[Indications for transnasal endoscopic and microscopic and external paranasal sinus operations. A critical intermediate report].
A comparison of the paranasal sinus operations performed in 1980/1981 (n = 310) and 1988/1989 (n = 540) in the author's clinic demonstrates an impressive shift to endonasal techniques. These operations have increased from 35.4% to 74.6%. About three-quarters of the operations for chronic sinusitis were done by the endoscopic technique. In a quarter of the cases we found an extremely extensive chronic recurring polyposis indicating systemic disease. We prefer the microscopic technique for these cases. The extranasal approaches are now used more rarely in the surgery of inflammatory lesions. Nevertheless, they are still important for the treatment of complications, injuries and tumours of the paranasal sinuses, and they constitute 18.9% of all operations.


The role of the subgenual anterior cingulate cortex in dorsomedial prefrontal-amygdala neural circuitry during positive-social emotion regulation.
Positive-social emotions mediate one's cognitive performance, mood, well-being, and social bonds, and represent a critical variable within therapeutic settings. It has been shown that the upregulation of positive emotions in social situations is associated with increased top-down signals that stem from the prefrontal cortices (PFC) which modulate bottom-up emotional responses in the amygdala. However, it remains unclear if positive-social emotion upregulation of the amygdala occurs directly through the dorsomedial PFC (dmPFC) or indirectly linking the bilateral amygdala with the dmPFC via the subgenual anterior cingulate cortex (sgACC), an area which typically serves as a gatekeeper between cognitive and emotion networks. We performed functional MRI (fMRI) experiments with and without effortful positive-social emotion upregulation to demonstrate the functional architecture of a network involving the amygdala, the dmPFC, and the sgACC. We found that effortful positive-social emotion upregulation was associated with an increase in top-down connectivity from the dmPFC on the amygdala via both direct and indirect connections with the sgACC. Conversely, we found that emotion processes without effortful regulation increased network modulation by the sgACC and amygdala. We also found that more anxious individuals with a greater tendency to suppress emotions and intrusive thoughts, were likely to display decreased amygdala, dmPFC, and sgACC activity and stronger connectivity strength from the sgACC onto the left amygdala during effortful emotion upregulation. Analyzed brain network suggests a more general role of the sgACC in cognitive control and sheds light on neurobiological informed treatment interventions.


The Influence of Students' Perceptions of Learning Environment on Coping with Academic Challenges: A Structural Equation Modeling Study.
Theory: Self-compassion has been identified as a promising interventional target enabling medical learners to respond effectively to stressors and challenges of medical training. Determining factors in the learning environment that support self-compassion is critical for developing such interventions. What is already known in terms of environmental or contextual factors is that learning environments that are supportive of students' basic psychological needs for autonomy, competence, and relatedness result in better learning and wellbeing outcomes. As such, satisfaction of basic psychological needs in the learning environment was tested for potential effects on self-compassion among medical students. Hypothesis: It was hypothesized that medical students who perceived their needs for autonomy, competence, and relatedness were supported in the learning environment would be more likely to respond to stressors and challenges by means of positive processes of self-compassion (common humanity, mindfulness, self-kindness) and less likely by means of negative processes of self-compassion (isolation, over-identification, self-judgment). Two models were tested: Model 1 contained the effects of the needs for autonomy, competence, and relatedness on two factors of self-compassion that comprise three positive and three negative processes, respectively. Model 2 contained the direct effects of the psychological needs on six individual processes of self-compassion. Method: Using two online surveys, authors collected data from medical students (n = 195) at a large Canadian university. The authors used the 12-item basic psychological needs scale to measure the degree of satisfaction of students' needs for autonomy, competence, and relatedness in the learning environment, as perceived by students. The 12-item self-compassion scale was used to measure the degree of compassion students exhibited toward themselves in challenging times in the medical program. The authors used structural equation modeling (SEM) to test the hypothesized relationships between basic psychological needs satisfaction and self-compassion. Results: The SEM results for Model 2 indicated an improved model fit over Model 1; however, not all the hypothesized effects were determined to be significant in the two models. In the better fitting model (Model 2), significant effects were observed between the needs for competence and relatedness and the three negative processes of self-compassion (isolation, over-identification, self-judgement). Specifically, the need for relatedness had comparable effects on all three negative processes of self-compassion. The need for competence had a significant effect only on isolation. The need for autonomy had no effects on self-compassion processes. None of the effects involving the positive processes of self-compassion (common humanity, mindfulness, self-kindness) were significant. Conclusions: Satisfaction of medical students' needs for competence and relatedness in the learning environment appears to reduce the negative processes of self-compassion. Future research is needed to determine why basic psychological needs satisfaction appears to have no effects on the positive processes of self-compassion and what factors are likely to foster these beneficial processes among medical students.


Coded aperture nuclear scintigraphy: a novel small animal imaging technique.
We introduce and demonstrate the utility of coded aperture (CA) nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 x 10(3) cps/Bq (9400 cpm/microCi), compared to 4.4 x 10(4) cps/Bq (990 cpm/microCi) for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4-6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator). Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a) CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b) CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c) CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.


Total and inorganic arsenic levels in some marine organisms from Izmir Bay (Eastern Aegean Sea): a risk assessment.
The arsenic compounds in marine biota were evaluated from Izmir Bay (Eastern Aegean) and found that inorganic arsenic occurred as a minor fraction. No information is available on the annual variations of arsenic in important edible biota species from Izmir Bay. Fish and mussel samples were taken from different regions of Izmir Bay between 2009 and 2011 (n=854 individual specimens). The average percentages of inorganic arsenic to total arsenic for all biota samples were 3.43±3.38% with a range of 0.11-11.8%. The importance of speciation analysis for arsenic is supported by our work, because arsenic is ubiquitous in the ecosystem, and flexible toxicity of arsenic is based on chemical form. The average total As levels in Mullus barbatus were 6 times higher than Diplodus annularis and Mytilus galloprovincialis. This study also revealed that spatial variation influenced the arsenic levels in the fish samples and the highest concentrations of arsenic were found in Gediz site. Our study showed that estimated daily intakes of arsenic via consumption of flesh fish and shell fish were below the BMDL0.5 values established by FAO/WHO.


Binding waste anthracite fines with Si-containing materials as an alternative fuel for foundry cupola furnaces.
An alternative fuel to replace foundry coke in cupolas was developed from waste anthracite fines. Waste anthracite fines were briquetted with Si-containing materials and treated in carbothermal (combination of heat and carbon) conditions that simulated the cupola preheat zone to form silicon carbide nanowires (SCNWs). SCNWs can provide hot crushing strengths, which are important in cupola operations. Lab-scale experiments confirmed that the redox level of the Si-source significantly affected the formation of SiC. With zerovalent silicon, SCNWs were formed within the anthracite pellets. Although amorphous Si (+4) plus anthracite formed SiC, these conditions did not transform the SiC into nanowires. Moreover, under the test conditions, SiC was not formed between crystallized Si (+4) and anthracite. In a full-scale demonstration, bricks made from anthracite fines and zerovalent silicon successfully replaced a part of the foundry coke in a full-scale cupola. In addition to saving in fuel cost, replacing coke by waste anthracite fines can reduce energy consumption and CO2 and other pollution associated with conventional coking.


Liver histopathology in scope of hematological disorders.
Liver involvement is commonly seen in various haematological disorders. They present clinically with elevation of liver enzymes and organomegaly, with or without mass lesions. However, liver involvement may be silent in many hematological disorders or there may be specific findings in liver biopsy that can lead to the diagnosis of clinically inapparent hematological disorders. Present review highlights features of hepatic manifestations in various hematological diseases with special emphasis on histopathological findings. Among RBC disorders, secondary hemochromatosis is the commonest among patients with hemolytic anemia; whereas Sickle Cell Hepatopathy is a well known complication in Sickle Cell Disease, characterised by sequestration of sickled RBCs in sinusoids. Vascular complications such as Budd Chiari syndrome and portal venopathy with portal vein thrombosis are seen in patients with myeloproliferative neoplasms. However, sometimes primary hematological disease may remain occult. Various lymphomas show characteristic pattern of hepatic involvement, most common being sinusoidal and portal infiltration. Pattern of infiltration may give clues to different types of lymphomas. Amongst all lymphomas, Diffuse large B cell lymphoma is the most common lymphoma involving liver. Disseminated intravascular coagulation is a fatal systemic condition and liver involvement by widespread fibrin thrombi, is not an exception. Assessing liver histopathology in context of hematological conditions makes better understanding of pathophysiology and progress of these diseases. It is important for hematologists and hepatologist to be aware of possible liver involvement in various hematological diseases presenting with elevated LFTs and have a logical approach to abnormal LFTs.


Reliability of a newly-developed immunochromatography diagnostic kit for pandemic influenza A/H1N1pdm virus: implications for drug administration.
For the diagnosis of seasonal influenza, clinicians rely on point-of-care testing (POCT) using commercially available kits developed against seasonal influenza viruses. However, POCT has not yet been established for the diagnosis of pandemic influenza A virus (H1N1pdm) infection due to the low sensitivity of the existing kits for H1N1pdm. An immunochromatography (IC) test kit was developed based on a monoclonal antibody against H1N1pdm, which does not cross-react with seasonal influenza A or B viruses. The efficacy of this kit (PDM-IC kit) for the diagnosis of H1N1pdm infection was compared with that of an existing kit for the detection of seasonal influenza viruses (SEA-IC kit). Nasal swabs (n = 542) were obtained from patients with flu-like syndrome at 13 clinics in Osaka, Japan during the winter of 2010/2011. Among the 542 samples, randomly selected 332 were further evaluated for viral presence by reverse transcriptase polymerase chain reaction (RT-PCR). The PDM-IC kit versus the SEA-IC kit showed higher sensitivity to and specificity for H1N1pdm, despite several inconsistencies between the two kits or between the kits and RT-PCR. Consequently, greater numbers of false-negative and false-positive cases were documented when the SEA-IC kit was employed. Significant correlation coefficients for sensitivity, specificity, and negative prediction values between the two kits were observed at individual clinics, indicating that the results could be affected by clinic-related techniques for sampling and kit handling. Importantly, many patients (especially influenza-negative cases) were prescribed anti-influenza drugs that were incongruous with their condition, largely due to physician preference for patient responses to questionnaires and patient symptomology, as opposed to actual viral presence. Concomitant use of SEA-IC and PDM-IC kits increased the likelihood of correct influenza diagnosis. Increasing the credibility of POCT is anticipated to decrease the inappropriate dispensing of anti-influenza drugs, thereby minimizing the emergence of drug-resistant H1N1pdm strains.


