Three-dimensional structure of a thermostable native cellobiohydrolase, CBH IB, and molecular characterization of the cel7 gene from the filamentous fungus, Talaromyces emersonii.
The X-ray structure of native cellobiohydrolase IB (CBH IB) from the filamentous fungus Talaromyces emersonii, PDB 1Q9H, was solved to 2.4 A by molecular replacement. 1Q9H is a glycoprotein that consists of a large, single domain with dimensions of approximately 60 A x 40 A x 50 A and an overall beta-sandwich structure, the characteristic fold of Family 7 glycosyl hydrolases (GH7). It is the first structure of a native glycoprotein and cellulase from this thermophilic eukaryote. The long cellulose-binding tunnel seen in GH7 Cel7A from Trichoderma reesei is conserved in 1Q9H, as are the catalytic residues. As a result of deletions and other changes in loop regions, the binding and catalytic properties of T. emersonii 1Q9H are different. The gene (cel7) encoding CBH IB was isolated from T. emersonii and expressed heterologously with an N-terminal polyHis-tag, in Escherichia coli. The deduced amino acid sequence of cel7 is homologous to fungal cellobiohydrolases in GH7. The recombinant cellobiohydrolase was virtually inactive against methylumberiferyl-cellobioside and chloronitrophenyl-lactoside, but partial activity could be restored after refolding of the urea-denatured enzyme. Profiles of cel7 expression in T. emersonii, investigated by Northern blot analysis, revealed that expression is regulated at the transcriptional level. Putative regulatory element consensus sequences for cellulase transcription factors have been identified in the upstream region of the cel7 genomic sequence.


Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets.
Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.


Two different sets of cis elements regulate scute to establish two different sensory patterns.
We have analysed the role of the achaete-scute gene complex in the development of the pattern of campaniform sensilla on the wing blade of Drosophila. We show that the complete pattern results from the superimposition of two independent subpatterns, one of which depends on the achaete gene and the other on scute. The scute subpattern comprises several clusters of sensilla, most of which seem to require the presence of control regions located upstream of the transcribed region. This is in contrast with the pattern of scute-dependent bristles, most of which depends on control elements located downstream of the transcribed region.


Relations among Adiposity and Insulin Resistance with Flow-Mediated Dilation, Carotid Intima-Media Thickness, and Arterial Stiffness in Children.
To determine the associations of adiposity and insulin resistance with measures of vascular structure and function in children. A cross-sectional study included 252 children (age 15.1 ± 2.4 years; body mass index percentile 68.2 ± 26.5%; Tanner 2-5). Measurements of body fat percentage were obtained with dual-energy X-ray absorptiometry and visceral adipose tissue (VAT) with computed tomography. Insulin resistance was measured with hyperinsulinemic euglycemic clamp. Vascular measurements for endothelial function (brachial artery flow-mediated dilation [FMD]), vascular structure (carotid intima-media thickness [cIMT]), vascular stiffness (carotid incremental elastic modulus), and pulse wave velocity were analyzed by tertiles of adiposity and insulin resistance. Additional analyses with ANCOVA and linear regression were adjusted for Tanner, sex, race, and family relationship; FMD was also adjusted for baseline artery diameter. FMD was positively associated with high adiposity (body mass index, body fat percentage, and VAT) (P < .01 all). Insulin resistance was not associated with FMD. cIMT was significantly, positively related to obesity, VAT, and insulin resistance (P < .05 all). No differences in carotid incremental elastic modulus and pulse wave velocity were observed in relation to adiposity or insulin resistance. The findings suggest that adiposity is associated with higher FMD, and insulin resistance and VAT are associated with higher cIMT in children. Further research is needed to clarify the progression of these relations.


Calculation of optical extinction from aerosol spectral data.
A major overwater experiment, MAGAT-80, has been undertaken to verify the use of aerosol spectrometers to calculate optical extinction in the marine boundary layer. Techniques for data averaging and for extrapolation to large particle sizes are described. Coincident optical, aerosol, and meteorological measurements by ship, aircraft, and an overwater optical range show that aerosol spectra can be used to predict extinction to within 40%.


Comparative study of the effects of percutaneous ethanol injection and radiofrequency ablation in cases treated with a straight or expandable electrode.
Radiofrequency ablation (RFA) has become mainstream among non-surgical treatment modalities in clinical settings for the treatment of hepatocellular carcinoma. We have previously described the novel combination therapy of percutaneous ethanol injection and RFA (PEI-RFA) and reported that this combination therapy was more effective than RFA alone in terms of the induced volume of coagulated necrosis and the energy requirement for the treatment. RFA instruments are mainly divided into two types according to the electrode used, either the straight or expandable type electrode. Although PEI-RFA can be performed by either of the electrodes, there may be some important differences in PEI-RFA according to the type of electrode used. In the present study, the effect of using the straight or expandable electrode in PEI-RFA was evaluated by analyzing the ablation time, volume of coagulated necrosis, the energy requirement for ablation and the amount of injected ethanol into HCC. The comparative study showed that ablation time, total energy requirement and per unit volume of energy requirement for whole and marginal coagulated necrosis were significantly smaller in the group treated with the expandable electrode (E group) than those in the group treated with the straight electrode (S group). The volume of coagulated necrosis was similar between these groups. In group E, the amount of injected ethanol showed a positive correlation with the volume of coagulated necrosis and the size of the tumors. These results suggest that prior injection of ethanol works mainly by shortening the time and energy requirement for ablation in the time-lag PEI-RFA using the expandable electrode. Thus, prior injection of ethanol before RFA may make RFA treatment less invasive in the time-lag PEI-RFA using the expandable electrode as previously shown HCC cases treated with straight electrode.


Use of inflammatory markers in the early detection of infectious complications after laparoscopic colorectal cancer surgery with the ERAS protocol.
Thanks to laparoscopy and enhanced recovery protocols (ERAS) it is possible to shorten hospitalization. Therefore, it seems reasonable to search for new early markers of infectious complications in order to select patients who are prone to development of complications. To assess the usefulness of serum levels of C-reactive protein, interleukin-6 and procalcitonin as early indicators of infectious complications in patients after laparoscopic colorectal surgery with ERAS. The prospective analysis included consecutive patients who underwent laparoscopic colorectal cancer resection. The following parameters were included in the analysis: C-reactive protein (CRP), interleukin 6 (IL-6) and procalcitonin measured on postoperative days (PODs) 1, 2, 3. Patients were divided into two groups: uncomplicated (group 1) and complicated (group 2). The difference in levels of the markers and the dynamics of changes observed in both groups were analyzed. Group 1 comprised 34 patients, and group 2 consisted of 17 patients. A significant increase of both absolute values and delta increments on all postoperative days was noted. ROC curve analysis showed that the best cut-off values indicating an infectious process were: CRP 129 mg/l on POD3 (92% sensitivity/80% specificity), IL-6 of 78 pg/ml on POD2 (91% sensitivity/97% specificity) and PCT 0.24 ng/ml on POD3 (93% sensitivity/68% specificity). Our study showed that regular measurement of all analyzed markers in the early postoperative days may be beneficial in the detection of postoperative infectious complications. Further studies are needed to fully assess the role of routine biochemical measurements in the postoperative period after laparoscopic surgery with the ERAS protocol.


In-process volumetric sensing of defects in multiple parts during powder bed fusion using ultrasound.
This letter reports on the integration of eight ultrasonic transducers into a build substrate for individual in-process monitoring of eight parts fabricated using powder bed fusion additive manufacturing. Ultrasound is shown to be able to sense poor fusion of parts to the substrate and also sensitivity to porosity. This technique demonstrates the utility of ultrasound as one of a few techniques able to interrogate the volume of additively manufactured parts during the process. Additionally, the ability to measure several parts during a single build can be used for efficient process parameter development studies, as the ultrasonic measurements can offer rapid information about part quality and integrity.


Contribution of insulin secretion and clearance to glucose-induced insulin concentration in african-american and caucasian children.
Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S(i)) and a higher acute insulin response to glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be predicted based on lower S(i). The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR(g) among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and second phase beta-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S(i) was lower and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase beta-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase beta-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR(g); however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR(g) after adjusting for S(i). The results of this study suggest that greater AIR(g) among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR(g) above that predicted based on lower S(i) is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.


Development of protein, peptide, and small molecule catalysts using catalysis-based selection strategies.
We have developed peptide catalysts and antibody catalysts that catalyze aldol, retro-aldol, and Michael reactions via an enamine mechanism using reaction-based selections with 1,3-diketone derivatives. Nucleophilic amino groups of the catalysts were covalently trapped during the selections. We have also developed fluorogenic substrates that are useful for real-time monitoring of the progress of bond-forming reactions, such as aldol reactions, by an increase in fluorescence. These fluorogenic substrates have been used to monitor peptide-catalyzed, antibody-catalyzed, enzyme-catalyzed, and small molecule-catalyzed reactions. Catalysis-based screening using fluorogenic substrates will accelerate rapid identification of superior catalysts and reaction conditions.


Investigation on the surface passivation of intrinsic a-Si:H thin films prepared by inductively coupled plasma-chemical vapor deposition for heterojunction solar cell applications.
Intrinsic a-Si:H thin films, which can have passivation functions on the surface of crystalline Si, were deposited by inductively coupled plasma chemical vapor deposition (ICP-CVD). The properties of the films were investigated at deposition temperatures ranging from 50 to 400 degrees C. The Si--H stretching mode at 2000 cm(-1), which indicates good film quality, was found in the range of 150-400 degrees C, but the film quality was not good at deposition temperatures below 150 degrees C. The passviation quality was determined by measuring the effective carrier lifetime using the quasi-steady state photoconductance (QSS-PC) technique. Two, 5, 7.5 and 10 nm thick films were deposited at 150 degrees C and annealed at 200 degrees C for 1 hour. The carrier lifetime of these films was approximately 3 times higher than that observed before annealing. A p a-SiC:H/i a-Si:H/n c-Si hetero-structure solar cell with a 7.8% efficiency and approximately 85% quantum efficiency (QE) was obtained by inserting an intrinsic a-Si:H thin film (5 nm) between the interfaces. These results highlight the potential applications of a passivation layer to heterojunction solar cells.


