Gene replacement therapy for genetic hepatocellular jaundice.
Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.


Tocilizumab for the Treatment of SLC29A3 Mutation Positive PHID Syndrome.
Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) is associated with recessive mutations in SLC29A3, encoding the equilibrative nucleoside transporter hENT3 expressed in mitochondria, causing PHID and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy-plus syndrome. Autoinflammation is increasingly recognized in these syndromes. We previously reported a 16-year-old girl with PHID syndrome associated with severe autoinflammation that was recalcitrant to interleukin-1 and tumor necrosis factor-α blockade. Tocilizumab is a humanized, monoclonal, anti-human interleukin-6 receptor antibody routinely used to treat arthritis in children and adults. Herein we report the first case of successful treatment of PHID syndrome using tocilizumab. Before commencing tocilizumab, there was evidence of significant systemic inflammation, and progressive sclerodermatous changes (physician global assessment [PGA] 7/10). Twelve weeks after starting tocilizumab (8 mg/kg every 2 weeks, intravenously) systemic inflammatory symptoms improved, and acute phase response markers normalized; serum amyloid A reduced from 178 to 8.4 mg/L. After a dose increase to 12 mg/kg every 2 weeks her energy levels, appetite, fevers, and night sweats further improved. Less skin tightness (PGA 5/10) was documented 12 months later. This excellent clinical and serological response was sustained over 48 months, and cutaneous sclerosis had improved further (PGA 3/10). Her height remained well below the 0.4th centile, and tocilizumab also had no impact on her diabetes or exocrine pancreatic insufficiency. Although the mechanism of autoinflammation of PHID remains uncertain, we suggest that tocilizumab should be the first choice when considering treatment of the autoinflammatory or cutaneous manifestations of this genetic disease.


Interprofessional Precepting: A Nursing-Medicine Partnership.
Interprofessional precepting can advance team-based collaboration. We evaluated the impact of nurse-led precepting of medical students on perceptions of nurse-physician relationships. Forty-six frontline nurses precepted 73 third year medical students in New York for a three-part clinical and classroom experience. Nurse preceptor and medical student attitudes toward healthcare teams and medical student attitudes toward nurse-physician collaboration improved after participation using validated scales. This pilot study suggests nurse-led interprofessional precepting can improve attitudes toward interprofessional collaboration.


[Ki-67 and p53 expressions versus differentiation degrees of colon adenocarcinoma].
The colon carcinoma prognostic is evaluated with respect to four categories of factors established by College of American Pathologists Consensus Statement 1999, among which a series of molecular markers is also included. Our study aimed to develop semiquantitative analysis of the immunohistochemistry pattern for proliferation and apoptosis markers, as well as of their connections with the histopathology subtypes of colon adenocarcinoma. The group of study included 5 cases of well-differentiated adenocarcinoma, 5 cases of moderately differentiated adenocarcinoma and 5 cases of poor differentiated adenocarcinoma. The Ki-67 and p53 antibodies (DAKO) and the streptavidin-biotin method (LSAB Kit, DAKO) were used for the immunohistochemical staining. The semiquantitative analysis provided the Ki-67 and p53 indices, and subsequently their values were statistically correlated with the histologic differentiation degrees. All the cases presented positive immunohistochemistry reaction for Ki-67, the Ki-67 index varying on a large scale, between 5% and 95%. For p53, 10 out of the 15 cases (66%) presented positive immunohistochemistry reaction, with the index value between 22% and 95%, and 5 cases were negative. The statistical analysis revealed no significant difference between the Ki-67 indices of the three histopathologic subtypes (p = 0.674), whereas important differences appeared for the p53 indices (p = 0.007). Our findings support the correct understanding of the role played by the immunohistochemical markers, in the sense of the risk involved by considering a pre-definite hierarchy in the diagnosis strategy.


Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo.
mRNA translation in eukaryotic cells involves a set of proteins termed translation initiation factors (eIFs), several of which are involved in the binding of ribosomes to mRNA. These include eIF4G, a modular scaffolding protein, and eIF4A, an RNA helicase, of which two closely related forms are known in mammals, eIF4A(I) and eIF4A(II). In mammals, eIF4G possesses two independent sites for binding eIF4A, whereas in other eukaryotes (e.g. yeast) only one site appears to be present, thus raising the issue of the stoichiometry of eIF4G.eIF4A complexes in different eukaryotes. We show that in human embryonic kidney cells eIF4G is associated with eIF4A(I) or eIF4A(II) but not with both simultaneously, suggesting a stoichiometry of 1:1 rather than 1:2. To confirm this, eIF4A(I) or eIF4A(II) was expressed in a tagged form in these cells, and complexes with eIF4G were again isolated. Complexes containing tagged eIF4A(I) or eIF4A(II) contained no endogenous eIF4A, supporting the notion that eIF4G binds only one molecule of eIF4A. Each binding site in eIF4G can bind either eIF4A(I) or eIF4A(II). The data imply that the second binding site in mammalian eIF4A does not bind an additional eIF4A molecule and that initiation factor complexes in different eukaryotes contain one eIF4A per eIF4G.


Determination of threshold concentrations of multiple allergenic extracts for equine intradermal testing using normal horses in three seasons.
Forty-one normal horses were evaluated for reactivity to intradermally injected aqueous allergens to determine allergen threshold concentrations (TC), with potential relevance to equine intradermal testing (IDT). Horses were tested three times over 1 year to assess seasonal variation in reactivity, using three to five serial dilutions of 27 allergens each time. Injection sites were evaluated after 15 min, 1 h, 4 h and 24 h. The highest allergen concentration at which < 10% of horses demonstrated positive reactivity (subjective score of > or = 2, scale of 0 to 4) at 15 min was considered the TC. The TC was determined for nine pollens (2000 to > 6000 PNU mL(-1)), four moulds (4000 to > 6000 PNU mL(-1)), seven insects (ant, horse fly 125 PNU mL(-1); house fly, cockroach 250 PNU mL(-1); moth 60 PNU mL(-1); mosquito 1000 PNU mL(-1); Culicoides nebeculosis 1 : 5000 w v(-1)) and three of four storage mites (1 : 10,000 w v(-1)). The TC was not determined due to excessive reactivity at the lowest concentrations tested for dust mites (Dermatophagoides farinae [< 1 : 12,000 w v(-1)], D. pteronyssinus [< 1 : 30,000 w v(-1)]), and Acarus siro (< 1 : 10,000 w v(-1)). Minor variation in the TC for specific allergens occurred in different seasons. Progressive sensitization with repeat testing occurred for grain mill dust mix. Positive reactivity at 1 h and 4 h occurred in > 10% of horses for nine of 19 allergens (pollens, mosquito, storage mites) at their determined TC. Positive reactivity was rare at 24 h. This study in normal horses suggests that appropriate testing concentrations of allergens for equine IDT in atopic horses may be > or = 1000 PNU mL(-1) for pollens and moulds, 60 to 250 PNU mL(-1) for most insects and < 1 : 12,000 w v(-1) for dust mites; and that reactions at 1-4 h may be insignificant.


Effect of inorganic nutrients on bacterial community composition in oil-bearing sandstones from the subsurface strata of an onshore oil reservoir and its potential use in Microbial Enhanced Oil Recovery.
Microbial Enhanced Oil Recovery (MEOR) is a promising strategy to improve recovery of residual oil in reservoirs, which can be performed by promoting specific indigenous microorganisms. In this study, we performed preliminary evaluation of the possibility of conducting MEOR at Mae Soon reservoir, an onshore reservoir in Northern Thailand. The reservoir's physicochemical characteristics, including the characteristics of the wells, the oil-bearing sandstone cores, and the reservoir's produced water, were determined. The microbiological characteristics of the oil wells in the reservoir were also investigated by submerging the reservoir's sandstone core samples, obtained from 6 oil wells, in the reservoir's produced water and in the produced water added with inorganic nutrients (KNO3 and NaH2PO4). The uncultured bacteria in both treatments were determined, using tagged 16S rRNA gene amplicon with Ion Torrent Sequencing Analysis. The effects of inorganic nutrients and the reservoir's parameters on the bacterial communities were analysed. A total number of 16,828 OTUs were taxonomically classified into 89 classes and 584 genera. In the controls (sandstone cores submerged in the produced water), the dominant bacterial populations were related to Deinococcus-Thermus, and Betaproteobacteria; while in the nutrient treated samples, there was a marked increase in the relative abundance of Gammaproteobacteria in three samples. Thermus, Acinetobacter, and Pseudomonas were the most abundant genera, and these are potential microorganisms for MEOR. Analysis of correlations between physiochemical properties of the reservoir and bacterial genera, using spearman's correlation analysis, suggested that some of the reservoir's properties, especially of the well and the rock, could influence some bacterial genera. To our knowledge, this is the first demonstration of the effect of inorganic nutrients on alteration of bacterial communities attached to reservoir's rock, and how the bacterial, physical, and chemical properties of a reservoir were co-analysed to serve as a basis for designing a MEOR process.


Asymmetric synthesis of the potent HIV-protease inhibitor, nelfinavir.
An asymmetric synthesis of nelfinavir is described starting from acrolein and (S)-methyl phenyl sulfoxide. The key features include (a) stereoselective preparation of a beta-protected amino-gamma,delta-unsaturated sulfoxide by the reaction of an alpha-sulfinyl carbanion with an unsaturated t-butyl sulfinylimine, (b) stereoselective bromohydrin formation using the pendant sulfoxide group as an intramolecular nucleophile, and (c) use of commercially or readily prepared inexpensive starting materials.


Angular resolution of parallel foils on a synchrotron powder diffractometer.
In an attempt to improve the resolution in flat-plate diffraction geometry, a new set of parallel foils, 100 microm spacing, 365 mm long with an aperture of 20 x 20 mm(2), has been commissioned. The study was carried out using the two-circle diffractometer of station 2.3 at the SRS. In order to properly quantify the improvements, a detailed and comparative study of the instrumental resolution using the new and existing foils, of 200 micron spacing, is reported. A number of cubic materials, BaF2, Si and CeO2, that are known to show well defined Bragg peaks over the full 2theta angular range available, were investigated.


Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.
Cyclin-dependent kinase (Cdk)2/cyclin E is imported into nuclei assembled in Xenopus egg extracts by a pathway that requires importin-alpha and -beta. Here, we identify a basic nuclear localization sequence (NLS) in the N-terminus of Xenopus cyclin E. Mutation of the NLS eliminated nuclear accumulation of both cyclin E and Cdk2, and such versions of cyclin E were unable to trigger DNA replication. Addition of a heterologous NLS from SV40 large T antigen restored both nuclear targeting of Cdk2/cyclin E and DNA replication. We present evidence indicating that Cdk2/cyclin E complexes must become highly concentrated within nuclei to support replication and find that cyclin A can trigger replication at much lower intranuclear concentrations. We confirmed that depletion of endogenous cyclin E increases the concentration of cyclin B necessary to promote entry into mitosis. In contrast to its inability to promote DNA replication, cyclin E lacking its NLS was able to cooperate with cyclin B in promoting mitotic entry.


Diagnostic efficacy of myeloperoxidase to identify acute coronary syndrome in subjects with chest pain.
Early diagnosis of acute coronary syndrome (ACS) is frequently a challenging task. To assess the role of novel biomarkers to identify ACS. Concentrations of lipids, lipoproteins, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), paraoxonase-1 (PON1), secretory phospholipase A2 (sPLA2), and myeloperoxidase (MPO) were measured in 703 patients (mean age 65.5 ± 11.2 years; 422 men, 281 women) without diabetes mellitus assigned to coronary angiogram. The subjects were divided into three groups: ACS (n = 242), stable angina pectoris (SAP) (n = 242), and normal coronary artery (NCA) (n = 219). HDL-cholesterol (HDL-C) (P < 0.001) and apolipoproteinA-I concentrations (P < 0.0001) were lowest in subjects with ACS. LDL-C (P = 0.008) and non-HDL (P < 0.0001) were higher in the ACS group than in the SAP group. Leukocyte count (P < 0.0001), oxLDL (P < 0.05), hsCRP (P < 0.001), sPLA2 (P < 0.05), and MPO (P < 0.0001) were highest in the ACS group. In multivariate models, comprising all biomarkers, elevated level of MPO had the best discriminatory power to identify patients with ACS. Receiver-operating characteristic curve with and without MPO comparison differed significantly (P = 0.03 for both ACS versus NCA and ACS versus SAP). Our study shows that ACS associates with low HDL-C and biomarkers of oxidative stress and inflammation. The addition of MPO in biomarker panels might improve diagnostic accuracy for ACS.


Targeted Lignan Profiling and Anti-Inflammatory Properties of Schisandra rubriflora and Schisandra chinensis Extracts.
Schisandra rubriflora is a dioecious plant of increasing importance due to its lignan composition, and therefore, possible therapeutic properties. The aim of the work was lignan profiling of fruits, leaves and shoots of female (F) and male (M) plants using UHPLC-MS/MS. Additionally, the anti-inflammatory activity of plant extracts and individual lignans was tested in vitro for the inhibition of 15-lipooxygenase (15-LOX), phospholipases A2 (sPLA₂), cyclooxygenase 1 and 2 (COX-1; COX-2) enzyme activities. The extracts of fruits, leaves and shoots of the pharmacopoeial species, S. chinensis, were tested for comparison. Twenty-four lignans were monitored. Lignan contents in S. rubriflora fruit extracts amounted to 1055.65 mg/100 g DW and the dominant compounds included schisanhenol, aneloylgomisin H, schisantherin B, schisandrin A, gomisin O, angeloylgomisin O and gomisin G. The content of lignan in leaf extracts was 853.33 (F) and 1106.80 (M) mg/100 g DW. Shoot extracts were poorer in lignans-559.97 (F) and 384.80 (M) mg/100 g DW. Schisantherin B, schisantherin A, 6-O-benzoylgomisin O and angeloylgomisin H were the dominant compounds in leaf and shoot extracts. The total content of detected lignans in S. chinensis fruit, leaf and shoot extracts was: 1686.95, 433.59 and 313.83 mg/100 g DW, respectively. Gomisin N, schisandrin A, schisandrin, gomisin D, schisantherin B, gomisin A, angeloylgomisin H and gomisin J were the dominant lignans in S. chinensis fruit extracts were. The results of anti-inflammatory assays revealed higher activity of S. rubriflora extracts. Individual lignans showed significant inhibitory activity against 15-LOX, COX-1 and COX-2 enzymes.


The mineralocorticoid hormone receptor and action in the eye.
Immunoblotting with a polyclonal antibody, directed against the mineralocorticoid receptor protein purified from rat kidney in presence of the receptor-specific ligand RU 26752, labeled a single 98-102 kDa band in soluble extracts from bovine retina and from cultured bovine retinal pigment epithelial cells, identical to the receptor in several other tissues from the rat. The antibody also immunoprecipitated the receptor-3H-RU 26752 complex in bovine retinal extract. The growth of the isolated pigment epithelial cells was inhibited by RU 26752 and ZK91587, two ligands specific to the mineralocorticoid receptor. Successive passages in culture led to the disappearance of immunoreactivity in Western blots, concurrently with the refractoriness of the cells to growth inhibition by the two antagonists. On sections of the human eye, mineralocorticoid receptor-specific immunofluorescence was observed in retinal cone cells, pigment epithelium, epithelium of ciliary body, iris, cornea and lens. To our knowledge, this is the first ever demonstration of the mineralocorticoid receptor in ocular tissues.


Unified Approach to the Detection and Classification of Speckle Texture in Diagnostic Ultrasound.
Second order statistics have been derived for the speckle in diagnostic ultrasound that arises from diffuse (incoherent) scattering in the presence of distributed and organized specular (coherent) scattering. They serve as the basis for a three-dimensional feature space in which tissue textures can be classified. The covariance matrix of the measurements in this space is a generalization of the speckle spot number or sampling concept that arises in the study of signal or lesion detectability.


Epidemiologic classics of Carter, Maxcy, Trudeau, and Smith.
Four great epidemiologists whose work so concisely linked clinical observations, epidemiologic clues, and logical preventive measures are discussed. Henry Rose Carter set the stage for the Walter Reed successes in Cuba by showing that 9-16 days must elapse after contact before yellow fever develops. This provided the link for the Reed group to allow the "virus" to incubate in the mosquito before becoming infectious. Kenneth Maxcy clarified the controversy between endemic typhus fever and Brill's disease in the southeastern United States. His clinical, epidemiologic, and laboratory findings led him to propose that the causative organism (Rickettsia typhi) was in rodents and the probable vector, fleas. When confirmed, effective control measures were applied. Two other American investigators, Edward L. Trudeau and Theobald Smith, helped prove Robert Koch wrong on three counts: (1) Tuberculin is not an effective therapeutic agent for tuberculosis; (2) there are two distinct types of tubercle bacillus, human and bovine; and (3) the bovine form of Mycobacterium tuberculosis is remarkably pathogenic for humans. The significance of these findings is unlimited.


Reproductive Health Care for Incarcerated People: Advancing Health Equity in Unequitable Settings.
There are over 150,000 incarcerated females in the United States. Structural inequities, including racism, adversely affect the reproductive health outcomes, autonomy, and access to care that people in custody face. This article reviews the status of reproductive health and health care among incarcerated women and describes ways that community OB/GYNs can address health inequities by providing comprehensive, compassionate care to incarcerated people, especially when they come to community settings for care while they are in custody. To address reproductive health disparities and inequities that adversely affect incarcerated individuals, community providers can implement these recommendations and also engage in advocacy.


Risk factors for HTLV-II infection in Peruvian men who have sex with men.
Human T-cell lymphotropic virus type-II (HTLV-II) infection is endemic in indigenous groups in the Americas and injection drug users (IDUs) worldwide. In Peru, HTLV-II infection was previously identified in two indigenous Amazonians. We examined risk factors for HTLV-II infection in 2,703 Peruvian men who have sex with men (MSM): 35 (1.3%) were HTLV-II positive. HTLV-II infection was associated with syphilis, HSV-2 infection, unprotected receptive anal intercourse, and older age. This is the first report of HTLV-II in a non-indigenous non-IDU population in Peru. Additional studies are needed to determine if HTLV-II is a sexually transmitted infection in this and other sexually active populations.


Mercury Content in Different Species of Mushrooms Grown in Spain.
The mercury content of 117 mushroom samples corresponding to 8 different species collected in the Sierra of Cordoba (Spain) was determined by cold vapor atomic absorption spectrophotometry. The results obtained showed that the mercury content differed according to the species and to the anatomical group examined. Samples of Psalliota xanthoderma showed maximum levels (0.669-0.210 mg/kg, fresh weight) and the ratio cap/stem obtained is 1.32. The concentration levels were compared to literature data and the contribution of mushrooms to the daily intake of mercury in Spain was evaluated.


[Contribution to the knowledge on natural history of giant hepatic angioma].
Hepatic haemangiomas are mostly discovered by chance because of their limited dimensions. Their treatment is optional and very often an observing conservative strategy is adopted whilst a danger is foreseeing from different facts. Very different is the case of giant haemangiomas discovered because their bulk and discomfort coming from the compression exerted on near structures. In this cases a surgical treatment, segmentectomy or hemiepatectomy, are the current demanding choices. But if the volume of haemangioma is too bulky and occupies most hepatic parenchyma the necessary resection may be too extended and possibly dangerous. The two observations of the paper refer to two patients followed conservatively for over 20 years. In fact the volume of the haemangiomas in both patients was too large, the symptoms were only related to the weight of the mass and therefore a surgical solution was deferred to a possible worsening of the symptomatology. Such worsening didn't happen in the time for both the patients, demonstrating that the natural history of such lesion can also be very benign over many years.


