Extraction of a novel water-soluble gum from nettle (Urtica dioica) seeds: Optimization and characterization.
Nettle seed gum (NSG) which is a novel potential source of hydrocolloid was characterized in terms of yield, physicochemical, rheological, functional and thermal properties. According to Response Surface Methodology, the maximum extraction yield was determined as 6.17% on dry basis. In order to clarify the structural information of the gum, the FT-IR analysis and monosaccharide composition determination were performed. In the results, the NSG had 8.48% moisture, 10.81% total ash, 2.89% total protein, 1.15% total oil and 76.67% total carbohydrate. The FT-IR analysis revealed the existence of carboxyl groups, which gives the gum the capability of ion binding. Furthermore, Mannose/Galactose ratio was calculated as 1.07, indicating the water solubility of gum. DSC analysis showed that the NSG was highly stable in thermal process. Intrinsic viscosity, average viscosity and molecular weight values were determined as 8.56 ± 0.4 dL/g and 1.89 ± 0.1 × 106 g/mol, respectively. The emulsification capacity, emulsion stability and foam formation capacity of the NSG were 48%, 40% and 4%, respectively. The NSG exhibited shear thinning behavior while dynamic rheological analysis indicated the NSG had viscoelastic properties and G' (the storage modulus) was higher than G″ (the loss modulus). In conclusion, the present study supplied novel knowledge on the NSG, which will be inestimable for clarifying its matchless functional properties.


Hot exciton transition for organic light-emitting diodes: tailoring excited-state properties and electroluminescence performances of donor-spacer-acceptor molecules.
The photophysical, electrochemical and electroluminescent properties of newly synthesized blue emitters with donor-π-acceptor geometry, namely, 4'-(1-(naphthalen-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-(2-[1,1'-biphenyl]vinyl)-4-amine (NSPI-TPA), 4'-(1-(2-methylnaphthalen-1-yl)-1H-phenanthro[9,10-d]imidazol-2-yl)-N,N-diphenyl-(2-[1,1'-biphenyl]vinyl)-4-amine (MNSPI-TPA), 4-(2-(4'-(diphenylamino)-(2-[1,1'-biphenyl]vinyl)-4-yl)-1H-phenanthro[9,10-d]imidazol-1-yl)-1-naphthalene-1-carbonitrile (SPNCN-TPA) and 4-(2-(4-(9H-carbazol-9-yl)styryl)-1H-phenanthro[9,10-d]imidazol-1-yl)naphthalene-1-carbonitrile (SPNCN-Cz) were analyzed. The conjugation length in the emitters is not conducive to pure emission and hence, a molecular twisting strategy was adopted in NSPI-TPA, MNSPI-TPA, SPNCN-TPA and SPNCN-Cz to enhance pure emission. The emissive state (HLCT) of twisted D-π-A molecules containing both LE and CT (HLCT) states was tuned for high PL (η PL) (LE) and high exciton utilization (η s) (CT) efficiencies by replacing triphenylamine (strong donor) with carbazole (weak donor). Among strong donor compounds, namely, NSPI-TPA, MNSPI-TPA and SPNCN-TPA, the SPNCN-TPA-based device exhibited blue emission (451 nm) with CIE coordinates (0.15, 0.08), maximum current efficiency (η c) of 2.32 cd A-1, power efficiency (η p) of 2.01 lm W-1 and external quantum efficiency (η ex) of 3.02%. The device with SPNCN-Cz emitter exhibited higher electroluminescence efficiencies than the SPNCN-TPA-based device, with pure blue emission (443 nm, CIE: 0.15,0.07), η ex of 3.15%, η c of 2.56 cd A-1 and η p of 2.45 lm W-1.


Polymer-Silica Hybrid On-Chip Amplifier with Vertical Pumping Method.
This article demonstrates a multilayer polymer-silica hybrid on-chip amplifier combining mode division multiplexing method. The multilayer amplifier consists of a pumping silica waveguide and an amplifying polymer waveguide. The pumping waveguide possesses the stability and the high damage threshold. The amplifying waveguide takes the advantages of the high compatibility and the high doping rate. The vertical pump of mode division multiplexing method can introduce the pumping light into the amplifying waveguide at any desired position of the chip. By the isolation method between signal and pumping light, the pumping light can be coupled into the amplifying waveguide, while the signal light cannot be coupled into the pumping waveguide. The parameters of doping rates, waveguide lengths, overlap factors, coupling parameters are calculated to optimize the gain characteristics of the amplifier. The amplifier with three position-optimized pumping light was designed achieving a maximum gain of 33.89 dB/cm with a waveguide length of 6 cm, a signal power of 0.1 mW and a pumping power of 300 mW. This polymer-silica hybrid amplifier is promising for the on-chip loss compensation of the 3D photonic integrated circuits and all optical transistors.


Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity.
Marginal zone (MZ) B cells, representing a distinct subset of innate-like B cells, mount rapid T-independent responses to blood-borne antigens. They express low-affinity polyreactive antigen receptors that recognize both foreign and self-structures. The spleen is considered the exclusive site for murine MZ B cells. However, we have here identified B cells with a MZ B-cell phenotype in the subcapsular sinuses of mouse lymph nodes. The nodal MZ (nMZ) B cells display high levels of IgM, costimulators and TLRs, and are represented by naïve and memory cells. The frequency of nMZ B cells is about 1-6% of nodal B cells depending on mouse strain, with higher numbers in older mice and a trend of increased numbers in females. There is a significant expansion of nMZ B cells following immunization with an autoantigen, but not after likewise immunization with a control protein or with the adjuvant alone. The nMZ B cells secrete autoantibodies upon activation and can efficiently present autoantigen to cognate T cells in vitro, inducing T-cell proliferation. The existence of self-reactive MZ B cells in lymph nodes may be a source of autoantigen-presenting cells that in an unfortunate environment may activate T cells leading to autoimmunity.


New shade guide for tooth whitening monitoring: visual assessment.
Shade guides currently used to monitor tooth bleaching lack logical order, uniform color distribution, and light shade tabs, thus, limiting the design of bleaching studies and diminishing the validity of obtained results. The purpose of this study was to perform a visual evaluation of a new shade guide designed primarily for monitoring tooth whitening and to compare this shade guide with 2 commercial shade guides. Tab arrangement of 3 shade guides (prototype of new VITA Bleachedguide 3D-Master (BG), value scale of Vitapan Classical (VC), and color-ordered Trubyte Bioform porcelain shade guide (TB)) was evaluated. The tabs from each shade guide, one at a time, were scattered and visually reordered from the lightest to the darkest by 15 observers under controlled conditions of a viewing booth. Visual ranking was compared to manufacturer-suggested ranking. Interobserver repeatability was compared using the Mann-Whitney U test (alpha=.05). All observers responded to a questionnaire grading the 3 shade guides using a Likert scale (1, strongly disagree, to 5, strongly agree). The Kolmogorov-Smirnov z-test (alpha=.05) was used to process the results obtained in the questionnaire Visually determined BG order was found to be identical to the order given by the manufacturer. This was not the case with the 2 other products: visual and manufacturers' order were identical for 7 of 16 VC tabs and 9 of 24 TB tabs. Interobserver repeatability for BG was significantly higher (P<.001) as compared to corresponding values recorded for VC and TB, whereas no statistically significant difference in interobserver repeatability between VC and TB was observed. Visually determined lightest to darkest order was identical to the suggested manufacturer order only for VITA Bleachedguide 3D-Master. The same shade guide was also superior based on the scores given in the questionnaire. These findings support the use of the new VITA Bleachedguide 3D-Master for monitoring tooth whitening.


Microplastics in urban waters and its effects on microbial communities: a critical review.
Microplastic (MP) pollution is one of the emerging threats to the water and terrestrial environment, forcing a new environmental challenge due to the growing trend of plastic released into the environment. Synthetic and non-synthetic plastic components can be found in rivers, lakes/reservoirs, oceans, mountains, and even remote areas, such as the Arctic and Antarctic ice sheets. MPs' main challenge is identifying, measuring, and evaluating their impacts on environmental behaviors, such as carbon and nutrient cycles, water and wastewater microbiome, and the associated side effects. However, until now, no standardized methodical protocols have been proposed for comparing the results of studies in different environments, especially in urban water and wastewater. This review briefly discusses MPs' sources, fate, and transport in urban waters and explains methodological uncertainty. The effects of MPs on urban water microbiomes, including urban runoff, sewage wastewater, stagnant water in plumbing networks, etc., are also examined in depth. Furthermore, this study highlights the pathway of MPs and their transport vectors to different parts of ecosystems and human life, particularly through mediating microbial communities, antibiotic-resistant genes, and biogeochemical cycles. Overall, we have briefly highlighted the present research gaps, the lack of appropriate policy for evaluating microplastics and their interactions with urban water microbiomes, and possible future initiatives.


Solid-state molecular organometallic chemistry. Single-crystal to single-crystal reactivity and catalysis with light hydrocarbon substrates.
Single-crystal to single-crystal solid/gas reactivity and catalysis starting from the precursor sigma-alkane complex [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF 4] (NBA = norbornane; ArF = 3,5-(CF3)2C6H3) is reported. By adding ethene, propene and 1-butene to this precursor in solid/gas reactions the resulting alkene complexes [Rh(Cy2PCH2CH2PCy2)(alkene) x ][BArF 4] are formed. The ethene (x = 2) complex, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF 4]-Oct, has been characterized in the solid-state (single-crystal X-ray diffraction) and by solution and solid-state NMR spectroscopy. Rapid, low temperature recrystallization using solution methods results in a different crystalline modification, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF 4]-Hex, that has a hexagonal microporous structure (P6322). The propene complex (x = 1) [Rh(Cy2PCH2CH2PCy2)(propene)][BArF 4] is characterized as having a π-bound alkene with a supporting γ-agostic Rh···H3C interaction at low temperature by single-crystal X-ray diffraction, variable temperature solution and solid-state NMR spectroscopy, as well as periodic density functional theory (DFT) calculations. A fluxional process occurs in both the solid-state and solution that is proposed to proceed via a tautomeric allyl-hydride. Gas/solid catalytic isomerization of d3-propene, H2C[double bond, length as m-dash]CHCD3, using [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF 4] scrambles the D-label into all possible positions of the propene, as shown by isotopic perturbation of equilibrium measurements for the agostic interaction. Periodic DFT calculations show a low barrier to H/D exchange (10.9 kcal mol-1, PBE-D3 level), and GIPAW chemical shift calculations guide the assignment of the experimental data. When synthesized using solution routes a bis-propene complex, [Rh(Cy2PCH2CH2PCy2)(propene)2][BArF 4], is formed. [Rh(Cy2PCH2CH2PCy2)(butene)][BArF 4] (x = 1) is characterized as having 2-butene bound as the cis-isomer and a single Rh···H3C agostic interaction. In the solid-state two low-energy fluxional processes are proposed. The first is a simple libration of the 2-butene that exchanges the agostic interaction, and the second is a butene isomerization process that proceeds via an allyl-hydride intermediate with a low computed barrier of 14.5 kcal mol-1. [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF 4] and the polymorphs of [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF 4] are shown to be effective in solid-state molecular organometallic catalysis (SMOM-Cat) for the isomerization of 1-butene to a mixture of cis- and trans-2-butene at 298 K and 1 atm, and studies suggest that catalysis is likely dominated by surface-active species. [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF 4] is also shown to catalyze the transfer dehydrogenation of butane to 2-butene at 298 K using ethene as the sacrificial acceptor.


