Dual gratings for enhanced light trapping in thin-film solar cells by a layer-transfer technique.
Thin film solar cells benefit significantly from the enhanced light trapping offered by photonic nanostructures. The thin film is typically patterned on one side only due to technological constraints. The ability to independently pattern both sides of the thin film increases the degrees of freedom available to the designer, as different functions can be combined, such as the reduction of surface reflection and the excitation of quasiguided modes for enhanced light absorption. Here, we demonstrate a technique based on simple layer transfer that allows us to independently pattern both sides of the thin film leading to enhanced light trapping. We used a 400 nm thin film of amorphous hydrogenated silicon and two simple 2D gratings for this proof-of-principle demonstration. Since the technique imposes no restrictions on the design parameters, any type of structure can be made.


The envirome and the connectome: exploring the structural noise in the human brain associated with socioeconomic deprivation.
Complex cognitive functions are widely recognized to be the result of a number of brain regions working together as large-scale networks. Recently, complex network analysis has been used to characterize various structural properties of the large-scale network organization of the brain. For example, the human brain has been found to have a modular architecture i.e., regions within the network form communities (modules) with more connections between regions within the community compared to regions outside it. The aim of this study was to examine the modular and overlapping modular architecture of the brain networks using complex network analysis. We also examined the association between neighborhood level deprivation and brain network structure-modularity and gray nodes. We compared network structure derived from anatomical MRI scans of 42 middle-aged neurologically healthy men from the least (LD) and the most deprived (MD) neighborhoods of Glasgow with their corresponding random networks. Cortical morphological covariance networks were constructed from the cortical thickness derived from the MRI scans of the brain. For a given modularity threshold, networks derived from the MD group showed similar number of modules compared to their corresponding random networks, while networks derived from the LD group had more modules compared to their corresponding random networks. The MD group also had fewer gray nodes-a measure of overlapping modular structure. These results suggest that apparent structural difference in brain networks may be driven by differences in cortical thicknesses between groups. This demonstrates a structural organization that is consistent with a system that is less robust and less efficient in information processing. These findings provide some evidence of the relationship between socioeconomic deprivation and brain network topology.


Random forest-based prediction of stroke outcome.
We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e-16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e-16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.


Antibiotic prescribing for adults in ambulatory care in the USA, 2007-09.
To determine patterns of ambulatory antibiotic prescribing in US adults, including the use of broad-spectrum versus narrow-spectrum agents, to provide a description of the diagnoses for which antibiotics are prescribed and to identify patient and physician factors associated with broad-spectrum antibiotic prescribing. We used data for patients aged ≥ 18 years from the National Ambulatory and National Hospital Ambulatory Medical Care Surveys (2007-09). These are nationally representative surveys of patient visits to offices, hospital outpatient departments and emergency departments (EDs) in the USA, collectively referred to as ambulatory visits. We determined the types of antibiotics prescribed, including the use of broad-spectrum versus narrow-spectrum antibiotics, and examined prescribing patterns by diagnoses. We used multivariable logistic regression to identify factors associated with broad-spectrum antibiotic prescribing. Antibiotics were prescribed during 101 million (95% CI: 91-111 million) ambulatory visits annually, representing 10% of all visits. Broad-spectrum agents were prescribed during 61% of visits in which antibiotics were prescribed. The most commonly prescribed antibiotics were quinolones (25% of antibiotics), macrolides (20%) and aminopenicillins (12%). Antibiotics were most commonly prescribed for respiratory conditions (41% of antibiotics), skin/mucosal conditions (18%) and urinary tract infections (9%). In multivariable analysis, among patients prescribed antibiotics, broad-spectrum agents were more likely to be prescribed than narrow-spectrum antibiotics for respiratory infections for which antibiotics are rarely indicated (e.g. bronchitis), during visits to EDs and for patients ≥ 60 years. Broad-spectrum agents constitute the majority of antibiotics in ambulatory care. More than 25% of prescriptions are for conditions for which antibiotics are rarely indicated. Antibiotic stewardship interventions targeting respiratory and non-respiratory conditions are needed in ambulatory care.


Polyamines as a common source of hydrogen peroxide in host- and nonhost hypersensitive response during pathogen infection.
The hypersensitive response (HR) is a powerful resistance system that plants have developed against pathogen attack. There are two major pathways for HR induction; one is through recognition of the pathogen by a specific host protein, and is known as the host HR. The other is through common biochemical changes upon infection--the nonhost HR. We previously demonstrated that hydrogen peroxide derived from polyamine degradation by polyamine oxidase triggers the typical host HR in tobacco plants upon infection with tobacco mosaic virus. However, it remains to be determined whether or not polyamines are involved in the nonhost HR in tobacco, and in the host HR in other plant species. When tobacco plants were infected with Pseudomonas cichorii, a representative nonhost pathogen, transcripts for six genes encoding enzymes for polyamine metabolism were simultaneously induced, and polyamines were accumulated in apoplasts. Hydrogen peroxide was concomitantly produced and hypersensitive cell death occurred at infected sites. Silencing of polyamine oxidase by the virus-induced gene silencing method resulted in suppression of hydrogen peroxide production and in disappearance of visible hypersensitive cell death with an increase in bacterial growth. Our results indicated that polyamines served as the source of hydrogen peroxide during the nonhost HR in tobacco plants. Further analysis revealed that polyamines were accumulated in apoplasts of Arabidopsis thaliana infected with Pseudomonas syringae, and of rice infected with Magnaporthe grisea, both causing the typical host HR. As in tobacco, it is conceivable that the same mechanism operates for nonhost HR in these plants. Our present observations thus suggested that polyamines are commonly utilized as the source of hydrogen peroxide during host- and nonhost HRs in higher plants.


A novel fluorimetric method for determination of pseudoephedrine hydrochloride in pharmaceutical formulations and blood serum.
An inexpensive, simple, highly sensitive, and rapid fluorimetric method was developed for the analysis of pseudoephedrine hydrochloride at trace levels. The method is based on the recovery of fluorescence of Rh6G dye due to the interaction of pseudoephedrine hydrochloride with Rh6G-Au NPs complex, which results in the release of Rh6G from the complex and halting fluorescence resonance energy transfer between Rh6G and Au NPs. The intensity of fluorescence was directly proportional to the concentration of the analyte, which was used for its determination. Experimental factors were optimized by response-surface methodology. Under optimum conditions, the calibration curve was linear over the range of 15-150 ng mL-1 and the limit of detection (LOD) was 10 ng mL-1. Percent relative standard deviation (n= 5) for determination of 50 ng mL-1 pseudoephedrine hydrochloride was 3.74%. The method was successfully used for determining the analyte in human blood serum and in pharmaceutical formulations. The possible mechanistic description of the analytical reaction was proposed on the basis of TEM, FT-IR, and fluorescence spectra analysis.


The derived generalization of thought suppression.
Thought suppression appears to be a relatively ineffective and even counterproductive strategy for dealing with unwanted thoughts. However, the psychological processes responsible for unsuccessful suppression are still underspecified. One process that may be implicated is derived stimulus relations, which may underlie the formation of unintentional relations that act to hamper suppression attempts. To test this prediction, participants were trained and tested for the formation of three derived equivalence relations using a match-to-sample procedure. Subsequently, they were instructed to suppress all thoughts of a particular target word that was a member of one of the three relations and were also allowed to selectively remove words that appeared on a computer screen in front of them by pressing the space bar. Results showed, as predicted, that participants not only removed the to-be-suppressed stimulus, but also removed words in derived relations with that stimulus, thus showing transformation of suppression/interference functions via derived equivalence. The theoretical implications of this demonstration, including its potential as a model for a key psychological process involved in unsuccessful thought suppression, are discussed.


A Mononuclear Non-heme Iron(III)-Peroxo Complex with an Unprecedented High O-O Stretch and Electrophilic Reactivity.
A mononuclear non-heme iron(III)-peroxo complex, [Fe(III)(O2)(13-TMC)]+ (1), was synthesized and characterized spectroscopically; the characterization with electron paramagnetic resonance, Mössbauer, X-ray absorption, and resonance Raman spectroscopies and mass spectrometry supported a high-spin S = 5/2 Fe(III) species binding an O2 unit. A notable observation was an unusually high νO-O at ∼1000 cm-1 for the peroxo ligand. With regard to reactivity, 1 showed electrophilic reactivity in H atom abstraction (HAA) and O atom transfer (OAT) reactions. In the HAT reaction, a kinetic isotope effect (KIE) value of 5.8 was obtained in the oxidation of 9,10-dihydroanthracene. In the OAT reaction, a negative ρ value of -0.61 in the Hammett plot was determined in the oxidation of p-X-substituted thioanisoles. Another interesting observation was the electrophilic reactivity of 1 in the oxidation of benzaldehyde derivatives, such as a negative ρ value of -0.77 in the Hammett plot and a KIE value of 2.2. To the best of our knowledge, the present study reports the first example of a mononuclear non-heme iron(III)-peroxo complex with an unusually high νO-O value and unprecedented electrophilic reactivity in oxidation reactions.