Insulin-like growth factors, insulin, and growth hormone signaling in breast cancer: implications for targeted therapy.
In recent decades, multiple therapeutics targeting the estrogen and human epidermal growth factor-2 (HER2) receptors have been approved for the treatment of breast cancer. This review discusses a number of growth factor pathways that have been implicated in resistance to both anti-estrogen and HER2-targeted therapies. The association between growth factors and breast cancer is well established. Over decades, numerous laboratories have studied the link between insulin-like growth factor (IGF), insulin, and growth hormone (GH) to the development and progression of breast cancer. Although preclinical data demonstrates that blockade of these receptors inhibits breast cancer growth, progression, and drug resistance, therapies targeting the IGF, insulin, and GH receptors (GHRs) have not been successful in producing significant increases in progression-free, disease-free, or overall survival for patients with breast cancer. The failure to demonstrate a benefit of growth factor blockade in clinical trials can be attributed to redundancy in IGF, insulin, and GHR signaling pathways. All 3 receptors are able to activate oncogenic phosphoinositide-3 kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Consequently, multitargeted blockade of growth factor receptors and their common downstream kinases will be necessary for the successful treatment of breast cancer.


Entamoeba histolytica: computer-assisted modeling of phosphofructokinase for the prediction of broad-spectrum antiparasitic agents.
Pyrophosphate-dependent phosphofructokinase (PPi-PFK) is the rate-limiting glycolytic enzyme found in the pathogenic protists Entamoeba histolytica, Giardia lamblia, Toxoplasma gondii, Trichomonas vaginalis, and Naegleria fowleri. The enzyme differs significantly from ATP-dependent phosphofructokinases found in humans and as such represents an important drug target. Current therapy for infections caused by these pathogens is inadequate, especially for children, pregnant women, and the immune compromised. The development of more selective, safer agents in imperative, as parasitic infections are currently a significant health threat worldwide and will likely become increasingly common agents of disease in the future. For the purpose of designing drugs to treat parasitic infections, we have constructed a model of PPi-PFK from E. histolytica based on the three-dimensional structure of the ATP-dependent PFK from Bacillus stearothermophilus. The model was used with the computer program Dock 3.5 (University of California, San Francisco) to predict the binding of pyrophosphate and selected bisphosphonates to the enzyme. The predicted drug-enzyme interactions suggested that two of these compounds would be competitive inhibitors of pyrophosphate. These drugs were tested against E. histolytica and inhibited the growth of amebae in vitro. This class of compounds may have broad-spectrum antiparasitic activity and, in the future, may facilitate the treatment of serious parasitic infections.


Estimating leaf day respiration from conventional gas exchange measurements.
Leaf day respiration (Rd ) strongly influences carbon-use efficiencies of whole plants and the global terrestrial biosphere. It has long been thought that Rd is slower than respiration in the dark at a given temperature, but measuring Rd by gas exchange remains a challenge because leaves in the light are also photosynthesizing. The Kok method and the Laisk method are widely used to estimate Rd . We highlight theoretical limitations of these popular methods, and recent progress toward their improvement by using additional information from chlorophyll fluorescence and by accounting for the photosynthetic reassimilation of respired CO2 . The latest evidence for daytime CO2 and energy release from the oxidative pentose phosphate pathway in chloroplasts appears to be important to understanding Rd .


Impact of new technologies on metabolic care in the intensive care unit.
Technological innovations in the ICU have lead to extraordinary advances in modern critical care. Renal replacement therapy (RRT) innovations and ventricular assist devices (VAD) are now becoming common interventions in the ICU environment. The purpose of this article is to describe the impact of RRT and VAD on critical care medicine with particular reference to metabolic care. Continuous venovenous hemofiltration and slow low efficient daily dialysis are effective modalities of RRT in hemodynamically unstable patients. These continuous forms of RRT can result in accentuated protein and nutrient losses but also provide an opportunity for intradialytic parenteral nutrition support. VAD patients typically have cardiac cachexia and develop chronic critical illness syndrome. Intensive metabolic support, incorporating trophic, concentrated, semielemental enteral nutrition, supplemental parenteral nutrition, and intensive insulin therapy is a rational strategy to implement in VAD patients. Unfortunately, there is insufficient evidence at this time to support the routine use of these nutritional interventions with RRT and VAD. Patients requiring RRT or VAD are at high nutritional risk, which negatively affects ICU outcome. Prompt nutritional risk assessment and early optimization of metabolic care is crucial in this patient population.


Effect of pre-cesarean foot reflexology massage on anxiety of primiparous women.
Introduction Anxiety is a common feeling in cesarean section and lack of attention to it is associated with negative consequences for health of mother and child. Reflexology is a way to reduce anxiety. So far, the effect of reflexology on pre-cesarean anxiety has not been evaluated. Therefore, we aimed to evaluate the effect of pre-cesarean foot reflexology massage on the anxiety of women during their first pregnancy. Materials and Methods This study is a three-group clinical trial that was conducted in 2019. The study sample consisted of 90 pregnant women hospitalized for cesarean section in Zahedan who were randomly divided into three groups of 30 women. The subjects completed the state section of Spielberger anxiety questionnaire. The control group did not receive any intervention. For two groups, 1 h before surgery, a group received reflexive massage, and the another group simple massage. Duration of massage for each group was 30 min. After 30 min, the subjects completed the state section of Spielberger questionnaire again. Statistical analysis was performed by SPSS software program, version 21.0. ANOVA and ANCOVA tests were used to compare between groups and paired t-test was used for intra-group comparisons. Results The results showed that the level of anxiety was significantly reduced in the reflexology massage group (from 55 ± 8 to 40 ± 7) as well as simple massage group (from 51 ± 10 to 47 ± 7) (p<0.001). In the control group, anxiety was increased (from 49 ± 9 to 56 ± 9) (p<0.001). Comparison between the three groups by ANCOVA indicated that reflexology massage and simple massage significantly decreased anxiety scores (p>0.001 and p>0.001,respectively). Reflexive massage significantly reduced anxiety scores (p>0.001) as compared to simple massage. Conclusion The results of this study revealed the positive effect of reflexology massage on pre-cesarean anxiety. Because reflexology massage is an inexpensive, simple, and easy approach, the use of this non-pharmaceutical method is recommended to reduce pre-cesarean anxiety.


Oxygen radicals generated at reflow induce peroxidation of membrane lipids in reperfused hearts.
To test whether generation of oxygen radicals during postischemic reperfusion might promote peroxidation of cardiac membrane lipids, four groups of Langendorff-perfused rabbit hearts were processed at the end of (a) control perfusion, (b) 30 min of total global ischemia at 37 degrees C without reperfusion, (c) 30 min of ischemia followed by reperfusion with standard perfusate, (d) 30 min of ischemia followed by reperfusion with the oxygen radical scavenger human recombinant superoxide dismutase (h-SOD). The left ventricle was homogenized and tissue content of malonyldialdehyde (MDA), an end product of lipid peroxidation, was measured on the whole homogenate as well as on various subcellular fractions. Reperfusion was accompanied by a significant increase in MDA content of the whole homogenate and of the fraction enriched in mitochondria and lysosomes. This phenomenon was not observed in hearts subjected to ischemia but not reperfused, and was similarly absent in those hearts which received h-SOD at reflow. Reperfused hearts also had significantly greater levels of conjugated dienes (another marker of lipid peroxidation) in the mitochondrial-lysosomal fraction. Again, this phenomenon did not occur in ischemic hearts or in reperfused hearts treated with h-SOD. Unlike the effect on tissue MDA and conjugated dienes, reperfusion did not significantly stimulate release of MDA in the cardiac effluent. Treatment with h-SOD was also associated with significant improvement in the recovery of cardiac function. In conclusion, these data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow.


Bacterial cell division proteins as antibiotic targets.
Proteins involved in bacterial cell division often do not have a counterpart in eukaryotic cells and they are essential for the survival of the bacteria. The genetic accessibility of many bacterial species in combination with the Green Fluorescence Protein revolution to study localization of proteins and the availability of crystal structures has increased our knowledge on bacterial cell division considerably in this century. Consequently, bacterial cell division proteins are more and more recognized as potential new antibiotic targets. An international effort to find small molecules that inhibit the cell division initiating protein FtsZ has yielded many compounds of which some are promising as leads for preclinical use. The essential transglycosylase activity of peptidoglycan synthases has recently become accessible to inhibitor screening. Enzymatic assays for and structural information on essential integral membrane proteins such as MraY and FtsW involved in lipid II (the peptidoglycan building block precursor) biosynthesis have put these proteins on the list of potential new targets. This review summarises and discusses the results and approaches to the development of lead compounds that inhibit bacterial cell division.


