Microbial lithotrophic oxidation of structural Fe(II) in biotite.
Microorganisms are known to participate in the weathering of primary phyllosilicate minerals through the production of organic ligands and acids and through the uptake of products of weathering. Here we show that the lithotrophic Fe(II)-oxidizing, nitrate-reducing enrichment culture described by Straub et al. (K. L. Straub, M. Benz, B. Schink, and F. Widdel, Appl. Environ. Microbiol. 62:1458-1460, 1996) can grow via oxidation of structural Fe(II) in biotite, a Fe(II)-rich trioctahedral mica found in granitic rocks. Oxidation of silt/clay-sized biotite particles was detected by a decrease in extractable Fe(II) content and simultaneous nitrate reduction. Mössbauer spectroscopy confirmed structural Fe(II) oxidation. Approximately 1.5 × 10(7) cells were produced per μmol of Fe(II) oxidized, in agreement with previous estimates of the growth yield of lithoautotrophic circumneutral-pH Fe(II)-oxidizing bacteria. Microbial oxidation of structural Fe(II) resulted in biotite alterations similar to those found in nature, including a decrease in the unit cell b dimension toward dioctahedral levels and Fe and K release. Structural Fe(II) oxidation may involve either direct enzymatic oxidation, followed by solid-state mineral transformation, or indirect oxidation as a result of the formation of aqueous Fe, followed by electron transfer from Fe(II) in the mineral to Fe(III) in solution. Although it is not possible to distinguish between these two mechanisms with available data, the complete absence of aqueous Fe in oxidation experiments favors the former alternative. The demonstration of microbial oxidation of structural Fe(II) suggests that microorganisms are directly responsible for the initial step in the weathering of biotite in granitic aquifers and the plant rhizosphere.


Hydrodynamic force on a particle oscillating in a viscous fluid near a wall with dynamic partial-slip boundary condition.
The hydrodynamic force on a particle oscillating in a viscous fluid near a wall with partial-slip boundary condition is studied on the basis of the linearized Navier-Stokes equations. Both incompressible and compressible fluids are considered. It is assumed that the slip length characterizing the partial-slip boundary condition depends on frequency. The consequences of this assumption for the spectrum of Brownian motion near a wall are investigated and compared with a recent experiment.


Bypass and flow reduction for complex basilar and vertebrobasilar junction aneurysms.
Giant aneurysms of the vertebral and basilar arteries are formidable lesions to treat. To evaluate the long-term outcomes of patients with vertebrobasilar aneurysms treated with extracranial-intracranial bypass and flow reduction. We retrospectively reviewed a prospective database of aneurysms cases treated between December 1993 and August 2011. Eleven patients (8 male, 3 female) with 12 aneurysms were treated. There were 3 basilar apex aneurysms, 2 aneurysms of the basilar trunk, and 7 vertebrobasilar junction aneurysms. There were 5 saccular and 7 fusiform aneurysms. All patients underwent extracranial-intracranial bypass and vessel occlusion. Flow was reversed or reduced by complete (n = 6) or partial occlusion of the basilar artery (n = 3) or by occlusion of the vertebral arteries distal to the posterior inferior cerebellar artery (n = 3). Postoperatively (mean follow-up, 71.6 months; range, 4-228; median, 49 months), the bypass patency rate was 92.3% (12/13). The perioperative mortality rate for the initial treatment was 18.2% (2/11). In 4 cases, the aneurysms continued to grow and required further treatment; after re-treatment, 3 of these patients died. Of the initial 11 patients, 6 were treated successfully and 5 died. The mean preoperative modified Rankin Scale score was 2.1 (range, 1-3; median, 2). At last follow-up for all patients, the mean modified Rankin Scale score was 3.45 (range, 1-6; median, 3) and 2.5 (range, 1-4; median, 2.5) for the 6 long-term survivors. Vertebrobasilar aneurysms are challenging lesions with limited microsurgical or endovascular options. Despite aggressive surgical treatment, the long-term outcome remains poor for most patients.


Controlling the location and spatial extent of nanobubbles using hydrophobically nanopatterned surfaces.
The presence of nanobubbles-as imaged with tapping-mode atomic force microscopy-is controlled using nanopatterned surfaces possessing repeating patterns of polystyrene (hydrophobic domains) and poly(methyl methacrylate) (hydrophilic domains). For nanobubbles to be present, we find that, in addition to controlling the degree of surface hydrophobicity, it is important for the spatial dimensions of the hydrophobic domains on the nanopatterned surface to be commensurate with the equilibrium topology of the nanobubbles.


Sexual and drug-related vulnerabilities for HIV infection among women engaged in survival sex work in Vancouver, Canada.
Women engaged in survival sex work face multiple sexual and drug-related harms that directly enhance their vulnerability to HIV infection. Although research on injection-drug-using women has explored predictors of sex work and HIV infection, little information currently exists on the complex vulnerabilities to HIV transmission faced by survival sex workers in this setting. This analysis aimed to determine HIV prevalence among women engaged in survival sex work, and explore sexual and drug-related vulnerabilities associated with baseline infection. Descriptive and univariate analysis were used to explore associations with baseline HIV infection. Variables found to be associated with baseline infection at the univariate level (p<0.05) were entered into a fixed logistic regression model, adjusted for age. Of a total of 198 women, baseline HIV prevalence was 26%. In multivariate logistic regression, baseline HIV infection was associated with early age of sex work initiation (<18 years) (aOR=1.8, 95% CI: 1.3-2.2), Aboriginal ethnicity (aOR=2.1, 95% CI: 1.4-3.8), daily cocaine injection (aOR=2.2, 95% CI: 1.3-3.5), intensive, daily crack smoking (aOR=2.7, 95% CI: 2.1-3.9), and unprotected sex with an intimate partner (aOR=2.8, 95% CI: 1.9-3.6). Innovative and evidence-based strategies are urgently needed that address the sexual and drug-related vulnerabilities to HIV infection among survival sex workers and in particular, interventions targeting the precursors to early initiation into sex work.


Bioengineering of carbon fixation, biofuels, and biochemicals in cyanobacteria and plants.
Development of sustainable energy is a pivotal step towards solutions for today's global challenges, including mitigating the progression of climate change and reducing dependence on fossil fuels. Biofuels derived from agricultural crops have already been commercialized. However the impacts on environmental sustainability and food supply have raised ethical questions about the current practices. Cyanobacteria have attracted interest as an alternative means for sustainable energy productions. Being aquatic photoautotrophs they can be cultivated in non-arable lands and do not compete for land for food production. Their rich genetic resources offer means to engineer metabolic pathways for synthesis of valuable bio-based products. Currently the major obstacle in industrial-scale exploitation of cyanobacteria as the economically sustainable production hosts is low yields. Much effort has been made to improve the carbon fixation and manipulating the carbon allocation in cyanobacteria and their evolutionary photosynthetic relatives, algae and plants. This review aims at providing an overview of the recent progress in the bioengineering of carbon fixation and allocation in cyanobacteria; wherever relevant, the progress made in plants and algae is also discussed as an inspiration for future application in cyanobacteria.


Minimal role of hepatitis B virus in posttransfusion non-A, non-B hepatitis in Taiwan: a study by polymerase chain reaction.
Using the polymerase chain reaction (PCR) for hepatitis B virus (HBV) DNA and an enzyme linked immunosorbant assay for the antibody to the hepatitis C virus (anti-HCV), we studied the serum samples of 18 patients with posttransfusion non-A, non-B (NANB) hepatitis in a prospective study. They were all negative for both the hepatitis B surface antigen (HBsAg) and the IgM antibody to the hepatitis B core antigen (IgM anti-HBc) by radioimmunoassay and were all negative for hepatitis B virus (HBV) DNA by dot blot hybridization. Eleven patients were positive for anti-HCV in the posttransfusion sera and 2 were already positive in the pretransfusion sera. Therefore, seroconversion of anti-HCV was noted in 9 patients. Two of these 18 patients were positive for HBV DNA by PCR in the posttransfusion sera and one of the 2 patients was also positive in the pretransfusion serum sample. The patient positive for HBV DNA in both pre and posttransfusion sera seroconverted to anti-HCV, while the patient positive for HBV DNA only in the posttransfusion sera was not seroconverted. We conclude that HBV plays minimal role in patients with posttransfusion NANB hepatitis in Taiwan even studied by PCR.


Role of cytosolic free calcium and phospholipase C in leukotriene-B4-stimulated secretion in human neutrophils. Comparison with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine.
Various leukotriene analogues were tested for their capacity to raise the cytosolic free calcium concentration, [Ca2+]i, and to stimulate exocytosis in human neutrophils. Their order of potency for both parameters was LTB4 greater than the stereochemical isomer of LTB4, (5S, 12S)-LTB4 much much greater than the sulphidopeptides LTD4, LTC4. The correlation between [Ca2+]i and secretion indicates that an increase of [Ca2+]i above a threshold level of about 300 nM is necessary for stimulating secretion with LTB4. This threshold is about an order of magnitude higher than that required for the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe). The increase in [Ca2+]i elicited by LTB4 was unaffected by increasing cellular cAMP, while secretion was completely inhibited. These results indicate, that similar to fMet-Leu-Phe, leukotrienes generate other signals in addition to [Ca2+]i elevations. Contrary to previous claims, leukotrienes stimulate polyphosphoinositide hydrolysis, as indicated by the increase in [3H]inositol trisphosphate, InsP3, observed upon stimulation of myo[3H]inositol-labelled neutrophils with LTB4 or (5S, 12S)-LTB4. The two InsP3 isomers [Ins(1,4,5)P3 and Ins(1,3,4P3] were separated by high-pressure liquid chromatographed and, as reported for other cell types, the formation of Ins(1,4,5)P3 precedes that of Ins(1,3,4)P3. Maximal stimulatory doses of LTB4 or (5S, 12S)-LTB4 produce about 50% the amount of InsP3 generated by equimolar concentrations of fMet-Leu-Phe. The present observations suggest that, though the transmembrane signalling systems activated by LTB4 and fMet-Leu-Phe are the same, the different efficacy of these two agonists at stimulating neutrophil functions is due, at least in part, to a different degree of activation of phospholipase C.