Autonomic neuropathy in diabetes mellitus.
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent definition, different diagnostic method, different patient cohorts studied. The pathogenesis is still unclear and probably multifactorial. Once DAN becomes clinically evident, no form of therapy has been identified, which can effectively stop or reverse it. Prevention strategies are based on strict glycemic control with intensive insulin treatment, multifactorial intervention, and lifestyle modification including control of hypertension, dyslipidemia, stop smoking, weight loss, and adequate physical exercise. The present review summarizes the latest knowledge regarding clinical presentation, epidemiology, pathogenesis, and management of DAN, with some mention to childhood and adolescent population.


Effect of Aging and Surface Interactions on the Diffusion of Endogenous Compounds in Latent Fingerprints Studied by Mass Spectrometry Imaging.
The ability to determine the age of fingerprints would be immeasurably beneficial in criminal investigations. We explore the possibility of determining the age of fingerprints by analyzing various compounds as they diffuse from the ridges to the valleys of fingerprints using matrix-assisted laser desorption/ionization mass spectrometry imaging. The diffusion of two classes of endogenous fingerprint compounds, fatty acids and triacylglycerols (TGs), was studied in fresh and aged fingerprints on four surfaces. We expected higher molecular weight TGs would diffuse slower than fatty acids and allow us to determine the age of older fingerprints. However, we found interactions between endogenous compounds and the surface have a much stronger impact on diffusion than molecular weight. For example, diffusion of TGs is faster on hydrophilic plain glass or partially hydrophilic stainless steel surfaces, than on a hydrophobic Rain-x treated surface. This result further complicates utilizing a diffusion model to age fingerprints.


CPD-photolyase adenovirus-mediated gene transfer in normal and DNA-repair-deficient human cells.
Cyclobutane pyrimidine dimers (CPDs) are the most frequent and deleterious lesions generated in the mammalian genome after UV-C irradiation. The persistence of these lesions in DNA can be toxic and mutagenic, and also represents a specific signal to apoptosis. To investigate the CPDs repair in situ and consequent UV-induced apoptosis in human cells, we generated a recombinant adenovirus vector containing the gene encoding a CPD-photolyase-EGFP fusion protein (Adphr-EGFP). Adphr-EGFP-infected cells are proficient in photorepair, which prevents apoptotic cell death in comparison with samples kept in the dark, indicating that the fusion protein is functional in CPD recognition and removal. By using local UV irradiation, foci of the photolyase fusion protein were observed in UV-damaged areas of the nuclei in colocalization with NER enzymes. Phr-EGFP migration to CPD sites and redistribution after photorepair was followed, and shown to present similar kinetics in normal or DNA-repair-deficient cells. To our knowledge, this is the first report of an investigation of CPDs repair in situ employing a CPD-photolyase-EGFP enzyme. The Adphr-EGFP vector can be an informative tool to investigate the repair and cellular consequences of UV-induced lesions in primary human cells.


Transcriptional reprogramming regulated by WRKY18 and WRKY40 facilitates powdery mildew infection of Arabidopsis.
The two closely related Arabidopsis transcription factors, WRKY18 and WRKY40, play a major and partly redundant role in PAMP-triggered basal defense. We monitored the transcriptional reprogramming induced by the powdery mildew fungus, Golovinomyces orontii, during early stages of infection with respect to the role of WRKY18/40. Expression of >1300 Arabidopsis genes was differentially altered already 8 hours post infection (hpi), indicating rapid pre-penetration signaling between the pathogen and the host. We found that WRKY18/40 negatively affects pre-invasion host defenses and deduced a subset of genes that appear to be under WRKY18/40 control. A mutant lacking the WRKY18/40 repressors executes pathogen-dependent but exaggerated expression of some defense genes leading, for example, to strongly elevated levels of camalexin. This implies that WRKY18/40 act in a feedback repression system controlling basal defense. Moreover, using chromatin immunoprecipitation (ChIP), direct in vivo interactions of WRKY40 to promoter regions containing W box elements of the regulatory gene EDS1, the AP2-type transcription factor gene RRTF1 and to JAZ8, a member of the JA-signaling repressor gene family were demonstrated. Our data support a model in which WRKY18/40 negatively modulate the expression of positive regulators of defense such as CYP71A13, EDS1 and PAD4, but positively modulate the expression of some key JA-signaling genes by partly suppressing the expression of JAZ repressors.


Improving the Surface-Enhanced Raman Scattering Performance of Silver Nanodendritic Substrates with Sprayed-On Graphene-Based Coatings.
This study examines the improvements in surface-enhanced Raman scattering (SERS) performance achieved when silver nanodendritic structures are coated with various graphene-based materials, namely graphene oxide (GO), reduced graphene oxide (rGO), and graphene nanoplatelets (GNPs). The tests are performed on our unique SERS-active substrates, prepared on the surface of planar microelectrode chips using an electric field-guided Ag nanoparticle assembly process. The graphene-based materials are introduced into the substrate by means of an in-house spray-coating technique. The SERS enhancement effect of each coating is examined as a function of spray nozzle passes (N) and optimal values are identified for each coating type. The enhancements found for GO, rGO, and GNP (6⁻9 graphene layers thick) coatings are 2.3 (N = 25), 2.5 (N = 5), and 1.6 (N = 1), respectively. Additionally, in comparison with their uncoated counterparts, substrates coated with rGO (N = 5) are shown to enhance the intensity of the methamphetamine (5 ppb) spectrum in artificial saliva by approximately 3-fold. Overall, it can be concluded that the introduction of GO or rGO to the SERS substrate using spray-coating, a simple and also scalable method, can produce substantial SERS performance enhancement.


Covalent functionalization of silica surface using "inert" poly(dimethylsiloxanes).
Methyl-terminated poly(dimethylsiloxanes) (PDMSs) are typically considered to be inert and not suitable for surface functionalization reactions because of the absence of readily hydrolyzable groups. Nevertheless, these siloxanes do react with silica and other oxides, producing chemically grafted organic surfaces. Known since the 1970s and then forgotten and recently rediscovered, this reaction provides a versatile yet simple method for the covalent functionalization of inorganic surfaces. In this work, we have explored the reactions of linear methyl-terminated and cyclic PDMS and bis-fluoroalkyl disiloxanes for the surface functionalization of mesoporous silica (Dpore ≈ 30-35 nm). The optimal reaction conditions included 24 h of contact of neat siloxane liquids and silica at 120-250 °C (depending on the siloxane). A study of the reactions of silicas with different extents of hydration demonstrated the critical role of water in facilitating the grafting of the siloxanes. The proposed reaction mechanism involved the hydrolysis of the adsorbed siloxanes by the Lewis acidic centers (presumably formed by water adsorbed onto surface defects) followed by the coupling of silanols to the surface to produce grafted siloxanes. For rigorously dehydrated silicas (calcination ∼1000 °C), an alternative pathway that did not require water and involved the reaction of the siloxanes with the strained siloxane rings was also plausible. According to FTIR and chemical analysis, the reactions of bis-fluoroalkyl disiloxanes and cyclic PDMS (D3-D5) produced covalently-attached monolayer surfaces, and the reactions of high-MM methyl-terminated PDMS produced polymeric grafted silicas with a PDMS mass content of up to 50%. As evidenced by the high contact angles of ∼130°/100° (adv/rec) and the negligible amount of water adsorption over the entire range of relative pressures, including saturation (p/p0 → 1), the siloxane-grafted porous silicas show uniform, high-quality hydrophobic surfaces. An overall comparison of siloxanes with classical silane coupling agents (i.e., silanes with readily hydrolyzable functionalities such as chloro, amino, etc.) demonstrated that the reactions of siloxanes produced surfaces of similar quality and, although requiring higher temperatures, used noncorrosive, less hazardous reagents, thereby providing an environmentally benign alternative to the chemical functionalization of metal oxide surfaces.


A silica monolithic column prepared by the sol-gel process for enantiomeric separation by capillary electrochromatography.
A method for the preparation of a silica monolithic capillary electrochromatography (CEC) column for the separation of enantiomers has been developed. The porous silica monolith was fabricated inside a fused-silica capillary column by using the sol-gel process. After gelation for 24 h, hydrothermal treatment at 100 degrees C for 24 h was performed to prevent the sol-gel matrix from cracking. The prepared monolith was then coated with Chirasil-beta-Dex which represents a chiral polymer prepared by grafting permethyl-beta-cyclodextrin to polymethylsiloxane with an octamethylene spacer. Immobilization of Chirasil-beta-Dex was performed by heat treatment at 120 degrees C for 48 h to give a nonextractable coating. The column performance was evaluated by using racemic hexobarbital as a model compound. The efficiency of 9.2 x 10(4) theoretical plates/m for the first eluted enantiomer of hexobarbital was obtained at an optimal flow rate of the mobile phase. The effect of mobile phase composition on enantiomeric separation of hexobarbital was also investigated. The column proved to be stable for more than one hundreds of runs during a two-months period. The enantiomers of several neutral and negatively charged chiral compounds were baseline separated on this column.