Changes in the distribution of laminin alpha1 chain in psoriatic skin: immunohistochemical study using confocal laser scanning microscopy.
Recent studies have demonstrated the presence in psoriatic skin of ultrastructural and molecular alterations in the basement membrane and an altered polarized distribution of the integrins. Previous studies have demonstrated the existence of some epithelial cell lines synthesizing only laminin beta and gamma chains that, in the absence of the laminin alpha chain, do not form a distinct basal lamina. To investigate a possible reduction/absence of the laminin alpha 1 chain in keratinocytes in psoriatic skin and to correlate this with fibronectin distribution. Using monoclonal antibodies against the laminin alpha1 chain or human plasma fibronectin and using confocal laser scanning microscopy, we evaluated the immunohistochemical expression of these two proteins in cutaneous biopsies from involved and uninvolved skin of the sacral region of 12 men with extensive chronic plaque psoriasis. Site-matched biopsies of normal skin from four men without psoriasis were used as controls. In normal skin antilaminin alpha 1 chain antibodies stained the dermal-epidermal junction in a regular and continuous manner. In involved and uninvolved psoriatic skin large regions of discontinuous immunostaining were observed, mainly at the apex of the dermal papillae; in the same regions, clusters of keratinocytes appeared markedly reactive and fibronectin was overexpressed in the papillary dermis under the interruptions of the basement membrane. The present study defines the location of the laminin alpha1 chain in involved and uninvolved psoriatic skin and suggests a possible role of the alteration of this chain, together with T-cell lymphokines and fibronectin, in the dysregulation of cell morphological processes.


Isolation and structural properties of murine SAA--the acute phase serum precursor of amyloid AA.
The murine serum protein SAA, has been found to have a structure similar to human SAA, the precursor of human secondary amyloid fibril protein AA. SAA is detected by its cross-reaction in radioimmunoassay with antibodies raised to denatured amyloid fibrils of protein AA isolated from tissues of mice with amyloidosis. Murine SAA exists in the native state as a 160,000 molecular weight species, and can be isolated as a 12,500 molecular weight moiety, SAAL, by gel filtration in 10% formic acid. The quaternary structure of SAA is such that its AA determinants are relatively inaccessible for immunoreaction. Unfolding of these determinants can occur spontaneously; however, it is promoted by dissociation of SAA to SAAL.


Integrating Theranostics Into Patient Care Pathways: AJR Expert Panel Narrative Review.
Theranostics describes the coupling of a diagnostic biomarker and a therapeutic agent (i.e., a theranostic pair) that have a common target in tumor cells or their microenvironment. The term is increasingly associated with in vivo nuclear medicine oncologic applications that couple diagnostic imaging by means of gamma radiation with concomitant localized high-energy particulate radiation to a tissue expressing the common target. Several theranostic pairs have been translated into clinical practice in the United States and are poised to become a mainstay of cancer treatment. The purposes of this article are to review experience with theranostics for solid-organ malignancies and to address the practical integration into care pathways of β-emitting therapies that include somatostatin analogue radioligands for neuroendocrine tumors, PSMA-directed therapy for prostate cancer, and 131I-MIBG therapy for tumors of neural crest origin. Toxicities related to theranostics administration and indications for cessation of therapy in patients who experience adverse events are also discussed. A multidisciplinary team-based approach for identifying patients most likely to respond to these agents, determining the optimal time for therapy delivery, and managing patient care throughout the therapeutic course is critical to the success of a radiotheranostic program.


Ulnar Nerve Compression at the Elbow Secondary to Intramuscular Lipoma of the Flexor Carpi Ulnaris: A Case Report.
A 62-year-old right-hand-dominant woman presented with 1 year of persistent radiating pain, weakness, and paresthesias in her left forearm and hand. Electromyography findings were significant for ulnar neuropathy distal to the branch innervating the flexor carpi ulnaris (FCU), without superimposed cervical radiculopathy or other focal entrapment neuropathy. During open ulnar nerve neurolysis, an intramuscular lipoma was encountered within the FCU. Lipoma excision and cubital tunnel release with ulnar nerve transposition were performed with complete relief of neuropraxia. We demonstrate full neurologic recovery after intramuscular lipoma excision and cubital tunnel release. Although rare, anomalous anatomy and tissue overgrowth should remain on the differential for patients presenting with atypical neuropraxia.


The construction of high efficient visible-light-driven 3D porous g-C3N4/Fe3O4 photocatalyst: A new photo-induced bacterial inactivation material enhanced by cascade photo-Fenton reaction.
Photocatalytic disinfection is considered a promising method for eliminating the hazards of pathogenic bacteria. Graphitic carbon nitride (g-C3N4) is an ideal photocatalytic bacterial inactivation material for its advantage of tunable band structure, good stability and easy preparation. This work has constructed a novel defective 3D porous g-C3N4 by cyanamide carbonation using dendritic mesoporous silica template. The direct loading of Fe3O4 nanoparticles provided an excellent pg-C3N4-Fe3O4 photocatalyst suitable for water disinfection. Compared to pristine g-C3N4, the prepared 3D porous defective g-C3N4-Fe3O4 exhibited the enhanced visible light absorbance as indicated by the band gap decreasing of 0.66 eV, and about 3 and 10 fold increase of photo-induced current response and O2 adsorption respectively. The pg-C3N4-Fe3O4 showed excellent visible-light-driven photocatalytic bactericidal activity. It could kill 1 × 107 cfu mL-1Escherichia coli completely within 1 h under visible-light illumination (100 mW cm-2) with good reusability, its logarithmic bacterial inactivation efficiency was about 2.5 fold higher than pg-C3N4. The enhanced bactericidal performance is mainly ascribed to the Fe3O4 involved cascade photo-Fenton reaction.


Outpatient drug oversupply at a teaching hospital in Thailand.
A part of rising drug expenditure in Thailand was causedfrom drug oversupply, which was a result from policy of civil servants to get direct reimbursement from Ministry ofFinance. Describe the problem oforal drug oversupply at outpatient service in a teaching hospital and determine the cost that affects hospital between October 1, 2008 and September 30, 2009. Data of oral drug prescribing for outpatients were retrievedfrom the hospital database in the format of Microsoft Visual Fox Pro 9.0 and analyzed by Microsoft Access 2007. Two assessment methods are applied to estimate drug oversupply more than 30 days, by month and by year. In addition, September 2009 was selected to study for a pattern of monthly drug oversupply. Total oversupply expenditure for fiscal year 2009 was 56.9 million Baht when summedfrom monthly basis and 62.0 million when performed as a whole year. Oversupply expenditure was 2.12 to 2.73%per month in term of money and 2.91 to 3.46% in term of quantity. In September 2009, cardiovascular & hematopoietic system had the most oversupply. By brand of drug, the most frequently oversupply were Calcium carbonate (7.60%), Simvastatin (3.69%) and Omeprazole (3.20%). In term of money, the top three highest costs were for Atorvastatin (7.27%), Clopidogrel (6.83%) and Rosuvastatin (4.24%). By health schemes, patients under CSMBS trend to be the most of prescribed drug oversupply at 8.31% (3.21 million Baht in September 2009) with average number of oversupply per patient at 1.83 items and average day left per drug item at 61.83 days. The most oversupply expenditures were for chronic diseases. These data will focus the problem for hospital administrators to plan for suitable strategy to control drug oversupply in their hospital.


Evaluation of the fate of Lactobacillus crispatus BC4, carried in Squacquerone cheese, throughout the simulator of the human intestinal microbial ecosystem (SHIME).
Lactobacillus crispatus strain BC4, isolated from the human healthy vaginal environment and characterised by a strong antimicrobial activity against urogenital pathogens and foodborne microorganisms, was employed as a probiotic culture in the cheesemaking of the soft cheese Squacquerone. Such cheese is intended as a "gender food", that could be used as a hedonistic dietary strategy to reduce the incidence of woman vaginal dysbiosis and infections, given the evidence that a probiotic strain able to survive to the entire digestive process once ingested, can pass from intestine to vagina. This work was aimed to evaluate the resistance of L. crispatus BC4, carried in Squacquerone cheese, to different challenges of the human gastrointestinal tract, including the colon stage. The digestion process was tested using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). The viability and metabolic activity of L. crispatus BC4 during the colon simulation were monitored by qPCR and gas chromatography, respectively, also in the presence of a complex microbiota. The results showed that L. crispatus BC4 survival was not affected by the gastric condition, while it was significantly affected by bile salts and pancreatic juice in small intestine conditions, where it decreased of approx. 0.6 log (colony-forming units) CFU/g. Differently, during colon simulation L. crispatus BC4 was able to grow in sterile colon conditions and to maintain viability in the presence of a complex microbiota. Moreover, during colon simulation, L. crispatus BC4 was metabolically active as demonstrated by the higher production of short chain fatty acids (SCFA) and lactate. In the presence of a complex gut microbiota, a decrease of lactate was observed, due to its conversion into propionate (anti-cholesterol activity) and butyrate (anti-inflammatory activity) by cross-feeding. However, no differences in propionate and butyrate production could be observed between control cheese and cheese containing L. crispatus BC4. Despite this may appear as a negative outcome, it must be taken into account that, in this setup, only a single dose of the cheese was tested and the outcome of the colonization and impact of the gut microbiota might be different when daily repeated doses are tested.


