Maternal low-level somatic mosaicism of Cys155Tyr of F9 in severe hemophilia B.
Hemophilia B is an X-linked bleeding disorder caused by deficient coagulation factor IX from a mutation in the F9 gene. Here, we report a family with two brothers having severe hemophilia B inherited from a mother with low-level somatic mosaicism of a F9 mutation. The proband was a 2-year-old boy with severe hemophilia B from a hemizygous mutation of F9, c.464G>A (p.Cys155Tyr). He was the first child and was considered a sporadic case based on the lack of family history of bleeding diathesis. His mother was tested for carrier status and was determined to be homozygous for wild-type genotypes (noncarrier). Subsequently, however, his brother was born and also had severe hemophilia B from Cys155Tyr. This prompted us to review the chromatogram of the mother, which revealed a small peak corresponding to the mutant genotype. On suspicion of somatic low-level mosaicism in the mother, we further performed allele-specific PCR and thymine and adenine cloning, and confirmed the presence of the mutant allele in the mother. To our knowledge, this is the first case of maternal somatic mosaicism for a cytosine-phosphate-guanine transition mutation in hemophilia B. The acknowledgment of somatic mosaicism and further molecular investigation are important in sporadic hemophilia B to deliver informative genetic counseling and risk assessment.


Platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in patients with rheumatoid arthritis.
It has been well documented that the platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) are associated with outcomes for patients with gastric cancer, non-small cell lung cancer and acute heart failure. Inflammation may be the hidden factor that explains the correlation between NLP, PLR, and these diseases. However, to date, the data concerning NLR, PLR, and its association with inflammation are lacking in patients with rheumatoid arthritis (RA), thus, our aim to discuss whether NLR and PLR are associated with RA. Patients with RA and healthy individuals were included according to the determined criteria, and laboratory indicators were measured. PLR and NLR were significantly higher in RA patients compared with healthy controls (3.20±2.06 vs. 1.56±0.47, P<0.01; 192.85±101.78 vs. 103.49±28.68, P<0.01). When leukocytes, neutrophil percentage, neutrophil, lymphocyte, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were considered as confounders (crude model), our results indicated that ESR and RF were correlated to RA. Of note, ESR, RF, and PLR were associated with RA after further adjustment based on crude model for PLR and NLR. Receiver operating characteristic (ROC) curves analysis showed that PLR values higher than >115.7 evaluated RA with a sensitivity of 82.5%, a specificity of 74.8% and area under the curve ( AUC ) of 0.847. Our results suggest that PLR is associated with RA, and PLR may be an underlying indicator indicating the chronic subclinical inflammation in patients with RA.


Utilization behavior and concomitant motor neglect by bilateral frontal lobe damage.
We reported on a patient who had bilateral mesial frontal lesions, presumably of a primary cerebral malignant lymphoma. The patient presented with a combination of unusual behavioral disorders of the upper extremities, which has not yet been documented in the literature: bilateral utilization and imitation behaviors and motor neglect of the left arm. Utilization behavior was closely associated with bilateral manual grasping behavior and was caused by the bifrontal lesions. Damage to the right supplementary motor area resulted most likely in concomitant motor neglect of the left hand. Discussion includes differentiation from other related behavioral disorders.


Furosemide and spironolactone reduce transmigration of leukocytes through endothelial cell monolayers.
Furosemide and spironolactone reduce transmigration of leukocytes through endothelial cell monolayers. Leukocytes play a tremendous role during inflammation. Leukocytes migrate from intravascular space into the tissue to attack microorganisms. Various agents are able to influence leukocyte recruitment. The influence of diuretics, such as furosemide and spironolactone, on inflammatory processes is not well known. The aim of our study was to examine the influence of furosemide and spironolactone on leukocyte migration through endothelial cell monolayers (ECM). Human umbilical vein endothelial cells were cultured on microporous membranes achieving a monolayer. Polymorphonuclear leukocytes (PMNL) were used in a currently described migration assay. PMNL and/or ECM were pretreated with furosemide and spironolactone using therapeutic, as well as higher and lower, concentrations. Furosemide (76 +/- 7.2%) and spironolactone (70 +/- 7.7%) were able to inhibit PMNL migration through ECM significantly, when both cell types were treated simulating the situation after an iv injection. Furosemide and spironolactone were identified as potent inhibitors of leukocyte migration through ECM.


Applications of fibrin sealant in surgery.
Fibrin sealant has been used with increasing frequency in a variety of surgical field for its unique hemostatic and adhesive abilities. Fibrin sealant mimics the last step of the coagulation cascade and takes place independently of the patient's coagulation status. With rapid advances in minimally invasive surgery, the potential uses for this type of biologic and synthetic material are expanding exponentially. This article reviews the data associated with the application of fibrin sealant in various surgical procedures. From reinforcing gastrointestinal anastomosis to repair perforated duodenal ulcers to mesh fixation in laparoscopic inguinal hernia repair, fibrin sealant is gaining increasing acceptance among surgeons. The applications of fibrin sealant are expanding, and new preparations of fibrin sealant are currently being evaluated.


The impact of genomics in understanding human melanoma progression and metastasis.
Recent technological advances in the analysis of the human genome have opened the door to improving our primitive understanding of the gene expression patterns in cancer. For the first time, we have an overview of the complexities of tumorigenesis and metastatic progression of cancer. The examination of the phenotypic and (epi)genetic changes in cutaneous melanoma has identified several genes deemed central to the development and progression of melanoma. A review of the recent literature was performed to determine the role of array-based high-throughput gene expression analysis in understanding the specific genes involved as well as the pathways and the comparative gene expression patterns of primary and metastatic melanoma. Most studies utilizing gene microarray analysis and other whole genome approaches reveal a wide array of genes and expression patterns in human melanoma. Furthermore, several of the same genes have been found in comparative studies, with some studies attempting correlation with clinical outcome. Several genes have been identified as potential prognostic markers of tumor progression and overall clinical outcome. High-throughput gene expression analysis has had a major impact in melanoma research. Several gene expression platforms have provided insight into the gene expression patterns in melanoma. Such data will provide the foundations for the future development of prognostic markers and improved targeted therapies for patients with melanoma.


Persistence of resistant Staphylococcus epidermidis after single course of clarithromycin.
We examined how a common therapy that includes clarithromycin affects normally colonizing Staphylococcus epidermidis. Samples from the nostrils of 5 patients receiving therapy were collected before, immediately after, 1 year after, and 4 years after treatment. From each patient and sample, S. epidermidis strains were isolated and analyzed for clarithromycin susceptibility and presence of the erm(C) gene. We show that macrolide-resistant strains of S. epidermidis were selected during therapy and that the same resistant strain may persist for 4 years, in the absence of further antimicrobial treatment.


Current peptidomics: applications, purification, identification, quantification, and functional analysis.
Peptidomics is an emerging field branching from proteomics that targets endogenously produced protein fragments. Endogenous peptides are often functional within the body-and can be both beneficial and detrimental. This review covers the use of peptidomics in understanding digestion, and identifying functional peptides and biomarkers. Various techniques for peptide and glycopeptide extraction, both at analytical and preparative scales, and available options for peptide detection with MS are discussed. Current algorithms for peptide sequence determination, and both analytical and computational techniques for quantification are compared. Techniques for statistical analysis, sequence mapping, enzyme prediction, and peptide function, and structure prediction are explored.


Long-term effects on the histology and function of livers and spleens in rats after 33% toploading of PEG-PLA-nano artificial red blood cells.
This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens.


Anatomic and Histological Study of Lingual Nerve and Its Clinical Implications.
Although the risk of injuring the lingual nerve in the mandibular molar area during dental treatment is high, it can be repaired by nerve grafting. However, from the perspective of clinical dentistry, the pathway and histomorphometric characteristics of this nerve remain to be documented in detail. The purpose of the present study was to morphologically elucidate the pathway of the lingual nerve to clarify its significance in a clinical setting. A histomorphometric analysis was also performed in consideration of nerve grafting. The vertical distance between the occlusal plane and the superior margin of the lingual nerve showed a gradual decrease from the premolar toward the distal molar area. This suggests that the risk of injuring the lingual nerve increases gradually toward the distal area. The average total fascicular area of the lingual nerve was 1.90 mm2, which was larger than that of the sural nerve. It is the first-choice donor nerve for grafting. Therefore, even though the total fascicular area of the donor nerve is a little smaller than that of the recipient nerve, nerve grafting should be successful.


Effect of lipopolysaccharide on intracellular killing of Leishmania enriettii and correlation with macrophage oxidative metabolism.
The effect of lipopolysaccharide (LPS) on the lymphokine (LK)-dependent activation of murine peritoneal macrophages for intracellular killing of Leishmania enriettii parasites was investigated. Exposure to LPS alone did not induce macrophages to kill the parasite. In the presence of LK or recombinant interferon-gamma, however, which by themselves rendered the macrophages only weakly cytotoxic, considerable stimulation of intracellular parasite killing was achieved already at a LPS concentration of 1 ng/ml. The response to LPS was of the same magnitude in macrophages tested for intracellular killing as in parallel assays of extracellular cytolysis of target cells. Acquisition of leishmanicidal activity by macrophages exposed to LK and LPS correlated with stimulation of the respiratory burst, as shown by increased hexose monophosphate shunt levels, and priming for elevated chemiluminescence and O2- and H2O2 production. Polymyxin B blocked both this LPS-dependent metabolic activity and intracellular parasite destruction. Intracellular killing was, however, not solely dependent on oxidative metabolism of macrophages since in the absence of LK, LPS stimulated respiratory burst activity, yet no intracellular killing was observed, and triggering of the respiratory burst by phorbol myristate acetate or zymosan did not affect intracellular parasite survival. These results suggest that, in this experimental model, efficient intracellular parasite killing depends both on increased production of oxygen metabolites and on the availability of so far unidentified factor(s), the synthesis of which requires exposure of macrophages to both LK and LPS.


