A Digital Health Program Targeting Physical Activity Among Adolescents With Overweight or Obesity: Open Trial.
Prior studies suggest that mobile health physical activity programs that provide only weekly or daily text-based health coaching evidence limit the efficacy in improving physical activity in adolescents with overweight or obesity. It is possible that incentives, combined with health coaching and daily feedback on goal success, may increase program efficacy; however, such programs have not yet been tested with adolescents with overweight and obesity. This study aims to examine the feasibility and acceptability of a 12-week, incentive-based, mobile health physical activity program with text-based health coaching, goal setting, and self-monitoring for adolescents with overweight or obesity. Program adherence and changes in tracked physical activity (ie, steps and active minutes while wearing a Fitbit [Google LLC]), body mass, and body fat are assessed. A total of 28 adolescents aged 13 to 18 years with a BMI ≥90th percentile participated in the program. Of the 28 participants, 2 (7%) were lost to follow-up; thus, data from 26 (93%) participants were used in analyses. Participant-reported acceptability was high, with all mean ratings of text-based coaching, Fitbit use, and the overall program being >5 on a 7-point scale. In addition, 85% (23/26) of participants reported that they would like to continue to wear the Fitbit. Program adherence was also high, as participants wore the Fitbit on 91.1% (SD 12.6%) of days on average and met their weekly goals for an average of 7 (SD 3.5) of 11 possible weeks. There were no demographic (ie, sex, age, and baseline body mass) differences in the percentage of days participants wore their Fitbit. Across the 12-week study, there were significant improvements in tracked daily active minutes (P=.006) and steps (P<.001) and significant pre- to posttest improvements in body fat percentage (P=.04). The pilot program improved adolescent physical activity and physical health. A larger factorial design trial with adaptive daily goals may clarify the role of each program component in driving physical activity.


Mitofusin 2 tethers endoplasmic reticulum to mitochondria.
Juxtaposition between endoplasmic reticulum (ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are unknown. Here we show that mitofusin 2, a mitochondrial dynamin-related protein mutated in the inherited motor neuropathy Charcot-Marie-Tooth type IIa, is enriched at the ER-mitochondria interface. Ablation or silencing of mitofusin 2 in mouse embryonic fibroblasts and HeLa cells disrupts ER morphology and loosens ER-mitochondria interactions, thereby reducing the efficiency of mitochondrial Ca(2+) uptake in response to stimuli that generate inositol-1,4,5-trisphosphate. An in vitro assay as well as genetic and biochemical evidences support a model in which mitofusin 2 on the ER bridges the two organelles by engaging in homotypic and heterotypic complexes with mitofusin 1 or 2 on the surface of mitochondria. Thus, mitofusin 2 tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake.


The vulnerabilities of age: burns in children and older adults.
Both children and older adults are thought to sustain burns serious enough to warrant hospitalization disproportionately more often than other age groups, but the incidence, injury characteristics, and outcome have not been precisely defined. Patients hospitalized with a burn diagnosis were identified from hospital discharge data from California, Florida, New Jersey, and New York for the 5-year period 2000-2004. In those states, 60,024 residents were hospitalized with a diagnosis of burn and/or inhalation injury according to the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. Using population data from the United States Census 2000, we found that the average annual incidence of hospitalization with a burn diagnosis in these 4 states was 155 per million (per M) (95% confidence interval,153-158). There were 13,453 children under 15 years of age: incidence, 163 per M (range, 157-169). Of these 9508 (70%) were under 5 years of age: incidence, 363 per M (range, 347-379). In contrast, there were 10,686 patients 65 years of age or older: incidence, 214 per M (range, 205-224), of whom 2091 were at least 85 years old: incidence, 347 per M (range, 314-380). The incidence of hospitalization with a burn diagnosis for patients 15 to 64 years of age was 141 per M (range, 138-145). Compared with children younger than 15 years, patients aged 65 years and older more often had flame burns (odds ratio [OR], 2.12), burns of 20% or more of body surface area (OR, 2.41), inhalation injury (OR, 2.88), respiratory failure (OR, 4.48), and death (OR, 16.53), all P < .0001. Older individuals are the most vulnerable to the morbidity and mortality of burn injury. Prevention strategies targeted to those older than 65 years should be developed.


Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults.
Plant-based diets are recommended for coronary heart disease (CHD) prevention. However, not all plant foods are necessarily beneficial for health. This study sought to examine associations between plant-based diet indices and CHD incidence. We included 73,710 women in NHS (Nurses' Health Study) (1984 to 2012), 92,329 women in NHS2 (1991 to 2013), and 43,259 men in Health Professionals Follow-up Study (1986 to 2012), free of chronic diseases at baseline. We created an overall plant-based diet index (PDI) from repeated semiquantitative food-frequency questionnaire data, by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful plant-based diet index (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, whereas less-healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. To create an unhealthful PDI (uPDI), we gave positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods. Over 4,833,042 person-years of follow-up, we documented 8,631 incident CHD cases. In pooled multivariable analysis, higher adherence to PDI was independently inversely associated with CHD (hazard ratio [HR] comparing extreme deciles: 0.92; 95% confidence interval [CI]: 0.83 to 1.01; p trend = 0.003). This inverse association was stronger for hDPI (HR: 0.75; 95% CI: 0.68 to 0.83; p trend <0.001). Conversely, uPDI was positively associated with CHD (HR: 1.32; 95% CI: 1.20 to 1.46; p trend <0.001). Higher intake of a plant-based diet index rich in healthier plant foods is associated with substantially lower CHD risk, whereas a plant-based diet index that emphasizes less-healthy plant foods is associated with higher CHD risk.


[Defects in immune system response by our organisms].
When some of the mechanisms in our immune response system fail, this can be due to external problems such as infections or transplants or due to congenital errors, known as Primary Immunologic Deficiencies. Dr. Español briefly reviews the most important characteristics of our immune response system, and then continues with an analysis of the defects of this system, especially those defects which are classified as Primary Immunologic Deficiencies.


Information Theory and Voting Based Consensus Clustering for Combining Multiple Clusterings of Chemical Structures.
Many consensus clustering methods have been applied in different areas such as pattern recognition, machine learning, information theory and bioinformatics. However, few methods have been used for chemical compounds clustering. In this paper, an information theory and voting based algorithm (Adaptive Cumulative Voting-based Aggregation Algorithm A-CVAA) was examined for combining multiple clusterings of chemical structures. The effectiveness of clusterings was evaluated based on the ability of the clustering method to separate active from inactive molecules in each cluster, and the results were compared with Ward's method. The chemical dataset MDL Drug Data Report (MDDR) and the Maximum Unbiased Validation (MUV) dataset were used. Experiments suggest that the adaptive cumulative voting-based consensus method can improve the effectiveness of combining multiple clusterings of chemical structures.


A new multimodal magnetic nanozyme and a reusable peroxymonosulfate oxidation catalyst: Manganese oxide coated-monodisperse-porous and magnetic core-shell microspheres.
Monodisperse-porous, polydopamine and manganese oxide coated, core-shell type, magnetic SiO2 (MagSiO2@PDA@MnO2) microspheres 6.4 μm in size were synthesized for the first time, using magnetic, monodisperse-porous SiO2 (MagSiO2) microspheres 6.2 μm in size as the starting material. MagSiO2 microspheres were obtained by a recently developed method namely "staged shape templated hydrolysis and condensation protocol". In the synthesis, MagSiO2 microspheres were consecutively coated by polydopamine (PDA) and then by a MnO2 layer in the aqueous medium. The pore volume and the specific surface area of monodisperse-porous MagSiO2@PDA@MnO2 microspheres were measured as 0.59 cm3 g-1 and 154 m2 g-1, respectively. Their Mn and Fe contents were determined as 66 ± 1 mg g-1 and 165 ± 5 mg g-1 respectively. MagSiO2@PDA@MnO2 microspheres exhibited multimodal enzyme mimetic behavior with highly superior catalase-like, oxidase-like and peroxidase-like activities. The effective production of singlet oxygen (1O2) and superoxide anion (O2-*) radicals in MagSiO2@PDA@MnO2-peroxymonosulfate (PMS) system was demonstrated by ESR spectroscopy. By evaluating this property, MagSiO2@PDA@MnO2 microspheres were tried as a reusable catalyst for dye removal via peroxymonosulfate (PMS) activation in batch experiments for the first time. The degradation runs were made with, rhodamine B (Rh B), methyl orange (MO) and methylene blue (MB) as the pollutant. The core-shell type design allowing the deposition of porous MnO2 layer onto a large surface area provided very fast, instant removals with all dyes, via both physical adsorption and degradation via PMS activation. In the reusability experiments, the removal yields of MO and Rh B decreased 1.8% and 8.9% over five consecutive runs in batch fashion. MagSiO2@PDA@MnO2 microspheres exhibited very good functional and structural stability in consecutive dye degradations. No significant change was observed in Fe content of microspheres while Mn content exhibited a decrease of 7.4% w/w over 5 consecutive degradation runs.


Optically Driven Both Classical and Quantum Unary, Binary, and Ternary Logic Gates on Co-Decorated Graphene Nanoflakes.
Nanospintronics holds great potential for providing high-speed, low-power, and high-density logic and memory elements in future computational devices. Here, using ab initio many-body theory, we suggest a nanoscale framework for building quantum computation elements, based on individual magnetic atoms deposited on graphene nanoflakes. We show the great possibilities of this proposal by exemplarily presenting four quantum gates, namely, the unary Pauli-X, Pauli-Y, Pauli-Z, and Hadamard gates, as well as the universal classical ternary Toffoli gate, which preserves information entropy and is therefore fully reversible and minimally energy consuming. All our gates operate within the subpicosecond time scale and reach fidelities well above 90%. We demonstrate the ability to control the spin direction and localization, as well as to create superposition states and to control the quantum phase of states, which are indispensable ingredients of quantum computers. Additionally, being optically driven, their predicted operating speed by far beats that of modern quantum computers.