Acidic Microenvironment Aggravates the Severity of Hepatic Ischemia/Reperfusion Injury by Modulating M1-Polarization Through Regulating PPAR-γ Signal.
Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages in vivo. Macrophages were cultured under low pH conditions to analyze the polarization of macrophages in vitro. Activation of the PPAR-γ signal was determined by Western blot. PPAR-γ agonist GW1929 was administrated to functionally test the role of PPAR-γ in regulating macrophage-mediated effects in the acidic microenvironment during HIRI. We demonstrate that acidic microenvironment aggravated HIRI while NaHCO3 reduced liver injury through neutralizing the acid, besides, liposome abolished the protective ability of NaHCO3 through depleting the macrophages. In vivo and vitro experiment showed that acidic microenvironment markedly promoted M1 polarization but inhibited M2 polarization of macrophage. Furthermore, the mechanistic study proved that the PPAR-γ signal was suppressed during the polarization of macrophages under pH = 6.5 culture media. The addition of PPAR-γ agonist GW1929 inhibited M1 polarization under acidic environment and reduced HIRI. Our results indicate that acidic microenvironment is a key regulator in HIRI which promoted M1 polarization of macrophages through regulating PPAR-γ. Conversely, PPAR-γ activation reduced liver injury, which provides a novel therapeutic concept to prevent HIRI.


[A case of acute eosinophilic pneumonia due to Sho-saiko-to].
A 16-year-boy who had taken a common over-the-counter cold remedy containing Sho-saiko-to, presented with fever, severe cough, sputum and dyspena. Two days later, he was admitted because a negative density, pulmonary edema-like shadow was noted on chest X-ray. A diagnosis of drug-induced pneumonia was strongly suspected, because an arterial blood gas analysis showed severe hypoxemia and leukocytosis with eosinophilia, and the chest X-ray showed a diffuse negative density pulmonary edema like shadow bilaterally. The findings on microscopic examination of transbronchial lung biopsy specimens were compatible with eosinophilic pneumonia. The eosinophil percentage in the bronchoalveolar lavage fluid was high. The result of a lymphocyte-stimulation test was positive for Sho-saiko-to, and Sho-saiko-to-induced pneumonia was strongly suspected. The patient ceased taking the cold remedy, and prednisolone was given. The clinical symptoms, severe hypoxemia, and chest X-ray findings markedly improved. To the best of our knowledge, there have been no previous reports of acute eosinophilic pneumonia induced by Sho-saiko-to.


The nature and correlates of Mexican-American adolescents' time with parents and peers.
Drawing on cultural-ecological and person-environment fit perspectives, this study examined links among Mexican-American adolescents' time with peers and parents, parents' cultural orientations, and adolescents' psychosocial adjustment and cultural orientations. Participants were 492 Mexican-American adolescents (Ms=15.7 and 12.8 years for older siblings and younger siblings) and their parents in 246 families. Family members described their family relationships, cultural orientations, and psychosocial functioning in home interviews, and time-use data were collected during a series of nightly phone calls. Mexican-American adolescents spent the majority of their peer time with Mexican youth. Some support was found for the hypothesis that the mismatch between parents' cultural orientations and adolescents' peer involvement is linked to adolescents' psychosocial functioning.


Electronic spectroscopy of toluene-rare-gas clusters: the external heavy atom effect and vibrational predissociation.
Toluene-X van der Waals clusters (where X = Ne, Ne2, Ar, Ar2, Kr, Xe) have been investigated by fluorescence excitation spectroscopy in the region of the S1-S0 transition. With the exception of Xe, for each rare-gas studied, we have assigned cluster transitions in the region of all the strong monomer vibrational bands up to 1000 cm(-1) above the origin band. We have further investigated the S1 relaxation dynamics for each vibrational level of each complex, via their fluorescence decay profiles. Clustering with neon has little appreciable effect on the vibrationless S1 lifetime. By contrast, the clusters with argon and krypton exhibit markedly shorter fluorescence lifetimes compared with the monomer. The effect is so severe in the case of toluene-Xe clusters that no fluorescence signals were observed. We interpret these results in terms of an external heavy atom effect in which the rate of intersystem crossing in toluene is influenced by the cluster partner. For clusters built upon excited S1 vibrational levels, the situation is potentially complicated by intramolecular vibrational redistribution and vibrational predissociation (VP). The majority of the fluorescence decay profiles were satisfactorily modeled using single exponential decays. The emission following pumping of the 37(1) level in the toluene-Kr cluster, however, is an exception. We have modeled the decay of this level with a simple kinetic scheme including VP and determined a predissociation rate of (1.04 +/- 0.54) x 10(7) s(-1).


[AGGLUTINATION OF MESOPHYLL PLASTIDS AND OBLITERATION OF PHLOEM SIEVE TUBES ARE THE TOTAL RESULT OF SEASONAL PAUSES IN PHOTOSYNTHATE EXPORT].
Chloroplast agglutination and sieve tube obliteration are related to the different plant tissues: the agglutination--to the leaf mesophyll, and the obliteration--to the axis phloem. Being equally produced by photosynthate export dynamics, both phenomena are synchronous and can be used for diagnostics of seasonal flashes and pauses of photosynthetic activity with equal success. The nature of the mobility of chloroplast and their shuttle displacements from the nuclear envelope to the cell periphery connected with export dynamics have been established. It is assumed that nuclear envelope is the base structure of the endoplasmic reticulum (ER) inside which the chloroplasts are localized. Activation of photosynthesis and sugar accumulation inside the ER induces its expansion followed by centrifugal diffusion of chloroplasts. Come back effect--ER collapse, its return to the source--can be induced by the blockade of photosynthesis. Centripetal collapse is accompanied by plastid concentration around the nuclear envelope. Displacements of ER and the chloroplasts dislocating inside it are reversible. It depends on seasonal fluctuations of photosynthesis and export intensities. Changes in the volume of sieve tubes, which are due to the same reason, are irreversible. Each seasonal wave of photosynthesis and sugar export forms new series of sieve tubes, replacing obliterated ones.


Dual-Responsive Molecular Switches Based on Dithienylethene-RuII Organometallics in Self-Assembled Monolayers Operating at Low Voltage.
Two carbon-rich ruthenium complexes bearing a dithienylethene (DTE) unit and a hexylthiol spacer were designed to be attached on gold surfaces. Both compounds display photochemically driven switching properties, allowing reversible conversion from open to closed forms of the DTE units upon irradiation in solution. In contrast, only the bimetallic complex undergoes an efficient electrochemical ring closure at low potential, (0.5 V vs. SCE), whereas the monometallic complex shows a simple one-electron reversible redox event. These appealing switching properties could be successfully transferred within diluted self-assembled monolayers (SAMs). Furthermore, the two immobilized organometallics exhibit fast electron-transfer kinetics. Therefore, this organometallic strategy allows us to obtain multifunctional surfaces with the possibility of combining switching events triggered by an electrochemical oxidation at low potential and by light at distinct wavelengths for a write-and-erase function, along with an access to different oxidation states. Importantly, a non-destructive electrochemical read-out is achieved at a sufficiently high scan rate that prevents any electrochemical closing. On the whole, the two surface-confined organometallic compounds exhibit appealing properties for application in molecular electronics.


Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain neurons.
Increased levels of unconjugated bilirubin, the end-product of heme catabolism, are detrimental to the central nervous system. To examine the role of apoptosis in bilirubin-induced toxicity and to characterize the biochemical pathway of cell death, we exposed developing rat brain neurons to purified unconjugated bilirubin at concentrations below and above saturation of human serum albumin. Isolated neurons treated with bilirubin showed increased levels of apoptosis. Mitochondrial cytochrome c was extensively released and accumulated in cytosol. Consistent with this observation, caspase-3 was activated and the full-length substrate poly(ADP)ribose polymerase (PARP) degraded, even in the presence of very modestly elevated concentrations of bilirubin. In parallel, all events were prevented in cells preincubated with ursodeoxycholate. Further experiments showed that bilirubin diminished mitochondrial transmembrane potential (DeltaPsi(m)) and increased mitochondrial-associated Bax protein levels, while directly disrupting membrane lipid and protein structure. In conclusion, bilirubin induces mitochondrial depolarization and Bax translocation via physical interaction with membranes, mediating the mitochondrial pathway of apoptosis in neurons exposed to bilirubin. These results provide a novel insight into the mechanism of bilirubin-induced toxicity.


Water-soluble carbohydrates and fructan structure patterns from Agave and Dasylirion species.
Fructans, storage carbohydrates with beta-fructofuranosyl linkages, are found in approximately 15% of higher plants. The metabolic flexibility of those molecules allows them easily to polymerize and depolymerize to soluble carbohydrates according to plant development stage and environmental conditions. In this work, water-soluble carbohydrates, including fructan structure patterns, were compared among Agave and Dasylirion species grown in different environmental regions in Mexico. Fructans were the main storage carbohydrate present in Agave stems, in addition to other carbohydrates related to its metabolism, whereas Dasylirion spp. presented a different carbohydrate distribution. A good correlation of water-soluble carbohydrate content with climatic conditions was observed. Fructans in Agave and Dasylirion genera were found in the form of polydisperse molecules, where structural heterogeneity in the same plant was evidenced by methylation linkage analysis and chromatographic methods. Fructans from the studied species were classified into three groups depending on DP and linkage-type abundance. These storage carbohydrates share structural characteristics with fructans in plants that belong to the Asparagales members. Agave and Dasylirion fructans can be categorized as graminans and branched neo-fructans, which we have termed agavins.


Investigating work-related neoplasia associated with solar radiation.
Both solar and non-solar exposures associated with occupation and work tasks have been reported as skin carcinogens. In the UK, there are well-established surveillance schemes providing relevant information, including when exposures took place, occupation, location of work and dates of symptom onset and diagnosis. To add to the evidence on work-related skin neoplasia, including causal agents, geographical exposure and time lag between exposure and diagnosis. This study investigated incident case reports of occupational skin disease originating from clinical specialists in dermatology reporting to a UK-wide surveillance scheme (EPIDERM) by analysing case reports of skin neoplasia from 1996 to 2012 in terms of diagnosis, employment, suspected causal agent and symptom onset. The suspected causal agent was 'sun/sunlight/ultraviolet light' in 99% of the reported work-related skin neoplasia cases. Most cases reported (91%) were in males, and the majority (62%) were aged over 65 at the time of reporting. More detailed information on exposure was available for 42% of the cases, with the median time from exposure to symptom onset ranging from 44 (melanoma) to 57 (squamous cell carcinoma) years. Irrespective of diagnostic category, the median duration of exposure to 'sun/sunlight/ultraviolet light' appeared longer where exposures occurred in the UK (range 39-51 years) rather than outside the UK (range 2.5-6.5 years). It is important to provide effective information about skin protection to workers exposed to solar radiation, especially to outdoor workers based outside the UK.


