Socioeconomic environmental factors and hospitalization for acute bronchiolitis during infancy.
Bronchiolitis is a major cause of hospitalization during infancy. The aim of this study was to evaluate the influence of socioeconomic factors on the hospitalization of infants with bronchiolitis. All infants below 1 y of age living in the city of Malmö, Sweden, and hospitalized at the University Hospital. Malmö, owing to bronchiolitis during the years 1998 and 1999 were identified. The bronchiolitis hospitalization rates (BHRs) were determined for the infants living in each of the 10 different administrative residential areas of Malmö and correlated with socioeconomic factors (percentage of immigrants, per capita income, unemployment rate and households receiving social benefit) in the respective residential areas. The severity of the disease on admission and during hospital care was assessed by comparing oxygen saturation, days with supplemental oxygen and length of stay. BHR varied more than fourfold between the 10 residential areas. BHR varied significantly with per capita income and the percentage of immigrants. Infants living in the area with the highest social burden were hospitalized almost twice as often as those from the rest of the city, but the severity of disease was similar. The association between socioeconomic factors and hospitalization indicates that these factors may have a significant influence on the hospitalization rate in bronchiolitis during infancy.


Measuring molecular rupture forces between single actin filaments and actin-binding proteins.
Actin-binding proteins (ABPs) regulate the assembly of actin filaments (F-actin) into networks and bundles that provide the structural integrity of the cell. Two of these ABPs, filamin and alpha-actinin, have been extensively used to model the mechanical properties of actin networks grown in vitro; however, there is a lack in the understanding of how the molecular interactions between ABPs and F-actin regulate the dynamic properties of the cytoskeleton. Here, we present a native-like assay geometry to test the rupture force of a complex formed by an ABP linking two quasiparallel actin filaments. We readily demonstrate the adaptability of this assay by testing it with two different ABPs: filamin and alpha-actinin. For filamin/actin and alpha-actinin/actin, we measured similar rupture forces of 40-80 pN for loading rates between 4 and 50 pN/s. Both ABP unfolding and conformational transition events were observed, demonstrating that both are important and may be a significant mechanism for the temporal regulation of the mechanical properties of the actin cytoskeleton. With this modular, single-molecule assay, a wide range of ABP/actin interactions can be studied to better understand cytoskeletal and cell dynamics.


Proton Chelating Ligands Drive Improved Chemical Separations for Rhodium.
Current methods for the extraction of rhodium carry the highest carbon footprint and worst pollution metrics of all of the elements used in modern technological applications. Improving upon existing methods is made difficult by the limited understanding of the molecular-level chemistry occurring in extraction processes, particularly in the hydrometallurgical separation step. While many of the precious metals can be separated by solvent extraction, there currently exist no commercial extractants for Rh. This is due to its complicated mixed speciation upon leaching into hydrochloric acid, which gives rise to difficulties in designing effective reagents for solvent extraction. Herein we show that the diamidoamine reagent N- n-hexylbis( N-methyl- N- n-octylethylamide)amine transports Rh(III) from aqueous HCl into an organic phase as the monoaquated dianion [RhCl5(H2O)]2- through the formation of an outer-sphere assembly; this assembly has been characterized by experimentation (slope analysis, FT-IR and NMR spectroscopy, EXAFS, SANS, and ESI-MS) and computational modeling. The paper demonstrates the importance of applying a broad range of techniques to obtain a convincing mode of action for the complex processes involved in anion recognition in the solution phase. A consistent and comprehensive understanding of how the ligand operates to achieve Rh(III) selectivity over the competitor anion Cl- has emerged. This knowledge will guide the design of extractants and thus offers promise for improving the sustainability of metal extraction from both traditional mining sources and the recycling of secondary source materials.


Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program.
Injection drug users constitute 60% of the more than 4 million people in the United States with hepatitis C virus (HCV), including many methadone maintenance patients. Few data exist describing clinical outcomes for patients receiving HCV treatment on-site in methadone maintenance settings. In this retrospective study, we describe clinical outcomes for 73 patients receiving HCV treatment on-site in a methadone maintenance treatment program. Fifty-five percent of patients achieved end-of-treatment response, and 45% achieved sustained viral response. These treatment response rates are nearly equivalent to previously published HCV treatment response rates, despite high prevalences of ongoing drug use (49%), psychiatric comorbidity (67%), and HIV coinfection (32%). These data show that on-site HCV treatment with pegylated interferon and ribavirin is effective in methadone-maintained patients, many of whom are active drug users, psychiatrically ill, or HIV coinfected, and that methadone maintenance treatment programs represent an opportunity to safely treat chronic hepatitis C.


Hydrolysis and condensation of monobutyltin chloride: reaction process analysis with DFT.
As the initial process of preparing transparent conductive oxide materials from monobutyltin chloride (MBTC) to tin oxide, the hydrolysis and condensation of MBTC to form a dimer Sn2 play a critical role. However, the specific mechanism of this process is still unclear. Here we develop a step-by-step searching method based on density functional theory calculation and empirical chemical criteria to determine possible reaction pathways and reveal the most likely reaction mechanism. The wave function analyses of various intermediate species provide more insights into the changes of atomic charge population, chemical bond strength, and coordination situation of central tin in the reaction process. Further investigation on the ring-containing Sn2 reveals the existence of unique three-center four-electron (3c-4e) interactions to stabilize the four-membered Sn2O2 ring structure, which serves as the true driving force for dimerization reaction. These results provide a more detailed understanding of the hydrolysis and condensation process of MBTC and would be helpful for the future optimization of the preparation process of tin oxide films.


Fabrication of coated polymer microneedles for transdermal drug delivery.
As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip-coating process is a versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip-coating process. In this study, to fabricate coated polymer microneedles with controlled drug loading, an adjustable apparatus that can be lifted and lowered was designed to immerse a polylactic acid (PLA) MN patch in the coating solutions. Using the coating solution containing 0.5% (w/w) sulforhodamine B, the drug loadings were up to 12ng, 14ng, and 18ng per needle for the MNs with heights of 550μm, 650μm, and 750μm, respectively. Moreover, for the MNs with a 650-μm height, when increasing the viscosity of the coating solutions from 150mPa·s to 1360mPa·s, 2850mPa·s, and 8200mPa·s, the drug loading increased from 2.5ng to 5ng, 14ng, and 22ng per needle, respectively. Meanwhile, the drug delivery efficiencies of these MNs were approximately 90%. In the insertion experiments, the MNs could successfully penetrate the skin and deliver the coated drug with approximately 90% efficiency when the MN tips were exposed to the outer environment. In vivo studies in mice indicated that the coated polymer MNs continuously delivered drugs, and the skin recovered without any injuries. These results demonstrated that the coated polymer MN was a safe and effective method for transdermal drug delivery.


NearTree, a data structure and a software toolkit for the nearest-neighbor problem.
Many problems in crystallography and other fields can be treated as nearest-neighbor problems. The neartree data structure provides a flexible way to organize and retrieve metric data. In some cases, it can provide near-optimal performance. NearTree is a software tool that constructs neartrees and provides a number of different query tools.


A convergent synthetic approach to the nucleoside-type liposidomycin antibiotics.
[reaction: see text] A synthetic approach toward the liposidomycins, a family of complex nucleoside-type antibiotics, is reported based on the synthesis of epoxy-amides derived from the reaction of sulfur ylides with the uridyl aldehyde derivative 6. To this end, the epoxy-amide derivative of indoline 14 was stereoselectively prepared and, after treatment with DDQ, transformed into the corresponding N-indole epoxyamide 15. The indole 15 provides ready access to a variety of structures related to the diazepanone core present in the liposidomycins by reaction with a variety of amines.


Nerolidol production in agroinfiltrated tobacco: Impact of protein stability and membrane targeting of strawberry (Fragraria ananassa) NEROLIDOL SYNTHASE1.
The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP), mediates plant-insect interactions across multiple trophic levels with major implications for pest management in agriculture. We compared nerolidol engineering strategies in tobacco using agroinfiltration to transiently express strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS), we have determined that FaNES1 directed to the ER via fusion to the transmembrane domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed significant improvements in terms of transcript levels, protein accumulation, and volatile production when compared to its cytosolic form. However, the highest levels of nerolidol production were observed when FaNES1 was fused to GFP and expressed in the cytosol. This SPME-GCMS method afforded a limit of detection and quantification of 1.54 and 5.13 pg, respectively. Nerolidol production levels, which ranged from 0.5 to 3.0 μg/g F.W., correlated more strongly to the accumulation of recombinant protein than transcript level, the former being highest in FaNES-GFP transfected plants. These results indicate that while the ER may represent an enriched source of FDP that can be exploited in metabolic engineering, protein accumulation is a better predictor of sesquiterpene production.


[Function of plant homeodomain-finger proteins in vernalization pathway in Arabidopsis and other cruciferous plants].
Vernalization makes Arabidopsis and other cruciferous plants flowering earlier. During this process, an important plant homeodomain-finger(PHD-finger) protein named VIN3 is involved. The PHD domain was a conserved zinc-finger domain in eukaryotic organism. It used to take part in the interaction between proteins, especially the modification on histone of nucleosome, such as methylation, acetylation and phosphorylation. In vernaliazation pathway, the proteins translated by VERNALIZATION INSENSITIVE 3(VIN3) and homologous genes could result in methylation on H3K9 and H3K27 and deacetylation on H3K9 and H3K14 on chromatin histone of FLOWERING LOCUS C, a gene that inhibited flowering. The structure state of FLC would be changed from relaxation into compression. Then the transcription activity of FLC could be restrained and it couldn't inhibit flowering any more, so it would induce flowering earlier. This paper reviewed the function of PHD-finger proteins in vernalization pathway in Arabidopsis and other cruciferous plants, and overviewed the vernalization mechanism.


Microvascular arterial disease of the brain and the heart: a shared pathogenesis.
Microvascular arterial disease in the heart manifest as coronary microvascular dysfunction. This condition causes microvascular angina and is associated increased morbidity and mortality. Microvascular arterial disease in the brain is referred to as cerebrovascular small vessel disease. This is responsible for 45% of dementias and 25% of ischaemic strokes. The heart and brain share similar vascular anatomy and common pathogenic risk factors are associated with the development of both coronary microvascular dysfunction and cerebrovascular small vessel disease. Microvascular disease in the heart and brain also appear to share common multisystem pathophysiological mechanisms. Further studies on diagnostic approaches, epidemiology and development of disease-modifying therapy seem warranted.