[Overview of quality standards of Eucommiae Cortex in China and overseas].
Eucommiae Cortex is an authentic medicinal material with broad growing areas( such as Hunan and Sichuan provinces in China. It is well-known for its efficacy in tonifying liver and kidney,strengthening muscles and bones,and stabilizing fetus. It has also been proven in pharmacology to possess the functions such as lowering blood pressure and lipids. Hence,Eucommiae Cortex has attracted increasing attention. The current quality standards of Eucommiae Cortex vary in different countries or regions. The quality of Eucommiae Cortex products on the market is affected by mix-ups of non-medicinal parts and insufficient growth years. In view of these problems,this paper summarizes the current quality standards and research progress of Eucommiae Cortex in China and overseas,aiming to provide a reference for the establishment of the quality standards of Eucommiae Cortex.


Discrimination, crime, ethnic identity, and parenting as correlates of depressive symptoms among African American children: a multilevel analysis.
This study investigated the correlates of childhood depressive symptoms in an African American sample. We included processes that are likely to operate for all children, regardless of race or ethnicity, as well as events and circumstances that are largely unique to children of color. These various constructs were assessed at both the individual and community level. The analyses consisted of hierarchical linear modeling with a sample of 810 African American families living in Iowa and Georgia. Three individual-level variables were associated with childhood depressive symptoms: uninvolved parenting, racial discrimination. and criminal victimization. At the community level, prevalence of both discrimination and criminal victimization were positively related and community ethnic identification was negatively related to depressive symptoms. Further, there was evidence that community ethnic identification and neighborhood poverty serve to moderate the relationship between criminal victimization and depressive symptoms. Overall, the findings underscore the importance of considering factors unique to the everyday lives of the cultural group that is the focus of study, while demonstrating the dangers of a 'one model fits all" approach to studying children of color.


The consumption of ultra-processed foods reduces overall quality of diet in pregnant women.
This study analyzed the role of ultra-processed foods (UPFs) in the food and nutritional profile of pregnant women's diet. This was a cross-sectional study conducted in a representative sample of pregnant women attending primary healthcare units in Maceió, capital of the State of Alagoas, Brazil. Food consumption was assessed with the application of two 24-hour food recalls on nonconsecutive days, and the consumption items were grouped according to the NOVA classification. Overall estimates were expressed as absolute dietary consumption (mean calorie intake) and relative consumption (percentage of total energy intake according to food groups and consumption items). Analysis of variance was used to compare mean energy and nutrient intake according to food groups. The association between quintiles of the energy share from UPFs (exposure variable) and (1) consumption items and food groups, (2) percentage of total energy from macronutrients, and (3) micronutrient density was analyzed via adjusted linear regression models. Mean energy intake in pregnant women was 1,966.9Kcal/day, 22% of which from UPFs. A direct relationship was observed between the percentage of energy from UPFs and total energy consumption (β = 228.78Kcal; SE = 21.26). In addition, an increase in the share of UPFs was associated with a statistically significant reduction in the intake of protein, fiber, magnesium, iron, potassium, zinc, selenium, folate, and vitamins D and E, as well as in the consumption of traditional foods such as protein, beans, roots, and tubers. Our data thus indicate that the consumption of UPFs reduces the overall nutritional and food quality of diet in pregnant women.


Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism.
Hyperglycemia is the main determinant of long-term diabetic complications, mainly through induction of oxidative stress. NAD(P)H oxidase is a major source of glucose-induced oxidative stress. In this study, we tested the hypothesis that rosiglitazone (RSG) is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. Intracellular ROS were measured using the fluoroprobe TEMPO-9-AC in HUVECs exposed to control (5 mmol/L) and moderately high (10 mmol/L) glucose concentrations. NAD(P)H oxidase and AMPK activities were determined by Western blot. We found that 10 mmol/L glucose increased significantly ROS production in comparison with 5 mmol/L glucose, and that this effect was completely abolished by RSG. Interestingly, inhibition of AMPK, but not PPARgamma, prevented this effect of RSG. AMPK phosphorylation by RSG was necessary for its ability to hamper NAD(P)H oxidase activation, which was indispensable for glucose-induced oxidative stress. Downstream of AMPK activation, RSG exerts antioxidative effects by inhibiting PKC. This study demonstrates that RSG activates AMPK which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through PKC inhibition. Therefore, RSG protects endothelial cells against glucose-induced oxidative stress with an AMPK-dependent and a PPARgamma-independent mechanism.


Olfactory Dysfunction in Autoimmune Central Nervous System Neuroinflammation.
Olfactory dysfunction is an early sign of neuroinflammation of the central nervous system (CNS). Microgliosis and astrogliosis are representative pathological changes that develop during neuroinflammation of CNS tissues. Autoimmune CNS inflammation, including human multiple sclerosis, is an occasional cause of olfactory disorders. We evaluated whether gliosis and olfactory dysfunction developed in animals with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Neuroinflammatory lesions characterized by infiltration of inflammatory cells and microglial cell activation were occasionally found in the olfactory bulbs of EAE-affected rats. Microglial activation, visualized by immunohistochemical staining of ionized calcium binding protein (Iba)-1, and astrogliosis in the olfactory bulb were also evident in the olfactory bulb of EAE rats. Inflammatory cells were found along the olfactory nerves and in the olfactory submucosa. Western blot analysis of olfactory marker protein (OMP) levels showed that OMP expression was significantly downregulated in the olfactory mucosa of EAE rats. On the buried food test, EAE-affected mice required significantly more time to find a bait pellet. Collectively, the results suggest that the olfactory dysfunction of EAE is closely linked to downregulation of OMP and the development of inflammatory foci in the olfactory system in an animal model of human multiple sclerosis.


The misconstruction of critical medical anthropology: a response to a cultural constructivist critique.
Since its emergence over a decade ago as a distinct theoretical framework, critical medical anthropology (CMA) has engaged in debate and dialogue with various other perspectives within medical anthropology, particularly clinical anthropology, medical ecology, and, to a lesser degree, postmodernism. While at least two genres of CMA have emerged, both of which are involved in a dialogue with each other, proponents of other perspectives often misread or "misconstruct" the agenda of CMA as both a theoretical framework and a strategy for health activism. This essay in particular critiques this process among proponents of the interpretative or cultural constructivist perspective. On a positive note, however, I urge critical medical anthropologists and cultural constructivists within medical anthropology to enter into a dialogue with each other because their two perspectives, despite the presence of obvious epistemological differences, share commonalities.


Inhibition of the RBMS1/PRNP axis improves ferroptosis resistance-mediated oxaliplatin chemoresistance in colorectal cancer.
The majority of patients with advanced colorectal cancer have chemoresistance to oxaliplatin, and studies on oxaliplatin resistance are limited. Our research showed that RNA-binding motif single-stranded interacting protein 1 (RBMS1) caused ferroptosis resistance in tumor cells, leading to oxaliplatin resistance. We employed bioinformatics to evaluate publically accessible data sets and discovered that RBMS1 was significantly upregulated in oxaliplatin-resistant colorectal cancer cells, in tandem with ferroptosis suppression. In vivo and in vitro studies revealed that inhibiting RBMS1 expression caused ferroptosis in colorectal cancer cells, restoring tumor cell sensitivity to oxaliplatin. Mechanistically, this is due to RBMS1 inducing prion protein translation, resulting in ferroptosis resistance in tumor cells. Validation of clinical specimens revealed that RBMS1 is similarly linked to tumor development and a poor prognosis. Overall, RBMS1 is a potential therapeutic target with clinical translational potential, particularly for oxaliplatin chemoresistance in colorectal cancer.


Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog.
In five dogs with gastric fistulas, Heidenhain pouches, and pancreatic fistulas, the effects of substance P (SP) and its C-terminal hexapeptide (SP6-11) on gastric acid and pancreatic secretions were determined under basal conditions and in response to secretory stimulation. SP or SP6-11 infused alone in graded doses (0.25-2.0 nmol.kg-1.h-1) caused a slight but significant increase in pancreatic secretions in fasted dogs, but, when given during the secretory stimulation, they caused significant inhibition of these secretions. They reduced gastric acid response to pentagastrin and peptone meal without affecting the serum gastrin level. They caused dose-dependent inhibition of secretin-induced pancreatic bicarbonate secretion and suppressed the pancreatic protein response to caerulein, feeding, and duodenal acidification. SP6-11 was equipotent on a molar basis with SP in the inhibition of gastric or pancreatic secretion, indicating that the C-terminal portion of SP exhibits a full spectrum of the biological action of the intact molecule. The inhibitory effects of SP and SP6-11 on the stomach and pancreas were observed at a dose range that was without any significant influence on the blood pressure, indicating that they are not caused by the interference of the blood flow to the pancreas.


Resistance to fracture of endodontically treated teeth restored with different post systems.
Very little is known about the resistance to fracture of endodontically treated teeth restored with newly developed esthetic post systems. Purpose. This in vitro study compared the effect of 1 titanium and 3 esthetic post systems on the fracture resistance and fracture patterns of crowned, endodontically treated teeth. A total of 40 recently extracted human maxillary canines with their crowns removed were endodontically treated. Four groups of 10 specimens were formed. Teeth were restored with titanium, quartz fiber, glass fiber, and zirconia posts and numbered as groups 1, 2, 3, and 4, respectively. All posts were cemented with Single Bond dental adhesive system and dual-polymerizing RelyX ARC adhesive resin cement. All teeth were restored with composite cores, and metal crowns were fabricated and cemented with glass ionomer cement. Each specimen was embedded in acrylic resin and then secured in a universal load-testing machine. A compressive load was applied at a 130-degree angle to the long axis of the tooth until fracture, at a crosshead speed of 1 mm/min. One-way analysis of variance and a Tukey test were used to determine the significance of the failure loads between groups (P<.001). A non-parametric chi(2) test was conducted for evaluation of the mode of failure (P<.001). The mean failure loads (kg) were 66.95, 91.20, 75.90, and 78.91 for groups 1 to 4, respectively. Teeth restored with quartz fiber posts (group 2) exhibited significantly higher resistance to fracture (P<.001) than the other 3 groups. Teeth restored with glass fiber and zirconia posts (groups 3 and 4) were statistically similar (P>.05). Fractures that would allow repair of the tooth were observed in groups 2 and 3, whereas unrestorable, catastrophic fractures were observed in groups 1 and 4 (P<.001). Within the limitations of this study, significantly higher failure loads were recorded for root canal treated teeth restored with quartz fiber posts. Fractures that would allow repeated repair were observed in teeth restored with quartz fiber and glass fiber posts.