Positive nin one binding protein expression predicts poor outcome in prostate cancer.
Nin one binding protein (NOB) 1 has been reported to be involved in cancer. However, the role of NOB1 in prostate cancer (PCa) has yet to be elucidated. The present study aimed to investigate the clinical role of NOB1 in PCa. The gene and protein expression levels of NOB1 were detected using quantitative polymerase chain reaction and western blot analysis in fresh samples of PCa and matched adjacent noncancerous tissues (n=32). NOB1 expression was also assessed using immunohistochemistry in a large number of patients with PCa (n=456) and paired adjacent noncancerous tissues between December 2003 and December 2010. The association between NOB1 expression and clinicopathological features and prognosis was investigated. The expression of NOB1 was found to be higher in the fresh samples of PCa than in the paired adjacent noncancerous tissues at the gene and protein levels. Immunohistochemistry revealed that the positive expression rates of NOB1 in PCa and the paired adjacent noncancerous tissues were 53% (242/456) and 6.1% (28/456), respectively. NOB1 expression was significantly correlated with Gleason score (P<0.001) and distant metastasis (P<0.001). Furthermore, patients with PCa with positive NOB1 expression had lower overall survival and recurrence‑free survival (RFS) compared with those with negative NOB1 expression. Multivariate analysis showed that NOB1 was an independent marker of RFS (hazard ratio, 3.45; 95% confidence interval, 1.41‑6.35; P=0.006). These findings suggest that NOB1 may be a potential prognostic indicator for PCa.


Fluorochemical mass flows in a municipal wastewater treatment facility.
Fluorochemicals have widespread applications and are released into municipal wastewater treatment plants via domestic wastewater. A field study was conducted at a full-scale municipal wastewater treatment plant to determine the mass flows of selected fluorochemicals. Flow-proportional, 24 h samples of raw influent, primary effluent, trickling filter effluent, secondary effluent, and final effluent and grab samples of primary, thickened, activated, and anaerobically digested sludge were collected over 10 days and analyzed by liquid chromatography electrospray-ionization tandem mass spectrometry. Significant decreases in the mass flows of perfluorohexane sulfonate and perfluorodecanoate occurred during trickling filtration and primary clarification, while activated sludge treatment decreased the mass flow of perfluorohexanoate. Mass flows of the 6:2 fluorotelomer sulfonate and perfluorooctanoate were unchanged as a result of wastewater treatment, which indicates that conventional wastewater treatment is not effective for removal of these compounds. A net increase in the mass flows for perfluorooctane and perfluorodecane sulfonates occurred from trickling filtration and activated sludge treatment. Mass flows for perfluoroalkylsulfonamides and perfluorononanoate also increased during activated sludge treatment and are attributed to degradation of precursor molecules.


Human autoantibodies as reagents in biomedical research.
Abstract Autoantibodies are typically associated with autoimmune diseases. In some instances the association of specific autoantibodies to a specific autoimmune disease have made their detection invaluable in clinical diagnosis. However, certain autoantibodies show no specific disease association and therefore have limited clinical utility. Nevertheless, autoantibodies are powerful tools for identification, characterization, and functional studies of their cognate antoantigens. In addition, the study of autoantibodies and their cognate autoantigens in human disease and in experimental animal models can provide valuable insight into disease mechanisms and the factors that ameliorate or reverse disease. This review will focus on three specific sets of autoantibodies, which were initially selected for investigation purely on the basis of their novel patterns of reactivity. These were observed when they were applied to a diagnostic HEp-2 test slide for antinuclear antibody detection by indirect immunofluorescence. The target autoantigens were identified as the trans-Golgi network protein GOLGA4 (Golgin 245 or p230), the early endosome antigen-1 (EEA1) and a yet to be identified and fully characterized phosphoepitope(s) restricted to chromosomal arms of condensed mitotic/meiotic chromosomes (MCA1). This laboratory has exploited sera which are reactive to these autoantigens for their identification and characterization, and in functional studies. This review highlights the uses of autoantibodies that may have limited diagnostic or prognostic utility, but are nonetheless novel reagents in the prosecution of molecular cell biology.


TNFSF15 facilitates differentiation and polarization of macrophages toward M1 phenotype to inhibit tumor growth.
Macrophages of the M2 phenotype in malignant tumors significantly aid tumor progression and metastasis, as opposed to the M1 phenotype that exhibits anti-cancer characteristics. Raising the ratio of M1/M2 is thus a promising strategy to ameliorate the tumor immunomicroenvironment toward cancer inhibition. We report here that tumor necrosis factor superfamily-15 (TNFSF15), a cytokine with anti-angiogenic activities, is able to facilitate the differentiation and polarization of macrophages toward M1 phenotype. We found that tumors formed in mice by Lewis lung carcinoma (LLC) cells artificially overexpressing TNFSF15 exhibited retarded growth. The tumors displayed a greater percentage of M1 macrophages than those formed by mock-transfected LLC cells. Treatment of mouse macrophage RAW264.7 cells with recombinant TNFSF15 led to augmentation of the phagocytic and pro-apoptotic capacity of the macrophages against cancer cells. Mechanistically, TNFSF15 activated STAT1/3 in bone marrow cells and MAPK, Akt and STAT1/3 in naive macrophages. Additionally, TNFSF15 activated STAT1/3 but inactivated STAT6 in M2 macrophages. Modulations of these signals gave rise to a reposition of macrophage phenotypes toward M1. The ability of TNFSF15 to promote macrophage differentiation and polarization toward M1 suggests that this unique cytokine may have a utility in the reconstruction of the immunomicroenvironment in favor of tumor suppression.


Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment.
Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.


Improving Prehospital Protocol Adherence Using Bundled Educational Interventions.
Seizures and anaphylaxis are life-threatening conditions that require immediate treatment in the prehospital setting. There is variation in treatment of pediatric prehospital patients for both anaphylaxis and seizures. This educational study was done to improve compliance with pediatric prehospital protocols, educate prehospital providers and decrease variation in care. To improve the quality of care for children with seizures and anaphylaxis in the prehospital setting using a bundled, multifaceted educational intervention. Evidence-based pediatric prehospital guidelines for seizures and anaphylaxis were used to create a curriculum for the paramedics in the EMS system. The curriculum included in-person training, videos, distribution of decision support tools, and a targeted social media campaign to reinforce the evidence-based guidelines. Prehospital charts were reviewed for pediatric patients with a chief complaint of anaphylaxis or seizures who were transported by paramedics to one of ten hospitals, including three children's hospitals, for 8 months prior to the intervention and eight months following the intervention. The primary outcome for seizures was whether midazolam was given via the preferred intranasal (IN) or intramuscular (IM) routes. The primary outcome for anaphylaxis was whether IM epinephrine was given. A total of 1,402 pediatric patients were transported for seizures by paramedics to during the study period. A total of 88 patients were actively seizing pre-intervention and 93 post-intervention. Of the actively seizing patients, 52 were given midazolam pre-intervention and 62 were given midazolam post-intervention. Pre-intervention, 29% (15/52) of the seizing patients received midazolam via the preferred IM or IN routes, compared to 74% (46/62) of the seizing patients post-intervention. A total of 45 patients with anaphylaxis were transported by paramedics, 30 pre-intervention and 15 post-intervention. Paramedics administered epinephrine to 17% (5/30) patients pre-intervention and 67% (10/15) patients post-intervention. The use of a bundled, multifaceted educational intervention including in-person training, decision support tools, and social media improved adherence to updated evidence-based pediatric prehospital protocols.


Methotrexate-induced mucositis in mucin 2-deficient mice.
The mucin Muc2 or Mycin2 (Muc2), which is the main structural component of the protective mucus layer, has shown to be upregulated during chemotherapy-induced mucositis. As Muc2 has shown to have protective capacities, upregulation of Muc2 may be a counter reaction of the intestine protecting against mucositis. Therefore, increasing Muc2 protein levels could be a therapeutic target in mucositis prevention or reduction. Our aim was to determine the role of Muc2 in chemotherapy-induced mucositis. Mucositis was induced in Muc2 knockout (Muc2(-/-)) and wild type (Muc2(+/+)) mice by injecting methotrexate (MTX). Animals were weighed and sacrificed on Days 2-6 after MTX treatment and jejunal segments were analyzed. Before MTX treatment, the small intestine of Muc2(+/+) and Muc2(-/-) mice were similar with respect to epithelial morphology and proliferation. Moreover, sucrase-isomaltase and trefoil factor-3 protein expression levels were comparable between Muc2(+/+) and Muc2(-/-) mice. Up to Day 3 after MTX treatment, percentages of weight-loss did not differ. Thereafter, Muc2(+/+) mice showed a trend towards regaining weight, whereas Muc2(-/-) mice continued to lose weight. Surprisingly, MTX-induced intestinal damage of Muc2(-/-) and Muc2(+/+) mice was comparable. Prior to MTX-injection, tumor necrosis factor-alpha and interleukin-10 mRNAs were upregulated in Muc2(-/-) mice, probably due to continuous exposure of the intestine to luminal antigens. Muc2 deficiency does not lead to an increase in chemotherapy-induced mucositis. A possible explanation is the mechanism by which Muc2 deficiency may trigger the immune system to release interleukin-10, an anti-inflammatory cytokine before MTX-treatment.


Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells.
Although many kinds of nicotinic acetylcholine receptor (nAChR) subtypes have been reported in the neuronal tissues, subtype differences in the nAChR-mediated intracellular signaling remains obscure. Using nAChR agonists and antagonists, the involvement of nAChRs in extracellular signal-regulated protein kinase (ERK) phosphorylation in PC12h cells was investigated. Cytisine and nicotine induced the phosphorylation of ERKs in a dose-dependent manner, whereas RJR-2403 had no effect. Cytisine, but not RJR-2403, also induced phosphorylation of CREB. Mecamylamine, dextromethorphan and 18-methoxycoronaridine inhibited nicotine-induced ERK phosphorylation with much higher affinity than dihydro-beta-erythroidine and alpha-conotoxin MII. These results suggest the involvement of alpha3beta4 nAChRs in ERK phosphorylation in PC12h cells.