Incidence of and reasons for excluding patients with acute myocardial infarction from thrombolytic therapy.
The percentage of patients with acute myocardial infarction (AMI) who were eligible for thrombolytic therapy was evaluated prospectively, with analysis of the causes for exclusion, in 857 patients with AMI hospitalized in the Chaim Sheba Medical Center, Tel-Hashomer, in 1988. Thrombolytic therapy was given to 127 patients (14.8%); 99 patients were treated with tissue plasminogen activating factor and 28 patients received streptokinase. Three hundred and sixty patients (42.0%) were rejected because of age (greater than 72 years). Other reasons for exclusion were duration of pain lasting for more than 4 h (28.5%), unknown time of onset of the chest pain (9.7%), absence of ST elevation on admission ECG (8.1%), systemic hypertension (4.4%), and presence of severe congestive heart failure upon admission (10.1%). Restricting thrombolytic therapy only to patients less than 72 years old with chest pain duration of 4 h limits the impact of this treatment on the general welfare of patients with AMI. By raising the age limit and extending the time interval between pain onset and treatment initiation, adding newer indications, and enhancing public awareness for early arrival to hospital, the benefit of thrombolytic therapy may be made available to more patients with AMI.


Dynein-dependent motility of microtubules and nucleation sites supports polarization of the tubulin array in the fungus Ustilago maydis.
Microtubules (MTs) are often organized by a nucleus-associated MT organizing center (MTOC). In addition, in neurons and epithelial cells, motor-based transport of assembled MTs determines the polarity of the MT array. Here, we show that MT motility participates in MT organization in the fungus Ustilago maydis. In budding cells, most MTs are nucleated by three to six small and motile gamma-tubulin-containing MTOCs at the boundary of mother and daughter cell, which results in a polarized MT array. In addition, free MTs and MTOCs move rapidly throughout the cytoplasm. Disruption of MTs with benomyl and subsequent washout led to an equal distribution of the MTOC and random formation of highly motile and randomly oriented MTs throughout the cytoplasm. Within 3 min after washout, MTOCs returned to the neck region and the polarized MT array was reestablished. MT motility and polarity of the MT array was lost in dynein mutants, indicating that dynein-based transport of MTs and MTOCs polarizes the MT cytoskeleton. Observation of green fluorescent protein-tagged dynein indicated that this is achieved by off-loading dynein from the plus-ends of motile MTs. We propose that MT organization in U. maydis involves dynein-mediated motility of MTs and nucleation sites.


Eye protection.
Eye injuries frequently occur in the home, at work and at play. Many result in legally blind eyes, and most are preventable. Awareness of potential hazards is essential to preventing eye injuries, particularly in children. In addition, protective devices must be used appropriately. We have developed eye protectors that have proved effective in reducing both the overall incidence and the severity of sports eye injuries.


Synthesis and characterization of hollow cadmium oxide sphere with carbon microsphere as template.
Cadmium Oxide (CdO) hollow spheres have been synthesized by using carbon microsphere as sacrificial template. The products were characterized by X-ray powder diffraction (XRD), scanning electronic microscopy (SEM) and transmission electron microscopy (TEM). The average diameter and shell thickness of as-prepared hollow spheres are about 600 nm and 50 nm, respectively. The formation of hollow spheres was investigated and it was found that the shell formed when the heating temperature reached about 673 K and the sequential heat treatment could remove the carbon template. Moreover, the influence of other experimental parameters including concentration (0.1-5 M) and type of cadmium salts (cadmium chloride, cadmium acetate and cadmium nitrate, etc.) as well as type of solvents (water, ethanol and dimethylfomamide) were also investigated.


Influence of boron on carrot cell wall structure and its resistance to fracture.
Plant cell wall structure integrity and associated tissue mechanical properties is one of key determinants for the perceived texture of plant-based foods. Carrots (Daucus carota) were used to investigate the effect of mineral supply of boron (B) and/or calcium (Ca), during plant growth, on the plant cell wall structure and mechanical properties of matured root tissues. Five commercial cultivars of carrots, Kuroda (orange), Dragon Purple, Kuttiger White, Yellow, and Nutri-Red, were cultivated under controlled glasshouse conditions over two seasons. Significant increases in the accumulation of B and Ca were found for all cultivars of carrots when additional B and Ca were included in the nutrient feeding solutions throughout the plant growth period. Elevated levels of B in carrot root tissue reduced the uptake of Ca and other mineral nutrients and enhanced plant cell wall structural integrity, its resistance to fracture, and the weight and size (both diameter and length) of carrots. Although higher amounts of Ca were accumulated in the plant materials, the additional supply of Ca did not have a significant effect on the mechanical properties of mature plant tissues or on the uptake of B by the plant. The results suggest that B cross-linking of pectin (rhamnogalacturonan II) has a greater influence on mature tissue mechanical properties than Ca cross-linking of pectin (homogalacturonan) when supplied during plant growth.


[Posterior reduction and interbody fusion for the treatment of thoracolumbar fractures and dislocations].
To explore efficacy of posterior reduction and interbody fusion in treating thoracolumbar fractures and dislocations. From August 2004 to May 2009, 24 patients (18 males and 6 females with an average of 38.2 years, ranged 24 to 56 years old) were treated. Among them, 14 cases were by traffic accident,6 cases were falling down, 2 cases were heavy hit, 2 cases were transverse crush. According to AO classification, 12 cases were type B1, 5 cases B2, 2 cases B3,3 cases C1, 2 cases C2. One cases in T(10,11), 2 cases in T(11,12), 5 cases in T12L1, 8 cases in L(1,2), 2 cases in L(2,3), 4 cases in L(3,4), 2 cases in L4/5. Acoording to Frankle classification,5 cases in grade A, 9 cases in grade B, 8 cases in grade C and 2 cases in grade D. The reduction, graft healing and recovery of nervous function were followed up. All patients were followed up from 8 to 33 months with an average of 16 months. The operation time was for 3.0 to 5.8 hours, meaned 3.7 h, and mean blood loss was 860 ml (ranged, 500 to 1800 ml). Cobb angle improved from preoperative (32.6 +/- 3.7) degrees to postoperative (13.7 +/- 2.4) degrees. The anterior high of fractured vertebrae increased from preoperative (41.0 +/- 11.6)% to postoperative (87.6 +/- 2.3)% .Three cases of 5 cases with Frankle A were not recovery, 1 case changed to grade B, 1 case changed to grade C; Five cases of 9 cases with Frankle B were changed to grade C, 3 cases to grade D, 1 case changed to grade E; Five cases of 8 cases with Frankle C were changed to Grade D, 3 cases to Grade E; Two cases with Frankle D were recoved to normal. Planting bone surface got bone fusion, and no internal fixation lossen, dislocation occurred. Posterior reduction and rigid interbody fusion for the treatment of thoracolumbar fractures and dislocations can receive satisfactory fusion based on recovering normal spinal sequence


Can blind persons accurately assess body size from the voice?
Vocal tract resonances provide reliable information about a speaker's body size that human listeners use for biosocial judgements as well as speech recognition. Although humans can accurately assess men's relative body size from the voice alone, how this ability is acquired remains unknown. In this study, we test the prediction that accurate voice-based size estimation is possible without prior audiovisual experience linking low frequencies to large bodies. Ninety-one healthy congenitally or early blind, late blind and sighted adults (aged 20-65) participated in the study. On the basis of vowel sounds alone, participants assessed the relative body sizes of male pairs of varying heights. Accuracy of voice-based body size assessments significantly exceeded chance and did not differ among participants who were sighted, or congenitally blind or who had lost their sight later in life. Accuracy increased significantly with relative differences in physical height between men, suggesting that both blind and sighted participants used reliable vocal cues to size (i.e. vocal tract resonances). Our findings demonstrate that prior visual experience is not necessary for accurate body size estimation. This capacity, integral to both nonverbal communication and speech perception, may be present at birth or may generalize from broader cross-modal correspondences.


Characteristics of bicycle crashes in an adolescent population in Flanders (Belgium).
In regions where transportation is mainly motorized, air pollution and traffic congestion are rife. Active transportation such as cycling might be a solution but safety is a major concern. An efficient science based safety policy is needed. The aim of this paper is to analyze in depth the bicycle crash causes and characteristics in an adolescent population (14-18 yr). By using questionnaires for self-reported bicycle crashes, bicycle crash data were collected from insurance companies (January 2014-June 2015) and from schools (November 2013-March 2014). Six bicycle crash causes were predefined and possible differences between schools and insurance companies were analyzed. Eighty-six school and 78 insurance registered crashes were analyzed. "Distraction of the cyclist" and "third party crossing a bicycle path failing to see the cyclist" are the main causes of bicycle crashes (both 29%). Bad (maintained) infrastructure accounted for 21% of the crash causes. Bicycle crashes reported at insurance companies needed significantly more medical attention and led to high absenteeism (57% at least one day of absenteeism). Only 21% of the bicycle crashes reported at insurance companies were also reported in the official police database. The human factor was the main cause accounting for 79% of the crashes. Bicycle crashes involving a car accounted for 42% and single bicycle crashes accounted for 31% of the total number of crashes. From the bicycle crashes registered at insurance companies 21% was also registered in official police statistics. A combination of information, education and changing the bicycle specific environment might reduce the consequences of human errors more efficiently.


Conserved F-actin dynamics and force transmission at cell adhesions.
Adhesions are a central mechanism by which cells mechanically interact with the surrounding extracellular matrix (ECM) and neighboring cells. In both cell-ECM and cell-cell adhesions, forces generated within the actin cytoskeleton are transmitted to the surrounding environment and are essential for numerous morphogenic processes. Despite differences in many molecular components that regulate cell-cell and cell-ECM adhesions, the roles of F-actin dynamics and mechanical forces in adhesion regulation are surprisingly similar. Moreover, force transmission at adhesions occurs concomitantly with dynamic F-actin; proteins comprising the adhesion of F-actin to the plasma membrane must accommodate this movement while still facilitating force transmission. Thus, despite different molecular architectures, integrin and cadherin-mediated adhesions operate with common biophysical characteristics to transmit and respond to mechanical forces in multicellular tissue.