Contrasting adrenergic effects on lipoprotein lipase gene expression in the brown adipose tissue of intact mice and in cultured brown adipocytes from mice.
To examine the regulation of lipoprotein lipase (LPL) gene expression, LPL mRNA levels in the brown adipose tissue of intact mice and in mouse brown adipocyte cultures were examined. In intact mice, exposure to cold resulted in a rapid, transient, 5-fold increase in LPL mRNA level. Norepinephrine (NE) injection could fully mimic the effect of acute exposure to cold, and LPL mRNA and enzymatic activity were increased in parallel after NE injection. These results indicated positive adrenergic control of LPL gene expression in the brown adipose tissue of intact mice. In cultured mouse brown adipocytes, the level of spontaneously expressed LPL mRNA decreased in parallel with the progression of brown adipocyte differentiation. NE treatment of undifferentiated cells led to a decrease in LPL mRNA levels. In brown adipocytes that had reached a mature state, NE had a small negative or no effect on LPL mRNA levels, irrespective of whether the experiment was performed in the presence or absence of insulin or of newborn-calf serum. It was concluded that LPL gene expression in brown adipose tissue in intact mice is under adrenergic control but that this gene is not under positive adrenergic control in cultured brown adipocytes from mice, although these cells are otherwise adrenergically sensitive. The presence of additional factors may be necessary to confer adrenergic sensitivity to the LPL gene in the cultured brown adipocytes; alternatively, cells other than the mature brown adipocytes may confer the positive adrenergic sensitivity to the brown adipose tissue depots in situ.


Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?
Parkinson's disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest that inadequate clearance may couple the two phenomena. If a neuron's autophagy machinery is overwhelmed, whether by excessive oxidative stress or by excessive protein aggregation, protein aggregates and dysfunctional mitochondria will both accumulate. Parkinson's disease may provide a unique window into this because there is evidence that both sides contribute. Mutations amplifying the aggregation of α-synuclein are associated with Parkinson's disease. Likewise, mutations in Parkin and PINK1, proteins involved in mitophagy, suggest that impaired mitochondrial clearance is also a contributing factor. Many have suggested that dopamine oxidation products lead to oxidative stress accounting for the dopaminergic selectivity of the disease. We have presented evidence for the specific involvement of hypochlorite-oxidized cysteinyl-dopamine (HOCD), a redox-cycling benzothiazine derivative. While toxins like 6-hydroxydopamine and 1-methyl-4-phenyl pyridinium (MPP+) have been used to study mitochondrial involvement in Parkinson's disease, HOCD may provide a more physiologically relevant approach. Understanding the role of mitochondrial dysfunction and oxidative stress in Parkinson's disease and their relation to α-synuclein proteinopathy is important to gain a full picture of the cause, especially for the great majority of cases which are idiopathic.


Role of bactericidal permeability-increasing protein in the treatment of gram-negative pneumonia.
Gram-negative infections are a major cause of morbidity and death. Bactericidal permeability-increasing protein (BPI) is an endotoxin-neutralizing protein that also exhibits potent bactericidal activity. This study compared the efficacy of a 23 kd recombinant N-terminal fragment of BPI (rBPI23) with that of antiendotoxin antibody E5 in a model of gram-negative sepsis. Sixty Swiss-Webster mice (Carworth farm) received an intratracheal inoculation of Escherichia coli (7 x 10(6) colony-forming units) and were randomized to three groups (20 per group). Starting immediately after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses), E5 (11 mg/kg intravenously every 24 hours for two doses), or an isotype control antibody B55 (11 mg/kg intravenously every 24 hours for two doses) and were followed up for survival. In a second survival study, 40 mice received the same intratracheal inoculation of E. coli and were randomized to two groups. Starting 2 hours after inoculation, the groups received either rBPI23 (4 mg/kg intravenously every 2 hours for four doses) or E5 (8 mg/kg intravenously every 12 hours for four doses) and were followed up for survival. In a third study, mice received an intratracheal inoculation of 3 x 10(6) colony-forming units E. coli, a sublethal dose, and were killed to determine pulmonary and blood clearance of bacteria. rBPI23 conferred significantly greater protection from death than either E5 or B55 when started immediately (95% survival vs 20% and 10%, respectively; p < 0.001) or 2 hours after inoculation (65% survival vs 25% for E5; p < 0.05). Both pulmonary and vascular clearance of bacteria was enhanced significantly by treatment with rBPI23. rBPI23 may be a novel therapeutic agent in the management of gram-negative sepsis.


Role of Al doping in the filament disruption in HfO2 resistance switches.
Resistance switching devices, whose operation is driven by formation (SET) and dissolution (RESET) of conductive paths shorting and disconnecting the two metal electrodes, have recently received great attention and a deep general comprehension of their operation has been achieved. However, the link between switching characteristics and material properties is still quite weak. In particular, doping of the switching oxide layer has often been investigated only for looking at performance upgrade and rarely for a meticulous investigation of the switching mechanism. In this paper, the impact of Al doping of HfO2 devices on their switching operations, retention loss mechanisms and random telegraph noise traces is investigated. In addition, phenomenological modeling of the switching operation is performed for device employing both undoped and doped HfO2. We demonstrate that Al doping influences the filament disruption process during the RESET operation and, in particular, it contributes in preventing an efficient restoration of the oxide with respect to undoped devices.


Clinical Research in the Managed Care Environment.
The authors present the conclusions of a workshop devoted to the challenges to clinical research in the changing environment of managed care and health care reform. They identify problems and concerns with current conditions and discuss promising opportunities for new approaches to research.


Effects of glycosylation on peptide conformation: a synergistic experimental and computational study.
Asparagine-linked glycosylation, the co-translational covalent attachment of carbohydrates to asparagine side chains, has a major effect on the folding, stability, and function of many proteins. The carbohydrate composition in mature glycoproteins is heterogeneous due to modification of the initial oligosaccharide by glycosidases and glycosyltransferases during the glycoprotein passage through the endoplasmic reticulum and Golgi apparatus. Despite the diversity of carbohydrate structures, the core beta-D-(GlcNAc)(2) remains conserved in all N-linked glycoproteins. Previously, results from our laboratory showed that the molecular composition of the core disaccharide has a critical and unique conformational effect on the peptide backbone. Herein, we employ a synergistic experimental and computational approach to study the effect of the stereochemistry of the carbohydrate--peptide linkage on glycopeptide structure. A glycopeptide derived from a hemagglutinin protein fragment was synthesized, with the carbohydrate attached to the peptide with an alpha-linked stereochemistry. Computational and biophysical analyses reveal that the conformations of the peptide and alpha- and beta-linked glycopeptides are uniquely influenced by the attached saccharide. The value of computational approaches for probing the influence of attached saccharides on polypeptide conformation is highlighted.


Does garlic have a role as an antidiabetic agent?
Diabetes affects a large segment of the population worldwide, and the prevalence of this disease is rapidly increasing. Despite the availability of medication for diabetes, traditional remedies are desirable and are currently being investigated. Garlic (Allium sativum), which is a common cooking spice and has a long history as a folk remedy, has been reported to have antidiabetic activity. However, there is no general agreement on the use of garlic for antidiabetic purposes, primarily because of a lack of scientific evidence from human studies and inconsistent data from animal studies. The validity of data from previous studies of the hypoglycemic effect of garlic in diabetic animals and the preventive effects of garlic on diabetes complications are discussed in this review. The role of garlic as both an insulin secretagogue and as an insulin sensitizer is reviewed. Evidence suggests that garlic's antioxidative, antiinflammatory, and antiglycative properties are responsible for garlic's role in preventing diabetes progression and the development of diabetes-related complications. Large-scale clinical studies with diabetic patients are warranted to confirm the usefulness of garlic in the treatment and prevention of diabetes.


Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist.
The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated - apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension - with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson's disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson's disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies.


Syntheses and structures of thermally stable diketiminato complexes of gold and copper.
While most metallic elements across the Periodic Table form stable chelating β-diketiminato complexes, examples of Au(I) are conspicuous by their absence. We report here the reaction of K[HC(F(3)CC=NR)(2)] with AuCl(PPh(3)) which provides a rare example of a thermally stable gold(I) diketiminato complex, (Ph(3)P)Au[RN=C(CF(3))CH(CF(3))C=NR] [R = 3,5-C(6)H(3)(CF(3))(2)]. The complex is highly fluxional in solution but in the solid state adopts a U-conformation. By contrast, the analogous reaction of K[HC(F(3)CC=NR)(2)] with CuBr(PPh(3))(3) gives the rigid 18-electron chelate complex (Ph(3)P)(2)Cu[κ(2)-HC{(CF(3))C=NR}(2)].


Green tea extract impedes dyslipidaemia and development of cardiac dysfunction in streptozotocin-diabetic rats.
1. The efficacy of green tea extract (GTE) on serum and cardiac lipids was investigated in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced in rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six weeks after the induction of diabetes, GTE was administered orally for 4 weeks (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight ratio, blood glucose, serum and cardiac lipids were determined in experimental rats. 3. In diabetic rats, there was a significant decrease in bodyweight with an increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had significantly increased serum levels of cholesterol, triglycerides, free fatty acids and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of high-density lipoprotein-cholesterol (HDL-C). In the hearts of diabetic rats, there was a significant increase in cholesterol, triglycerides and free fatty acids levels, with an increase in lipoprotein lipase activity. 4. The administration of GTE to diabetic rats resulted in significant recovery in bodyweight, heart weight : bodyweight ratio and blood glucose levels. The administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL-C levels, and increased HDL-C levels, in the serum of diabetic rats. In addition, GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein lipase activity in the myocardium of diabetic rats. These beneficial effects of GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In conclusion, green tea can reduce the risk of cardiovascular disease in diabetes with a significant improvement in lipid metabolism.