Salso-bromo-iodine thermal water: a nonpharmacological alternative treatment for postnasal drip-related cough in children with upper respiratory tract infections.
Postnasal drip (PND)-related cough is a very common symptom in patients with upper respiratory tract infections (URTIs). At present, there is not a standard treatment for postnasal drip and postnasal drip-related cough. The aim of this pilot study was to evaluate the efficacy of a specific salso-bromo-iodine thermal water containing hyaluronic acid and grapefruit seed extract (SBI-H-GSE) comparing it with a normal saline solution in children with URTIs who refer PND-related symptoms. The study was randomized, single-blind, and controlled. Study group (75 children) was treated with SBI-H-GSE and control group (65 children) was treated with a normal saline solution; both compounds were administered by nasal nebulization with Rinowash nasal douche twice/day for 10 days a month for 3 consecutive months. Parent Cough-Specific Quality of Life questionnaire (PC-QOL) average score, the prevalence of symptoms and signs related to post-nasal drip, nasal mucociliary transport time (NMTT), duration and number of URTI episodes, antibiotic usage and days of absence from school were evaluated at baseline and after treatment. SBI-H-GSE therapy shows better and statistically significant trend after treatment when compared to control group for PC-QOL average score (p=0.011), NMTT (p=0.047), symptoms and signs related to post-nasal drip (all p<0.005, except for the cobblestone appearance of the mucosa), duration (in days) with URTI symptoms (p=0.023) and a usage of antibiotic therapy (p=0.011). The current randomized-controlled pilot study demonstrated that SBI-H-GSE solution was effective in the treatment of children with URTIs who refer PND-related symptoms.


Abnormalities in circadian patterns of bone resorption and renal calcium conservation in type I osteoporosis.
We compared changes over 24 h in 15 postmenopausal normal women (mean [+/- SD] age, 64 +/- 7 yr) with those in 15 postmenopausal women with type I osteoporosis and vertebral fractures (mean age, 64 +/- 5 yr). The serum osteocalcin concentration, a sensitive index of bone formation, increased by about 5% at night in both groups. Urinary deoxypyridinoline excretion, a sensitive index of bone resorption, increased by 48% at night (P less than 0.01) in the normal women, whereas in the osteoporotic women it was 62% higher overall (P less than 0.05), and the increase persisted into the morning. At night, urinary fractional excretion of calcium decreased by 20% (P less than 0.001) in the normal women, but was unchanged in the osteoporotic women; this circadian pattern differed between groups (P less than 0.05). The serum ionized calcium concentration did not change at night in either group. There was a trend (P = 0.07) for blunting of the nocturnal increase in the serum intact PTH level in osteoporotic women. Thus, the nocturnal serum ionized calcium level is maintained by decreased urinary calcium excretion and increased bone resorption in postmenopausal normal women, but almost entirely by increased resorption in postmenopausal osteoporotic women. This greater dependence on bone resorption during the nocturnal fast may account in part for the greater bone loss in osteoporotic women.


Association between fruit juice consumption and self-reported body mass index among adult Canadians.
The prevalence of obesity and being overweight is rising among adult Canadians and diet is recognised as one of the main causes of obesity. The consumption of fruit and vegetables is shown to be protective against obesity and being overweight but little is known about the association of fruit juice consumption and obesity and being overweight. The present study aimed to investigate the association between fruit juice consumption and self-reported body mass index (BMI) among adult Canadians. This analysis is based on the Canadian Community Health Survey, Cycle 3.1. A regression method was used to assess the association of fruit juice consumption with self-reported BMI in 18-64-year-old Canadians who had been adjusted for sex, age, total household income, education, self-rated health, and daily energy expenditure. Because the analysis is based on a cross-sectional dataset, it does not imply a cause and effect relationship. Almost 38.6% of adult Canadians reported a fruit juice intake of 0.5-1.4 times per day and 18.2% consumed fruit juice more than 1.5 times per day. Participants with normal weight were likely to consume more fruit juice than obese individuals. Regression analysis showed a negative association between fruit juice consumption and BMI after adjusting for age, sex, education, marital status, income, total fruit and vegetable intake, daily energy expenditure, and self-rated health. On average, for each daily serving of fruit juice, a -0.22 unit (95% confidence interval = -0.33 to -0.11) decrease in BMI was observed. The results obtained showed a moderate negative association between fruit juice intake and BMI, which may suggest that a moderate daily consumption of fruit juice is associated with normal weight status.


Surface-Embedded Stretchable Electrodes by Direct Printing and their Uses to Fabricate Ultrathin Vibration Sensors and Circuits for 3D Structures.
Printing is one of the easy and quick ways to make a stretchable wearable electronics. Conventional printing methods deposit conductive materials "on" or "inside" a rubber substrate. The conductors made by such printing methods cannot be used as device electrodes because of the large surface topology, poor stretchability, or weak adhesion between the substrate and the conducting material. Here, a method is presented by which conductive materials are printed in the way of being surface-embedded in the rubber substrate; hence, the conductors can be widely used as device electrodes and circuits. The printing process involves a direct printing of a metal precursor solution in a block-copolymer rubber substrate and chemical reduction of the precursor into metal nanoparticles. The electrical conductivity and sensitivity to the mechanical deformation can be controlled by adjusting the number of printing operations. The fabrication of highly sensitive vibration sensors is thus presented, which can detect weak pulses and sound waves. In addition, this work takes advantage of the viscoelasticity of the composite conductor to fabricate highly conductive stretchable circuits for complicated 3D structures. The printed electrodes are also used to fabricate a stretchable electrochemiluminescence display.


Epidemiological response to a suspected excess of cancer among a group of workers exposed to multiple radiological and chemical hazards.
An excess of cancer was suspected by workers of the metallurgy department at the French Atomic Energy Commissariat (CEA) after several deaths from cancer were reported in 1983 and 1984. After a descriptive study performed by the CEA in 1985 the results of which were not conclusive enough to put an end to the controversy, the present cohort study was undertaken in 1989. As no specific exposure, or a precise cancer site was suspected, it was decided to include all subjects who had worked at the metallurgy department for at least 1 year between 1950 and 1968. The cohort was followed up to 31 December 1990. Individual occupational exposures were determined retrospectively for each year from 1950 to 1990, both qualitatively (annual job, and hazard records, and assistance from former workers) and quantitatively (for external radiation). On the basis of these exposures, three types of occupational tasks were identified: handling of chemicals, radionuclides, and external radiation. Standardised mortality ratios (SMRs) were calculated to estimate the risk of death, and the existence of an association between risk of cancer and each of the three tasks was tested. The cohort included 356 workers, followed up for an average of 30 years (total of 10,820 person-years). The number of deaths from all causes and from all cancer sites were respectively 44 and 21. No excess of cancer deaths was found for the study period (SMR 0.77), nor was there a peak in 1983-4. The risk of death from all cancer sites increased with the duration of exposure to chemicals. The results do not justify the workers' impression of an excess of cancer. They suggest, however, that the duration of work at some tasks that involved handling chemicals may be an indicator of risk of cancer. Communication to the workers during the study played an important part in reducing their concern, contributing to their better understanding of the results.


Reduced surgical success rate of rectus muscle plication compared to resection.
To evaluate the surgical success of rectus muscle plication compared to resection and to compare the short- and long-term changes in ocular alignment after both procedures. The medical records of all patients who underwent a rectus muscle tightening procedure (resection or plication) at a single institution over a 5-year period by a single surgeon were reviewed retrospectively. Binocular alignment was recorded before and immediately after surgery and again at 6-12 weeks and final follow-up visit. Primary outcome was surgical success rate, defined as distance alignment of ≤10Δ for horizontal and ≤6Δ for vertical strabismus. Secondary outcomes were reoperation rate and postoperative alignment drift. A total of 72 surgeries were identified for inclusion: 48 resections and 24 plications. Surgical success was significantly higher in the resection group than in the plication group (89% vs 58%; P = 0.005) at both 6-12 weeks' follow-up (P = 0.005) and at mean final follow-up of 19 ± 13 months (range, 3-56 months [n = 48]; P = 0.03). Reoperations were performed in 3 patients in the plication group (12.5%), all for undercorrection; there were no reoperations in the resection group (P = 0.03). Rectus muscle plication has many potential advantages over resection, including sparing of the ciliary circulation. In our experience, however, patients treated with plication had lower surgical success rates and a higher reoperation rate. Surgeons should monitor their long-term results before considering plication as their procedure of choice over resection.


Effects of Leucine-Enriched Whey Protein Supplementation on Physical Function in Post-Hospitalized Older Adults Participating in 12-Weeks of Resistance Training Program: A Randomized Controlled Trial.
Age-related strength and muscle mass loss is further increased after acute periods of inactivity. To avoid this, resistance training has been proposed as an effective countermeasure, but the additional effect of a protein supplement is not so clear. The aim of this study was to examine the effect of a whey protein supplement enriched with leucine after resistance training on muscle mass and strength gains in a post-hospitalized elderly population. A total of 28 participants were included and allocated to either protein supplementation or placebo supplementation following resistance training for 12 weeks (2 days/week). Physical function (lower and upper body strength, aerobic capacity and the Short Physical Performance Battery (SPPB) test), mini nutritional assessment (MNA) and body composition (Dual X-ray Absorptiometry) were assessed at baseline and after 12 weeks of resistance training. Both groups showed improvements in physical function after the intervention (p < 0.01), but there were no further effects for the protein group (p > 0.05). Muscle mass did not improve after resistance training in either group (p > 0.05). In conclusion, 12 weeks of resistance training are enough to improve physical function in a post-hospitalized elderly population with no further benefits for the protein-supplemented group.