Some eighteenth century authorities on the resuscitation of the apparently drowned.
Attempts to resuscitate the apparently drowned began seriously in the eighteenth century. The theories and methods of resuscitation used or advocated by some of the early European workers have been reviewed. Many of these, including artificial ventilation, chest compression, endotracheal intubation and electrical stimulation of the heart seem to have been forgotten during the nineteenth century and not used again until recent times.


Hormones and their Structural and Functional Effects on the Brain: How Can We Change our Practice Moving Forward?
Is hormone treatment an invasive procedure? In this paper, we discuss aspects related to the choice of treating disorders of sex development (DSD) using hormones. Specifically, we focus on some of the challenging issues related to this treatment and the need to establish a standard of care for the use of hormone therapy in this patient population. The objectives of this paper are to: 1) Enhance understanding of the uncertainties in the decision-making process regarding hormonal interventions to treat patients with DSD. 2) Recognize that the effects of hormonal interventions might require a consent process similar to that applied for surgical procedures. 3) Emphasize the need to establish treatment algorithms that could form the basis of a standard of care for this patient population.


A single amino acid mutation affects elicitor and expansins-like activities of cerato-platanin, a non-catalytic fungal protein.
Cerato-platanin (CP) is a non-catalytic, cysteine-rich protein, the first member of the cerato-platanin family. It is a single-domain protein with a double Ψ/β barrel domain resembling the D1 domain of plant and bacterial expansins. Similarly to expansins, CP shows a cell wall-loosening activity on cellulose and can be defined as an expanisin-like protein, in spite of the missing D2 domain, normally present in plant expansins. The weakening activity shown on cellulose may facilitate the CP-host interaction, corroborating the role of CP in eliciting plant defence response. Indeed, CP is an elicitor of primary defences acting as a Pathogen-Associated Molecular Patterns (PAMP). So far, structure-function relationship study has been mainly performed on the bacterial BsEXLX1 expansin, probably due to difficulties in expressing plant expansins in heterologous systems. Here, we report a subcloning and purification method of CP in the engineered E. coli SHuffle cells, which proved to be suitable to obtain the properly folded and biologically active protein. The method also enabled the production of the mutant D77A, rationally designed to be inactive. The wild-type and the mutated CP were characterized for cellulose weakening activity and for PAMP activity (i.e. induction of Reactive Oxygen Species synthesis and phytoalexins production). Our analysis reveals that the carboxyl group of D77 is crucial for expansin-like and PAMP activities, thus permitting to establish a correlation between the ability to weaken cellulose and the capacity to induce defence responses in plants. Our results enable the structural and functional characterization of a mono-domain eukaryotic expansin and identify the essential role of a specific aspartic residue in cellulose weakening.


NMR solution structure of human parathyroid hormone(1-34).
The aqueous solution structure of the biologically-active N-terminal domain of human parathyroid hormone (residues 1-34) was studied by two-dimensional proton nuclear magnetic resonance (2D NMR) spectroscopy, distance geometry, and dynamic simulated annealing. Unambiguous NMR assignments of all backbone and side chain hydrogens were made with the aid of totally correlated spectroscopy experiments, which provided through-bond 1H-1H connectivities, and nuclear Overhauser effect spectroscopy, which provided through-space and sequential backbone connectivities. The NMR data acquired were utilized in a distance geometry algorithm to generate a family of structures which were then refined using dynamic simulated annealing. The major structural feature evident is alpha-helix extending from residues Glu4 to Lys13 and from Val21 to Gln29 with a turn incorporating Asn16-Glu19 resulting in a quite globular C-terminal domain with a hydrophobic core comprising Leu15, Leu18, Trp23, and Val31. Structure-activity studies are interpreted in terms of the deduced conformation of the PTH structure with particular reference to the likely PTH receptor binding site formed primarily by the bulk of the C-terminal helix.


[Digital and analog radiographic techniques in the case of thoracic diagnosis].
Up to now digital luminescens radiography has not been used widely in veterinary medicine. This paper gives an overview of the first experiences with the application of the digital ADC-System (Agfa Diagnostic Center) for imaging pulmonary nodules and other lung diseases in dogs in comparison to the conventional method. For this, we used radiographs of dogs of several weight groups with lung diseases. To compare both systems (conventional and digital) we took pictures with either method in the same positioning. Compared to the analog film screen system, the phosphor storage radiographs enhance the detection of fine details. Additionally, the digital technology gives an opportunity for post-processing of image data in order to optimize the discrimination of various image details and offers a wide latitude for exposure, which means less retakes and a wider range for dose selection. The advantage of digital filing stations is on the one hand the possibility of space saving and storage unlimited by time, on the other hand it offers the possibility to recover X ray pictures in very short time.


Treatment options for chronic hepatitis B and C infection in children.
There has been a dramatic increase in treatment options for both chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infection in adults over the past 5-10 years, resulting in standardized regimes for initial treatment, relapsers and even infection in the setting of recurrence post-liver transplantation. These regimes have resulted in the halting of the disease progression, reduction in the risk of hepatocellular carcinoma and removal of these infections as a contraindication for liver transplantation. However, treatment in children must be considered carefully in the context of the natural history of these infections and host factors, particularly the immunological mileu, which may affect response to therapy. The as yet unknown long-term effects of medications must also be balanced with the probability of significant life-long morbidity or mortality from chronic hepatitis and its complications. Furthermore, the development of drug resistance, particularly in the case of CHB, has significant implications for the pediatric patient who may exhaust effective therapeutic options at a relatively young age. For these reasons, initiation of therapy must be based on sound criteria. Based on the current data, we recommend that therapy should be offered to children with CHB who have an elevation in alanine aminotransferase (>2-3 x upper limit of normal) for more than 6 months. Therapy with interferon-alpha should be offered in the majority of cases with the aim of immune clearance as measured by early antigen seroconversion. By contrast, treatment indication for CHC in children remains controversial. If used, combination therapy with pegylated interferon and ribavirin is likely to produce the highest rates of sustained viral response.


The Burden of Power: Construing Power as Responsibility (Rather Than as Opportunity) Alters Threat-Challenge Responses.
Power usually lowers stress responses. In stressful situations, having high (vs. low) power heightens challenge and lowers threat. Yet, even power-holders may experience threat when becoming aware of the responsibility that accompanies their power. Power-holders can construe (i.e., understand) a high-power position primarily as opportunity to "make things happen" or as responsibility to "take care of things." Power-holders construing power as responsibility (rather than opportunity) may be more likely to experience demands-such as taking care of important decisions under their control-as outweighing their resources, resulting in less challenge and more threat. Four experiments with subjective and cardiovascular threat-challenge indicators support this. Going beyond prior work on structural aspects (e.g., power instability) that induce stress, we show that merely the way how power-holders construe their power can evoke stress. Specifically, we find that power construed as responsibility (vs. opportunity) is more likely to imply a "burden" for the power-holder.


[Genetic testing, prevention and health care insurance markets].
Since this special issue of medecine/sciences is devoted to personalized medicine, it seems unnecessary for two economists to summarize or discuss, from a medical perspective, recent advances in genetic research. We rather focus on the consequences of improved genetic testing on the health insurance market, on how this market may be affected and on the degree of coverage offered to consumers according to the regulations implemented. More precisely, we first study the value of the information conveyed by genetic tests and we then decompose this value into several components according to the regulations implemented in various health insurance markets.


Dear health diary...
Many women, from teenagers to those approaching the menopause, experience problems related to their menstrual cycle. A health diary can identify trends and patterns.


5 nm Ultrathin Crystalline Ferroelectric P(VDF-TrFE)-Brush Tuned for Hysteresis-Free Sub 60 mV dec-1 Negative-Capacitance Transistors.
Negative-capacitance field-effect transistors (NC-FETs) have gathered enormous interest as a way to reduce subthreshold swing (SS) and overcome the issue of power dissipation in modern integrated circuits. For stable NC behavior at low operating voltages, the development of ultrathin ferroelectrics (FE), which are compatible with the industrial process, is of great interest. Here, a new scalable ultrathin ferroelectric polymer layer is developed based on trichloromethyl (CCl3 )-terminated poly(vinylidene difluoride-co-trifloroethylene) (P(VDF-TrFE)) to achieve the state-of-the-art performance of NC-FETs. The crystalline phase of 5-10 nm ultrathin P(VDF-TrFE) is prepared on AlOX by a newly developed brush method, which enables an FE/dielectric (DE) bilayer. FE/DE thickness ratios are then systematically tuned at ease to achieve ideal capacitance matching. NC-FETs with optimized FE/DE thickness at a thickness limit demonstrate hysteresis-free operation with an SS of 28 mV dec-1 at ≈1.5 V, which competes with the best reports. This P(VDF-TrFE)-brush layer can be broadly adapted to NC-FETs, opening an exciting avenue for low-power devices.


Is Root Catalase a Bifunctional Catalase-Peroxidase?
Plant catalases exhibit spatial and temporal distribution of their activity. Moreover, except from the typical monofunctional catalase, a bifunctional catalase-peroxidase has been reported. The aim of this study was to investigate whether the leaf and root catalases from six different plant species (Lactuca sativa, Cichorium endivia, Apium graveolens, Petroselinum crispum, Lycopersicon esculentum, and Solanum melongena) correspond to the monofunctional or the bifunctional type based on their sensitivity to the inhibitor 3-amino-1,2,4-triazole (3-AT). The leaf catalases from all species seem to be monofunctional since they are very sensitive to 3-AT. On the other hand, the root enzymes from Lactuca sativa, Cichorium endivia, Lycopersicon esculentum, and Solanum melongena seem to be bifunctional catalase-peroxidases, considering that they are relatively insensitive to 3-AT, whereas the catalases from Apium graveolens and Petroselinum crispum display the same monofunctional characteristics as the leaves' enzymes. The leaf catalase activity is usually higher (Lactuca sativa, Petroselinum crispum, and Solanum melongena) or similar (Cichorium endivia and Apium graveolens) to the root one, except for the enzyme from Lycopersicon esculentum, while in all plant species the leaf protein concentration is significantly higher than the root protein concentration. These results suggest that there are differences between leaf and root catalases-differences that may correspond to their physiological role.