Expression, Purification and Functional Identification of Extracellular Part of Discoidin Domain Receptor 2.
Discoidin domain receptor 2 (DDR2) is a new type of receptor tyrosine kinases, and was thought to be involved in the metastasis of some tumors. Its ligand is fibrillar collagen. The activation of DDR2 induced by collagen mediates the over-expression of matrix metalloproteinase 1 (MMP-1) in cells. A specific inhibitor of DDR2 was necessary for the study of DDR2 function. Theoretically, a soluble receptor could possibly be used as specific inhibitor for the native receptor on cell membrane. In this report, a fragment (DB) of extracellular part of DDR2 was cloned and expressed for the use as potential inhibitor. This DB fragment corresponded to the polypeptide from the 23rd amino acid residue to the 293rd amino acid residue of DDR2. The fragment was amplified by RT-PCR from human lung cancer tissue, and the product was cloned into pMD18-T vector. After identification by sequence analysis, the fragment was sub-cloned into pGEX-4T-1 vector. Fusion protein of GST-DB was expressed in JM109 E.coli cells as expected and the soluble part accounted for about 13% of the total fusion protein. The soluble fusion protein was then purified with glutathione affinity resin, and GST-DB with purity of 86.1% was obtained. Competitive combination inhibitory test showed that the purified GST-DB inhibited the interaction between collagen II and DDR2 on the surface of RA synovial fibroblasts. Zymography analysis showed that the level of MMP-1 of both NIH 3T3 cell and RA synovial fibroblasts with collagen II-stimulation decreased after adding GST-DB fusion protein. The results indicated that the fusion protein GST-DB could inhibit the function of DDR2 on cells, and DDR2 might mediate collagen II-induced over-expression of MMP-1 in these cells.


Coma After Acute Head Injury.
Coma after acute head injury is always alarming. Depending on the type of injury, immediate treatment may be life-saving. About a quarter of a million patients are treated for traumatic brain injury in Germany each year. Treatment recommendations must be updated continually in the light of advancing knowledge. This review of treatment recommendations, prognostic factors, and the pathophysiology of coma after acute head injury is based on a 2015 German guideline for the treatment of head injury in adults and on pertinent publications retrieved by a selective search in PubMed for literature on post-traumatic coma. As soon as the vital functions have been secured, patients with acute head injury should undergo cranial computed tomography, which is the method of choice for identifying intracranial injuries needing immediate treatment. Patients who have an intracranial hematoma with mass effect should be taken to surgery at once. The prognosis is significantly correlated with the patient's age, the duration of coma, accompanying neurological manifestations, and the site of brain injury. The case fatality rate of patients who have been comatose for 24 hours and who have accompanying lateralizing signs, a unilaterally absent pupillary light reflex, or hemiparesis lies between 30% and 50%. This figure rises to 50-60% in patients with abnormal extensor reflexes and to over 90% in those with bilaterally absent pupillary light reflexes. Current neuropathological and neuroradiological studies indicate that coma after acute head injury is due to reversible or irreversible dysfunction of the brainstem. Brain tissue can tolerate ischemia and elevated pressure only for a very limited time. Comatose head-injured patients must therefore be evaluated urgently to determine whether they can be helped by the surgical removal of a hematoma or by a decompressive hemicraniectomy.


Challenges inherent in optimizing speech-language pathology outcomes: it's not just about counting the hours.
Determining the optimal amount of intervention is possibly the biggest challenge facing speech-language pathologists (SLPs) today. Baker (2012) has provided an erudite and pithy summary of the relevant literature in the field of optimizing intervention outcomes, and proposed a conceptual framework to measure all the inputs and acts that may contribute to the algorithm of intervention intensity. In the following article, two issues are discussed: first, that the use of technological advances to increase intensity should focus on everyday communication outcomes and, secondly, that measuring the effects of treatments which aim to increase intensity should include the perceptions of the client. Describing the evidence-based kernels underlying treatment success is a complex endeavour, particularly when the target treatment outcome is improved conversation. A recent qualitative study is described where clients with brain injury and their families were asked about their perceptions of a communication partner training program, to help determine which part of the treatment worked and why. It is argued that such an approach may provide important information regarding the "active ingredients" of treatment success.


Successful results of a program combining live and inactivated poliovirus vaccines to control poliomyelitis in Gaza.
Trivalent oral poliovirus vaccine ( TOPV ) has been used in Gaza since 1967. After an initial decrease of 33% in the incidence of the paralytic disease, no further decrease could be noted. The mean annual incidence until 1977 was 10 per 100,000 inhabitants. Two outbreaks caused by poliovirus type 1 were registered in 1974 and 1976 with an incidence of 18 per 100,000 inhabitants. In these outbreaks, 34% and 50% of the affected children, respectively, had received three to four doses of TOPV . A new vaccination schedule was introduced in 1978, combining live and inactivated poliovirus vaccines. In the years 1978-1980, the incidence decreased to 2.6 per 100,000 inhabitants; and during 1981-1982, only three cases were recorded. These results indicate that a schedule like the one used in Gaza could serve as a model to control poliomyelitis in developing countries where TOPV alone is not successful.


The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C.
Severe sepsis syndrome has important consequences to healthcare systems as the incidence is increasing, there is significant attributed morbidity and mortality and there is a substantial cost for in-hospital and post-discharge care. Current treatment includes the use of antimicrobials, local source control and aggressive physiological support, usually in an intensive care unit setting. Drotrecogin-alpha (activated) or recombinant human activated protein C (rhAPC) is the only biological agent approved for use in severe sepsis syndrome that has demonstrated efficacy in reducing 28-day all-cause mortality and new data suggests a trend towards longer term survival. However, given the evidence of a variable effect on survival rates in patient subgroups and its acquisition cost, controversy has arisen concerning its appropriate use. This review discusses the epidemiology of sepsis, preclinical and clinical evidence supporting the use of rhAPC use, controversies about the evidence of efficacy in severe sepsis syndrome and cost-effectiveness data.


Fathers make a difference: positive relationships with mother and baby in relation to infant colic.
Maternal psychological factors like depression, anxiety and stress have been associated with infant fussiness or colic. However, little research exists on whether positive factors such as social support and the happiness of the mother-partner relationship are associated with lower rates of infant fussiness or colic. We investigated the association between infant colic and three types of maternal support: general maternal social support (during pregnancy and post partum), the happiness of the mother-partner relationship (during pregnancy and post partum) and partner involvement in caring for the newborn. Participants were 3006 women in the First Baby Study, a prospective study of the effect of mode of first delivery on subsequent childbearing. Women were interviewed by telephone during pregnancy and 1 month after first childbirth and asked about social support and if their baby had a variety of problems since birth, including 'Colic - crying or fussiness three or more hours a day'. Multivariable logistic regression models were used to model the association between maternal support and infant colic, controlling for confounders, including maternal race or ethnicity, insurance, marital status, smoking, mode of delivery, maternal post-partum depression, breastfeeding, other neonatal illnesses and newborn gestational age. Infant colic was reported by 11.6% of new mothers. High general maternal social support (in comparison with low), measured during pregnancy, was associated with lower reported infant colic (adjusted odds ratio (AOR), 0.55, 95% confidence interval (CI), 0.40-0.75) and measured post partum (AOR, 0.51, 95% CI, 0.39-0.67); high relationship happiness (in comparison with low), measured during pregnancy (AOR, 0.71, 95% CI, 0.54-0.93), and measured post partum (AOR, 0.22, 95% CI, 0.12-0.40); and high partner involvement with newborn care (in comparison with low) (AOR, 0.60, 95% CI, 0.44-0.81). Higher levels of maternal social support during pregnancy and post partum are associated with lower rates of maternal reported infant colic.


Early detection of pathologic pregnancy by transvaginal sonography.
Vaginal ultrasonography, by virtue of its excellent resolution, has resulted in changing our concepts about early pregnancy both in normal and abnormal gestations. The purpose of this report is to examine the clinical application of this technique in abnormal early pregnancy. Pathologic pregnancy ultimately will prove to be either (1) an ectopic pregnancy or (2) an intrauterine gestation that may be destined to failure. (A third group, fetuses with anomalies, will be dealt with elsewhere). Vaginal sonography has enhanced very early pathologic diagnosis in pregnancy because of its ability to image things previously not seen with such clarity, and because the scanning process can be carried out at the time of pelvic examination when the clinical indication is first encountered.


Antinociceptive action of Vanillosmopsis arborea in male mice.
Vanillosmopsis arborea Baker (Asteraceae) has high economic value from Chapada to Araripe and its bark essential oil is a potential source of alpha-bisabolol. The present study aimed to elucidate the antinociceptive and antipruritic properties of the essential oil of V. arborea Baker (EOVA) in mice. The antinociceptive activity was assessed using the capsaicin, glutamate, hot plate and cold allodynia tests. The antipuritic effects were also verified based on histamine-induced scratching behavior. EOVA reduced the paw licking induced by capsaicin, but not that induced by glutamate. The essential oil increased the latency time in the hot plate, attenuated the cold allodynia induced by acetone and inhibited histamine-induced scratching behavior. The experimental data demonstrated that EOVA showed central and peripheral antinociceptive activity and antipruritic effect.


