aims to provide a reference for the establishment of normal BP, FPG, and BL interval values in the longevity people in China. A total of 7417 people were selected from the natural longevity cohort in Guangxi, with an age range of 20-110 years old, including 7093 classified as the non-longevity (20-89 years old) (94.02%) and 324 classified as the longevity (≥90 years old) (5.98%); there were 4309 men (58.1%) and 3108 women (41.9%). FPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels were defined as desirable levels when they were below the 75th percentile (P75), borderline levels from the 75th to 90th percentile (P75-P90), and high levels above P90; triglyceride (TG) levels above P90 were defined as high; and high-density lipoprotein cholesterol (HDL-C) levels below the 5th percentile (P5) were defined as low levels. The reference interval values of FPG in the longevity were as follows: desirable levels <6.15 mmol/L, borderline levels 6.15-7.45 mmol/L, high levels ≥7.45 mmol/L. Reference interval values of systolic blood pressure (SBP) were as follows: desirable levels <160.00 mmHg, borderline levels 160.00-174.50 mmHg, high levels ≥175.00 mmHg. DBP reference interval values were as follows: desirable levels <88.00 mmHg, borderline levels 88.00-90.00 mmHg, high levels ≥90.00 mmHg. TC reference interval values were as follows: desirable levels <5.59 mmol/L, borderline levels 5.59-6.45 mmol/L, high levels ≥6.45 mmol/L. LDL-C reference interval values were as follows: desirable levels <3.30 mmol/L, borderline levels 3.30-3.85 mmol/L, high levels ≥3.85 mmol/L. TG reference interval values were as follows: desirable levels <2.82 mmol/L, high levels ≥2.82 mmol/L. HDL-C reference interval values were as follows: low levels <0.80 mmol/L, desirable levels ≥0.80 mmol/L. The reference interval values of BP, FPG, and BL are different between the longevity population and the non-longevity population, and the interval values change with increasing age.


MRI reconstruction from 2D truncated k-space.
To shorten acquisition time by means of both partial scanning and partial echo acquisition and to reconstruct images from such 2D partial k-space acquisitions. We propose an approach to reconstructing magnetic resonance images from 2D truncated k-space in which the k-space is truncated in both phase- and frequency-encoding directions. Unlike conventional reconstruction techniques, the proposed approach is based on a newly developed 2D singularity function analysis (SFA) model and a sparse representation of an image whose parameters can be estimated from the 2D partial k-space data. Such a sparse representation leads to an accurate recovery of the missing k-space data and, hence, an accurate reconstruction of the image. The proposed approach can reconstruct an image from as little as 20%-30% of the k-space data and the quality of the reconstructed image is comparable to the reference image that is reconstructed from the complete k-space data. Despite the high asymmetry of a 2D truncated k-space, the proposed approach allows for accurate reconstruction without the need of phase correction and, thus, overcomes the assumption of slow phase variations that is usually required by the existing reconstruction methods. It provides a new way of fast imaging for applications that require a significant reduction of the acquisition time.


Distinct Expression Patterns of Carbonic Anhydrase IX in Clear Cell, Microcystic, and Angiomatous Meningiomas.
Clear cell, microcytic, and angiomatous meningiomas are 3 vasculature-rich variants with overlapping morphological features but different prognostic and treatment implications. Distinction between them is not always straightforward. We compared the expression patterns of the hypoxia marker carbonic anhydrase IX (CA-IX) in meningiomas with predominant clear cell (n = 15), microcystic (n = 9), or angiomatous (n = 11) morphologies, as well as 117 cases of other World Health Organization recognized histological meningioma variants. Immunostaining for SMARCE1 protein, whose loss-of-function has been associated with clear cell meningiomas, was performed on all clear cell meningiomas, and selected variants of meningiomas as controls. All clear cell meningiomas showed absence of CA-IX expression and loss of nuclear SMARCE1 expression. All microcystic and angiomatous meningiomas showed diffuse CA-IX immunoreactivity and retained nuclear SMARCE1 expression. In other meningioma variants, CA-IX was expressed in a hypoxia-restricted pattern and was highly associated with atypical features such as necrosis, small cell change, and focal clear cell change. In conclusion, CA-IX may serve as a useful diagnostic marker in differentiating clear cell, microcystic, and angiomatous meningiomas.


Pharmacokinetics of R(-) and S(+) carprofen after administration of racemic carprofen in donkeys and horses.
To compare plasma disposition of the R(-) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses. 5 clinically normal donkeys and 3 clinically normal horses. Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentrationtime curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables. In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(-) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(-) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (CIT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and CIT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys. Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys.