Use of molecule imprinting-chemiluminescence method for the determination of tamoxifen in breast cancer sufferers' urine.
The reaction between soluble Mn(IV) and tamoxifen can produce chemiluminescence and formaldehyde can enhance this chemiluminescence reaction. A tamoxifen molecular imprinted polymer (MIP) was synthesized and its adsorption selectivity to tamoxifen in aqueous solution was evaluated. Using a synthesized tamoxifen MIP as the recognition material and a soluble Mn(IV)-formaldehyde-tamoxifen chemiluminesence system as the detection system, a new molecule imprinting-chemiluminesence method of determination of tamoxifen was established. The response range of this method was 1.0 x 10(-7)-6.0 x 10(-6) g/mL, with a linear correlation coefficient of 0.997. The detection limit was 4 x 10(-8) g/mL. The relative standard deviation for 5.0 x 10(-7) g/mL tamoxifen solution was 4.1% (n = 9).


Contrast-enhanced multidetector computed tomography to diagnose pulmonary thromboembolism in an awake dog with pyothorax.
To (1) describe the use of contrast-enhanced multidetector computed tomography (CE-MDCT) for identifying pulmonary thromboembolism (PTE) in an awake dog with pyothorax, (2) report the first documented case of PTE associated with pyothorax in veterinary medicine, and (3) review diagnostic imaging modalities and therapeutic options for PTE. A 5-year, 4-month-old female neutered Labrador Retriever was presented for respiratory distress secondary to a pyothorax. The dog underwent thoracic exploratory surgery in which no underlying etiology was identified. Aerobic bacterial culture grew Streptococcus canis. The patient remained hypoxemic despite thoracocentesis and surgery. CE-MDCT was performed without general anesthesia and showed luminal-filling defects in the right cranial and right and left caudal lobar primary pulmonary arteries consistent with PTE. Anticoagulant therapy using unfractionated heparin was initiated. The dog responded well and was discharged 3 days postoperatively. To the authors' knowledge, this is the first reported case of PTE diagnosed in a dog with pyothorax using CE-MDCT.


Inverse agonist action of Leu-enkephalin at delta(2)-opioid receptors mediates spinal antianalgesia.
Dynorphin A(1-17) given intrathecally releases spinal cholecystokinin to produce an antianalgesic action against spinal morphine in the tail-flick test in CD-1 mice. The present study showed that following the cholecystokinin step, a delta(2)-opioid inverse agonist action of Leu-enkephalin (LE), was involved. Pretreatment with intrathecal LE antiserum eliminated dynorphin and cholecystokinin-8s antianalgesia. A small dose of LE intrathecally produced antianalgesia that like that from dynorphin A(1-17) and cholecystokinin was eliminated by naltriben but not 7-benzylidenenaltrexone (delta(2)- and delta(1)-opioid receptor antagonist, respectively). This LE step was followed by N-methyl-D-aspartate (NMDA) receptor activation. MK801, an NMDA receptor antagonist, eliminated the antianalgesia from dynorphin A(1-17), cholecystokinin-8s, and LE. Furthermore, none of the three were effective against morphine analgesia in 129S6/SvEv mice possibly because of their deficiency in NMDA receptor response. In 129S6/SvEv mice, [D-Ser(2)]-Leu-enkephalin-Thr analgesia was not attenuated by LE; thus, this delta(2)-analgesic agonist and LE inverse agonist action did not occur through competition at the same delta(2)-receptor in CD-1 mice. In CD-1 mice, a linear sequence of dynorphin A(1-17) --> cholecystokinin --> LE --> NMDA receptors was indicated: cholecystokinin antiserum inhibited cholecystokinin but not LE; naltriben inhibited LE but not NMDA. The uniqueness of LE in linking dynorphin A(1-17), cholecystokinin, delta(2)-opioid, and NMDA receptor activation may unify the separate known mechanisms involved in the antiopioid actions of these components against morphine.


Residential exposure to solar ultraviolet radiation and incidence of childhood hematological malignancies in France.
Few studies have investigated the relationship between solar ultraviolet radiation (UV) and childhood hematological malignancies (CHM). This study addresses the associations between residential UV exposure at diagnosis and the incidence of types and subtypes of CHM, by age and gender, in France, over a long period, on the fine scale of the 36,326 Communes that constitute mainland France. The 9,082 cases of acute leukemia and 3,563 cases of lymphoma diagnosed before the age of 15 years from 1990 to 2009 were provided by the French National Registry of Childhood Hematological Malignancies. The incidence of CHM was calculated by Commune, year, age and gender and expressed as the standardized incidence ratio (SIR). UV data from 1988 to 2007 were extracted from the EUROSUN database. The annual daily average UV exposure of the children ranged from 85.5 to 137.8 J/cm(2). For each additional 25 J/cm(2), there was a significant increase in precursor B-cell acute lymphoblastic leukemia (PBC-ALL) in children aged less than 5 years (SIR 1.18; 95% CI 1.10-1.27). Further analysis of PBC-ALL in the young children suggested a better fit of models with a threshold, with the risk increasing above 100 J/cm(2), for which the SIR was 1.24 (95% CI 1.14-1.36) for a 25 J/cm(2) increase. The results remained stable in analyses stratifying by deprivation index or degree of urbanization of the Communes. The study suggests that higher residential UV exposure may be positively associated with a higher incidence of PBC-ALL in early childhood.


On-chip all-dielectric fabrication-tolerant zero-index metamaterials.
Zero-index metamaterials (ZIMs) offer unprecedented ways to manipulate the flow of light, and are of interest for wide range of applications including optical cloaking, super-coupling, and unconventional phase-matching properties in nonlinear optics. Impedance-matched ZIMs can be obtained through a photonic Dirac-cone (PDC) dispersion induced by an accidental degeneracy of an electric monopole and a transverse magnetic dipole mode at the center of the Brillouin zone. Therefore, PDC is very sensitive to fabrication imperfections. In this work, we propose and demonstrate fabrication-tolerant all-dielectric ZIM in telecom regime that supports near PDC dispersion over much wider parameter space than conventional designs. The prism device integrated with Si photonics is fabricated and measured for the verification.


Research priorities in geriatric palliative care: multimorbidity.
With global aging and scientific advances extending survival, the number of adults experiencing multiple chronic conditions has grown substantially and is projected to increase by another third between 2000 and 2030. Among the many challenges posed by multimorbidity, some of the most pressing include how to characterize and measure comorbid conditions, understand symptoms and illness burden, and provide person-centered care in the context of competing health care priorities and increasing complexity. In this white paper emanating from a National Institute on Aging supported conference to discuss research gaps at the geriatrics-palliative care interface, the authors review common definitions of multimorbidity; describe the association between multimorbidity and quality of life, functional status, quality of care, and health care utilization; note content and methodological gaps in multimorbidity evidence; and make recommendations regarding research priorities in this area of expanding public health impact.


Galectin-3: A Positive Regulator of Leukocyte Recruitment in the Inflamed Microcirculation.
In vivo and ex vivo imaging were used to investigate the function of galectin-3 (Gal-3) during the process of leukocyte recruitment to the inflamed microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3-/-, and CX3CR1gfp/+ mice were assessed by intravital microscopy after PBS, IL-1β, TNF-α, or recombinant Gal-3 treatment. These cellular responses were investigated further using flow-chamber assays, confocal microscopy, flow cytometry, PCR analysis, and proteome array. We show that mechanisms mediating leukocyte slow rolling and emigration are impaired in Gal-3-/- mice, which could be because of impaired expression of cell adhesion molecules and an altered cell surface glycoproteome. Local (intrascrotal) administration of recombinant Gal-3 to wild-type mice resulted in a dose-dependent reduction in rolling velocity associated with increased numbers of adherent and emigrated leukocytes, ∼50% of which were Ly6G+ neutrophils. Intrascrotal administration of Gal-3 to CX3CR1gfp/+ mice confirmed that approximately equal numbers of monocytes are also recruited in response to this lectin. Exogenous Gal-3 treatment was accompanied by increased proinflammatory cytokines and chemokines within the local tissue. In conclusion, this study unveils novel biology for both exogenous and endogenous Gal-3 in promoting leukocyte recruitment during acute inflammation.


Genetic control of gamete quality in the mouse--a tribute to Halina Krzanowska.
In this article, we summarise the principal research findings of the distinguished Polish scientist, Professor Halina Krzanowska, related to the genetic control of mammalian gamete quality. During the early stages of her career, Halina Krzanowska conducted experiments on poultry and then she moved on to work on mice. All her research on gamete quality was conducted on the research models, consomic, congenic and recombinant inbred strains, which Krzanowska developed herself. These models differed mostly in their fertility. Krzanowska was one of the first researchers to demonstrate the influence of chromosome Y on the morphology of mice spermatozoa. She also showed that the uterotubal junction is in vivo a selection barrier for the morphologically abnormal spermatozoa, whereas in vitro abnormal spermatozoa are able to participate in fertilization, the function of selective barrier being performed by the granulosa cell layer and the zona pellucida. Another model which Krzanowska produced were chimaeras, which she used to find out if the percentage of abnormal spermatozoa and the efficiency of fertilization are determined by germ cells themselves or by environmental factors and she discovered that sperm head shape, the proportion of abnormal sperm and fertilizing capacity are determined mainly by the genotype of germ cells and only minimally by environmental factors.