[Study on the score criteria of severe hand, foot and mouth disease cases].
To explore the score criteria of severe hand, foot and mouth disease (HFMD) cases and to provide evidence for unified criteria and treatment on severe HFMD cases. All severe cases and partial mild cases reported by two designated hospitals of HFMD in Fuyang during March to June, 2008 were scored by the methods of criteria constructed in advance. ROC curve was adopted to evaluate the score criteria and the gold standard was defined according to ICU, intubation and clinical outcomes, etc. Sensitivity, specificity and Youden's index were used to determine the division scores on critical, severe and mild cases. 97% of the cases (34 cases) were scored less than 6 points. 88% of cases (24 cases) who were intubated or mechanical ventilated had the scores of 6 points or higher. 79% of deaths (11 cases) were scored 10 points or higher. The area of receiver operation characteristic (ROC) curve was 0.90 (95%CI: 0.83 - 0.98) between severe and mild cases and the area of ROC curve was 0.95 (95%CI: 0.92 - 0.98) between critical and severe, mild cases. When comprehensively considering the sensitivity and specificity, severe cases were best judged when score was 4 points (sensitivity, specificity and Youden's index were 0.94, 0.68 and 0.62 respectively). When score was 6 points, critical cases were judged very well (sensitivity, specificity and Youden's index were 0.92, 0.84 and 0.76 respectively). Score criteria could be quantified to determine the degree of seriousness and with high-value for diagnosis on HFMD.


Localized intravascular coagulation in the mesenteric region.
Coagulation and fibrinolysis were measured in the portal and peripheral circulation in 15 rabbits after ligation of the superior mesenteric artery. It was found that the local coagulation syndrome in the mesenteric region can be recognized by tests in blood samples taken from the peripheral circulation area.


Aphasic performance on a battery of constructional, visuo-spatial, and quantitative tasks: factorial structure and CT scan localization.
This study examined the performance of aphasics on those functions associated with the parietal lobe of the left hemisphere. Data from the Parietal Lobe Battery (PLB) (Goodglass & Kaplan, 1972) were analyzed in 163 right-handed male aphasics with unilateral left-hemisphere lesions. Factor analysis on the 18 subtests of the PLB yielded a substantial general factor before rotation and four meaningful factors following rotation, involving construction, visual schemata, verbal components of the Gerstmann Syndrome, and visual finger recognition. Diverse aphasia subtypes were relatively homogeneous in their performance on the PLB. Upon examination of the influence of linguistic, demographic, and neurological factors, writing and auditory comprehension were found to make significant contributions to overall PLB performance. When considering lesion localization, as verified by CT scans in 36% of our sample, a lesion involving both parietal and frontal structures was the strongest predictor of impairment on the PLB.


Risk factors associated with sensitive skin and potential role of lifestyle habits: a cross-sectional study.
Sensitive skin (SS) is a widespread condition, but still not completely understood. To identify risk factors that increase the likelihood of SS, 258 women aged between 20 and 65 years old and resident in the Netherlands were surveyed by questionnaire, which included questions on sociodemographic characteristics (age group, Fitzpatrick skin type, hormonal status), health state (atopic predisposition, skin diseases) and lifestyle habits (history of smoking and of sun exposure, frequency of physical exercise). Analysis of the responses confirmed that atopic predisposition, presence of skin diseases and Fitzpatrick skin types I and II are risk factors significantly associated with SS. In addition, as current or past smoking and a history of low sun exposure showed a trend to increase the likelihood of reporting SS, we suggest that the potential role of lifestyle factors in the onset or exacerbation of SS should be investigated further.


Prospect of Sodium-Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new family of antidiabetic drugs that reduce blood glucose independent of insulin. In this review, we present the advantages and adverse effects of SGLT2 inhibitors plus insulin therapy as a treatment regimen for patients with type 2 diabetes (T2D). Compared with placebo, SGLT2 inhibitors plus insulin therapy could significantly decrease fasting blood glucose and HbA1c, thereby reducing the daily required dose of insulin. A reduction in body weight and improvements in insulin resistance and β-cell function have also been widely reported with this therapy, and other potential advantages, including the reduction in blood pressure, adverse cardiovascular outcomes, and visceral adipose tissue volume, have been revealed. SGLT2 inhibitors cause a greater reduction than dipeptidyl peptidase-4 (DPP-4) inhibitors in body weight and the risk of cardiovascular disease. Furthermore, compared with glucagon-like peptide-1 (GLP-1) agonists, SGLT2 inhibitors reduce blood pressure, and heart failure. As this therapy is an oral preparation, an improvement in patient compliance is also achieved. Despite these advantages, however, combination therapy with SGLT2 inhibitors and insulin has several risks. Although no difference has been found in the incidence of hypoglycemic events and urinary tract infection between the administration of this combination and that of placebo, the risk of genital tract infections was reported to increase with the combination therapy. Additionally, bone adverse effects, euglycemic diabetic ketoacidosis, and volume depletion-and osmotic diuresis-related adverse effects have been observed. Altogether, we could conclude that SGLT2 inhibitors plus insulin therapy is an efficient treatment option for patients with T2D, especially those requiring high daily insulin doses and those with insulin resistance, obesity, and a high risk of cardiovascular events. However, careful monitoring of the adverse effects of this combination is also warranted.


Properties of Equilibria and Glassy Phases of the Random Lotka-Volterra Model with Demographic Noise.
We study a reference model in theoretical ecology, the disordered Lotka-Volterra model for ecological communities, in the presence of finite demographic noise. Our theoretical analysis, valid for symmetric interactions, shows that for sufficiently heterogeneous interactions and low demographic noise the system displays a multiple equilibria phase, which we fully characterize. In particular, we show that in this phase the number of locally stable equilibria is exponential in the number of species. Upon further decreasing the demographic noise, we unveil the presence of a second transition like the so-called "Gardner" transition to a marginally stable phase similar to that observed in the jamming of amorphous materials. We confirm and complement our analytical results by numerical simulations. Furthermore, we extend their relevance by showing that they hold for other interacting random dynamical systems such as the random replicant model. Finally, we discuss their extension to the case of asymmetric couplings.


Differential detection of Hammondia hammondi from Toxoplasma gondii using polymerase chain reaction.
Hammondia hammondi and Toxoplasma gondii are two related coccidian parasites, with cats as definitive hosts and warm-blooded animals as intermediate hosts. It is difficult to differentiate them by morphological and serological parameters. In the present study, primers were designed to specifically amplify the ITS-1 region of H. hammondi to differentiate it from T. gondii. Attempts were made to detect the presence of H. hammondi DNA in the tissues of mice infected with H. hammondi alone, as well as from mixed infections with T. gondii, using the newly designed primers. The de novo primers effectively amplified the H. hammondi-specific target fragment from all samples containing H. hammondi, including those with concomitant T. gondii infection. Further, the primers did not amplify any fragment from the related parasites like T. gondii, Neospora caninum and Hammondia heydorni. The new primers provide simple and efficient means to differentially diagnose H. hammondi from T. gondii even in samples containing both parasites, thus obviating the need for other labourious techniques like mouse bioassay and in vitro cultivation.


Environmental friendly method for urban wastewater monitoring of micropollutants defined in the Directive 2013/39/EU and Decision 2015/495/EU.
The fate and removal of organic micropollutants in the environment is a demanding issue evidenced by the recent European policy. This work presents an analytical method for the trace quantification of 37 micropollutants including Priority Substances (Directive 2013/39/EU), substances of the recent watch list (Decision 2015/495/EU) and contaminants of emerging concern: pesticides, multi-class pharmaceuticals and a metabolite, estrogens and one industrial compound. The analytical method was based on solid phase extraction (SPE) followed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS), using eco-friendly solvents (ethanol and ultrapure water) both in the SPE and UHPLC, according to green analytical chemistry principles. Briefly, Oasis(®) HLB cartridges were used to preconcentrate 100mL of water samples and the reconstituted extracts were analyzed with a Kinetex™ column under reversed mode, the linear ranges extended to 200ngL(-1) (R(2)>0.99) for all the analytes. The method detection limits were between 0.04 and 2.26ngL(-1) and the method quantification limits were between 0.13 and 6.85ngL(-1). The identity of the compounds was confirmed using two MS/MS transitions and its ion ratios, according to Decision 2002/657/EC. The validated method was applied to wastewater treatment plant samples, assessing the concentration of micropollutants after secondary biological and tertiary UV treatments. Lab-scale photolysis and ozonation experiments were also performed with the secondary effluents, with ozonation showing the best performance for the removal of most of the determined micropollutants.


Comparative effectiveness analysis between entrectinib clinical trial and crizotinib real-world data in ROS1+ NSCLC.
Aim: Generating direct comparative evidence in prospective randomized trials is difficult for rare diseases. Real-world cohorts may supplement control populations. Methods: Entrectinib-treated adults with advanced ROS1 fusion-positive NSCLC (n = 94) from Phase I/II trials (ALKA-372-001 [EudraCT2012-00148-88], STARTRK-1 [NCT02097810], and STARTRK-2 [NCT02568267]) were compared with a real-world crizotinib-treated cohort (n = 65). Primary end point, time-to-treatment discontinuation (TTD); secondary end points, PFS and OS. Results: Median (95% CI) weighted TTD: 12.9 (9.9-17.4) months for entrectinib; 8.8 (6.2-9.9) months for crizotinib (weighted hazard ratio: 0.72 [0.51-1.02]). Median OS with entrectinib was not reached, weighted median OS with crizotinib was 18.5 (15.1-19.9) months. Conclusion: Entrectinib administered in clinical trials may be associated with longer TTD than a real-world crizotinib population.