Cardiac transplantation: a review for the intensivists.
Cardiac transplantation has now become accepted therapy for the treatment of end-stage heart disease in both children and adults, and literally thousands of patients are bearers of cardiac grafts. Because of these patients' susceptibility to infections, rejection, coronary disease, and malignancy, as well as to serious illnesses unrelated to their transplantation, they will often be encountered at hospital centers both close to their homes and distant from the site of their surgery. The intensive care unit physician's role will be a demanding one when caring for these patients because of the broad differential diagnosis of infections, frequency of drug interactions and altered immunosuppression, and continuous uncertainty regarding the possibility of rejection, particularly during the first year after transplantation.


Long-term treatment of hyperphosphatemia with bixalomer in Japanese hemodialysis patients.
Bixalomer is a nonabsorbable polymer that binds phosphate in the gastrointestinal tract and lowers the serum phosphate level by inhibiting phosphate absorption. The safety and efficacy of long-term bixalomer treatment were assessed in Japanese hemodialysis patients with hyperphosphatemia. This was a multicenter open-label study with a 48-week treatment period. The main efficacy endpoints were the serum phosphate level and rate of achieving the target serum phosphate range (3.5-6.0 mg/dL). Bixalomer was initiated at a dose of 1.5 g/day, which was increased to a maximum of 7.5 g/day depending on the serum phosphate response. Of 248 subjects who started treatment, 179 completed the study. The mean serum phosphate level decreased over time and remained around 5.5 mg/dL from weeks 16 to 48. The target serum phosphate level was reached in >50% of subjects by week 7 and was maintained in 65.2% to 75.9% until week 48. The incidence of adverse events and adverse drug reactions was 94.4% and 29.4%, respectively. There was a potential relationship with the study drug for four serious adverse events (ischemic colitis, hemorrhagic intestinal diverticulum, esophageal ulcer, and acute cholecystitis), which occurred in one patient each. Constipation was the most common adverse drug reaction (21.0%). Most adverse events and adverse drug reactions occurred soon after starting administration, and their incidence did not increase during long-term treatment. Bixalomer did not reduce the bicarbonate level or promote metabolic acidosis. Bixalomer is clinically useful for the long-term treatment of hyperphosphatemia.


[The state of and ways to improve diagnostic efficacy in the main forms of malignant neoplasms].
The state of diagnosis of malignant tumors in Ukraine concerning the indexes of opportunity, activity, accuracy was analysed. Complex of measures for an early detection of oncologic patients in all ranks of medical-sanitary aid to population was proposed.


Separation of nucleoside phosphoramidate diastereoisomers by high performance liquid chromatography and capillary electrophoresis.
Separations of five diastereoisomers of nucleoside phosphoramidate derivatives (pronucleotides) were performed by both HPLC method using derivatized cellulose and amylose chiral stationary phases and CE method using anionic cyclodextrins added in the background electrolyte (BGE). An optimal baseline separation (Rs > 1.5) was readily obtained with all silica-based celluloses and amyloses using in a normal-phase methodology. Capillary electrophoresis was used as an alternative technique to HPLC for the separation of pronucleotides. The diastereoisomers were fully resolved with sulfated cyclodextrins at both BGE pH (2.5 and 6.2). Limits of detection and limits of quantification, calculated for both methods, are up to 200 times higher in CE separations than in HPLC separations. The analytical HPLC method was then applied in a preliminary study for the pronucleotide 1 quantification in cellular extract.


Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.


Dental developmental status of southern Chinese girls in Hong Kong.
Dental developmental status of the permanent canines, premolars and second molars were studied in one hundred and two twelve-year-old Southern Chinese girls born and brought up in Hong Kong. Eruption of these teeth were defined as gingival emergence during the clinical examination while the root development was assessed from orthopantomographs. Root resorption pattern of the primary canines and molars were also studied with the aid of the orthopantomographs. Two-thirds of girls presented with permanent dentition stage. The root resorption patterns of the primary teeth were different from their order of exfoliation. The mandibular permanent teeth were in advanced in both eruption and root development than the corresponding maxillary teeth, except the first premolars.


Psychological status and recurrent aphthous ulceration.
Recurrent aphthous ulceration (RAU) are a disease of an unknown etiology and mediated through T-cell lymphocytes. Evidence suggests that RAU is connected with chronic bowel disease, haematinic deficiencies, AIDS, food hypersensitivity and severe stress. The aim of this study was to determine whether differences in anxiety and depression could be seen in patients with RAU during acute phase and remision period and in comparison to the healthy controls. There were 30 patients with RAU (age range 36.27 +/- 15.308) and 30 controls aged 29.83 +/- 9.082. Every participant with RAU fullfilled STAI and Beck Depression Inventory II test during acute phase and during remission period as well as controls. Statistical analysis was performed by use of descriptive statistics and t-test. There are no differences in the level of depression and stress between the two phases of the RAU (acute versus remission period) as well as in comparison to the controls. Patients with acute RAU are more anxious than patients with RAU during remission period. We might conclude that psychological disturbances do not preceed the development of RAU and that the patients with acute RAU are more anxious when compared to the condition when they do not have RAU due to the discomfort they experience.


Effects of lysine and other amino acids on kidney structure and function in the rat.
Lysine is a major constituent of amino acid parenteral nutrition solutions which have recently been shown to increase the severity of various types of acute renal failure in the rat. In previous studies the authors have shown that high-dose lysine alone is capable of causing acute renal failure. However, it has remained unclear what the morphologic expression of this type of acute renal failure is in the maintenance phase of the syndrome, whether other amino acids produce a similar lesion, and whether lysine in lower doses also produces acute renal failure. In the present study the authors show that lysine, when given in a dose of 600 mg/rat over 4 hours, produced persisting acute renal failure which at 48 hours was characterized morphologically by a picture similar to that in human "acute tubular necrosis"--little overt tubular necrosis, but a focal loss of individual tubular cells with regenerative changes and mitotic figures. Extensive hyaline cast formation was seen, particularly in the thin limbs of the loops of Henle, and these thin limb casts were shown to contain Tamm-Horsfall protein. Equivalent doses of glycine, arginine, and glutamic acid and lower doses of lysine produced no significant renal morphologic or functional changes.


Voltage-gated Na+ channel EOIII-segment-like immunoreactivity in fish retinal ganglion cells.
Although single-channel and whole-cell patch-clamp recordings have demonstrated the presence of Na+ currents in retinal ganglion cell somata, it has not previously been reported that an anti-Na+-channel antiserum stains both retinal ganglion cell somata and proteins with molecular weights corresponding to complexes of alpha and beta subunits. We probed adult goldfish retinas for Na+ channel-like immunoreactivity with a polyclonal antibody directed against the EOIII segment of vertebrate voltage-gated Na+ channels. In vertical sections and whole mounts, this antibody consistently stained the somata, axons, and proximal dendrites of retinal ganglion cells. Some somata in the proximal third of the inner nuclear layer were also stained. In Western blots, this antibody specifically stained multiple protein bands from retina and optic nerve, all with apparent molecular weights between 200 and 315 kDa. The largest of these molecular weights agrees with that reported previously for complexes of alpha and beta subunits in mammalian neurons, including retinal ganglion cells. The intermediate and lowest molecular weights are consistent with the presence of multiple Na+ channel alpha subunits, either in individual proximal retinal neurons or in different morphological subtypes.


An in vitro investigation of immunomodulatory properties of Lactobacillus plantarum and L. delbrueckii cells and their extracellular polysaccharides.
Many probiotic lactobacilli and their extracellular polysaccharides (EPS) have beneficial immunological properties. However, it is unclear how they elicit the host immune response. We thus investigated the immunological properties of UV-killed Lactobacillus delbrueckii TU-1 and L. plantarum KM-9 cells as well as their extracellular polysaccharides (EPSs). High-performance liquid chromatography and ion exchange chromatography analyses showed that their EPSs differ in sugar composition and sugar fractionation. The immunological properties were evaluated in a semi-intestinal model using a Transwell co-culture system that employed human intestinal epithelial (Caco-2) cells on the apical side and murine macrophage (RAW264.7) cells on the basolateral side. The UV-killed cells and EPSs were added to the apical side to allow direct contact with Caco-2 cells and incubated for 6 hr. After incubation, the amounts of tumor necrosis factor-α and several cytokines released by RAW264.7 or Caco-2 cells were quantified by cytotoxic activity on L929 cells (murine fibrosarcoma cell line) and quantitative reverse-transcriptase PCR. We found that the UV-killed cells and their EPSs had immunological effects on RAW264.7 cells via Caco-2 cells. The RAW264.7 cells showed different cytokine production profiles when treated with UV-killed cells and EPSs. The UV-killed cells and EPSs promoted a Th1-type cellular response. Furthermore, we found that the UV-killed cells sent positive signals through Toll-like receptor (TLR) 2. Meanwhile, neither EPS sent a positive signal through TLR4 and TLR2. This evidence suggests that both UV-killed cells of the lactobacillus strains and their EPSs trigger a Th1-type immune response in a human host, with the former triggering the response via the TLRs expressed on its epithelium and the latter employing a mechanism yet to be determined, possibly involving a novel receptor that is designed to recognize specific patterns of repeating sugar in the EPSs.