A miniature glucose sensor, implantable in the blood stream.
We have developed a miniature glucose sensor using an oxygen electrode with a glucose oxidase membrane. The special character of this sensor is that the electrodes can be placed in a blood vessel and can measure the glucose level directly from the arterial blood stream if placed into an external A-V shunt. Its second notable characteristic is that the enzyme membrane is covered with a semipermeable membrane, which partially allows passage of glucose but only sufficient oxygen. This sensor is able to respond to glucose concentrations of up to 700 mg/dl in blood. This sensor loses 10% of its activity at about 200 h of continuous use, and 30% after 400 h of use. While the sensor cannot be sterilized by conventional mechanical or gas methods, certain antibiotics can be used for sterilization. To shorten the response delay of the sensor during the decreasing phase of glucose concentration, a thinner membrane is under development.


Rectus Abdominis Motor Nerves as Donor Option for Free Functional Muscle Transfer: A Cadaver Study and Case Series.
Current management of brachial plexus injuries includes nerve grafts and nerve transfers. However, in cases of late presentation or pan plexus injuries, free functional muscle transfers are an option to restore function. The purpose of our study was to describe and evaluate the rectus abdominis motor nerves histomorphologically and functionally as a donor nerve option for free functional muscle transfer for the reconstruction of brachial plexus injuries. High intercostal, rectus abdominis, thoracodorsal, and medial pectoral nerves were harvested for histomorphometric analysis from 4 cadavers from levels T3-8. A retrospective chart review was performed of all free functional muscle transfers from 2001 to 2014 by a single surgeon. Rectus abdominis nerve branches provide a significant quantity of motor axons compared with high intercostal nerves and are comparable to the anterior branch of the thoracodorsal nerve and medial pectoral nerve branches. Clinically, the average recovery of elbow flexion was comparable to conventional donors for 2-stage muscle transfer. Rectus abdominis motor nerves have similar nerve counts to thoracodorsal, medial pectoral nerves, and significantly more than high intercostal nerves alone. The use of rectus abdominis motor nerve branches allows restoration of elbow flexion comparable to other standard donors. In cases where multiple high intercostal nerves are not available as donors (rib fractures, phrenic nerve injury), rectus abdominis nerves provide a potential option for motor reconstruction without adversely affecting respiration.


Altered oxidative metabolism in selenium-deficient rat granulocytes.
Rats fed a selenium-deficient diet for 12 to 15 wk became selenium-depleted, measured by the selenium content of liver and granulocytes. The activity of granulocyte glutathione peroxidase, a selenoenzyme, in deficient rats was 11% of the activity in replete rat granulocytes. When stimulated with an H2O2 generating system, the HMPS activity of the deficient granulocytes was 50% of replete; however, when stimulated with methylene blue, the HMPS activity in deficient and replete granulocytes was the same. When granulocytes were incubated with PMA or OPZ, deficient granulocytes initially had the same O-2-generating activity as replete granulocytes; however, with increasing duration of stimulation, granulocytes from deficient rats generated less O-2 than replete rats. After 20 min in an H2O2-generating system, deficient granulocytes stimulated with PMA or OPZ generated less O-2 than replete granulocytes. These results indicate that deficient granulocytes did not metabolize H2O2 as well as replete granulocytes and that H2O2 caused damage to the O2-generating system. Measurement of O-2 generation in membrane-enriched particles showed the above effects were due to inactivation of the NADPH-dependent O2-generating system. Deficient granulocytes stimulated with OPZ for 20 min had 70% less membrane O-2-generating activity than controls. In addition, when membrane-enriched particles were made from cells that had been stressed with an H2O2-generating system, NADPH-dependent O-2-generating activity in deficient granulocytes was 50% of replete. In selenium-deficient granulocytes with low GSH-Px activity, prolonged incubation with stimulants and prior incubations with an H2O2-generating system caused loss of activity of the membrane-bound, NADPH-dependent, O-2-generating system.


"Change yourself and the whole world will become kinder": Russian activists for reproductive health and the limits of claims making for women.
This article views reproductive health activism as a fruitful site for analyzing the cultural logics through which legitimate claims for women's needs become expressed and circumscribed. It begins from the observation that in the United States and Britain, reproductive health has been a key arena for feminist political claims and struggles for women's rights, bodily integrity, access to health care, and demands for authority in relations with experts. These concerns and struggles have not, however, emerged in all postsocialist contexts, and new activism in Russia reveals strikingly different agendas. Innovative groups of health providers seeking to increase women's access to birth control methods and safe sex, home birth opportunities, and improved health services work outside of feminist perspectives and reject political paths for change. By examining the ideological inspirations, cultural logics, and political-economic constraints shaping the outreach work of Russian health practitioners, the article explains how and why health activism became a site for personal "spiritual" revival and the strengthening of nuclear families. It also explores how conditions following the collapse of socialism have further legitimized activists' rejection of political agendas for change.