Care Practices for Patients With Advanced Kidney Disease Who Forgo Maintenance Dialysis.
Although maintenance dialysis is a treatment choice with potential benefits and harms, little is known about care practices for patients with advanced chronic kidney disease who forgo this treatment. To describe how decisions not to start dialysis unfold in the clinical setting. A qualitative study was performed of documentation in the electronic medical records of 851 adults receiving care from the US Veterans Health Administration between January 1, 2000, and October 1, 2011, who had chosen not to start dialysis. Qualitative analysis was performed between March 1, 2017, and April 1, 2018. Dominant themes that emerged from clinician documentation of clinical events and health care interactions between patients, family members, and clinicians relevant to the decision to forgo dialysis. In the cohort of 851 patients (842 men and 9 women; mean [SD] age, 75.0 [10.3] years), 567 (66.6%) were white. Three major dynamics relevant to understanding how decisions to forgo dialysis unfolded were identified. The first dynamic was that of dialysis as the norm: when patients expressed a desire to forgo dialysis, it was unusual for clinicians to readily accept patients' decisions. Clinicians tended to repeatedly question this preference over time, deliberated about patients' competency to make this decision, used a variety of strategies to encourage patients to initiate dialysis, and prepared for patients to change their minds and start dialysis. The second dynamic arose when patients were not candidates for dialysis: clinicians viewed particular patients as not candidates or appropriate for dialysis, usually on the basis of specific characteristics and/or expected prognosis, rather than after consideration of patients' goals and values. When clinicians decided patients were not candidates for dialysis, there seemed to be little room for uncertainty in these decisions. The third dynamic occurred when clinicians believed they had little to offer patients beyond dialysis: when it was clear that patients would not be starting dialysis, nephrologists often signed off from their care and had few recommendations other than referral to hospice care. These findings describe an all-or-nothing approach to caring for patients with advanced chronic kidney disease in which initiation of dialysis served as a powerful default option with few perceived alternatives. Stronger efforts are needed to develop a more patient-centered approach to caring for patients with advanced chronic kidney disease that is capable of proactively supporting those who do not wish to start dialysis.


β-human chorionic gonadotropin-secreting intracranial germ-cell tumor associated with high testosterone in an adult man: A case report.
A 38-year-old male patient presented with general weakness, polydipsia and a body weight loss of 10 kg in two years. Hypopituitarism with central hypothyroidism and central adrenal insufficiency were noted at Taipei City Hospital (Taipei, Taiwan). However, hypogonadotropic hypergonadism was also observed. The patient was diagnosed with an intracranial β-human chorionic gonadotropin (β-hCG) secreting germ-cell tumor, and brain magnetic resonance imaging revealed that the tumor involved the pineal gland, stalk, posterior pituitary gland, right basal ganglion, hypothalamus, corpus callosum and posterior hippocampus. The cerebrospinal fluid (CSF) β-hCG level was 1936 IU/l, while the α-fetoprotein (AFP) level was <0.24 ng/ml. The serum AFP level of the patient was 3.28 ng/ml, and the β-hCG level was 178 IU/l with a CSF:serum β-hCG ratio >2:1. The patient was successfully treated with chemotherapy and radiotherapy, as demonstrated by a marked decrease in size of the tumor and in the serum β-hCG levels. Intracranial β-hCG secreting germ-cell tumors are rare in adults and manifest differently compared with patients of early pubertal age. In contrast with the precocious puberty frequently observed in young patients, the diagnosis of adult patients is often delayed and the symptoms are associated with tumor size and location. The present case report described an adult male with an intracranial β-hCG secreting GCT, demonstrating hypopituitarism and asymptomatic hyperandrogenemia, and reviews and discusses the literature relevant to the case.


Do school classrooms meet the visual requirements of children and recommended vision standards?
Visual demands of school children tend to vary with diverse classroom environments. The study aimed to evaluate the distance and near Visual Acuity (VA) demand in Indian school classrooms and their comparison with the recommended vision standards. The distance and near VA demands were assessed in 33 classrooms (grades 4 to 12) of eight schools. The VA threshold demand relied on the smallest size of distance and near visual task material and viewing distance. The logMAR equivalents of minimum VA demand at specific seating positions (desk) and among different grades were evaluated. The near threshold was converted into actual near VA demand by including the acuity reserve. The existing dimensions of chalkboard and classroom, gross area in a classroom per student and class size in all the measured classrooms were compared to the government recommended standards. In 33 classrooms assessed (35±10 students per room), the average distance and near logMAR VA threshold demand was 0.31±0.17 and 0.44±0.14 respectively. The mean distance VA demand (minimum) in front desk position was 0.56±0.18 logMAR. Increased distance threshold demand (logMAR range -0.06, 0.19) was noted in 7 classrooms (21%). The mean VA demand in grades 4 to 8 and grades 9 to 12 was 0.35±0.16 and 0.24±0.16 logMAR respectively and the difference was not statistically significant (p = 0.055). The distance from board to front desk was greater than the recommended standard of 2.2m in 27 classrooms (82%). The other measured parameters were noted to be different from the proposed standards in majority of the classrooms. The study suggests the inclusion of task demand assessment in school vision screening protocol to provide relevant guidance to school authorities. These findings can serve as evidence to accommodate children with mild to moderate visual impairment in the regular classrooms.


[Bilateral capitulum humeri fracture, a case report and review of the literature].
Fracture of the capitellum is an intra-articular fracture of the distal humeral metaphysis and usually occurs in the frontal plane. It is a rare fracture and even more unusual when bilateral. The authors report a case of bilateral isolated fracture of the capitellum (Hahn-Steinthal type I) in a woman aged 28 years, treated surgically. A posterolateral approach was used for both elbows. Internal fixation was performed using two Herbert screws in the right elbow, and AO screws in the left elbow. Both elbows were immobilised for 3 weeks before commencing an intensive mobilization program guided by a physiotherapist. The end result was very satisfactory: both elbows were pain-free, with a complete range of movement on the right and a 10 degrees loss of extension on the left. Radiologically, consolidation was complete and there were no signs of avascular necrosis. Based on a review of the literature, the authors favour the use of Herbert screws in the treatment of capitellar fractures. They give good inter-fragmentary compression and reduce the risk of damaging the articular surface due to their subarticular position.


Isovaline in naturally occurring peptides: A nondestructive methodology for configurational assignment.
The nonproteinogenic, C(α)-tetrasubstituted, helicogenic, chiral α-amino acid isovaline (Iva) is remarkably spread in the biosphere. Together with its achiral, lower homolog α-aminoisobutyric acid (Aib), it represents a characteristic marker of a class of naturally occurring peptide antibiotics, for which the acronym "peptaibiotics" became established. In these peptides, Iva occurs as the (S)-(= L) or the (R)-(= D) enantiomer, but peptide sequences containing both Iva enantiomers are also common. Here, we applied our recently developed (1)H-NMR method, which enables the nondestructive assignment of the configuration of each Iva residue in a peptide of known helical screw sense, to natural and synthetic peptaibiotics. Our method proved to be generally applicable and provided evidence that, in the peptaibiotic bergofungin A, the Iva(12) configuration is (R) and not (S) as reported previously. Moreover, we extended our NMR method by including a (13)C-NMR parameter. A statistical analysis of the preferred main- and side-chain conformations of the Iva residues in peptides, performed based on their published X-ray diffraction structures, allowed us to provide a sound rationale to the NMR criteria exploited to establish the configuration of this amino acid.


Near-instantaneous battery End-of-Discharge prognosis via uncertain event likelihood functions.
The prediction of the time of occurrence of future events has been studied for decades in various scientific disciplines. Such events have historically been defined as moments where variables of interest (or indicators) hit pre-determined thresholds (i.e. the first-hitting time). Recently, semi-closed mathematical expressions were reported in the literature to analytically characterize the probability distribution of the occurrence time of future events, extending the event triggering criteria based on thresholds to a more general and intuitive threshold-less approach, where the occurrence of events is declared through the use of uncertain event likelihood functions. The End-of-Discharge time prognosis problem is formalized in this article via the definition of uncertain event likelihood functions. Moreover, a novel numerical method is proposed to compute the probability distribution of its future time of occurrence based on this conceptualization and exploiting the capability of uncertain event likelihood functions to assimilate uncertainty in analytic expressions. A case study related to energy autonomy in electromobility applications is considered; specifically an electric bicycle. Obtained results show that the proposed method achieves an extraordinary level of convergence in less than a tenth of a second, while the same level of convergence using Monte Carlo simulations under the traditional threshold crossing approach takes hours to be achieved.


Pure red cell aplasia associated with administration of sustained-release procainamide.
Pure red cell aplasia developed in a patient with small-cell lung cancer who was also taking sustained-release procainamide. Shortly after discontinuation of the procainamide preparation, a reticulocytosis and increasing hemoglobin level were observed.


Biologically inspired strategies for combating bacterial biofilms.
Infections caused by bacterial biofilms are a significant global health problem, causing considerable patient morbidity and mortality and contributing to the economic burden of infectious disease. This review describes diverse strategies to combat bacterial biofilms, focusing firstly on small molecule interference with bacterial communication and signaling pathways, including quorum sensing and two-component signal transduction systems. Secondly we discuss enzymatic approaches to the degradation of extracellular matrix components to effect biofilm dispersal. Both of these approaches are based upon non-microbicidal mechanisms of action, and thereby do not place a direct evolutionary pressure on the bacteria to develop resistance. Such approaches have the potential to, in combination with conventional antibiotics, play an important role in the eradication of biofilm based bacterial infections.


Interaction of natural killer cells with extracellular matrix induces early intracellular signalling events and enhances cytotoxic functions.
NK cells are endowed with a wide array of adhesion molecules which mediate their interaction with endothelium and extracellular matrix components. We have shown that cross-linking of beta 1 integrins and CD44 on human NK cells induces a signal transduction pathway involving both tyrosine kinase activation and the modulation of intracellular calcium levels. Our studies have also demonstrated the ability of beta 1 integrins and CD44 to upregulate both the spontaneous and the CD16-triggered cytotoxic activity of human NK cells. Although the molecular mechanisms responsible for this costimulatory activity have not been defined yet, our studies indicate that the simultaneous cross-linking of beta 1 integrins and CD44 results in a synergistic effect on CD16-mediated enhancement of intracellular free calcium concentration, and suggest that this may be relevant for the cooperation observed.