Cellular memory: neutrophil orientation reverses during temporally decreasing chemoattractant concentrations.
Cell directional orientation or shape polarization is the first cellular step in neutrophil locomotion. To better understand how chemoattractants interact with cells, we studied neutrophil polarization (or shape changes) during exposure to a temporally decreasing chemoattractant signal of N-formyl-methionyl-leucyl-phenylalanine (FMLP) in the absence of a spatial concentration gradient. To accomplish this objective, we used a manifold of differing FMLP concentrations attached to a stopped-flow microscope chamber. Spatial gradients of a fluorescent chemotactic peptide could not be detected in the chamber by using microfluorometry. When FMLP was injected at continually increasing concentrations at 10-s intervals, the shape and relative direction of the neutrophil persisted. However, when temporally decreasing FMLP concentrations were injected, approximately 80% of the cells changed their direction with 44% of the total cells swinging about to 180 degrees +/- 15 degrees. Most of these directional changes involved dissolution of both the lamellipodium and uropod and reformation of these structures 180 degrees from their original positions. This research suggests that neutrophils reverse their morphological polarity when exposed to temporally decreasing ligand concentrations by "remembering" their ligand exposure history and relative direction.


A short-term exercise program in patients with multiple sclerosis: is body mass index important?
Obesity is a health problem that can exacerbate the symptoms of multiple sclerosis (MS). In the current study, we aimed to investigate the effectiveness of a short-term exercise program on fatigue, depression, anxiety, and walking performance in normal-weight and overweight patients with MS (PwMS). Sixty-two PwMS were divided into groups according to their BMI (BMI normal/BMI high). Also, they were all included in the exercise program. The participants took a moderate-intensity walking program 5 days a week for 4 weeks, including 30 min between 5 min of warm-up and 5 min of cooling periods. Also, patients underwent breathing, posture, flexibility, and stretching exercises for 4 weeks. Fatigue, depression, anxiety, 6-minute walking test (6MWT), and BMI were measured before and after the 4 weeks. After the exercise program, there were statistically significant improvements in fatigue, depression, anxiety, and the 6MWT. However, no relation could be detected between the examined variables and BMI. All patients participated effectively in the exercise program, regardless of BMI. The results obtained from this study support that a short-term exercise program is an effective therapeutic intervention, unrelated to BMI, in improving fatigue, depression, anxiety, and walking performance in PwMS.


Human immunodeficiency virus type 1 Vif induces cell cycle delay via recruitment of the same E3 ubiquitin ligase complex that targets APOBEC3 proteins for degradation.
Human immunodeficiency virus type 1 (HIV-1) Vif recruits a Cullin 5 ubiquitin ligase that targets APOBEC3 proteins for degradation. Recently, Vif has also been shown to induce cell cycle disturbance in G(2). We show that in contrast to the expression of Vpr, the expression of Vif does not preclude cell division, and therefore, Vif causes delay and not arrest in G(2). We also demonstrate that the interaction of Vif with the ubiquitin ligase is required for cell cycle disruption, as was previously shown for HIV-1 Vpr. The presence of APOBEC3 D/E, F, and G had no influence on Vif-induced alteration of the cell cycle. We conclude that cell cycle delay by Vif is a result of ubiquitination and degradation of a cellular protein that is different from the known APOBEC3 family members.


Nanodrugs for the Treatment of Ischemic Stroke: A Systematic Review.
Ischemic stroke, a significant neurovascular disorder, currently lacks effective restorative medication. However, recently developed nanomedicines bring renewed promise for alleviating ischemia's effects and facilitating the healing of neurological and physical functions. The aim of this systematic review was to evaluate the efficacy of nanotherapies in animal models of stroke and their potential impact on future stroke therapies. We also assessed the scientific quality of current research focused on nanoparticle-based treatments for ischemic stroke in animal models. We summarized the effectiveness of nanotherapies in these models, considering multiple factors such as their anti-inflammatory, antioxidant, and angiogenetic properties, as well as their safety and biodistribution. We conclude that the application of nanomedicines may reduce infarct size and improve neurological function post-stroke without causing significant organ toxicity.


Patients' Perspectives on Outcomes of Care After Discharge From the Emergency Department: A Qualitative Study.
Much effort has been expended to understand what care experiences patients value in the emergency department (ED), yet little is known about which outcomes patients value after ED care. Our goal is to define outcomes of ED care that are valued by patients discharged from the ED, with the goal of informing the development of a patient-reported outcome measure for ED care. We conducted qualitative semistructured interviews with patients recruited during their care at 1 of 2 EDs and interviewed in either English or French 1 to 9 days after their visit. Patients who were hospitalized were excluded. Interviews focused on perceived outcomes of care since the ED visit and expectations of care before the ED visit. We identified themes with standard descriptive content analysis techniques and a modified version of the constant comparative method, drawing on grounded theory methods. We interviewed 46 patients in English (n=38) or French (n=8). Participants with diverse reasons for seeking care appeared to value common outcomes from ED care that centered around 4 themes: understanding the cause and expected trajectory of their symptoms; reassurance; symptom relief; and having a plan to manage their symptoms, resolve their issue, or pursue further medical care. These themes were also reflected in the expectations participants recalled having when they decided to seek care in the ED. The 4 outcomes defined constitute areas for improvement and will inform the development of an ED patient-reported outcome questionnaire. Consideration should be given to measuring patient-reported outcomes separately from patient experience.


Keys to buying a dental practice and successful transition planning.
So, you want to buy your own dental practice. Sounds great, but proceed with caution and follow the critical steps to success. Having spent the last 15-plus years in her management consulting business assisting dentists with selling, buying, and practice transitions, the author has outlined key steps to ensure a smooth transition from evaluating the practice to ownership.


Physical diseases and elderly suicide in rural China: A case-control psychological autopsy study.
Physical diseases are well-established risk factor for suicide, particularly among older adults. However, little is known about the underlying mechanism of the association. This study aimed to describe the prevalence of physical diseases and their influences on the elderly in rural China and to examine the underlying mechanisms of the relationship between physical diseases and suicide. This matched case-control psychological autopsy study was conducted from June 2014 to September 2015. Consecutive suicide cases (242) among people aged 60 years or above were identified in three Chinese provinces. The suicide cases were 1:1 matched with living comparisons based on age, gender and residential area. Two informants for each participant were interviewed to collect data on their demographic characteristics, the severity index of physical diseases, depressive symptoms, feelings of hopelessness, mental disorders and social support. A significant difference was found between suicide cases and living comparisons regarding the prevalence of physical diseases (83.5% vs 66.5%, p < 0.001) and their severity (11.3 ± 6.2 vs 6.7 ± 5.3, p < 0.001). Independent risks of suicide included the following: not currently married (OR = 2.81, 95% CI = [1.04, 7.62]), mental disorders (OR = 7.18, 95% CI = [1.83, 28.13]), depressive symptoms (OR = 1.15, 95% CI = [1.05, 1.26]) and feelings of hopelessness (OR = 1.51, 95% CI = [1.20, 1.90]). The structural equation model indicated that the relationship between the severity index of physical diseases and suicide was mediated by depressive symptoms, feelings of hopelessness and mental disorders. The severity and number of physical diseases were found to be correlated with suicide among the elderly in rural China, after controlling for demographic characteristics. Physical diseases elevate one's suicide risk by increasing depressive symptoms, feelings of hopelessness and mental disorders. Efforts for suicide prevention should be integrated with strategies to treat physical diseases along with psychological interventions.


Molecular basis of the mucosal immune system: from fundamental concepts to advances in liposome-based vaccines.
The mucosal immune system, the primary portal for entry of most prevalent and devastating pathogens, is guarded by the special lymphoid tissues (mucosally associated lymphoid tissues) for immunity. Mucosal immune infection results in induction of IgA-manifested humoral immunity. Cell-mediated immunity may also be generated, marked by the presence of CD4(+) Th1 and CD8(+) cells. Furthermore, the immunity generated at the mucosal site is transported to the distal mucosal site as well as to systemic tissues. An understanding of the molecular basis of the mucosal immune system provides a unique platform for designing a mucosal vaccine. Coadministration of immunostimulatory molecules further accelerates functioning of the immune system. Mimicking receptor-mediated binding of the pathogen may be achieved by direct conjugation of antigen with an immunostimulatory molecule or encapsulation in a carrier followed by anchoring of a ligand having affinity to the cells of the mucosal immune system. Nanotechnology has played a significant role in mucosal vaccine development and among the available options liposomes are the most promising. Liposomes are phospholipid bilayered vesicles that can encapsulate protein as well as DNA-based vaccines and offer coencapsulation of adjuvant along with the antigen. At the same, time ligand-conjugated liposomes augment interaction of antigen with the cells of the mucosal immune system and thereby serve as suitable candidates for the mucosal delivery of vaccines. This article exhaustively explores strategies involved in the generation of mucosal immunity and also provides an insight to the progress that has been made in the development of liposome-based mucosal vaccine.


Is quality of life impairment associated with chronic diseases dependent on educational level?
Previous research indicates that quality of life impairment as a result of chronic diseases differs between socioeconomic groups, but the pattern seems to vary between health-related quality of life (HRQOL) outcomes. We tested for a one-item and a multi-item outcome whether associations between diseases and HRQOL varied between educational levels. Data come from Dutch participants of HELIUS (N =4615, aged 18-70). Education was defined as low, middle or high. Myocardial infarction, angina pectoris, hypertension, diabetes, obesity and depressed mood were measured using physical examination and/or self-report. Outcomes were fair/poor self-rated health (SRH) and physical (PCS) and mental (MCS) SF-12 scores. Interaction terms and relative excess risk due to interaction (RERI) were used as measures of additive interaction. SRH and PCS were worst in lower educated participants, whereas MCS was worst in middle educated participants. Out of thirty-six interactions tested, four were statistically significant, with risks of poor HRQOL being both larger and smaller in low vs. high education groups. Obesity was associated with smaller risk of fair/poor SRH in low vs. high educated [RERI=-2.49 (-4.66; -0.33)]. Depressed mood was associated with more [b=-3.34 (-6.14; -0.54)] and hypertension with less reduction in PCS [b=1.23 (0.18; 2.27)] in middle vs. high educated. Depressed mood was highly associated with MCS, but less so in middle vs. high educated [b=4.09 (0.72; 7.47)]. Despite a higher prevalence of diseases in low education groups, if measured in absolute terms, most diseases were not associated with larger impairment of HRQOL in lower vs. higher educated groups, regardless of the outcome measure used.