A new repetitive element of the CR1 family downstream of the chicken vitellogenin gene.
We have analyzed a repetitive DNA sequence found in the 3'-flanking region of the chicken vitellogenin gene. By its sequence, the repetitive DNA has been identified as a hitherto unreported member of the chicken CR1 family of repetitive elements. The CR1 sequence displays the structural characteristics of a long terminal repeat located at the 3' end of an avian retrovirus. The CR1 element lies 2.2 kb downstream of the vitellogenin gene and 'points' away from the gene rather than toward it. In this respect, this element differs from other CR1 repeats. The CR1 element is embedded in a region showing changes in chromatin structure implying a potential role for this sequence in determining the structural state of the local chromatin.


Untreated intra-articular entrapment of the medial humeral epicondyle.
Six children with entrapment of the medial epicondyle in the elbow after closed reduction of a posterior dislocation were seen an average of 14 weeks after injury. The elbows were painful and the average range of flexion was 22 degrees. Two children had ulnar nerve involvement which recovered after operation. The epicondyle was removed from the joint and either reattached to the humerus or excised, and the muscles reattached. Two children had anterior transposition of the ulnar nerve, one for pre-operative hyperaesthesia, and the other to relieve tension on the nerve. At follow-up, at an average of 15 months after operation, flexion had increased fivefold, none of the children had pain and all were leading normal lives.


Bioluminescent cell-based NAD(P)/NAD(P)H assays for rapid dinucleotide measurement and inhibitor screening.
Abstract The central role of nicotinamide adenine dinucleotides in cellular energy metabolism and signaling makes them important nodes that link the metabolic state of cells with energy homeostasis and gene regulation. In this study, we describe the implementation of cell-based bioluminescence assays for rapid and sensitive measurement of those important redox cofactors. We show that the sensitivity of the assays (limit of detection ∼0.5 nM) enables the selective detection of total amounts of nonphosphorylated or phosphorylated dinucleotides directly in cell lysates. The total amount of NAD+NADH or NADP+NADPH levels can be detected in as low as 300 or 600 cells/well, respectively. The signal remains linear up to 5,000 cells/well with the maximum signal-to-background ratios ranging from 100 to 200 for NAD+NADH and from 50 to 100 for NADP+NADPH detection. The assays are robust (Z' value >0.7) and the inhibitor response curves generated using a known NAD biosynthetic pathway inhibitor FK866 correlate well with the reported data. More importantly, by multiplexing the dinucleotide detection assays with a fluorescent nonmetabolic cell viability assay, we show that dinucleotide levels can be decreased dramatically (>80%) by FK866 treatment before changes in cell viability are detected. The utility of the assays to identify modulators of intracellular nicotinamide adenine dinucleotide levels was further confirmed using an oncology active compound library, where novel dinucleotide regulating compounds were identified. For example, the histone deacetylase inhibitor entinostat was a potent inhibitor of cellular nicotinamide adenine dinucleotides, whereas the selective estrogen receptor modulator raloxifene unexpectedly caused a twofold increase in cellular nicotinamide adenine dinucleotide levels.


Structure and specificity of the bacterial cysteine methyltransferase effector NleE suggests a novel substrate in human DNA repair pathway.
Enteropathogenic E. coli (EPEC) and related enterobacteria rely on a type III secretion system (T3SS) effector NleE to block host NF-κB signaling. NleE is a first in class, novel S-adenosyl-L-methionine (SAM)-dependent methyltransferase that methylates a zinc-coordinating cysteine in the Npl4-like Zinc Finger (NZF) domains in TAB2/3 adaptors in the NF-κB pathway, but its mechanism of action and other human substrates are unknown. Here we solve crystal structure of NleE-SAM complex, which reveals a methyltransferase fold different from those of known ones. The SAM, cradled snugly at the bottom of a deep and narrow cavity, adopts a unique conformation ready for nucleophilic attack by the methyl acceptor. The substrate NZF domain can be well docked into the cavity, and molecular dynamic simulation indicates that Cys673 in TAB2-NZF is spatially and energetically favorable for attacking the SAM. We further identify a new NleE substrate, ZRANB3, that functions in PCNA binding and remodeling of stalled replication forks at the DNA damage sites. Specific inactivation of the NZF domain in ZRANB3 by NleE offers a unique opportunity to suggest that ZRANB3-NZF domain functions in DNA repair processes other than ZRANB3 recruitment to DNA damage sites. Our analyses suggest a novel and unexpected link between EPEC infection, virulence proteins and genome integrity.


Impacts of anions on the oxygen reduction reaction kinetics on platinum and palladium surfaces in alkaline solutions.
The fundamental understanding of the impacts induced by anions on oxygen reduction reaction (ORR) in alkaline media is of great importance in the design of more advanced catalysts for alkaline fuel cells (AFC). In this study, the specific adsorption of F-, Cl-, ClO4-, CO32-, SO42-, and citrate anions on Pt/C and Pd/C catalysts, and their impacts on the ORR kinetics in alkaline solutions were systematically studied. It was found that F-, Cl- and ClO4- did not specifically adsorb on Pt or Pd surfaces and had no poisoning effect on ORR. CO32- and SO42- had significant effects on Pt/C and lowered the activity even at a very low concentration. On the other hand, their impacts on Pd/C were negligible. Self-dissociation of citrate anions was found to occur on both Pt/C and Pd/C in the H adsorption/desorption and double layer regions. For the first time, surface enhanced infrared absorption spectroscopy (SEIRAS) with the attenuated total reflection (ATR) technique was used to investigate the self-dissociation of citrate on Pt and Pd thin film electrodes. The breaking of carboxylic groups and the carbon backbone was proposed as a possible dissociation pathway for citrate. The adsorbed species have a negligible effect on ORR activity on Pt/C as they are removed by oxidation before 0.75 V. In contrast, their oxidation on Pd/C surfaces is not completed until 0.91 V, which causes a lower ORR activity observed in rotating disk electrode measurements. The findings in this paper emphasize the importance of specific adsorption of anions and double-layer interfacial effects on the ORR activity measurement in alkaline solutions.


Impact of cefoperazone therapy on fecal flora.
To evaluate the effects of parenteral cefoperazone therapy upon human fecal flora, fecal specimens obtained from four patients before and during therapy (as well as after therapy for one patient) were cultured quantitatively for facultative, aerobic, and anaerobic bacteria and for fungi. Cefoperazone therapy was associated with major changes in fecal flora. There was suppression to undetectable levels or an appreciable reduction in all anaerobic bacteria as well as suppression of all initially detected Enterobacteriaceae. During therapy, there was acquisition or an increase in counts of Candida spp., so that these became the most numerous fecal microorganisms in all patients. In addition, Pseudomonas spp. and coagulase-negative Staphylococcus sp. were acquired by three patients. These marked alterations in flora have potentially important consequences.


Electrochemical and spectrophotometrical investigation of the electron-accepting strength of organic superelectrophiles: X-ray structure of their charge transfer complexes with tetrathiafulvalene.
Nitro Benzoxadiazoles (benzofurazans), benzoxadiazoles-N-oxide (benzofuroxans) and benzothiadiazoles are ranked amongst the strongest electrophiles known to date. In the past twenty years, their propensity to act as electron organic acceptors has been less studied. In this paper, we report on the study of their electrochemical behavior and on the structural characterization of charge transfer complexes (CTC) deriving from their interaction with tetrathiafulvalene (TTF) derivatives, both in solution and in the solid state. The first half wave reduction potentials (E(1/2)(I)) associated with a reversible monoelectronic transfer process of a large set of nitro substituted benzoxadiazoles (benzofurazans), benzoxadiazoles-N-oxide (benzofuroxans) and benzothiadiazoles have been determined through a detailed electrochemical approach in acetonitrile with a microelectrode network using the ferrocene as an internal reference potential in this electrochemical study. Determination of the electron affinity (EA(CT)) of this series of substituted electrodeficient heteroaromatics as well as their LUMO energy was performed using the Charge Transfer Spectroscopic (CTS) method in solution and by DFT calculations, respectively. The use of the correlation EA(CT) versus the reversible half wave potential (E(1/2)(I)) appears to be a useful tool to estimate readily the E(1/2)(I) or EA(CT) values when they cannot be experimentally determined. The diffusion coefficient of these electrophiles has, for the first time, been determined in acetonitrile. These air stable electrodeficient heteroaromatics have been explored as potential new organic acceptors in the formation of charge transfer (CT) complexes with TTF derivatives. Crystallographic data of two CT complexes with TTF (especially the C-C and C-S bond lengths of the TTF moieties) indicate that these complexes exhibit weak electron delocalization and that both molecules remain neutral. Their resulting levels of charge transfer were probed using UV-visible, IR spectroscopy and by DFT calculations.


Depression in diabetic patients attending University of Gondar Hospital Diabetic Clinic, Northwest Ethiopia.
Diabetes mellitus, frequently associated with comorbid depression, contributes to the double burden of individual patients and community. Depression remains undiagnosed in as many as 50%-75% of diabetes cases. This study aimed to determine the prevalence and associated factors of depression among diabetic patients attending the University of Gondar Hospital Diabetic Clinic, Northwest Ethiopia. An institution-based cross-sectional study was conducted from March to May 2014 among 422 sampled diabetic patients attending the University of Gondar Hospital Diabetic Clinic. The participants were selected using systematic random sampling. Data were collected by face-to-face interview using a standardized and pretested questionnaire linked with patient record review. Depression was assessed using the Patient Health Questionnaire-9. Data were entered to EPI INFO version 7 and analyzed by SPSS version 20 software. Binary logistic regression analysis was performed to identify factors associated with depression. A total of 415 diabetic patients participated in the study with a response rate of 98.3%. The prevalence of depression among diabetic patients was found to be 15.4% (95% confidence interval (CI): 11.7-19.2). Only religion (adjusted odds ratio [AOR] =2.65 and 95% CI: 1.1-6.0) and duration of diabetes (AOR =0.27 and 95% CI: 0.07-0.92) were the factors associated with depression among diabetic patients. The prevalence of depression was low as compared to other similar studies elsewhere. Disease (diabetes) duration of 10 years and above and being a Muslim religion follower (as compared to Christian) were the factors significantly associated with depression. Early screening of depression and treating depression as a routine component of diabetes care are recommended. Further research with a large sample size, wider geographical coverage, and segregation of type of diabetes mellitus is recommended.