[Nutritional knowledge and consumption frequency of foods--a case study].
The relationship between nutritional knowledge and the consumption frequency of preferred food-types was studied among one sample of Uruguayan consumers. A locally-adapted version of Parmenter & Wardle's General Nutrition Knowledge Questionnaire and a food consumption survey based on 39 food groups were completed by a total of 270 participants. Cluster Analysis enabled the identification of two clusters showing different levels of nutritional knowledge--cluster 1 (n = 177) and cluster 2 (n = 93), providing an average of 73.6% and 52.9% of correct answers, respectively. These clusters differed significantly (p < or = 0.05) in age and educational distribution--cluster 1 was composed mainly by older adults and persons with a higher educational level. A number of areas were identified where nutritional knowledge was extremely poor, as was the case with the recommended daily fruit and vegetable intake and the caloric content of the nutrients. Overall, nutritional knowledge was found to have a positive influence on food preferences and consumption frequency, those participants with a higher nutritional knowledge reporting a higher consumption of fruits, vegetables and low-fat products, in addition to a lower consumption of high-fat and high-sugar foods.


Medial parietal cortex activation related to attention control involving alcohol cues.
Automatic attentional engagement toward and disengagement from alcohol cues play a role in alcohol use and dependence. In the current study, social drinkers performed a spatial cueing task designed to evoke conflict between such automatic processes and task instructions, a potentially important task feature from the perspective of recent dual-process models of addiction. Subjects received instructions either to direct their attention toward pictures of alcoholic beverages, and away from non-alcohol beverages; or to direct their attention toward pictures of non-alcoholic beverages, and away from alcohol beverages. Instructions were varied per block. Activation in medial parietal cortex was found during "approach alcohol" versus "avoid-alcohol" blocks. This region is associated with the, possibly automatic, shifting of attention between stimulus features. Subjects thus appeared to shift attention away from certain features of alcoholic cues when attention had to be directed toward their location. Further, activation in voxels located close to this region was negatively correlated with riskier drinking behavior. A tentative interpretation of the results is that risky drinking may be associated with a reduced automatic tendency to shift attention away from potentially distracting task-irrelevant alcohol cues. Future study is needed to test this interpretation, and to further determine the role of medial posterior regions in automatic alcohol-related attentional processes in general.


Local motion effects on form in radial frequency patterns.
Sinusoidal modulation of radial speed around a circular path of tangentially oriented Gabor patches results in the percept of modulation of the radius. These patterns have been called motion radial frequency (RF) patterns. Sensitivity to these patterns has been attributed to global summation of local speed by mechanisms, analogous to those proposed to explain sensitivity to spatial RF patterns, which are sensitive to particular radial frequencies of speed modulation. We demonstrate that: Adaptation to spatial RF patterns results in a phase specific after effect in motion RF patterns and vice versa; the rate of change of perceived displacement of a Gabor patch with a moving grating with increasing speed of that grating, is independent of whether the patch is or is not incorporated into a circular path; in the absence of local motion direction cues, global integration across 1, 2 and 3 cycles of motion and spatial RF modulation conforms to a power function with the same index; and finally that the magnitude of the motion position illusion is sufficient and necessary to account for sensitivity to motion RF patterns. We therefore propose that motion RF patterns are analyzed by the same mechanisms responsible for sensitivity to spatial RF patterns using perceived rather than actual local positions of the Gabor patches.


Comparison of the incidence of fetal prolonged deceleration after induction of labor analgesia between dural puncture epidural and combined spinal epidural technique: a pilot study.
Abnormal cardiotocogram (CTG) tracing may appear after induction of neuraxial labor analgesia. Non-reassuring fetal status (NRFS) indicated by severely abnormal tracings, such as prolonged deceleration (PD) or bradycardia, can necessitate immediate operative delivery. Combined spinal epidural analgesia (CSEA) is known to result in more frequent abnormal tracings than epidural analgesia (EA); however, the corresponding data related to dural puncture epidural (DPE) are unclear. We aimed to evaluate the rates of incidence of severe abnormal CTG after induction of DPE and CSEA. In this study of nulliparous women with full-term pregnancy, data for the DPE intervention group were prospectively collected, while those for the CSEA control group were obtained from medical records. Neuraxial analgesia was performed with cervical dilation ≤ 5 cm, administering initial epidural dosing of 15 mL of 0.125% levobupivacaine with fentanyl 2.5µg/mL for DPE, and intrathecal 0.5% bupivacaine 2.5 mg (0.5ml), fentanyl 10 µg (0.2ml), and 1.3 mL of saline for CSEA. The primary outcome was the incidence of PD, defined as a fetal heart rate reduction ≥ 15 bpm below the baseline and with a lowest value < 80 bpm, and lasting for ≥ 2 min but < 10 min (fetal heart rate < 80 bpm does not have to last for ≥ 2 min), within 90 min after induction of neuraxial labor analgesia. A total of 302 patients were analyzed, with 151 in each group. The incidence of PD after DPE induction was significantly lower than that after CSEA induction (4.0% vs. 14.6%, P = 0.0015, odds ratio = 0.243, 95% confidence interval = 0.095-0.617). DPE appears to be a safer method compared to CSEA for neuraxial labor analgesia in the early stages of labor for nulliparous women. UMIN-CTR: UMIN000035153 . Date registered: 01/01/2019.


Characterization and storage stability of chlorophylls microencapsulated in different combination of gum Arabic and maltodextrin.
Detailed investigations on the physicochemical and structural characterization of chlorophyll loaded microcapsules and their storage stability have not previously been conducted. Therefore, our objective was to encapsulate unstable chlorophylls using different blends of gum Arabic (GA) and maltodextrin (MD) (GA-MD ratios of 5:5, 3:7, and 0:10) by spray-drying to improve storage stability of chlorophylls. An increase in concentration of MD in wall materials was associated with lower moisture content (0.56%), higher encapsulation efficiency (77.19%), chlorophyll content (46.78 µg/g dry powder), degree of crystallinity, and thermal stability of microcapsules. Furthermore, FTIR, XRD, and DSC analyses confirmed inclusion of chlorophylls within microcapsules. The entrapment of chlorophylls within microcapsules enhanced their storage stability at all temperatures (4, 20, and 40 °C) for ten days; notably, microcapsules coated with MD alone showed the highest storage stability (94.7-97.5%). In conclusion, microencapsulation of chlorophylls using MD alone was optimal for enhancing chlorophylls' storage stability.


SARS-CoV-2 Testing of Emergency Department Patients Using cobas® Liat® and eazyplex® Rapid Molecular Assays.
Rapid testing for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) of patients presenting to emergency departments (EDs) facilitates the decision for isolation on admission to hospital wards. Differences in the sensitivity of molecular assays have implications for diagnostic workflows. This study evaluated the performance of the cobas® Liat® RT-PCR, which is routinely used as the initial test for ED patients in our hospitals, compared with the eazyplex® RT-LAMP. A total of 378 oropharyngeal and nasal swabs with positive Liat® results were analysed. Residual sample aliquots were tested using NeuMoDx™, cobas® RT-PCR, and the eazyplex® assay. Patients were divided into asymptomatic (n = 157) and symptomatic (n = 221) groups according to the WHO case definition. Overall, 14% of positive Liat® results were not confirmed by RT-PCR. These samples were mainly attributed to 26.8% of asymptomatic patients, compared to 3.8% of the symptomatic group. Therefore, positive Liat® results were used to provisionally isolate patients in the ED until RT-PCR results were available. The eazyplex® assay identified 62% and 90.6% of RT-PCR-confirmed cases in asymptomatic and symptomatic patients, respectively. False-negative eazyplex® results were associated with RT-PCR Ct values > 30, and were more frequent in the asymptomatic group than in the symptomatic group (38.1% vs. 5.1%, respectively). Both the Liat® and eazyplex® assays are suitable for testing symptomatic patients. Their use in screening asymptomatic patients depends on the need to exclude any infection or identify those at high risk of transmission.


Interaction with touchscreen smartphones in patients with essential tremor and healthy individuals.
Smartphones use in biomedical research is becoming more prevalent in different clinical settings. We performed a pilot study to obtain information on smartphone use by patients with essential tremor (ET) and healthy controls, with a view to determining whether performance of touchscreen tasks is different between these groups and describing touchscreen interaction factors. A total of 31 patients with ET and 40 sex- and age-matched healthy controls completed a descriptive questionnaire about the use of smartphones. Participants subsequently interacted with an under-development Android application, and performed 4 tests evaluating typical touchscreen interaction gestures; each test was performed 5 times. The type of smartphone use and touchscreen interaction were not significantly different between patients and controls. Age and frequency of smartphone use are key factors in touchscreen interaction. Our results support the use of smartphone touchscreens for research into ET, although further studies are required.


Prevalence of Leptospira and Brucella antibodies in wild boars (Sus scrofa) in Tuscany, Italy.
Five hundred sixty-two blood samples were collected from wild boars (Sus scrofa) shot in six districts of Tuscany, central Italy, between 1997 and 2000. Sera were examined for antibodies specific for Leptospira interrogans by microagglutination test and Brucella spp. by the Rose Bengal test and indirect enzyme-linked immunosorbent assay. Thirty-four (6.0%) samples tested positive for anti-Leptospira antibodies, 29 (5.1%) sera were positive for anti-L. interrogans serovar bratislava antibodies (titres ranging from 1:100-1:400), and 5 (0.9%) sera were positive for anti-L. interrogans serovar icterohaemorrhagiae antibodies (titres 1:100). All the examined sera were negative for anti-Brucella antibodies.