An integrated overview of the midgut bacterial flora composition of Phlebotomus perniciosus, a vector of zoonotic visceral leishmaniasis in the Western Mediterranean Basin.
The Leishmania developmental life cycle within its sand fly vector occurs exclusively in the lumen of the insect's digestive tract in the presence of symbiotic bacteria. The composition of the gut microbiota and the factors that influence its composition are currently poorly understood. A set of factors, including the host and its environment, may influence this composition. It has been demonstrated that the insect gut microbiota influences the development of several human pathogens, such as Plasmodium falciparum. For sand flies and Leishmania, understanding the interactions between the parasite and the microbial environment of the vector midgut can provide new tools to control Leishmania transmission. The midguts of female Phlebotomus perniciosus from laboratory colonies or from the field were collected during the months of July, September and October 2011 and dissected. The midguts were analyzed by culture-dependent and culture-independent methods. A total of 441 and 115 cultivable isolates were assigned to 30 and 11 phylotypes from field-collected and colonized P. perniciosus, respectively. Analysis of monthly variations in microbiota composition shows a species diversity decline in October, which is to the end of the Leishmania infantum transmission period. In parallel, a compilation and a meta-analysis of all available data concerning the microbiota of two Psychodidae genera, namely Phlebotomus and Lutzomyia, was performed and compared to P. perniciosus, data obtained herein. This integrated analysis did not reveal any substantial divergences between Old and New world sand flies with regards to the midgut bacterial phyla and genera diversity. But clearly, most bacterial species (>76%) are sparsely distributed between Phlebotominae species. Our results pinpoint the need for a more exhaustive understanding of the bacterial richness and abundance at the species level in Phlebotominae sand flies in order to capture the role of midgut bacteria during Leishmania development and transmission. The occurrence of Bacillus subtilis in P. perniciosus and at least two other sand fly species studied so far suggests that this bacterial species is a potential candidate for paratransgenic or biolological approaches for the control of sand fly populations in order to prevent Leishmania transmission.


Trisomy recurrence: a reconsideration based on North American data.
Few reliable data exist concerning the recurrence risk for individual trisomies or the risk for recurrence of trisomy for a different chromosome. We collected records from two sources: (1) prenatal diagnoses performed at the Hopital Sainte-Justine in Montreal and (2) karyotype analyses performed at Genzyme. Using the standardized morbidity ratio (SMR), we compared the observed number of trisomies at prenatal diagnosis with the expected numbers, given maternal age-specific rates (by single year). SMRs were calculated both for recurrence of the same trisomy (homotrisomy) and of a different trisomy (heterotrisomy). After all cases with an index trisomy 21 were combined, the SMR for homotrisomy was 2.4 (90% CI 1.6-3.4; P=.0005). For women with both the index trisomy and subsequent prenatal diagnosis at age <30 years, the SMR was 8.0; it was 2.1 for women with both pregnancies at age >/=30 years. For the other index viable trisomies (13, 18, XXX, and XXY) combined, the SMR for homotrisomy was 2.5 (90% CI 0.7-8.0). For heterotrisomy, the SMR after an index trisomy 21 was 2.3 (90% CI 1.5-3.8, P=.0007); the SMR did not vary with maternal age at the first trisomy. When all cases with index viable trisomies were combined, the SMR for heterotrisomy was 1.6 (90% CI 1.1-2.4; P=.04). For prenatal diagnoses following a nonviable trisomy diagnosed in a spontaneous abortion (from Genzyme data only), the SMR for a viable trisomy was 1.8 (90% CI 1.1-3.0; P=.04). The significantly increased risk for heterotrisomy supports the hypothesis that some women have a risk for nondisjunction higher than do others of the same age.


Alendronate-induced esophagitis: possible pathogenic role of hypersensitivity to alendronate.
Upper gastrointestinal tract mucosal irritations, such as esophagitis, have been reported as rare adverse events due to a variety of aminobisphosphonates, including alendronate sodium, which have been widely used to treat osteoporosis. Although the pathogenesis of aminobisphosphonate-induced esophageal mucosal irritation has not been clearly understood, direct chemical esophageal irritation with prolonged local mucosal exposure to the drug with gastric contents might be the most plausible mechanism according to the previously reported literature. Here we report a young adult man with severe ulcerative esophagitis due to alendronate who demonstrated a strongly positive result on a drug lymphocyte stimulation test against alendronate. This case report provides the new concept that T-cell mediated delayed hypersensitivity to the drug may be involved in the pathogenesis of alendronate-induced esophagitis.


Efficacy and safety of once-weekly semaglutide for the treatment of type 2 diabetes.
Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety. Glucagon-likepeptide1 (GLP-1) receptor analogues are appealing due to the improved glycemic control in a glucose-dependent manner, modest weight loss and low risk of hypoglycemia. Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1 analogue, is currently in the phase III clinical trial for the treatment of type 2 diabetes. This article aims to review the pharmacological and clinical profiles of semaglutide based on the available clinical data. Expert opinion: Semaglutide achieved greater reduction from baseline in HbA1c in comparison to placebo. The greater proportion of patients in semaglutide group than that in placebo group achieved target HbA1c <7.0% and <6.5%, respectively. Semaglutide is the second GLP-1 analogue contributing to the reduced bodyweight and improving obesity related complications. More importantly, semaglutide is beneficial to diabetic patients with high cardiovascular risk according to the recently completed phase III trial. The incidence of gastrointestinal adverse effects increased with semaglutide dose.


Triiodothyroacetic acid in health and disease.
Thyroid hormone (TH) is crucial for development and metabolism of many tissues. The physiological relevance and therapeutic potential of TH analogs have gained attention in the field for many years. In particular, the relevance and use of 3,3',5-triiodothyroacetic acid (Triac, TA3) has been explored over the last decades. Although TA3 closely resembles the bioactive hormone T3, differences in transmembrane transport and receptor isoform-specific transcriptional activation potency exist. For these reasons, the application of TA3 as a treatment for resistance to TH (RTH) syndromes, especially MCT8 deficiency, is topic of ongoing research. This review is a summary of all currently available literature about the formation, metabolism, action and therapeutic applications of TA3.


Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.
The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders.


[Preservation of anal transitional zone in restorative proctocolectomy].
Since 1980, restorative proctocolectomy has been established for surgical therapy to ulcerative colitis. The crucial points of this procedure are mucosectomy of the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult due to long standing acute and chronic inflammation and incomplete microscopically and leakage of pouch anal anastomosis is relatively high probably due to steroid given prior to surgery or direct effect of anorectal mucosal inflammation. Regards to postoperative bowel function, nocternal soiling is frequently recognized in the patients who received this operation. To overcome these technical and functional disadvantages, anal transitional zone preservation without mucosectomy and stapled anastomosis between pouch and the upper rim of the puborectalis muscle has been performed. Our series of 84 cases with this modified method, anastomotic leakage was significantly decreased and nocternal soiling was completely disappeared within 7 months postoperatively. And one stage procedure became possible unless severe, or high doses of steroid given prior to surgery. Only one case of mild dysplasia was experienced in the remaining rectal mucosa which was disappeared at the next examination. Medical treatment to the remaining lesion was not necessary in the most of cases. Anal canal preservation is superior to mucosectomy in the points of bowel function and minimizing postoperative complications.


Interaction between L-arginine: no system and cyclooxygenase metabolic products of arachidonic acid in coronary autoregulation.
Coronary autoregulation (CA) is the intrinsic ability of the heart to maintain its nutritive blood supply constant over a wide range of perfusion pressure. This phenomenon is regulated through several control mechanisms, while metabolic and myogenic control mechanism have dominant effects. In last few years, endothelial control mechanism, which is part of metabolic control, was intensive investigated. Dominant topic of endothelial-investigation was bioregulatory L-arginine: NO system, with his effective product--nitric oxide (NO). On the other hand, cyclooxygenase metabolic pathway products of arachidonic acid plays an important role in the control of vasomotor tone of coronary arteries. For this purpose, the aim of our study was to evaluate role of L-arginine: NO system, cyclooxygenase metabolites of arachidonic acid, as well as, their interactions in the control of CA of the isolated rat heart.. In our study rat hearts autoregulate CF between 50 and 90 cm H2O of CPP. Basal release (at 60 cm H2O) of NO (as nitrite), cAMP, cGMP and HX+X (i.e. adenosine) amounted to 2.85+/-0.25 nmol/min/g wt, 29.45+/-2.22 pmol/min/g wt, 0.43+/-0.08 pmol/min/g wt and 37.50+/-2.89 nmol/min/g wt respectively. Release of NO, cAMP and cGMP were strictly parallel with CPP-CF curve, while release of adenosine (i.e. HX + X) was an inverse function of perfusion pressure. Inhibition of NOS (L-NAME, 30 micromol/l) significantly widened autoregulatory range (40-100 cm H2O), with significant reduction in CF and NO- and cGMP release, while release of cAMP was completely reversed in the presence of L-NAME. However, inhibition of cyclooxygenase didn't influence autoregulatory range, with similar changes of NO- and cAMP-release and completely inversed values of released adenosine. When L-NAME an indomethacin (an nonspecific COX-inhibitor), 3 micromol/l where added together, they exhibit interactions between these two enzymatic systems. Namely, when L-NAME was added first, indomethacin didn't influence hemodynamic effects of NOS-inhibitor. On the other hand, when COX-inhibitor was added first, L-NAME widened autoregulatory range in small manner as after control autoregulatory experiments (40-90 cm H2O). All hemodynamic changes were followed with similar changes in NO-release, what suggest that exist interaction between L-arginine: NO system and COX-metabolites in the regulation of coronary autoregulation.