Isolation of putative probionts from cod rearing environment.
Survival problems are encountered at early stages of intensive fish rearing and antibiotics are widely used to remedy the situation. Probiotics may provide a potential alternative method to protect larvae from opportunistic and pathogenic bacteria and promote a balanced environment. This study was designed to search for new probiotics to target this critical period in cod rearing. Potential probionts were selected from the natural microbiota of cod aquacultural environment. The selection was based on several criteria: pathogen inhibition potential, growth characteristics, strain identification, metabolite production and adhesion to fish cell lines. Our study demonstrated that 14% of screened bacteria (n=188) had antagonistic properties towards fish pathogens. The majority of these isolates were Gram-positive (81%), belonging to Firmicutes (69.2%) and Actinobacteria (11.5%) phyla based on 16S rRNA gene sequencing. Only 6 (3.2%) of 188 isolates could inhibit all three pathogens tested: Vibrio anguillarum, Aeromonas salmonicida subsp. achromogenes and Vibrio salmonicida. Differences observed in activity intensity and spectrum among inhibitory isolates emphasise the need to develop probiotic mixtures for efficient prophylactic methods. Comparison of growth behaviour of inhibitory isolates and pathogens at cod rearing temperatures, metabolite production and adhesion capacity were considered for final probiont selection. Four promising isolates that could be used as a mixed supplement to rearing water were identified as putative probiotic bacteria. This study emphasises the importance and potential of lactic acid bacteria in aquaculture.


[The functional activity of the regulator region of virus SV40 integrated into recombinant plasmids].
We propose the system for transfection of eucaryotic SV40-based vectors. The method comprises simultaneous transfection of permissive monkey cells with plasmid DNA and the virus SV40. It is likely that the induction of replication of recombinant plasmids by the SV40 T-antigen is an indicator of functional activity of the SV40 regulatory region integrated into recombinant plasmids.


Label-free fluorescence detection of kinase activity using a gold nanoparticle based indicator displacement assay.
A straightforward indicator-displacement assay (IDA) has been developed for the quantitative analysis of ATP→ADP conversion. The IDA relies on the use of gold nanoparticles passivated with a monolayer of thiols terminating with a 1,4,7-triazacyclononane (TACN)·Zn(2+) head group. The analytes ATP and ADP compete to a different extent with a fluorescent probe for binding to the monolayer surface. In the presence of ATP the fluorescent probe is free in solution, whereas in the presence of ADP the fluorescent probe is captured by the nanoparticles and its fluorescence is quenched. The linear response of the fluorescence signal towards different ratios of ATP : ADP permitted the detection of protein kinase activity simply by adding aliquots of the enzyme solution to the assay solution followed by measurement of the fluorescent intensity. The assay poses no restrictions on the target kinase nor does it require labeling of the kinase substrate. The assay was tested on the protein kinases PIM-1 and Src and validated through a direct comparison with the classical radiometric assay using the [γ-(32)P]-labeled ATP.


Vertigo: An Atypical Presentation of Neurocysticercosis Successfully Treated With Albendazole.
A 20-year-old male presented to our facility with a worsening sensation of "the room spinning around" himself for the past three weeks. In the last week, he began to experience daily spells lasting for three hours each without losing consciousness. The patient had recently migrated from Central America six weeks prior to admission. On physical examination, his vital signs were within normal limits, with no focal neurological deficits. Magnetic resonance imaging (MRI) of the brain revealed a cystic-appearing lesion in the fourth ventricle with associated mass effect on the posterior aspect of the brainstem and mild periventricular edema. Laboratory studies were unremarkable except for a positive anti-cysticercus IgG antibody, which confirmed the diagnosis of neurocysticercosis. Initially, surgery was considered, but the neurosurgeons advised medical management due to the small size of the lesion. The patient was started on albendazole 400 mg orally twice daily and dexamethasone 6 mg orally daily for 14 days. The patient responded well; his symptoms resolved by the eighth day. He was discharged home to complete his treatment and remained asymptomatic at the follow-up appointment two weeks later.


The Process and Regulatory Components of Inflammation in Brain Oncogenesis.
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers. The roles of reactive astrocytes, tumor associated microglia and macrophages, metabolic alterations, microsatellite instability, O⁶-methylguanine DNA methyltransferase (MGMT) DNA repair and epigenetic alterations mediated by the isocitrate dehydrogenase 1 (IDH1) mutations have been discussed. The inflammatory pathways with relevance to the brain cancer treatments have been highlighted.


Accumulation of Microcystin (LR, RR and YR) in Three Freshwater Bivalves in Microcystis aeruginosa Bloom Using Dual Isotope Tracer.
Abstract: Stable isotope tracers were first applied to evaluate the Microcystis cell assimilation efficiency of Sinanodonta bivalves, since the past identification method has been limited to tracking the changes of each chl-a, clearity, and nutrient. The toxicity profile and accumulation of MC-LR, -RR and -YR in different organs (foot and digestive organs) from the three filter-feeders (Sinanodonta woodina, Sinanodonta arcaeformis, and Unio douglasiae) were assessed under the condition of toxigenic cyanobacteria (Microcystis aeruginosa) blooms through an in situ pond experiment using 13C and 15N dual isotope tracers. Chl-a concentration in the manipulated pond was dramatically decreased after the beginning of the second day, ranging from 217.5 to 15.6 μg·L-1. The highest amount of MCs was incorporated into muscle and gland tissues in U. douglasiae during the study period, at nearly 2 or 3 times higher than in S.woodiana and S. arcaeformis. In addition, the incorporated 13C and 15N atom % in the U. douglasiae bivalve showed lower values than in other bivalves. The results demonstrate that U. douglasiae has less capacity to assimilate toxic cyanobacteria derived from diet. However, the incorporated 13C and 15N atom % of S. arcaeformis showed a larger feeding capacity than U. douglasiae and S. wodiana. Our results therefore also indicate that S. arcaeformis can eliminate the toxin more rapidly than U. douglasiae, having a larger detoxification capacity.


Psychotropic drugs: influence on respiratory function.
The authors investigated, in 22 normal subjects and 22 bronchopneumopathic patients, the action of two anxiolytic drugs on ventilatory function and on the associated respiratory function. The analyses carried out before drug administration and 1, 2, 6 hours later showed that while a drug did not cause any important variation in the ventilatory parameters and O2 uptake, both in healthy subjects and in patients, the second one clearly reduced the ventilatory efficacy and O2 uptake. This behavior was quite evident 1 and 2 hours after the assumption of the drug while after 6 hours the parameters returned to the initial values. The influence of the circadian rhythm after 6 hours was more evident in both groups after the assumption of the second anxyolitic drug than with the first. Furthermore, evaluation drawn up among the healthy subjects, during simulated driving tests, demonstrated that the second anxyolytic drug provoked a standard depression unevenly distributed like that obtained after the ingestion of a fixed dose of an alcoholic drink.


The (1->6)-β-glucan moiety represents a cross-reactive epitope of infection-induced malignancy surveillance.
Exposure to pathogen-associated molecular patterns (PAMPs) by vaccination or infection is known to have beneficial effects on neoplastic diseases, although the underlying molecular mechanisms are so far unclear. In this article, we report that Abs against (1→6)-β-d-glucan, a typical microbial PAMP and a major target for high titer circulating natural Abs in healthy human subjects, cross-recognize a novel tumor-associated carbohydrate Ag on cancer cells. The (1→6)-β-glucan cross-reactive moiety is immunologically dominant in tumor cells, as C57BL/6 mice harboring EL-4 solid tumors produced anti-(1→6)-β-glucan Abs and the titer of which significantly correlated with enhanced survival and smaller tumor burden. Moreover, the (1→6)-β-glucan-specific Abs exhibited potent tumoricidal activities in vitro. C57BL/6 mice immunized with Candida albicans produced protective immunity against inoculated EL-4 tumors, which was attributed to the formation of (1→6)-β-glucan-specific Abs. Importantly, (1→6)-β-glucan-specific Abs significantly prolonged the survival and reduced the tumor size in mice inoculated with EL-4 tumors. Our results demonstrate that the (1→6)-β-glucan cross-reactive moiety represents a focal point between infection immunity and cancer surveillance, and natural Abs against this epitope may contribute to the first-line antitumor surveillance in humans. Our data also provide important explanation for the long-observed relationship between feverish infection and concurrent remission from cancer.


WWOX hypomorphic mice display a higher incidence of B-cell lymphomas and develop testicular atrophy.
WWOX is a putative tumor suppressor gene encoded within common chromosomal fragile site region FRA16D, in chromosome band 16q23. Multiple studies have demonstrated that WWOX expression is often reduced or lost in various tumor types. WWOX tumor suppressor activity was suggested by re-expressing WWOX in breast, ovarian, and lung tumor cell lines leading to tumor growth inhibition in vivo. To determine whether loss of Wwox gene expression has a role in tumorigenesis, we generated a mouse strain containing a Wwox gene mutated by a gene-trap vector. Homozygous Wwox gene-trap mice (Wwox(gt/gt)) had no detectable Wwox protein in most tissues examined, although, a low level could be detected in a minority of tissues. Because of these observations, we concluded that these mice are Wwox hypomorphs. Remarkably, Wwox hypomorphic mice are viable in contrast to the recently reported postnatal lethality of Wwox knockout mice. Testes from Wwox(gt/gt) males had high numbers of atrophic seminiferous tubules and reduced fertility when compared with wild-type counterparts. We observed that the Wwox(gt/gt) mice had a significantly shorter lifespan, and female hypomorphs had a higher incidence of spontaneous B-cell lymphomas. In conclusion, we describe a novel Wwox hypomorphic mouse model that overcomes postnatal lethality that was recently observed in Wwox knockout mice. Therefore, tumorigenesis studies using this model more closely recapitulates the loss of WWOX expression observed in human cancers. Importantly, our observation that Wwox hypomorphs had an increased incidence of B-cell lymphomas supports a role of Wwox as a tumor suppressor.