Recombinant Protein Expression in Escherichia coli (E.coli): What We Need to Know.
Host, vector, and culture conditions (including cultivation media) are considered among the three main elements contributing to a successful production of recombinant proteins. Accordingly, one of the most common hosts to produce recombinant therapeutic proteins is Escherichia coli. A comprehensive literature review was performed to identify important factors affecting production of recombinant proteins in Escherichia coli. Escherichia coli is taken into account as the easiest, quickest, and cheapest host with a fully known genome. Thus, numerous modifications have been carried out on Escherichia coli to optimize it as a good candidate for protein expression and; as a result, several engineered strains of Escherichia coli have been designed. In general; host strain, vector, and cultivation parameters are recognized as crucial ones determining success of recombinant protein expression in Escherichia coli. In this review, the role of host, vector, and culture conditions along with current pros and cons of different types of these factors leading to success of recombinant protein expression in Escherichia coli were discussed. Successful protein expression in Escherichia coli necessitates a broad knowledge about physicochemical properties of recombinant proteins, selection among common strains of Escherichia coli and vectors, as well as factors related to media including time, temperature, and inducer.


New sciaphilic plakinids (Porifera, Homoscleromorpha) from the Central-Western Pacific.
The sponge class Homoscleromorpha is a key model for the evolutionary biology of the Metazoa but its diversity remains poorly known. Here we describe six new species of the homoscleromorph family Plakinidae found in shaded habitats (submarine caves, tunnels and overhangs) of New Caledonia and Marquesas Islands, Central-Western Pacific. The new species belong to four genera: Corticium (Corticium vaceleti sp. nov.), Plakina (Plakina finispinata sp. nov.), Plakinastrella (Plakinastrella osculifera sp. nov., Plakinastrella nicoleae sp. nov. and Plakinastrella pseudolopha sp. nov.), and Plakortis (Plakortis ruetzleri sp. nov.). Plakinastrella pseudolopha sp. nov. has a novel spicule type called here 'pseudolophose spicules'. The diversity of Homoscleromorpha is raised to 50 species in the Pacific Ocean and 120 spp. worldwide.


Type 1 Arnold-Chiari malformation and Noonan syndrome. A new diagnostic feature?
Noonan syndrome is a clinically and genetically heterogeneous genetic condition. Arnold-Chiari malformation has been previously reported in three cases of Noonan syndrome. We describe a fourth case with this association. We suggest that brain and cervical spine MRI should be performed if neurological symptoms are present.


Cardiopulmonary Bypass Settings for the Prevention of Early Hypotension During CABG.
Vasoplegic syndrome is a form of vasodilatory shock that can occur before, during or after cardiopulmonary bypass (CPB). We introduce a strategy to reduce the incidence of early hypotension phenomena during Coronary Artery Bypass Graft (CABG) procedures. In this prospective cohort study, 100 patients underwent elective CABG with two perioperative CPB settings. The study group (50 patients) was managed with retrograde autologous priming (RAP), 3-minute stepwise for the institution of CPB, and pulsatile flow (PP). The control group (50 patients) was managed without RAP, with the rapid initiation of CPB, and non-pulsatile (NP) flow. The primary endpoints were MAP (mmHg), number of hypotensive phenomena (MAP < 50 mmHg for > 30 sec), the venous return volume on CPB (ml), the cardiac index (L/min/m2), hemoglobin (g/dL), indexed oxygen delivery (DO2i, ml/min/m2), the systemic vascular resistance index (SVRI, dynes s m2/cm5), number of 1-ml boluses of a vasoactive substance (norepinephrine), the positive fluid balance (ml), and the number of red blood cell units for transfusion. During CPB, the mean values in the study and control groups were as follows: MAP, 68± 7 vs 56 ± 7 (p-value, 0.0019); hypotensive phenomena, 3 ± 1 vs 8 ±2 (p-value, 0.019); venous return volume, 840±79 vs 1129 ±123 (p-value, 0.0017); cardiac index, 2.4 ± 0.4 vs 2.7 ±0.2 (p-value, 0.0023); hemoglobin, 9.13 ± 0.29 vs 7.8± 0.23 (p-value, 0.0001); DO2i, 301± 12 vs 276±23 (p-value, 0.0011); SVRI, 1879 ±280 vs 2210 ±140 (p-value, 0.0017); norepinephrine, 1±2 vs 8 ±3 (p-value, 0.0023); positive fluid balance, 750 ±212 vs 1450 ±220 (p-value, 0.005); and total number of red blood cell units for transfusion, 16 ±4.2 vs 27 ± 5.3 (p-value, 0.008). In this prospective cohort study, during CPB, the study group showed a better preservation of MAP, SVRI, and DO2i, and a reduction of vasoconstrictor use in a CPB setting with the RAP technique, 3-minute stepwise for the initiation of CPB and pulsatile pump flow, compared to the control group. Further studies are needed to validate this perioperative approach to CPB.


Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and intrinsic fluorescence.
Glycation of proteins leads to the formation of advanced glycation endproducts (AGEs) of diverse molecular structure and biological function. Serum albumin derivatives modified to minimal and high extents by methylglyoxal and glucose in vitro have been used in many studies as model AGE proteins. The early and advanced glycation adduct contents of these proteins were investigated using the 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate (AQC) chromatographic assay of enzymic hydrolysates. AGEs derived from methylglyoxal, glyoxal and 3-deoxyglucosone, the hydroimidazolones N(delta)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1), N(delta)-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) and N(delta)-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine (3DG-H1), bis(lysyl)imidazolium cross-links methylglyoxal-derived lysine dimer (MOLD), glyoxal-derived lysine dimer (GOLD), 3-deoxyglucosone-derived lysine dimer (DOLD), monolysyl adducts N(epsilon)-(1-carboxyethyl)lysine (CEL), N(epsilon)-carboxymethyl-lysine (CML) and pyrraline, other AGEs, N(delta)-(4-carboxy-4,6-dimethyl-5,6-dihydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)ornithine (THP), argpyrimidine and pentosidine, and fructosyl-lysine were determined. AGEs with intrinsic fluorescence (argpyrimidine and pentosidine) were assayed without derivatization. Human serum albumin (HSA) glycated minimally by methylglyoxal in vitro contained mainly MG-H1 with minor amounts of THP and argpyrimidine. Similar AGEs were found in prothrombin glycated minimally by methylglyoxal and in N(alpha)-t-butyloxycarbonyl-arginine incubated with methylglyoxal. HSA glycated highly by methylglyoxal contained mainly argpyrimidine, MG-H1 and THP, with minor amounts of CEL and MOLD. HSA glycated minimally by glucose in vitro contained mainly fructosyl-lysine and CML, with minor amounts of THP, MG-H1, G-H1, 3DG-H1, argpyrimidine and DOLD. HSA glycated highly by glucose contained these AGEs and pyrraline, and very high amounts ( approximately 8 mol/mol of protein) of fructosyl-lysine. Most AGEs in albumin glycated minimally by methylglyoxal and glucose were identified. Significant proportions of arginine and lysine-derived AGEs in albumin modified highly by methylglyoxal, and lysine-derived AGEs in albumin modified highly by glucose, remain to be identified.


Linalool from Lippia alba: study of the reproducibility of the essential oil profile and the enantiomeric purity.
A new chemotype of the aromatic Verbenaceae species Lippia alba Mill. N. E. Br. from southeastern Brazil has recently been shown to have a high content of linalool in the leaf essential oil. Vegetative propagation of this chemotype was conducted at six different locations in Brazil, and the variation of the content and the optical purity of linalool in the oils were verified. Yields (0.6-0.9%, hydrodistillation), chemical composition, linalool content, and optical purity of the oils from all the plants were compared, using GC-FID, GC-MS, chiral chromatography, and retention index calculation. No plant exceeded the matrix in linalool content (46.5 to 90.7%), and the chemical profile of the oils was the same for all the samples. Purification of linalool to a content close to 100% was effected by vacuum distillation of the crude oil. Chiral analysis showed exclusively the presence of S-linalool in all the crude oils and in the distilled samples.


Risk of falls in older people during fast-walking--the TASCOG study.
To investigate the relationship between fast-walking and falls in older people. Individuals aged 60-86 years were randomly selected from the electoral roll (n=176). Gait speed, step length, cadence and a walk ratio were recorded during preferred- and fast-walking using an instrumented walkway. Falls were recorded prospectively over 12 months. Log multinomial regression was used to estimate the relative risk of single and multiple falls associated with gait variables during fast-walking and change between preferred- and fast-walking. Covariates included age, sex, mood, physical activity, sensorimotor and cognitive measures. The risk of multiple falls was increased for those with a smaller walk ratio (shorter steps, faster cadence) during fast-walking (RR 0.92, CI 0.87, 0.97) and greater reduction in the walk ratio (smaller increase in step length, larger increase in cadence) when changing to fast-walking (RR 0.73, CI 0.63, 0.85). These gait patterns were associated with poorer physiological and cognitive function (p<0.05). A higher risk of multiple falls was also seen for those in the fastest quarter of gait speed (p=0.01) at fast-walking. A trend for better reaction time, balance, memory and physical activity for higher categories of gait speed was stronger for fallers than non-fallers (p<0.05). Tests of fast-walking may be useful in identifying older individuals at risk of multiple falls. There may be two distinct groups at risk--the frail person with short shuffling steps, and the healthy person exposed to greater risk.