[Isolated sphenoid sinus lesions: a clinical analysis of 44 cases].
We reviewed isolated sphenoid sinus lesion (ISL), a relatively uncommon entity found mostly in departments other than otolaryngology. We retrospectively studied 44 cases of ISL at the Department of Otolaryngology, Kagoshima City Hospital, Kagoshima, Japan, for the 5 years between 1999 and 2003. Data was obtained for each patient regarding age, present symptoms, first department visit, pathological classification, and therapy. Eighty percent of patients first visited departments other than otolaryngology. Of these, 32 had inflammatory disease, 8 mucocele, 1 a benign tumor, and 3 malignant tumors. The most common symptoms were headache at 59% followed by ocular symptoms at 27%. Ocular symptoms included ocular pain in 60% of those with inflammatory disease, visual disturbance in 63% of those with mucocele, and diplopia in all of those with neoplasms. The type of ocular symptom largely depends on ISL pathology. Patients with headaches and diplopia have a high ratio of malignant neoplasms. Endoscopic sinus surgery was useful in diagnosing and treating ISL in cases in which conservative therapy was ineffective. It is most important to differentiate pathological disease that requires early diagnosis and therapy such as acute inflammatory disease, mucocele with visual disturbance, and malignant tumors.


Construction and characterization of infectious human T-cell leukemia virus type 1 molecular clones.
Molecular clones of human T-cell leukemia virus type 1 (HTLV-1) have been constructed and stably propagated in plasmids in Escherichia coli. Expression of Tax could be demonstrated from these clones in fibroblast and epithelial cell lines. HOS cells stably transfected with HTLV-1 clone ACH produced all three classes of viral transcripts and Gag proteins. Virus-like particles were also produced from ACH transfected HOS cells as demonstrated by sucrose gradient and electron microscopic analyses. Transfection of peripheral blood mononuclear cells with ACH resulted in production of infectious virus particles which induced lymphocyte proliferation. This study describes useful reagents for further examination of the biological properties of HTLV-1.


Predicting attention-deficit/hyperactivity disorder severity from psychosocial stress and stress-response genes: a random forest regression approach.
Identifying genetic variants contributing to attention-deficit/hyperactivity disorder (ADHD) is complicated by the involvement of numerous common genetic variants with small effects, interacting with each other as well as with environmental factors, such as stress exposure. Random forest regression is well suited to explore this complexity, as it allows for the analysis of many predictors simultaneously, taking into account any higher-order interactions among them. Using random forest regression, we predicted ADHD severity, measured by Conners' Parent Rating Scales, from 686 adolescents and young adults (of which 281 were diagnosed with ADHD). The analysis included 17 374 single-nucleotide polymorphisms (SNPs) across 29 genes previously linked to hypothalamic-pituitary-adrenal (HPA) axis activity, together with information on exposure to 24 individual long-term difficulties or stressful life events. The model explained 12.5% of variance in ADHD severity. The most important SNP, which also showed the strongest interaction with stress exposure, was located in a region regulating the expression of telomerase reverse transcriptase (TERT). Other high-ranking SNPs were found in or near NPSR1, ESR1, GABRA6, PER3, NR3C2 and DRD4. Chronic stressors were more influential than single, severe, life events. Top hits were partly shared with conduct problems. We conclude that random forest regression may be used to investigate how multiple genetic and environmental factors jointly contribute to ADHD. It is able to implicate novel SNPs of interest, interacting with stress exposure, and may explain inconsistent findings in ADHD genetics. This exploratory approach may be best combined with more hypothesis-driven research; top predictors and their interactions with one another should be replicated in independent samples.


Measurement of tartrate-resistant acid phosphatase and the brain isoenzyme of creatine kinase accurately diagnoses type II autosomal dominant osteopetrosis but does not identify gene carriers.
Autosomal dominant osteopetrosis type II (ADO2) is typically diagnosed from radiographs, which demonstrate the pathognomonic findings of osteosclerosis and endobone formation. Individuals with ADO2 also have elevated serum levels of tartrate-resistant acid phosphatase (TRAP) and the BB isoenzyme of creatine kinase (CK-BB). In the current study, we tested the utility of these enzymes in making or refuting a diagnosis of ADO2. Furthermore, because ADO2 has incomplete penetrance, we examined whether TRAP and CK-BB were helpful in identifying gene carriers. We studied eight families, measured serum levels of TRAP and CK-BB in 52 affected individuals and 12 obligate gene carriers, and compared their values with age-matched controls. Our results demonstrate that affected patients have significantly elevated levels of both TRAP and CK-BB. In contrast, gene carriers have values that are not different from controls. Furthermore, in our study population, TRAP and CK-BB have a high diagnostic sensitivity and specificity, particularly in children. From this large study of ADO2 patients and carriers, we conclude that: 1) TRAP and CK-BB are significantly elevated in patients with ADO2, 2) obligate carriers cannot be adequately identified by measurement of these analytes, and 3) TRAP and CK-BB are highly sensitive and specific diagnostic tests that can efficiently and effectively screen high-risk individuals who have not had previous radiographic assessment.


Transgenic pigs designed to express human CD59 and H-transferase to avoid humoral xenograft rejection.
Research in pig-to-primate xenotransplantation aims to solve the increasing shortage of organs for human allotransplantation and develop new cell- and tissue-based therapies. Progress towards its clinical application has been hampered by the presence of xenoreactive natural antibodies that bind to the foreign cell surface and activate complement, causing humoral graft rejection. Genetic engineering of donor cells and animals to express human complement inhibitors such as hCD59 significantly prolonged graft survival. Strategies to decrease the deposition of natural antibodies were also developed. Expression of human alpha1,2-fucosyltransferase (H transferase, HT) in pigs modifies the cell-surface carbohydrate phenotype resulting in reduced Galalpha1,3-Gal expression and decreased antibody binding. We have developed transgenic pigs that coexpress hCD59 and HT in various cells and tissues to address both natural antibody binding and complement activation. Functional studies with peripheral blood mononuclear cells and aortic endothelial cells isolated from the double transgenic pigs showed that coexpression of hCD59 and HT markedly increased their resistance to human serum-mediated lysis. This resistance was greater than with cells transgenic for either hCD59 or HT alone. Moreover, transgene expression was enhanced and protection maintained in pig endothelial cells that were exposed for 24 h to pro-inflammatory cytokines. These studies suggest that engineering donor pigs to express multiple molecules that address different humoral components of xenograft rejection represents an important step toward enhancing xenograft survival and improving the prospect of clinical xenotransplantation.


Synthesis of 3 alpha, 5 alpha-tetrahydroaldosterone.
3 alpha, 5 alpha-Tetrahydroaldosterone (12a), a metabolite of aldosterone, has been synthesized from the lactone 2a or, preferably 11 beta, 21-dihydroxy-5-pregnene-3,20-dione-18-oic acid 3,20-di-(ethylene glycol)-ketal (18----11) lactone 21-acetate (6b), via 11 beta, 21-dihydroxy-5 alpha-pregnane-3,20-dione-18-oic acid 3,20-di-(ethylene glycol) ketal (18----11) lactone 21-acetate (4b). Selective hydrolysis of the latter at C-3 furnished the monoketal 5 which, on reduction with potassium tri-sec-butylborohydride, yielded predominantly 3 alpha, 11 beta, 21-trihydroxy-5 alpha-pregnan-20-one-18-oic acid 20-(ethylene glycol)-ketal (18----11) lactone (8a) and its acetate 8b. Further reduction with diisobutylaluminum hydride afforded 3 alpha, 5 alpha-tetrahydroaldosterone-20-ketal (10a), which was directly hydrolyzed to 12a with dilute acid in tetrahydrofuran-dioxan. Periodate oxidation led to the gamma-etiolactone 14a, which was then further converted into 5 alpha-dihydroaldosterone-gamma-etiolactone (14c).


Multispectral LIF-Based Standoff Detection System for the Classification of CBE Hazards by Spectral and Temporal Features.
Laser-induced fluorescence (LIF) is a well-established technique for monitoring chemical processes and for the standoff detection of biological substances because of its simple technical implementation and high sensitivity. Frequently, standoff LIF spectra from large molecules and bio-agents are only slightly structured and a gain of deeper information, such as classification, let alone identification, might become challenging. Improving the LIF technology by recording spectral and additionally time-resolved fluorescence emission, a significant gain of information can be achieved. This work presents results from a LIF based detection system and an analysis of the influence of time-resolved data on the classification accuracy. A multi-wavelength sub-nanosecond laser source is used to acquire spectral and time-resolved data from a standoff distance of 3.5 m. The data set contains data from seven different bacterial species and six types of oil. Classification is performed with a decision tree algorithm separately for spectral data, time-resolved data and the combination of both. The first findings show a valuable contribution of time-resolved fluorescence data to the classification of the investigated chemical and biological agents to their species level. Temporal and spectral data have been proven as partly complementary. The classification accuracy is increased from 86% for spectral data only to more than 92%.


Endosonographic features of unicentric Castleman Disease.
Castleman disease (CD) is a rare lymphoproliferative disorder most frequently occurring in the mediastinum. Peripancreatic forms are less frequent. Few cases of endoscopic ultrasonography-fine-needle aspiration (EUS-FNA) findings of this lesion have been reported, where no real-time tissue elastography (RTTE) has been described in the literature to our knowledge. We describe the endosonographic, elastographic, cytologic and immunocytochemistry findings in two cases of unicentric CD of the hyaline vascular variant. Two females, aged 41 and 34 year were referred to our hospital for further EUS evaluation of a peripancreatic mass found incidentally on computed tomography. EUS examination revealed around, well-demarcated, uniformly hypoechoic mass measuring 52 and 23 mm respectively, with smaller adjacent hypoechoic lymph nodes. Doppler examination revealed intense peripheral vascularity, together with prominent penetrating feeding vessels entering a distinct hilum. RTTE revealed a relatively homogenous soft elastographic pattern. EUS-FNA provided smears with clusters of lymphocytes in a hemorrhagic background. Cell block preparation showed immature lymphocytes surrounding lymphocyte-poor centers with vascular proliferation. Immunohistochemical staining of the cell block sections showed CD45-leukocyte common antigen, CD20, CD23, CD79a, Bcl-2 and CD5 positivity in small lymphocytes. Cytology was suggestive of non-Hodgkin's lymphoma. Surgical excision was performed in both cases and histopathology was consistent with CD of the hyaline vascular type. The echo features of a solitary hypoechoic homogenous well-demarcated mass with prominent vasculature and increased elasticity should raise the possibility of unicentric CD. EUS-FNA usually cannot make a definitive distinction from certain kinds of lymphoma.