Real-world performance of the new C3 Gore Excluder stent-graft: 1-year results from the European C3 module of the Global Registry for Endovascular Aortic Treatment (GREAT).
The European C3 module of the Global Registry for Endovascular Aortic Treatment (GREAT) provides "real-world" outcomes for the new C3 Gore Excluder stent-graft, and evaluates the new deployment mechanism. This report presents the 1-year results from 400 patients enrolled in this registry. Between August 2010 and December 2012, 400 patients (86.8% male, mean age 73.9 ± 7.8 years) from 13 European sites were enrolled in this registry. Patient demographics, treatment indication, case planning, operative details including repositioning and technical results, and clinical outcome were analyzed. Technical success was achieved in 396/400 (99%) patients. Two patients needed intraoperative open conversion, one for iliac rupture, the second because the stent-graft was pulled down during a cross-over catheterization in an angulated anatomy. Two patients required an unplanned chimney renal stent to treat partial coverage of the left renal artery because of upward displacement of the stent-graft. Graft repositioning occurred in 192/399 (48.1%) patients, most frequently for level readjustment with regard to the renal arteries, and less commonly for contralateral gate reorientation. Final intended position of the stent-graft below the renal arteries was achieved in 96.2% of patients. Thirty-day mortality was two (0.5%) patients. Early reintervention (≤30 days) was required in two (0.5%) patients. Mean follow-up duration was 15.9 ± 8.8 months (range 0-37 months). Late reintervention (>30 days) was required in 26 (6.5%) patients. Estimated freedom from reintervention at 1 year was 95.2% (95% CI 92.3-97%), and at 2 years 91.5% (95% CI 86.8-94.5%). Estimated patient survival at 1 year was 96% (95% CI 93.3-97.6%) and at 2 years 90.6% (95% CI 85.6-93.9%). Early real-world experience shows that the new C3 delivery system offers advantages in terms of device repositioning resulting in high deployment accuracy. Longer follow-up is required to confirm that this high deployment accuracy results in improved long-term durability.


Autoimmune retinopathy.
To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly possible future therapies. Perspective based on literature review and clinical expertise. Interpretation of current literature, relying on the authors' clinical experience. Autoimmune retinopathy is a rare immunologic disease characterized by the presence of circulating antiretinal antibodies along with electroretinographic and visual field abnormalities. An ophthalmic examination can be normal or show minimal findings. The diagnosis of autoimmune retinopathy is made difficult by diagnostic criteria that are both limited and nonstandardized. Currently, the diagnosis is made based on the demonstration of serum antiretinal antibodies and the presence of clinical manifestations (including abnormal electroretinographic findings). The mere presence of these antibodies is not diagnostic. Lack of an accepted gold standard for antiretinal antibodies detection and poor interlaboratory concordance make the diagnosis challenging. There are anecdotal reports of immunosuppressive therapy in autoimmune retinopathy; however, the response to treatment is variable, with more favorable results achieved in paraneoplastic retinopathy, particularly cancer-associated retinopathy, with a combination of chemotherapy and immunosuppression. Whether an earlier attempt to treat nonparaneoplastic autoimmune retinopathy would be more beneficial is unknown. Early treatment attempts are limited by lack of sensitive and specific assays and definitive clinical criteria. Little is known about the clinical course, prognosis and treatment of autoimmune retinopathy. Additional studies should examine the specificity and pathogenicity of antiretinal antibodies and screen for biomarkers, and they should be conducted concurrently with studies seeking to identify appropriate treatment.


Older adults at greater risk for Alzheimer's disease show stronger associations between sleep apnea severity and verbal memory.
Background : Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimer's disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. Methods : Eighty-one adults (mean age:61.7±6.0 years, 62% females, 32% a polipoprotein E ε4 allele ( APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. Results : Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60+ years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. Conclusion : Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.


Transverse Density Fluctuations around the Ground State Distribution of Counterions near One Charged Plate: Stochastic Density Functional View.
We consider the Dean-Kawasaki (DK) equation of overdamped Brownian particles that forms the basis of the stochastic density functional theory. Recently, the linearized DK equation has successfully reproduced the full Onsager theory of symmetric electrolyte conductivity. In this paper, the linear DK equation is applied to investigate density fluctuations around the ground state distribution of strongly coupled counterions near a charged plate, focusing especially on the transverse dynamics along the plate surface. Consequently, we find a crossover scale above which the transverse density dynamics appears frozen and below which diffusive behavior of counterions can be observed on the charged plate. The linear DK equation provides a characteristic length of the dynamical crossover that is similar to the Wigner-Seitz radius used in equilibrium theory for the 2D one-component plasma, which is our main result. Incidentally, general representations of longitudinal dynamics vertical to the plate further suggest the existence of advective and electrical reverse-flows; these effects remain to be quantitatively investigated.


Overview of organic amendments for management of plant-parasitic nematodes, with case studies from Florida.
Organic amendments have been widely used for management of plant-parasitic nematodes. Relatively rapid declines in nematode population levels may occur when decomposing materials release toxic compounds, while longer-term effects might include increases in nematode antagonists. Improved crop nutrition and plant growth following amendment use may lead to tolerance of plant-parasitic nematodes. Results depend on a great variety of factors such as material used, processing/composting of material, application rate, test arena, crop rotation and agronomic practices, soil type, climate, and other environmental factors. Reasons for variable performance and interpretation of results from amendment studies are discussed. Case studies of amendments for nematode management are reviewed from Florida, where composts and crop residues are the most frequently used amendments. Plant growth was often improved by amendment application, free-living nematodes (especially bacterivores) were often stimulated, but suppression of plant-parasitic nematodes was inconsistent. Amendments were generally not as effective as soil fumigation with methyl bromide for managing root-knot nematodes (Meloidogyne spp.), and often population levels or galling of root-knot nematodes in amended plots did not differ from those in non-amended control plots. While amendments may improve plant growth and stimulate soil food webs, additional study and testing are needed before they could be used reliably for management of plant-parasitic nematodes under Florida conditions.


Potential Modulation of Human NAD[P]H-Quinone Oxidoreductase 1 (NQO1) by EGCG and Its Metabolites-A Systematic Computational Study.
At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o-quinone metabolites of gallic acid or EGCG are causative agents for this hepatotoxicity. However, no experimental information is available at the molecular level on the possible role of NQO1 in the detoxification of EGCG and its metabolites, including reactive intermediates. In the present study, we investigated the possibility of NQO1 inhibition by EGCG and its metabolites by studying their interaction profiles and binding mechanism at the active site of NQO1 using molecular docking, binding free energy calculations, and molecular dynamics (MD) simulations. The binding free energy calculations showed that some metabolites exhibited strong predicted binding affinity and found that the binding orientation of the EGCG metabolites overlapped with that of dicoumarol found in an NQO1 X-ray crystal structure. The results suggest that these metabolites may act as strong NQO1 inhibitors, highlighting the need for experimental validation of this with appropriate biological methods. The Prime MM-GBSA computed average binding free energies after MD simulations of compounds 1, 2, 24, 31, and 33 revealed that these compounds highly favored van der Waals (VdW) and Coulombic interactions with NQO1. In addition, the MD results revealed that selected EGCG metabolites formed a stable and strong complex with NQO1, with amino acids W105, Y126, Y128, H161, F178, H194, F232, and F236 being critical for potential NQO1 binding. The current results together with experimental data as well as studies of the polymorphisms of NQO1 (especially C609T) may explain the observed idiosyncratic hepatotoxicity caused by the consumption of green tea and its constituents.


[Single-stage total removal of the cervical vertebrae in plasmacytoma].
The article includes the description of successful case of surgical treatment of a patient (53 years old) with VC plasmocytoma, complicated with upper paraparesis, tetanoid paraplegia and pelvic disturbances. The patient has been subjected to complete removal of VC in one stage of 2 accesses. The patient's spine has been fixed by means of implant, made of corundum porous ceramic, metal plate and lavsan band. A year after the operation--no tumor recurrence, the patient walks without additional support. In the process of discussion of the given observation the authors suggest that the technical difficulties of the operation are quite surmountable and its expediency is obvious.


Toxicity testing of nanomaterials.
The large-scale production and consumer exposure to a variety of nanotechnology innovations has stirred interest concerning the health consequences of human exposure to nanomaterials. In order to investigate these questions, in vitro systems are used to rapidly and inexpensively predict the effects of nanomaterials at the cellular level. Recent advances in the toxicity testing of nanomaterials are beginning to shed light on the characteristics, uptake and mechanisms of their toxicity in a variety of cell types. Once the nanomaterials have been satisfactorily characterized, the evaluation of their interactions with cells can be studied with microscopy and biochemical assays. The combination of viability testing, observation of morphology and the generation of oxidative stress provide clues to the mechanisms of nanomaterial toxicity. The results of these studies are used to better understand how the size, chemical composition, shape and functionalization may contribute to their toxicity. This chapter will introduce the reader to the impact of nanomaterials in the workplace and marketplace with an emphasis on carbon-based and metal-based nanomaterials, which are most commonly encountered. While most purified carbon nanomaterials were nontoxic to many cell lines, many metal nanoparticles (e.g., silver or manganese) were more toxic. Other side- effects of nanoparticle interactions with cells can also occur, such as increased branching and dopamine depletion. Further investigation into the characteristics, uptake and mechanisms of nanomaterial toxicity will continue to elucidate this fascinating and rapidly growing area of science.