Identification of functional rare variants in genome-wide association studies using stability selection based on random collapsing.
Genome-wide association studies are a powerful approach used to identify common variants for complex disease. However, the traditional genome-wide association methods may not be optimal when they are applied to rare variants because of the rare variants' low frequencies and weak signals. To alleviate the difficulty, investigators have proposed many methods that collapse rare variants. In this paper, we propose a novel ranking method, which we call stability selection based on random collapsing, to rank the candidate rare variants. We use the simulated mini-exome data sets of unrelated individuals from Genetic Analysis Workshop 17 for the analysis. The numerical results suggest that the selection based on a random collapsing method is promising for identifying functional rare variants in genome-wide association studies. Further research to examine the error control property of the proposed method is underway.


Complications of spinal and epidural anesthesia.
In conclusion, major complications after neuraxial techniques are rare but can be devastating to the patient and the anesthesiologist. Prevention and management begin during the preoperative visit with a careful evaluation of the patient's medical history and appropriate preoperative discussion of the risks and benefits of the available anesthetic techniques. Alternative anesthetic techniques, such as peripheral regional techniques or general anesthesia, should be considered for patients at increased risk for neurologic complications following neuraxial block. The decision to perform a regional anesthetic technique on an anesthetized patient must be made with care, as these patients are unable to report pain on needle placement or injection of local anesthetic. Efforts should also be made to decrease neural injury in the operating room through careful patient positioning. Postoperatively, patients must be followed closely to detect potentially treatable sources of neurologic injury, including expanding spinal hematoma or epidural abscess, constrictive dressings, improperly applied casts, and increased pressure on neurologically vulnerable sites. New neurologic deficits should be evaluated promptly by a neurologist, or neurosurgeon, to document formally the patient's evolving neurologic status, arrange further testing or intervention, and provide long-term follow-up.


Recurrent pneumothorax: A rare complication of miliary tuberculosis.
Recurrent pneumothorax is common in cavitory pulmonary tuberculosis, but it is extremely rare in miliary tuberculosis. A 25 year old female patient presented to us with the complains of shortness of breath since 3 days. She was also having fever and cough since 3 months. Chest roentgenogram (PA view) on admission showed a left sided pneumothorax with miliary mottling. An intercostals tube drainage was done on the left side resulting in relief of symptoms. Two days post intercostals tube drainage chest X ray (PA view) showed complete resolution of pneumothorax, and intercostals tube was removed. Patient was discharged on antitubercular drugs. After 1 month patient again presented to us with severe breathlessness, on repeat chest X ray pneumothorax again developed on left side, urgent intercostals tube drainage was done, and patient relieved immediately. Patient was kept in the hospital for 12 days and, and was discharged after intercostals tube removal. If a patient of miliary tuberculosis presents with shortness of breath diagnosis of pneumothorax should be considered.


Electromyogram median frequency, spectral compression and muscle fibre conduction velocity during sustained sub-maximal contraction of the brachioradialis muscle.
Changes in the median frequency of the power spectrum of the surface electromyogram (EMG) are commonly used to detect muscle fatigue. Previous research has indicated that changes in the median frequency are related to decreases in muscle fibre conduction velocity (MFCV) during sustained fatiguing contractions. However, in experimental studies the median frequency has been consistently observed to decrease by a relatively greater amount than MFCV. In this paper, a new estimate of EMG frequency compression, the Spectral Compression Estimate (SCE), is compared with the median frequency of the EMG power spectrum, the median frequency of the EMG amplitude spectrum and MFCV measured during sustained, isometric, fatiguing contractions of the brachioradialis muscle at 30, 50 and 80% maximum voluntary contraction (MVC). The SCE is found to provide a better estimate of the observed changes in MFCV than the median frequency of either the EMG power spectrum or EMG amplitude spectrum.


Bile acid synthesis: down-regulation by monohydroxy bile acids.
The regulation of bile acid synthesis was studied in rabbits after interruption of the enterohepatic circulation by choledochoureteral anastomosis. Total daily bile acid output was 772 +/- 130 (SD) mumol/24 h, of which greater than 95% was glycocholic acid. Administration of deoxycholic or cholic acid or their conjugates (300-800 mumol) or gall-bladder bile failed to down-regulate endogenous bile acid synthesis. In contrast, chenodeoxycholic acid administration did down-regulate bile acid synthesis, but this effect was related to the formation and excretion of lithocholic acid. This observation was confirmed by the finding that i.v. infusion of 10-20 mumol of either lithocholic acid or 3 beta-hydroxy-5-cholenoic acid significantly reduced cholic acid synthesis. Thus monohydroxy bile acids, derived from either hepatic or intestinal sources, participate in the down-regulation of bile acid synthesis.


Determination of malarial antibodies by means of screening and differentiating antigens.
4455 human sera with malarial antibodies were analysed with regard to their reactivity to screening antigens (Plasmodium fieldi and P. falciparum) and to differentiating antigens (P. vivax, P. ovale and P. malariae/brasilianum). Results were obtained by indirect fluorescent antibody test. The identification rate of antibodies was significantly higher with P. fieldi than with P. falciparum antigen, and was lowest for both of the screening antigens in sera with antibodies to P. ovale. The highest cross reactivity was between P. vivax and P. fieldi, the lowest between P. falciparum and P. fieldi. The majority of sera not reactive to screening antigens was reactive to P. ovale. The reactivity of sera to one of the screening antigens was higher in the group of immigrants from malaria endemic areas in comparison to European travellers, the overall pattern of results, however, was similar in both groups of patients.


Treatment of FIGO 2018 stage IIIC cervical cancer with different local tumor factors.
To compare the oncological outcomes of patients with FIGO 2018 stage IIIC cervical cancer (CC) involving different local tumor factors who underwent abdominal radical hysterectomy (ARH), neoadjuvant chemotherapy and radical surgery (NACT), or radical chemoradiotherapy (R-CT). Based on tumor staging, patients with stage IIIC were divided into T1, T2a, T2b, and T3 groups. Kaplan-Meier and Cox proportional hazards regression analysis were used to compare their overall survival (OS) and disease-free survival (DFS) of 5 years. We included 4,086 patients (1,117, 1,019, 869, and 1,081 in the T1, T2a, T2b, and T3 groups, respectively). In the T1 group, NACT was correlated with a decrease in OS (hazard ratio [HR] = 1.631, 95% confidence interval [CI]: 1.150-2.315, P = 0.006) and DFS (HR = 1.665, 95% CI: 1.255-2.182, P < 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.226 and P = 0.921) or DFS (P = 0.343 and P = 0.535) than R-CT. In the T2a group, NACT was correlated with a decrease in OS (HR = 1.454, 95% CI: 1.057-2.000, P = 0.021) and DFS (HR = 1.529, 95% CI: 1.185-1.974, P = 0.001) than ARH. ARH and NACT were not correlated with OS (P = 0.736 and P = 0.267) or DFS (P = 0.714 and P = 0.087) than R-CT. In the T2b group, NACT was correlated with a decrease in DFS (HR = 1.847, 95% CI: 1.347-2.532, P < 0.001) than R-CT nevertheless was not correlated with OS (P = 0.146); ARH was not correlated with OS (P = 0.056) and DFS (P = 0.676). In the T3 group, the OS rates of ARH (n = 10), NACT (n = 18), and R-CT (n = 1053) were 67.5%, 53.1%, and 64.7% (P = 0.941), and the DFS rates were 68.6%, 45.5%, and 61.1%, respectively (P = 0.761). R-CT oncological outcomes were not entirely superior to those of NACT or ARH under different local tumor factors with stage IIIC. NACT is not suitable for stage T1, T2a, and T2b. Nevertheless ARH is potentially applicable to stage T1, T2a, T2b and T3. The results of stage T3 require confirmation through further research due to disparity in case numbers in each subgroup.


Neonatal hypothermia detection by ThermoSpot in Indian urban slum dwellings.
To look at the performance of ThermoSpot liquid crystal thermometry in detecting neonatal hypothermia. A comparison was made between skin temperatures taken by ThermoSpot and axillary temperatures taken by digital electric thermometry. Non-medically trained local volunteers performed daily paired recordings on infants on days 1, 2, 3, 4, 5, 6, and 7 of life. This is a non-hospital based study set in the homes of neonates in an underprivileged urban slum community in the developing world. babies born at home. hospital admission; parental refusal. The ThermoSpot was stuck to the neonate's abdomen over the liver area on day 1 and removed on day 7. Fixed test properties of ThermoSpot. Over 180 paired observations, the fixed test properties of ThermoSpot in the detection of hypothermia were: sensitivity 88%; specificity 97%; positive likelihood ratio 29; negative likelihood ratio 0.13. ThermoSpot performed well when used by non-medically trained volunteers for the detection of neonatal hypothermia in the homes of an urban slum community.


Cloning and expression of a Streptomyces plicatus chitinase (chitinase-63) in Escherichia coli.
4-Methylumbelliferyl (4-MU) glycosides of N-acetylglucosamine oligosaccharides were used as substrates to detect expression of a Streptomyces chitinase in Escherichia coli. Low levels of enzyme were detected when S. plicatus DNA was cloned into a bacteriophage lambda vector (EMBL-4). Subcloning into E. coli plasmids also gave low but detectable levels of enzyme expression. High level expression was achieved by resection of the cloned S. plicatus DNA with Bal31 followed by in-frame fusion to the amino-terminal peptide sequence of beta-galactosidase found in the pUC vectors. The Streptomyces chitinase was secreted into the periplasmic space of E. coli, and its signal sequence was removed. We characterized the activity of the cloned enzyme and compared it to three other purified Streptomyces plicatus chitinases with respect to hydrolysis of the 4-MU oligosaccharides. We found that two of the enzymes form 4-methylumbelliferone much more rapidly from the 4-MU disaccharide than from the trisaccharide. These same enzymes convert the 4-MU trisaccharide primarily to diacetylchitobiose and the 4-MU monosaccharide, a nonfluorescent product. The latter compound is not hydrolyzed appreciably by any of the enzymes. On the basis of these results, we suggest a new definition of "exo" and "endo" chitinase that differs from that found in the literature. We propose that exochitinase activity be defined as processive action starting at the nonreducing ends of chitin chains with release of successive diacetylchitobiose units, and that endochitinase activity be defined as random cleavage at internal points in chitin chains.