The impact of semantics on aspect level opinion mining.
Recently, many users prefer online shopping to purchase items from the web. Shopping websites allow customers to submit comments and provide their feedback for the purchased products. Opinion mining and sentiment analysis are used to analyze products' comments to help sellers and purchasers decide to buy products or not. However, the nature of online comments affects the performance of the opinion mining process because they may contain negation words or unrelated aspects to the product. To address these problems, a semantic-based aspect level opinion mining (SALOM) model is proposed. The SALOM extracts the product aspects based on the semantic similarity and classifies the comments. The proposed model considers the negation words and other types of product aspects such as aspects' synonyms, hyponyms, and hypernyms to improve the accuracy of classification. Three different datasets are used to evaluate the proposed SALOM. The experimental results are promising in terms of Precision, Recall, and F-measure. The performance reaches 94.8% precision, 93% recall, and 92.6% f-measure.


A macrochip interconnection network enabled by silicon nanophotonic devices.
We present an advanced wavelength-division multiplexing point-to-point network enabled by silicon nanophotonic devices. This network offers strictly non-blocking all-to-all connectivity while maximizing bisection bandwidth, making it ideal for multi-core and multi-processor interconnections. We introduce one of the key components, the nanophotonic grating coupler, and discuss, for the first time, how this device can be useful for practical implementations of the wavelength-division multiplexing network using optical proximity communications. Finite difference time-domain simulation of the nanophotonic grating coupler device indicates that it can be made compact (20 microm x 50 microm), low loss (3.8 dB), and broadband (100 nm). These couplers require subwavelength material modulation at the nanoscale to achieve the desired functionality. We show that optical proximity communication provides unmatched optical I/O bandwidth density to electrical chips, which enables the application of wavelength-division multiplexing point-to-point network in macrochip with unprecedented bandwidth-density. The envisioned physical implementation is discussed. The benefits of such an interconnect network include a 5-6x improvement in latency when compared to a purely electronic implementation. Performance analysis shows that the wavelength-division multiplexing point-to-point network offers better overall performance over other optical network architectures.


The Role of Pharmacists as Immunizers in North Carolina.
Pharmacists are well-equipped to provide information to other health care providers on immunizations that may benefit patients, and can administer these immunizations in the pharmacy setting. Pharmacists have positively impacted vaccination rates, especially among patients who infrequently visit other health care providers or have reduced access to care. North Carolina has expanded the list of vaccinations pharmacists can provide, which helps to promote disease prevention and improve population health.


Overview of orexin/hypocretin system.
A series of recent studies has established the orexin/hypocretin system as a critical regulator of sleep/wake states. Its deficiency results in the sleep disorder narcolepsy in humans, dogs, and rodents. These findings have brought about the possibility of novel therapies for sleep disorders including narcolepsy and insomnia. Moreover, accumulating evidence indicates that the orexin/hypocretin system regulates sleep and wakefulness through interactions with neuronal systems that regulate emotion, reward, and energy homeostasis. Here, we briefly summarize the progress of orexin/hypocretin studies and future perspectives.


Isotopic and geochemical assessment of in situ biodegradation of chlorinated hydrocarbons.
Currently there is no in situ method to detect and quantify complete mineralization of chlorinated hydrocarbons (CHCs) to CO2. Combined isotopic measurements in conjunction with traditional chemical techniques were used to assess in situ biodegradation of trichloroethylene (TCE) and carbon tetrachloride (CT). Vadose zone CHC, ethene, ethane, methane, O2, and CO2 concentrations were analyzed using gas chromatography over 114 days at the Savannah River Site. delta13C of CHC and delta13C and 14C of vadose zone CO2, sediment organic matter, and groundwater dissolved inorganic carbon (DIC)were measured. Intermediate metabolites of TCE and CT accounted for < or = 10% of total CHCs. Delta13C of cis-1,2-dichloroethylene (DCE) was always heavier than TCE indicating substantial DCE biodegradation. 14C-CO2 values ranged from 84 to 128 percent modern carbon (pMC), suggesting that plant root-respired CO2 was dominant. 14C-CO2 values decreased over time (up to 12 pMC), and contaminated groundwater 14C-DIC (76 pMC) was substantially depleted relative to the control (121 pMC). 14C provided a direct measure of complete CHC mineralization in vadose zone and groundwater in situ and may improve remediation strategies.


Invited Review: Role of mechanophysiology in aging of ECM: effects of changes in mechanochemical transduction.
Mechanical forces play a role in the development and evolution of extracellular matrices (ECMs) found in connective tissue. Gravitational forces acting on mammalian tissues increase the net muscle forces required for movement of vertebrates. As body mass increases during development, musculoskeletal tissues and other ECMs are able to adapt their size to meet the increased mechanical requirements. However, the control mechanisms that allow for rapid growth in tissue size during development are altered during maturation and aging. The purpose of this mini-review is to examine the relationship between mechanical loading and cellular events that are associated with downregulation of mechanochemical transduction, which appears to contribute to aging of connective tissue. These changes result from decreases in growth factor and hormone levels, as well as decreased activation of the phosphorelay system that controls cell division, gene expression, and protein synthesis. Studies pertaining to the interactions among mechanical forces, growth factors, hormones, and their receptors will better define the relationship between mechanochemical transduction processes and cellular behavior in aging tissues.


Metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor in rat: relationship of metabolism to MAO-B inhibitory potency.
Deprenyl, a selective inhibitor of monoamine oxidase type B (MAO-B), was metabolized in rats to methamphetamine (MAP), amphetamine (AP) and their corresponding p-hydroxylated metabolites, p-hydroxy-MAP and p-hydroxy-AP. Recovery of metabolites in 24 h urine was 25% of the dose, and there was no urinary excretion of unchanged deprenyl. Deprenyl was converted into MAP, AP and nordeprenyl when incubated in vitro with rat-liver microsomes in the presence of NADPH. This metabolism was inhibited in an atmosphere of N2 and by CO, and by SKF 525-A, but to a lesser extent by methimazole. Liver microsomes from phenobarbital (PB)-treated rats, but not 3-methylcholanthrene (3-MC)-treated rats, stimulated the metabolism of deprenyl in vitro to MAP and AP, but not to nordeprenyl. In contrast, microsomes from SKF 525-A-treated rats showed decreased activity in the metabolism of deprenyl to all three metabolites. The inhibitory effect of the drug on hepatic MAO-B activity was annulled by pretreatment of rats with PB, but not 3-MC, and augmented by pretreatment with SKF 525-A.


Demystifying Balint culture and its impact: An autoethnographic analysis.
Balint groups are a structured group process designed for physicians and other helping professionals to provide feedback to each other concerning troublesome patient encounters. The process of Balint groups has survived and even thrived for more than a half century since their inception, suggesting their inherent value. However, measuring the impact in order to communicate the nature of that value has been elusive. A recent literature review highlighted the equivocal nature of research results and suggested that well-designed qualitative research may be more effective in selecting target measures which could result in better evidence for this group process. This paper describes such an effort using a qualitative analysis of the author's own reflections about significant moments and learnings while participating in Balint groups.


Mitochondrial Adaptive Responses to Hypertriglyceridemia and Bioactive Lipids.
Significance: Altered plasma triglyceride metabolism and changes in dietary fatty acid types and levels are major contributors to the development of metabolic and cardiovascular diseases such as fatty liver disease, obesity, diabetes, and atherosclerosis. Lipid accumulation in visceral adipose tissue and ectopically in other organs, as well as lipid-induced redox imbalance, is connected to mitochondrial dysfunction in a range of oxidative stress-associated metabolic and degenerative disorders. Recent Advances: Successful mitochondrial adaptive responses in the context of hypertriglyceridemia and dietary bioactive polyunsaturated fatty acids contribute to increase body energy expenditure and reduce oxidative stress, thus allowing several cell types to cope with metabolic challenges and stresses. These responses include mitochondrial redox signaling, mild uncoupling, and changes in network dynamic behavior. Critical Issues: Mitochondrial bioenergetics and redox changes in a lipid overload context are relatively well characterized. However, the turning point between adaptive and maladaptive mitochondrial responses remains a critical issue to be elucidated. In addition, the relationship between changes in fusion/fission machinery and mitochondrial function is less well understood. Future Directions: The effective mitochondrial responses described here support the research for new drug design and diet or nutraceutical formulations targeting mitochondrial mild uncoupling and effective quality control as putative strategies for cardiometabolic diseases. Antioxid. Redox Signal. 36, 953-968.


Detection of apical inflammatory root resorption associated with periapical lesion using different methods.
The aim of this study was to detect apical inflammatory root resorption (AIRR) associated with periapical lesion using cone beam computed tomography (CBCT) and scanning electronic microscopy (SEM). This clinical study evaluated AIRR in 88 root apexes, from 52 permanent teeth of 14 patients, extracted for different reasons. The patients were submitted to a clinical interview, review of dental/medical histories and clinical/imaging examinations for treatment planning. All selected teeth showed unrestorable condition because of the extensive coronal breakdown due to carious lesions, and root canal infection associated with periapical lesions. CBCT images were obtained from the patients with the aim of diagnosing the periapical diseases which showed complex or doubtful conditions. Two examiners assessed the presence or absence of AIRR. Apices were also analyzed under SEM. Chi-square test was used to compare the imaging methods for detection of AIRR. The level of statistical significance was set at 5%. AIRR associated with root canal infection and apical periodontitis was found in 61.4% of the cases studied by using SEM, and at least half of the cases by CBCT. The microscopic analysis remains as a reference standard against the imaging method to identify AIRR.