Outbreak of cryptosporidiosis in dairy goats in Brazil.
An outbreak of cryptosporidiosis is reported among 22 suckling kids aged one to two weeks which were maintained for experimental purposes at the veterinary hospital of the University of Minas Gerais. They were divided into three groups. Group A consisted of 10 animals with acute diarrhoea; initially their faeces were pasty but later they were excreted in watery streams. The animals were treated with gentamicin and fluid therapy but did not respond to treatment and died within a week. Postmortem examination revealed liquid intestinal contents, enlarged mesenteric lymph nodes, and hyperaemia and haemorrhage were observed in the final third of the small intestine of some of the animals. Of the 10 animals in group B four had diarrhoea and six were normal; postmortem examination showed that the macroscopic changes were similar to those observed in group A. Three of the animals with diarrhoea had a massive Cryptosporidium infection in the final third of the small intestine, caecum and colon. Four of the six normal animals had a moderate Cryptosporidium infection in the same organs. The two kids in group C died; they had pasty faeces, and there were many Cryptosporidium oocysts in the faecal smears.


Vitiligo treatment update.
Vitiligo is a common depigmenting disease that can affect the skin and mucosal surfaces. Various treatments have been used over the years with varying repigmentation rates. This review looks at the evidence of commonly used therapies for vitiligo.


[Malignant lymphoma of the thyroid gland].
During the past 14 years, 14 cases involving a malignant lymphoma of the thyroid have been treated at our department. These cases have been histologically reviewed and reclassified, according to the Working Formulation. Four cases involved a low grade malignancy (LGM), 9 cases an intermediate malignancy (IGM), and 4 cases a high grade malignancy (HGM). Thirteen lymphomas were of the B-cell type, and the remaining lymphoma was of the T-cell type. The coexistence of a chronic thyroiditis was noted in 9 cases. Survivors were only found in the LGM and IGM groups. We consider it necessary to treat malignant lymphomas of the thyroid according to the subtype of the Working Formulation.


(1)H NMR based metabolomics approach to study the toxic effects of herbicide butachlor on goldfish (Carassius auratus).
Butachlor, one of the most widely used herbicides in agriculture, has been reported with high ecotoxicity to aquatic plants and animals. In this study, a (1)H NMR based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively investigate the toxic effects of butachlor on four important organs (gill, brain, liver and kidney) of goldfish (Carassius auratus) for the first time. After 10 days' butachlor exposure at two dosages of 3.2 and 0.64 μmol/L, fish tissues (gill, brain, liver and kidney) and serum were collected. Histopathological inspection revealed severe impairment of gill filaments and obvious cellular edema in livers and kidneys. The increase of glutathione peroxidase (GSH-Px) activity in gill and methane dicarboxylic aldehyde (MDA) level in four tissues reflected the disturbance of antioxidative system in the intoxicated goldfish. Serum lactate dehydrogenase (LDH) activity and creatinine (CRE) level were increased in butachlor exposure groups, suggesting liver and kidney injuries induced by butachlor. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) of NMR profiles disclosed metabolic changes that were related to the toxic effects of butachlor including oxidative stress, disorder of energy metabolism and amino acids metabolism, and disturbance of neurotransmitter balance in butachlor exposed goldfish. This integrated metabolomics approach provided a molecular basis underlying the toxicity of butachlor and demonstrated that metabolomics was a powerful and highly effective approach to elucidate the toxicity and underlying mechanisms of herbicides and pesticides, applicable for their risk assessment.


Evolution by polyploidy and gene regulation in Anura.
The evolution of the metazoa has been characterized by gene redundancy, generated by polyploidy, tandem duplication and retrotransposition. Polyploidy can be detected by looking for duplicated chromosomes or segments of orthologous chromosomes in post-polyploid animals. It has been proposed that the evolutionary role of polyploidy is to provide extra-copies of genes, whose subsequent alteration leads to new functions, increased biological complexity, and, ultimately, speciation. We review the theory of evolution by genome duplication, basing our arguments on findings from autopolyploid anurans and fish, undergoing post-polyploidy diploidization. We conclude that: 1) the high genetic variability of autotetraploid anurans is a result of tetrasomic expression, based on studies of isozymes and other proteins. 2) Epigenetic mechanisms mediate the reduced expression or silencing of redundant copies of genes in the regulation of gene expression of these tetraploids. This conclusion is based on data concerning ribosomal and hemoglobin gene activity. 3) Duplication of the genome may have occurred more than once in the phylogeny of the anurans, as exemplified by 4n and 8n Leptodactylidae species.


Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner.
Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females.


Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support.
This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump-type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200° produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges.


Evolution and function of innate immune receptors--insights from marine invertebrates.
Innate, nonadaptive immune receptors represent phylogenetically ancient first-line sensors of invariant non-self patterns and other cellular danger signals. From lower animal phyla to vertebrates, most pathogens are immediately detected by various recognition systems and are destroyed by induction of defense effectors like antimicrobial peptides. Toll-like receptors, nucleotide-binding and oligomerization domain-like receptors and scavenger receptor cysteine-rich proteins represent archetypes of the innate immune receptors, which mediate the complex interaction between the host and microbiota at the interface of epithelial barriers. In this review, we will use knowledge gained from marine invertebrates as a paradigm to describe how this constant molecular crosstalk within the holobiont, i.e. the animal with all its associated microorganisms, contributes to epithelial homeostasis, immunological integrity and maintenance of the resident microbial diversity.


Donepezil can improve daily activities and promote rehabilitation for severe Alzheimer's patients in long-term care health facilities.
Cholinesterase inhibitors can delay the progression of Alzheimer's disease (AD). Several clinical trials of the drug in moderate to severe AD have consistently reported clinically positive effects. A combining effect with psychosocial intervention was reported in mild to moderate AD patients. Since a therapeutic approach or rehabilitation combined with cholinesterase inhibitors for severe AD patients remains controversial, we performed a prospective intervention for patients in Long-Term Care Health Facilities (LTCHF). Two LTCHFs (N1, N2) were enrolled. N1 is a 126-bed facility that does not treat with donepezil but rather with psychosocial intervention (reality orientation and reminiscence). N2 is a 150-bed facility with a 50-bed special dementia unit, in which the physician can prescribe donepezil. On top of the similar psychosocial intervention, rehabilitation is performed in N2. Thirty-two severe AD patients (MMSE < 6) in N1 and N2 (16 vs. 16) were compared for the effect of donepezil (10 mg/d for 3 months) with or without psychosocial intervention (n = 8 vs. 8 for each facility). The Vitality Index was used to assess daily activities and the introduction of rehabilitation. The response ratio (MMSE 3+) of donepezil was 37.5% in N2. The combination of donepezil with the psychosocial intervention improved the Vitality Index total score, and Communication, Eating, and Rehabilitation subscores (Wilcoxon, p = 0.016, 0.038, 0.023, and 0.011, respectively). Most of them were smoothly introduced to rehabilitation, and the proportion of accidental falls decreased. Psychosocial intervention in N1 without the drug only improved the total score (Wilcoxon, p = 0.046). A combined therapeutic approach of donepezil and psychosocial intervention can have a positive effect, even for severe patients through the introduction of rehabilitation and decreasing accidental falls. However, these findings require replication in a larger cohort.


[Magnetic resonance imaging in the diagnosis of adrenal pathology].
M.R.I. allows a good delineation of adrenals, due to the high contrast with fat and to the use of frontal planes. We showed on post operative adrenal lesions samples that the lipid percentages, high in normal and hyperplasic glands, was still high in most benign adenomas, and very low (under 5%) in adrenal carcinomas. MRI, with Dixon sequence, allows to evaluate this lipid percentage in adrenal lesions. Post-operative controls show a good agreement between in vivo and in vitro measurements. This simple technique should allow to discriminate between malignant and benign adrenal cortex lesions.


Endocrinological Features of Hartsfield Syndrome in an Adult Patient With a Novel Mutation of FGFR1.
Hartsfield syndrome (HS: OMIM 615465) is a rare congenital disease associated with a mutation of the fibroblast growth factor receptor 1 gene (FGFR1) with the main features of holoprosencephaly and ectrodactyly. Patients with HS also present with endocrinological deficits, such as isolated hypogonadotropic hypogonadism and central diabetes insipidus. Although there are several studies on infancy/childhood history, there is no study of infant/childhood/adolescent/young adult HS natural history and endocrinological findings. Here, we report a male patient with HS associated with a novel de novo FGFR1 mutation (c. 1868A > C). The endocrinological profile was evaluated at ages 1 and 31 years. This long-term follow-up study highlights functional changes in the posterior pituitary gland and features of bone metabolism disorder. We also describe the anterior pituitary function. To our knowledge this is the first description of the natural history of an HS patient through birth to young adult age. Although the HS infants reported in the literature develop central diabetes insipidus, little is known about the serial changes in pituitary gland function during growth in HS patients. In this study we describe an adult patient with HS who showed improvement of hypernatremia during early adulthood. In addition, we emphasize the importance of prevention and treatment of osteoporosis in HS.


Further observations on mandibular anaesthesia.
Recent studies have emphasized that none of the accepted intraoral landmarks used in the conventional mandibular block technique is completely reliable, nor can they presage those instances in which the lingula presents an obstruction to the needle pathway. An answer to this problem is suggested by the use of extraoral landmarks to assist in estimating the height and expected depth of needle penetration. The importance of palpating for the anterior border of the medial pterygoid muscle deep in the pterygotemporal depression is reaffirmed.


IFN-gamma downregulates interleukin-4 functional activity on monocytes by multiple mechanisms.
Interleukin-4 (IL-4) has potent anti-inflammatory properties on monocytes and suppresses lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and IL-1beta production. Culture with interferon (IFN-gamma) alters human monocyte responses to IL-4 by multiple mechanisms. As previously published, IFN-gamma reduced IL-4-activated signal transducer and activator of transcription-6 (STAT-6). This correlated with an inability of IL-4 to suppress LPS-induced TNF-alpha but not IL-1beta production. A second mechanism, apparent some 48 h after exposure to IFN-gamma, involved a significant suppression of IL-4 receptor (IL-4R) expression at the cell surface, and this correlated with the loss of additional functional responses to IL-4, including IL-4-induced suppression of LPS-induced IL-1beta production. This study identified a further role of IFN-gamma on IL-4 responses, including reduced IL-4R surface expression by human monocytes. Increased release of soluble gammac from IFN-gamma-treated monocytes provides an additional mechanism by which IFN-gamma may control the functional activity of IL-4. This study characterizes further the opposing effects of the type 1 and type 2 cytokine regulatory systems.