Latent class growth analysis successfully identified subgroups of participants during a weight loss intervention trial.
Weight loss interventions often present small mean weight changes over time, despite the fact that a substantial proportion of the participants lost more weight. This effect is often leveled out by the substantial proportion of participants who gained weight during the trial. The aim of this study is to identify and describe distinct subgroups of participants with different weight change trajectories during and after a weight loss intervention. We used data from a weight loss intervention that was part of a randomized controlled trial on the preventive effect of a tailor-made weight loss intervention and oral glucosamine sulfate on the incidence of knee osteoarthritis in 407 overweight women aged 50 to 60 years. Latent class growth analysis (LCGA) was used to identify subgroups of participants with different weight change trajectories over time. Using LCGA, we identified three subgroups with different trajectories of weight change, one large group (n = 298) with almost no change over time, and two smaller groups (both n = 48), of which one represents participants who steadily gained weight over time, whereas the other represents participants who steadily lost weight over time. Participants that had relatively low body weight around their 40th year of life and that gained weight in the year preceding the study were most likely to belong to the group that lost weight. LCGA was a suitable method to identify three distinct groups of participants with different trajectories of weight change. Low body weight at age 40 and weight gain in the year preceding the study were associated with a higher chance of membership of the group that lost weight. It seems weight loss that occurred during this weight loss intervention was mostly recently gained weight.


In vivo safety evaluation of polyarginine coated magnetic nanovectors.
Safety and efficacy are of critical importance to any nanomaterial-based diagnostic and therapy. The innocuity and functionality of a nanomaterial in vivo is largely dependent on the physicochemical properties of the material, particularly its surface coating. Here, we evaluated the influence of polycationic coating on the efficacy, clearance organ uptake, and safety of magnetic nanovectors designed for siRNA delivery. Polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (NPs) of 12 nm in core diameter were modified with a polycationic coating of either poly-l-arginine (pArg) or polyethylenimine (PEI) and further covalently functionalized with siRNA oligonucleotides. The produced NP-pArg-siRNA and NP-PEI-siRNA nanovectors were similar in hydrodynamic size (21 and 22 nm, respectively) but significantly differed in zeta potentials (+2.1 mV and +29.8 mV, respectively). Fluorescence quantification assays revealed that the NP-pArg-siRNA nanovector was 3-fold more potent than NP-PEI-siRNA in delivering siRNA and 1.8-fold more effective in gene silencing when tested in rat C6 glioblastoma cells. In vivo, both nanovector formulations were similarly taken up by the spleen and liver as determined by histopathological and hemopathological assays. However, PEI coated nanovectors elicited severe hemoincompatibility and damage to the liver and spleen, while pArg coated nanovectors were found to be safe and tolerable. Combined, our findings suggest that polycationic coatings of pArg were more effective and safer than commonly used PEI coatings for preparation of nanovectors. The NP-pArg-siRNA nanovector formulation developed here shows great potential for in vivo based biomedical applications.


Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan.
Wheat provides more than 50% of the protein and calorie intake of the population of Pakistan. Legumes and animal protein that could complement the amino acid pattern of wheat, in which lysine is the first limiting amino acid for utilization of protein, are not affordable by members of lower socioeconomic groups in developing countries. The purpose of the study was to determine whether lysine fortification of wheat flour would have a positive impact on populations consuming a predominantly wheat-based diet. A double-blind study was carried out for three months on the outskirts of Peshawar, Pakistan. Forty families received wheat flour fortified with lysine, and 40 families received wheat flour without lysine. Wheat provided 59% of the protein for men, 65% for women, and 58% for children. The weight and height of the children in both groups increased during the study, but the increase was significantly greater in the lysine group. Hemoglobin increased significantly in the women receiving lysine-fortified flour. Transferrin levels increased significantly in men, women, and children in the lysine group as compared with those in the control group. Prealbumin increased significantly in adults receiving additional lysine but decreased in children. Men, women, and children in the lysine-supplemented families had significant increases in CD4, CD8, and complement C3 as compared with controls. These results indicate that lysine fortification of wheat flour can significantly improve sensitive indicators of nutritional status in a population consuming a diet in which 58% to 65% of the protein, depending on age and sex, is supplied by wheat.


Cerebral Microbleeds: Relationship to Antithrombotic Medications.
Cerebral microbleeds (CMBs) are represented by small areas of hemosiderin deposition, detected on brain magnetic resonance imaging (MRI), and found in ≈23% of the cognitively normal population over age of 60 years. CMBs predict risk of hemorrhagic and ischemic stroke. They correlate with increased cardiovascular mortality. In this article, we sought to determine in a population-based study whether antithrombotic medications correlate with CMBs and, if present, whether the association was direct or mediated by another variable. The study consisted of 1253 participants from the population-based Mayo Clinic Study of Aging who underwent T2* gradient-recalled echo magnetic resonance imaging. We tested the relationship between antithrombotic medications and CMB presence and location, using multivariable logistic-regression models. Ordinal logistic models tested the relationship between antithrombotics and CMB frequency. Using structural equation models, we assessed the effect of antithrombotic medications on presence/absence of CMBs and count of CMBs in the CMB-positive group, after considering the effects of age, sex, vascular risk factors, amyloid load by positron emission tomography, and apoE. Two hundred ninety-five participants (26.3%) had CMBs. Among 678 participants taking only antiplatelet medications, 185 (27.3%) had CMBs. Among 95 participants taking only an anticoagulant, 43 (45.3%) had CMBs. Among 44 participants taking an anticoagulant and antiplatelet therapy, 21 (48.8%) had CMBs. Anticoagulants correlated with the presence and frequency of CMBs, whereas antiplatelet agents were not. Structural equation models showed that predictors for presence/absence of CMBs included older age at magnetic resonance imaging, male sex, and anticoagulant use. Predictors of CMB count in the CMB-positive group were male sex and amyloid load. Anticoagulant use correlated with presence of CMBs in the general population. Amyloid positron emission tomography correlated with the count of CMBs in the CMB-positive group.


[Role of A.A Ukhtomskiĭ in the development of the problems of work, working capacity and fatigue (peculiarities and characteristics of these states in various age periods)].
The data of research which has been carried out for years, are summarized. They are presented in a succession conforming to the A.A. Ukhtomsky views on the gradual enlargement of amplitude of muscles contraction, on capacity for work, and on fatigue. In the early postnatal period the phenomenon of gradual enlargement of amplitude of muscles contraction does not yet exist. It only appears after realizaiton of standing posture, when skeletal muscles transit from the type of tonic activity to the phasic--tetanic type. This phenomenon is due to that the first contractions induce hyperrelaxation which leads to the subsequent higher amplitude of contraction. The steady state of work capacity of neuromuscular system without any changes of amplitude, in the conditions of undisturbed circulation in the organism as a whole, can be maintained in all the periods of age for a long time without any signs of fatigue. This phenomenon takes place during the intervals between the contraction activity, the anabolic process having ample time to be completed. Such a form of work capacity is called stability. If the anabolic processes are unable to be completed during the intervals between the contractions, their amplitude gradually decreases reflecting the beginning of fatigue. The contractile activity which is going on during the fatigue state, is called endurance.


[Lack of correlation between performances in a simulator and in reality].
Simulation-based training provides obvious benefits for patients and doctors in education. Frequently, virtual reality simulators are expensive and evidence for their efficacy is poor, particularly as a result of studies with poor methodology and few test participants. In medical simulated training- and evaluation programmes it is always a question of transfer to the real clinical world. To illustrate this problem a study comparing the test performance of persons on a bowling simulator with their performance in a real bowling alley was conducted. Twenty-five test subjects played two rounds of bowling on a Nintendo Wii and 25 days later on a real bowling alley. Correlations of the scores in the first and second round (test-retest-reliability) and of the scores on the simulator and in reality (criterion validation) were studied and there was tested for any difference between female and male performance. The intraclass correlation coefficient equalled 0.76, i.e. the simulator fairly accurately measured participant performance. In contrast to this there was absolutely no correlation between participants' real bowling abilities and their scores on the simulator (Pearson's r = 0.06). There was no significant difference between female and male abilities. Simulation-based testing and training must be based on evidence. More studies are needed to include an adequate number of subjects. Bowling competence should not be based on Nintendo Wii measurements. Simulated training- and evaluation programmes should be validated before introduction, to ensure consistency with the real world.


Night eating syndrome: impact on bariatric surgery.
Individuals with night eating syndrome (NES) display a time-delayed pattern of food intake, outside the natural circadian rhythm. High prevalence estimates have been reported among bariatric surgery candidates, and some evidence suggests that NES is positively associated with obesity, negatively associated with weight loss efficacy, and follows a chronic course. In order to evaluate current NES theory, and the association between NES and bariatric surgery, literature searches were conducted to identify relevant literature published in English up to 2005. Because of inconsistencies in NES characterization, and significant heterogeneity in study design and methods, a qualitative assessment of NES and its relation to bariatric surgery was then undertaken. Within the literature, variable NES definitions highlight the distinct lack of clarity as to which behavioral features constitute a clinically meaningful entity. Prevalence estimates appear high among persons seeking bariatric surgery; however, no consistent pre- or postoperative demographic, clinical, or psychological factors reliably differentiate NES from non-NES. Further examination of the clinical significance, correlates, and course of NES in general and surgical samples is important, given the link with obesity. The ways in which NES departs from "normal" eating behavior must be clarified. Behavioral and psychological traits of NES need elucidation, and the establishment of agreed diagnostic criteria is essential for research to move forward. Therapy options should focus on aspects of the syndrome that cause greatest impairment, distress, or health risk.


Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response.
The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study, we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. Either CD45(+)/FoxP3(+) Tregs or CD45(+)/FoxP3 (-) non-Tregs were adoptively transferred into Rag1 (-/-) mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. Mitigation of lung inflammation and fibrosis was observed only in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be transforming growth factor-beta (TGFβ)-dependent. Furthermore, polarisation of macrophages from M1 to M2 occurred only in animals that received hAECs and Tregs. This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages, and T-cell subsets is central to understanding the mechanisms by which hAECs elicit lung repair.


Amine functionalized ZrO2 nanoparticles as biocompatible and luminescent probes for ligand specific cellular imaging.
Surface functionalized ZrO2 nanoparticles show strong photoluminescence and are a versatile tool for cellular targeting due to their chemical functionality. They are highly photostable, biocompatible and amenable to coupling with bioligands (e.g. secondary goat anti-rabbit antibody (GAR) and tri-phenyl phosphine (TPP)) via carbodiimide chemistry. Antibody (GAR) functionalized ZrO2 nanoparticles were used to image the nuclear protein Sirt6, whereas triphenyl phosphonium ion (TPP) functionalized ZrO2 nanoparticles specifically targeted the mitochondria. The versatility and easiness of the ZrO2 surface modification opens up new possibilities for designing non-toxic water dispersible and photostable photoluminescent NPs.


High power 2 µm femtosecond fiber laser.
A high power polarization maintaining femtosecond Tm-doped fiber laser system is demonstrated. A chirped fiber Bragg grating with normal dispersion was used to compensate the anomalous dispersion from the regular fiber in the 2 µm seed oscillator to generate mode locked pulses with a pulse repetition rate of 30.84 MHz. After chirped pulse amplification, an amplified power of 78 W was obtained. The pulse was compressed by a chirped volume Bragg grating based pulse compressor. A pulse duration of 760 fs and an average power of 36 W were obtained after compressor.


Host genetics and tuberculosis: Theory of genetic polymorphism and tuberculosis.
Tuberculosis (TB), the leading cause of morbidity and mortality by a single infectious agent, Mycobacterium tuberculosis, is still a major health problem in the world. To date, many studies have shown evidence of association between host genetic polymorphisms and TB susceptibility, including chemokine (C-C motif) ligand 2 (CCL-2)/monocyte chemoattractant protein1 (MCP-1), natural resistance-associated macrophage protein 1 (NRAMP-1)/solute carrier protein 11A1 (SLC11A1), Immunity-related GTPase family M protein (IRGMI), interleukin (IL)-8, toll-like receptor (TLR), and nucleotide-binding oligomerization domain containing protein-2 (NOD-2) genes. Most of these genes participate in immune response, and their polymorphism can alter immunity and lead to genetic susceptibility to TB. This is a special article compiled with reference to various case-control studies, meta-analysis, and other research work on different genes and TB. The genes selected and a number of studies from different countries and ethnic groups for this article are shown below. The genes selected for the study are: NRAMP-1 (SLC11 A1), Vitamin D receptor, low molecular weight polypeptide/transporter with antigen processing, CCL-2/MCP-1, IRGM-1, IL-1, IL-8, IL-10, IL-12, TLR, NOD-2, human leukocyte antigen, mannose-binding lectin, major histocompatibility complex, tumor necrosis factor, P2X 7, epiregulin, SP110, and interferon gamma (IFN-gamma). Genetic polymorphisms in different genes showed variable levels of significance in relation to TB. All these were proved by the researchers using appropriate statistical methods and tools. Based on different research works across the world, there is sufficient evidence to prove that TB is a genetically primed and determined infectious disease caused by M. tuberculosis and the genetic polymorphism is the mechanism that leads to progression from infection to TB disease. Why only 10-15% of the people infected with M. tuberculosis progress toward TB disease has continued to be an unresolved debate. Hence, for provoking thoughts and encouraging more research in the field of genetics and TB I formulated hypothesis and algorithms, and theory. Genetic susceptibility to TB has been substantiated based on the extensive literature review and the research findings that are well narrated.


Inducible synthesis of bacterial luciferase: specificity and kinetics of induction.
A nitrate-utilizing strain of marine bacteria was isolated in which luciferase was inducible by l-arginine. The induction was highly specific; structural analogues of arginine were ineffective, as were other natural amino acids. Several metabolites of arginine acted as weak inducers but did not affect the rate of induction in limiting concentrations of arginine. Hence, these compounds probably exerted a sparing effect on intracellular arginine. The kinetics of induction were followed by measurement of light output from intact cells, under conditions in which in vivo light output was determined only by the luciferase level. No enzyme appeared in the cells for 12 min after the addition of inducer, although the primary structure of the luciferase molecule was apparently synthesized within 2 to 4 min. It is proposed that during the remaining 8 to 10 min a precursor of luciferase was converted to active enzyme. The differential rate of synthesis rose during the first 5 min of induction, apparently as messenger ribonucleic acid accumulates in the cells; thereafter it remained constant for approximately 100 min.


The evaluation of cardiovascular response to exercise in healthy Turkish children.
The purpose of our study was to determine the normal cardiovascular responses of healthy Turkish children to exercise and to determine the reference values. Two hundred and eighty-four healthy children (115 girls, 169 boys) aged 5-14 were enrolled in the study. Exercise time (ET), workload that can be tolerated with exercise (MET value), change in heart rate (A HR), peak systolic and peak diastolic blood pressures (SBPmax and DBPmax), change in systolic blood pressure (delta SBP), and peak rate-pressure product (RPPmax) were positively correlated with age. There was no correlation between peak heart rate (HRmax) and age and there was also no significant increase in change in diastolic blood pressure (delta DBP) with increasing age. The means +/- SD values for ET, workload, HRmax, delta HR, SBPmax, DBPmax, delta SBP, deltaDBP, and RPPmax were 13.18 +/- 1.4 min, 8.56 +/- 0.93 MET, 171.46 +/- 1.91/min, 67.22 +/- 6.65/min, 125.16 +/- 13.36 mmHg, 73.32 +/- 4.06 mmHg, 24.3 +/- 5.96 mmHg, 7.2 +/- 6.9 mmHg, and 21504.7 +/- 2176.4, respectively. The values found in our study may be accepted as reference values of healthy Turkish children for exercise testing. The formula modified as (200-age) x 0.85 is thought to be more suitable to predict the target heart rate in children.


Flotation using sodium dodecyl sulphate and sodium lauroyl isethionate for rapid dewatering of Mg(OH)2 radwaste suspensions.
Mg(OH)2 suspensions were floated utilising sodium dodecyl sulphate (SDS) and sodium lauroyl isethionate (SLI) collectors, for rapid dewatering of radwaste suspensions. Freundlich adsorption isotherms were first used to compare the adsorption densities of SDS and SLI on Mg(OH)2 surfaces, to determine the maximum monolayer coverage capacity, and were found to be 0.11 μmol m-2 at a dosed concentration of 172 μM for SDS and 0.05 μmol m-2 at a dosed concentration of 188 μM for SLI. The natural and salt induced coagulation kinetics of Mg(OH)2 were examined using static light scattering, where the influence of collector adsorption on particle size distributions was also investigated, to probe potential hydrodynamic limitations of flotation. Particle stabilised foam formation was then characterised using a Bikerman column test, where the dynamic foamability indices (DFIs) of SDS and SLI were determined to be 49 × 103 s L mol-1 and 321 × 103 s L mol-1 respectively. Flotation performance was measured, and a collection efficiency factor used to compare the solid-liquid separation ability of mixed 2.5 vol% suspensions with SDS or SLI, as well as MIBC frother. Optimal performance aligned with collector concentrations relating to predicted maximum monolayer coverage, and whilst both surfactants were effective, SDS systems performed better than SLI in all metrics. Recoveries of >80% of the Mg(OH)2 wastes were achieved, whilst only transferring 35% of the water mass at the optimum SDS dosed concentration of 82 μM, likely due to its denser surface adsorption and minimised lamella water entrainment.


Speaking the right language: the scientific method as a framework for a continuous quality improvement program within academic medical research compliance units.
The authors developed a novel continuous quality improvement (CQI) process for academic biomedical research compliance administration. A challenge in developing a quality improvement program in a nonbusiness environment is that the terminology and processes are often foreign. Rather than training staff in an existing quality improvement process, the authors opted to develop a novel process based on the scientific method--a paradigm familiar to all team members. The CQI process included our research compliance units. Unit leaders identified problems in compliance administration where a resolution would have a positive impact and which could be resolved or improved with current resources. They then generated testable hypotheses about a change to standard practice expected to improve the problem, and they developed methods and metrics to assess the impact of the change. The CQI process was managed in a "peer review" environment. The program included processes to reduce the incidence of infections in animal colonies, decrease research protocol-approval times, improve compliance and protection of animal and human research subjects, and improve research protocol quality. This novel CQI approach is well suited to the needs and the unique processes of research compliance administration. Using the scientific method as the improvement paradigm fostered acceptance of the project by unit leaders and facilitated the development of specific improvement projects. These quality initiatives will allow us to improve support for investigators while ensuring that compliance standards continue to be met. We believe that our CQI process can readily be used in other academically based offices of research.