Maternal sevoflurane exposure affects neural stem cell differentiation in offspring rats through NRF2 signaling.
Studies have shown that sevoflurane, a halogenated inhalational anesthetic, interferes with neurogenesis in the developing rodent brain. However, the mechanisms by which sevoflurane affects neural stem cells (NSCs) differentiation require further elucidation. Pregnant rats (gestational day 14) were anesthetized with 3.5% sevoflurane for 2 h, with or without ML385 pretreatment. ML385 is a specific nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor. NRF2 expression and the downstream Sonic Hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) signaling cascade were determined by western blotting in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure. Immunofluorescence and western blotting were performed to evaluate NSC neuronal and astrocytic differentiation in fetal brain tissues at 24 h and 72 h post-anesthesia as well as in the hippocampus on postnatal day (P) 28. Nissl staining was performed to measure the neuronal density on P28. Morris Water Maze tests were used to evaluate learning and memory function on P28-33. Neuronal and astrocytic differentiation of NSCs was markedly promoted in the fetal brain at 24 h and 72 h after maternal sevoflurane exposure, accompanied by upregulated NRF2. However, neuronal reduction and astrocyte proliferation were observed in the rat hippocampus at P28. Pretreatment with ML385 reversed sevoflurane-induced premature differentiation of NSCs, accompanied by suppression of SHH/GLI1 signaling. Furthermore, ML385 rescued sevoflurane-induced decreased neuronal density and impaired learning and memory function in the offspring. Prenatal sevoflurane exposure promotes neuronal and astrocytic differentiation of NSCs in the fetal rat brain, leading to long-term neuron reduction but astrocyte proliferation in the postnatal rat hippocampus. Prenatal sevoflurane exposure modulates NSC differentiation through NRF2/SHH/GLI1.


Manure- and straw-derived biochars reduce the ecological risk of PBDE and promote nitrogen cycling by shaping microbiomes in PBDE-contaminated soil.
Pyrolysis of agricultural waste into biochar for soil remediation is a useful solid waste management strategy. However, it is still unclear how different agricultural feedstocks affect the properties of biochars and their effectiveness in remediation of PBDE-contaminated soil. In this study, we systematically investigated dynamic alterations of soil properties, microbial communities, and PBDE dissipation and bioavailability induced by the application of biochars from manure (MBC) and straw (SBC) to PBDE-contaminated soil. The results showed that soil properties, microbial community structure, and diversity changed differently with the incorporation of the two biochars. MBC had a larger surface area (17.4 m2/g) and a higher nutrient content (45.1% ash content), making it more suitable for use as a soil additive to improve soil quality and nutrient conditions, as well as to stimulate microbial growth. SBC showed higher adsorption capacity for 2,2',4,4'-Tetrabromodiphenyl Ether (BDE-47) (26.73 ± 0.65 mg/g), thus lowering the bioavailability and ecological risk of BDE-47 in soil. BDE-47 was stepwise debrominated into lower brominated PBDE by PBDE-degrading bacteria. MBC accelerated the debromination of BDE-47 (10.1%) by promoting PBDE-degrading microorganisms, while this was inhibited by SBC (3.5%) due to strong adsorption of BDE-47. In addition, we found that both types of biochar favored Nitrospirae bacteria and promoted N cycling. Overall, biochars from manure and straw can positively shape soil microbial communities differently by altering soil properties, soil fertility and nutrient availability, and the fate and the effects of contaminants, which ultimately led to a difference in the potential of biochars for their use in soil remediation.


Determination of 4-aminophenol impurities in multicomponent analgesic preparations by HPLC with amperometric detection.
A method for the determination of 4-aminophenol, the main impurity of paracetamol, by high-performance liquid chromatographic (HPLC) method with amperometric detection has been developed. The analysis was performed in an isocratic mode on a reversed phase Luna column 5 microm C-18 (100 x 4.6 mm). A mobile phase (0.05 mol l(-1) LiCl solution containing 18% methanol adjusted to pH 4.0 with orthophosphoric acid) was suitable for the separation and determination of 4-APh. Chromatograms were recorded for 250 s by means of an amperometric detector at a potential of +325 mV of the glassy carbon electrode versus the reference electrode Ag/AgCl. The proposed liquid chromatographic method was successfully applied to the analysis of commercially available multicomponent dosage forms. The sensitivity of the detection for 4-aminophenol was 1 ng ml(-1) for substance and 4 ng ml(-1) for tablets or capsules. The method developed in this study is sensitive and selective and can be applied for routine studies of pharmaceuticals in the form of tablets or capsules.


Fabrication of cellulose/rectorite composite films for sustainable packaging.
In order to reduce the environmental pollution caused by plastic packaging, the development of biodegradable high-performance packaging materials has become a research hotspot. Cellulose is a promising food packaging material, but it usually lacks sufficient ultraviolet (UV) shielding property and mechanical strength. In this work, rectorite microplates were incorporated into the cellulose matrix by a facile blending method to fabricate the composite films. The structure and properties of the composite films were characterized by FT-IR, X-ray diffraction, scanning electron microscopy, UV-vis and mechanical properties test etc. The results indicated that rectorite microplates were uniformly distributed in the cellulose matrix. The blocking percentages for UVA and UVB for the cellulose/rectorite composite film with 14 wt% rectorite content (RCRF-14) could reach as high as 97.8 % and 96.0 %, respectively, showing a good UV shielding property. Meanwhile, the addition of rectorite obviously improved the mechanical properties and decreased the water vapor and oxygen permeabilities of the cellulose film, showing a potential application as a sustainable food packaging material.


Cell membrane vesicles as a tool for the study of direct epithelial-stromal interaction: lessons from CD147.
Communication between the epithelial and stromal tissue layers, separated by basement membrane, is known to provide the information necessary for development, differentiation, and homeostasis. These interactions are altered in benign or malignant diseases, in particular when the basement membrane barrier is disrupted allowing a greater proximity between the two cell layers that triggers tissue remodeling. Epithelial-stromal interactions (ESI) have been examined in vitro by various approaches that can be broadly divided into interactions arising from secreted diffusible factors and interactions through direct cell-cell contact. Here we describe a method for the study of direct ESI through CD147, an adhesion molecule present on the epithelial cell surface and which is known to interact with stromal cells, such as fibroblasts and endothelial cells, and signal them to increase production of matrix metalloproteinases. This method can be extended to other adhesion molecules involved in ESI.


Extracellular Vesicles Derived from Intermittent Hypoxia-Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression.
Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, has been known as a dominant cause of OSA-related endothelial dysfunction and hypertension. However, the underlying mechanism still remains unclear. Extracellular vesicles (EVs), small vesicles secreted by various cells, can be absorbed by endothelial cells and then influence vascular function. The aim of this research is to clarify whether and how EVs shedding from red blood cells (RBCs) are involved in IH-induced endothelial dysfunction. EVs were extracted by ultracentrifugation. After the identification of property and purity, EVs from IH-exposed RBCs (IH REVs) and normoxia-exposed RBCs (NOR REVs) or from OSA and non-OSA patient RBCs were utilized to treat C57BL/6 mouse aortas or human umbilical vein endothelial cells (HUVECs) for mechanistic exploration. Functional results demonstrated that REVs from OSA patients dramatically impaired endothelium-dependent relaxations (EDRs). Similarly, in vivo and ex vivo studies showed that IH REVs caused significant endothelial dysfunction compared to control group. Further results presented that IH REVs blocked endothelial nitric oxide synthase (eNOS) phosphorylation through inhibiting PI3K/Akt pathway and enhanced endothelin-1 (ET-1) expression through activating Erk1/2 pathway in endothelial cells. Meanwhile, endothelial dysfunction caused by IH REVs was reversed by Akt activator SC79 as well as Erk kinase inhibitor PD98059, suggesting that PI3K/Akt/eNOS and Erk1/2/ET-1 pathways were implicated in IH REV-induced impaired EDRs. This study reveals a novel role of REVs in endothelial dysfunction under IH and dissects the relevant mechanism involved in this process, which will help to establish a comprehensive understanding of OSA or IH-related endothelial dysfunction from a new scope.


Pacritinib: First Approval.
Pacritinib (VONJO™) is an orally administered, small molecule kinase inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis and graft-versus-host disease. Pacritinib received its first approval in February 2022 in the USA for the treatment of adults with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L. The accelerated approval was based on results from the randomized, active-controlled, phase III PERSIST-2 trial, in which spleen volume reduction was demonstrated in pacritinib recipients. This article summarizes the milestones in the development of pacritinib leading to this first approval for myelofibrosis.


Four new species of the subfamily Homoneurinae (Diptera, Lauxaniidae) from southwestern China.
Four species of Homoneurinae from southwestern China are described as new to science: Cestrotus abdominalis sp. nov., Cestrotus albifacies sp. nov., Phobeticomyia motuoensis sp. nov., and Prosopophorella longa sp. nov. An updated key to the species of the genera Cestrotus, Phobeticomyia, and Prosopophorella recorded in China is presented.


Lumbar-spinal somatosensory evoked potentials in the rat after stimulation of the tibial nerve.
Spinal somatosensory evoked potentials after stimulation of the tibial nerve were recorded from the lumbospinal cord of rats. Their components and the respective latencies recorded over L5/6 and L1/2 in 40 normal animals are described. Using this method exact statements concerning lesions particularly of the proximal segment of the peripheral nerves and their roots can be made.


The art and design of genetic screens: Drosophila melanogaster.
The success of Drosophila melanogaster as a model organism is largely due to the power of forward genetic screens to identify the genes that are involved in a biological process. Traditional screens, such as the Nobel-prize-winning screen for embryonic-patterning mutants, can only identify the earliest phenotype of a mutation. This review describes the ingenious approaches that have been devised to circumvent this problem: modifier screens, for example, have been invaluable for elucidating signal-transduction pathways, whereas clonal screens now make it possible to screen for almost any phenotype in any cell at any stage of development.


A rare cause of acute intestinal obstruction: Ileo-sigmoid knotting type IIA.
Ileosigmoid Knotting is a rare cause of intestinal obstruction which occurs as a consequence of ileum or sigmoid colon wrapping around the base of each other resulting in double closed-loop bowel obstruction. We report a case of a 52-year-old male who presented in the emergency department with sudden onset of abdominal pain and vomiting. On clinical examination, the abdomen was tender and distended. A chest and abdomen x-ray showed a distended stomach and no sign of bowel obstruction. A computed tomographic scan (CT) revealed a closed-loop intestinal obstruction. We planned urgent Surgery, and the finding was an Ileosigmoid knotting typeIIA is rarely encountered in surgical practice.