Geometry of interplanar residue contacts in protein structures.
The relative spatial disposition of interacting side-chain planar groups (aromatic, guanidinium, amide, carboxyl, imidazole) is analyzed for 186 non-homologous well-resolved protein structures. The dihedral angle of amide or carboxyl planar groups with other planar groups accords with a random distribution of planes. By contrast, the dihedral angle of the planes between close aromatic rings or of the histidine ring interacting with aromatic residues is significantly nonrandom, showing an approximately uniform distribution. Our results indicate that edge-to-edge and edge-to-center spatial dispositions of residue planar sections are prevalent, while complete stacking configurations are uncommon. The hypothesis that electrostatic forces are a major determinant of the geometry of interactions between side-chain planar groups is discussed.


Breastfeeding and infant sleep patterns: an Australian population study.
Our purpose was to determine if babies breastfed at 6 months of age were more likely to wake at night and less likely to sleep alone than formula-fed babies. Data were drawn from the first wave of The Longitudinal Study of Australian Children, an ongoing, nationally representative study of the growth and development of Australia's children. The 4507 participants met the criteria for this study. The measures examined infant sleep problems as the outcome and breastfeeding at 6 months of age as the exposure in addition to the demographic data, maternal mental health, infant birthweight and gestational age at delivery. After adjustment for covariates, reports by mothers of infants that breastfed at 6 months of age suggested infants were 66% more likely to wake during the night and 72% more likely to report difficulty sleeping alone. However, breastfeeding had a strongly protective effect on wheezing, coughing, snoring and breathing problems, and it was not associated with restless sleep or problems getting to sleep for the infant. Breastfeeding was found to be associated with increased night waking and this is consistent with other studies. There are biological reasons why this might be required to ensure breastfeeding continues to 6 months and beyond. The current low rates of sustained breastfeeding in many Western countries needs to be reconsidered in relation to parental and public health practices promoting prolonged nocturnal infant sleep patterns.


How long does stridor at rest persist in croup after the administration of oral prednisolone?
To determine the duration of stridor at rest (SAR) after the administration of oral prednisolone (1 mg/kg) to children admitted to hospital with croup from the ED. The secondary objective was to determine whether children with mild croup had a more rapid resolution of SAR. This was a retrospective explicit chart review of all children admitted to the paediatric ward of a community, paediatric teaching hospital with a diagnosis of croup over one year. Data collected included patient demographics, Westley and Geelhoed croup scores on presentation to the ED and the duration of SAR after administration of steroids. For the 188 cases analyzed, median duration of SAR was 6.5 h (95% CI 6-7 h, range 0.5-82 h). Children with a Westley score of < or = 2 or a Geelhoed score of < or = 3 had a shorter duration of SAR than those with higher scores (6 h vs. 7 h, P < 0.05), which although statistically significant is unlikely to be of clinical significance. Stridor at rest resolves promptly after the administration of oral steroids in the vast majority of cases. This suggests that a subset of patients previously admitted to hospital with croup may be able to be treated and discharged from the ED.


T-cell deficiency and hyperinflammatory monocyte responses associate with Mycobacterium avium complex lung disease.
Immunological mechanisms of susceptibility to nontuberculous mycobacterial (NTM) disease are poorly understood. To understand NTM pathogenesis, we evaluated innate and antigen-specific adaptive immune responses to Mycobacterium avium complex (MAC) in asymptomatic individuals with a previous history of MAC lung disease (MACDZ). We hypothesized that Mav-specific immune responses are associated with susceptibility to MAC lung disease. We measured MAC-, NTM-, or MAC/Mtb-specific T-cell responses by cytokine production, expression of surface markers, and analysis of global gene expression in 27 MACDZ individuals and 32 healthy controls. We also analyzed global gene expression in Mycobacterium avium-infected and uninfected peripheral blood monocytes from 17 MACDZ and 17 healthy controls. We were unable to detect increased T-cell responses against MAC-specific reagents in MACDZ compared to controls, while the responses to non-mycobacteria derived antigens were preserved. MACDZ individuals had a lower frequency of Th1 and Th1* T-cell populations. In addition, MACDZ subjects had lower transcriptional responses in PBMCs stimulated with a mycobacterial peptide pool (MTB300). By contrast, global gene expression analysis demonstrated upregulation of proinflammatory pathways in uninfected and M. avium-infected monocytes, i.e. a hyperinflammatory in vitro response, derived from MACDZ subjects compared to controls. Together, these data suggest a novel immunologic defect which underlies MAC pathogenesis and includes concurrent innate and adaptive dysregulation which persists years after completion of treatment.


Fedbatch culture and dynamic nutrient feeding.
In the past decade, we have seen a rapid expansion in mammalian cell based therapeutic proteins reaching clinical applications. This increased demand has been met with much increased productivity through intensive process development. During this time, fedbatch culture processes have emerged as the predominant mode for producing recombinant proteins. In this review, we discuss the fundamentals of fedbatch culture process design, focusing on the use of stoichiometric nutrient requirements for feed medium formulation, and articulating the need and potential means for devising rational dynamic feeding schemes. Incorporation of on-line nutrient measurement will play a key role in further refinement of process control for the development of a much sought after generic feeding strategy that can respond to the changing demands of different cell lines in a fluctuating culture environment. The future of process engineering will likely require a combination of current process engineering strategies along with a better understanding and control over cell physiology. Process development will likely to entail not only optimizing traditional engineering parameters but also engineering cell lines with desired characteristics. The integration of cell engineering and process intensification will likely provide the stimuli that propel the limits of growth and productivity to the next high level.


Modulation of Irisin and Physical Activity on Executive Functions in Obesity and Morbid obesity.
Whether the executive profile is different between obesity (OB) and morbid obesity (MO) remains unclear. Recent evidence suggests that physical activity (PA) can act as a cognitive enhancer. Irisin is a recently discovered hormone associated with some of the positive effects of PA. The objective of the study was to investigate the executive profile in OB and MO, and to explore the role of PA and irisin. 114 participants were included (21 OB, 44 MO and 49 healthy controls-HC) in the study and assessed with the Wisconsin Card Sorting Test, Stroop Color and Word Test, and Iowa Gambling Task. All participants were female, aged between 18 and 60 years. Results showed a similar dysfunctional profile on decision making in OB and MO compared with HC. Thus, no specific neuropsychological profiles between OB and MO can be clearly observed in our sample. However, a negative correlation was found between irisin and executive functioning. These results demonstrate a specific executive profile in OB and a relevant and negative modulation of irisin on executive functioning. Although irisin might be a promising target for the treatment of obesity, its effects on cognition might be considered when thinking about its therapeutic use.


Control of tunnel barriers in multi-wall carbon nanotubes using focused ion beam irradiation.
We have formed tunnel barriers in individual multi-wall carbon nanotubes using the Ga focused ion beam irradiation. The barrier height was estimated by the temperature dependence of the current (Arrhenius plot) and the current-voltage curves (Fowler-Nordheim plot). It is shown that the barrier height has a strong correlation with the barrier resistance that is controlled by the dose. Possible origins for the variation in observed barrier characteristics are discussed. Finally, the single electron transistor with two barriers is demonstrated.


Influence of growth media on Escherichia coli cell composition and ceftazidime susceptibility.
Cell composition and surface properties of Escherichia coli were modified by using various growth media to investigate the role of yet uncharacterized components in ceftazidime susceptibility. An eightfold dilution of Luria broth was used as the basic growth medium and was supplemented with up to 4% phosphate, 5% glucose, or 12% L-glutamate. Decreases in cephaloridine and ceftazidime susceptibility, of two- and eightfold, respectively, were observed only in the glucose-enriched medium. The outer membrane permeability to ceftazidime and cephaloridine was evaluated by crypticity indices. Indices were unchanged under all growth conditions. Fluorometry of whole cells with 1-N-phenylnaphthylamine showed that glucose does not affect the interaction of this hydrophobic probe with the membranes but showed that elevated concentrations of phosphate or glutamate cause a marked increase in cell hydrophobicity, which, in turn, correlates with an increase in the susceptibility of E. coli to nalidixic acid. Growth in phosphate- or glutamate-enriched media caused an augmentation in major phospholipid species and may explain the increased hydrophobicity and susceptibility of E. coli to nalidixic acid. These data showed that E. coli susceptibility to ceftazidime is not influenced by cell surface hydrophobicity and suggested that the contribution of a nonspecific lipophilic diffusion route for entry of ceftazidime into cells is not likely to occur or is distinct from that of more hydrophobic molecules such as nalidixic acid. Finally, the penicillin-binding proteins of the E. coli cells were also investigated. Penicillin-binding protein 8 was only markedly labeled with 125I-penicillin V in inner membranes extracted from cells grown with glucose. Results of this study suggest that the unexpected change in penicillin-binding protein 8 observed in the presence of glucose may be responsible for the increase in MICs of cephaloridine and ceftazidime.


The action of (+/-)-MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system.
The mechanism of action of systemically administered (+/-)-MDMA (3,4-methylenedioxymethamphetamine) on spontaneously active neurons in the medial prefrontal cortex (mPFc) of chloral hydrate anesthetized rats was examined using standard single unit extracellular recording techniques. Intravenously administered MDMA dose-dependently decreased the firing rates of the majority of mPFc neurons in control rats. In contrast, in rats that were pretreated with p-chlorophenylalanine (PCPA), which depletes the brain serotonin (5-hydroxytryptamine, 5-HT) content by inhibiting tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, MDMA was largely ineffective in inhibiting the firing of mPFc cells. In PCPA-treated animals, the administration of 5-hydroxytryptophan (5-HTP), which presumably restored the brain 5-HT content, but not L-DOPA, reinstated MDMA's inhibitory action in PCPA-treated rats. In rats that were pretreated with alpha-methyl-p-tyrosine (AMPT), which depletes the brain dopamine (DA) content by inhibiting tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of DA, MDMA inhibited the firing of all of the mPFc cells. MDMA's effect on mPFc neurons was reversed by 5-HT receptor antagonists such as granisetron and metergoline. These results strongly suggest that MDMA exerts its action on mPFc cells indirectly by releasing endogenous 5-HT.


Changes in the characteristics of a Gaussian beam weakly diffracted by a circular aperture.
A Gaussian beam weakly diffracted by a circular aperture can be approximated in the far field by another Gaussian beam with slightly different characteristics. Equations giving the intensity, the divergence, and the radius of the modified beam are derived in simple practical form for experimentalists. These approximated formulas show that, even in the case of negligible power losses through the aperture, the diffracted beam characteristics may appreciably differ from those of the incident beam. In a first approximation, diffraction effects may be ignored only if the ratio a/r(0) of the aperture radius a to the l/e intensity beam radius r(0) in the aperture plane is larger than 3.