Computational discovery of novel low micromolar human pregnane X receptor antagonists.
Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulation of xenobiotic metabolism and transporter genes. A recent novel pharmacophore for PXR antagonists was developed using three azoles and consisted of two hydrogen bond acceptor regions and two hydrophobic features. This pharmacophore also suggested an overall small binding site that was identified on the outer surface of the receptor at the AF-2 site and validated by docking studies. Using computational approaches to search libraries of known drugs or commercially available molecules is preferred over random screening. We have now described several new smaller antagonists of PXR discovered with the antagonist pharmacophore with in vitro activity in the low micromolar range [S-p-tolyl 3',5-dimethyl-3,5'-biisoxazole-4'-carbothioate (SPB03255) (IC(50), 6.3 microM) and 4-(3-chlorophenyl)-5-(2,4-dichlorobenzylthio)-4H-1,2,4-triazol-3-ol (SPB00574) (IC(50), 24.8 microM)]. We have also used our computational pharmacophore and docking tools to suggest that most of the known PXR antagonists, such as coumestrol and sulforaphane, could also interact on the outer surface of PXR at the AF-2 domain. The involvement of this domain was also suggested by further site-directed mutagenesis work. We have additionally described an FDA approved prodrug, leflunomide (IC(50), 6.8 microM), that seems to be a PXR antagonist in vitro. These observations are important for predicting whether further molecules may interact with PXR as antagonists in vivo with potential therapeutic applications.


The 1.5-A resolution crystal structure of bacterial luciferase in low salt conditions.
Bacterial luciferase is a flavin monooxygenase that catalyzes the oxidation of a long-chain aldehyde and releases energy in the form of visible light. A new crystal form of luciferase cloned from Vibrio harveyi has been grown under low-salt concentrations, which diffract x-rays beyond 1.5-A resolution. The x-ray structure of bacterial luciferase has been refined to a conventional R-factor of 18.2% for all recorded synchrotron data between 30.0 and 1.50-A resolution. Bacterial luciferase is an alpha-beta heterodimer, and the individual subunits fold into a single domain (beta/alpha)8 barrel. The high resolution structure reveals a non-prolyl cis peptide bond that forms between Ala74 and Ala75 in the alpha subunit near the putative active site. This cis peptide bond may have functional significance for creating a cavity at the active site. Bacterial luciferase employs reduced flavin as a substrate rather than a cofactor. The structure presented was determined in the absence of substrates. A comparison of the structural similarities between luciferase and a nonfluorescent flavoprotein, which is expressed in the lux operon of one genus of bioluminescent bacteria, suggests that the two proteins originated from a common ancestor. However, the flavin binding sites of the nonfluorescent protein are likely not representative of the flavin binding site on luciferase. The structure presented here will furnish a detailed molecular model for all bacterial luciferases.


Second-hand smoke exposure: responses from home care and therapeutic group home nurses: a call to action.
Home care visiting nurses and those working in a therapeutic group home expressed concerns about their inadvertent exposure to secondhand smoke when caring for patients who live where cigarettes or tobacco products are used. The American Lung Association Fact Sheet on Secondhand Smoke Exposure cites the Environmental Protection Agency (EPA) classification of secondhand smoke as a cause of human cancer. Secondhand smoke causes approximately 3,400 lung cancer deaths and 22,700 to 69,600 heart disease deaths among adult nonsmokers in the United States each year (American Lung Association, 2009). For this study, home care nurses and those working in a therapeutic group home for the mentally ill in Augusta, Maine, were interviewed. This report describes their exposure and how secondhand smoke can be eliminated with minimal disruption to patient care. The interviewed nurses discussed the repeated exposures they experienced while caring for multiple smoking patients in residences that included apartment buildings and group homes and while transporting patients with private automobiles in which the use of cigarettes, cigarillos, cigars, pipes, and tobacco products can be common. Concerns about secondhand smoke exposures frequently focused on the unpleasant smoke odor retained on clothes and nursing equipment when people smoke during a patient visit. Protective actions also were reported. Strategies for action are discussed.


[Investigation of the factors that contribute to the onset of insomnia in hypertensive patients by using a post-marketing surveillance database].
Many factors contribute to the onset of insomnia. However, few studies have identified the factors related to the onset of insomnia in hypertensive patients. We conducted a pharmacoepidemiologic study to examine the incidence of insomnia in hypertensive patients by using a post-marketing surveillance database. The insomnia onset was defined as the time of first prescription of hypnotics. The insomnia incidence rate in hypertensive patients under antihypertensive therapy was 0.77/100 person-years. The median insomnia onset date was 5 weeks. The insomnia type in 50.2% of the patients was difficulty in initiating sleep. We assessed the factors contributing to insomnia by using a nested case-control design. We selected 10 time-matched controls for every case. The hypotensive effect induced by antihypertensive therapy on the case group was lesser than that on the control group (p<0.01). The odds ratios (ORs) were estimated using multivariate conditional logistic regression. The factors contributing to insomnia onset were α blockers (OR, 2.38; 95% confidence interval [CI], 1.14-4.98), β blockers (OR, 1.54; 95% CI, 0.99-2.39), and calcium channel blockers (OR, 0.62; 95% CI, 0.43-0.90) compared with angiotensin-converting enzyme inhibitors; female sex (OR, 1.76; 95% CI, 1.27-2.44); complication of gastric/duodenal disorders (OR, 2.35; 95% CI, 1.14-4.86) or musculoskeletal system/connective tissue disorders (OR, 2.43; 95% CI, 1.23-4.79); and concomitant antihypertensive therapy (OR, 0.44; 95% CI, 0.31-0.63). This study identified the potential factors that may help to predict insomnia onset in hypertensive patients under antihypertensive therapy.


Efficacy and Safety of Rituximab Therapy for Lupus Nephritis Among SLE Female Patients; a Retrospective Hospital-Based Study.
Renal affection in systemic lupus erythematosus (SLE) is a high-risk manifestation in which novel treatment strategies are required, particularly in patients who show lower response to conventional therapy. Rituximab has been used as an off-label treatment for lupus nephritis (LN) for the last ten years. This study aims to assess the outcome of the use of rituximab to treat LN patients. A retrospective cross-sectional study included 40 LN patients on Rituximab therapy who attended the Rheumatology clinic at Omdurman Military Hospital, Khartoum, Sudan. Between January to July 2020. Data were collected from the hospital records and included demographic, duration of disease and Rituximab doses. Renal biopsy, renal function parameters, albumin-creatinine ratio, hematological parameters and inflammatory markers. Assessment of the outcomes was conducted by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI score). Data were analyzed by using Statistical Package for Social Studies Program (SPSS, V. 21.0. IBM; Chicago). Chi-square test was used as significance test, the P. value was considered as significant at level 0.05 and akk continues variables had a normal distribution with Kolmogorov-Smirnov test. Renal function test showed significant improvement after 6 months of treatment with Rituximab. In addition, the mean of the SLE Activity Index 2000 (SLEDAI 2K) was significantly decreased with remarkable improvement in the histological degree of LN. The histology of renal biopsy of the patients commonly was diffuse proliferative nephritis followed by minimal mesangial glomerulonephritis, mesangial proliferative LN then membranous nephritis respectively. Improvement was common among the patients aged 20-39 years, those with disease duration less than 5 years, who received 4 doses and rituximab as the initial modality. Rituximab therapy is effectively managing patients with lupus nephritis, after 6 months of follow-up, Patients showed remarkable clinical and laboratory improvement.


Glucocorticoids turn over slowly in human adipose tissue in vivo.
Lipophilic plasma glucocorticoids are thought to gain rapid access to intracellular compartments in adipose tissue. In other organs, transport can be regulated in a steroid- and tissue-specific manner. Moreover, 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) generates additional cortisol within adipose. The aim was to measure the rate of exchange of cortisol between plasma and adipose for comparison with rates of intracellular cortisol generation by 11βHSD1. With ethical approval, otherwise healthy females (n = 6) undergoing hysterectomy for benign indications were infused with tracer 9,11,12,12-[(2)H](4)cortisol (d4-cortisol). Adipose biopsies and peripheral venous samples were obtained during surgery after 3.9-5.5 h of infusion. Glucocorticoids were quantified using liquid chromatography tandem mass spectrometry. In plasma, d4-cortisol concentrations and appearance rates of cortisol and d3-cortisol (reflecting 11βHSD1 activity) did not change during surgery. In both omental and sc adipose, cortisol concentrations were lower than in plasma, consistent with differences in corticosteroid binding globulin, and enrichment with d4-cortisol was low (sc, 7.2 ± 0.6%; omental, 7.4 ± 0.7%; vs. plasma, 15.5 ± 1.0%). The rate of accumulation of d4-cortisol in adipose depots was 0.5 ± 0.1 (sc) and 0.4 ± 0.1 (omental) nmol/kg · h, and the proportion of intraadipose cortisol replaced each hour only 10.7 ± 1.0 and 10.4 ± 0.7%, respectively. The contribution of 11βHSD1 to this turnover could not be quantified because very little substrate d3-cortisone accumulated in adipose during infusion. Slow turnover of the adipose glucocorticoid pool suggests that rapid acute fluctuations in circulating cortisol are not reflected in adipose, so that 11βHSD1 activity (previously estimated to generate 9 nmol cortisol/kg · h in sc adipose) may play a relatively important role in modulating activation of glucocorticoid receptors.