Poc (Pox), a term for various infectious diseases in the history of public health and epidemiology: the dreaded Smallpox, the almost unknown Alastrim and the Mpox.
In 2022, the appearance of cases of Mpox outside the countries where the disease is endemic, and of some cases of human-to-human transmission, alerted the scientific community to a virus that is closely related to the smallpox virus. Mpox is a zoonosis and can be transmitted to humans. Following the eradication of smallpox in 1980 and the subsequent cessation of smallpox vaccination, it is emerging as the most important Orthopoxvirus in terms of public health impact. In outlining the current situation of Mpox in the world, the authors frame the virus responsible within a broader reflection on the Orthopoxvirus family, focusing particular attention on the Variola virus, which formerly caused millions of deaths. Since Edward Jenner initiated the practice of vaccination, a progressive and careful vaccination campaign has led to the eradication not only of human smallpox but also of a minor form, called Alastrim, which was caused by the same virus. The mode of transmission of Mpox has been debated. At first, it seemed that the disease mainly, though not exclusively, affected men who had sex with other men. This conviction has been partially revised and the WHO recently changed the name of the disease from Monkeypox to Mpox, thereby alleviating the stigma involved. The recent human cases of Mpox have prompted greater surveillance and research into the biology of MPXV and other closely related poxviruses. Studies have focused on the natural history of the virus, its transmission, pathogenesis, host interactions and evolution, and on the development of drugs and vaccines to prevent its spread.


Behavioral and psychological symptoms of dementia.
To identify the frequency of behavioral and psychological symptoms of dementia (BPSD) and to explore the different characteristics between subgroup and severity of dementia. Sixty-seven patients with Alzheimer's disease, vascular dementia, and mixed dementia were recruited to our cross-sectional study. Neuropsychiatric batteries including the Mini Mental Status Examination-Thai 2002, Thai Geriatric Depression Scale, 23 items from Alzheimer's Disease co-operative Study activities of daily living inventory, Behavioralpathology in Alzheimer's disease rating scale, and Pittsburg Sleep Quality Index were tested. The most common behavioral and psychological symptoms of dementia (BPSD) were sleep problems (100%), paranoid/delusion (59.7%), diurnal disturbance (49.2%) and aggressiveness (46.3%). Hallucination and affective problems were more severe in AD than in VaD/mixed dementia. Sleep problems were identified more severe in mild dementia than moderate-to-severe dementia. With longer duration of having dementia, exceptfor affective problem, there was no diffemence in behavioral and psychological symptoms observed compared to the shorter dementia group. Behavioral and psychological symptoms were very common in Alzheimer disease, vascular dementia, and mixed dementia. Since these symptoms cause cognitive and functional decline, institutionalization, caregiver distress and increase direct costs ofcare, the problem must be identified and addressed.


pH dependence of adsorption of n-dodecyl-beta-D-maltoside on solids.
Adsorption of surfactants on solids plays an important role in industrial operations such as separation, lubrication, flotation, dispersion, chemical mechanical polishing, and enhanced oil recovery. In this work, adsorption of a typical biodegradable nonionic surfactant, n-dodecyl-beta-d-maltoside, on solids was studied to explore its potential applications. Even though it is a nonionic surfactant, significant pH-dependence was revealed for the adsorption on alumina in the range from pH 4 to 7. The adsorption density was found to be proportional to the concentration of surface AlOH group among Al(OH(2))(+) and AlO(-) groups. The equilibriums among the surface species are governed by pH through surface ionization reactions. The surface AlOH group evidently determines the formation of hydrogen bonding between the surfactant molecules and the solid surface and thus the adsorption. Similar correlation was also found in the case of hematite. The results help to understand the mechanism of adsorption of sugar-based surfactant on solids.


Identification of the anti-CD3-unresponsive subpopulation of CD4+, CD45RA+ peripheral T lymphocytes.
The majority of peripheral CD4+ T lymphocytes proliferate in vitro in response to anti-CD3 in presence of autologous APC. The present study describes a subpopulation of CD4+ T cells that cannot be activated and progress into cell cycle by stimulation with anti-CD3 plus APC or with mitogenic combinations of anti-CD2. The in vitro responses of these anti-CD3-unresponsive CD4+ T cells were investigated with a panel of mAb to CD2, CD3, and CD28, and found to be similar to those previously observed for mature thymocytes: only the combination of anti-CD2 plus anti-CD28 produced cell proliferation. Anti-CD3-unresponsive T cells were CD45RA+, but represented only 14 to 22% of the CD4+, CD45RA+ T cell population. Activation with anti-CD2 plus anti-CD28 mAb resulted in major changes in the cell surface phenotype and functional properties: a loss of CD45RA+ occurred and an increased expression of CD45RO, CD29, and CD58 (LFA3), as well as a gain in responsiveness to anti-CD3 and anti-CD2. This change in CD45 phenotype from CD45RA to CD45RO occurs in both the anti-CD3-responsive and in the anti-CD3-unresponsive subsets of the CD45RA+, CD4+ cells after cell proliferation. The anti-CD3-unresponsive subset may represent a pool of not yet fully differentiated peripheral T cells. The acquisition of anti-CD3 responsiveness could occur as a consequence of Ag priming or by an Ag-independent mechanism. Involvement of the CD28 Ag in this process is suggested from the present study.


Electronic Properties of Functionalized Diamanes for Field-Emission Displays.
Ultrathin diamond films, or diamanes, are promising quasi-2D materials that are characterized by high stiffness, extreme wear resistance, high thermal conductivity, and chemical stability. Surface functionalization of multilayer graphene with different stackings of layers could be an interesting opportunity to induce proper electronic properties into diamanes. Combination of these electronic properties together with extraordinary mechanical ones will lead to their applications as field-emission displays substituting original devices with light-emitting diodes or organic light-emitting diodes. In the present study, we focus on the electronic properties of fluorinated and hydrogenated diamanes with (111), (110), (0001), (101̅0), and (2̅110) crystallographic orientations of surfaces of various thicknesses by using first-principles calculations and Bader analysis of electron density. We see that fluorine induces an occupied surface electronic state, while hydrogen modifies the occupied bulk state and also induces unoccupied surface states. Furthermore, a lower number of layers is necessary for hydrogenated diamanes to achieve the convergence of the work function in comparison with fluorinated diamanes, with the exception of fluorinated (110) and (2̅110) films that achieve rapid convergence and have the same behavior as other hydrogenated surfaces. This induces a modification of the work function with an increase of the number of layers that makes hydrogenated (2̅110) diamanes the most suitable surface for field-emission displays, better than the fluorinated counterparts. In addition, a quasi-quantitative descriptor of surface dipole moment based on the Tantardini-Oganov electronegativity scale is introduced as the average of bond dipole moments between the surface atoms. This new fundamental descriptor is capable of predicting a priori the bond dipole moment and may be considered as a new useful feature for crystal structure prediction based on artificial intelligence.


Rodent nutritional model of non-alcoholic steatohepatitis: species, strain and sex difference studies.
The methionine choline-deficient (MCD) diet leads to steatohepatitis in rodents. The aim of the present study was to investigate species, strain and sex differences in this nutritional model of non-alcoholic steatohepatitis (NASH). Male and female Wistar, Long-Evans and Sprague-Dawley rats, and C57/BL6 mice (n = 6 per group) were fed a MCD diet for 4 weeks. Control groups received an identical diet supplemented with choline bitartrate (0.2% w/w) and methionine (0.3% w/w). Liver pathology (steatosis and inflammation) and ultrastructure, liver lipid profile (total lipids, triglycerides, lipid peroxidation products), liver : body mass ratios and serum alanine aminotransferase (ALT) levels were compared between these groups. The MCD diet-fed male rats developed greater steatosis (P < 0.001), had higher liver lipid content (P < 0.05) and had higher serum ALT levels (P < 0.005) than did female rats. Wistar rats (both sexes) had higher liver lipid levels (P < 0.05), serum ALT levels (P < 0.05), and liver mass : body mass ratios (P < 0.025) than did Long-Evans and Sprague-Dawley rats. In female groups, Wistar rats showed greater fatty change than did the other two strains (P < 0.05). All rats fed the MCD diet developed hepatic steatosis, but necrosis and inflammation were minor features and fibrosis was absent. Compared with Wistar rats, male C57/BL6 mice showed a marked increase in inflammatory foci (P < 0.001), end products of lipid peroxidation (free thiobarbituric acid reactive substances) (P < 0.005), and mitochondrial injury, while showing less steatosis (P < 0.005), lower hepatic triglyceride levels, (P < 0.005) and lower early lipid peroxidation products (conjugated dienes and lipid hydroperoxides; P < 0.005 and P < 0.01, respectively). The Wistar strain and the male sex are associated with the greatest degree of steatosis in rats subjected to the MCD diet. Of the groups studied, male C57/BL6 mice develop the most inflammation and necrosis, lipid peroxidation, and ultrastructural injury, and best approximate the histological features of NASH.


Microtubule-associated protein tau as a therapeutic target in Alzheimer's disease.
Alzheimer's disease (AD) is a major public health problem in modern society and as yet, other than a few symptomatic drugs, there is no disease-modifying treatment for this disease available. Neurofibrillary pathology, which is made up from abnormally hyperphosphorylated microtubule-associated protein tau, is both a hallmark and key lesion of AD and related tauopathies. The density of neurofibrillary pathology in the cerebral cortex correlates with the degree of dementia. Both experimental and transgenic animal studies have consistently shown that abnormal hyperphosphorylation of tau causes cognitive impairment. Abnormal hyperphosphorylation of tau converts it from a microtubule assembly-promoting to a microtubule-disrupting protein and promotes its self-assembly into paired helical filaments. To date, the bulk of studies have shown that abnormal hyperphosphorylation is the key gain of toxic function step though some cell culture and transgenic mouse studies have also reported that aggregated tau can lead to neurodegeneration. In this article, we have reviewed data from our lab and that from PubMed search on the molecular mechanism of tau pathology and the potential of tau as a therapeutic target for AD and related disorders. In our opinion, inhibition of abnormal hyperphosphorylation of tau is the most rational therapeutic target. Therapeutic approaches include restoration of the activity of protein phosphatase-2A, which is the major regulator of tau phosphorylation and the activity of which is compromised in AD brain, inhibition of one or more tau protein kinases which include GSK-3β, cyclin-dependent protein kinase-5, dual-specificity tyrosine phosphorylated-regulated kinase 1A, Ca(2+)/calmodulin-activated protein kinase II and casein kinase I, enhancement of O-GlcNAcylation of tau, and tau immunization.