[Variation of different carbon sources in the sewage treatment process].
The biodegradability and speciation of organics were studied through long-term analysis of A2/O treatment. The majority of the organic matters were particle organics which accounted for 61% of the total organics. The proportions of rapidly degradable, slowly degradable and refractory organics were 15. 8% , 54. 2% and 30% respectively. Rapidly biodegradable organics were mainly dissolved organics while slowly biodegradable organics were particle organics. The variation of these two kinds of carbon sources was analyzed during the treatment process. It was noted that microbial hydrolysis fermentation took place in the anaerobic and anoxic tanks, which led to the transformation of slowly biodegradable organics and the anaerobic tank had the highest transformation rate. The transformation and utilization of rapidly/slowly biodegradable organics were analyzed through calculation. The results showed that the transformation efficiency of slowly biodegradable organics in the anaerobic and anoxic tanks in two hours was 33% and 20%, respectively. Furthermore, the amount and species of aliphatic acid increased in the anaerobic and anoxic tanks comparing with raw water.


[Screening: careful considerations versus commercial medicine].
People no longer seem to view their state of health in a light-hearted manner. The worried well hunger for every scrap of information they can find about their physical well-being, with the result that a veritable diagnostic industry is developing. Is the early detection of a disease always better than waiting for its signs or symptoms? It is difficult to answer this question and properly weigh up the beneficial effects against the side effects. Two main reasons are given for this. First of all, studies on the early detection of disease report the results selectively: beneficial effects are overstated and side effects are underreported. A more comprehensive evaluation method is needed. Secondly, new technological and therapeutic innovations are in competition with the existing techniques under investigation, which makes a long-term evaluation almost impossible. Moreover, this approach obscures questions fundamental to screening practices. There is a widening gulf between medical screening and traditional medicine, with the result that care is being transformed into a commercial product with a huge market. These developments in diagnostics pose new scientific and ethical questions that need to be answered.


Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine and its redistribution in ischemic cerebrovascular disease.
The relation between the redistribution phenomenon and regional cerebral blood flow and its clinical significance were investigated in stroke patients. Single-photon emission computed tomography studies using N-isopropyl-p-[123I]iodoamphetamine were performed on 16 patients (26 to 77 years old) with chronic infarction and 10 age-matched normal control subjects. Regional cerebral blood flow was quantitatively measured by a microsphere model, and the redistribution on delayed images was analyzed in ischemic lesions. Supratentorial mean cerebral blood flow and the ratio of gray matter to white matter in normal subjects were 52.7 +/- 5.0 mL/100 g per minute and 2.34, respectively. Low-activity areas of ischemic lesions on early images were classified into two abnormal zones, an infarct area and a peri-infarct area. These regions were characterized by regional blood flow averaging 9 to 20 mL/100 g per minute and 22 to 41 mL/100 g per minute, respectively. Redistribution, which was minimally present in the infarct area, was markedly enhanced in the peri-infarct area. After bypass surgery, we observed a significant increase of blood flow (+22%) in the peri-infarct area. The data indicate that the redistribution phenomenon depends on the maintenance of a minimal blood flow that would sustain cellular function and that this phenomenon is useful to evaluate bypass surgery in patients with chronic infarction.


Mitochondrial haplogroups and polymorphisms reveal no association with sporadic prostate cancer in a southern European population.
It is known that mitochondria play an important role in certain cancers (prostate, renal, breast, or colorectal) and coronary disease. These organelles play an essential role in apoptosis and the production of reactive oxygen species; in addition, mtDNA also reveals the history of populations and ancient human migration. All these events and variations in the mitochondrial genome are thought to cause some cancers, including prostate cancer, and also help us to group individuals into common origin groups. The aim of the present study is to analyze the different haplogroups and variations in the sequence in the mitochondrial genome of a southern European population consisting of subjects affected (n = 239) and non-affected (n = 150) by sporadic prostate cancer. Using primer extension analysis and DNA sequencing, we identified the nine major European haplogroups and CR polymorphisms. The frequencies of the haplogroups did not differ between patients and control cohorts, whereas the CR polymorphism T16356C was significantly higher in patients with PC compared to the controls (p = 0.029). PSA, staging, and Gleason score were associated with none of the nine major European haplogroups. The CR polymorphisms G16129A (p = 0.007) and T16224C (p = 0.022) were significantly associated with Gleason score, whereas T16311C (p = 0.046) was linked with T-stage. Our results do not suggest that mtDNA haplogroups could be involved in sporadic prostate cancer etiology and pathogenesis as previous studies performed in middle Europe population. Although some significant associations have been obtained in studying CR polymorphisms, further studies should be performed to validate these results.


Transanal resection for villous adenomas using the Fansler proctoscope.
Benign rectal tumours represent a frequently occurring condition that often requires surgical treatment. In the literature, Transanal Endoscopic Microsurgery (TEM) has claimed a position as the gold standard for this kind of transanal surgery. In this study, we evaluate the results in a series of 34 patients who underwent a transanal resection after an extensive pre-operative work-up, using the Fansler proctoscope. Although the level of evidence in retrospective studies may have its limitations, our results seem to meet those of TEM in the literature. Also, the Fansler proctoscope provides us with a much more economical and easier to learn method. We conclude that the Fansler proctoscope approach can be a valuable alternative to TEM in the treatment of benign rectal tumours.


Knowledge and awareness of children's food safety among school-based street food vendors in Dhaka, Bangladesh.
We carried out a cross-sectional study to determine the level of knowledge and awareness regarding children's food safety issues among the school-based street food vendors in Dhaka city. A total of 250 school-based street food vendors were interviewed employing a pre-tested structured questionnaire comprising foodborne illness and food hygiene-related questions. We used a scoring system based on the responses obtained from them, and categorized the overall level of knowledge and awareness into "adequate" and "inadequate." Multivariable logistic regression was used to explore the association between selected sociodemographic characteristics and the level of knowledge and awareness. The most common food item vended by school-based street food vendors was chotpoti/fuchka (37.2%). The median number of schoolchildren customers was 120 per vendor per day. All (100%) vendors were male with a mean age of 30.95±8.8 years, and their mean daily income was 131.16±62.54 Bangladeshi Taka (1.97±0.94 USD). Most (40.1%) of the respondents belonged to the age group 25-34 years, and the majority (43.6%) did not have any formal education. More than two-thirds (68%) vendors could not show adequate level of knowledge and awareness of children's food safety issues. The most common source of obtaining food safety information by vendors was electronic media (91.8%). Elderly (≥45 years) vendors were 17.73 times more likely to have adequate level of knowledge and awareness than the vendors belonging to age group 15-24 years (p<0.001; adjusted OR=17.73; 95% CI=4.38-71.73). Individuals who had an education of higher than primary level were 9.87 times more likely to possess adequate level of knowledge and awareness than those who did not have any formal education (p<0.01; adjusted OR=9.87; 95% CI=2.07-46.93). The majority of school-based street food vendors showed an inadequate level of knowledge and awareness of children's food safety issues.


Successful management of complex regional pain syndrome type 1 using single injection interscalene brachial plexus block.
Complex regional pain syndrome (CRPS) type 1 of the upper limb is a painful and debilitating condition. Interscalene brachial plexus block (ISB) in conjugation with other modalities was shown to be a feasible therapy with variable success. We reported a case of CRPS type 1 as diagnosed by International Association for the Study of Pain criteria in which pharmacological approaches failed to achieve adequate pain relief and even were associated with progressive dysfunction of the upper extremity. Single injection ISB, in combination with physical therapy and botulinum toxin injection, was successful to alleviate pain with functional restoration.


[Intestinal duplications. A survey of 18 cases].
The present study analyses the experience of two centers in the management of intestinal duplications in children. We retrospectively reviewed the medical records of a series of 18 children with intestinal duplication (January 1993 to December 1999). The median age was 11 months (range: 9 days to 12 years). The variables analysed were: clinical presentation, diagnosis, localization, anatomic type, treatment, and complications. The relationship between age and clinical presentation was also analysed. Most cases were located in the ileum (n 14; 78 %) and presented with rectal bleeding (36 %) or intussusception (36 %). Most symptomatic cases in the first year of life presented with intussusception (n 5/6). All duplications, except one located in the ascending colon, were cystic. 99mTc-pertechnate abdominal scan was positive in three out of five patients. One case was diagnosed by prenatal ultrasonography. Diagnosis was confirmed by laparoscopy in three patients and by laparotomy in the remaining patients. In one patient, cystic esophageal duplication presented in the neonatal period as respiratory distress. Diagnosis as well as excision was performed by thoracoscopy. Of the two gastric duplications, one was diagnosed by prenatal ultrasonography and the other by laparotomy. Treatment consisted of segmental enterectomy (n 14) or excision of the lesion without enterectomy (n 4). No complications were found during a mean follow-up of 3 years. The onset of intestinal duplication may be late. The lesions were most commonly located in the ileum and were cystic. Clinical presentation was related to age. Minimally invasive surgery plays an important role in the management of these lesions.


The effect of cycloleucine on SFV A7(74) infection in mice.
Cycloleucine (CL), a non-metabolizable amino acid analogue, was found to reduce thymus and spleen weights in Semliki Forest virus (SFV) strain A7(74) infected and control mice. The maximum effects were seen when three daily doses of CL were given to mice 24 h after an SFV A7(74) infection. In these mice thymus atrophy led to abolition of thymus dependent immune responses and changes in the pathological features of the viral infection--the most striking feature being prevention of demyelination. In addition virus titres in the brains of CL treated infected mice were increased and prolonged. These results show that demyelination following an SFV A7(74) infection is not a result of direct virus action, but of a T-cell mediated mechanism.