Geographic variation in the sensitivity of an herbivore-induced seaweed defense.
Intraspecific variation in primary producer induced defenses may affect how these defenses contribute to population and community regulation. For instance, inducible defenses may play larger roles in primary producer populations that are sensitive to low levels of grazing than populations that only respond to high levels of grazing. Although the incidence of herbivore-induced defenses is well documented, and there are examples of geographic variation in these defenses, we have limited knowledge of the factors that affect sensitivity to grazing (i.e., the minimum grazer density needed to elicit these responses) within and among populations. Filling this gap is necessary to understand the importance of these defenses under different conditions. To address whether the sensitivity of seaweed induced defenses varies geographically, we exposed Northern and Southern California populations of the seaweed Silvetia compressa to five densities of the snail Tegula funebralis, under ambient, regional environmental conditions. Southern seaweeds required high levels of grazing to induce defenses, while all levels of herbivory decreased Northern seaweed palatability. To better understand these different responses to low levels of grazing, we conducted common garden experiments to directly test the roles of experimental environment and herbivore source. Consistent with initial experiments, Northern Silvetia responded to low levels of grazing, regardless of environmental conditions, while Southern Silvetia never responded to low levels of grazing, even after being acclimated to Northern environmental conditions for 24 d. Additionally, Southern Silvetia did not respond to grazing by Northern snails, suggesting that herbivore source did not explain this geographic pattern in inducible seaweed defenses. Together, these observations suggest that the seaweed source explains this geographic pattern in sensitivity. Trade-offs with constitutive defenses did not help explain this pattern, as Southern Silvetia had weaker constitutive defenses than Northern seaweeds. This may be due to a combination of low grazing pressure and low predictability of attack in the South. Thus, population variation in sensitivity may be due to long-term differences in environmental histories, resulting in local adaptation or legacy effects from exposure to local conditions. Overall, our results indicate that these herbivore-induced responses may be more important in Northern Silvetia populations than Southern ones.


Anatomic and refractional correlations in earliest glaucomatous visual field defects.
In glaucoma, initial visual field scotomas can be peripheral or central, whereas central scotomas are more severe and can disrupt daily activities. Individual anatomical features may influence the distribution of retinal nerve fibers and the starting site of visual field defects in glaucoma. In this study, we aimed to correlate myopia and hyperopia or anatomical variation of the disk-fovea angle with initial central or peripheral lesions in the visual field. This cross-sectional study included patients with primary open-angle glaucoma divided into a group of isolated central or peripheral scotomas in the visual field with MD > or equal to -6 dB, correlating with the degree of ametropia and anatomical variations, such as the disk-fovea angle. We included 52 patients with glaucoma. Of 20 myopic patients, 6 (30%) had central scotomas, and 14 (70%) had peripheral scotomas. Of 32 hyperopic patients, 12 (37.5%) had central scotomas, and 20 (63.5%) had peripheral scotomas. Regarding the disk-fovea angle, 25 eyes had the disk-fovea angle of < -7°, with 9 (36%) eyes presenting with central scotoma, and 27 eyes presented with the disk-fovea angle of > -7°, with 9 (33.3%) eyes presenting with a central scotoma. This study showed an association between ametropia and scotomas on the perimetry in patients with glaucoma. Patients had a higher incidence of peripheral scotomas, but hyperopic patients had a greater number of central scotomas than myopic patients, and myopic patients had more peripheral scotomas than hyperopic patients. The disk-fovea angle was not correlated with scotomas in initial glaucoma.


Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.
Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations. As its computational engine, the tool uses a custom implementation of the forward stagewise algorithm for sparse regression and nonnegative least squares for numerical optimization. Analysis of 2,700 synthetic cancer genomes with and without noise demonstrates that SigProfilerAssignment outperforms four commonly used approaches for assigning mutational signatures. SigProfilerAssignment is freely available at https://github.com/AlexandrovLab/SigProfilerAssignment with a web implementation at https://cancer.sanger.ac.uk/signatures/assignment/.


Frontal sinus surgery: endoscopic technique and preliminary results.
Endoscopic frontal sinus surgery, once the last frontier in the evolution of endoscopic sinus surgery, is considered difficult, risky to the patient, and likely to result in a high failure rate. We clarify the surgical anatomy for frontal sinus surgery that, based on a review of our data, provides safe and predictable access to the frontal sinus. We studied 200 consecutive patients with respect to indications, endoscopic and radiographic findings, results, and complications. The study will describe the technique in detail, including the following points: 1) computed tomography identification of the superior attachment of the uncinate process; 2) complete removal of the uncinate process, including its superior attachments, by using the microdebrider; 3) removal of the agger nasi cell, if present; and 4) verification of an open frontal sinus by a transillumination or image-guided system. Postoperative assessment of patients' symptoms and the confirmation of a patent frontal sinus by office endoscopy and transillumination indicated a 90% patency for short-term follow-up (average 12.2 months). There were no major complications. Postoperative complications included frontal recess stenosis, polypoid mucosa occluding the frontal recess, and middle turbinate lateralization. All of these situations may lead to recurrence of infection and symptoms. In-depth understanding of anatomic variations of the uncinate process and precise surgical removal of its superior attachments provide surgical access to the frontal sinus that is based on the natural ostia and is, therefore, more likely to remain patent.


MicroRNA-148b enhances the radiosensitivity of non-Hodgkin's Lymphoma cells by promoting radiation-induced apoptosis.
Growing evidence has demonstrated that microRNAs (miRNAs) play an important role in regulating cellular radiosensitivity. This study aimed to explore the role of miRNAs in non-Hodgkin's lymphoma (NHL) radiosensitivity. Microarray was employed to compare the miRNA expression profiles in B cell lymphoma cell line Raji before and after a 2-Gy dose of radiation. A total of 20 differentially expressed miRNAs were identified including 10 up-regulated and 10 down-regulated (defined as P < 0.05). Among the differentially expressed miRNAs, miR-148b was up-regulated 1.53-fold in response to radiation treatment. A quantitative real-time polymerase chain reaction (PCR) assay confirmed the up-regulation of miR-148b after radiation. Transient transfection experiments showed that miR-148b was up-regulated by miR-148b mimic and down-regulated by miR-148b inhibitor in the Raji cells. A proliferation assay showed that miR-148b could inhibit the proliferation of Raji cells before and after radiation. A clonogenic assay demonstrated that miR-148b sensitized Raji cells to radiotherapy. MiR-148b did not affect the cell cycle profile of post-radiation Raji cells compared with controls. An apoptosis assay showed that miR-148b enhanced apoptosis of Raji cells after irradiation. Taken together, these results demonstrate that miR-148b increased the radiosensitivity of NHL cells probably by promoting radiation-induced apoptosis, which suggests that miR-148b plays an important role in the response of NHL to ionizing radiation.


Metabolic syndrome in schizophrenia.
To review the data with respect to prevalence of metabolic syndrome (MetS) and its correlates in schizophrenia. For this review, electronic search engines PUBMED, Sciencedirect, and Google Scholar were used. Available data suggests that most of the studies have been of cross-sectional design. Prevalence rates of MetS have varied from 11% to 69% in medicated patients, and 4-26% in drug naive patients in cross-sectional evaluations. Longitudinal studies have shown the prevalence rates to range from 0% to 14% at the baseline in drug naive patients, which increase to as high as 52.4% by 3 months of antipsychotic medication treatment. The prevalence rates of MetS in patients with schizophrenia are much higher than that seen in general population or healthy controls. Though there is no causal association with any demographic or clinical variables, the risk increases with increase in age. Among antipsychotics, there seems to be an association between MetS and atypical antipsychotics like clozapine and olanzapine. Therefore, the psychiatrists should be more vigilant regarding the presence of MetS in these high risk groups. Research on biological correlates of MetS in schizophrenia is still in its primitive stage, however, these is some evidence to suggest an association of MetS with adiponectin levels, hematological indices, methylenetetrahydrofolate reductase (MTHFR) and Alpha-1A adrenergic receptor (ADRA1A) gene. These areas hold promise, and targeting these with appropriate interventions may help us to prevent the occurrence of MetS in patients with schizophrenia in future.


Characterization of ZnO as substrate for DSSC.
We present a complete analysis of the photoinjection process in 3 nm spherical ZnO nanoparticles with different dyes attached to their surface. The study was carried using a TD-DFTB model to describe the quantum dynamics of charge transfer in the presence of an external time dependent electric field simulating resonant illumination. The ZnO + dye systems have been classified according to the injection process (type I and type II) that they present. In addition, the calculated charge transfer shows that many dyes present hole injection into the nanoparticle. We have classified the charge transfer into holes or electron and compare these results with the TiO2 + dye system obtained from the literature.


Destination memory in social interaction: better memory for older than for younger destinations in normal aging?
Destination memory, a memory component allowing the attribution of information to its appropriate receiver (e.g., to whom did I lend my pen?), is compromised in normal aging. The present paper investigated whether older adults might show better memory for older destinations than for younger destinations. This hypothesis is based on empirical research showing better memory for older faces than for younger faces in older adults. Forty-one older adults and 44 younger adults were asked to tell proverbs to older and younger destinations (i.e., coloured faces). On a later recognition test, participants had to decide whether they had previously told some proverb to an older/younger destination or not. Prior to this task, participants reported their frequency of contact with other-age groups. The results showed lower destination memory in older adults than in younger adults. Interestingly, older adults displayed better memory for older than for younger destinations. The opposite pattern was seen in younger adults. The low memory for younger destinations, as observed in older adults, was significantly correlated with limited exposure to younger individuals. These findings suggest that for older adults, the social experience can play a crucial role in the destination memory, at least as far as exposure to other-age groups is concerned.


A systematic review of primary healthcare provider education and training using the Chronic Care Model for childhood obesity.
The purpose of this systematic review was to examine 15 studies which evaluated interventions aimed at improving primary care providers' identification, assessment, prevention and/or management of obesity in children and adolescents. Interventions were evaluated in terms of length, components addressing nutrition, physical activity and behavioural counselling consistent with expert recommendations, and inclusion of components of the Chronic Care Model. Overall, training interventions were delivered face to face or in a combination of lecture, assigned readings, preceptorship with experienced providers, and critiqued evaluations of interactions of the provider with the patient and family. Many studies incorporated training of providers as an initial step prior to delivering an obesity intervention for children and adolescents measuring weight loss and behaviour change as outcomes. Each study was evaluated for components of the Chronic Care Model. The interventions most frequently utilized the elements of self-management support (69%), decision support (100%), delivery system support (77%) and clinical information systems (23%). Although science in this area is emerging, results suggest that intervention programmes that included more components of the Chronic Care Model were more effective.