[Comparative efficiency of 1 direct and 2 indirect methods for the detection of differences in erythrocyte aggregation, in normal blood and in blood with echinocytosis].
There are many different methods for assessing red cell aggregation, but they have been evaluated in isolated form. The aim of this work was to compare the efficacy and reliability of three different methods for evaluating red cell aggregation. Blood was drawn on trisodium citrate, and after removal of platelet-rich plasma, the red cell were washed with sodium chloride, and blood was reconstituted until a haematocrit of 40% was achieved. Aspirin or dipyridamole were added, the latter for inducing echinocyte formation. Three methods of assessment of red cell aggregation were used; two of them, indirect, were based upon blood viscosimetry under shear rates indices, and sedimentation rate of centrifuged blood. The third, direct method was based on microscope observation of aggregation and digital analysis of its images for statistical evaluation. Both descriptive methods and analysis of variance were used. The addition of aspirin and dipyridamole increased blood viscosity with respect to the control (p < 0.001 and p < 0.005, respectively), thus showing increased red cell aggregation. Sedimentation rate was also increased, with, statistical significance in the case of dipyridamole (p < 0.05). Digital analysis of images showed significant increase of red cell aggregation with aspirin (37.48 +/- 2.16 vs 27.99 +/- 1.55 in controls, p < 0.05). The presence of dipyridamole-induced echinocytes impeded an adequate evaluation of red cell aggregation indices. It was included from these studies that blood viscosimetry proved to be as efficient as digital analysis of images for assessing the differences in red cell aggregation. Nevertheless, microscope examination was necessary for a correct evaluation of this phenomenon, and the presence of echinocytes invalidated any attempt to compare red cell aggregation with respect to normal blood.


Skin tightening.
There are many undesirable manifestations that arise as one ages. One of the most notable undesired effects is increasing skin laxity. Traditionally, the gold standard of treatment is surgical correction of skin laxity. However, demand for noninvasive aesthetic procedures has grown due to minimal risk and accelerated recovery time. Over the years, many new devices have become available for addressing skin laxity including laser therapy, radiofrequency (RF), ultrasound, and intense pulsed light (IPL). This article discusses these various noninvasive treatment options and seeks to give providers details of the science behind each device.


Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris.
The effects of intravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. After nicardipine, coronary blood flow and oxygen content in the coronary sinus increased significantly. The indices of inotropic state increased slightly, and the rate of isovolumic LV pressure fall improved. Myocardial oxygen consumption was unchanged despite the significant reduction in pressure-rate product, but LV lactate uptake increased, particularly during the cold pressor test. When nicardipine was administered after propranolol, the indices of inotropic state were unaffected. The lack of direct effect of nicardipine on LV inotropic state was further confirmed by intracoronary injection of 0.1 and 0.2 mg in a separate group of 10 patients. It is concluded that the nicardipine-induced coronary dilatation seems to improve perfusion and aerobic metabolism in areas with chronic ischaemia, resulting in reduced lactate production and augmented oxygen consumption.


Discovery of a Natural Syk Inhibitor from Chinese Medicine through a Docking-Based Virtual Screening and Biological Assay Study.
Spleen tyrosine kinase (Syk) is a critical target protein for treating immunoreceptor signalling-mediated allergies. In this study, a virtual screening of an in-house Chinese medicine database followed by biological assays was carried out to identify novel Syk inhibitors. A molecular docking method was employed to screen for compounds with potential Syk inhibitory activity. Then, an in vitro kinase inhibition assay was performed to verify the Syk inhibitory activity of the virtual screening hits. Subsequently, a β-hexosaminidase release assay was conducted to evaluate the anti-mast cell degranulation activity of the active compounds. Finally, tanshinone I was confirmed as a Syk inhibitor (IC50 = 1.64 μM) and exhibited anti-mast cell degranulation activity in vitro (IC50 = 2.76 μM). Docking studies showed that Pro455, Gln462, Leu377, and Lys458 were key amino acid residues for Syk inhibitory activity. This study demonstrated that tanshinone I is a Syk inhibitor with mast cell degranulation inhibitory activity. Tanshinone I may be a potential lead compound for developing effective and safe Syk-inhibiting drugs.


An immunohistochemical study of collagens in trachoma and vernal keratoconjunctivitis.
To analyse the distribution and types of collagen in the conjunctiva of patients with trachoma and vernal keratoconjunctivitis (VKC). Conjunctival biopsy specimens were collected from 9 patients with active trachoma, 9 patients with scarred trachoma, 6 patients with active VKC and 9 control subjects. The presence and distribution of collagen was assessed microscopically with immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against types I, III, IV and V collagen. In normal conjunctiva, the staining for types I and III collagen was localised to the substantia propria. Type IV collagen was located in the epithelial, vascular endothelial and accessory lacrimal gland basement membranes. Staining for type V collagen was absent. New type V collagen deposition close to basement membranes was noted in active trachoma, scarred trachoma and VKC. The extent of deposition of type V collagen was markedly increased in scarred trachoma when compared with active trachoma. Staining for type IV collagen showed irregularly thickened epithelial basement membrane in active trachoma, and a marked increase in basement membrane type IV collagen was noted in scarred trachoma. Immunoreactivity of types I and III collagen increased in active trachoma and decreased in scarred trachoma. VKC conjunctiva contained increased amounts of types I, III and IV collagen due to marked increase in the thickness of vascular endothelial basement membrane and very prominent deposition of types I and III collagen around stromal vessels. Our data indicate new type V collagen formation in the conjunctiva from patients with active trachoma, scarred trachoma and VKC. Increased deposition of types I, III and IV collagen is noted in VKC and active trachoma. Our findings suggest that increased deposition of type IV collagen and new type V collagen formation contributes to the development of conjunctival fibrosis in scarred trachoma.


Carbonation and Chloride Ions' Penetration of Alkali-Activated Materials: A Review.
Alkali-activated materials (AAMs) are widely recognized as potential alternatives to ordinary Portland cement (OPC) due to their lower carbon footprint. However, like OPC, AAMs can also generate some durable problems when exposed to aggressive environments and the mechanisms and possible improvements are still not fully clear in existing investigations. Furthermore, the corrosion mechanisms of AAMs are different from OPC due to the discrepant reaction products and pore structures. Thus, this study's aim is to review the chemical reaction mechanisms, factors, and mitigation methods when AAMs are attacked by carbonation and chloride ions, along with a summative discussion regarding instructive insights to durable problems of AAMs.


Mathematical models in GnRH research.
Mathematical modelling is an indispensable tool in modern biosciences, enabling quantitative analysis and integration of biological data, transparent formulation of our understanding of complex biological systems, and efficient experimental design based on model predictions. This review article provides an overview of the impact that mathematical models had on GnRH research. Indeed, over the last 20 years mathematical modelling has been used to describe and explore the physiology of the GnRH neuron, the mechanisms underlying GnRH pulsatile secretion, and GnRH signalling to the pituitary. Importantly, these models have contributed to GnRH research via novel hypotheses and predictions regarding the bursting behaviour of the GnRH neuron, the role of kisspeptin neurons in the emergence of pulsatile GnRH dynamics, and the decoding of GnRH signals by biochemical signalling networks. We envisage that with the advent of novel experimental technologies, mathematical modelling will have an even greater role to play in our endeavour to understand the complex spatiotemporal dynamics underlying the reproductive neuroendocrine system.


Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake.
One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[3H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[3H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake.


In vivo effects of deltamethrin exposure on activity and distribution of molecular forms of carp AChE.
The in vivo effects of the insecticide deltamethrin (DM) on the activity and molecular forms of acetylcholinesterase (AChE, EC 22.214.171.124) were examined in different organs (brain, blood serum, heart, liver, and skeletal muscle) of carp. The chosen exposure conditions were a DM concentration of 2 micrograms/liter in the water (12 +/- 1 degrees C) for 3 days. All the treated fish survived the experiment, though the effects of the treatment were very visible: the fish always turned on their side, and the skin/scales became infected during the exposure to DM. DM did not result in a significant change in the AChE activity in any of the studied organs except the blood plasma, where the exposure resulted in an AChE activity decrease of as much as 20%. The ratio of membrane-bound to salt-soluble AChE forms was determined in the control fish. This ratio increased in the sequence heart, skeletal muscle, liver, and brain. The distribution of the AChE molecular forms was studied in the above tissues. The brain and liver contained forms G1, G4, and A12, the heart and skeletal muscle G4, A4, and A12, and the blood serum G1 and G4. The exposure to 2 micrograms/liter DM for 3 days caused hardly any changes in the pattern of the different AChE molecular forms. A small, but significant (P < 0.05) increase in the proportion of the G4 form was observed in the liver, while G1 and A12 decreased by a few percent (but insignificantly). No other tissues investigated exhibited any changes in the distribution of the AChE molecular forms.(ABSTRACT TRUNCATED AT 250 WORDS)


[Medical expenses by site of cancer and survival time among cancer patients in the last one year of life].
To analyze medical expenses by cancer site and survival time among cancer patients in their last year of life. The study subjects were 45,394 people that had died of cancers in 2002, were registered by the Korea Central Cancer Registry and received National Health Insurance benefit in the last year (360 days) of life. Personal identification data, general characteristics, dates of death and cancer incidence, and site of cancer were collected from the National Statistical Office and the Korea Central Cancer Registry, and merged with the data of the individual medical expenses of the Health Insurance Review Agency. Average monthly cost curves were U-shaped with high costs near the time of diagnosis and death, and lower costs in between. Medical expenses in the last year of life were around 30.3, 16.7, 13.0, and 12.1 million won among leukemia, lymphoma, ovarian cancer, and breast cancer patients, respectively. Digestive organ cancers including stomach, esophagus, liver, pancreas, and colorectal cancers had relatively low medical expenses. Medical expenses in the last year of life were inverse Ushaped with high expenses near one year of survival. Average monthly cost in the 12 months before death among the patients who had survived 10-15 years were more than two-fold greater than the cost before diagnosis among those who had survived for less than one year. Leukemia was the most expensive cancer. It is possible that once diagnosed as cancer, medical expenses do not return to the level before diagnosis. Further research will be needed to understand the magnitude and change of the medical expenses among cancer patients with long term follow up data.