3D Living Dressing Improves Healing and Modulates Immune Response in a Thermal Injury Model.
Thermal injury trauma can induce a state of immunosuppression, causing wounds to become chronic in nature. Stem cell-based therapies represent a promising new approach to treat such wounds due to their capacity to self-renew and their multi-lineage potential. Mesenchymal stem cells (MSCs) are known to secrete endogenous factors that stimulate wound healing by promoting angiogenesis, extracellular matrix remodeling, skin regeneration, and by dampening down inflammation. MSC delivery in a biomaterial construct can augment their wound-healing capacity by concentrating cells at the burn site and upregulating trophic factor secretion. The work presented is the first to evaluate repair in an in vitro raft thermal injury model using a regenerative, dual cell delivery three-dimensional (3D) core/shell (c/s) "living dressing" construct. This previously characterized 3D c/s bioprinted construct, which delivers both MSCs and endothelial cells, was used to treat an in vitro 3D raft skin thermal injury wound model. The mesenchymal stromal cell line (T0523) was encapsulated within a gelatin-based shell bioink, and human umbilical vein endothelial cells within a chitosan-based core bioink to biofabricate a living dressing for enhanced thermal injury repair and regeneration. We hypothesized that the cell-laden c/s tissue engineered construct (TEC) would strengthen the wound's proangiogenic, anti-inflammatory, and skin regeneration potential. An in vitro thermal injury in a 3D raft skin model showed a slight delay in wound closure in the presence of the c/s TEC but was augmented by corresponding increases in the release of wound-healing factors, epidermal growth factor, matrix metalloproteinases-9, transforming growth factor-α, platelet-derived growth factor; a decrease in pro-inflammatory factor interleukin-6, and evidence of neovascularization.


Naloxone in renal ischemia: a functional and microanatomical study.
Naloxone HCl (Nx) improves cardiopulmonary performance, reverses cellular hypoxia, and stabilizes lysosomal membranes in shock states. However, no detailed study has yet explored its potential role in renal ischemia, which is inevitable in transplantation and surgical and nonsurgical conditions associated with hypotension and shock. This functional and microanatomical study was carried out on dogs subjected to renal warm ischemia with contralateral nephrectomy. Group I (control; N = 4) had bilateral renal dissection and right nephrectomy. Groups II-IV had their kidney pedicles cross-clamped for 60 min and then reperfused. Group II (N = 9) ischemic kidneys received no treatment. Group III (N = 6) kidneys were flushed with pure Nx HCl (2 mg/kg) during ischemia. Group IV (N = 6) dogs received one iv Nx bolus (2 mg/kg) before clamping and another dose before declamping. Biopsies for adenine nucleotides, histology, and ultrastructure were obtained before ischemia, before reflow, and 15 min and 7 days after reflow. Serum creatinine and blood urea nitrogen were measured daily. Ischemia induced significant renal dysfunction, which was reversed by systemic Nx. Nx offered a remarkable protection against postischemic structural damage. Seventy percent of Group II cortical sections showed grade 4 acute tubular necrosis (ATN), and severe residual damage after a week. Eighty-three percent of Group IV sections showed grade 1 ATN and no residual damage after a week. One week survival was 33% in Group II and 100% in Group IV. Nx can be useful in prevention of acute renal failure in clinical situations with arterial hypotension and shock.


The reaction specificities of the pea and a cyanobacterial thylakoid processing peptidase are similar but not identical.
The thylakoid processing peptidase from the cyanobacterium Phormidium laminosum has been extracted from thylakoid membranes by solubilization with Triton X-100. Its reaction specificity has been compared with the analogous pea peptidase by processing in vitro of radiolabelled wheat and P. laminosum thylakoid lumenal precursor polypeptides. The cyanobacterial polypeptide is processed to the mature size through an intermediate by the P. laminosum peptidase, but to a polypeptide that has a slightly greater apparent molecular weight than the intermediate by the pea peptidase. Both peptidases correctly process the wheat polypeptide. This suggests that the reaction specificities of the two peptidases are similar, but not identical.


Cancer incidence among migrant populations in South Australia.
South Australian Cancer Registry data for 1977-1986 have been used to compare the incidence of cancer for overseas-born populations and for the State as a whole. British and Irish migrants were found to have a higher incidence of all cancer sites combined, largely because of elevations in the incidence of cancers of the lung, stomach and female breast, whereas southern-European migrants showed a lower incidence of cancer, mostly as a result of low incidence rates for cancers of the colon, prostate, lung (women only), melanoma and female breast. Differences in incidence also were evident by country of birth for cancers of the buccal cavity, oropharynx, nasopharynx, oesophagus, liver, larynx, pleura, testes, uterine body, bladder and kidney, and various lymphohaematopoietic cancers. The aetiological implications of these findings, particularly in relation to environmental and life-style factors, are considered.


Oxidation of M252 but not M428 in hu-IgG1 is responsible for decreased binding to and activation of hu-FcγRIIa (His131).
Oxidation of monoclonal therapeutic antibodies (mAbs) can affect binding to Fc-receptors and potentially influence pharmacokinetics or effector functions like e.g. antibody dependent cellular phagocytosis (ADCP). Recently, it has been demonstrated that binding to FcγRIIa (H131) is affected by methionine oxidation of the Fc-portion but it is currently unknown which methionine is responsible for decreased binding. We separated an oxidized IgG1 monoclonal antibody based on the oxidation state of methionine 252 and analyzed fractionated material in receptor binding experiments as well as in functional (cell-based) assays. Although the unfractionated mixture demonstrated weaker interaction/activation of the receptor, differently oxidized isolated subspecies can lead both to stronger as well as weaker binding and activation of the histidine variant of FcγRIIa.


Role of gap junctions in endothelium-derived hyperpolarizing factor responses and mechanisms of K(+)-relaxation.
We have examined the effects of ouabain (1 mM), the gap junction inhibitors, 18 alpha-glycyrrhetinic acid (100 microM), N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10 microM) and palmitoleic acid (50 microM), and clotrimazole (10 microM) against endothelium-derived hyperpolarizing factor (EDHF)-mediated and K(+)-induced vasorelaxations in the rat mesentery. In the presence of indomethacin (10 microM) and 300-microM N(G)nitro-L-arginine methyl ester (L-NAME), carbachol caused EDHF-mediated relaxations (R(max)=85.3+/-4.0%). In the presence of ouabain, these responses were substantially reduced (R(max)=11.0+/-2.3%). 18 alpha-glycyrrhetinic acid, SR141716A, palmitoleic acid and clotrimazole also significantly inhibited these EDHF-mediated responses. K(+) caused vasorelaxation of preparations perfused with K(+)-free buffer (R(max)=73.7+/-2.4%), which were reduced by 10-microM indomethacin (R(max)=56.4+/-6.2%). K(+) vasorelaxation was essentially abolished by endothelial denudation. Both ouabain and 18 alpha-glycyrrhetinic acid opposed K(+) relaxations, however, neither SR141716A, clotrimazole nor palmitoleic acid had any effect. Direct cell-cell coupling via gap junctions was attenuated by ouabain, clotrimazole and palmitoleic acid. We conclude that: (i) that gap junctional communication plays a major role in EDHF-mediated relaxations, (ii) that K(+)-vasorelaxation is endothelium-dependent (thus, K(+) is unlikely to represent an EDHF), and (iii) that the inhibitory actions of ouabain and clotrimazole on gap junctions might contribute towards their effects against EDHF.


Serum squamous cell carcinoma antigen levels in patients with invasive squamous vulvar and vaginal cancer: a preliminary report.
Pretreatment serum squamous cell carcinoma antigen (SCC) levels were obtained in 12 patients with invasive vulvar and 5 patients with invasive vaginal squamous cancer. Only 4 of 12 (33%) patients with vulvar cancer and 1 of 5 (20%) patients with vaginal cancer, usually those with more advanced disease, had elevated serum SCC levels at the time of diagnosis.


Livedo reticularis and nodules due to cholesterol embolism in the lower extremities.
A case is described of livedo reticularis and nodules, resembling polyarteritis nodosa but shown to be due to emboli of cholesterol crystals.


Indirect inhibitory effect of succinylcholine on acetylcholine-activated channel activities and its modulation by external Ca2+ in mouse skeletal muscles.
1. The effect of extracellular calcium on single acetylcholine (ACh)-activated channel activities when desensitizing concentrations of succinylcholine (SuCh) were applied to the surrounding endplate membrane was investigated by the cell-attached patch-clamp technique at endplates of single skeletal muscle (flexor digitorum brevis) fibres of adult mice. 2. Bath-applied SuCh (0.1-3 microM, in 2.5 mM Ca2+) increased in a concentration-dependent manner the mean open time of ACh-activated channel currents recorded at membrane potentials which cancelled the SuCh-induced depolarizations. 3. In the presence of 0.5 and 2.5 mM external Ca2+, SuCh (3 microM) applied outside the patch pipette prolonged the mean open time of ACh-activated channel currents in a time-dependent manner (by 45% and 52%, respectively), and simultaneously significantly decreased the single channel conductance (by 14% and 10%, respectively). These SuCh-induced effects did not occur in a nominally Ca(2+)-free extracellular medium. 4. Under the same conditions, SuCh (3 microM) augmented the time-dependent decline in the opening frequency of ACh-activated channel currents obtained in nominally Ca(2+)-free medium. 5. These results suggest that external calcium ions act to modulate nicotinic ACh receptor channel activity, and accelerate desensitization of the receptor.


A single segment substitution line population for identifying traits relevant to drought tolerance and avoidance.
A population of chromosome segment substitution lines was developed using KDML105 as the recurrent parent and one of DH212 (IR68586-F2-CA-143) or DH103 (IR68586-F2-CA-31) as the donor parent. The donor parents are part of a doubled haploid population from a cross between CT9993, an upland japonica accession, and IR62266, a lowland indica accession. Multiple QTL that are relevant to drought avoidance, drought tolerance and yield traits under drought stress were mapped in this doubled haploid population and the segments selected for the chromosome segment substitution lines were chosen to capture these QTL. The chromosome segment substitution line population was phenotyped under irrigated and mild drought stress conditions, which identified that many yield traits under drought stress had been introduced into the chromosome segment substitution lines.


Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion.
Intracellular recordings were obtained from the somata of type A and C primary afferents in the isolated bullfrog dorsal root ganglion (DRG) preparation. Bath application of serotonin (5-HT) in concentrations of 0.25-1.0 mM led to slow and fast depolarizing responses. Slow, maintained 5-HT depolarizations were observed in 47% of type A and 70% of type C neurons. These slow depolarizations were associated with an underlying increase in input resistance (Rin). In some type A neurons, the Rin increase was masked by a decrease in Rin due to depolarization-induced rectification. The slow 5-HT depolarization of type A, but not type C neurons showed pronounced tachyphylaxis to repeated 5-HT applications. In type C afferents, serotonin's slow action was often accompanied by spontaneous firing. Manganese decreased slow 5-HT depolarizations of both cell types. A slow depolarization and excitation of type C afferents by methysergide and cinanserin was also observed. Fast transient 5-HT depolarizations accompanied by a rapid decrease in Rin were observed in 7% of type A and 24% of type C neurons. In some DRG cells the fast and slow depolarizations combined to form a biphasic response. The actions of 5-HT reported here resemble in some ways 5-HT responses recorded extracellularly from the spinal terminations of primary afferents.