Management patterns of non-ST segment elevation acute coronary syndromes in relation to prior coronary revascularization.
Contemporary guidelines support an early invasive strategy for non-ST elevation acute coronary syndrome (NSTE-ACS) patients who had prior coronary revascularization. However, little is known about the management pattern of these patients in "real world." We analyzed 3 consecutive Canadian registries (ACS I, ACS II, and Global Registry of Acute Coronary Events [GRACE]/expanded-GRACE) that recruited 12,483 NSTE-ACS patients from June 1999 to December 2007. We stratified the study population according to prior coronary revascularization status into 4 groups and compared their clinical characteristics, in-hospital use of medications, and cardiac procedures. Of the 12,483 NSTE-ACS patients, 71.2% had no prior revascularization, 14.2% had percutaneous coronary intervention (PCI) only, 9.5% had coronary artery bypass graft surgery (CABG) only, and 5% had both PCI and CABG. Compared to their counterparts without prior revascularization, patients with previous PCI and/or CABG were more likely to be male, to have diabetes, myocardial infarction, and heart failure but less likely to have ST-segment deviation or positive cardiac biomarker on presentation. Early use of evidence-based medications was higher among patients with previous PCI only and lower among patients with previous CABG only. After adjusting for possible confounders including GRACE risk score, prior PCI was independently associated with in-hospital use of cardiac catheterization (adjusted odds ratio [OR] 1.18, 95% CI 1.04-1.34, P = .008). In contrast, previous CABG was an independent negative predictor (adjusted OR .77, 95% CI 0.68-0.87, P < .001). There was no significant interaction (P = .93) between previous PCI and CABG. The NSTE-ACS patients with previous PCI were more likely to be treated invasively. Conversely, patients with prior CABG less frequently received invasive therapy. Future studies should determine the appropriateness of this treatment discrepancy.


Practical training framework for fitting a function and its derivatives.
This paper describes a practical framework for using multilayer feedforward neural networks to simultaneously fit both a function and its first derivatives. This framework involves two steps. The first step is to train the network to optimize a performance index, which includes both the error in fitting the function and the error in fitting the derivatives. The second step is to prune the network by removing neurons that cause overfitting and then to retrain it. This paper describes two novel types of overfitting that are only observed when simultaneously fitting both a function and its first derivatives. A new pruning algorithm is proposed to eliminate these types of overfitting. Experimental results show that the pruning algorithm successfully eliminates the overfitting and produces the smoothest responses and the best generalization among all the training algorithms that we have tested.


A contemporary examination of workplace learning culture: an ethnomethodology study.
Creating and maintaining a sustainable workforce is currently an international concern. Extensive literature suggest that students and staff need to be 'engaged', that is they need to interact with the health team if they are to maximise learning opportunities. Despite many studies since the 1970s into what creates a 'good' learning environment, ongoing issues continue to challenge healthcare organisations and educators. A 'good' learning environment has been an intangible element for many professions as learning is hindered by the complexity of practice and by limitations on practitioners' time available to assist and guide novices. This study sought to explore the nature of the learning interactions and experiences in clinical nursing practice that enhance a 'good' workplace learning culture for both nursing students and qualified nurses. An ethnomethodology study. A range of clinical settings in Victoria and Queensland, Australia. Students and registered nurses (n=95). Fieldwork observations were carried out on student nurses and registered nurses, followed by an individual interview with each participant. An iterative approach to analysis was undertaken; field notes of observations were reviewed, interviews transcribed verbatim and entered into NVivo10. Major themes were then extracted. Three central themes: learning by doing, navigating through communication, and 'entrustability', emerged providing insights into common practices potentially enhancing or detracting from learning in the workplace. Students' and registered nurses' learning is constrained by a myriad of interactions and embedded workplace practices, which can either enhance the individual's opportunities for learning or detract from the richness of affordances that healthcare workplace settings have to offer. Until the culture/or routine practices of the healthcare workplace are challenged, the trust and meaningful communication essential to learning in practice, will be achievable only serendipitously.


Role of Academics in Transferring Knowledge and Skills on Artificial Intelligence, Internet of Things and Edge Computing.
Universities play an essential role in preparing human resources for the industry of the future. By providing the proper knowledge, they can ensure that graduates will be able to adapt to the ever-changing industrial sector. However, to achieve this, the courses provided by academia must cover the current and future industrial needs by considering the trends in scientific research and emerging technologies such as Artificial Intelligence (AI), Internet of Things (IoT), and Edge Computing (EC). This work presents the survey results conducted among academics to assess the current state of university courses, regarding the level of knowledge and skills provided to students about the Internet of Things, Artificial Intelligence, and Edge Computing. The novelty of the work is that (a) the research was carried out in several European countries, (b) the current curricula of universities from different countries were analyzed, and (c) the results present the teachers' perspective. To conduct the research, the analysis of the relevant literature took place initially to explore the issues of the presented subject, which will increasingly concern the industry in the near future. Based on the literature review results and analysis of the universities' curricula involved in this study, a questionnaire was prepared and shared with academics. The outcomes of the analysis reveal the areas that require more attention from scholars and possibly modernization of curricula.


Development of a light-activated STING agonist.
The STING pathway is critical to innate immunity and is being investigated as a potential therapeutic target. Existing agents targeting STING suffer from several undesirable effects, particularly the possibility of systematic activation, which increases the risk of autoimmune disorders. In this proof-of-concept study, we report the development of a light-activated STING agonist, based on the potent compound SR-717. We first screened the activity of the non-caged agonist toward 5 human STING variants to identify the most viable target. A photocaged agonist was designed and synthesized in order to block an essential interaction between the carboxy acid group of the ligand with the R238 residue of the STING protein. We then investigated the selective activation of STING with the photocaged agonist, demonstrating an irradiation-dependent response. The development and characterization of this selective agonist expands the growing toolbox of conditionally controlled STING agonists to avoid systematic immune activation.


Evidence that intermediate filament reorganization is induced by ATP-dependent contraction of the actomyosin cortex in permeabilized fibroblasts.
Intermediate filaments (IFs) undergo specific rearrangements in cells, some aspects of which can be induced experimentally. Centripetal aggregation of the IF network, for example, can be produced by a variety of perturbations. However, the source of motive force is clear for neither in vivo nor experimentally generated IF movements, since, unlike microtubules and actin filaments, IFs have no known force-generating system directly associated with them. We recently obtained evidence that the drug-induced aggregation of vimentin IFs in fibroblasts is an active event, which requires ATP and involves the actin cytoskeleton. In the present study, we sought to test the hypothesis that IF aggregation is driven by a centripetally directed contraction of the actomyosin cortex. To that end, we have permeabilized fibroblasts with Triton X-100 in a stabilizing buffer and reactivated cytoskeletal movements in vitro, under defined solution conditions. Upon nucleotide treatment, these permeabilized cells undergo a nucleotide-dependent centripetal aggregation of vimentin IFs similar in appearance and time course to that induced in intact cells by drug treatment. During in vitro IF aggregation, the permeabilized cells remain fully spread and adherent to the substratum, and the distal ends of the microtubules and actin microfilaments retain their positions in the cell periphery, IF aggregation is accompanied by a contraction of F-actin and myosin into focal aggregates in the same perinuclear region in which the IFs accumulate. If permeabilized cells are treated with the actin-severing protein gelsolin prior to the reactivation of IF movement, the actin cytoskeleton is eliminated and IF aggregation fails to occur when ATP is added. These results strongly support a model in which the motive force for IF movement is supplied indirectly by association with a contracting actomyosin network.


Phylogenomic analyses recover a clade of large-bodied decapodiform cephalopods.
Phylogenetic relationships among the squids and cuttlefishes (Cephalopoda:Decapodiformes) have resisted clarification for decades, despite multiple analyses of morphological, molecular and combined data sets. More recently, analyses of complete mitochondrial genomes and hundreds of nuclear loci have yielded similarly ambiguous results. In this study, we re-evaluate hypotheses of decapodiform relationships by increasing taxonomic breadth and utilizing higher-quality genome and transcriptome data for several taxa. We also employ analytical approaches to (1) identify contamination in transcriptome data, (2) better assess model adequacy, and (3) account for potential biases. Using this larger data set, we consistently recover a clade comprising Myopsida (closed-eye squid), Sepiida (cuttlefishes), and Oegopsida (open-eye squid) that is sister to a Sepiolida (bobtail and bottletail squid) clade. Idiosepiida (pygmy squid) is consistently recovered as the sister group to all sampled decapodiform lineages. Further, a weighted Shimodaira-Hasegawa test applied to one of our larger data matrices rejects all alternatives to these ordinal-level relationships. At present, available nuclear genome-scale data support nested clades of relatively large-bodied decapodiform cephalopods to the exclusion of pygmy squids, but improved taxon sampling and additional genomic data will be needed to test these novel hypotheses rigorously.