West Texas nursing education portal project: developing a regional centralized application system.
Because of the nursing shortage and a demand for maximum enrollment, a group of five baccalaureate and seven associate degree nursing programs in West Texas first met in 2007 to form the West Texas Nursing Education Consortium (WTNEC). To emphasize the importance of scale and distance, the West Texas region is larger than all of the northeastern states combined. The founding group agreed that the first mission of WTNEC should be to pool resources in order to increase admission and graduation rates for WTNEC schools. Two years later, this mission is being accomplished by the implementation of a plan designed to increase participating schools' admissions, retention, and graduation rates. A grant proposal was written and funded to develop a central regionalization of the application process for entry into WTNEC generic programs (associates degree in nursing and bachelor of science in nursing), with the goal of decreasing and possibly eliminating student vacancy rates in member schools and perhaps reducing the resources needed by each school for the admission process. The implemented centralized application system allowed prospective students to apply online to the centralized admission portal. Students maintained the freedom to choose the nursing program(s) they wanted to attend, but they were also made aware of possible openings in other participating schools. The admission portal also saved potential students time and money by submitting one centralized application, resulting in consolidation of the nursing school application process. Eleven of the 12 consortium schools participated in the centralized application system.


Ethical and legal issues in research involving human subjects: do you want a piece of me?
The conduct of biomedical research involving the participation of human beings implicates a variety of ethical concerns pertaining to such values as dignity, bodily integrity, autonomy, and privacy. These ethical concerns have been translated into a complex regulatory apparatus in the USA, containing specific legal provisions concerning such matters as participant safety, informed consent, and confidentiality. A topic of particular interest for pathologists is the handling of human tissue specimens that may be used for present, or stored for future, research purposes. This article examines the ethical and legal ramifications of obtaining and storing tissue samples for research purposes, with special attention to the issues of informed consent and confidentiality.


The arbuscular mycorrhizal fungus Rhizophagus irregularis uses the copper exporting ATPase RiCRD1 as a major strategy for copper detoxification.
Arbuscular mycorrhizal (AM) fungi establish a mutualistic symbiosis with most land plants. AM fungi regulate plant copper (Cu) acquisition both in Cu deficient and polluted soils. Here, we report characterization of RiCRD1, a Rhizophagus irregularis gene putatively encoding a Cu transporting ATPase. Based on its sequence analysis, RiCRD1 was identified as a plasma membrane Cu + efflux protein of the P1B1-ATPase subfamily. As revealed by heterologous complementation assays in yeast, RiCRD1 encodes a functional protein capable of conferring increased tolerance against Cu. In the extraradical mycelium, RiCRD1 expression was highly up-regulated in response to high concentrations of Cu in the medium. Comparison of the expression patterns of different players of metal tolerance in R. irregularis under high Cu levels suggests that this fungus could mainly use a metal efflux based-strategy to cope with Cu toxicity. RiCRD1 was also expressed in the intraradical fungal structures and, more specifically, in the arbuscules, which suggests a role for RiCRD1 in Cu release from the fungus to the symbiotic interface. Overall, our results show that RiCRD1 encodes a protein which could have a pivotal dual role in Cu homeostasis in R. irregularis, playing a role in Cu detoxification in the extraradical mycelium and in Cu transfer to the apoplast of the symbiotic interface in the arbuscules.


Possible ranitidine hepatitis.
A 63-year-old woman developed anicteric hepatitis after two weeks of therapy with ranitidine. Despite continuation of therapy, her symptoms resolved within five days and transaminase levels returned to normal in the next four weeks, at which time use of the drug ceased. The gamma-glutamyl transpeptidase level returned to normal two weeks later. Although liver biopsy and drug rechallenge were not performed, no other cause for the reaction could be found.


Genotypic characterization and historical perspective of Mycobacterium tuberculosis among older and younger Finns, 2008-2011.
The Mycobacterium tuberculosis genotypes obtained from elderly Finns were assessed and compared with those obtained from younger Finns to comprehend the epidemiology of tuberculosis (TB) in Finland. From 2008 to 2011, a total of 1021 M. tuberculosis isolates were characterized by spoligotyping and 15-locus mycobacterial interspersed repetitive units-variable number tandem repeat typing. In total, 733 Finnish-born cases were included in the study, of which 466 (64%) were born before 1945 (older Finns). Of these, 63 (14%) shared an M. tuberculosis genotype with foreign-born or younger Finnish cases (born after 1945), and 59 (13%) shared a genotype with older Finnish cases. Eighty-five per cent had a unique genotypic profile while 70% belonged to T or Haarlem families, suggesting that ongoing transmission is infrequent among young and elderly Finns. Simultaneous reactivation of TB among older Finns was the most likely cause for clustering. As most isolates belonged to Haarlem or T, Finland was most likely affected by a similar TB epidemic at the beginning of the twentieth century as that seen in Sweden and Norway. Younger Finns were significantly more likely to be clustered (56% versus 27%, p<0.001), have pulmonary TB (87% versus 71%, p<0.001) and to be sputum smear positive (57% versus 48%, p<0.05) indicating that the risk of TB transmission from younger Finns is likely to be larger than from older Finns. The M. tuberculosis isolates from elderly Finns were associated with dominant lineages of the early twentieth century and differed from the heterogeneous lineages found among younger TB patients. Additionally, younger TB patients were more likely to transmit TB than elderly Finns.


Tandem affinity purification and identification of heterotrimeric g protein-associated proteins.
Heterotrimeric G proteins are the main signal-transducing molecules activated by G protein-coupled receptors. Their GTP-dependent activation leads to the regulation of different effectors such as adenylyl cyclases, phospholipases, and RhoGEFs. To understand the full biological consequences of GPCR signalling and to further understand the cross-talk with other signalling pathways, the complement of proteins associating with heterotrimeric G proteins needs to be identified. Here we describe our mass spectrometry-based proteomic approaches for the study of Gβγ and Gα protein complexes. This approach is predicated on the establishment of mammalian cell lines constitutively or inducibly expressing affinity-tagged versions of Gβγ or wild-type and constitutively active Gα subunits, respectively.


Optimization of artificial urine formula for in vitro cellular study compared with native urine.
Several artificial urine (AU) formulas have been developed to mimic the normal urine. Most of them are protein-free, particularly when secreted proteins (secretome) is to be analyzed. However, the normal urine actually contains a tiny amount of proteins. We hypothesized that urinary proteins at physiologic level play a role in preservation of renal cell biology and function. This study evaluated the effects from supplementation of 0-10% fetal bovine serum (FBS) into the well-established AU-Siriraj protocol on MDCK renal tubular cells. Time to deformation (TD) was reduced by both native urine and AU-Siriraj without/with FBS compared with complete culture medium (control). Among the native urine and AU-Siriraj without/with FBS, the cells in AU-Siriraj+2.5% FBS had the longest TD. Supplementation of FBS increased cell death in a dose-dependent manner (but still <10%). Transepithelial electrical resistance (TER) of the polarized cells in the native urine was comparable to the control, whereas that of the cells in AU-Siriraj+2.5% FBS had the highest TER. These data indicate that supplementation of 2.5% FBS into AU-Siriraj can prolong time to deformation and enhance polarization of renal tubular cells. Therefore, AU-Siriraj+2.5% FBS is highly recommended for in vitro study of cell biology and function (when secretome is not subjected to analysis).


A new nanosuspension prepared with wet milling method for oral delivery of highly variable drug Cyclosporine A: development, optimization and in vivo evaluation.
Cyclosporine A (CsA) is a cyclic polypeptide, that has been widely used for immunosuppression. This study aims to develop nanosuspension for oral administration of CsA using the wet milling (WM) method one of the top-down technologies. The WM method was optimized by studying the effects of critical process parameters for WM on the particle size (PS), particle size distribution (PDI), and zeta potential (ZP) of nanosuspensions using the Design of Experiment (DoE) approach. Nanosuspension was developed using hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS) and in vitro characterization studies were performed. In vitro dissolution and in vivo pharmacokinetic studies were conducted with biorelevant media (fasted and fed state simulated fluids) and fasted and fed states in rats, respectively. In vivo immunological studies were also performed. PS, PDI, and ZP values for nanosuspension were approximately 600 nm, 0.4, -25 mV, respectively. The solubility of CsA was increased by 4.5-folds by nanosuspensions. Dissolution studies showed that nanosuspension had higher dissolution than the commercial product in the FeSSIF medium. The pharmacokinetic study indicated that AUC0-24 values of CsA nanosuspension were to be 2.09 and 5.51-fold higher than coarse powder in fasted and fed conditions, respectively. Immunological studies were carried out after oral administration of nanosuspension for 21 days, the ratio of CD4+/CD8+ was found to be more acceptable than the commercial product. These results demonstrated that nanosuspension is a promising approach for increasing the bioavailability and avoiding the food effect on absorption of CsA which one of the highly variable drugs.