What factors affect documentation by midwives? A prospective study assessing relationship between length of shift, workload and quality of note keeping.
The objective of this study was to assess the association between the quality of basic note keeping and partogram documentation with progression of shift and workload on labour ward. This was a prospective observational study. The setting of this study was a labour ward of a teaching district hospital in an inner city London hospital. Intrapartum notes and partograms of 61 consecutive labouring women were assessed for quality of midwifery documentation at the beginning, middle and end of a 12-h shift. The measurements of this study were a basic note-keeping composite score based on validated criteria by the Nursing and Midwifery Record Keeping Guidance 2010 and a partogram completion score based on the National Institute for Clinical Excellence (NICE) Guidelines for Intrapartum Care 2007. The basic note keeping deteriorated between the middle and the end of the 12-h shift, but it appeared unaffected by workload, with no statistically significant difference between day and night shifts. Partogram documentation was poorer in the middle compared to the beginning of the shift, and there was no statistical difference between day and night shifts. Partogram completion appeared to be influenced by women: midwife ratio as well as progression through a shift. The basic note keeping and partogram documentation were best at the beginning of the shift, and fatigue may play a role in poorer documentation towards the middle and the end of the shifts. Appropriately scheduled breaks especially during the final third of the shifts may help improve the quality of documentation.


Rho family GTPase signaling through type II p21-activated kinases.
Signaling from the Rho family small GTPases controls a wide range of signaling outcomes. Key among the downstream effectors for many of the Rho GTPases are the p21-activated kinases, or PAK group. The PAK family comprises two types, the type I PAKs (PAK1, 2 and 3) and the type II PAKs (PAK4, 5 and 6), which have distinct structures and mechanisms of regulation. In this review, we discuss signal transduction from Rho GTPases with a focus on the type II PAKs. We discuss the role of PAKs in signal transduction pathways and selectivity of Rho GTPases for PAK family members. We consider the less well studied of the Rho GTPases and their PAK-related signaling. We then discuss the molecular basis for kinase domain recognition of substrates and for regulation of signaling. We conclude with a discussion of the role of PAKs in cross talk between Rho family small GTPases and the roles of PAKs in disease.


Treating an edentulous mandible with an implant-supported prosthesis with a shape-memory alloy abutment system.
This clinical report describes a treatment protocol for completely edentulous patients using digital implant planning for an all-on-4 treatment of both the maxilla and mandible as well as the use of a shape-memory alloy retention system to secure a complete-arch restoration to the mandible.


A Patient with a 40% Ejection Fraction Undergoes Atrioventricular Nodal Ablation for the Management of Atrial Fibrillation with Rapid Ventricular Rates. What Type of Device Should He Receive?
Patients with symptomatic atrial fibrillation not amenable to pharmacologic therapy or catheter ablation may be appropriate candidates for atrioventricular nodal (AVN) ablation and placement of a permanent pacemaker. The question arises as to whether to implant a right ventricular (RV)-only pacing device or a cardiac resynchronization therapy (CRT) device. This article examines 2 similar cases of patients presenting for AVN ablation who received RV-only pacing devices but had different clinical outcomes. This article discusses existing guidelines and studies that can help clinicians address the challenging question of whether an initial implant of a CRT pacing device is warranted in such patients.


Psychotic homicides in Copenhagen from 1959 to 1983.
During the years from 1959 to 1983, 263 Copenhagen defendants of homicide underwent a psychiatric examination for the court. Twenty-three percent of the defendants were held to be psychotic at the time of the crime. The psychotic defendants differed from the non-psychotic by being older, less often substance abusing and by choosing victims inside their families. It is discussed whether a reduction in the available number of psychiatric beds could be a contributional reason for the increase in especially the number of schizophrenic defendants. About one third of all defendants were by the examining psychiatrists found in need of a sanction different from ordinary punishment; furthermore, a tendency towards sanctions of treatment instead of just placement in a psychiatric hospital was documented and is discussed. The increasing demand of capacity for forensic, psychiatric patients is mentioned.


Topical ciprofloxacin versus topical fortified antibiotics in rabbit models of Staphylococcus and Pseudomonas keratitis.
We tested the antibacterial activity of ophthalmic 0.3% ciprofloxacin against that of 5.0% cefazolin and 1.36% tobramycin in two experimental models of keratitis, using a methicillin-sensitive strain of Staphylococcus aureus and an aminoglycoside-sensitive strain of Pseudomonas aeruginosa, respectively. Both corneas of New Zealand white rabbits were intrastromally injected with either S. aureus or P. aeruginosa. Twenty-four hours later, each eye was topically treated hourly for 24 hours. In the S. aureus model, the control group received Tears Naturale Free (Alcon Laboratories, Inc., Fort Worth, TX), the ciprofloxacin group received 0.3%, ciprofloxacin and the cefazolin group received 5.0% cefazolin. In the P. aeruginosa model, the control group received Tears Naturale Free, the ciprofloxacin group received 0.3% ciprofloxacin, and the tobramycin group received 1.36% tobramycin. One hour after the last eyedrops were administered, the rabbits were killed, and their corneas were processed for quantification of bacteria. For the S. aureus model, the mean (+/- SEM) colony forming units (CFU) of the control, 7.1 x 10(6) (+/- 4.0 x 10(6)); ciprofloxacin, 6.4 x 10(2) (+/- 1.6 x 10(2)); and cefazolin, 1.3 x 10(3) (+/- 1.8 x 10(2)) groups were different (F = 17.5; p = 0.001). The ciprofloxacin and cefazolin groups were not different from each other (p = 0.034). The mean (+/- SEM) CFU for the control group in the P. aeruginosa model was 2.8 x 10(8) (+/- 1.7 x 10(7)). All corneas in the ciprofloxacin and tobramycin groups were sterile.(ABSTRACT TRUNCATED AT 250 WORDS)


Apparatus for measuring the fall velocity of anemochorous diaspores, with results from two plant communities.
A simple and easy to handle apparatus for measuring the fall velocity of anemochorous diaspores is described. Plumed and winged diaspores from two plant communities of different densities and stabilities were compared. Diaspores of species from an unstable pioneer community had a significantly better flight ability than diaspores from a denser and more stable community.


Activation of the cGAS-STING pathway combined with CRISPR-Cas9 gene editing triggering long-term immunotherapy.
Effective activation of cGAS-STING pathway combined with immune checkpoint blockade (ICB) within the immunosuppressive tumor microenvironment to induce stronger immune responsiveness yet remains challenging. CRISPR-Cas9 gene editing technology, which offers the benefits of permanence and irreversibility, could recognize the target genome sequence with sgRNA (Guide RNA) and guide the Cas9 protease to knock down the target gene. Herein, a nanoplatform (HMnMPH) for dual activation of cGAS-STING pathway in combination with CRISPR-Cas9 gene editing to silence programmed death ligand 1 (PD-L1) to trigger long-term immunotherapy was reported. The HMnMPH consists of hollow manganese dioxide (HMn) loaded with STING agonist (MSA-2) and CRISPR-Cas9/sg-PD-L1 plasmid with further modification of hyaluronic acid (HA). In acidic and GSH overexpressed tumor environment, HMnPMH was degraded to release large amounts of Mn ions and STING agonists, strongly and persistently activating the cGAS-STING pathway to promote the release of type I interferon and pro-inflammatory factors. Meanwhile, the released CRISPR-Cas9 plasmid could knockdown the PD-L1 immune checkpoint and restart immunosuppressive T cells to differentiate into cytotoxic T lymphocytes significantly, which reduced the activity of primary and distal tumors and demonstrated a long-term immune memory effect on distal tumors.


MAST conversion of paroxysmal supraventricular tachycardia in Wolff-Parkinson-White syndrome.
A 48-year-old man with Wolff-Parkinson-White syndrome presented with paroxysmal supraventricular tachycardia. Prior episodes had required inpatient drug therapy or cardioversion. Attempts at conversion to normal sinus rhythm with vagal maneuvers were unsuccessful. Inflation of military antishock trousers resulted in rapid termination of the arrhythmia and avoidance of hospitalization.


Should chloroquine be laid to rest?
Chloroquine (CQ) has been the front line antimalarial drug due to its efficacy, low cost and scanty side effects, until resistance has evolved. Although its use has been officially discontinued in most malaria-affected countries, it is still widely used. Practical and pharmacological considerations indicate that it could be still used in semi-immune adults and that more efficient treatment protocols could be devised to treat even patients infected with CQ-resistant parasite strains. Since its antimalarial activity is pleiotropic, drug resistance may be due to different mechanisms, each amenable to reversal by drug combination.


Infantile congenital parotid lipomatosis: a rare case report.
A case of congenital parotid lipomatosis in an infant is reported and literature is reviewed. This rare condition in children presents as gradually increasing parotid swelling, which is difficult to diagnose preoperatively as this condition is not considered in the differential diagnosis of a parotid mass. Complete excision with superficial or total parotidectomy with preservation of facial nerve is the treatment of choice.


Pericentric inversions inv(2)(p11q13) and inv(2)(p13q11) in 2 unrelated families.
Pericentric inversions in chromosome 2 were traced in 2 unrelated North American black families. In the case of inv(2)(p13q11) no effect on reproduction was observed. In the case of inv(2)(p11q13) some reproductive abnormalities were noted which might be related to the inversion.