Intergenerational effects of in utero exposure to Ramadan in Tunisia.
We have reported that changes in the lifestyle of pregnant women during Ramadan affect more than one generation. In a series of newborn babies in Saudi Arabia, those whose mothers had been in utero during Ramadan differed from those whose mothers had not been in utero during Ramadan. These were unexpected findings and require replication. We examined body size at birth in 1,321 babies (682 boys and 639 girls) born in Gafsa, a small city in Tunisia. Babies whose mothers had been in utero during Ramadan were smaller and thinner, and had smaller placentas, than those whose mothers had not been in utero during Ramadan. After adjustment for sex, the babies were 93 g lighter (95% confidence interval, 32-153, P=0.003) than those whose mother had not been in utero during Ramadan, their mean ponderal index was 0.52 kg/m(3) lower (0.24-0.79, P<0.001) and their placental weight was 21 g lower (5-37, P=0.01). The findings did not differ by trimester of maternal exposure to Ramadan. They were similar in boys and girls and in primiparous and multiparous mothers This study provides further evidence that changes in lifestyle during Ramadan have intergenerational effects.


Influence of bone density on implant stability parameters and implant success: a retrospective clinical study.
The aim of the present clinical study was to determine the local bone density in dental implant recipient sites using computerized tomography (CT) and to investigate the influence of local bone density on implant stability parameters and implant success. A total of 300 implants were placed in 111 patients between 2003 and 2005. The bone density in each implant recipient site was determined using CT. Insertion torque and resonance frequency analysis were used as implant stability parameters. The peak insertion torque values were recorded with OsseoCare machine. The resonance frequency analysis measurements were performed with Osstell instrument immediately after implant placement, 6, and 12 months later. Of 300 implants placed, 20 were lost, meaning a survival rate of %. 93.3 after three years (average 3.7 +/- 0.7 years). The mean bone density, insertion torque and RFA recordings of all 300 implants were 620 +/- 251 HU, 36.1 +/- 8 Ncm, and 65.7 +/- 9 ISQ at implant placement respectively; which indicated statistically significant correlations between bone density and insertion torque values (p < 0.001), bone density and ISQ values (p < 0.001), and insertion torque and ISQ values (p < 0.001). The mean bone density, insertion torque and RFA values were 645 +/- 240 HU, 37.2 +/- 7 Ncm, and 67.1 +/- 7 ISQ for 280 successful implants at implant placement, while corresponding values were 267 +/- 47 HU, 21.8 +/- 4 Ncm, and 46.5 +/- 4 ISQ for 20 failed implants; which indicated statistically significant differences for each parameter (p < 0.001). CT is a useful tool to determine the bone density in the implant recipient sites, and the local bone density has a prevailing influence on primary implant stability, which is an important determinant for implant success.


Direct mass spectrometric analysis of intact proteins of the yeast large ribosomal subunit using capillary LC/FTICR.
Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry coupled with capillary reverse-phase liquid chromatography was used to characterize intact proteins from the large subunit of the yeast ribosome. High mass measurement accuracy, achieved by "mass locking" with an internal standard from a dual electrospray ionization source, allowed identification of ribosomal proteins. Analyses of the intact proteins revealed information on cotranslational and posttranslational modifications of the ribosomal proteins that included loss of the initiating methionine, acetylation, methylation, and proteolytic maturation. High-resolution separations permitted differentiation of protein isoforms having high structural similarity as well as proteins from their modified forms, facilitating unequivocal assignments. The study identified 42 of the 43 core large ribosomal subunit proteins and 58 (of 64 possible) core large subunit protein isoforms having unique masses in a single analysis. These results demonstrate the basis for the high-throughput analyses of complex mixtures of intact proteins, which we believe will be an important complement to other approaches for defining protein modifications and their changes resulting from physiological processes or environmental perturbations.


Association of hand grip strength with disease activity, disability and quality of life in children and adolescents with Juvenile Idiopathic Arthritis.
Juvenile idiopathic arthritis (JIA) affects wrist and hand joints leading to decrease hand function and patients' daily living activities. The assessment of hand grip strength (HGS) in children and adolescents with JIA is of major importance, and the association of HGS with JIA disease activity, disability and quality of life has not been explored. The primary objective of this study was to evaluate hand grip strength (HGS) in children and adolescents with Juvenile Idiopathic Arthritis (JIA) compared to matched healthy peers. The secondary objective was to explore the relationship between HGS and JIA disease activity, disability, and quality of life. This study involved 23 patients with JIA and 46 age and sex matched healthy controls. Hand held dynamometer was used to evaluate HGS for all study participants. Anthropometric parameters for all study participants were measured. Disease activity, physical function, and quality of life were assessed for the JIA group using juvenile arthritis disease activity score (JADAS-27), juvenile arthritis functionality scale (JAFS), and pediatric quality of life inventory (PedsQL) respectively. Laboratory marker of inflammation, erythrocyte sedimentation rate (ESR), and plain radiography of hands were performed for all patients. Hand grip strength of children and adolescents with JIA was significantly weaker compared to matched controls (p < 0.001). Hand grip strength had a significant inverse correlation with JADAS-27 (r = - 0.467, p = 0.025), JAFS (r = - 0.650, p = 0.001) and a significant direct correlation with PedsQL (r = 0.438, p = 0.036). In addition, HGS was negatively correlated with ESR and duration of morning stiffness (r = - 0.489, p = 0.018 and r = - 0.201, p = 0.359, respectively). HGS was detected as an independent predictor of disease activity, disability, and quality of life in JIA patients in multivariate linear regression. Assessment of HGS could be a simple non-invasive tool for assessing disease activity, disability and quality of life in JIA patients in clinical practice.


Can tourism support resource circularity in small islands? On-field analysis and intervention proposals in Madagascar.
Open dumping and burning of solid waste are common practices in low-income countries. On small and touristic islands, the problem is exacerbated due to the additional volume of waste amount generated by tourists. This article presents how, using Nosy Be island in Madagascar as a case study, waste recovery and recycling can be fostered by tourism to tackle the waste challenge. About 95% of the waste of Nosy Be is openly dumped, discarded to sea or openly burned. Field analysis, interviews with local stakeholders and waste flow analysis served as methodological tools to assess the current solid waste management (SWM) system of Nosy Be. Stakeholder mapping and involvement as well as first exchange among local and international actors provided the basis to identify key practice and opportunities. Research findings highlight the importance of active participation and involvement of local partners supported by international experts, to suggest how touristic centres can serve as core of circular approaches. The article presents potential circular models to be implemented in Nosy Be, taking tourism as the entry point including the aspects of financial support, separated waste flows and the interest in 'green tourism marketing'. This case study underlines how international cooperation, touristic activities and common efforts can potentially help low-income communities improve their SWM practices.


Application of dynamic mechanical testing to characterize the viscoelastic properties of powder-filled semisolids.
A nondestructive technique, dynamic mechanical testing, was used to characterize the viscoelastic properties of dispersions of powdered starch in anhydrous lanolin. The elastic shear modulus (G'), viscous shear modulus (G"), and loss tangent (damping; tan delta) were determined as a function of shear frequency, temperature, and the volume fraction of starch. The results of these studies show that constitutive mathematical models, derived to predict the mechanical behavior of solid-filled polymeric materials, can be applied to solid-filled semisolid pharmaceuticals. In particular, the Kerner equation was useful in describing the influence of starch on the G' of the dispersions. Even though the Kerner equation was unable to predict viscoelastic behavior at all shear frequencies, temperatures, and starch volume fractions, it proved beneficial in postulating mechanisms for starch-starch and starch-anhydrous lanolin interactions within the dispersions. In addition, damping was able to differentiate the influence of temperature. Data obtained from three temperature ranges, where anhydrous lanolin exists in three different structural states, shows that the influence of starch on damping is dictated by the structural state of anhydrous lanolin.


Prevention of Lethal Murine Hypophosphatasia by Neonatal Ex Vivo Gene Therapy Using Lentivirally Transduced Bone Marrow Cells.
Hypophosphatasia (HPP) is an inherited skeletal and dental disease caused by loss-of-function mutations in the gene that encodes tissue-nonspecific alkaline phosphatase (TNALP). The major symptoms of severe forms of the disease are bone defects, respiratory insufficiency, and epileptic seizures. In 2015, enzyme replacement therapy (ERT) using recombinant bone-targeted TNALP with deca-aspartate (D10) motif was approved to treat pediatric HPP patients in Japan, Canada, and Europe. However, the ERT requires repeated subcutaneous administration of the enzyme because of the short half-life in serum. In the present study, we evaluated the feasibility of neonatal ex vivo gene therapy in TNALP knockout (Akp2(-/-)) HPP mice using lentivirally transduced bone marrow cells (BMC) expressing bone-targeted TNALP in which a D10 sequence was linked to the C-terminus of soluble TNALP (TNALP-D10). The Akp2(-/-) mice usually die within 20 days because of growth failure, epileptic seizures, and hypomineralization. However, an intravenous transplantation of BMC expressing TNALP-D10 (ALP-BMC) into neonatal Akp2(-/-) mice prolonged survival of the mice with improved bone mineralization compared with untransduced BMC-transplanted Akp2(-/-) mice. The treated Akp2(-/-) mice were normal in appearance and experienced no seizures during the experimental period. The lentivirally transduced BMC were efficiently engrafted in the recipient mice and supplied TNALP-D10 continuously at a therapeutic level for at least 3 months. Moreover, TNALP-D10 overexpression did not affect multilineage reconstitution in the recipient mice. The plasma ALP activity was sustained at high levels in the treated mice, and tissue ALP activity was selectively detected on bone surfaces, not in the kidneys or other organs. No ectopic calcification was observed in the ALP-BMC-treated mice. These results indicate that lentivirally transduced BMC can serve as a reservoir for stem cell-based ERT to rescue the Akp2(-/-) phenotype. Neonatal ex vivo gene therapy thus appears to be a possible treatment option for treating severe HPP.