Experimental Nanopulse Ablation of Multiple Membrane Parasite on Ex Vivo Hydatid Cyst.
The impact of ultrashort nanopulse on cellular membrane is of biological significance and thus has been studied intensively. Different from cell study, this ex vivo study aims to investigate the biological effects of nanosecond pulsed electric field (nsPEF) on an independent multimembrane parasite, human hydatid cyst, to observe the unique influence of nanopulse on macromembrane structure, permeabilization, and biochemistry. The 300 ns nsPEF was delivered on an experimental model of single human hydatid cyst ex vivo with eight different parameters. Then pathological changes during 7 days of 48 parasite cysts were followed up after nsPEF. The laminated layer, the germinal layer, the protoscolex, and cyst fluid were evaluated by the morphological, pathological, and biochemical measurements. The parameter screening found that nsPEF can damage hydatid cyst effectively when the field strength is higher than 14 kV/cm. When nsPEF is higher than 29 kV/cm, nsPEF destroy hydatid cyst completely by collapsing the germinal layer, destructing protoscolices, and exhausting the nutrition.


A genome-wide methylation study on obesity: differential variability and differential methylation.
Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.


Improved Pain and Function After TTC Fusion With a Custom Cage.
Three-dimensional custom cages can be used to treat complex ankle and hindfoot pathology and bone loss with potentially better patient satisfaction and higher fusion rates than tibiotalocalcaneal (TTC) fusion alone or in combination with bulk femoral head allograft. Yet there is limited literature to support this procedure. The purpose of this study is to objectively quantify the clinical and radiologic outcomes of patients undergoing patient-specific 3D-printed custom cage implantation to fill large defects around the ankle joint region as part of a limb-salvaging TTC fusion. This is a retrospective review of 21 patients (mean age 59.3 years) who underwent custom cage implantation with a TTC retrograde fusion nail by a single surgeon for massive bone loss of the ankle and hindfoot. Patient charts were reviewed for pain and functional outcomes, complications, and various demographics, including number of previous surgeries to the ipsilateral ankle. Mean follow-up was 32 months. All 21 patients had preoperative and postoperative pain and function scores available for analysis. A total of 20 (95.2%) of the 21 patients had their cage in situ at final follow-up. Overall, with the numbers available, visual analog scale (VAS) for pain, Foot and Ankle Ability Measure (FAAM) activities of daily living subscale, and the 12-Item Short Form Health Survey (SF-12) mental and physical health scores significantly improved from preoperative to final follow-up. However, when compared to the overall US population of age-matched 55- to 64-year-old individuals, patients still remained relatively disabled. There were 2 failures, one of which required amputation and the other was treated nonoperatively with bracing. In conclusion, in this relatively small, single-surgeon series, we found that 3D-printed custom cage technology offered a viable option for complex TTC fusion procedures performed in the presence of significant bone loss, with good fusion rates, however relatively modest improvement in functional outcomes. Level IV, retrospective case series.


Use of study days to develop the healthcare assistant role.
The Department of Health's strategies to combat staff shortages and an ageing workforce have now turned their focus to the delivery of patient care by HCAs. This article describes how a trust redesigned the role of HCAs and implemented a study day in order to enhance both theoretical knowledge and clinical practice for this role.


On being cool and collected: mood regulation in anticipation of social interaction.
This study examined the influence of anticipated social interaction on the regulation of moods. Study 1 induced happy and sad moods through exposure to music. All participants expected to perform a second, unrelated experimental task either by themselves of with another participant. Participants who expected to do the task alone subsequently selected positive and negative news stories equally, but those who expected to interact preferred stories containing material incongruent with their mood. Study 2 confirmed this outcome, but showed it was confined primarily to anticipation of interaction with partners who are expected to be in neutral or good moods themselves. In Study 3, participants whose mood was not manipulated reduced self-exposure to cheerful or depressing videos when they expected to interact with another.


Induction of a chloracne phenotype in an epidermal equivalent model by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on aryl hydrocarbon receptor activation and is not reproduced by aryl hydrocarbon receptor knock down.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent activator of the aryl hydrocarbon receptor (AhR) and causes chloracne in humans. The pathogenesis and role of AhR in chloracne remains incompletely understood. To elucidate the mechanisms contributing to the development of the chloracne-like phenotype in a human epidermal equivalent model and identify potential biomarkers. Using primary normal human epidermal keratinocytes (NHEK), we studied AhR activation by XRE-luciferase, AhR degradation and CYP1A1 induction. We treated epidermal equivalents with high affinity TCDD or two non-chloracnegens: β-naphthoflavone (β-NF) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Using Western blotting and immunochemistry for filaggrin (FLG), involucrin (INV) and transglutaminase-1 (TGM-1), we compared the effects of the ligands on keratinocyte differentiation and development of the chloracne-like phenotype by H&E. In NHEKs, activation of an XRE-luciferase and CYP1A1 protein induction correlated with ligand binding affinity: TCDD>β-NF>ITE. AhR degradation was induced by all ligands. In epidermal equivalents, TCDD induced a chloracne-like phenotype, whereas β-NF or ITE did not. All three ligands induced involucrin and TGM-1 protein expression in epidermal equivalents whereas FLG protein expression decreased following treatment with TCDD and β-NF. Inhibition of AhR by α-NF blocked TCDD-induced AhR activation in NHEKs and blocked phenotypic changes in epidermal equivalents; however, AhR knock down did not reproduce the phenotype. Ligand-induced CYP1A1 and AhR degradation did not correlate with their chloracnegenic potential, indicating that neither CYP1A1 nor AhR are suitable biomarkers. Mechanistic studies showed that the TCDD-induced chloracne-like phenotype depends on AhR activation whereas AhR knock down did not appear sufficient to induce the phenotype.


Free-Standing, Foldable V2 O3 /Multichannel Carbon Nanofibers Electrode for Flexible Li-Ion Batteries with Ultralong Lifespan.
Free-standing electrodes with high energy density and long life are of critical importance to the development of lithium-ion batteries (LIBs) for flexible/wearable electronic devices. Herein, the free-standing and foldable V2 O3 /multichannel carbon nanofibers (V2 O3 /MCCNFs) composites are prepared via electrospinning and subsequent carbonization. Such V2 O3 /MCCNFs electrode delivers a superior capacity of 881.1 mAh g-1 at 0.1 A g-1 after 240 cycles. More importantly, the ultralong lifespan is achieved with a high capacity of 487.8 mAh g-1 even after 5000 cycles at a high current density of 5 A g-1 with only 0.00323% decay rate, which shows the best performance among the reported V2 O3 -based anodes and other metal oxides based free-standing anodes. Furthermore, this flexible electrode is further applied to the pouch cell, which exhibits prominent capacity of 348.3 mAh g-1 after 500 cycles at 1 A g-1 with 0.094% decay per cycle. The unprecedented performance can be ascribed to synergetic contributions of V2 O3 and multichannel carbon nanofibers, which not only promote the penetration of electrolyte and reduce the transport length of Li+ , but also increase active material/electrolyte contact area and buffer the volume change. This work paves the way to develop free-standing electrode for flexible/wearable electronic devices with ultralong lifespan.


Intra-Species Diversity of Leishmania major and L. tropica from Clinical Isolates of Cutaneous Leishmaniasis in Southwest Iran Inferred by ITS1-rDNA.
Cutaneous leishmaniasis (CL) as a public health concern is increasingly circulating by causative agents of Leishmania tropica and L. major in Iran. As regard to recent treatment failure and controlling problems, the accurate elucidation of heterogeneity traits and taxonomic status of Leishmania spp. should be broadly addressed by policymakers. This study was designed to determine the genetic variability and molecular characterization of L. major and L. tropica from Iranian CL patients. One hundred positive Giemsa-stained slides were taken from clinical isolates of CL at Pol-e-Dokhtar County, Southwest Iran, from May 2014 to Sep 2016. DNAs were directly extracted and amplified by targeting ribosomal internal transcribed spacer (ITS) gene following microscopic observation. To identify Leishmania spp. amplicons were digested by restriction enzyme HaeIII subsequent PCR-RFLP technique. To reconfirm, the isolates were directly sequenced to conduct diversity indices and phylogenetic analysis. Based upon the RFLP patterns, 84 and 16 isolates were explicitly identified to L. tropica and L. major respectively. No co-infection was found in clinical isolates. The high genetic diversity of L. tropica (Haplotype diversity 0.9) was characterized compared to L. major isolates (Hd 0.476). The intra-species diversity for L. tropica and L. major isolates corresponded to 3%-3.9% and 0%-0.4%, respectively. Findings indicate the L. tropica isolates with remarkable heterogeneity than L. major are predominantly circulating at Pol-e-Dokhtar County. Occurrence of high genetic variability of L. tropica may be noticed in probable treatment failure and/or emerging of new haplotypes; however, more studies are warranted from various geographic regions of Southwest Iran, using large sample size.


[Postoperative Candida Iris nodules: report of a case].
Description of an uncommon case of postoperative Candida iris nodules. A 70-year-old immunocompetent patient developed whitish iris nodules after phacoemulsification in the left eye, without any other signs of endophthalmitis. Histophathological examination showed spores of candida. These nodules did not respond to intracameral amphotericin B but disappeared with oral fluconazole. However, the functional outcome was poor because of persistant inflammation of the anterior segment. In the presence of postoperative iris nodules, fungal etiology must be considered.