Aspartic acid and epidermal growth factor modified decellularized rabbit conjunctiva for conjunctival reconstruction.
Conjunctival reconstruction is an indispensable part of ocular surface regeneration. Decellularized matrix has been considered as an ideal conjunctival substitution for conjunctival reconstruction. In the present study, we report the use of a decellularized rabbit conjunctiva (DRC) for conjunctival reconstruction in the rabbit surgical trauma model. Prepared by the phospholipase A2 decellularized method, the DRC was nearly DNA free while the collagen structure and natural extracellular matrix (ECM) were well preserved. In order to improve the performance of DRC, aspartic acid (Asp) was used as a spacer arm to crosslink epidermal growth factor (EGF) on the DRC to obtain DRC-Asp-EGF. The conjunctival epithelial cells cultured on the DRC-Asp-EGF showed a higher survival rates and a greater potential to differentiate into conjunctival goblet cells (CGCs) than those on the DRC. Finally, three groups were set to evaluate the transplantation effects in the rabbit surgical trauma model for 28 days: DRC-Asp-EGF group, amniotic membrane (AM) group, and ungrafted group. The DRC-Asp-EGF group was completely re-epithelized, and more CGCs were regenerated than the AM group, while no significant improvements were observed in the ungrafted group. Intact collagen structure, angiogenesis, and no scar formation were also observed in the DRC-Asp-EGF group. These results suggest that DRC-Asp-EGF is a feasible and effective transplant for conjunctival reconstruction and ocular surface regeneration.


Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models.
Delphinidin (Del), [3,5,7,3'-,4'-,5'-hexahydroxyflavylium], an anthocyanidin and a potent antioxidant abundantly found in pigmented fruits and vegetables exhibits proapoptotic effects in many cancer cells. Here, we determined the effect of Del on growth, apoptosis and differentiation of normal human epidermal keratinocytes (NHEKs) in vitro in submerged cultures and examined its effects in a three-dimensional (3D) epidermal equivalent (EE) model that permits complete differentiation reminiscent of in vivo skin. Treatment of NHEKs with Del (10-40 μm; 24-48 h) significantly enhanced keratinocyte differentiation. In Del-treated cells, there was marked increase in human involucrin (hINV) promoter activity with simultaneous increase in the mRNA and protein expressions of involucrin and other epidermal differentiation markers including procaspase-14 and transglutaminase-1 (TGM1), but without any effect on TGM2. Del treatment of NHEKs was associated with minimal decrease in cell viability, which was not associated with apoptosis as evident by lack of modulation of caspases, apoptosis-related proteins including Bcl-2 family of proteins and poly(ADP-ribose) polymerase cleavage. To establish the in vivo relevance of our observations in submerged cultures, we then validated these effects in a 3D EE model, where Del was found to significantly enhance cornification and increase the protein expression of cornification markers including caspase-14 and keratin 1. For the first time, we show that Del induces epidermal differentiation using an experimental system that closely mimics in vivo human skin. These observations suggest that Del could be a useful agent for dermatoses associated with epidermal barrier defects including aberrant keratinization, hyperproliferation or inflammation observed in skin diseases like psoriasis and ichthyoses.


Increased retinal vascular tortuosity in gestational diabetes mellitus.
The authors report the first study which demonstrates that women with gestational diabetes mellitus (GDM) have increased tortuosity of their retinal vessels. Women with GDM underwent fundus photography and were compared with a normal control group (NC) and a pregnant nondiabetic control group (PC). Five ophthalmologists evaluated the unlabeled photographs, resulting in a combined mean prevalence of tortuosity of 21.6% NC, 24.7% PC, and 60.3% GDM. Statistical analysis showed that the GDM group was significantly different from both the NC and PC groups. Tortuosity was unrelated to acute elevation in blood glucose and was still present at 5 months postpartum.


Association of glucose-6-phosphate dehydrogenase deficiency and X-linked chronic granulomatous disease in a child with anemia and recurrent infections.
Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus-transformed B-lymphocytes from the proband was similar to healthy controls. Molecular studies showed that the G6PD deficiency was due a 202 G-->A mutation, the A- variant common in African ethnic groups. The proband also exhibited severely impaired respiratory burst activity, as observed in X-linked CGD. Sequence analysis of genomic DNA showed a 264 G-->A substitution at the 3' splice junction of gp91-phox exon 3. The cDNA sequence showed a deletion of gp91-phox exon 3, giving rise to an unstable or nonfunctional mutant gp91-phox and to the phenotype of X-linked CGD. We propose that clinicians treating a patient with G6PD deficiency during a severe infection episode consider the possibility of temporary or permanent impairment of the phagocytes' microbicidal activity and the eventual association of G6PD deficiency and chronic granulomatous disease.


Lack of association between COMT and working memory in a population-based cohort of healthy young adults.
The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene is an important regulator of dopamine in the prefrontal cortex, an area critical to working memory. Working memory deficits are present in several psychiatric disorders, and there is wide variation in working memory capacity in the normal population. Association studies of COMT and working memory in healthy volunteers have yielded inconsistent results, possibly because of small sample sizes. Here we examine COMT in relation to N-Back working memory task performance in a large population-based cohort of young adults. We predicted individuals with one or two copies of the Met allele would perform better, and that this relationship would be more evident in males than females. Participants (N=1857-2659) tested at 18 years of age, were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). We used multiple regression to examine effects of sex and COMT genotype on N-Back hits, false positives, discriminability (d'), and reaction time while controlling for important covariates. COMT genotype did not predict hits or d'. There was a nominally significant interaction between COMT and sex on false positives, but this was not in the predicted direction, and was not significant after controlling for covariates. COMT genotype was not related to working memory in this large population-based cohort. It is possible COMT is not meaningfully associated with working memory in healthy young adults, or that COMT effects are detectable only in assessments reflecting neural processes underlying cognition, such as fMRI, rather than in behavioral performance.


Impact of Concomitant Tricuspid Annuloplasty on Tricuspid Regurgitation, Right Ventricular Function, and Pulmonary Artery Hypertension After Repair of Mitral Valve Prolapse.
For patients undergoing mitral valve (MV) repair, the indications for and results of concomitant tricuspid annuloplasty remain controversial. This study was designed to compare a strategy of routine concomitant tricuspid annuloplasty for moderate tricuspid regurgitation (TR) or tricuspid annular dilation in patients undergoing degenerative MV surgery. Of 645 consecutive patients (mean age 57±13 years) undergoing primary repair of degenerative mitral regurgitation between 2003 and 2011, 419 (65%) underwent concomitant tricuspid annuloplasty for moderate TR and/or tricuspid annular dilation. These patients were retrospectively analyzed with longitudinal echocardiographic follow-up. Patients undergoing tricuspid valve repair were older (mean age 59.2 years vs. 52.3 years), had worse right and left ventricular function and higher pulmonary artery pressures, and were more likely to have had atrial fibrillation than patients undergoing isolated MV repair (all p<0.05). No significant difference in 30-day mortality, morbidity, or permanent pacemaker requirement was seen between treatment groups. Freedom from moderate TR at 7 years was not significantly different in the 2 groups, but multivariate analysis showed that tricuspid annuloplasty was independently associated with freedom from late moderate TR (p=0.04), and was an independent predictor of recovery of right ventricular function (p=0.02). In patients with moderate TR or tricuspid annular dilation who were undergoing degenerative mitral repair, concomitant tricuspid annuloplasty is safe, effective, and associated with improved long-term right-sided remodeling. Routine treatment of moderate TR or tricuspid annular dilation at the time of MV repair appears to be beneficial.


Synthesis and structure of a 3D porous network containing aromatic 1D chains of Li(6) rings: experimental and computational studies.
A bimetallic 3D network containing 1D chains of Li(6) unit rings has been synthesized by using a molybdenum containing metalloligand and the DFT calculations reveal that the rings are aromatic in behavior and resemble the corresponding hydrocarbon analogues.


Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics.
Cancer represents an evolutionary process through which growing malignant populations genetically diversify, leading to tumour progression, relapse and resistance to therapy. In addition to genetic diversity, the cell-to-cell variation that fuels evolutionary selection also manifests in cellular states, epigenetic profiles, spatial distributions and interactions with the microenvironment. Therefore, the study of cancer requires the integration of multiple heritable dimensions at the resolution of the single cell - the atomic unit of somatic evolution. In this Review, we discuss emerging analytic and experimental technologies for single-cell multi-omics that enable the capture and integration of multiple data modalities to inform the study of cancer evolution. These data show that cancer results from a complex interplay between genetic and non-genetic determinants of somatic evolution.


Labelling of diazepam-sensitive and -insensitive benzodiazepine receptors with [3H]tert-butyl-8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a][1,4]benzodiazepine 3-carboxylate (ZG-63).
A diazepam-insensitive subtype of benzodiazepine receptor has been identified in the cerebella of several species, including man. t-Butyl-8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine 3-carboxylate (ZG-63) was recently described as a selective, high affinity ligand at diazepam-insensitive benzodiazepine receptors. This compound was tritiated, and its properties as a radioligand evaluated in rat brain membranes. Consistent with the high affinity and selectivity described for the non-radioactive form of this compound, saturation analyses of [3H]ZG-63 binding to cerebellar diazepam-insensitive and other, diazepam-sensitive benzodiazepine receptors revealed Kd values of 2.6 +/- 0.2 nM and 10.6 +/- 1.4 nM, respectively. The density (Bmax) of cerebellar diazepam-insensitive receptors labelled with [3H]ZG-63 was not significantly different from values obtained with the prototypical diazepam-insensitive receptor ligand [3H]Ro 15-4513, representing approximately 30% of total cerebellar benzodiazepine receptors. [3H]ZG-63 also labelled cortical diazepam-sensitive benzodiazepine receptors, with Bmax values that were not significantly different from those obtained with [3H]flunitrazepam. Diazepam-insensitive benzodiazepine receptors in rat cerebral cortex could be detected with [3H]ZG-63, but the densities of these sites are a very minor component (< or = 5%) of total benzodiazepine receptors. In the presence of GABA, [3H]ZG-63 behaved as a 'gamma-aminobutyric acid (GABA) -positive', 'GABA-negative', and 'GABA-neutral' ligand at cortical diazepam-sensitive receptors, cerebellar diazepam-sensitive receptors, and cerebellar diazepam-insensitive benzodiazepine receptors, respectively. This profile differs from the prototype diazepam-insensitive receptor ligand, [3H]Ro 15-4513. Competition studies demonstrated a very high correlation (r2 = 0.98; P < 0.002) between the potencies of a series of benzodiazepine receptor ligands to inhibit [3H]ZG-63 and [3H]Ro 15-4513 binding to cerebellar diazepam-insensitive receptors. The high affinity and selectivity of [3H]ZG-63 for diazepam-insensitive receptors (diazepam-insensitive/diazepam-sensitive ratio of approximately 0.25) together with a GABA-shift profile which differs from Ro 15-4513 suggests that this compound may be useful in elucidating the function(s) of this benzodiazepine receptor subtype.