Laparoscopic antireflux surgery: five-year results and beyond in 1340 patients.
Although the long-term results of open fundoplication for gastroesophageal reflux disease are well documented, few reports exist on the long-term results of laparoscopic fundoplication. Retrospective study with clinical evaluation or mailed survey for patients unable to return to the hospital center. Multicenter studies (ie, private medical centers, institutional hospitals, and university hospitals). Between January 1992 and December 1998, 2684 patients with gastroesophageal reflux disease underwent laparoscopic fundoplication in 31 hospital centers. Outcome data covering a period of 5 or more years after surgery were available for 1340 patients: 711 who underwent complete fundoplication, 559 who underwent partial posterior fundoplication, and 70 who underwent partial anterior fundoplication. Evaluation of clinical and quality-of-life actions used to treat the symptoms of gastroesophageal reflux disease. The overall residual severe dysphagia rate was 5.1% (n = 68). A further surgical procedure was required for 59 patients (4.4%) for a total of 63 interventions. Subsequent operation was performed laparoscopically in 32 cases (50.8%). Twelve of these procedures were for the repair of a paraesophageal hiatus hernia, 11 were for dysphagia (4 because of a tight esophageal hiatus and 7 for conversion of Nissen fundoplication to a posterior partial fundoplication procedure), 31 were for recurrent reflux (wrap undone), 2 were for intestinal obstruction (adhesiolysis), 1 was for incisional hernia, 1 was for abdominal abscess (drainage), and 1 was for gastroparesis (pyloroplasty). The recurrence rate was 10.1% (n = 136), and 122 patients (9.1%) resumed taking antisecretory medication. Gas bloat syndrome was present in 101 patients (7.5%). A total of 93.1% of the patients were satisfied (Visick classification, grades 1 and 2) and 6.9% were unsatisfied, with no difference among the 3 procedures. After 5 years of experience, laparoscopic fundoplication remains an effective antireflux procedure.


Calculating interaction energies in transition metal complexes with local electron correlation methods.
The results of density fitting and local approximations applied to the calculation of transition metal-ligand binding energies using second order Møller-Plesset perturbation theory are reported. This procedure accurately reproduces counterpoise corrected binding energies from the canonical method for a range of test complexes. While counterpoise corrections for basis set superposition error are generally small, this procedure can be time consuming, and in some cases gives rise to unphysical dissociation of complexes. In circumventing this correction, a local treatment of electron correlation offers major efficiency savings with little loss of accuracy. The use of density fitting for the underlying Hartree-Fock calculations is also tested for sample Ru complexes, leading to further efficiency gains but essentially no loss in accuracy.


Occurrence, toxicity and adsorptive removal of the chloramphenicol antibiotic in water: a review.
Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, hydrogen bonding, and electrostatic interactions. We also discuss isotherms, kinetics, thermodynamic data, selection of eluents, desorption efficiency, and regeneration of adsorbents. Porous carbon-based adsorbents exhibit excellent adsorption capacities of 500-1240 mg g-1. Most adsorbents can be reused over at least four cycles.


QuickStats: Percentage* of Children and Teens Aged 5-17 Years Who Missed >10 School Days in the Past 12 Months Because of Illness or Injury,† by Sex and Age - National Health Interview Survey, 2013-2015§.
During 2013-2015, 3.9% of boys and 4.3% of girls missed >10 school days in the past 12 months because of illness or injury. Among children aged 15-17 years, girls were more likely than boys to miss >10 school days (6.8% compared with 3.9%). Among girls, those aged 15-17 years were more likely than girls aged 5-10 years and girls aged 11-14 years to miss >10 school days (6.8% compared with 3.2% and 4.0%, respectively). Among boys, there was no difference by age.


Evaluation of isoelectric focusing running conditions during two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis: variation of gel patterns with changing conditions and optimized isoelectric focusing conditions.
Five major isoelectric focusing (IEF) parameters--volt-hours; concentrations of acrylamide, NaOH, and H3PO4; and equilibration time--were systematically varied to determine the effect of each on two-dimensional IEF/sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel patterns and to optimize IEF conditions. Alterations in each parameter affected the gel pattern, frequently causing uncertainty in the identification of spots between conditions. The results emphasize the need for internal analytical consistency, and indicate that gel pattern comparisons between laboratories can be complicated if different IEF conditions are employed. The systematic evaluation indicated that optimized patterns were obtained when increased concentrations of NaOH and H3PO4 (to 50 and 25 mM, respectively) and run durations of 10,000 V-h or longer were used.


Acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD) continues to be a problem in allogeneic transplantation. Recent advances in the understanding of the induction and propagation of GVHD have lead to new transplant strategies and treatment of aGVHD. This overview covers the basic pathophysiology, prophylaxis and treatment of this disorder.


Isolation and Analysis of Xenopus Germinal Vesicles.
The giant nucleus or germinal vesicle (GV) of Xenopus oocytes provides an unusual opportunity to analyze nuclear structure and function in exquisite detail by light microscopy. Detailed here are two rapid procedures for using manually isolated GVs in combination with fluorescent reporter proteins to investigate the lampbrush chromosomes and nuclear bodies of oocytes. One procedure provides spreads of nuclear components in an unfixed and life-like, although not living, form. The other describes the isolation of intact, functional GVs directly into mineral oil offering possibilities for direct observation of nuclear dynamics.


The enhancing effect of mitogens on the in vivo immune response of rabbits.
The effect of Con A and PHA on the primary humoral immune response in rabbits was investigated and compared with the effect of LPS and irradiation. Both Con A and PHA enhanced PFC levels and precipitating antibody titers to HuIgG when injected simultaneously with AHuIgG. Comparable enhancement of the response to HuIgG was obtained by simultaneous injection of LPS with AHuIgG or by irradiating rabbits (500 R) 24 hr after injection of the antigen. Further studies with Con A showed that its adjuvant effect was not restricted to a particular antigen since it also enhanced antibody responses to both SRBC and Bov Tg when injected simultaneously with either of these antigens. Although optimal enhancement of the response to HuIgG occurred when antigen and mitogen were injected simultaneously, some enhancement was obtained if Con A was injected 2 days after antigen, whereas the response was decreased if Con A was injected 2 days before antigen. Splenic PFC in A/J mice injected with doses of AHuIgG and Con A equivalent on a body weight basis to those used in rabbits were also enhanced by simultaneous injection of Con A with the antigen.


[A Papua New Guinean with three foot ulcers].
A 25-year-old Papuan presented with three painless foot ulcers with undermined edges, induration and oedema. The appearance was typical for Buruli ulcer, which is caused by Mycobacterium ulcerans. A smear was positive for acid fast bacilli. Buruli ulcers are found in patients from humid and tropical regions and are treated with rifampicin and streptomycin during eight weeks.


Taking varenicline for smoking cessation: A rare cause of pulmonary thromboembolism with infarction.
Varenicline (Champix®, Chantix®) is a partial agonist of the α4β2 nicotinic acetylcholine receptor (nAChR) and a full agonist of the α7 nAChR. It has been used for smoking cessation since 2006. Varenicline has been associated with adverse cardiovascular (CV) events, including myocardial infarction, which may be caused by activation of the α7 nAChR receptor that in turn stimulates parasympathetic output from the brainstem to the heart, release of catecholamines, and has a prothrombotic effect. However, among the adverse CV events, the issue related to the varenicline-induced pulmonary thromboembolism (PTE) has not being addressed. We report a case of PTE with pulmonary infarction presenting as right flank pain that resulted from the use of varenicline (the total score of adverse drug reaction probability scale, 6; probable association between varenicline and pulmonary PTE) in a patient without underlying CV disease and in whom low probability of PTE (Wells score was zero) was identified.


The life cycle of a horsehair worm, Gordius robustus (Nematomorpha: Gordioidea).
Aspects of the life cycle of the nematomorph Gordius robustus were investigated. Gordius robustus larvae fed to Tenebrio molitor (Coleoptera: Tenebrionidae) readily penetrated and subsequently encysted in the posterior portion of the midgut wall. Parasite development was then arrested in each infected beetle. Upon feeding these cysts to laboratory-reared Gryllus firmus, worm larvae developed to adults in the cricket hemocoel. In an additional experiment, G. robustus larvae fed to G. firmus did not develop to adults. These findings are in contrast to other studies that found direct infection to be an alternative mode of infection. This experiment is the first employing a laboratory-maintained stock of hosts to rear nematomorph worms.


In Search of the Perfect Thrombosis and Bleeding-Associated Cancer Scale.
Thrombosis and bleeding are commonly observed in cancer patients, and their management is crucial for positive patient outcomes. A comprehensive, prophylactic, and therapeutic management of venous thrombosis should focus on identifying the patients who would benefit most from treatment to reduce mortality and minimize the risk of thrombosis recurrence without significantly increasing the risk of bleeding. Existing cancer scales provide valuable information for assessing the overall burden of cancer and guiding treatment decisions, but their ability to predict thrombotic and bleeding events remains limited. With increasing knowledge of the pathophysiology of cancer and the availability of advanced anticancer therapies, new risk factors for cancer-associated thrombosis and bleeding are being identified. In this report, we analyze the current literature and identify new risk factors for venous thrombosis and bleeding which are not included in routinely used risk scores. While some existing cancer scales partially capture the risk of thrombosis and bleeding, there is a need for more specific and accurate scales tailored to these complications. The development of such scales could improve risk stratification, aid in treatment selection, and enhance patient care. Therefore, further research and development of novel cancer scales focused on thrombosis and bleeding are warranted to optimize patient management and outcomes.