[A comparison of several measurement scales for assessing dyspnea in their daily activities in patients with chronic obstructive lung disease].
The objective of this study was to compare two instruments for measuring dyspnea to functional capacity, defined as maximal oxygen uptake in a stress test limited by symptoms. We carried out a descriptive study to determine correlation between the methods. Subjects with severe chronic obstructive pulmonary disease were enrolled and dyspnea during daily activities was evaluated using the Medical Research Council (MRC) scale and the chronic respiratory disease health perception questionnaire (CRQ). Dyspnea was also assessed on a visual analog scale (VAS) and the Borg scale. Patients performed a progressive treadmill test limited by symptoms to measure peak VO2 and VE. Correlation analysis of the two measures of dyspnea and the objective measures of functional capacity (peak VO2 and VE) showed that the clinical dyspnea measures (CRQ and MRC) correlated well with peak aerobic capacity and with maximal ventilation, whereas the VAS and Borg scale were not significantly related to the aforementioned variables. We also observed that the clinical scales for dyspnea correlated with each other, as did the VAS and Borg scale, but that there was no correlation between the two types of measurement. We conclude that clinical dyspnea indexes (CRQ and MRC) correlate well with maximal aerobic capacity and with each other. However, the VAS and Borg scale do not correlate with functional capacity measured by peak VO2 and VE.


Expeditious synthesis of Mycobacterium tuberculosis sulfolipids SL-1 and Ac2SGL analogues.
M. tuberculosis sulfoglycolipids SL-1 and Ac2SGL are highly immunogenic and potential vaccine candidates. A short and efficient methodology is reported for the synthesis of SL-1 and Ac2SGL analogues via regioselective functionalization of α,α-D-trehalose employing a highly regioselective late stage sulfation, as a key step. The SL-1 analogues 3a and 4 were obtained in 10 and 9 steps in 13.4% and 23.9% overall yields, respectively. The Ac2SGL analogue 5 was synthesized in 5 steps in 18.4% yield.


No Dose Adjustment for Isavuconazole Based on Age or Sex.
This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n = 12 each in groups of nonelderly males and females and elderly males and females). All subjects received a single oral dose of 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). PK samples were collected for analysis of isavuconazole plasma concentrations from the predose time point up to 336 h postdose. Data were analyzed using population pharmacokinetic (PPK) analysis. The resulting PPK model included two compartments with Weibull absorption function as well as interindividual variability with respect to clearance, intercompartment clearance, volumes of central and peripheral compartments, and two Weibull absorption parameters, RA and KAMAX. The PPK analysis showed that elderly females had the highest exposure versus males (ratio of total area under the time-concentration curve [AUC], 138; 90% confidence interval [CI], 118 to 161) and versus nonelderly females (ratio of AUC, 147; 90% CI, 123 to 176). Higher exposures in elderly females were not associated with significant toxicity or treatment-emergent adverse events, as measured in this study. No dose adjustments appear to be necessary based on either age group or sex even with an increase in exposure for elderly females. (This study has been registered at ClinicalTrials.gov under registration no. NCT01657890.).


[Microbial enzymes and their inhibitors].
Several proteolytic enzymes and dehydrogenases of microbial origin were studied with special regard to structure-activity relationship. Enzyme genes of Zn-proteases, subtilisin and pyroglutamyl aminopeptidase from genus Bacillus, prolyl endopeptidases from Flavobacterium and Aeromonas, and of protease II from E. coli were cloned, sequenced and overproduced in E. coli, their active site structures being elucidated by chemical modification as well as by site-directed mutagenesis. Homology analysis revealed that there is a prolyl endopeptidase family as a new family of serine endopeptidases. In addition, enzymatic properties and the primary structures of glutathione-independent formaldehyde dehydrogenase of Pseudomonas putida and 7 alpha-hydroxysteroid dehydrogenase from E. coli were elucidated. Amino acid sequences deduced from the nucleotide sequences of their genes indicated that the former enzyme should be classified into a long-chain metallo alcohol dehydrogenase family, and the latter belongs to a member of the short-chain nonmetallo-alcohol dehydrogenase family.


The laparoscopic experience of recently trained Canadian urologists.
While laparoscopy represents an increasingly important aspect of operative urology, the experience of Canadian urology trainees is poorly defined. The purpose of this study was to determine the level of laparoscopic training of Canadian urology trainees during residency as well as their comfort level with various laparoscopic techniques. An e-mail-and web-based questionnaire was administered to the two most recent cohorts of Canadian-trained urologists (residencies completed in 2003 or 2004). A total of 50 questionnaires were sent. Overall laparoscopic experience and experience with specific laparoscopic tasks (e.g. colonic mobilization) were assessed. Subjects also reported on their relative comfort level (Likert scale of 1 to 5) with various laparoscopic procedures and tasks. Finally, attitudes towards the future role of laparoscopy in the practice of urology were determined. Thirty-six individuals (72%) responded to the questionnaire. Of the respondents, 28 (78%) were performing fellowships; of those pursuing fellowship training, 13 (36%) involved laparoscopy. Thirty-five respondents (97%) had received some laparoscopic exposure during residency; 29 (81%) had mobilized the colon, spleen or liver and 27 (75%) had dissected the renal vessels. Only 7 out of 33 respondents (21%) felt that their residency adequately prepared them to perform laparoscopy independently. There were no significant differences between the responses of the two cohorts. Most Canadian urology trainees are being exposed to laparoscopy, but more exposure is required in order to perform laparoscopy in practice. Many residents still require fellowship training to become facile in laparoscopy.


Identification and characterisation of a cDNA sequence encoding a glutamic acid-rich protein specifically transcribed in Trichinella spiralis newborn larvae and recognised by infected swine serum.
Presently, little is known of the mechanism by which Trichinella penetrates and modulates reprogramming of muscle cells. In light of evidence demonstrating strong protective characteristics of antigens derived from this stage, understanding this process may shed light on potential targets for effective abatement of infection. To this end, a PCR-derived cDNA expression library was constructed using 0.5 micro g of total RNA from Trichinella spiralis newborn larvae. The library consisted of >125000 insert-containing clones. Approximately 40-50 x 10(3) clones were screened immunologically using sera from pigs experimentally infected with 7000 Trichinella L1. Multiple clones reacting positively with the swine infection serum and encoding portions of a glutamic acid-rich protein were identified. Northern and Southern blots indicated at least two distinct genes that encoded the glutamic acid-rich proteins and that these genes were transcribed specifically in the newborn larvae stage. cDNA sequence data predicted open reading frames of 1497 and 1,716 bp generating proteins of 498 amino acids and 571 amino acids, respectively. Both sequences consisted of approximately 39% glutamic acid and 16% serine residues, and differed by the presence of a 219 bp fragment present in the 1716 bp sequence that was absent from the 1497 bp sequence. PCR data indicated that additional isoforms exist within this gene family that are different in length from those described above. In addition, it was found that more than one isoform can exist within a single worm and that this pattern can vary between individual worms within a population. Mouse antibodies to recombinant antigen localised the glutamic acid-rich proteins to the periphery of the developing stichocyte cells within the newborn larvae consistent with the hypothesis that the newborn larval antigens are secreted.


Systolic mechanical performance of heterotopically transplanted hearts in rats treated with cyclosporin.
The aim was to compare left ventricular mechanical performance of the heterotopic cardiac transplant undergoing atrophy and the in situ recipient hearts of immunosuppressed rats. The hearts of outbred male Wistar rats were transplanted, with a part of the lungs, into the abdomen of recipients of the same strain by attaching the stump of the aorta end to side to the abdominal aorta of the recipient. The animals were treated with cyclosporin A at a daily dose of 15 mg.kg-1 for seven consecutive days after the operation. Ventricular function was assessed in the isolated perfused "non-working" heart under isovolumetric conditions. Within three, 14, and 28 days after transplantation the mass of the left ventricle of the transplant decreased to 84, 54, and 43% compared with corresponding recipients. The developed pressure, maximum rate of pressure development, and the slope of the systolic stress-strain relation were unaffected in the atrophic ventricles of the transplants; the rate of relaxation, however, significantly decreased. Similar results were obtained with inbred Lewis rats receiving no immunosuppression. The data indicate that systolic mechanical performance of the heterotopically transplanted hearts was maintained during the development of atrophy; the cardiotoxic effect of cyclosporin did not manifest itself under these conditions.


Evaluation of risks from urban air pollutants in the southeast Chicago area.
Region V of the U.S. Environmental Protection Agency has conducted a comprehensive study of cancer risks from urban exposure to air pollutants in the Southeast Chicago area. This study estimated emissions of a list of 30 air carcinogens from a broad range of nontraditional, as well as traditional, source types. Using dispersion modeling and applying the appropriate unit risk factors and population data, this study estimated the risks at each receptor location and the total number of cancer cases attributable to air pollution in the area. This analysis estimated that current concentrations would cause 77 cases of cancer over the next 70 years, an average risk of 2.0 X 10(-4). Contributions from different source types and different pollutants were estimated. The total contribution from nontraditional source types was less than 0.3 percent. Although these estimates are highly uncertain, the study does suggest the nature and general magnitude of cancer risks from air pollution in the urban area studied.


[What is ghrelin for gastric cancer?].
Ghrelin is a novel and 28-amino-acid peptide hormone. It was identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor by a Japanese researcher in 1999. Besides the stimulation, ghrelin has been known to have a wide spectrum of biological functions such as regulation of appetite and food intake, gastrointestinal motility, gastric acid secretion, cell proliferation, glucose and lipid metabolism, and cardiovascular and immunologic processes. Therefore, studies of ghrelin have been rapidly increasing. However, the reports on the relationship between ghrelin and gastric cancer are few, though ghrelin is secreted mainly from the stomach. The purpose of this review is to consider what ghrelin is from a gastric cancer perspective. The studies and clinical applications of ghrelin in near future are also discussed.