Peroxisome Proliferator-Activated Receptor Gamma Modulator Promotes Neonatal Mouse Primordial Follicle Activation In Vitro.
Peroxisome proliferator-activated receptor gamma (PPARγ) is known as a regulator of cellular functions, including adipogenesis and immune cell activation. The objectives of this study were to investigate the expression of PPARγ and identify the mechanism of primordial follicle activation via PPARγ modulators in mouse ovaries. We first measured the gene expression of PPARγ and determined its relationship with phosphatase and tensin homolog (PTEN), protein kinase B (AKT1), and forkhead box O3a (FOXO3a) expression in neonatal mouse ovaries. We then incubated neonatal mouse ovaries with PPARγ modulators, including rosiglitazone (a synthetic agonist of PPARγ), GW9662 (a synthetic antagonist of PPARγ), and cyclic phosphatidic acid (cPA, a physiological inhibitor of PPARγ), followed by transplantation into adult ovariectomized mice. After the maturation of the transplanted ovaries, primordial follicle growth activation, follicle growth, and embryonic development were evaluated. Finally, the delivery of live pups after embryo transfer into recipient mice was assessed. While PPARγ was expressed in ovaries from mice of all ages, its levels were significantly increased in ovaries from 20-day-old mice. In GW9662-treated ovaries in vitro, PTEN levels were decreased, AKT was activated, and FOXO3a was excluded from the nuclei of primordial follicles. After 1 month, cPA-pretreated, transplanted ovaries produced the highest numbers of oocytes and polar bodies, exhibited the most advanced embryonic development, and had the greatest blastocyst formation rate compared to the rosiglitazone- and GW9662-pretreated groups. Additionally, the successful delivery of live pups after embryo transfer into the recipient mice transplanted with cPA-pretreated ovaries was confirmed. Our study demonstrates that PPARγ participates in primordial follicle activation and development, possibly mediated in part by the PI3K/AKT signaling pathway. Although more studies are required, adapting these findings for the activation of human primordial follicles may lead to treatments for infertility that originates from poor ovarian reserves.


Nursing research.
As a registered nurse working in a community setting, I encounter a diverse range of patient healthcare needs every day. Holistic assessment and individualised care plans are essential to meet patients' needs.


Inhibition of aggregation of aluminum hydroxide adjuvant during freezing and drying.
Aluminum-salt adjuvants are widely used to increase immunogenicity of recombinant protein vaccines. However, when vaccines formulated with these adjuvants are frozen or lyophilized, losses of efficacy are often reported. This loss of potency is usually attributed to the aggregation of adjuvant particles during processing. In this study, we examine the aggregation behavior of Alhydrogel, a commercial aluminum hydroxide adjuvant, during freeze-thawing and freeze-drying. By cooling Alhydrogel formulations at faster rates or by the addition of sufficient amounts of a glass forming excipient such as trehalose, aggregation of Alhydrogel, can be prevented or minimized. We propose that freeze-concentration of buffer salts induces modifications in adjuvant surface chemistry and crystallinity, which in turn favor aggregation. These modifications, and the resulting aggregation of Alhydrogel particles can be minimized through choice of buffer ions, or kinetically inhibited by rapidly forming a glassy state during freezing.


Successful preimplantation genetic diagnosis for alpha- and beta-thalassemia in China.
In southern China, the average carrier rates of alpha-thalassemia and beta-thalassemia in the population are as high as 10.3% and 2.8%, respectively. Because of the high rates, they are known as 'social diseases' in some regions. In this study, the fluorescent gap PCR, which can detect the alpha-thalassemia Southeast Asia deletion (SEA deletion), was applied in four clinical applications of preimplantation genetic diagnosis (PGD) on four couples, among whom both partners were alpha-thalassemia carriers. Two patients became pregnant and two healthy babies were born, which confirmed the PGD results. The single cell multiplex nested PCR followed by reverse dot blot (RDB), which can simultaneously detect the 16 beta-thalassemia mutations in the Chinese population, was applied in four clinical PGD cycles on four couples among whom both partners were beta-thalassemia carriers. One pregnancy was achieved and it resulted in a live healthy birth, which confirmed the results of PGD. The amplification efficiencies of the two protocols described above were 89.5% and 93.9%, respectively. The allele drop-out (ADO) rates of these two protocols were 5.9% and 10.9%, respectively. These studies represent the successful applications of PGD protocols that can detect more than 95% of alpha- and beta -thalassemia mutations in the Chinese population.


Novel cationic triazine dyes for protein purification.
The effectiveness of a new immobilized cationic triazine dye was investigated alongside two new amphoteric triazine dyes and two well known anionic triazine dyes, Procion Red H-3B and Procion Blue H-B, as chromatographic media for binding four familiar proteases-trypsin, chymotrypsin, thrombin and carboxypeptidase-B-as well as a typical oxidoreductase, lactate dehydrogenase, and human serum albumin. The new affinity adsorbent, CL-Sepharose-immobilized Cationic Dye, specifically binds trypsin-like proteases such as trypsin, thrombin, and carboxypeptidase-B, but none of the other proteins tested. In contrast, the amphoteric and anionic immobilized dyes bind all the other proteins tested in a similar fashion. The specificity of the cationic dye was exploited in the resolution of trypsin and chymotrypsin from a crude activated bovine pancreatic extract. The procedure described here affords trypsin with specific activity of 7400 units/mg with a 79% overall yield in a single step. The immobilized cationic dye, unlike previously reported adsorbents for trypsin, is inexpensive, readily synthesized, and displays a workable capacity of 4000 trypsin units or 0.55 mg protein/g moist weight gel (1.2 mumol dye/g moist weight gel) from a crude bovine pancreatic extract and, thus, is potentially amenable to process-scale operations.


Effect of health insurance type on health care utilization in patients with hypertension: a national health insurance database study in Korea.
Higher utilization of healthcare services has been observed among individuals who receive public aid compared to individuals who do not receive public aid in many countries. However, no systematic investigations have explored whether this pattern of higher utilization persists after correcting for a number of factors in Korea. In this study, we sought to examine whether the type of health insurance, wage-based contributory insurance (Health Insurance, HI) or government-subsidized public assistance (Medical Aid, MA), affects the utilization of inpatient services after controlling for baseline patient and institutional characteristics among patients with hypertension in Korea. The Korean National Health Insurance claims database from 2006 and 2007 was used for analysis. To avoid biased estimates, we determined the most appropriate type of multivariate model for each outcome variable: a logistic regression model for the likelihood of hospitalization, a zero-inflated negative binomial model for the length of stay (LOS), and a generalized linear model with a log-link function for hospitalization costs. Adjusted odds ratio (OR) and factor changes showed that MA patients (n = 21,539) had a significantly higher likelihood of hospitalization (OR: 1.41-1.71), average LOS per patient (factor change: 1.31-1.42), and hospitalization costs per patient (factor change: 1.10-1.41) compared to HI patients (n = 304,027). The pattern of higher healthcare utilization among MA patients persists even after controlling for baseline health conditions. This finding confirms that the type of health insurance affects the utilization of healthcare resources, and suggests that effective strategies are necessary to prevent the potential overutilization of inpatient care by MA patients with hypertension in Korea.


Reliability of MR imaging-based virtual cystoscopy in the diagnosis of cancer of the urinary bladder.
Our purpose was to evaluate MR imaging-based virtual endoscopy in patients with urinary bladder cancer compared with conventional cystoscopy as the gold standard. Twenty-five patients with urinary bladder cancer diagnosed on conventional cystoscopy underwent MR imaging of the pelvis. Patients were examined without external bladder filling or administration of IV contrast medium. No medications were administered. The data obtained by MR imaging were reconstructed for virtual endoscopy on a workstation. The locations and sizes of tumors were individually determined and compared with results of conventional cystoscopy. Twenty-four patients were evaluated; one patient's examination was excluded from analysis because of metallic artifacts. Seventeen patients were diagnosed with a single bladder tumor. Five patients had two tumors each, and two patients had three tumors. Tumor diameter ranged from 0.4 to 6.4 cm. Thirty (90.9%) of 33 tumors detected on cystoscopy were visualized with virtual endoscopy. The detection rate for 23 tumors of 1 cm or greater was 100%. Difficult conditions for conventional cystoscopy, including hematuria, anterior wall involvement, and urethral strictures, had no deleterious impact on virtual cystoscopy. Difficulties in detection on virtual endoscopy were associated with flat bladder tumors with minimal surface elevation. The results of this study suggest a high reliability in the diagnosis of urinary bladder cancer by MR imaging-based virtual cystoscopy-a noninvasive method, independent of medication or contrast enhancement, that may be of value for screening, primary diagnosis, and surveillance. Virtual MR cystoscopy may be indicated when conventional cystoscopy cannot be performed or is ineffective.


Detection of phosphotyrosine-containing 34,000-dalton protein in the framework of cells transformed with Rous sarcoma virus.
Phosphotyrosine-containing 34,000-dalton protein is detected by treatment of a two-dimensional gel of cellular framework with 1 M NaOH at 40 degrees C for 1 hr. The alkali-resistant 32PO4-labeled 34,000-dalton protein is detected in various cell lines transformed by Rous sarcoma virus but not in lines transformed by simian virus 40, polyoma virus, herpes simplex II virus, adenovirus type 2, or chemical carcinogens. In addition, interferons or fibronectin matrices have no detectable effect on the phosphorylation of the 34,000-dalton protein in Rous sarcoma virus-transformed cells.


An unusual cause of epidemic thyrotoxicosis.
We describe the case of four patients consulting for headache and tachycardia of brutal onset. Their biological data were compatible with primary hyperthyroidism with low TSH and high T4 serum levels. Serum thyroglobulin level was low and Tc-scintigraphy showed decreased uptake with a homogenous pattern. These results allowed to conclude a thyrotoxicosis caused by thyroid hormones intake. History taking revealed consumption of beef neck meat containing all or parts of the bovine thyroid gland. Evolution was favourable with beta-blockers. A literature review of « hamburger thyrotoxicosis » is presented.