Mucopolysaccharidosis type II (Hunter's syndrome) in Taiwan.
The mucopolysaccharidoses are a group of inherited disorders of lysosomal storage of glycosaminoglycans. Among them, mucopolysaccharidosis (MPS) type II (Hunter's syndrome), caused by a deficiency in iduronate sulfatase, is the only one inherited in an X-linked recessive manner. We describe 12 Hunter's syndrome patients and seven carriers, with precise analysis of glycosaminoglycan content in urine and iduronate sulfatase activity in cultured fibroblasts and plasma. Their ages at the time of diagnosis ranged from 1 year 10 months to 11 years (mean 4.3 yr). The delay in diagnosis was from 1 month to 5 years (mean 2.1 yr) after the initial presentation. The most frequent initial complaints of the patients were delayed developmental milestones (75%) and speech (67%), although all patients were found to have coarsening of facial features at diagnosis. The difficulties in disease recognition allowed disease recurrence in four of the 11 families. Prompt clinical suspicion and referral will be important in genetic counseling for MPS type II and its management, if definitive therapy becomes available.


Evaluation of the relationship between the static measurement of transverse arch flexibility of the forefoot and gait parameters in healthy subjects.
[Purpose] To investigate the relationship between the static measurement of the transverse arch of the forefoot, using a 3-dimensional (3D) foot scanner, and kinetics and kinematics of gait parameters in the sagittal plane. [Subjects and Methods] Twenty healthy subjects participated in this study. The transverse arch of the forefoot was measured under three conditions as follows: condition 1, sitting; condition 2, standing; and condition 3, foot forward and lower leg tilting anteriorly to the maximum position with heel contact. Gait parameters were recorded using a 3D motion analysis system and force plate. Correlation coefficients between TAF for each comparison of conditions and gait parameters were calculated using the Spearman correlation analysis. [Results] Rates of the transverse arch of the forefoot width and height between condition 2 and condition 3 were significantly correlated with the anterior and posterior component of ground reaction forces, the hip joint extension angle, and the ankle plantar flexion moment. [Conclusion] Our study's findings indicated that increased stiffness of the transverse arch of the forefoot was related to the increase in ankle plantar moment, and decreased stiffness of the transverse arch of the forefoot was related to the increase in hip joint extension angle during gait.


Factor Xa releases matrix metalloproteinase-2 (MMP-2) from human vascular smooth muscle cells and stimulates the conversion of pro-MMP-2 to MMP-2: role of MMP-2 in factor Xa-induced DNA synthesis and matrix invasion.
Pro-matrix metalloproteinase-2 (pro-MMP-2) is expressed in vascular smooth muscle cells (SMCs). We report that activated coagulation factor X (FXa) induces the release of MMP-2 (65 kDa) from human SMCs. In addition, FXa cleaves pro-MMP-2 (72 kDa) into MMP-2. Pro-MMP-2 and MMP-2 were determined by gelatin zymography. MMP-2 was generated in conditioned medium containing pro-MMP-2 in a concentration-dependent fashion by FXa (3 to 100 nmol/L). FX at concentrations up to 300 nmol/L was ineffective. The conversion of pro-MMP-2 to MMP-2 was inhibited by a selective FXa inhibitor (DX-9065a) at 3 to 10 micromol/L. There was a concentration-dependent induction of an intermediate MMP-2 form (68 kDa) in lysates of FXa-treated cells. This indicates that cellular mechanisms are involved in FXa-induced conversion of pro-MMP-2. As a possible biological consequence of MMP-2 activation by FXa, DNA synthesis and matrix invasion of SMCs were determined. Both were stimulated by FXa and inhibited by the selective FXa inhibitor DX-9065a and the MMP inhibitor GM 6001 but not by hirudin or aprotinin. It is concluded that stimulation of SMCs by FXa increases the levels of MMP-2 in the extracellular space and that two different mechanisms are involved: release of active MMP-2 and cleavage of secreted pro-MMP-2. Both might contribute to the mitogenic potency of FXa and FXa-stimulated matrix invasion of SMCs.


Learning curves for minimally invasive spine surgeries: Are they worth it?
Minimally invasive surgery (MIS) spine procedures were developed to limit operative time, the extent of dissection, and reduce perioperative morbidity. Here, we asked what are the "learning curves" for these MIS spine procedures? We reviewed studies in the literature that discussed the "learning curves" attributed to performing different MIS spine surgical procedures. Of interest, the majority were single-surgeon series. Very few articles assessed the learning curves for different MIS spine procedures. One study reported no learning curve for open vs. MIS discectomy/laminotomy. Another study indicated that 20-30 cases were required for a surgeon to become proficient in performing a variety of MIS spine fusions [e.g., cervical MIS fusions, MIS anterior lumbar interbody fusions (ALIF), MIS transforaminal lumbar interbody fusions (TLIF), and MIS pedicle/screw placement in the thoracic/lumbar spine]. Several other studies specifically cited that, to become proficient in the performance of TLIF, surgeons had to have performed between 10, to 32, to 40, to 44 such cases. There is a very limited literature available that focuses on the "learning curves" associated with the performance of different types of MIS spine procedures. The number of cases required to satisfy the "learning curves" for different operations varied from 0 for MIS vs. open discectomy/laminotomy, to 20-30 for a variety of cervical-thoracic-lumbar procedures, and up to 44 cases for TLIF. Shouldn't we ask whether better oversight measures and/or mentoring programs could limit the morbidity/AE occurring during these "learning curves" in the future?


Gas1 is a pleiotropic regulator of cellular functions: from embryonic development to molecular actions in cancer gene therapy.
Cellular homeostasis is governed by a precise regulation of the molecular mechanisms of action of several proteins in a given time. There is a group of proteins that have a particular role depending on the cellular context in which they are present and are known as pleiotropic proteins. The Gas1 (Growth Arrest Specific 1) gene was isolated from a subtraction library from serum arrested versus growing NIH3T3 mouse fibroblast. Gas1 is a member of the alpha receptors (GFRα) for the family of GDNF ligands (GFL), we have previously shown that Gas1 acts as a negative modulator of the GDNF-induced intracellular signaling and induces cell arrest and apoptosis. This modulating activity is the cause of the capacity of Gas1 to act as a tumor suppressor. On the other hand, several studies have shown the interaction between Gas1 and Hh (Hedgehog) proteins to potentiate the positive regulation of this pathway, which is involved in the development of the nervous system, and in both the origin and progression of different tumors. This review summarizes our current understanding of the structure of Gas1 and the molecular mechanism of action in different cellular functions, both during embryonic development, in the adult and its effects inhibiting cell growth and inducing apoptosis of cancer cells.


Analysis of the pediocin AcH gene cluster from plasmid pSMB74 and its expression in a pediocin-negative Pediococcus acidilactici strain.
The 3,500-bp pap operon in the 8,877-bp plasmid pSMB74 contains a cluster of four genes, papABCD, of which papA encodes prepediocin (A. M. Motlagh, M. Bukhtiyarova, and B. Ray, Lett. Appl. Microbiol. 18:305-312, 1994). The cluster without the promoter was cloned in the shuttle vector pHPS9. An Escherichia coli strain and a pediocin-sensitive Pediococcus acidilactici strain transformed with the recombinant plasmid, pMBR1.0, produced pediocin AcH. Deletion analysis by introducing mutations in the four genes in pMBR1.0 revealed that only papA and papD were required for pediocin AcH production and that the gene product of papD has both translocation and processing functions. In the transformed minicells of E. coli chi 925 the proteins of the pap cluster were synthesized, indicating no polar effect due to deletion.


Density measurements of liquid under high pressure and high temperature.
A new method for density measurements by means of X-ray absorption under high pressure and high temperature using synchrotron radiation has been developed. The method has been modified for a large-volume Paris-Edinburgh press and combined with intense high-energy X-rays at the ESRF. In order to overcome effects of deformation of sample shape under pressure, a ruby cylinder was used as a sample container. The density was determined from the intensity profile of transmitted X-rays. The densities of crystalline and liquid Bi were successfully measured up to 750 K at 1 GPa.


Epigallocatechin Gallate Alleviates Staphylococcal Enterotoxin A-Induced Intestinal Barrier Damage by Regulating Gut Microbiota and Inhibiting the TLR4-NF-κB/MAPKs-NLRP3 Inflammatory Cascade.
Natural phytochemicals have attracted increasing attention because of their promising ability to tackle bacteriotoxin-induced public safety concerns. However, it is unclear how natural phytochemicals regulate the intestinal barrier dysfunction caused by bacteriotoxin, such as staphylococcal enterotoxin A (SEA). This study aims to illustrate the in vitro and in vivo protective mechanism of epigallocatechin gallate (EGCG) on SEA-triggered intestinal barrier damage and inflammation. Results show that EGCG alleviates intestinal barrier damage by effectively inhibiting SEA-induced intestinal permeability increase, tight junction protein and mucin loss, and intestinal cell apoptosis. EGCG also reduces intestinal inflammation by suppressing the TLR4-NF-κB/MAPKs-NLRP3 pathway. Importantly, EGCG reverses gut microbiota dysbiosis and short-chain fatty acid (SCFA) content decrease induced by SEA. It is worth noting that this study also detects the direct interaction between the phytochemical and virulence factors and finds that EGCG effectively not only inhibits the secretion of SEA but also binds with the secreted SEA to attenuate its toxicity. Taken together, EGCG mitigates SEA-induced intestinal barrier dysfunction via gut microbiota SCFA-mediated TLR4-NF-κB/MAPKs-NLRP3 inflammatory cascade inhibition. Overall, this research provides enlightening insight into the application of bacteriotoxin-targeting natural compounds in the field of food safety and human wellness.


Inhibition Effect of Dictyophora Polysaccharides on Human Hepatocellular Carcinoma Cell Line HCC-LM3.
BACKGROUND It has been reported that polysaccharides have potential novel anti-cancer properties. Previously, we confirmed that Dictyophora polysaccharides could significantly inhibit liver transplantation tumors in mice. However, the mechanism of Dictyophora polysaccharide action on human liver cancer is unclear. Here, we aimed to clarify the mechanism of Dictyophora polysaccharide action on human hepatocellular carcinoma cells, namely the effect on cell proliferation, the cell cycle, and apoptosis, and on the apoptosis-related genes and proteins in vitro. MATERIAL AND METHODS The HCC-LM3 cell line was incubated with 2.5 mg/mL Dictyophora polysaccharides for 24, 48, and 72 h. The cell growth inhibition rate was evaluated using Cell Counting Kit-8. Cell cycle and apoptosis were measured with flow cytometry. The expression of apoptosis-related genes and proteins was measured using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. RESULTS The Dictyophora polysaccharides inhibited HCC-LM3 cell proliferation in a time- and dose-dependent manner and blocked the cell cycle in the G₂/M phase. In addition, Bax and caspase-3 expression were significantly increased after Dictyophora polysaccharides treatment. CONCLUSIONS To the best of our knowledge, this is the first published study on the mechanism of Dictyophora polysaccharide inhibition of HCC-LM3 cell proliferation.