Plasma vasopressin concentrations in healthy foals from birth to 3 months of age.
Arginine vasopressin (AVP) has received increased attention in equine critical care but there is minimal information of AVP concentration in foals. The clinical usefulness of measuring AVP in ill foals depends on knowledge of age-related changes in AVP concentrations in healthy foals. Plasma AVP concentrations will be significantly different when measured from birth to 3 months of age in healthy foals. Thirteen healthy university-owned foals. Prospective, observational study. Blood was collected from healthy foals at birth and 3, 5, 7, 10, 14, 21, 28, 42, 56, and 84 days of age. Plasma was harvested and plasma AVP concentrations were determined by radioimmunoassay. No statistically significant differences were detected in plasma AVP concentrations over the study period. Plasma AVP concentrations over the entire study period was 6.2+/-2.5 pg/mL. There was no age-related variation in plasma AVP concentrations detected in healthy foals from birth to 3 months of age suggesting that AVP concentrations are similar across foals of these ages.


An H-NS Family Protein, Sfh, Regulates Acid Resistance by Inhibition of Glutamate Decarboxylase Expression in Shigella flexneri 2457T.
The glutamate-dependent acid-resistance system is the most effective acid tolerance pathway in Shigella, allowing survival in extremely acidic environments. However, the regulation of this system in Shigella remains elusive. In the current study, we identified significant differences in the levels of glutamate decarboxylase between three Shigella flexneri strains with different levels of acid resistance using blue native-polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF)/sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The results showed that the degree of acid resistance and the levels of GadA/B were significantly lower in strain 2457T compared with two other S. flexneri strains. It has been reported that plasmid pSf-R27 is expressed in strain 2457T but not in the other 142 sequenced S. flexneri isolates. pSf-R27 encodes protein Sfh, which belongs to a family of histone-like nucleoid-structuring (H-NS) proteins that participate in the transcriptional control of glutamate-dependent acid resistance, implicating pSf-R27 in the lower acid resistance of strain 2457T. Transformation of pSf-R27 or sfh alone into strain 301 resulted in decreased expression of GadA/B in the recombinant strains. Thus, we confirmed that H-NS family protein Sfh, bound to the gadA/B regulatory region and regulates the expression of glutamate decarboxylase at the transcriptional level. We also examined the acid tolerance of the wild-type and recombinant strains using flow cytometry and determined that the acid tolerance of S. flexneri is closely related to the expression of GadA/B. These findings further our understanding of the acid tolerance of S. flexneri, especially via the glutamate-dependent pathway.


Seasonal Patterns of Nitrate Reductase and Nitrogenase Activities in Phaseolus vulgaris L.
The patterns of nitrate reductase activity (NRA) in the leaves (in vivo assay) and root nodule nitrogenase activity (C(2)H(2) reduction) were investigated throughout the season in field-grown Phaseolus vulgaris plants.Maximal NRA (per g fresh weight) occurred at early stages of leaf development but total activity (per leaf) was maximal when the leaf reached full size. In mature plants, most NRA was associated with the upper leaves. Nitrogenase activity was initiated about 2 weeks after sowing, reached a maximum at flowering (5 weeks after sowing) and declined rapidly thereafter. Nitrogenase activity followed the pattern of nodule development. After flowering, P. vulgaris was apparently able to take up and assimilate NO(-) (3) as evidenced by the increase in NO(-) (3) content of the stem and the high levels of NRA in the leaves. Total plant NRA was maximal after flowering and addition of NH(4)NO(3) to the soil at flowering resulted in even higher levels of NRA through most of the pod-filling period, thus resulting in higher seed yields (59% over control).It is proposed that P. vulgaris can benefit from both N(2) fixation and NO(-) (3) assimilation and that nitrate reductase plays an important role in the assimilation of nitrogen after flowering.


Management of the patient for transcatheter aortic valve implantation in the perioperative period.
Aortic stenosis is a prevalent valvular disease among aging patients, and surgical correction is the most definitive treatment. Yet many elderly patients are deemed to be "inoperable" or at excessive risk to undergo open surgical aortic valve replacement (AVR). Transcatheter aortic valve implantation (TAVI), either through a transfemoral or transapical approach, has become a potential option for these high-risk patients. Although TAVI technology will continue to be developed and perfected, most studies at this time reveal that symptoms are improved and that 1-year morbidity and mortality are similar to those for open surgical AVR. Anesthetic management for patients undergoing TAVI involves maintaining hemodynamic stability during periods of rapidly changing conditions and providing echocardiographic guidance and assessment. Postoperative care includes a variety of challenges such as managing pain control, monitoring for potential complications, and providing hemodynamic management.


The platelet level indicates the erythropoietic capacity for preoperative autologous blood donation.
The erythropoietic capacity for preoperative autologous blood donation (ECPABD) shows marked inter individual variability. This study was performed to evaluate factors useful to predict individual ECPABD from data available before the first donation. The subjects consisted of 74 adult patients who received autologous blood donation, with a mean of 61 +/- 12.8 yr (SD). We classified the patients into four groups using our criteria for evaluating the ECPABD and investigated the relationships among age, disease, pre-platelet count, and the rate of platelet increase. (1) Advanced age and the status of disease were not distinctly correlated with low ECPABD. (2) Patients with a high pre-platelet levels had a low ECPABD regardless of the haemoglobin. (3) Patients in which the platelet count increased in accordance with the level of collection exhibited low pre-platelet counts and high ECPABD. In patients with high pre-platelet levels, we reduced the amount collected, considered early use of recombinant human erythropoietin and reevaluated the application of autologous blood donation.


Temperature-independent singlet exciton fission in tetracene.
We use transient absorption spectroscopy to demonstrate that the dynamics of singlet exciton fission in tetracene are independent of temperature (10–270 K). Low-intensity, broad-band measurements allow the identification of spectral features while minimizing bimolecular recombination. Hence, by directly observing both species, we find that the time constant for the conversion of singlets to triplet pairs is ~90 ps. However, in contrast to pentacene, where fission is effectively unidirectional, we confirm that the emissive singlet in tetracene is readily regenerated from spin-correlated "geminate" triplets following fission, leading to equilibrium dynamics. Although free triplets are efficiently generated at room temperature, the interplay of superradiance and frustrated triplet diffusion contributes to a nearly 20-fold increase in the steady-state fluorescence as the sample is cooled. Together, these results require that singlets and triplet pairs in tetracene are effectively degenerate in energy, and begin to reconcile the temperature dependence of many macroscopic observables with a fission process which does not require thermal activation.


Guidelines for monitoring drug therapy in rheumatoid arthritis. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines.
Drugs used to treat RA may cause death, disability, and diseases, especially if the treatment continues in the setting of undetected toxicity. Prevention of toxicity may be enhanced by pretreatment assessment of individual risk factors for toxicity and by careful patient and physician education about safe use of the drug. Patients and their physicians must be alert to the signs and symptoms of toxicity that should prompt discontinuation of the drug and physician reassessment. Some drug toxicity may be discovered by appropriate laboratory monitoring before serious problems become clinically apparent. The 3 major drug categories for the treatment of RA are the NSAIDs, DMARDs, and glucocorticoids. Most NSAIDs have common GI and renal toxicity that may be averted by careful patient selection and administration of the drug. The individual DMARDs have specific toxicities for which monitoring protocols have been developed. The serious side effects of systemic glucocorticoids are largely related to dose and duration of treatment. The recommendations summarized in Table 1 are for basic monitoring in patients with uncomplicated RA. Additional monitoring may be appropriate for patients with comorbid disease, concurrent medication, or other risk factors.


Quantitative electroencephalography of medetomidine, medetomidine-midazolam and medetomidine-midazolam-butorphanol in dogs.
The purpose of this study was to evaluate the effects of the administration of an alpha2-adrenoceptor agonist alone and in combination with other derivatives on brain wave activity. In addition, the diagnostic values of the electroencephalogram (EEG) for judging the depth of the balanced anaesthesia with an alpha2-adrenoceptor agonist was evaluated. The treatments comprised 20 microg/kg medetomidine (Me-20), 80 microg/kg medetomidine (Me-80), 20 microg/kg medetomidine and 0.5 mg/kg midazolam (Me-Mi) administered intramuscularly, and 20 microg/kg medetomidine with 0.5 mg/kg midazolam and 0.1 mg/kg butorphanol (Me-Mi-Bu). The EEG was recorded continuously at pre-administration, and at 7, 10, 20, 30, 45 and 60 min after administration. The recorded data were analysed by separating the power spectrum into 1-3, 4-7, 8-13 and 14-30 Hz bands. Spectral-edge analysis was used to calculate the spectral edge frequency 90 (SEF90) and the median edge frequency (MEF). Time-related changes in power spectrum analysis showed a significant increase in the Me-80 group in the 1-3 Hz band. The power for 1-3 Hz in the Me-80 group was significantly higher than in all the other groups. In the 14-30 Hz band, there was a significant reduction of power in all groups following administration of the agents. The SEF90 frequencies were significantly reduced in all groups except for the Me-20 group after administration of the agents. The SEF90 frequencies in the Me-20, Me-Mi and Me-Mi-Bu were all significantly higher than those in the Me-80 group. However, there was no significant difference between the Me-20, Me-Mi and Me-Mi-Bu groups in any analyses. Our results demonstrated that the changes in quantitative EEG made by the Me-Mi-Bu and Me-Mi groups were similar to those made by Me-20 groups. Present results suggest that the EEG should be interpreted with caution in assessing the anaesthetic level in balanced anaesthesia in dogs.


[Pertussis vaccine in adolescents and adults].
Despite high immunisation rates in infancy, Bordetella pertussis is still circulating in industrialised countries, causing severe infections in infants too young to be vaccinated, as well as an important number of long lasting cough episodes in older children, adolescents and young adults. The limited duration of the protection resulting from vaccination in the 2 first years of life is probably responsible for the insufficient control of the disease. The development of acellular pertussis vaccines has allowed immunisation of school age children, and an adult formulation is now available. The indications of this vaccine will be discussed.