Visual field (Octopus 1-2-3) in normal subjects divided into homogeneous age-groups.
To determine the values in decibels of retinal sensitivity within the central 26 degrees of the visual field of normal subjects divided into homogenous age groups using the Octopus 1-2-3; to compare the values of retinal sensitivity we have found with those considered normal in the statistical package obtained by a multicenter study performed in 1994 with Octopus 201. 181 subjects divided into 6 homogeneous age groups (10 to 19 yr; 20 to 29 yr; 30 to 39 yr; 40 to 49 yr; 50 to 59 yr and 60 year-old or older) were evaluated. Data on visual sensitivity and age, average sensitivity of central and paracentral regions and eccentricity were calculated. The average visual sensitivity of all groups was 26.77 +/- 1.74 dB. Correlation between visual sensitivity and age evaluated by linear regression was 28.4 - 0.040 x (age) for the whole sample and 28.7 - 0.050 x (age) for subjects aged 20 or more. Sensitivity reduction by eccentricity was -0.30 dB/degree for the whole sample and for subjects aged 20 or more. Correlation between retinal sensitivity values and age based on the autoperimeter Octopus 201 (average sensitivity of 31.2 - 0.064 x age) is different from that found in this study: average sensitivity of 28.4 - 0.040 x (age) for the whole sample; 28.7 - 0.050 x (age) for subjects aged 20 or more. Values obtained with the Octopus 1-2-3 autoperimeter cannot be compared with those by other Octopus models (101, 201 and 500) due to their distinct features.


Low-dose combined spinal-epidural anaesthesia vs. conventional epidural anaesthesia for Caesarean section in pre-eclampsia: a retrospective analysis.
Epidural anaesthesia is the preferred technique of anaesthesia for Caesarean section in pre-eclampsia. Spinal anaesthesia is considered by some as a safe and effective alternative, which is especially useful in emergency situations. Combined spinal-epidural anaesthesia, using low doses of local anaesthetics with opioids, is effective and reduces the incidence of hypotension in normal pregnancy. We performed a retrospective chart analysis to evaluate the effects of combined spinal-epidural anaesthesia on maternal haemodynamics and fetal outcome compared to conventional epidural anaesthesia. A retrospective anaesthesia chart analysis of all pre-eclamptic patients who underwent Caesarean section over a 4 yr period was performed. Patient characteristic, obstetric, haemodynamic, fetal and neonatal data were gathered and analysed according to the anaesthetic technique used. Seventy-seven pre-eclamptic parturients undergoing Caesarean section were identified (26 women were severely pre-eclamptic and 51 demonstrated mild pre-eclampsia). Epidural anaesthesia was performed in 62 patients and combined spinal-epidural anaesthesia was performed in 15. No differences in patient characteristic and obstetric data were noted. Highest mean arterial pressure prior to anaesthesia was comparable between the groups (epidural: 106 +/- 12 vs. combined spinal-epidural anaesthesia: 109 +/- 18 mmHg) as well as the lowest recorded mean arterial pressure following anaesthesia (epidural: 93 +/- 13 vs. combined spinal-epidural anaesthesia: 98 +/- 17 mmHg). In the combined spinal-epidural anaesthesia group more ephedrine was used compared to the epidural group (14.6 +/- 4.4 vs. 3.6 +/- 4.6 mg, P < 0.05). However, more lactated Ringer's was used in the epidural group. Umbilical artery pH was lower in the epidural group (7.26 +/- 0.01 vs. 7.29 +/- 0.02, P < 0.05). Similar results were noted in 26 severely pre-eclamptic patients. Seven women underwent combined spinal-epidural anaesthesia and 19 underwent epidural anaesthesia in the severely pre-eclamptic group. Also more ephedrine was used in the combined spinal-epidural anaesthesia group. A tendency towards a lower umbilical artery pH was observed in the epidural group but this difference did not reach statistical significance. Combined spinal-epidural anaesthesia appears to be safe as anaesthetic technique for pre-eclampsia and severe pre-eclampsia. However, it is important to consider the retrospective design of the study and the large number of epidural anaesthetics performed.


Rapid sensitive fluorescence detection of cadmium (II) with pyrene excimer switching aptasensor.
Heavy metal cadmium (II) contamination often occurs, causing great health risk to human due to high toxicity of cadmium (II). Rapid, sensitive and simple detection of cadmium (II) are of great importance in environmental monitoring. Taking advantage of aptamer in specific recognition, easy modification, and capability of binding-induced structure change, here we reported a simple fluorescent sensor with rapid and sensitive response for Cd2+ using aptamer pyrene excimer switch. The aptamer was labeled with dual pyrene molecules at two ends of the sequence. The binding of Cd2+ to this aptamer probe brought the pyrene labels into close proximity and enhanced formation of a pyrene excimer, which generated increased fluorescence at 485 nm. By measuring the fluorescence of pyrene excimer, we achieved detection of Cd2+ with this aptasensor. Under the optimum experimental conditions, the detection limit of Cd2+ reached nanomolar levels. This method was selective and allowed for the detection of Cd2+ in tap water. This fluorescence aptasensor is promising for rapid detection of Cd2+ in broad applications.


Sexual dimorphism and postnatal growth of intrauterine growth retarded rats.
The intrauterine growth retardation (IUGR) is a complex phenomenon since it causes variability in postnatal growth responses. The aim of the present study was to analyze the effects of lactational rehabilitation on body and cranial growth and sexual dimorphism in IUGR rats. IUGR model was carried out by means of uterine vessels bending in pregnant rats at the first day of pregnancy. Control and sham-operated animals were also included. During suckling, IUGR and sham-operated pups were cross-fostered to a control dam. The animals were x-rayed every four days, from birth to weaning. Body weight and length, and neural and facial variables were measured. The reduced placental blood flow delayed growth in pups. Facial growth was more impaired than the neural one. An incomplete catch up growth was found, since males reached sham values only in neurocranial height and females--except facial length and width--were similar to sham. Because of sex differences in growth recovery, normal sexual dimorphism in body and craniofacial pattern was not expressed in the IUGR group. This study suggests that reduced uteroplacental blood supply in the rat interferes with the full expression of normal dimorphism based on gender and confirms the impact of IUGR on postnatal growth.


Overview of the spaceflight radiation environment and its impact on cell biology experiments.
Variables studied in typical cellular radiation biology experiments are cell killing, mutagenesis, transformation to malignancy, heritable damage, and DNA damage and repair. Dose response curves for cells exposed to low-LET radiations and some high LET radiations are well known. The low-LET dose rate in low earth orbit is roughly 1.0 mSv/day, the heavy-ion (Z>2) flux is about 1.0 particle/cm2-s corresponding to about 0.3 mSv/day, and the integrated neutron flux is roughly 2 neutrons/cm2-s corresponding to 0.012 mGy/d or, assuming a QF of 10, 0.12 mSv/d. Published dose-response curves were used to estimate the probability that a mammalian cell will be affected by each of the above types of damage. As a general approximation the exposure of an experimental cell population to the space radiation environment for 100 days will result in the following probabilities of damage per cell: cell killing based on clonogenicity 0.02, mutagenesis per locus based on phenotype analysis 1 x 10(-6), point mutation induction 2 x 10(-8) per locus, malignant transformation in vitro based on colony morphology 1.2 x 10(-5), heritable damage based on colony size 0.02, and induced DNA double-strand breaks based on fragment analysis by electrophoresis 3.5/cell or 0.26/cell after repair. Most of these figures are accurate to within a factor of 2. Thus the spaceflight radiation environment has essentially undetectable impact on typical cell biology experiments unless experimental goals involve the precise measurement of one of the above end-points. Other in vitro end-points, such as tissue morphogenesis and cell differentiation, are expected to be similarly unaffected by the spaceflight radiation environment.


Evaluation of enzyme-linked immunosorbent assay and indirect hemagglutination assay for detection of leptospiral antibody by using three different antigens.
Evaluation of enzyme linked immunosorbent assay (ELISA) and indirect hemagglutination assay (IHA) for detection of leptospiral antibody were performed using three different soluble antigens extracted from Leptospira interrogans serovar Bataviae including heat extracted antigen (HEA), sonicated antigen (SA) and deoxycholate extracted antigen (DEA). One hundred seventy-eight sera from 85 confirmed leptospirosis cases and 202 non-leptospirosis cases were examined SA-IHA showed the highest sensitivity of 98.8% followed by SA-ELISA-IgM and DEA-ELISA-IgM which showed an equal sensitivity of 97.6%. SA-ELISA-IgM was the most specific (96.5%) test followed by DEA-ELISA-IgM and SA-IHA which gave an equal specificity of 94.1%. The IgG-ELISA tests were less sensitive and specific than the others. These data indicated that the IgG-ELISA tests were not suitable as diagnostic tests for acute leptospirosis in humans. Using acute phase sera the sensitivity of DEA-ELISA-IgM, SA-ELISA-IgM and HEA-ELISA-IgM were 22.4%, 20.0% and 20.0% respectively, while those of the IgG ELISA tests were 32.9%, 17.6% and 10.6% respectively, the sensitivity of SA-IHA and DEA-IHA were 22.4% and 10.6% respectively. In conclusion, both the IgM-ELISA tests using SA and DEA and the IHA using SA are not different in diagnosis of human leptospirosis. SA is the most suitable antigen for detection of leptospiral antibody by IgM ELISA and IHA.


Total synthesis of (±)-sacidumlignans D and A through Ueno-Stork radical cyclization reaction.
Efficient synthesis of (±)-sacidumlignan D (4) has been successfully achieved employing Ueno-Stork radical cyclization of α-bromo acetal 21 as a key step. Two synthetic approaches for the symmetrical diaryl ketone 19 have been discussed in detail. Notably, sacidumlignan A (1) can be also efficiently synthesized in only 7 steps with 25% overall yield, where acid triggered tandem reaction starting from analogous Ueno-Stork cyclization product 27 played an important role. Moreover, potentially biomimetic conversion from (±)-sacidumlignan D (4) to sacidumlignan A (1) could be realized.