Expression of the P(₁B) -type ATPase AtHMA4 in tobacco modifies Zn and Cd root to shoot partitioning and metal tolerance.
Genetic modification of Zn/Cd accumulation in roots and shoots for biofortification or phytoremediation is a focus of this manuscript. We expressed AtHMA4 (a P(₁B) ATPase involved in Zn and Cd transport), AtHMA4-trunc (lacking the C-terminal region) and AtHMA4-C terminus (the C-terminal region alone) in tobacco under the CaMV 35S constitutive promoter and examined accumulation and tolerance to both metals. Expression of AtHMA4 enhanced Zn translocation to the shoots only at 10 μM Zn but not at 0.5, 100 and 200 μM Zn. AtHMA4-trunc did not show this effect and instead reduced Zn translocation to the shoot. AtHMA4-expressing plants showed a decrease in cadmium uptake when exposed to 0.25 and 5 μM Cd; this was also observed with AtHMA4-trunc-expressing lines, although to a lesser extent. Expression of AtHMA4-C-terminus containing potential metal binding sites increased cadmium and zinc concentrations in roots and shoots up to fourfold. We have demonstrated that both AtHMA4 and AtHMA4 C-terminus could be candidate genes/sequences for engineering modifications of zinc and cadmium root/shoot partitioning. However, the phenotype of transformants depended on the external metal concentration, thus it might be difficult to engineer a plant displaying the desired metal-related phenotype when grown under varying conditions of metal supply.


Prostate focal therapy: the rule or exception?
Prostate focal therapy has the potential to preserve urinary and sexual function while eliminating clinically significant cancer in a subset of men with low-volume, organ-confined prostate cancer. This systematic review aims to examine current evidence to determine the efficacy and safety of focal therapy for standard clinical application. Focal therapy reduces the rate of cancer progression and conversion to radical therapy in men on active surveillance for prostate cancer. As a strategy, success in focal therapy is heavily dependent on the use of imaging and targeted biopsies. Despite advances in these areas, there remains a small but significant risk of under-detecting clinically significant cancer. Similarly, under-estimation of tumor volume may contribute to infield recurrences and close attention must be paid to the ablation margin. Although long-term oncological outcomes remain lacking, focal therapy has a low complication rate, minimal impact on urinary continence and a moderate impact on erectile function. With the appropriate expertise in imaging, targeted biopsy and targeted ablation, focal therapy is a good option in men with low-intermediate risk cancer who are willing to maximize their urinary and sexual function. However, close posttreatment surveillance and the possibility of conversion to whole gland therapy must be accepted.


Centrin gene disruption impairs stage-specific basal body duplication and cell cycle progression in Leishmania.
Centrin is a calcium-binding cytoskeletal protein involved in the duplication of centrosomes in higher eukaryotes. To explore the role of centrin in the protozoan parasite Leishmania, we created Leishmania deficient in the centrin gene (LdCEN). Remarkably, centrin null mutants (LdCEN(-/-)) showed selective growth arrest as axenic amastigotes but not as promastigotes. Flow cytometry analysis confirmed that the mutant axenic amastigotes have a cell cycle arrest at the G(2)/M stage. The axenic amastigotes also showed failure of basal body duplication and failure of cytokinesis resulting in multinucleated "large" cells. Increased terminal deoxy uridine triphosphate nick end labeling positivity was observed in centrin mutant axenic amastigotes compared with wild type cells, suggesting the activation of a programmed cell death pathway. Growth of LdCEN(-/-) amastigotes in infected macrophages in vitro was inhibited and also resulted in large multinucleated parasites. Normal basal body duplication and cell division in the LdCEN knockout promastigote is unique and surprising. Further, this is the first report where disruption of a centrin gene displays stage-specific/cell type-specific failure in cell division in a eukaryote. The centrin null mutant defective in amastigote growth could be useful as a vaccine candidate against leishmaniasis.


Coating of LaCoO3 thin film with sol-gel dip coating method.
LaCoO3 thin film was coated on Al2O3 single crystal by sol-gel route. Appropriate composition of precursors, chelating agents and the solvent put together into a flask and magnetically stirred on a magnetic stirrer. After having the red transparent solution, it was stirred for 12 hours before coating. Ultrasonically cleaned substrate is dipped into the solution and taken immediately into vertical furnace which is preheated at 550 degrees C. A dense amorphous film is coated on the substrate. Fired amorphous films are annealed at temperature between 900 degrees C and 1000 degrees C for 20 minutes in the air. Then coated film was characterized by means of XRD, AFM, and SEM. Conductivity of the film was measured to be -0.1819 for 881 degrees C for the log sigma value by assuming the thickness as


[Idiopathic Lambert-Eaton myasthenic syndrome: report of one case].
Lambert-Eaton myasthenic syndrome (LEMS) is an autoinmune idiopathic or paraneoplastic syndrome producing antibodies agaisnt presynaptic voltage calcium channels. The clinical features of patients with LEMS are muscle weakness and autonomic dysfunction. We report a 40 years old man with a four years history of proximal weakness, absent tendon reflexes and dry mouth. The diagnosis was confirmed by characteristic electromyographic findings, showing a low-amplitude muscle response that increased dramatically after activation. Circulating antibodies to voltage-gated calcium channel were present. The search for malignant tumors was negative. The patient was treated with prednisone and azathioprine and after four months, he was able to walk and signs of autonomic dysfunction started to subside.


The current strategy of repair of tetralogy of Fallot in children and adults.
The strategies of repair of tetralogy of Fallot change with the age of patients. In children older than 4 years and adults, the optimal strategy may be to use different method of reconstruction of the right ventricular outflow tract from those followed in younger children, so as to avoid, or reduce, the pulmonary insufficiency that is increasingly known to compromise right ventricular function. From April, 2001, through May, 2008, we undertook complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3 years +/-0.4 years, and a range from 4 to 48 years, with typical clinical and morphological features of tetralogy of Fallot, including 42 patients with the ventriculo-arterial connection of double outlet right ventricle. The operation was performed under moderate hypothermia using blood cardioplegia. The ventricular septal defect was closed with a Dacron patch. When it was considered necessary to resect the musculature within the right ventricular outflow tract, or perform pulmonary valvotomy, we sought to preserve the function of the pulmonary valve by protecting as far as possible the native leaflets, or creating a folded monocusp of autologous pericardium. The repair was achieved completely through right atrium in 192, through the right ventricular outflow tract in 83, and through the right atrium, the outflow tract, and the pulmonary trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non-valved in all but 9. There were no differences regarding the periods of aortic cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no influence noted for the transjunctional patch. Of those having a non-valved patch inserted, three-tenths had pulmonary regurgitation of various degree, while those having a valved patch had minimal pulmonary insufficiency and good right ventricular function postoperatively, this being maintained after follow-up of 8 to 24-months. Based on our experience, we suggest that the current strategy of repair of tetralogy of Fallot in older children and adults should be based on minimizing the insertion of transjunctional patches, this being indicated only in those with very small ventriculo-pulmonary junctions. If such a patch is necessary, then steps should be taken to preserve the function of the pulmonary valve.


Advances in pharmacotherapy for treating female sexual dysfunction.
'Female sexual dysfunction' (FSD) is an umbrella term comprising a range of common disorders, including hypoactive sexual desire, reduced subjective and/or physical genital arousal (poor sensation, vasocongestion, lubrication), sexual pain and inability to achieve orgasm/satisfaction, which are multidimensional by nature and often coexisting. Psychological and contextual factors have a significant influence on organic components of sexual response and behavior and a tailored medical approach to sexual symptoms is inevitably limited. The paper reports the most recent advances in pharmacotherapy for women taking into account the biopsychosocial model. Hormone therapy, including estrogens, testosterone, tibolone and dehydroepiandrosterone, are discussed in term of efficacy and safety in postmenopausal women both for female sexual interest/arousal disorder (FSIAD) and genito-pelvic pain/penetration disorder. Ospemifene, a selective estrogen receptor modulator, approved to treat dyspareunia at menopause, is also discussed. Data on psychoactive agents for treatment of FSIAD in premenopausal women are discussed, including the potential use of on-demand combined hormonal (testosterone) and non-hormonal (buspirone or sildenafil) treatments to address possible neurophysiological profiles of women. We are still waiting for an approved pharmacotherapy for FSD. This is not the result of gender inequality in sexual medicine, but it reflects the need of balancing benefits and risks in order to provide effective and safe treatments to women of any age.


Bacterial wilt resistance in tomato, pepper, and eggplant: genetic resources respond to diverse strains in the Ralstonia solanacearum species complex.
Bacterial wilt, caused by strains belonging to the Ralstonia solanacearum species complex, inflicts severe economic losses in many crops worldwide. Host resistance remains the most effective control strategy against this disease. However, wilt resistance is often overcome due to the considerable variation among pathogen strains. To help breeders circumvent this problem, we assembled a worldwide collection of 30 accessions of tomato, eggplant and pepper (Core-TEP), most of which are commonly used as sources of resistance to R. solanacearum or for mapping quantitative trait loci. The Core-TEP lines were challenged with a core collection of 12 pathogen strains (Core-Rs2) representing the phylogenetic diversity of R. solanacearum. We observed six interaction phenotypes, from highly susceptible to highly resistant. Intermediate phenotypes resulted from the plants' ability to tolerate latent infections (i.e., bacterial colonization of vascular elements with limited or no wilting). The Core-Rs2 strains partitioned into three pathotypes on pepper accessions, five on tomato, and six on eggplant. A "pathoprofile" concept was developed to characterize the strain clusters, which displayed six virulence patterns on the whole set of Core-TEP host accessions. Neither pathotypes nor pathoprofiles were phylotype specific. Pathoprofiles with high aggressiveness were mainly found in strains from phylotypes I, IIB, and III. One pathoprofile included a strain that overcame almost all resistance sources.