Characterization of human reflex tear proteome reveals high expression of lacrimal proline-rich protein 4 (PRR4).
In-depth studies on the proteome of reflex tears are still inadequate. Hence, further studies on this subject will unravel the key proteins which are conjectured to possess vital functions in the protection of the ocular surface. Therefore, this study investigated the differences in the expression levels in proteome of reflex compared to basal tears. Basal (n = 10) and reflex (n = 10) tear samples from healthy subjects were collected employing the capillary method, subsequently pooled and the proteomes were characterized employing 1DE combined with LC-ESI-MS/MS strategy for label-free quantitative (LFQ) analysis. The differentially expressed proteins were validated by 2DE combined with LC-ESI-MS/MS and targeted-MS approach called accurate inclusion mass screening (AIMS) strategies. The analysis of the reflex tear proteome demonstrated increased abundance in proline-rich protein 4 (PRR4) and zymogen granule protein 16 homolog B (ZG16B) for the first time. Other abundant lacrimal proteins, e.g. lactotransferrin and lysozyme remained constant. Predominantly, the lacrimal gland-specific PRR4 represents the major increased protein in reflex tears in an attempt to wash out irritants that come into contact with the eye. Conversely, decreased abundance in Ig alpha-1 chain C, polymeric immunoglobulin receptor, cystatin S/SN, clusterin and mammaglobin were observed. This study had further unraveled the intricate proteome regulation during reflex tearing, especially the potential role of PRR4, which may be the key player in the protection and maintenance of dynamic balance of the ocular surface.


The supraclavicular artery island flap in head and neck reconstruction: applications and limitations.
The supraclavicular artery island (SAI) rotational flap may have advantages compared with free-tissue transfer in head and neck reconstruction. Because this flap has not been extensively described for head and neck reconstruction of oncologic defects, guidelines for its indications would benefit the reconstructive surgeon. To describe the applications and limitations of the SAI flap as an alternative to free-tissue transfer in reconstruction of head and neck defects. Retrospective case series of 45 patients with defects related to malignant and nonmalignant disease undergoing reconstructive surgery from August 18, 2010, through September 28, 2012, at an academic, tertiary referral center. Each defect was deemed unsuitable for primary or local flap closure and would require regional tissue or free-tissue transfer. Mean follow-up was 10.3 (range, 1-31) months. Use of the SAI flap for reconstruction of soft-tissue defects of the head and neck. Defect site, flap dimensions, time to raise the flap, and complications. Defects of the oral cavity, oropharynx, laryngopharynx, esophagus, trachea, temporal bone, and cervicofacial skin underwent reconstruction. Mean flap dimensions were 6.1 cm wide and 21.4 cm long, with a mean skin paddle length of 7.9 cm. Harvest time was less than 1 hour. Donor-site complications included minor dehiscence in 6 patients and prolonged wound care in 2. Partial skin flap necrosis occurred in 8 patients, whereas 2 had complete loss of the skin paddle. Seven patients developed a salivary fistula, 4 of which healed spontaneously. Flap length greater than 22 cm correlated with flap necrosis (P = .02). A history positive for smoking correlated with an increased risk of flap dehiscence (P = .02). The SAI flap provides an alternative to free-tissue transfer for soft-tissue reconstruction after head and neck oncologic surgery. This flap is easy to harvest and versatile. However, the SAI flap has limitations in length and, because it is a rotational flap, is less capable of reconstructing some complex head and neck defects.


Activation of Alpha-7 Nicotinic Acetylcholine Receptors (α7nAchR) Promotes the Protective Autophagy in LPS-Induced Acute Lung Injury (ALI) In Vitro and In Vivo.
The release of inflammatory cytokines and chemokines and autophagy has been reported to be involved in the pathogenic mechanism of acute lung injury (ALI). Reportedly, alpha-7 nicotinic acetylcholine receptors (α7nAchR) might play a protective role in LPS-induced ALI. In the current research, we established LPS-induced ALI model in mice and α7nAchR agonist PNU-282987 improved LPS-induced injury. In MH-S cells, LPS stimulation inhibited, whereas α7nAchR agonist PNU-282987 enhanced the autophagy. α7nAchR agonist PNU-282987 protected MH-S cells from LPS-induced inflammation by reducing the concentrations of IL-6, TNF-α, and IL-1β. Finally, LPS stimulation dramatically inhibited MH-S cell viability but enhanced cell apoptosis, whereas PNU-282987 treatment exerted opposite effects; α7nAchR might regulate the cellular homeostasis via affecting the crosstalk between the autophagy and apoptosis in MH-S cells; in other words, α7nAChR agonist enhances MH-S cell autophagy and inhibits MH-S cell apoptosis. In conclusion, α7nAchR promote the protective autophagy in LPS-induced ALI model in mice and MH-S cells. The application of α7nAchR agonist is considered a potent target for LPS-induced ALI, which needs further clinical investigation.


[Molecular mechanisms of neuronal connective tissue genesis during the course of cerebral cortex development].
The cerebral cortex constitutes one of the most complex structures in our brain. In correlation with its elaborate functions, it is characterized by the great complexity of its neuronal connections, but the mechanisms responsible for the generation of these connections remain poorly known. We have recently initiated the characterization of a new multigenic family of axon guidance factors, the ephrin/Eph gene family, during the development of neuronal connections in the mouse cortex. Combining expression studies, in vitro guidance essays, and in vivo analysis of mutant mice, enabled us to demonstrate the critical role of ephrin/Eph genes in the development of cortical networks. Mutant mice for ephrin/Eph genes display a topographic distortion of their cortical somatosensory map, as well as ectopic projections from the motor thalamus to the somatosensory cortex. The identification of factors like ephrins, capable to (re)specify the pattern of neuronal connections, has implications for our understanding of pathological brain development (epilepsy, abnormal movements, psychiatric diseases), and in the perspective of the rational design of cell therapies of neurodegenerative diseases.


Staphylococcus epidermidis and Staphylococcus xylosus in a secondary root canal infection with persistent symptoms: a case report.
The aim of this case report is to highlight the importance of maintaining the aseptic chain during endodontic treatment. This paper describes a clinical situation in which persistent symptoms had developed after the first appointment to treat a vital pulp case. Microbiological analysis of the case indicated that symptoms were probably due to a secondary root canal infection by two species of coagulase-negative staphylococci--Staphylococcus epidermidis and Staphylococcus xylosus. Symptoms had persisted in spite of using various intracanal antimicrobial agents and systemic antibiotic therapy.


Monoclonal Antibody Therapies Beyond Complement for NMOSD and MOGAD.
Aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (AQP4-IgG seropositive NMOSD) and myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) are inflammatory demyelinating disorders distinct from each other and from multiple sclerosis (MS).While anti-CD20 treatments can be used to treat MS and AQP4-IgG seropositive NMOSD, some MS medications are ineffective or could exacerbate AQP4-IgG seropositive NMOSD including beta-interferons, natalizumab, and fingolimod. AQP4-IgG seropositive NMOSD has a relapsing course in most cases, and preventative maintenance treatments should be started after the initial attack. Rituximab, eculizumab, inebilizumab, and satralizumab all have class 1 evidence for use in AQP4-IgG seropositive NMOSD, and the latter three have been approved by the US Food and Drug Administration (FDA). MOGAD is much more likely to be monophasic than AQP4-IgG seropositive NMOSD, and preventative therapy is usually reserved for those who have had a disease relapse. There is a lack of any class 1 evidence for MOGAD preventative treatment. Observational benefit has been suggested from oral immunosuppressants, intravenous immunoglobulin (IVIg), rituximab, and tocilizumab. Randomized placebo-controlled trials are urgently needed in this area.


The Ubiquitin System and A20: Implications in Health and Disease.
Inflammation is triggered by stimulation of innate sensors that recognize pathogens, chemical and physical irritants, and damaged cells subsequently initiating a well-orchestrated adaptive immune response. Immune cell activation is a strictly regulated and self-resolving process supported by an array of negative feedback mechanisms to sustain tissue homeostasis. The disruption of these regulatory pathways forms the basis of chronic inflammatory diseases, including periodontitis. Ubiquitination, a covalent posttranslational modification of target proteins with ubiquitin, has a profound effect on the stability and activity of its substrates, thereby regulating the immune system at molecular and cellular levels. Through the cooperative actions of E3 ubiquitin ligases and deubiquitinases, ubiquitin modifications are implicated in several biological processes, including proteasomal degradation, transcriptional regulation, regulation of protein-protein interactions, endocytosis, autophagy, DNA repair, and cell cycle regulation. A20 (tumor necrosis factor α-induced protein 3 or TNFAIP3) is a ubiquitin-editing enzyme that mainly functions as an endogenous regulator of inflammation through termination of nuclear factor (NF)-κB activation as part of a negative feedback loop. A20 interacts with substrates that reside downstream of immune sensors, including Toll-like receptors, nucleotide-binding oligomerization domain-containing receptors, lymphocyte receptors, and cytokine receptors. Due to its pleiotropic functions as a ubiquitin binding protein, deubiquitinase and ubiquitin ligase, and its versatile role in various signaling pathways, aberrant A20 levels are associated with numerous conditions such as rheumatoid arthritis, diabetes, systemic lupus erythematosus, inflammatory bowel disease, psoriasis, Sjögren syndrome, coronary artery disease, multiple sclerosis, cystic fibrosis, asthma, cancer, neurological disorders, and aging-related sequelae. Similarly, A20 has recently been implicated as an essential regulator of inflammation in the oral cavity. This review presents information on the ubiquitin system and regulation of NF-κB by ubiquitination using A20 as a representative molecule and highlights how the dysregulation of this system can lead to several immune pathologies, including oral cavity-related disorders mainly focusing on periodontitis.