Imaging for Crohn disease: use of 3-T MRI in a paediatric setting.
This study was carried out to review our experience with 3-T MRI in the assessment of Crohn disease in a paediatric population. Twenty-four patients with biopsy proven Crohn disease identified on the radiology information system underwent abdominal MRI, with or without pelvic MRI. Twenty-eight studies were carried out on a 3-T scanner at a tertiary paediatric hospital. Eight of 24 of these (30%) had a gastrointestinal barium study, 2 of 24 (8%) a CT and 9 of 24 (38%) an abdominal ultrasound. The different MRI sequences were rated for observation of the bowel wall and abnormalities (0-5). The findings were correlated to relevant findings on endoscopy, examination under anaesthesia (EUA) and where available surgery, barium studies, CT and ultrasound. In this study, the colon was involved in 5 of 28 (18%), small bowel in 7 of 28 (25%), terminal ileum in 5 of 28 (18%). All the perineal studies (9 of 9) showed abnormalities. Sinus tracts or fistulas were identified in 7 of 28 (25%) studies. The mean rating of the different MRI sequences in showing bowel wall and changes of Crohn disease was T2 TSE 3.6, T2 half fourier aquisition single shot turbo spin echo (HASTE) with a long TE 3.6, T2 HASTE with short TE 3.4, true fast imaging with steady state precession (FISP) 2.7, T1 4.1 and Post-contrast T1 4.3. The T2 HASTE sequences with thinner slices improved observation. Detection of superficial abnormalities was similar on the 3D VIBE images and on the post-contrast T1 spin-echo (SE) sequences. In five of nine (56%) of those that had ultrasound, both studies were abnormal, with incomplete correlation of the abnormalities. Computed tomography and MRI were abnormal in two of two (100%) patients with good correlation of the abnormalities in one; in the other there was a minimal discrepancy in the estimation of the length of involved bowel. In 7 of 11 (64%) the barium study was abnormal. Good correlation to MRI findings was found in five of seven (71%) of patients. In two of seven (29%) both studies were abnormal, with incomplete correlation of the abnormalities. Barium underestimated the length of involved segment in these patients with inflammatory ileal thickening and ulceration. Notably, in both studies compression was limited because of patient discomfort and the involved segments obscured by overlap. Abdominal and pelvic MRI at 3 T is a useful imaging technique for evaluation of Crohn disease in the children. The extent of bowel wall involvement and extra-intestinal complications, such as abscesses and fistulas can be accurately assessed non-invasively, without the use of ionizing radiation or sedation.


New beta cis folded organocobalt derivatives with a salen-type ligand.
The reduction of [Co(III)(tmsalen)py(2)](+)ClO(4)(-), where tmsalen = 4,4',7,7'-tetramethylsalen, with NaBH(4)/PdCl(2) in alkaline methanolic solution, followed by the oxidative addition of CH(2)ClI, leads to the expected trans organometallic dimeric species 1, [CH(2)ClCo(tmsalen)](2), provided that the product is recovered from the reaction mixture immediately after the completion of the reaction. If 1 is left for longer time in contact with the reaction mixture, the intramolecular reaction of the axial chloromethyl group with the equatorial chelate leads to the formation of the monocationic complex 2, containing a seven-membered ring. In this complex the novel tetradentate ligand coordinates Co in a cis fashion, the other two positions being occupied by one py and one water molecule. The resulting complex is chiral, even if the reaction product is a racemic compound. The unidentate ligands of 2 have been exchanged quantitatively for N-MeIm, and the resulting complex 3 still maintains the beta cis geometry. Therefore, 2 may be considered the precursor of a new class of organocobalt derivatives with a folded tetradentate ligand and two adjacent exchangeable sites. On the basis of the geometry of the tetradentate Schiff bases in complexes, where they adopt a planar geometry, it was suggested that there is a significant electron density delocalization involving the metal center over the two chemically equivalent moieties of Co(chel). Comparison of the geometry of the planar salicylaldiminate (sal) moiety with that of the cyclized methoxy-iminate one (imi) in 2 and 3 strongly supports that the delocalization, still present in sal, is essentially either lost or strongly reduced in imi.


Gastric inhibitory polypeptide immunoneutralization attenuates development of obesity in mice.
Previous reports have suggested that the abrogation of gastric inhibitory polypeptide (GIP) signaling could be exploited to prevent and treat obesity and obesity-related disorders in humans. This study was designed to determine whether immunoneutralization of GIP, using a newly developed specific monoclonal antibody (mAb), would prevent the development of obesity. Specific mAb directed against the carboxy terminus of mouse GIP was identified, and its effects on the insulin response to oral and to intraperitoneal (ip) glucose and on weight gain were evaluated. Administration of mAb (30 mg/kg body wt, BW) to mice attenuated the insulin response to oral glucose by 70% and completely eliminated the response to ip glucose coadministered with human GIP. Nine-week-old C57BL/6 mice injected with GIP mAbs (60 mg·kg BW(-1)·wk(-1)) for 17 wk gained 46.5% less weight than control mice fed an identical high-fat diet (P < 0.001). No significant differences in the quantity of food consumed were detected between the two treatment groups. Furthermore, magnetic resonance imaging demonstrated that subcutaneous, omental, and hepatic fat were 1.97-, 3.46-, and 2.15-fold, respectively, lower in mAb-treated animals than in controls. Moreover, serum insulin, leptin, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides were significantly reduced, whereas the high-density lipoprotein (HDL)/TC ratio was 1.25-fold higher in treated animals than in controls. These studies support the hypothesis that a reduction in GIP signaling using a GIP-neutralizing mAb might provide a useful method for the treatment and prevention of obesity and related disorders.


Microencephaloceles: another dual pathology of intractable temporal lobe epilepsy in childhood.
Temporal lobe encephaloceles can be associated with temporal lobe epilepsy. The authors report on the case of an adolescent with multiple microencephaloceles, in the anterolateral middle fossa floor, identified at surgery (temporal lobectomy) for intractable partial-onset seizures of temporal origin. Magnetic resonance imaging revealed only hippocampal atrophy. Subdural electrodes demonstrated ictal activity arising primarily from the anterior and lateral temporal lobe, close to the microencephaloceles, spreading to the anterior and posterior mesial structures. Pathological examination revealed diffuse temporal gliosis involving the hippocampus, together with microdysgenesis of the amygdala. The literature on epilepsy secondary to encephaloceles is reviewed and the contribution of the microencephaloceles to the seizure disorder in this patient is discussed.


Characterization and use of polyclonal antibody to Na+,K+-ATPase: immunocytochemical localization in salt glands of the duck.
The amount of Na+,K+-ATPase of the avian salt gland increased concomitantly with plasma membrane surface area during salt feeding of ducklings (adaptation), and both enzyme content and membrane surface area decreased upon return to fresh water (deadaptation). In a further study of the enzyme, a marker for plasma membrane biogenesis, polyvalent antibodies were raised to the denatured alpha-subunit of the purified ATPase. Antisera did not inhibit enzymatic activity but immunoprecipitated the phosphorylated intermediate of the alpha-subunit. Furthermore, the alpha-subunit, which was not glycosylated, was immunoprecipitated from homogenates of tissue slices metabolically labelled with [35S]-methionine, using antisera raised against either duck salt gland or dog kidney alpha-subunit. The former antisera also recognized the alpha-subunit in the brain, heart, kidney, liver, intestine and skeletal muscle of the duck. Immunocytochemistry with the antisera raised to the duck salt gland alpha-subunit revealed reaction at basolateral as well as apical plasma membrane in the duck salt gland principal cells, with essentially no deposits on peripheral cells, fibroblasts, erythrocytes, endothelial cells and neural elements. Within the principal cells, immunolabelling was also detected on small vesicles, multivesicular bodies and lysosomes; deposits on extracellular debris and vesicles in the lateral and lumenal spaces were also apparent. The labelling patterns were qualitatively but not quantitatively similar in salt glands of control, adapted and deadapted ducklings, and are discussed in the context of a model for plasma membrane biogenesis and turnover in which degradative events may play a major role.


Transcription termination and chromatin structure of the active immunoglobulin kappa gene locus.
To investigate the chromatin surrounding an active gene, we have determined the distribution of RNA polymerase molecules, the intactness of nucleosomal structure, and the subnuclear compartmentalization along 15 kilobase pairs (kb) of the mouse kappa immunoglobulin locus of MPC-11 plasmacytoma cells. Hybridization of in vitro nuclear transcripts to probes specific for the template strand reveals that transcription terminates within the region between 1.1 and 2.3 kb downstream from the poly(A) addition site. Ten different short sequences (8-13 base pairs) reside within 460 base pairs of this termination region that exhibit homology with sequences found in the termination regions of mouse beta-globin and chicken ovalbumin genes. Transcription of the nontemplate strand occurs on either side of this termination region. We find that both within the transcription unit and 6.5 kb downstream of the termination region of the kappa gene, the canonical nucleosomal structure is perturbed, the chromatin exhibits pronounced insolubility, and the nucleosomes liberated by micrococcal nuclease appear to lack histone H1. The insolubility is characterized by interactions that are disrupted by 0.3 to 0.6 M NaCl treatment. We conclude that the active chromatin phenotype spreads a considerable distance along the kappa locus, well beyond the region of transcription termination.


Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity.
Resistance to anticancer medications often leads to poor outcomes. The present study explored an effective approach for enhancing chemotherapy targeted against human cancer cells. Real-time quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed overexpression of members of aldo-keto reductase (AKR) 1C family, AKR1C1, AKR1C2, AKR1C3, and AKR1C4, in cisplatin, cis-diamminedichloroplatinum (II) (CDDP)-resistant human cancer cell lines, HeLa (cervical cancer cells) and Sa3 (oral squamous cell carcinoma cells). The genes were downregulated using small-interfering RNA (siRNA) transfection, and the sensitivity to CDDP or 5-fluorouracil (5-FU) was investigated. When the genes were knocked down, sensitivity to CDDP and 5-FU was restored. Furthermore, we found that administration of mefenamic acid, a widely used non-steroidal anti-inflammatory drug (NSAID) and a known inhibitor of AKR1Cs, enhanced sensitivity to CDDP and 5-FU. The present study suggests that AKR1C family is closely associated with drug resistance to CDDP and 5-FU, and mefenamic acid enhances their sensitivity through its inhibitory activity in drug-resistant human cancer cells. Thus, the use of mefenamic acid to control biological function of AKR1C may lead to effective clinical outcomes by overcoming anticancer drug resistance.


Spontaneous upper eyelid ecchymosis: A rare presenting sign for frontal sinus mucocele.
Paranasal sinus mucoceles are benign lesions that commonly present with orbital signs due to their anatomic proximity. We are reporting a case of bilateral frontal sinus mucocele presenting with spontaneous eyelid ecchymosis. To our knowledge this is the first case report of eyelid ecchymosis as the initial sign of this condition. In addition, our patient lacked commonly described symptoms such as diplopia or pain. This report highlights the importance of including frontal sinus mucocele in the differential diagnosis of spontaneous periorbital ecchymosis.