Blue LED light exposure develops intracellular reactive oxygen species, lipid peroxidation, and subsequent cellular injuries in cultured bovine retinal pigment epithelial cells.
The effects of blue light emitter diode (LED) light exposure on retinal pigment epithelial cells (RPE cells) were examined to detect cellular damage or change and to clarify its mechanisms. The RPE cells were cultured and exposed by blue (470 nm) LED at 4.8 mW/cm(2). The cellular viability was determined by XTT assay and cellular injury was determined by the lactate dehydrogenase activity in medium. Intracellular reactive oxygen species (ROS) generation was determined by confocal laser microscope image analysis using dihydrorhodamine 123 and lipid peroxidation was determined by 4-hydroxy-2-nonenal protein-adducts immunofluorescent staining (HNE). At 24 h after 50 J/cm(2) exposures, cellular viability was significantly decreased to 74% and cellular injury was significantly increased to 365% of control. Immediately after the light exposure, ROS generation was significantly increased to 154%, 177%, and 395% of control and HNE intensity was increased to 211%, 359%, and 746% of control by 1, 10, and 50 J/cm(2), respectively. These results suggest, at least in part, that oxidative stress is an early step leading to cellular damage by blue LED exposure and cellular oxidative damage would be caused by the blue light exposure at even lower dose (1, 10 J/cm(2)).


Flow focusing through gels as a tool to generate 3D concentration profiles in hydrogel-filled microfluidic chips.
Laminar flow patterning is an iconic microfluidic technology used to deliver chemicals to specific regions on a two-dimensional surface with high spatial fidelity. Here we present a novel extension of this technology using Darcy flow within a three-dimensional (3D) hydrogel. Our test device is a simple 3-inlet microfluidic channel, totally filled with collagen, a cured biological hydrogel, where the concentration profiles of solutes are manipulated via the inlet pressures. This method allows solutes to be delivered with 50 micron accuracy within the gel, as we evidence by controlling concentration profiles of 40 kDa and 1 kDa fluorescent polysaccharide dyes. Furthermore, we design and test a 3D-printed version of our device with an extra two inlets for control of the vertical position of the concentration profile, demonstrating that this method is easily extensible to control of the concentration profile in 3D.


Transmural variation and anisotropy of microvascular flow conductivity in the rat myocardium.
Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.


The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis.
most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. this was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNβ-1a), subcutaneous IFNβ-1a, IFNβ-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs.


Microvascular pressure in venules of skeletal muscle during arterial pressure reduction.
It has been suggested from whole organ studies that the viscosity of blood in skeletal muscle venules varies inversely with flow over physiological flow ranges. If this is the case, the hydrostatic pressure gradient in venules should change less than flow as flow is altered. To test this hypothesis, pressure in venules of cat sartorius muscle was measured during stepwise arterial pressure reduction to 20 mmHg. Large vein pressure remained constant at about 5 mmHg. Average pressures in the large venules (40-185 microns) ranged from 13.6 to 10.0 mmHg. The difference between pressure in these venules and large vein pressure fell in proportion to the reduction in blood pressure and blood flow. Pressures in the smallest venules studied (25 microns) averaged 19.7 +/- 6.2 (SD) mmHg. The pressure difference between the smallest venules and the large vein fell less than the arteriovenous pressure difference or blood flow when arterial pressure was reduced. During reactive hyperemia the pressure gradient between the smallest venules and the large vein rose proportionately less than blood flow. The stability of pressure in the smallest venules is consistent with the hypothesis that blood viscosity varies inversely with flow rate.


Mosaicism for trisomy 12: four cases with varying outcomes.
Trisomy 12 observed in chorionic villus sampling (CVS) may reflect generalized mosaicism or indicate mosaicism confined to only the placenta. In this report, four cases of trisomy 12 observed in CVS or cultured placental biopsies with varying outcomes are presented. Seven dinucleotide repeat polymorphisms for chromosome 12 were used to determine the chromosome 12 origins in the fetus or child and to delineate the mechanism(s) that gave rise to the trisomy. In two cases (cases A and C), the mosaicism was confined to the placenta, resulting in normal liveborns. Although, in one case, the molecular results suggested an apparent duplication of one paternal chromosome 12 in the placenta, normal biparental inheritance was found in the diploid fetal cell line in both cases. In two other cases (cases B and D), trisomy 12 was observed in both extraembryonic and fetal tissues. In one of these pregnancies, a child was born by Caesarean section at 37 weeks because of intrauterine growth retardation and oligohydramnios, and resulted in neonatal death. Molecular markers and fluorescence in situ hybridization (FISH) revealed low-level trisomy 12 mosaicism in the spleen. In the fourth case, fetal abnormalities were detected on ultrasound and low-level trisomy 12 mosaicism was observed in amniotic fluid cells using conventional cytogenetics and FISH. Molecular markers revealed a maternal meiosis I non-disjunction of chromosome 12 in DNA from a cultured placental biopsy. Although predicting the outcomes of pregnancies involving confined placental mosaicism remains difficult, molecular techniques are valuable tools for distinguishing uniparental from biparental disomy and mechanisms of mosaicism.


General Class of Continuous Variable Entanglement Criteria.
We present a general class of entanglement criteria for continuous variable systems. Our criteria are based on the Husimi Q distribution and allow for optimization over the set of all concave functions rendering them extremely general and versatile. We show that several entropic criteria and second moment criteria are obtained as special cases. Our criteria reveal entanglement of families of states undetected by any commonly used criteria and provide clear advantages under typical experimental constraints such as finite detector resolution and measurement statistics.


Exposure to Inorganic Arsenic in Rice in Brazil: A Human Health Risk Assessment.
In certain populations, rice is the main source of exposure to inorganic arsenic (iAs), which is associated with cancer and non-cancer effects. Although rice is a staple food in Brazil, there have been few studies about the health risks for the Brazilian population. The objective of this study was to assess the risks of exposure to iAs from white rice and brown rice in Brazil, in terms of the carcinogenic and non-carcinogenic effects, and to propose measures to mitigate those risks. The incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) were calculated in a probabilistic framework. The mean ILCR was 1.5 × 10-4 for white rice and 6.0 × 10-6 for brown rice. The HQ for white and brown rice was under 1. The ILCR for white and brown rice was high, even though the iAs concentration in rice is below the maximum contaminant level. The risk for brown rice consumption was lower, which was not expected. Various mitigation measures discussed in this report are estimated to reduce the risk from rice consumption by 5-67%. With the support of public policies, measures to reduce these risks for the Brazilian population would have a positive impact on public health.


[Obstetric management of fetal growth retardation].
Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.


Reduction of Salmonella in ground chicken using a bacteriophage.
This study's goal was to ascertain the effectiveness of a commercially available Salmonella bacteriophage during ground chicken production focusing on: water source, different Salmonella serovars, and time. Salmonella-free boneless, skinless chicken meat was inoculated with 4.0 Log CFU/cm2 of either a cocktail of 3 Salmonella isolates derived from ground chicken (GC) or a cocktail of 3 Salmonella strains not isolated from ground chicken (non-GC). Bacteriophages were spread onto the chicken using sterile tap or filtered water for 30 min or 8 h. Salmonella was recovered using standard plating method. Greater Salmonella reduction was observed when the bacteriophage was diluted in sterile tap water than in sterile filtered water: 0.39 Log CFU/cm2 and 0.23 Log CFU/cm2 reduction after 30 min, respectively (P < 0.05). The non-GC isolates showed reductions of 0.71 Log CFU/cm2 and 0.90 Log CFU/cm2 after 30 min and 8 h, respectively (P < 0.05). The GC isolates were less sensitive to the bacteriophage: 0.39 Log CFU/cm2 and 0.67 Log CFU/cm2 reductions after 30 min and 8 h, respectively (P < 0.05). In conclusion, bacteriophage reduction was dependent on water used to dilute the bacteriophage, Salmonella's susceptibility to the bacteriophage, and treatment time.


A Case of Hidradenitis Suppurativa in a Genetically Confirmed Lowe Syndrome Patient.
Lowe syndrome (LS), also known as oculocerebrorenal syndrome, is an X-linked multisystemic disorder caused by mutations in OCRL1, which encodes a member of the inositol-5-phosphatase family. As implied by its name, congenital cataracts, defects in the central nervous system, and renal manifestations are the main symptoms. Early hidradenitis suppurativa (HS) occurrence in Dent disease 2 (DD2), which is a mild variant of LS and shares the OCRL1 gene mutation, has been reported, although not in LS patients. Here, we report a case of HS in a 17-year-old boy with genetically confirmed LS, which suggests that defects in the OCRL1 gene may contribute to HS pathogenesis.


[Spontaneous rupture of the esophagus: diagnostic problem in the emergency service].
We present two case of a spontaneous perforation of the esophagus (Boerhaave's syndrome), they were associated with different symptoms. Both of them the diagnosis was make on the second admission to the emergency service. The Boerhaave's syndrome is potentially lethal, relatively rare and the difficult diagnosis in the initial phases. It's a life threatening condition demanding early diagnosis and rapid aggressive management to prevent fulminant death.