Comprehensive analysis of transcriptome-wide N6-methyladenosine methylomes in the Barrett's esophagus in rats.
As the most abundant RNA modification, N6-methyladenosine (m6A) methylation plays crucial roles in various diseases. The aim of this study is to comprehensively map the landscape of the mRNA m6A modification pattern in Barrett's esophagus (BE) in order to find key genes and potential therapy for BE and even esophageal adenocarcinoma (EAC). Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) were performed to compare the difference in mRNA m6A methylation and differentially expressed mRNAs between BE and normal control (NC) tissues. Bioinformatics analysis was used to describe the m6A modification pattern and specific genes in BE and NC tissues. Through MeRIP-seq, we obtained m6A methylation profiling in BE and NC tissues. In total, 11,026 unique peaks were detected in the BE groups, whereas 8564 unique peaks were detected in the NC groups. Peaks were primarily enriched within CDS with GGACU motifs and most of the peaks were within 1000 bp in width. Moreover, functional enrichment analysis demonstrated that hypermethylated and hypomethylated genes were significantly enriched in coronavirus disease pathway, calcium signaling pathway and MAPK signaling pathways. Furthermore, PPI network was conducted and 18 hub genes were identified via STRING database and Cystoscope. Among them, ACTA1, CDC20, CKM, KIF20a, MYH11, TPM2, MYL9, DES, TNNT3 were overexpressed in EAC in the GEPIA gene bank and TPM1, KIF20a impaired patients' survival in the Kaplan-Meier plotter database. Finally, functional enrichment analysis demonstrated that co-expressed genes of TPM1 were significantly enriched in calcium signaling pathway, cGMP-PKG signaling pathway and PI3K-Akt signaling pathway. Our study is the first to perform comprehensive and transcriptome-wide maps to identify the potential roles played by m6A methylation in BE, which widely involved in oxidative stress. This foresees a guiding role in revealing the molecular mechanism of m6A-mediated genes that govern the pathogenesis and progression of BE and EAC.


Numerical analysis of modal dispersion in graded-index plastic optical fibers.
Modal dispersion properties of a fabricated plastic optical fiber are numerically calculated through a finite-element method. The modal index, group delay, impulse response, and output pulse shape are compared with those for the power-law profile plastic optical fiber; the influence of index profile deviations from the power-law profile is described. It is shown that index profile fluctuations in the actual index profile strongly affect the group delays, even though they are relatively small. On the other hand, they have little effect on the modal indices.


Characterization of 20-S and 40-S non-polysomal cytoplasmic messenger ribonucleoprotein particles from rat liver.
Two populations of free messenger ribonucleoprotein (mRNP) particles, sedimenting at 20 S and 40 S respectively, were isolated from a rat liver postpolysomal supernatant. After treatment with 0.5 M KCl and recentrifugation through a sucrose layer, the mRNP particles were characterized with respect to their low-molecular-weight RNA and protein components. 40-S and 20-S particles show very different RNA patterns. Four distinct low-molecular-weight RNA species of approximately 105, 139, 187 and 256 nucleotides were found as components of the 40-S mRNPs. The 20-S mRNP particles contain one major low-Mr RNA species of approximately 243 nucleotides and a characteristic pattern of low-Mr RNAs similar to the one found in nuclear ribonucleoprotein particles. In contrast to the low-Mr RNAs found in nuclear RNP particles most of the low-Mr RNA species present in 20-S and 40-S mRNP particles are rapidly labeled after [3H]orotate administration. Whereas the low-Mr RNA composition of 20-S and 40-S mRNP particles is very different, the protein patterns of both mRNP complexes are very similar. Six major polypeptides with the following molecular weights of 117000, 79800, 76700, 53800, 43900, 36300 and several minor ones were found in both 20-S and 40-S mRNPs. In a cell-free system from wheat germs neither 20-S nor 40-S mRNP particles stimulated the incorporation of [3H]leucine into proteins. However, phenol-extracted RNA from 20-S and 40-S mRNPs stimulated total protein synthesis 16-fold and 3-fold, respectively. Furthermore, the RNA from both mRNP pools directed the synthesis of albumin in vitro.


Comparisons of the morbidities of a double gastrocnemius flap and a medial gastrocnemius flap in the orthoplastic reconstruction around the knee.
The pedicled gastrocnemius flap is commonly used to treat lower limb defects. Either the medial, lateral, or both heads can be used. When extended soft tissue defects are present, a double gastrocnemius (DG) flap may be used. However, no data of the additional donor site morbidity compared to a medial gastrocnemius (MG) flap are available. The aim of this study was to compare the donor site morbidity of a DG with that of a MG. Patients with a soft tissue defect around the knee, treated with a gastrocnemius flap between 2018 and 2021 at the University Hospital of Lausanne and Bari, with a minimum follow-up of 12 months, were included. According to the size and the position of the defect, it was decided whether one (10 patients) or two (9 patients) heads of the gastrocnemius were necessary for the coverage. The mean age was 61 years (range 42-82) in DG, and 63 years (range 45-78) in MG. The average defect size was 89.8 cm2 in the DG group and 53.4 cm2 in the MG group. The etiologies were trauma (n = 10), infection (n = 7) and sarcoma (n = 2). A medial approach or a posterior midline approach was used for the harvesting of the gastrocnemius muscle. Once the flap was harvested, it was rotated and transposed anteriorly over the defect, either through a subcutaneous tunnel or by dividing the intervening skin bridge, depending on the soft tissue defect. A split-thickness skin graft was used to close the skin over the remaining exposed muscle flap. The active range of motion of the ankle and knee joints was measured. Muscle strength was assessed with a hand-held dynamometer and by the ability to stand on tiptoe. Physical function was evaluated through the Lower Extremity Functional Scale (LEFS). The two groups were homogeneous, with no significant difference in age, sex, and BMI. All flaps survived in both groups. Both groups showed lower values in strength and range of motion of the operated leg, when compared to contralateral side. In plantar flexion, this accounted for a reduction in MG by 3.8 ± 1.0 kg of strength and 8 ± 3° of ROM, and in DG by 4.7 ± 1.7 kg and 16 ± 4°, respectively. For knee flexion, the reduction in MG was 4.4 ± 0.6 kg and 16 ± 7°, while in DG 5.6 ± 1.0 kg and 28 ± 6°. In the MG group, 60% were able to stand on the tiptoe of the operated leg, as opposed to 0% in DG. The average LEFS score in DG was lower by 10.9 points (p < .05). Questions concerning running and jumping had a lower score in DG (p < .01). The harvesting of both gastrocnemii led to significant additional donor site morbidity compared to the harvesting of the medial gastrocnemius alone. However, the additional morbidity did not have an impact on activities of daily living and walking, even though it limited the ability to perform more demanding tasks such as running and jumping. Therefore, based on our study, the choice of a DG flap should be critically assessed in younger, more demanding patients.


The total synthesis of (+/-)-11-O-debenzoyltashironin.
The total synthesis of the putative non-peptidyl neurotrophic factor 11-O-debenzoyltashironin has been accomplished. The key transformation involves a biomimetic oxidative dearomatization/transannular Diels-Alder sequence that closes the tetracyclic carbon skeleton present in the natural product.


Cost of chronic disease in California: estimates at the county level.
An estimated 39% of people in California suffer from at least one chronic condition or disease. While the increased coverage provided by the Affordable Care Act will result in greater access to primary health care, coordinated strategies are needed to prevent chronic conditions. To identify cost-effective strategies, local health departments and other agencies need accurate information on the costs of chronic conditions in their region. To present a methodology for estimating the cost of chronic conditions for counties. Estimates of the attributable cost of 6 chronic conditions-arthritis, asthma, cancer, cardiovascular disease, diabetes, and depression-from the Centers for Disease Control and Prevention's Chronic Disease Cost Calculator were combined with prevalence rates from the various sources and census data for California counties to estimate the number of cases and costs of each condition. The estimates were adjusted for differences in prices using Medicare geographical adjusters. An estimated $98 billion is currently spent on treating chronic conditions in California. There is significant variation between counties in the percentage of total health care expenditure due to chronic conditions and county size, ranging from a low 32% to a high of 63%. The variations between counties result from differing rates of chronic conditions across age, ethnicity, and gender. Information on the cost of chronic conditions is important for planning prevention and control efforts. This study demonstrates a method for providing local health departments with estimates of the scope of the problems in their region. Combining the cost estimates with information on current prevention strategies can identify gaps in prevention activities and the prevention measures that promise the greatest return on investment for each county.