[Neonatal reflexes variability in the normal full term neonate during the neurological exam].
It has been stated that findings in neonatal neurological examinations can play a role as a pointer to adverse developmental outcome. The description of the examinations, and their presence or absence differed among authors without clear reference to their physiological variability ranges. We approached the study of some neonatal behaviours and reflexes in 143 examinations made on 113 healthy newborn babies from the maternity wards by looking at the influence that perinatal environmental factors which are considered normal, can play in these examinations. The results showed that the flexion answer of the Babinski reflex increased significantly between the first and third day of life (c2= 4.4478; p= 0.03495) in the same way there was an increase in the stepping reflex (c2= 3.999; p= 0.04552) in the righting reflex (c2= 4.9342; p= 0.02633) and in the supporting reaction (c2= 11.7874; p= 0.0006). This was significantly reduced in the caesarean section deliveries (c2= 7.1209; p= 0.0076). Head reaction was only detectable during the Brazelton behavioural states 1 to 3 (c2= 3.8911; p= 0.04854) and the same thing happened with the stepping reflex (c2= 4.9370; p= 0.02629). We discuss the utility of neonatal reflexes scoring scales in predicting the neurodevelopmental outcome of the newborn baby.


Attentional Capture to a Singleton Distractor Degrades Visual Marking in Visual Search.
Visual search is easier after observing some distractors in advance; it is as if the previewed distractors were excluded from the search. This effect is referred to as the preview benefit, and a memory template that visually marks the old locations of the distractors is thought to help in prioritizing the locations of newly presented items. One remaining question is whether the presence of a conspicuous item during the sequential shift of attention within the new items reduces this preview benefit. To address this issue, we combined the above preview search and a conventional visual search paradigm using a singleton distractor and examined whether the search performance was affected by the presence of the singleton. The results showed that the slope of reaction time as a function of set size became steeper in the presence of a singleton, indicating that the singleton distractor reduced the preview benefit. Furthermore, this degradation effect was positively correlated with the degree of conventional attentional capture to a singleton measured in a separate experiment with simultaneous search. These findings suggest that the mechanism of visual marking shares common attentional resources with the search process.


Stopping Oxytocin in Active Labor Rather Than Continuing it until Delivery: A Viable Option for the Induction of Labor.
Induction of labor (IOL), using intravenous oxytocin, is the artificial initiation of labor before its spontaneous onset for the purpose of delivery of the fetoplacental unit. Although there are various studies looking at dosages of oxytocin, only a few have addressed the issue of discontinuation of oxytocin in the active stage of labor. Thus, our study was conducted to evaluate the need for continuation versus discontinuation of oxytocin during active labor. This prospective, randomized controlled trial included 106 women who needed IOL. Oxytocin infusion was initiated at a rate of 3mIU/min and was incremental until 4-6cm cervical dilation. At this point the patients were randomly assigned into one of two groups. In group one, oxytocin was discontinued, and infusion was continued with 0.9% sodium chloride solution. In group two, oxytocin was continued at the same dose until delivery. The duration of oxytocin infusion was 5.5 hours in the oxytocin discontinuation group and 11.0 hours in oxytocin continuation group (p<0.001). The total dose of oxytocin was significantly higher in group two (6.1 units vs. 16.5 units; p=<0.001). The induction-delivery interval was significantly less in group one (9.1 and 11.2 hours in group one and group two, respectively; p=0.023). Oxytocin discontinuation in the active stage of labor did not prolong the active stage. The total duration of labor and total oxytocin dose were significantly less in the oxytocin discontinuation group. Our results suggest that oxytocin discontinuation is an alternative and viable option particularly in resource poor and economically challenged settings. It not only reduces the need for intense monitoring and prolonged oxytocin use-associated dangers but reduces the total cost of labor management.


Rotated balance in humans due to repetitive rotational movement.
We show how asymmetries in the movement patterns during the process of regaining balance after perturbation from quiet stance can be modeled by a set of coupled vector fields for the derivative with respect to time of the angles between the resultant ground reaction forces and the vertical in the anteroposterior and mediolateral directions. In our model, which is an adaption of the model of Stirling and Zakynthinaki (2004), the critical curve, defining the set of maximum angles one can lean to and still correct to regain balance, can be rotated and skewed so as to model the effects of a repetitive training of a rotational movement pattern. For the purposes of our study a rotation and a skew matrix is applied to the critical curve of the model. We present here a linear stability analysis of the modified model, as well as a fit of the model to experimental data of two characteristic "asymmetric" elite athletes and to a "symmetric" elite athlete for comparison. The new adapted model has many uses not just in sport but also in rehabilitation, as many work place injuries are caused by excessive repetition of unaligned and rotational movement patterns.


Role of apoptosis in myocardial stunning after open heart surgery.
Myocardial preservation during open heart surgery is a subject of intense investigation. A prerequisite for further improvement is a better understanding of the underlying pathophysiologic mechanisms responsible for postoperative myocardial stunning. In this report, we analyzed the role of apoptosis in myocardial stunning. Myocardial samples were obtained from 11 patients undergoing elective coronary artery bypass grafting before (control) and after cardioplegic arrest and reperfusion. Specimens were examined for apoptosis by electron microscopy, in situ end-labeling of DNA fragments, and biochemically for mitochondrial cytochrome c release. Electron microscopy revealed condensation and margination of nuclear chromatin after surgery, as well as swelling and membrane rupture in mitochondria of single myocytes surrounded by healthy cells. TUNEL-positive cells were also found. Cytochrome c release, an initial step in apoptosis, revealed a 3.4 +/- 0.4-fold increase during surgery (p < 0.0001). Furthermore, cytochrome c release from otherwise intact mitochondria showed a negative correlation with left ventricular function and a positive correlation with the duration of cardioplegic arrest and reperfusion (p < 0.05). Our data demonstrate that programmed cell death is evident early after open heart surgery and correlates with declining cardiac contractility. We conclude that apoptosis may be an important mechanism in postoperative myocardial stunning.


The Cost-effectiveness of Genetic Screening for Familial Hypercholesterolemia: a Systematic Review.
Familial hypercholesterolemia (FH) is a genetic disorder that leads to elevated plasma LDL-cholesterol levels and premature coronary heart disease (CHD). An understanding of the mutations responsible for FH and the effectiveness of statins in lowering the risk of CHD in FH patients has increased interest in genetic screening strategies to improve FH diagnosis. In this study, we aimed to evaluate the cost-effectiveness of such strategies. We performed a systematic review of full economic evaluations that assessed the cost-effectiveness of FH genetic screening strategies. We used relevant search terms to investigate Medline, Scopus, Web of Science, the Database of Abstracts of Reviews of Effects, the Health Technology Assessment Database, and the National Health Service Economic Evaluation Database. Data extraction and assessment of the quality of the studies were performed independently by two reviewers. The key features of the included studies are summarized in a narrative synthesis. We included seven economic evaluations that assessed the cost-effectiveness of genetic screening for FH, published mainly in Europe between 2002 and 2015. Most studies had a no-screening strategy as a comparator, focused on relatives of index cases with genetic or clinical diagnosis of FH (cascade screening), considered a lifetime horizon and adopted a health care payer viewpoint. Cascade screening, based on genetic testing of relatives of an index case with confirmed clinical or genetic diagnosis of FH, was shown to be cost-effective in most settings. Our review confirms the cost-effectiveness of cascade genetic screening for the diagnosis of FH. Further research may be needed to assess the cost-effectiveness of cascade screening following the introduction of newly recommended therapeutic regimes and next-generation sequencing.


Expression of the human fibroblast interferon gene in Escherichia coli.
We applied the method of Guarente et al. [Guarente, L., Lauer, G., Roberts, T.M. & Ptashne, M. (1980) Cell 20, 543-553] to construct plasmids that direct expression in Escherichia coli of the human fibroblast interferon (F-IF) gene. Two plasmids were recovered. One directs efficient synthesis of a protein whose primary sequence is that of pre-F-IF and the other, that of mature F-IF. Extracts of bacteria synthesizing mature F-IF display antiviral activity characteristic of human F-IF. This activity is lower than that expected from the differential rate of synthesis of the protein. We have detected no such activity in extracts of bacteria synthesizing pre-F-IF.


Audiologist Perception on Reporting Hearing Assessment Results to State Early Hearing Detection and Intervention Programs.
To describe an evaluation conducted by 39 state Early Hearing Detection and Intervention (EHDI) programs on the reporting process and system usability for audiologists when reporting the hearing test results to the EHDI program and the barriers encountered during reporting. Each author independently extracted numbers, percentages, and texts from the evaluation reports into an Excel spreadsheet, which then became the dataset. Authors then compared and cross-checked the datasets before coding. Texts conveying similar concepts were coded with the same name and organized into categories. Finally, thematic identification and analysis were performed when a theme(s) or concept(s) that pertained to similar challenges encountered by audiologists was identified and organized under a higher-order domain. Some audiologists reported no barriers when reporting hearing test results to the state EHDI programs. Among those audiologists who reported barriers, the most recurrent barrier was a non-user-friendly data system design. The second most recurrent barrier was not having adequate administrative time to report data as a busy clinician. The third most recurrent barrier was an incomplete understanding of the state EHDI reporting requirements. Finally, the method audiologists were required to use when reporting results also posed some challenges, such as no internet connection in rural areas when required to report via an internet portal. Because of the wide variety of barriers faced by audiologists, multiple strategies to improve the reporting process would likely be beneficial.


Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is a worldwide problem that affects 5 million people in the United States alone. Until the approval of tacrine in the mid-1990s, there was no effective therapy for the cognitive symptoms of AD. Although cholinergic therapy provides modest but significant symptomatic relief, the development of effective disease-modifying therapy is essential. It has been demonstrated that a number of inflammatory processes are active in the brain of patients with AD, and therefore it is believed that an anti-inflammatory regimen may offer some degree of neuroprotection. Several studies have indicated that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with delayed onset and/or slowed cognitive decline in AD. Although not currently approved for this condition, recent findings have demonstrated that cyclooxygenase (COX)-2 is of primary importance in the inflammatory response and may have a role in neurodegeneration. Therefore, selective COX-2 inhibitors (coxibs) may have an advantage over traditional NSAIDs as potential therapeutic agents in AD. The Alzheimer's Disease Cooperative Study (ADCS) is conducting an ongoing multicenter, double-blind, placebo-controlled trial to determine whether rofecoxib, a coxib, or naproxen, a nonselective NSAID, will slow the rate of cognitive and clinical decline in AD. This study, along with other clinical studies currently under way, will determine the utility of selective and nonselective COX inhibitors for the prevention and treatment of AD.


Secret lanthanides.
Lanthanides are a group of 15 chemical elements which, together with their salts, have come to be used in the last decade as homoeopathic remedies. The effective introduction of lanthanides and their salts into the clinical use, as homoeopathic remedies was based on the idea of Jan Scholten, MD to relate their physicochemical properties shown in the periodic table of elements to their homoeopathic potential. The lanthanides and their salts were prepared as homoeopathic remedies by Pharmacist Robert Münz.


Canine adipose tissue-derived mesenchymal stem cells pre-treated with TNF-alpha enhance immunomodulatory effects in inflammatory bowel disease in mice.
Canine inflammatory bowel disease (IBD) is an intractable autoimmune disorder that results in various gastrointestinal and systemic symptoms. Mesenchymal stem cells (MSCs), which release immunomodulatory factors such as tumor necrosis factor-α (TNF-α)-induced gene/protein 6 (TSG-6) and prostaglandin E2 (PGE2), have been suggested as an alternative therapeutic option for IBD treatment in veterinary medicine. Furthermore, although it is known that MSCs pre-treated with pro-inflammatory cytokines show enhanced anti-inflammatory properties via the secretion of soluble factors, the underlying mechanisms of IBD remain unclear. The aim of this study was to demonstrate the therapeutic effects and corresponding mechanisms of canine adipose tissue-derived (cAT)-MSCs stimulated with TNF-α in mouse models of IBD. Mice with dextran sulfate sodium (DSS)- or dinitrobenzene sulfonic acid (DNBS)-induced colitis were injected intraperitoneally with cAT-MSCs pre-treated with TNF-α. Colitis severity was assessed and colon tissues were collected for histopathological, enzyme-linked immunosorbent assay, and flow cytometry analysis. cAT-MSCs stimulated with TNF-α secreted higher concentrations of immunomodulatory factors such as TSG-6 and PGE2, which play a key role in inducing phenotypic alterations in macrophages. Consequently, TNF-α-pre-treated cAT-MSCs further regulated colonic inflammatory cytokines such as interleukin (IL)-1β, IL-6, and IL-10, and ameliorated DSS- or DNBS-induced colitis in mice. Additionally, we demonstrated that M1 macrophages (F4/80+/iNOS+ cells) were decreased in colon tissues from mice treated with TNF-α-pre-treated cAT-MSCs, whereas M2 macrophages (F4/80+/CD206+ cells) were increased. These results may suggest a new cell-based therapeutic option for treating IBD.


Granulomatosis with polyangiitis in Tunisia.
Granulomatosis with polyangiitis (GPA) is more frequent in Northern rather than Southern countries. Very few studies have been conducted in Africa. We have performed a retrospective descriptive study including clinical and laboratory profiles of 30 Tunisian GPA patients seen at the department of Internal Medicine of the University Hospital of la Rabta from 2000 to 2014. Mean age at initial GPA diagnosis was 46±12 years, and the average number of months between the onset of symptoms and diagnosis was 25. Seventeen (56%) were male, and 13 (44%) were female. Ear/nose/throat involvement occurred in 83%. Lung and renal involvement were observed in respectively 70% and 56% followed by mucocutaneous (50%), neurological (50%), ocular (33%), vascular (20%), ureteral (16%), and cardiac involvement in 10%. Cytoplasmic pattern-antineutrophil cytoplasmic antibodies (ANCA) was detected in 27 (90%) patients. Induction therapy consisted of intravenous cyclophosphamide pulses in 27 patients (90%) and oral methotrexate in 3 patients (10%). Trimethoprime-sulfamethoxazole was used in 26 patients (86%). Maintenance therapy consisted of azathioprine in 17 cases and methotrexate in 13 cases. Relapses occurred in 36%. Eighteen patients had favorable outcome and 12 died. Our patients had a distinct phenotype with high prevalence of pleural involvement, lymph node enlargement, sensorimotor neuropathy and ureter stenosis. ENT symptoms were less frequent as inaugural presentation. Overall 2-year survival was 60%.


Arthrobacter liuii sp. nov., resuscitated from Xinjiang desert soil.
A Gram-stain positive, aerobic, non-motile actinobacterium, designated DSXY973(T), was isolated from soil samples collected from Xinjiang desert using medium supplemented with resuscitation-promoting factor, and subjected to a polyphasic taxonomic investigation. Phylogenetic analysis based on 16S rRNA gene sequences revealed that DSXY973(T) belonged to the genus Arthrobacter and was most closely related to Arthrobacter oryzae JCM 15922(T) with 97.1 % similarity. The DNA G+C content was 67.6 %. Cells of strain DSXY973(T) mainly contained MK-9(H2), and the cell wall contained l-lysine as the primary diamino acid. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. Strain DSXY973(T) was positive for catalase and negative for oxidase activity. On the basis of its phylogenetic position and phenotypic properties, strain DSXY973(T) represents a novel species of the genus Arthrobacter, for which the name Arthrobacter liuii sp. nov. is proposed. The type strain is DSXY973(T) ( = CGMCC1.12778(T) = JCM 19864(T)).


A Nominal Group Technique Study of Patients Who Identify as Black or African American and Access to Renal Transplantation.
Introduction: Completion of the renal transplant evaluation has been associated with several barriers for patients who identify as Black or African American. This study sought to prioritize barriers to and motivators of completing the renal transplant evaluation. Methods/Approach: Semi-structured interviews and focus groups with a nominal group technique were used to generate priority scores. Transplant professionals (N = 23) were recruited from 9 transplant centers in the Mid-Atlantic, Mid-Western, and Southeastern parts of the United States. Black or African American identifying renal patients (N = 30) diagnosed with end-stage kidney disease were recruited from 1 transplant center in the Mid-Atlantic region. Findings: Priority scores were created to assess the quantitative data of participant rankings of top barriers and motivators. The most significant barriers identified by both patients and transplant professionals comprised financial constraints, insurance issues, difficulty navigating the healthcare system, transportation difficulties, and multiple health problems. Facilitators consisted of family/social support, transplant education, patient navigators, comprehensive insurance, and physician repertoire and investment. A qualitative description of the ranked factors resulted in themes classified as intrapersonal, health, socioeconomic, transplant-specific healthcare, and general healthcare. Conclusion: These findings provided vital information to transplant centers nationwide about assessing the influences of renal transplant evaluation completion. Achieving equity in access to transplantation for Black or African American renal patients requires multilayered approaches.


Poly(ethylene glycol)-poly(ε-caprolactone)-based micelles for solubilization and tumor-targeted delivery of silibinin.
Introduction: Silibinin is a naturally occurring compound with known positive impacts on prevention and treatment of many types of human illnesses in general and cancer in particular. Silibinin is poorly water soluble which results in its insufficient bioavailability and lack of therapeutic efficacy in cancer. Here, we proposed to examine the potential of micelles composed of poly(ethylene glycol) (PEG) as the hydrophilic block and poly(ε-caprolactone) (PCL), poly(α-benzylcarboxylate-ε-caprolactone) (PBCL), or poly(lactide)-(PBCL) (PLA-PBCL) as hydrophobic blocks for enhancing the water solubility of silibinin and its targeted delivery to tumor. Methods: Co-solvent evaporation method was used to incorporate silibinin into PEG-PCL based micelles. Drug release profiles were assessed using dialysis bag method. MTT assay also was used to analyze functional activity of drug delivery in B16 melanoma cells. Results: Silibinin encapsulated micelles were shown to be less than 60 nm in size. Among different structures under study, the one with PEG-PBCL could incorporate silibinin with the highest encapsulation efficiency being 95.5%, on average. PEG-PBCL micelles could solubilize 1 mg silibinin in 1 mL water while the soluble amount of silibinin was found to be 0.092 mg/mL in the absence of polymeric micelles. PEG-PBCL micelles provided the sustained release of silibinin indicated with less than 30% release of silibinin within 24 hours. Silibinin encapsulated in PEG-PBCL micelles resulted in growth inhibitory effect in B16 cancer cells which was significantly higher than what observed with free drug. Conclusion: Our findings showed that PEG-PBCL micellar nanocarriers can be a useful vehicle for solubilization and targeted delivery of silibinin.


Brucellar spondylodiscitis affecting non-contiguous spine levels.
Brucellosis is a zoonosis that affects several organs. The spine is the most common site of musculoskeletal involvement. However, multiple-level spinal involvement is rare in brucella spondylodiscitis. The authors report a case of a 56-year-old male shepherd who had developed a spondylodiscitis affecting simultaneously the cervical, thoracic and lumbar regions. The diagnosis was established by using MRI after the brucella-agglutination test was found to be positive. A high degree of suspicion in the diagnosis of brucellar spondylodiscitis is essential to reduce the delay for the treatment. Thus, it should be essentially included in the differential diagnosis of longstanding cervical, thoracic or back pain, particularly in regions where brucellosis is endemic. Screening serological tests for brucella should be used more widely in cases with low index of suspicion, especially in endemic areas.