A biological solution to a fundamental distributed computing problem.
Computational and biological systems are often distributed so that processors (cells) jointly solve a task, without any of them receiving all inputs or observing all outputs. Maximal independent set (MIS) selection is a fundamental distributed computing procedure that seeks to elect a set of local leaders in a network. A variant of this problem is solved during the development of the fly's nervous system, when sensory organ precursor (SOP) cells are chosen. By studying SOP selection, we derived a fast algorithm for MIS selection that combines two attractive features. First, processors do not need to know their degree; second, it has an optimal message complexity while only using one-bit messages. Our findings suggest that simple and efficient algorithms can be developed on the basis of biologically derived insights.


Dissemination and implementation of the ICAMP.
The current rate of immunizations for older adults does not meet the immunization goals for Healthy People 2020. Using a Social Ecological Model and Social Cognitive Theory, the purpose of this study was to disseminate and implement the Immunization Champions, Advocates and Mentors Program (ICAMP) into a variety of health care settings. This study used a single group pre-/post-test design. Champions were recruited nationally. Five geographically diverse face-to-face meetings were held to train health care providers to be ICAMP immunization champions. Dissemination and implementation of ICAMP was evaluated using the Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) model. Participants were surveyed at baseline for descriptive information and were asked to gather immunization rates for at least one particular vaccine and provide follow-up data on progress toward goal achievement. A total of 212 champions from 82 settings participated in ICAMP. The majority were nurses (111/212, 52%). With regard to reach, we obtained 212 applications from individuals in a variety of settings interested in becoming champions. With regard to effectiveness, the majority of the champions (n = 178/212, 84%) used ICAMP material, 88% (n = 186/212) made changes related to immunization processes within their setting, and all reported that immunization practices improved. The majority used the toolkit materials up through 60 days following ICAMP. Sustained use of materials after the 60-day follow-up was less evident. ICAMP was implemented as intended and was effective in changing processes around immunizations. Ongoing work is needed to determine whether ICAMP improves immunization rates.


Comparative molecular analysis of chemolithoautotrophic bacterial diversity and community structure from coastal saline soils, Gujarat, India.
Soils harbour high diversity of obligate as well as facultative chemolithoautotrophic bacteria that contribute significantly to CO2 dynamics in soil. In this study, we used culture dependent and independent methods to assess the community structure and diversity of chemolithoautotrophs in agricultural and coastal barren saline soils (low and high salinity). We studied the composition and distribution of chemolithoautotrophs by means of functional marker gene cbbL encoding large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase and a phylogenetic marker 16S rRNA gene. The cbbL form IA and IC genes associated with carbon fixation were analyzed to gain insight into metabolic potential of chemolithoautotrophs in three soil types of coastal ecosystems which had a very different salt load and sulphur content. In cbbL libraries, the cbbL form IA was retrieved only from high saline soil whereas form IC was found in all three soil types. The form IC cbbL was also amplified from bacterial isolates obtained from all soil types. A number of novel monophyletic lineages affiliated with form IA and IC phylogenetic trees were found. These were distantly related to the known cbbL sequences from agroecosystem, volcanic ashes and marine environments. In 16S rRNA clone libraries, the agricultural soil was dominated by chemolithoautotrophs (Betaproteobacteria) whereas photoautotrophic Chloroflexi and sulphide oxidizers dominated saline ecosystems. Environmental specificity was apparently visible at both higher taxonomic levels (phylum) and lower taxonomic levels (genus and species). The differentiation in community structure and diversity in three soil ecosystems was supported by LIBSHUFF (P = 0.001) and UniFrac. This study may provide fundamentally new insights into the role of chemolithoautotrophic and photoautotrophic bacterial diversity in biochemical carbon cycling in barren saline soils. The bacterial communities varied greatly among the three sites, probably because of differences in salinity, carbon and sulphur contents. The cbbL form IA-containing sulphide-oxidizing chemolithotrophs were found only in high saline soil clone library, thus giving the indication of sulphide availability in this soil ecosystem. This is the first comparative study of the community structure and diversity of chemolithoautotrophic bacteria in coastal agricultural and saline barren soils using functional (cbbL) and phylogenetic (16S rDNA) marker genes.