InsP3-mediated intracellular calcium signalling is altered by expression of synaptojanin-1.
Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] plays an important physiological role as a precursor for the InsP3-mediated intracellular calcium (Ca2+) signalling cascade. It also regulates membrane trafficking, actin function and transmembrane proteins. SJ-1 (synaptojanin-1), a phosphoinositide phosphatase, regulates the turnover of a PtdIns(4,5)P2 pool involved in clathrin and actin dynamics at the cell surface. We tested the interrelationship of this pool with PtdIns(4,5)P2 pools involved in Ca2+ signalling by expressing in Chinese-hamster ovary cells full-length SJ-1 or its 5-Pase (inositol 5-phosphatase) domain. SJ-1 significantly attenuated the generation of Ca2+ oscillations induced by ATP and the 5-Pase domain mimicked this effect. These changes correlated with increased PtdIns(4,5)P2 phosphatase activity of cellular extracts. Overexpression of the endoplasmic reticulum-anchored PtdIns(4)P phosphatase Sac1 did not affect Ca2+ oscillations, although it increased the Ca2+ efflux rate from intracellular stores. The ability of SJ-1 to alter intracellular Ca2+ signalling indicates a close functional interrelationship between plasma membrane PtdIns(4,5)P2 pools that control actin and endocytosis and those involved in the regulation of specific spatio-temporal Ca2+ signals.


HTRA1 polymorphism in dry and wet age-related macular degeneration.
To investigate HTRA1 polymorphisms in unrelated Taiwan Chinese patients with age-related macular degeneration (AMD) and control subjects without AMD. A total of 95 unrelated Taiwan Chinese patients with AMD and 90 age- and sex-matched control subjects were enrolled in the study. Genomic DNA was prepared from peripheral blood obtained from all patients with AMD and control subjects. Polymerase chain reactions were used to analyze two HTRA1 single-nucleotide polymorphisms (rs11200638 [G/A] and rs10490924 [G/T]). Of the 95 participants with AMD, dry AMD was diagnosed in 52 patients and wet AMD in 43 patients. Both rs11200638 (G/A) and rs10490924 (G/T) were significantly associated with all AMD (rs11200638: P = 6.7 x 10(-7) for an additive allele-dosage model, OR(het) = 1.97 [0.81, 4.81], OR(hom) = 8.59 [3.28, 22.49], A allele: 73% in all AMD versus 47% in controls; rs10490924: P = 9.2 x 10(-6), OR(het) = 1.86 [0.79, 4.35], OR(hom) = 5.08 [2.21, 11.70], T allele: 73% in all AMD versus 50% in controls). In terms of significance of association, rs11200638 was the most significantly associated variant. Subtype analysis including dry and wet AMD also revealed similar results. Haplotype analysis demonstrated that AT was significantly associated with wet and all AMD (P = 0.011 and 0.004, respectively), whereas GG was significantly associated with the control group when compared with all AMD (P = 0.035). The study demonstrated that both single-nucleotide polymorphisms were significantly associated with dry and wet AMD and rs11200638 was the most significantly associated variant in a Taiwan Chinese population.


Long-acting slow effective release antiretroviral therapy.
Advances in long-acting antiretroviral therapy (ART) can revolutionize current HIV/AIDS treatments. We coined the term 'long-acting slow effective release ART' (LASER ART) to highlight the required formulation properties of slow drug dissolution, poor water-solubility, bioavailability, little-to-no off-target toxicities and improved regimen adherence. Drug carrier technologies characterized by high antiretroviral drug (ARV) payloads in a single carrier improve the pharmacokinetic and pharmacodynamic profiles. The surface modifications of ARV carriers target monocyte-macrophages and facilitate drug transport across physiological barriers and to virus-susceptible CD4 + T cells. Areas covered: The review highlights developments of reservoir-targeted LASER ART for improved therapeutic outcomes. Such nanoART delivery platforms include decorated multifunctional nano- and micro-particles, prodrugs and polymer conjugates. Therapeutic strategies such as gene-editing technologies boost ART effectiveness. Expert opinion: The persistence of HIV-1 in lymphoid, gut and nervous system reservoirs poses a challenge to viral eradication. Emerging slow-release drug carriers can target intracellular pathogens, activate antiviral immunity, promote genome editing, sustain drug depots and combine therapeutics with image contrast agents, and can meet unmet clinical needs for HIV-infected patients. Such efforts will bring the medicines to reservoir sites and accelerate viral clearance.


Effects of anthropogenic and demographic factors on patterns of parasitism in African small mammal communities.
Habitat disturbance often results in alterations in community structure of small mammals. Additionally, the parasites harboured by these small mammals may be impacted by environmental changes or indirectly affected by changes in available hosts. To improve our understanding of this interplay, we examined the patterns of parasitism in small mammal communities from a variety of habitats in forested Uganda. Small mammals were collected from areas experiencing variable habitat disturbance, host density and species richness. The analysis focused on 3 most abundant rodent species, Lophuromys aquilus, Praomys jacksoni and Hylomyscus stella, and a diverse group of parasites they harbour. The impact of various habitat and host community factors on parasite prevalence was examined using linear regression and Spearman's rank-order correlation. We further investigated the parasite communities associated with each individual using correspondence analysis. We determined that, parasite prevalence and richness may be occasionally influenced by community and habitat factors, but taxonomy is a driving force in influencing the parasite community harboured by an individual host. Ultimately, applying general principles across a broad range of disturbance levels and diverse host communities needs to be approached with caution in complex communities.


Machine Learning Approach for Active Vaccine Safety Monitoring.
Vaccine safety surveillance is important because it is related to vaccine hesitancy, which affects vaccination rate. To increase confidence in vaccination, the active monitoring of vaccine adverse events is important. For effective active surveillance, we developed and verified a machine learning-based active surveillance system using national claim data. We used two databases, one from the Korea Disease Control and Prevention Agency, which contains flu vaccination records for the elderly, and another from the National Health Insurance Service, which contains the claim data of vaccinated people. We developed a case-crossover design based machine learning model to predict the health outcome of interest events (anaphylaxis and agranulocytosis) using a random forest. Feature importance values were evaluated to determine candidate associations with each outcome. We investigated the relationship of the features to each event via a literature review, comparison with the Side Effect Resource, and using the Local Interpretable Model-agnostic Explanation method. The trained model predicted each health outcome of interest with a high accuracy (approximately 70%). We found literature supporting our results, and most of the important drug-related features were listed in the Side Effect Resource database as inducing the health outcome of interest. For anaphylaxis, flu vaccination ranked high in our feature importance analysis and had a positive association in Local Interpretable Model-Agnostic Explanation analysis. Although the feature importance of vaccination was lower for agranulocytosis, it also had a positive relationship in the Local Interpretable Model-Agnostic Explanation analysis. We developed a machine learning-based active surveillance system for detecting possible factors that can induce adverse events using health claim and vaccination databases. The results of the study demonstrated a potentially useful application of two linked national health record databases. Our model can contribute to the establishment of a system for conducting active surveillance on vaccination.


Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein.
Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated) and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18-25 million years ago (Mya). CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7-12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them) to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function.


Mediterranean diet as a natural supplemental resource for athletes and physical activity.
The WHO Global Action Plan on physical activity underlines the binomial "diet and physical activity" for the maintenance of well-being state. The adequate nutritional intake is required for sport and can be achieved by a well-adjusted diet without adding artificial food supplements, whose abuse can even represent a risk and appear as an antechamber of doping. Within a national doping prevention project, a peer education tool was realized in the form of a book and e-book, based on the principle of the Mediterranean Diet as an effective nutritional support in sport and physical activity. This health-literacy book contains recipes from all Italian regions revised for their capability to satisfy sport nutritional needs.


Neonatal outcome after active perinatal management of the very premature infant between 23 and 27 weeks' gestation.
To record the effect of aggressive perinatal management on neonatal outcome in the very premature infant. A retrospective chart review of 114 infants born between 23 and 27 weeks' gestation, managed by one perinatal transport service at one hospital between July 1989 and December 1993. Fetuses > 23 weeks' gestation were considered viable and were managed with tocolytics, antibiotics, and surfactant at the discretion of the treating physician. Morbidity and mortality rates in the first 6 months, including stillbirths were analyzed. A major neurologic condition was defined as ultrasonographic evidence of grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia. Both neonatal mortality rate and the incidence of stillbirths decreased with advancing gestational age. Of 24 infants born at 23 weeks' gestation, 33% were stillborn and 13% were alive at 6 months. This survival rate improved to 48% for infants delivered at 24 weeks' gestation, and to 68%, 75%, and 71% for those delivered at 25, 26, and 27 weeks' gestation, respectively. The percentage of infants who survived without a major neurologic condition increased with advancing gestational age at delivery from 13% at 23 weeks' gestation to 40% at 24 weeks, 48% at 25 weeks, 70% at 26 weeks, and 71% at 27 weeks. The incidence of retinitis of prematurity, respiratory complications, and days spent in the hospital decreased with greater gestational age. An active plan of management for all gestations of > 23.9 weeks seems appropriate.


[L-arginine therapy on MELAS].
MELAS is the most dominant clinical features among mitochondrial disorders. However the natural course of MELAS has not been clarified yet. In order to elucidate the natural course of MELAS, we have done the Japanese Cohort study on MELAS. By the age of onset, we divided MELAS into two subgroups, a juvenile form (onset is less than 18 years of age) and an adult form (onset is more than 18 years of age). Juvenile form is significantly different from adult form not only in the mean age of onset, but the mean age of death and survival rate (juvenile has 3.2 times higher chance of death than adult). Our date indicate that juvenile form of MELAS is more severe and poor prognosis than those seen in adult form. Based on the hypothesis that MELAS is caused by impaired vasodilation in an intracerebral artery, we evaluated the effects of administering L-arginine, a nitric oxide precursor. Patients were administered L-arginine intravenously at acute phase, or per orally at interictal phase. L-arginine infusions significantly improved all stroke-like symptoms suggesting stroke within 30 min, and oral administration significantly decreased frequency and severity of stroke-like episodes. L-arginine therapy showed promise in treating stroke-like episodes in MELAS.