Characteristics and outcomes of patients with chronic obstructive pulmonary disease admitted to the intensive care unit due to acute hypercapnic respiratory failure.
The study aimed to describe the clinical course, outcomes, and prognostic factors of chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure. This retrospective study involved patients with acute hypercapnic respiratory failure due to COPD of any cause admitted to the intensive care unit (ICU) for non-invasive or invasive mechanical ventilation (IMV) support between December 2015 and February 2020. One hundred patients were evaluated. The main causes of acute hypercapnic respiratory failure were bronchitis, pneumonia, and heart failure. The patients' mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 23.0±7.2, and their IMV rate was 43%. ICU, in-hospital, and 90-day mortality rates were 21%, 29%, and 39%, respectively. Non-survivors had more pneumonia, shock within the first 24 hours of admission, IMV, vasopressor use, and renal replacement therapy, along with higher APACHE II scores, lower admission albumin levels and PaO2/ FiO2 ratios, and longer ICU and hospital stays than survivors. Logistic regression analysis identified APACHE II score (odds ratio [OR], 1.157; 95% confidence interval [CI], 1.017-1.317; P=0.026), admission PaO2/FiO2 ratio (OR, 0.989; 95% CI, 0.978-0.999; P=0.046), and vasopressor use (OR, 8.827; 95% CI, 1.650-47.215; P=0.011) as predictors of ICU mortality. APACHE II score (OR, 1.099; 95% CI, 1.021-1.182; P=0.011) and admission albumin level (OR, 0.169; 95% CI, 0.056-0.514; P=0.002) emerged as predictors of 90-day mortality. APACHE II scores, the PaO2/FiO2 ratio, vasopressor use, and albumin levels are significant short-term mortality predictors in severely ill COPD patients with acute hypercapnic respiratory failure.


Optimal rate of enteral glucose administration in children with glycogen storage disease type I.
Rates of administration of enteral carbohydrate to maintain the plasma glucose concentration and suppress organic acidemia in young children with glycogen storage disease Type I have not been clearly established. Therefore, we studied six children with the disease during sequential nasogastric infusions of carbohydrate at four different rates (10.5, 8.6, 5.8, and 3 mg of carbohydrate per kilogram of body weight per minute). The rates at which total and endogenous glucose appeared in the plasma were measured with [2H2] glucose. The infusion rates of carbohydrate were linearly correlated (r = 0.88, P less than 0.001) with the plasma glucose concentration, which was about 90 mg per deciliter at a rate of 8.6 mg per kilogram per minute. The mean (+/- SE) rate of appearance of endogenous glucose was 1.4 +/- 0.1 mg per kilogram per minute at a nasogastric infusion rate of 5.8 mg of carbohydrate per kilogram per minute (a rate similar to that of hepatic glucose production in normal children who have fasted overnight), and was completely suppressed at 10.5 mg of carbohydrate per kilogram per minute. Concentrations of plasma lactate, pyruvate, free fatty acids, and ketone bodies were inversely related to the rate of carbohydrate administration below 8.6 mg per kilogram per minute. We conclude that the minimal nocturnal nasogastric infusion rate of carbohydrate needed to maintain plasma glucose concentrations and minimize organic acidemia in young children with glycogen storage disease Type I is approximately 8 to 9 mg per kilogram per minute.


Metformin rescues the myocardium from doxorubicin-induced energy starvation and mitochondrial damage in rats.
Clinical use of doxorubicin (DOX) is limited by its cardiotoxic side effects. Recent studies established that metformin (MET), an oral antidiabetic drug, possesses an antioxidant activity. However, whether it can protect against DOX-induced energy starvation and mitochondrial damage has not been reported. Our results, in a rat model of DOX-induced cardiotoxicity, show that DOX treatment significantly increased serum levels of LDH and CK-MB, indicators of cardiac injury, and induced expression of hypertrophic gene markers. DOX also caused marked decreases in the cardiac levels of glutathione, CoA-SH and ATP, and mRNA expression of catalase and NQO-1. These biochemical changes were associated with myocardial histopathological and ultrastructural deteriorations, as observed by light and electron microscopy, respectively. Cotreatment with MET (500 mg/kg) eliminated all DOX-induced biochemical, histopathological, and ultrastructural changes. These findings demonstrate that MET successfully prevents DOX-induced cardiotoxicity in vivo by inhibiting DOX-induced oxidative stress, energy starvation, and depletion of intramitochondrial CoA-SH.


Large full band gaps for photonic crystals in two dimensions computed by an inverse method with multigrid acceleration.
In this study, two fast and accurate methods of inverse iteration with multigrid acceleration are developed to compute band structures of photonic crystals of general shape. In particular, we report two-dimensional photonic crystals of silicon air with an optimal full band gap of gap-midgap ratio Deltaomega/omega(mid)=0.2421, which is 30% larger than ever reported in the literature. The crystals consist of a hexagonal array of circular columns, each connected to its nearest neighbors by slender rectangular rods. A systematic study with respect to the geometric parameters of the photonic crystals was made possible with the present method in drawing a three-dimensional band-gap diagram with reasonable computing time.


Effects of inspiratory muscle training on exertional breathlessness in patients with unilateral diaphragm dysfunction: a randomised trial.
Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD. 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure (PI,max), n=10) or sham training (10% PI,max, n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal (Pes) and gastric (Pga) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise. The IMT group (from 45±6 to 62±23% PI,max) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. PI,max, TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH2O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, Pes, Pga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05). The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles.


Acceptance and expressed emotion in Mexican American caregivers of relatives with schizophrenia.
The relation between Expressed Emotion (EE) and caregiver acceptance was tested with the use of video-recorded interactions between 31 Mexican American family caregivers and their relatives with schizophrenia. Borrowing the concept from Integrative Behavioral Couple Therapy, acceptance was defined as caregiver's engagement with the ill relative along with low levels of expectations for behavioral change. Three aspects of caregiver acceptance were measured: global acceptance of the patient, unified detachment (i.e., nonblaming but engaged problem discussion), and low aversive responses to patient behavior (e.g., criticisms and demanding change). Relative to high EE caregivers, low EE caregivers were consistently more accepting of their ill relatives across the three measures of acceptance. Unified detachment was negatively associated with emotional overinvolvement and aversive responses were positively related to criticism. Warmth was not related to acceptance. The findings suggest that the study of acceptance in family caregivers is a heuristic avenue for future research due to its potential to shed light on specifically what family members do in caring for their ill relatives with schizophrenia.


Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats.
As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats. The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats. High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F(1alpha) was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 +/- 4.4 ng/mL; control, 22.3 +/- 3.3 ng/mL; P =.0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 +/- 0.039; control, 0.88 +/- 0.051; P =.0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 +/- 2.01 pg/mg protein; control, 19.94 +/- 2.82 pg/mg protein; P =.0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group (P =.0375). This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension.


Bio-inspired artificial somatic index for reflecting the travel experience of passenger agents under a flexible transportation scenario.
This work analyzes the implementation of an artificial mechanism inspired by a biological somatic marker that ables a passenger agent to both, react to changes in the service, as well as keep said reactions as a memory for future decisions. An artificial mental model was designed, and the passenger agent was implemented as an autonomous decision-making system, where both, the choice of the transport operator and the evaluation of the received service were fully delegated to the system. The evaluation of the service experience is not only based on rational aspects (such as the cost of the trip) but also on subjective aspects related to the satisfaction level derived from the passenger's experience. The experimental scenario considered 10,000 trip requests simulated within an artificial map that emulates characteristics that are usually present in a city, such as vehicular congestion, the unsafety of certain streets, or the benefits of an area with tourist interest. The results show that the option to travel under a transport operator with a touristic profile is a trend. Unlike current cases in the industry, this research work explores the scenario where the passenger can have as a client a trip profile with memory, differentiated from other clients, and can receive more than one trip proposal for the same trip request, according to the different conditions that the passenger is looking for.


Cystic Fibrosis: Emerging Understanding and Therapies.
Cystic fibrosis (CF) is the most common life-limiting genetic disease in Caucasian patients. Continued advances have led to improved survival, and adults with CF now outnumber children. As our understanding of the disease improves, new therapies have emerged that improve the basic defect, enabling patient-specific treatment and improved outcomes. However, recurrent exacerbations continue to lead to morbidity and mortality, and new pathogens have been identified that may lead to worse outcomes. In addition, new complications, such as CF-related diabetes and increased risk of gastrointestinal cancers, are creating new challenges in management. For patients with end-stage disease, lung transplantation has remained one of the few treatment options, but challenges in identifying the most appropriate patients remain.


Advanced Therapy Medicinal Products for Rare Diseases: State of Play of Incentives Supporting Development in Europe.
In 2008, the European Union introduced the Advanced Medicines Regulation aiming to improve regulation of advanced therapy medicinal products (ATMPs). We applied the ATMPs classification definitions in this Regulation to understand the link of this emerging group of medicinal products and the use of the Orphan Regulation. A total of 185 products that can be classified as ATMPs based on this Regulation have been submitted for orphan designation. Prior to its introduction in 2008, 4.5% of the products submitted for orphan designation met these criteria. This percentage went up to 15% after 2008. We analyzed several parameters associated with active ATMP ODDs focusing on sponsor type and EU-Member State origin, therapeutic area targeted, and ATMP classification [i.e., somatic cell therapy medicinal product, tissue-engineered product (TEP), or gene therapy medicinal product (GTMP)] and the use of regulatory services linked to incentives such as the use of protocol assistance (PA) and other Committees [Committee for Advanced Therapies (CAT) and the Pediatric Committee]. The aim here was to gain insight on the use of different services. The UK submits the largest number of ATMPs for ODD representing ~30% of the total to date. Few submissions have been received from central and Eastern European Member States as well as some of the larger Member States such as Germany (3.6%). ATMPs ODDs were primarily GTMPs (48.7%) and SCTMPs (43.3%). TEPs only represented 8% of all submissions for this medicinal class. This is different from non-ODDs ATMPs where GTMPs make only 20% of ATMPs. A total of 11.7% of ATMP ODDs had received formal CAT classification. A total of 29.8% of all orphan drug (OD) ATMPs requested PA. A total of 71.8% did not have an agreed pediatric investigation plan (PIP). Four products (Glybera one PA; Zalmoxis two; Holoclar one; Strimvelis three) have received a marketing authorization (MAA) and a 10-year market exclusivity. Strimvelis also completed their PIP, which was compliant and received the additional 2-year extension to their 10-year market exclusivity. One OD ATMP (Cerepro) received a negative opinion for MAA. The use of services linked to incentives offered by different legislations for ATMP ODDs is low, indicating a need for increasing awareness.