Activities of APh, gamma-GT, GlDH and GPT and bile acid concentrations in serum after bile duct obstruction and cycloheximide in the rat.
The aim of this study was to investigate the effect of the protein synthesis inhibitor cycloheximide on the serum activities of gamma-Glutamyltransferase, Glutamate dehydrogenase and Glutamate pyruvate transaminase after bile duct obstruction in rats. The results showed that the increase of these enzyme activities after bile duct obstruction is further augmented by cycloheximide. Determinations of total bile acids in serum and liver showed that also the bile acid concentrations rise to a higher level after bile duct obstruction + cycloheximide than after bile duct obstruction alone. It is concluded that the effect of cycloheximide on the serum enzyme activities in extrahepatic cholestasis is produced via an influence on the metabolism of bile acids. This stresses the central role of bile acids for alterations of enzyme activities in extrahepatic cholestasis. Further, the effect of cycloheximide on bile acids after bile duct obstruction has not been reported before.


Quantitative Analysis of Remineralization of Artificial Carious Lesions with Commercially Available Newer Remineralizing Agents Using SEM-EDX- In Vitro Study".
The basic principle of remineralization is by advocating a biological or non-invasive approach rather than the surgical approach for early enamel lesions. There are relatively newer products available for remineralization, latest being the resin-infiltration technique, commercially available as Icon. The aim of the study was to evaluate the remineralizing potential of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP), Vantej and Icon by the quantitative evaluation of mineral gain. Seventy eight maxillary premolars were decoronated at Cemento-Enamel Junction (CEJ) and then sectioned mesio-distally using diamond disc into two halves. Mineral content of the sound specimens were recorded using Energy Dispersive X-ray (EDAX) micro-analyser. The samples were then subjected to demineralization by using demineralizing solution. The samples were grouped (n=26) based on the remineralizing agent used, Group 1: Vantej, Group 2: CPP-ACP, Group 3: Icon. After the application of remineralizing agent, the mineral content was measured using EDAX. After remineralization, there was a significant difference between the groups when calcium and phosphorous ratios (Ca:P) were compared, showing greater potential of remineralization for CPP-ACP followed by Vantej and Icon group. CPP-ACP performed better than Vantej and Icon in remineralizing the demineralized enamel.


[Treatment of malignant tracheo-bronchial tumors. The lost generation].
250,000 new cases of endobronchial carcinoma are diagnosed each year in France. Risk factors are well known: 80-90% are related to smoking. With an overall 5-year survival rate of only 10%, preventive measures must be our number one priority, especially for young patients, but are their parents a lost generation? Curative therapy has made some progress, particularly with surgery, although only 20% of the patients are potential candidates at diagnosis, and chemotherapy, sometimes in combination with radiotherapy for nonoperable patients. Interesting results have also been achieved with gene therapy where direct intratumoral injection of cytokine genes on recombinant adenoviruses has provided response in certain cases. Interventional bronchoendoscopy provides another promising option as demonstrated by Jeanfaivre and Tuchais who report their results with electrotherapy in this issue of La Presse Médicale.


The relationship between task mastery, role clarity, social acceptance, and stress: An intensive longitudinal study with a sample of newly registered nurses.
Transitioning into a new professional role is challenging. Unfortunately, little is currently known about how to reduce experiences of stress among new professionals. The socialization processes role clarity, task mastery, and social acceptance are assumed to reduce experiences of stress as they mediate new professionals' acquisition of knowledge, skills, attitudes, and behaviors. However, little prospective data is available on the actual effect of the processes on stress. To prospectively investigate how the socialization processes relate to experiences of stress among new nurses during the first three months of professional working life. Specifically, to investigate development over time, as well as how episodes of increased or decreased levels of the socialization processes relate to concurrent levels of stress. The general purpose of this investigation was to examine the suitability of the socialization processes as targets of an intervention seeking to reduce stress among new professionals. An intensive longitudinal study with weekly data collections over three months. 264 newly graduated Swedish nurses who started their first job during the period of the study. The participants were followed prospectively during 14 consecutive weeks after their professional entry. Data on stress (Stress and Energy Questionnaire), role clarity (General Questionnaire for Psychological and Social Factors at Work), task mastery, and social acceptance (Needs Satisfaction and Frustration Scale) were collected weekly using digital surveys (mean response rate 82.7%). Data was analyzed using a multilevel model for intensive longitudinal data. For the typical nurse, stress decreased by 0.13 units per month, role clarity and task mastery increased by 0.08 and 0.05 units, and social acceptance decreased by 0.08 units. In addition, the slopes of 95 percent of the new nurses varied within 1.18 (stress), 0.72 (role clarity), 0.44 (task mastery), and 0.86 (social acceptance) units of the typical nurse. Most importantly, when the new nurses experienced higher levels of task mastery, role clarity, and social acceptance, they experienced lower levels of stress (within-person parameter estimates: task mastery -0.40, p = .001; role clarity -0.34, p = .001; and social acceptance -0.33, p = .001). Supporting the development of the socialization processes could be one theoretically based strategy to reduce levels of stress among new nurses. As stress among new professionals is not unique to the nursing profession, and the processes are considered important mediators of new professionals' adaptation in general, the results from this study should likely be generalizable to other professions.


Acoustic modulation of neural activity in the hypothalamus of the leopard frog.
Horseradish applications in the ventral hypothalamus of the northern leopard frog, Rana pipiens, demonstrated inputs from three auditory nuclei, the anterior and central thalamic nuclei and the secondary isthmal nucleus, in a pattern identical to that seen in Rana catesbeiana. Single-unit recordings from the area receiving these inputs revealed neurons with high spontaneous firing rates. In approximately half of the isolated neurons, the firing rate could be increased or, less often, decreased, by more than 20% by the presentation of a repetitive noise burst or conspecific mating call. Treatment with human chorionic gonadotropin prior to recording resulted in no significant differences in the number or response properties of the acoustically sensitive hypothalamic cells. These results suggest that acoustic signals such as those used for intraspecific communication can modulate neural activity in a part of the basal forebrain involved in endocrine regulation.


A yellow fluorescent protein with reduced chloride sensitivity engineered by loop-insertion.
Light it up! We demonstrate a novel way to reduce the chloride sensitivity of yellow fluorescent protein by inserting glycine residues in its loop region. The length and position for the insertion were optimized experimentally, and a plausible underlying mechanism is proposed.


The visual mismatch negativity elicited with visual speech stimuli.
The visual mismatch negativity (vMMN), deriving from the brain's response to stimulus deviance, is thought to be generated by the cortex that represents the stimulus. The vMMN response to visual speech stimuli was used in a study of the lateralization of visual speech processing. Previous research suggested that the right posterior temporal cortex has specialization for processing simple non-speech face gestures, and the left posterior temporal cortex has specialization for processing visual speech gestures. Here, visual speech consonant-vowel (CV) stimuli with controlled perceptual dissimilarities were presented in an electroencephalography (EEG) vMMN paradigm. The vMMNs were obtained using the comparison of event-related potentials (ERPs) for separate CVs in their roles as deviant vs. their roles as standard. Four separate vMMN contrasts were tested, two with the perceptually far deviants (i.e., "zha" or "fa") and two with the near deviants (i.e., "zha" or "ta"). Only far deviants evoked the vMMN response over the left posterior temporal cortex. All four deviants evoked vMMNs over the right posterior temporal cortex. The results are interpreted as evidence that the left posterior temporal cortex represents speech contrasts that are perceived as different consonants, and the right posterior temporal cortex represents face gestures that may not be perceived as different CVs.


Contrast injection protocols for coronary computed tomography angiography using a 64-detector scanner: comparison between patient weight-adjusted- and fixed iodine-dose protocols.
To compare patient-weight-adjusted and fixed iodine-dose protocols at coronary computed tomography angiography (CTA) using a 64-detector scanner and computer-assisted bolus tracking. Approval from our institutional review board and patient prior informed consent were obtained before entering 60 patients with suspected coronary disease in this study. The patients were randomly assigned to one of 2 protocols. In the fixed iodine-dose protocol, they received a fixed dose of 80 mL Iopamidol-370; the injection duration was 20 seconds. In the weight-adjusted iodine-dose protocol, the dose was tailored to the patient body weight; this group received 1.0 mL/kg and the injection duration was shorter, ie, 15 seconds. Imaging was on a 64-detector CT scanner using a computer-assisted bolus tracking technique. A radiologist blinded to the protocol used measured the Hounsfield density number of the large vessels and coronary arteries. CT attenuation in the aortic root was compared in patients whose weight was less than 58 kg (group 1) or 58 kg or more (group 2). The standard deviation (SD) of CT attenuation in the aortic root and the myocardium was compared with evaluate image noise. Using a 3-point scale, 2 radiologists independently evaluated beam-hardening artifacts and coronary enhancement. Statistical analysis was with the two-tailed Student t test and the Mann-Whitney U test. There was no significant difference between the protocols with respect to CT attenuation of the ascending aorta and coronary arteries. Under the fixed-iodine-dose protocol, mean CT attenuation in the aortic root was 421.3 +/- 51.5 Hounsfield unit (HU) in the lighter-, and 397.2 +/- 42.3 HU in the heavier weight group, respectively; the difference was statistically significant (P = 0.03). Under the weight-adjusted iodine-dose protocol, these values were 407.6 +/- 85.1 and 409.2 +/- 47.9 HU, respectively and the difference was not statistically significant (P = 0.17). The SD of the ascending aorta and myocardium was significantly higher for the fixed- than the weight-adjusted iodine-dose protocol. The mean visual score for beam-hardening artifacts was significantly lower in the weight-adjusted- than the fixed-iodine-dose protocol (P < 0.01), however, there was no significant difference in the enhancement of the coronary arteries (P = 0.82). At 64-detector CTA of the heart, the patient weight-tailored dose protocol with the 15-second injection duration yielded significantly better image quality than the fixed-dose, 20-second injection duration protocol.