Progress toward poliomyelitis eradication--Nigeria, January 2004-July 2005.
After the 1988 World Health Assembly resolution to eradicate polio, the number of countries where polio is endemic decreased from 125 in 1988 to six in 2003. However, the Global Polio Eradication Initiative faced critical challenges during 2003-2005, when a resurgence of polio cases occurred across Africa. Nigeria, the most populous country of the continent, experienced increased wild poliovirus (WPV) transmission throughout the country after suspension of supplementary immunization activities (SIAs) in certain northern states because of misconceptions regarding vaccine safety. The resurgence in Nigeria resulted in the spread of WPV during 2003-2005 into 18 countries that had been polio-free for 1 or more years, including three countries outside Africa. Transmission was reestablished and is ongoing in six of these countries. The Nigerian states that suspended campaigns subsequently resumed SIAs in 2004, in synchrony with SIAs being conducted in other countries across West and Central Africa. This report summarizes polio eradication activities and WPV circulation in Nigeria during January 2004-July 2005 and the actions under way to interrupt WPV transmission.


Abdominal obesity is essential for the risk of venous thromboembolism in the metabolic syndrome: the Tromsø study.
The metabolic syndrome is a cluster of cardiovascular risk factors, including abdominal obesity, hypertension, dyslipidemia and insulin resistance, associated with increased risk of cardiovascular diseases and all cause mortality. The purpose of the study was to assess the impact of the metabolic syndrome, and its individual components, on the risk of venous thromboembolism (VTE) in a prospective population-based study. Individual components of the metabolic syndrome were registered in 6170 subjects aged 25-84 years in the Tromsø Study in 1994-1995, and first ever VTE events were registered until 1 September 2007. The metabolic syndrome was present in 21.9% (1350 subjects) of the population. There were 194 validated first VTE events (2.92 per 1000 person-years) during a mean of 10.8 years of follow-up. Presence of metabolic syndrome was associated with increased risk of VTE (HR, 1.65; 95% CI, 1.22-2.23) in age- and gender-adjusted analysis. The risk of VTE increased with the number of components in the metabolic syndrome (P < 0.001). Abdominal obesity was the only component significantly associated with VTE in multivariable analysis including age, gender, and the individual components of the syndrome (HR, 2.03; 95% CI, 1.49-2.75). When abdominal obesity was omitted as a diagnostic criterion, none of the other components, alone or in cluster, was associated with increased risk of VTE. Our study provides evidence for the metabolic syndrome as a risk factor for TE. Abdominal obesity appeared to be the pivotal risk factor among the individual components of the syndrome.


Mucinous adenocarcinoma of the renal pelvis presenting as pyonephrosis: a case report.
Tumours of the renal pelvis are rare. We present a case of primary mucinous adenocarcinoma of the renal pelvis masquerading as pyonephrosis clinically and diagnosed on histopathologic examination. Patient presented with pyonephrosis of the left kidney due to a large staghorn calculus and was treated with tube nephrostomy followed by nephrectomy.


Longitudinal associations between appearance-related social media consciousness and adolescents' depressive symptoms.
Frequent social media use among adolescents is associated with depressive symptoms, though prior work has overwhelmingly used cross-sectional designs and focused on "screen time." Subjective social media experiences, such as the concern with one's physical appearance on social media, may be more relevant to adolescents' depressive symptoms than mere frequency of use. Appearance-related social media consciousness (ASMC) is the preoccupation with one's physical attractiveness in social media photos and has been associated with depressive symptoms above and beyond frequency of social media use in prior cross-sectional work. In this brief report, we assessed this association longitudinally over 1 year within a diverse sample of highschool adolescents in the Southeastern US (n = 163, M age = 16.19; 55.8% girls; 44.8% White, 23.9% Black, 26.4% Hispanic/Latinx; 49.7% received free or reduced-price lunch). Baseline ASMC was associated with higher depressive symptoms 1 year later, even when controlling for time spent on social media. Although girls reported higher levels of ASMC, associations were similar for adolescent boys and girls. No evidence was found that heightened depressive symptoms at baseline were associated with higher ASMC 1 year later. The findings highlight the importance of physical appearance concerns on social media-above and beyond the frequency of use-in the development of depressive symptoms among adolescents. Implications for future research to examine the role of subjective social media experiences in adolescents' depressive symptoms are discussed.


Delayed visual maturation: ophthalmic and neurodevelopmental aspects.
Delayed visual maturation (DVM) can present as an isolated anomaly (type 1A), but can be compounded by perinatal problems (type 1B), severe neurodevelopmental delay (type 2), or ocular anomalies/nystagmus (type 3), in which group the common feature appears to be nystagmus. The neurodevelopmental and ophthalmic aspects of 26 infants with DVM were studied. Onset of visual improvement, rate of acquisition of normal vision and eventual outcome were studied quantitatively, using an adaptation of the acuity card procedure. Neurodevelopmental assessment was performed after visual improvement. The results support the long-held clinical impression that if blindness is the presenting feature, neurodevelopmental outlook is excellent. DVM could represent a defect in the extrageniculostriate visual system, and the onset of vision in all types--and the development of nystagmus in type 3--could herald the emergence of geniculostriate function.


Evaluation of aztreonam in experimental bacterial meningitis and cerebritis.
Aztreonam (SQ 26,776), a new monocyclic beta-lactam agent, was compared with ampicillin, ampicillin plus chloramphenicol, and gentamicin in rabbits with experimental meningitis induced by, respectively, ampicillin-susceptible Haemophilus influenzae, ampicillin-resistant H. influenzae, and Escherichia coli. Aztreonam was also compared with gentamicin in experimentally induced E. coli cerebritis in rats. Doses of the various agents were delivered that produced near-peak concentrations in serum comparable to those attained in humans on standard parenteral regimens. The percent penetration [( concentration in cerebrospinal fluid/concentration in serum] X 100) of aztreonam into purulent rabbit cerebrospinal fluid was 23% (versus 12, 27, and 21%, respectively, for ampicillin, chloramphenicol, and gentamicin). In experimental meningitis in vivo, aztreonam was more rapidly bactericidal than was ampicillin in ampicillin-susceptible H. influenzae meningitis, ampicillin or chloramphenicol in ampicillin-resistant H. influenzae meningitis, or gentamicin in E. coli meningitis. In the therapy of experimental cerebritis, the early stage of brain abscess formation, aztreonam reduced the numbers of E. coli in rat brain as rapidly as did gentamicin. Aztreonam deserves further evaluation in acute gram-negative bacterial infections of the central nervous system in both experimental animals and in humans.


Transient spatiotemporal chaos is extensive in three reaction-diffusion networks.
Extensive (asymptotic) spatiotemporal chaos is comprised of statistically similar subsystems that interact only weakly. A systematic study of transient spatiotemporal chaos reveals extensive system behavior in all three reaction-diffusion networks for various boundary conditions. The Lyapunov dimension, the sum of positive Lyapunov exponents, and the logarithm of the transient lifetime grow linearly with the system size. The unstable manifold of the chaotic saddle has nearly the same dimension as the saddle itself, and the stable manifold is nearly space filling.


Coating of an anti-Fas antibody on silicone: first in vivo results.
Although the etiology of capsular contracture after breast augmentation has not yet been definitively clarified, the literature contains numerous reports placing the blame on a foreign body reaction. We have developed a procedure for covalently activating a silicone surface with an anti-Fas antibody, which might suppress the foreign body reaction on the silicone surface. The authors evaluate whether surrounding tissue might be influenced by anti-Fas antibody coating on silicone disks in comparison to untreated silicone disks in an in vivo model. During this study, 4-mm anti-Fas-coated silicone disks were implanted subcutaneously in the paravertebral region of mice (C57/BL6). Silicone disks passing the activation coating process without anti-Fas antibody incubation were defined as the control group. Twelve weeks after implantation, the disks were removed and the surrounding tissue examined. The tissue surrounding the silicone disks in the experimental group showed significantly increased levels of collagen type 3, elevated levels of matrix metalloproteinase 9, markedly decreased levels of transforming growth factor β2, and a reduced CD68 expression in the pericapsular tissue. The first in vivo data reveal that the tissue surrounding a silicone surface can be influenced by the vectored binding of an anti-Fas antibody.


Cost efficiency of canagliflozin versus sitagliptin for type 2 diabetes mellitus.
To compare 1-year clinical outcomes and cost efficiency of treating adults with type 2 diabetes mellitus (T2DM) with canagliflozin (300 mg/day) or sitagliptin (100 mg/day), both added on a background of metformin and sulfonylurea. An economic model integrated data from an active-controlled, randomized trial, claims database analyses, and published literature. The model adopted a US managed care payer perspective and included the clinical and economic impact of achieving specific clinical quality goals. The model was run separately for 2 single clinical quality metrics, glycated hemoglobin (A1C) < 7% (used as base case) or < 8%, and 4 composite metrics (A1C < 7% or < 8% combined with body mass index < 30 kg/m2 and blood pressure < 140/90 mm Hg or low-density lipoprotein cholesterol < 100 mg/dL). Cost savings of achieving versus not achieving metrics were derived from a claims database analysis. Drug and adverse event costs were included. In the base case, compared with sitagliptin 100 mg, treatment with canagliflozin 300 mg resulted in $215 in annual cost savings and 12.3 absolute percentage points more patients achieving goal. Similar findings were found across all other quality metrics (difference in proportion achieving goal ranging from 6.7% to 19.0% and annual savings ranging from $1 to $669). Canagliflozin remained cost saving versus sitagliptin in sensitivity analyses. Canagliflozin 300 mg may represent a cost-efficient T2DM treatment option versus sitagliptin 100 mg for patients on metformin plus sulfonylurea due to lower overall costs and better achievement of A1C and quality composite goals.