Photoelectrochemical Properties of Graphene and Its Derivatives.
Graphene and its derivatives combine a numerous range of supreme properties that can be useful in many applications. The purpose of this review is to analyse the photoelectrochemical properties of pristine graphene, graphene oxide (GO) and reduced graphene oxide (rGO) and their impact on semiconductor catalysts/quantum dots. The mechanism that this group of materials follows to improve their performance will be cleared by explaining how those properties can be exploited in several applications such as photo-catalysts (degradation of pollutants) and photovoltaics (solar cells).


Fabrication of chiral Langmuir-Schaefer films of achiral amphiphilic Schiff base derivatives through an interfacial organization.
Supramolecular chirality in the Langmuir-Schaefer (LS) films of two achiral amphiphilic Schiff bases, 2-(2'-benzimidazolyliminomethyl)-4-octadecyloxyphenol (BSC18) and 2-(2'-benzthiazolyliminomethyl)-4-octadecyloxyphenol (TSC18), was investigated. Both of these amphiphiles could form LS films from the water surface or coordinate with Ag(I) in the subphase to form Ag(I)-coordinated LS films. Although both of these amphiphiles were achiral, TSC18 formed a chiral LS film from the water surface, while BSC18 formed a chiral Ag(I)-coordinated LS film from the aqueous AgNO3 subphase. The supramolecular chirality in these LS films was suggested to be due to a cooperative stereoregular pi-pi stacking of the functional groups together with the long alkyl chains in a helical sense. The relationship between the chirality of the LS films and the molecular structures of TSC18 and BSC18 as well as their H-bond or coordination behaviors was discussed. The Schiff base films showed a reversible color change upon exposure to HCl and NH3 gas alternatively; however, the supramolecular chirality was irreversible during these processes.


Comparison of the efficacy of single and multiple regimens of carbimazole in the treatment of thyrotoxicosis.
Carbimazole, in 3 divided daily doses, is commonly prescribed for the treatment of thyrotoxicosis. However, based on its long intra-thyroid half-life, the drug may be effective when used as a single or twice daily dose. This study was undertaken to determine the effect of once, twice or thrice daily doses of carbimazole on thyroid function in patients with thyrotoxicosis. Seventy previously untreated thyrotoxic patients were randomly allocated to receive carbimazole 30 mg once (group 1), 15 mg twice (group 2) and 10 mg thrice (group 3) daily. All patients were also prescribed propranolol 20 mg thrice daily for the first 4 weeks. Blood was taken for total T3, T4, TSH, blood counts and liver enzymes determinations at the beginning and at 6 weeks of treatment. Only 48 (68.6%) patients were included in the analysis, as the rest defaulted follow-up (20.0%) or blood samples were not available at review (11.4%). Of the 48 patients, 17 were in group 1, 16 in group 2 and 15 in group 3. Following 6 weeks of treatment, there was no significant difference in the mean serum levels of total T3 and T4 between the 3 groups. However, there was a significant decrease in the mean serum levels of total T3 and T4 as compared to the start of the treatment. Four patients (23.5%) in group 1, 4 patients (25%) in group 2 and 3 patients (20%) in group 3 were still thyrotoxic at 6 weeks of treatment, whilst 10 patients (58.8%) in group 1, 6 patients (37.5%) in group 2 and 3 (20%) in group 3 were biochemically hypothyroid.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of experimentally induced mouse prostatic hyperplasia by castration or steroid antagonist administration.
Mouse prostatic hyperplasia has been induced experimentally by implanting fetal urogenital sinus tissue into the prostate gland of syngeneic mice. We compared the effects of castration and steroid antagonist administration on the growth of the prostate gland during both the early (15 days) and late (30 days) phases of prostatic enlargement. Castration at the time of induction of prostatic hyperplasia is by far the most effective method of inhibiting prostatic overgrowth. A comparison of castration for 7 days with the short-term (7 days) administration of steroid antagonists showed that during the early phase of prostatic enlargement castration is more effective than antiandrogen, which is more effective than 5 alpha-reductase inhibitors. In the late phase of mouse prostatic enlargement, castration for 7 days is less effective than treatment with either antiandrogen or a 5 alpha-reductase inhibitor. Our data indicate that treatment with a combination of an antiestrogen (keoxifene) with a 5 alpha-reductase inhibitor (in particular, 6-methylene progesterone) is the most effective combination for reducing prostatic overgrowth. The antiestrogen (keoxifene) treatment alone was ineffective in both the early and late phases of prostatic overgrowth.


Diffraction-based solid immersion lens.
A solid immersion lens based on diffraction (dSIL) is proposed as an alternative to the conventional design based on refraction. A design analogous to a Fresnel zone plate is derived in accordance with the Huygens-Fresnel principle. Fabrication of a binary dSIL is achieved by electron-beam lithography and reactive-ion etching on LaSF35, with index n = 2.014. Measurement of the point-spread function is performed with near-field optical microscopy. The results are in accord with the expected resolution enhancement of a factor n with respect to the diffraction limit.


Another knotted epidural catheter.
A lumbar epidural catheter inserted in a 24-year-old woman for labour analgesia, and subsequently used for post-caesarean epidural analgesia, proved difficult to remove. After multiple attempts, the entrapped catheter was dislodged intact, revealing a knot near its distal tip. Knotting of an epidural catheter leading to entrapment is a rare complication of epidural catheterization.


Fluoroquinolone use and risk factors for Clostridium difficile-associated disease within a Veterans Administration health care system.
Prompted by the changing profile of Clostridium difficile infection and the impact of formulary policies in hospitals, we performed this study when an increase in the incidence of C. difficile-associated disease was noted at our health care center (Veterans Administration Puget Sound Health Care System, Seattle, Washington). A retrospective, matched case-control study of patients presenting to the Veterans Administration Puget Sound Health Care System, Seattle, Washington during 2004 was performed. Conditional logistic analysis determined risk factors for case patients, defined as individuals with diarrhea and test results (i.e., culture or toxin assay results) positive for C. difficile, and control subjects, defined as individuals with diarrhea and test results negative for C. difficile. C. difficile-associated disease incidence was 29.2 cases per 10,000 inpatient-days. The increase in the incidence of C. difficile-associated diarrhea that paralleled increased gatifloxacin use was not attributable to use of the antimicrobial but was a reflection of seasonal variation in the rate of C. difficile-associated disease. Multivariate analysis controlling for the time at which the assay was performed, the age of the patient, ward, and source of acquisition (community-acquired vs. nosocomial disease) found 6 significant risk factors for C. difficile-associated diarrhea: receipt of clindamycin (adjusted odds ratio [aOR], 29.9; 95% confidence interval [CI], 3.58-249.4), receipt of penicillin (aOR, 4.1; 95% CI, 1.2-13.9), having a lower intestinal condition (aOR, 2.8; 95% CI, 1.3-6.1), total number of antibiotics received (aOR, 1.4; 95% CI, 1.1-1.7), number of prior hospital admissions (aOR, 1.3; 95% CI, 1.1-1.6), and number of comorbid conditions (aOR, 1.3; 95% CI, 1.1-1.5). The increase in the number of cases of C. difficile-associated disease was not attributable to a formulary change of fluoroquinolones; instead, the incidence was within expected seasonal variations for C. difficile-associated disease. Recognition of community-acquired cases and the use of culture may help to identify additional cases of C. difficile-associated disease. Early diagnosis and treatment of C. difficile cases may shorten the duration of hospital stays and reduce the number of outbreaks and readmissions, mortality, and other consequences of C. difficile infection.


Expression of the calcium-sensing receptor on human antral gastrin cells in culture.
The presence of the extracellular calcium-sensing receptor on human antral gastrin cells was investigated. Reverse transcription PCR using mRNA isolated from gastrin cell- enriched cell cultures identified a product with a sequence identical to part of the human parathyroid-secreting cell calcium-sensing receptor. Immunocytochemistry with an antibody to the extracellular region of the receptor immunostained all gastrin cells (but not mucin or somatostatin cells), and detected appropriate-sized bands in Western blots of whole cell lysates. Increasing extracellular calcium levels from 0.5 to 9 mM stimulated gastrin release in a concentration-dependent manner, with maximal release obtained at 7.2 mM. A known agonist of the calcium receptor, spermine also stimulated gastrin release. Microfluorimetry of identified gastrin cells demonstrated that increasing extracellular calcium resulted in an initial rapid rise in intracellular calcium followed by a plateau level that returned to basal levels immediately after removal of the elevated calcium. The traces were consistent with activation of a receptor-mediated mechanism rather than a concentration-dependent influx of calcium. In conclusion, these data indicate that G cells express the calcium-sensing receptor, and that activation of the receptor may explain the acid rebound phenomenon associated with calcium-containing antacid preparations.


The origin of surface stress induced by adsorption of iodine on gold.
The cantilever technique for the measurement of film stress on both macroscopic and microscopic cantilevers is validated, then applied to the experimental determination of film stress induced by the adsorption of a monolayer of iodine onto a gold substrate. A model is proposed that relates the change in the interatom potential upon chemisorption of iodine onto gold to the measured film stress. Excellent agreement is found with the experimentally determined value. This result gives insight into the origins of film stress that is observed in all thin film and coating applications.