A systematic review of the effectiveness and complications of fat grafting in the facial region.
The objective of this study was to evaluate the safety and efficacy of fat grafting to the facial region for the reconstruction and aesthetic enhancement of facial contour. A systematic literature review of the National Library of Medicine (PubMed), MEDLINE and Cochrane databases was performed. Studies involving the outcomes of autologous fat grafting to correct or enhance contour defects of the face were included. Extracted data included patient demographics, harvest and injection sites, graft harvesting and injection technique, mean injected volume, retained volume percentage and complications. Forty-three articles met the inclusion criteria, resulting in 4577 patients with various facial contour defects treated with autologous fat grafting. Injection sites were categorized by anatomic facial regions as upper (32.5%), middle (53%) and lower face (14.5%). The mean volume of injected fat was 16.9 ml. The mean weighted volume retention of non-enriched grafts was 41.63% at the time of follow up (mean 13.9 months). A total of 104 (2.27%) complications were reported including asymmetry (74), skin irregularities (14), prolonged edema (4), graft hypertrophy (4), fat necrosis (3), infection (2), erythema (1), telangiectasia (1), and activation of acne (1). The present study represents the first systematic review of fat grafting in the facial region, a widely-performed procedure within plastic surgery practice. Importantly, it presents pooled important data such as retained grafting volume and complication rates in this anatomical region, providing clinicians with more accurate information with which to guide their decision-making and patient education.


Thyroid metastases from renal cell carcinoma. Report of a case and review of the literature.
Metastases to thyroid gland are a rare occurrence in surgical practice. The most frequent primitive tumor is renal cell carcinoma. We report a case of thyroid metastasis from renal cell carcinoma in a 70-year-old man who underwent left nephrectomy ten years earlier, presented with a diagnosis of multinodular goiter, associated with thyroiditis and right laterocervical lymphadenopathy. A total and the surgical excision of laterocervical lymph node were performed. The results, according to the histological examination, were metastases from renal cell carcinoma, involving both the thyroid gland and the lymph node. Therefore, since the delay of presentation and the difficulties of diagnosis, we recommend log-term follow-up of the head and neck region, for those patients with renal cell carcinoma diagnosis.


Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase.
Sustained and complete inhibition of HER3 and its output to PI3K/Akt are required for the optimal antitumor effect of therapeutic inhibitors of the HER2 oncogene. Here, we show that, after inhibition of the HER2 tyrosine kinase with lapatinib, there is PI3K/Akt and FoxO3a-dependent up-regulation of HER3 mRNA and protein. Up-regulated HER3 was then phosphorylated by residual HER2 activity, thus partially maintaining P-Akt and limiting the antitumor action of lapatinib. Inhibition of HER3 with siRNA or a neutralizing HER3 antibody sensitized HER2+ breast cancer cells and xenografts to lapatinib both in vitro and in vivo. Combined blockade of HER2 and HER3 inhibited pharmacodynamic biomarkers of PI3K/Akt activity more effectively than each inhibitor alone. These results suggest that because of HER3-mediated compensation, current clinical inhibitors of HER2 and PI3K/Akt will not block the PI3K pathway completely. They also suggest that therapeutic inhibitors of HER3 should be used in combination with HER2 inhibitors and PI3K pathway inhibitors in patients with HER2- and PI3K-dependent cancers.


Onset of puberty, menstrual frequency, and body fat in elite rhythmic gymnasts compared with normal controls.
To assess the prevalence of delayed menarche and abnormal menstrual patterns, as well as the association of menstrual status with physical training in elite rhythmic gymnasts from Greece and Canada. Fifteen Greek (mean (SEM) age 14.5 (0.2) years) and 30 Canadian (mean (SEM) age 14.7 (0.4) years) rhythmic gymnasts were surveyed for age at menarche, menstrual frequency, and training profile, and measured for height, weight, and percentage body fat (%BF). Seventy eight healthy adolescents served as country specific non-active controls: 38 Greek non-athletes (mean (SEM) age 14.5 (0.1) years) and 40 Canadian non-athletes (mean (SEM) 14.2 (0.1) years). Of the Greek gymnasts, 79% had not yet menstruated compared with 34% of the Canadian gymnasts. Menarche was significantly (p<0.01) delayed in the rhythmic gymnasts (composite mean 13.8 (0.3) years, n = 45) compared with the controls (composite mean 12.5 (0.1) years, n = 78). There was no significant difference between Greek and Canadian gymnasts for the age at menarche (14.2 (0.3) v 13.6 (1.2) years respectively). Menstrual irregularities were reported in 78% (61% oligomenorrhoeic and 17% amenorrhoeic) of the menarcheal athletes. Menarcheal gymnasts were found to be significantly (p<0.05) taller and heavier, with a higher %BF and a lower training frequency and training duration (p<0.05) than the premenarcheal gymnasts. Overall, the mean %BF of the gymnasts was significantly lower (p<0.05) than that of the control subjects. The Canadian controls exhibited a significantly (p<0.05) greater %BF than the Greek controls of the same age. Delayed menarche, menstrual irregularities, and low body fat are common in elite rhythmic gymnasts. Premenarcheal gymnasts train more often and for longer, and have a lower body mass index and less body fat, than menarcheal gymnasts. Prospective studies are needed to explore further these and other factors associated with delayed menarche and menstrual irregularities in female athletes.