Nucleotide and deduced amino acid sequence of the hydrophobic surfactant protein SP-C from rat: expression in alveolar type II cells and homology with SP-C from other species.
Pulmonary surfactant lowers surface tension in the lung. Its deficiency leads to the severe physiologic abnormalities seen in the respiratory distress syndrome. The hydrophobic surfactant proteins, SP-B and SP-C, appear to be especially important in the surface-spreading characteristics of pulmonary surfactant. We report the nucleotide sequence of cDNA clones for rat SP-C and compare the deduced amino acid sequence for SP-C from several species. A highly conserved domain exists within the confines of mature human SP-C. An Eisenberg plot of this region predicts a membrane-associated helix. We also demonstrate by Northern analysis the tissue-specific expression of SP-C. A comparison of signal strength between total lung RNA and RNA derived from isolated type II cells supports the idea that most SP-C messenger RNA in total lung can be accounted for by that present in alveolar type II cells.


Endometriosis and associated symptoms among Nigerian women.
To determine the prevalence of endometriosis and identify associated symptoms among Nigerian women. A cross-sectional study was conducted at a center in Ibadan, Nigeria, between October 2008 and December 2010. All women aged 18-45 years scheduled for their first diagnostic laparoscopy for gynecologic indications were enrolled. Participants completed a previously validated self-administered questionnaire. Endometriosis was diagnosed on the basis of visual evidence. Among 239 women analyzed, 115 (48.1%) had endometriotic lesions. Endometriosis was more common among women reporting dysmenorrhea and pelvic pain than among those not reporting these symptoms (20/28 [71.4%] vs 95/211 [45.0%]; P=0.009). Women who reported dysmenorrhea were significantly more likely to have endometriosis than were those without dysmenorrhea (90/171 [52.6%] vs 25/68 [36.8%]; P=0.027). The risk of endometriosis was not significantly increased in women with one pain symptom (odds ratio [OR]1.69; 95% confidence interval [CI] 0.67-4.27), but was significantly increased in women with two (OR 2.70; 95% CI 1.13-6.52) or three (OR 4.87; 95% CI 1.88-12.82) pain symptoms (χ(2)trend=15.5; P<0.001). In a multivariate logistic regression model, only pain other than dysmenorrhea or dyspareunia independently predicted endometriosis (P=0.017). Endometriosis is fairly common among Nigerian women. Efforts to increase the awareness of endometriosis among the public, researchers, and clinicians are needed.


Clinical establishment of a laboratory developed quantitative HDV PCR assay on the cobas6800 high-throughput system.
Currently available HDV PCR assays are characterized by considerable run-to-run and inter-laboratory variability. Hence, we established a quantitative reverse transcription real-time PCR (RT-qPCR) assay on the open channel of a fully automated PCR platform (cobas6800, Roche) offering improved consistency and reliability. A primer/probe-set targeting a highly conserved region upstream of the HDV antigen was adapted for use on the cobas6800. The lower limit of detection (LLOD) was determined using a dilution panel of the HDV WHO standard (n = 21/dilution). Linearity and inclusivity were tested by preparing 10-fold dilution series of cell culture-derived virus (genotype [GT]1-8; n = 5/dilution). Patient samples containing a variety of bloodborne viral pathogens were tested to confirm exclusivity (n = 60). The LLOD of the HDV utility-channel (HDV_UTC) assay was determined as 3.86 IU/ml (95% CI 2.95-5.05 IU/ml) with a linear range from 10-10ˆ8 IU/ml (GT1). Linear relationships were observed for all HDV GTs with slopes ranging from -3.481 to -4.134 cycles/log and R2 from 0.918 to 0.994. Inter-run and intra-run variability were 0.3 and 0.6 Ct (3xLLOD), respectively. No false-positive results were observed. To evaluate clinical performance, 110 serum samples of anti-HDV-Ab+ patients were analyzed using the HDV_UTC and CE-IVD RoboGene assays. 58/110 and 49/110 samples were concordant positive or negative, respectively (overall agreement 97.3%). Quantitative comparison demonstrated a strong correlation (R2 0.8733; 95% CI 0.8914-0.9609; p value <0.0001). The use of highly automated, sample-to-result solutions for molecular diagnostics holds many inherent benefits over manual workflows, including improved reliability, reproducibility and dynamic scaling of testing capacity. The assay we established showed excellent analytical and clinical performance, with inclusivity for all HDV GTs and a limit of quantification of 10 IU/ml, making it a sensitive new tool for HDV screening and viral load monitoring. The hepatitis delta virus (HDV) causes a severe form of inflammation in the liver. We developed a tool for molecular diagnostics, a polymerase chain reaction HDV assay that showed great performance. It can be used to improve diagnosis of HDV, as well as for monitoring treatment responses. The assay allows for quantification of the virus in the tested samples and is performed on a fully automated platform (cobas6800), which provides various benefits including less hands-on time and excellent comparability of test results.


Frequency and duration of paratyphoid organism shedding by experimentally infected bobwhite quail (Colinus virginianus).
Four-week old bobwhite quail (Colinus virginianus) were experimentally infected with Salmonella urbana, S. infantis, S. newport, S. gaminara, S. braenderup, and S. litchfield. Rates of mortality varied from 0 to 50%. The rate of shedding of paratyphoid organisms varied from 14 to 100% for 18 or more days after infection. The maximum duration of shedding was 53 days by 12% of the quail infected with S. braenderup and the minimum duration was 18 days by 14% of the quail infected with S. litchfield.


MLL insertion with MLL-MLLT3 gene fusion in acute leukemia: case report and review of the literature.
A new chromosomal insertion involving the MLL gene was detected by fluorescence in situ hybridization in a patient with acute myeloblastic leukemia (AML) and a t(9;11)(p21;q13). Genomic polymerase chain reaction confirmed the MLL-MLLT3 gene fusion. A review of the literature on MLL insertions shows that the opposite orientation of the genes involved in the fusion plays a role in the genesis of the rearrangement in most of the cases reported.


Multidimensional outcomes of suburethral synthetic midurethral sling removal.
To report multidimensional outcomes encompassing pain, dyspareunia, and recurrent urinary tract infections (UTIs), following suburethral sling removal (SSR) of synthetic midurethral slings (MUS) placed for female stress urinary incontinence. We reviewed a prospectively maintained, IRB-approved database of women undergoing SSR at our institution. Demographic data, type of sling, and symptoms along with Urogenital Distress Inventory-Short Form (UDI-6) scores both before and after SSR were analyzed. Success was defined using several modalities including patient-reported symptoms (ideal outcome) and UDI-6 questionnaire. From 3/2006-2/2017, 443 women underwent SSR of which 230 met study criteria with median overall follow-up of 23 months (mean 30 months). 180/230 (78%) patients reported 3 or more symptoms at presentation. Median most recent post-SSR total UDI-6 score was 38 vs. 50 at baseline (p < 0.0001). By UDI-6, 53% of patients achieved success post-SSR. An ideal outcome was attained in 22/230 (10%) patients. A modified outcome allowing for one minimally invasive anti-incontinence procedure and excluding sexual activity classified 112/230 (49%) patients as successes. While patients with MUS present with multiple symptoms, following SSR, there is sustained improvement in multiple symptom domains, including pain and urinary incontinence. Allowing for minimally invasive anti-incontinence procedures (not inclusive of subsequent suburethral sling), the rate of success was 49%, which was comparable to that derived from UDI-6 scores (53%).


MFG-E8 activates proliferation of vascular smooth muscle cells via integrin signaling.
An accumulation of milk fat globule EGF-8 protein (MFG-E8) occurs within the context of arterial wall inflammatory remodeling during aging, hypertension, diabetes mellitus, or atherosclerosis. MFG-E8 induces VSMC invasion, but whether it affects VSMC proliferation, a salient feature of arterial inflammation, is unknown. Here, we show that in the rat arterial wall in vivo, PCNA and Ki67, markers of cell cycle activation, increase with age between 8 and 30 months. In fresh and early passage VSMC isolated from old aortae, an increase in CDK4 and PCNA, an increase in the acceleration of cell cycle S and G2 phases, decrease in the G1/G0 phase, and an increase in PDGF and its receptors confer elevated proliferative capacity, compared to young VSMC. Increased coexpression and physical interaction of MFG-E8 and integrin αvβ5 occur with aging in both the rat aortic wall in vivo and in VSMC in vitro. In young VSMC in vitro, MFG-E8 added exogenously, or overexpressed endogenously, triggers phosphorylation of ERK1/2, augmented levels of PCNA and CDK4, increased BrdU incorporation, and promotes proliferation, via αvβ5 integrins. MFG-E8 silencing, or its receptor inhibition, or the blockade of ERK1/2 phosphorylation in these cells reduces PCNA and CDK4 levels and decelerates the cell cycle S phase, conferring a reduction in proliferative capacity. Collectively, these results indicate that MFG-E8 in a dose-dependent manner coordinates the expression of cell cycle molecules and facilitates VSMC proliferation via integrin/ERK1/2 signaling. Thus, an increase in MFG-E8 signaling is a mechanism of the age-associated increase in aortic VSMC proliferation.


Critical incidents related to invasive mechanical ventilation in the ICU: preliminary descriptive study.
To establish a preliminary list of critical incidents (CIs) associated with mechanical ventilation and to describe a CI reporting method. A list of CIs was established based on a consensus among ICU caregivers. The list was compared to CIs collected prospectively during a predefined study period. The clinical observations were conducted in two intensive care units. All patients receiving mechanical ventilation were included. The list of CIs included death and 62 other CI types categorized as immediately life-threatening, secondarily life-threatening, or non-life-threatening. The observational study identified 527 CIs in 137 patients. Virtually all non-life-threatening CIs were ascribed to failure to comply with safety rules or to equipment failure and 40% of life-threatening CIs to the course of the disease or to patient-related factors. The match between CI types on the list and CI types observed in the ICUs was excellent. Use of our reporting method to create a CI database in a multicenter study including ICUs with varying recruitment patterns may help to identify markers suitable for routine continuous use as part of a quality-assurance program.


Different neuropathological effects of intrahippocampal injections of kainic acid and tetanus toxin.
Behavioral and neuroanatomical effects of hippocampal injections of kainic acid (KA) and tetanus toxin (TT) were investigated in rats. Injections of KA resulted in both local and distant neuroanatomical damage, but not in clear signs of epilepsy; injections of TT on the other hand were followed (in some of the rats) by prolonged seizure attacks, but not by neuronal damage. Based on these results it is suggested that the widespread neuronal damage following KA lesions cannot be primarily attributed to orthodromic activation of epileptic discharges. Instead, specific properties of KA and their interactions with certain transmitters may provoke widespread neuroanatomical damage.


β-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells.
Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived β-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, β-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.