Topological mapping of the P1-adhesin of Mycoplasma pneumoniae with adherence-inhibiting monoclonal antibodies.
Five adherence-inhibiting monoclonal antibodies (mAbs) were used for topological mapping of the binding sites of the 169 kDa membrane-integrated adhesin of Mycoplasma pneumoniae. Antibody binding sites were characterized using overlapping synthetic octapeptides. Three regions of the protein seem to be involved in adherence: the N-terminal region [N-reg, epitopes beginning at amino acid (aa) 1 to aa 14 and aa 231 to aa 238, respectively]; a domain (D1) approximately in the middle of the molecule (beginning at aa 851 to aa 858 and aa 921 to aa 928); and a domain (D2) closer to the C-terminus (beginning at aa 1303 to aa 1310, aa 1391 to aa 1398 and aa 1407 to aa 1414). Each of the mAbs P1.26 and P1.62 reacted with two primary amino acid sequences. Both antibodies bound to the D1 region, but mAb P1.62 showed additional binding to a sequence (aa 231 to aa 238) near the N-terminus, and mAb P1.26 reacted with a second epitope in the D2 domain (aa 1303 to aa 1310). Such dual binding by the two antibodies suggests that in the native protein the epitopes are composed of two sequences which are located on two different sites of the molecule (D1/N-reg and D1/D2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Unsplinted Attachment Systems and Peri-implant Outcomes in Two-implant-retained Mandibular Overdentures: A Systematic Review of Randomized Controlled Trials.
The purpose of this review is to compare randomized clinical trials evaluating the peri-implant tissue outcomes using different unsplinted attachment systems in two implant-retained mandibular overdentures. Literature lacks information on various unsplinted attachment systems and their effect on peri-implant tissue health. A focus question (as per PICOS) was set as follows: Does one particular unsplinted attachment system (I) compared with another (C) results in better peri-implant outcomes (O) in two implant-retained mandibular overdentures (P) using randomized controlled trials (RCTs) (S)? The literature search was conducted in the PubMed, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases between January 2011 and December 2021. The keywords used were "denture, overlay," "denture," "overlay" AND "dental prosthesis, implant supported," "dental implants," "dental implant abutment design" AND "jaw, edentulous," "mouth, edentulous" AND "mandible." Only RCTs on two implant-retained mandibular overdentures using unsplinted attachment systems measuring peri-implant tissue outcomes with minimum 1-year follow-up were selected. In total, 224 studies were identified in initial search, and 25 were shortlisted for full-text evaluation. Four studies were included for systematic review upon considering inclusion and exclusion criteria. The risk of bias was evaluated using Cochrane Risk of Bias Tool 2.0 (RoB 2.0). A total of 41 patients received ball attachments (in 3 studies), 36 patients received low-profile attachments (in 3 studies), 16 patients received magnet attachments (in 1 study), and 13 patients received telescopic attachments (in 1 study). All four studies used standard sized implants, however, differed in implant manufacturers. Two studies which compared ball attachments low-profile attachments revealed-similar peri-implant tissue health parameters but differed in crestal bone-level changes. One study compared ball with telescopic attachments and revealed similar results in crestal bone-level changes and all four peri-implant tissue health parameters. Single study compared magnets with low-profile attachments and shown lesser bone loss with magnet attachments. Single study was judged to have low risk of bias, single with some concerns, and remaining two to have high risk of bias. Gingival index and bleeding index of the patients were not influenced by any of the unsplinted overdenture attachment (stud, magnet, telescopic) system. Inconclusive results found among the studies evaluated comparing crestal bone loss and plaque index. This review manuscript has simplified comparative analysis of different unsplinted attachment systems used in two implant mandibular overdentures to help clinicians choose correct system in such situation.


A noninvasive technique for monitoring changes in canine prostatic size in vivo.
We describe a procedure for monitoring changes in canine prostatic size. Metal beads were sutured to the surface of the prostate and the interbead distances were derived from two X-rays taken at right angles. Prostatic hyperplasia was induced by castration and injection of 5 alpha-androstane-3 alpha, 17 beta-diol and 17 beta-estradiol. Prostatic regression was caused by castration without further treatment. Although growth of the prostate was nonuniform, changes in prostatic volume were shown to be related to the third power of the distance between appropriate beads. This monitoring technique can be repeated every 2nd day if necessary, and thus has an advantage over procedures that require repeated laparotomies. Significant increases in prostatic volume could be detected within 5 days after steroid injection.


The role of biochemical risk factors in the etiology of AIS in children and adults.
Stroke is an abrupt onset of both focal and global neurological deficits secondary to a vascular event lasting more than 24 h and with a vascular background as its only cause. It can be triggered by a rupture of a blood vessel, aneurysm (hemorrhagic stroke, HS), thrombosis or embolisms (ischemic stroke, IS). In developed countries, it is the third most common cause of death in the adult population. Stroke in children is a rare disorder with a reported frequency of about 3 cases per 100,000 children per year. The history of acute brain ischemia is burdened with neurological complications such as motor impairment, speech impairment and intellectual delay. Moreover, in children after AIS seizures and epilepsy are also quite common. Stroke is a heterogeneous disorder; its risk factors in adults are well known, however, in pediatrics, in more than 20% cases, the cause of stroke is impossible to determine. Due to the fact that stroke usually arises as a consequence of the cerebral thrombosis, many of the mechanisms responsible for its occurrence can be considered as risk factors. We have reviewed the recent case-control studies conducted on pediatric patients regarding biochemical risk factors such as elevated levels of homocysteine, fibrinogen, protein C, protein S, antithrombin III, lipoprotein(a), cholesterol and its fractions, and compared them with the results obtained from adult patients.


A pilot study of serotonergic modulation after long-term administration of oxytocin in autism spectrum disorder.
Oxytocin (OT) and the serotonergic system putatively play important roles in autism spectrum disorder (ASD) etiology and symptoms, but no direct neurobiological evidence exists for long-term OT administration effects on the brain's serotonergic system. This pilot study examined 10 male participants with ASD who were administered OT intranasally for 8-10 weeks in an open-label, single-arm, nonrandomized, and uncontrolled manner. Positron emission tomography (PET) with a radiotracer (11 C)-3-amino-4-(2-[(dimethylamino)methyl]phenylthio)benzonitrile (11 C-DASB) was used before and after OT treatment. The binding potential of serotonin transporter (11 C-DASB BPND ) was then estimated. The main outcome measures were changes in 11 C-DASB BPND and their correlation with changes in symptoms. ASD participants showed significantly elevated 11 C-DASB BPND in the left inferior frontal gyrus extending to the left middle frontal gyrus. No significant correlation was found between the change in any clinical symptom and the change in 11 C-DASB BPND . This report of a pilot study is the first describing long-term effects of OT on the brain's serotonin system in ASD. Additional randomized controlled studies must be conducted to confirm whether activation of the serotonergic system contributes to the prosocial effect of OT in people with ASD. Autism Res 2017, 10: 821-828. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.


Consumer perspectives on pediatric rheumatology care and service delivery: a qualitative study.
This study aimed to elicit parental and adolescent perspectives on pediatric rheumatology care and service delivery and to describe the impact of this process on a proposed model of care addressing pediatric rheumatology service delivery. Adolescents with juvenile idiopathic arthritis (JIA) and caregivers in New South Wales, Australia, participated in focus groups or semistructured interviews conducted from August to November 2011. Transcripts were coded and thematically analyzed. Changes to the model of care as a result of this process were identified. Thirty-seven parents and 13 adolescents participated. Five main themes were identified including (1) optimize service efficiency (promoting awareness about JIA, minimizing delays in diagnosis and treatment, continuity of care, holistic and integrated care, access to health care providers with JIA expertise, extending pharmacy services, regional outreach programs); (2) transitional care (trust and rapport with the adult rheumatologist, comprehensive information transfer of patient history); (3) psychosocial support (social and financial aid, mental health services, vocational guidance, peer support); (4) informational needs (medicine adverse effects, nutritional guidance, pain management, administering medications, obtaining medical equipment); and (5) school-based support and advocacy (to promote acceptance, provide academic assistance, facilitate environmental modifications, offer alternative activities). The model of care was extended to include consumer-focused concerns. A well-coordinated network of services, timely and accurate information about the illness, treatment and support services, adequate pharmacy support, and school-based advocacy are proposed to be needed to ensure pediatric rheumatology services that are accessible and responsive to the needs of patients and their families.


The Relationship Between How Participants Articulate Their Goals and Accomplishments and Weight Loss Outcomes: Secondary Analysis of a Pilot of a Web-Based Weight Loss Intervention.
In behavioral weight loss interventions, participants are asked to set weekly goals to support long-term habits that lead to weight loss. Although participants are asked to set and accomplish weekly goals, we do not know how often they do this and whether doing so is associated with weight loss. Web-based weight loss interventions allow for the analysis of participant engagement data, including how participants articulate their goals and accomplishments. Using engagement data from a web-based weight loss intervention, we examined whether participants articulating their goals and accomplishments in measurable and repeating terms were associated with greater weight loss. Adults with overweight or obesity received a 12-week Facebook-delivered weight loss intervention based on the Diabetes Prevention Program Lifestyle Intervention. Participants replied to conversation threads that queried about their goals and accomplishments. Two independent coders classified participants' posts that articulated goals or accomplishments as measurable or repeating. Crude and age-adjusted linear regression models were used to examine the relationship between the frequency of post type and percent weight loss. Participants (N=53; n=48, 91% female; n=48, 91% non-Hispanic White) were on average 46.2 (SD 10.5) years old with a mean BMI of 32.4 (SD 4.8) kg/m2. Over 12 weeks, participants shared a median of 4 (IQR 1-8) posts that reported goals and 10 (IQR 4-24) posts that reported accomplishments. Most participants shared ≥1 post with a goal (n=43, 81%) and ≥1 post with an accomplishment (n=47, 89%). Each post reporting a goal was associated with 0.2% greater weight loss (95% CI -0.3% to 0.0%). Sharing ≥1 post with a repeating goal was associated with an average of 2.2% greater weight loss (95% CI -3.9% to -0.4%). Each post with a repeating goal was associated with an average of 0.5% greater weight loss (95% CI -1.0% to 0.0%). Sharing ≥1 post with measurable and repeating goals was associated with an average of 1.9% greater weight loss (95% CI -3.7% to -0.2%). Sharing each post with an accomplishment was associated with an average of 0.1% greater weight loss (95% CI -0.1% to 0.0%). Every post with an accomplishment that was repeating was associated with an average of 0.2% greater weight loss (95% CI -0.3% to 0.0%). Sharing other types of goals and accomplishments was not associated with weight loss. In a web-based weight loss intervention, stating goals in repeating or both measurable and repeating terms was associated with greater weight loss, but simply stating them in measurable terms was not. For accomplishments, only those articulated in repeating terms were associated with greater weight loss. Posts about one-time goals and accomplishments represent an opportunity to encourage planning for future behaviors. Future research should examine if stating goals and accomplishments in repeating terms signals habit formation.