Synthesis of Methanesulfonic Acid Directly from Methane: The Cation Mechanism or the Radical Mechanism?
In 2019, Diaz-Urrutia and Ott developed a high-yield method for direct conversion of methane to methanesulfonic acid and proposed a cationic chain reaction mechanism. However, Roytman and Singleton questioned this mechanism, and they favored a free-radical mechanism. In the present paper, we studied both the cationic chain and radical mechanisms and found the radical mechanism is more favorable, since it has a much lower energy barrier. However, the radical mechanism has not considered the effect of ions for the reaction taking place in oleum. Thus, we studied a simple model of a protonated radical mechanism, which further lowers the energy barrier. Although the true mechanism for the CH4 + SO3 reaction could be more complicated in electrolyte solutions, this model should be helpful for the further study of the mechanism of this reaction.


Spectral and entropic characterizations of Wigner functions: applications to model vibrational systems.
The Wigner function for the pure quantum states is used as an integral kernel of the non-Hermitian operator K, to which the standard singular value decomposition (SVD) is applied. It provides a set of the squared singular values treated as probabilities of the individual phase-space processes, the latter being described by eigenfunctions of KK(+) (for coordinate variables) and K(+)K (for momentum variables). Such a SVD representation is employed to obviate the well-known difficulties in the definition of the phase-space entropy measures in terms of the Wigner function that usually allows negative values. In particular, the new measures of nonclassicality are constructed in the form that automatically satisfies additivity for systems composed of noninteracting parts. Furthermore, the emphasis is given on the geometrical interpretation of the full entropy measure as the effective phase-space volume in the Wigner picture of quantum mechanics. The approach is exemplified by considering some generic vibrational systems. Specifically, for eigenstates of the harmonic oscillator and a superposition of coherent states, the singular value spectrum is evaluated analytically. Numerical computations are given for the nonlinear problems (the Morse and double well oscillators, and the Henon-Heiles system). We also discuss the difficulties in implementation of a similar technique for electronic problems.


Characterization of HIV-related periodontitis in AIDS patients: HIV-infected macrophage exudate in gingival crevicular fluid as a hallmark of distinctive etiology.
In an attempt to clarify the immunobiological events featuring periodontitis lesions of AIDS patients in the late stage of the disease, peripheral blood (PB) and gingival crevicular fluid (GCF) leucocytes from periodontitis lesions of 23 late-stage AIDS patients were analysed by three-colour flow cytometry for detection and identification of intracytoplasmic p24+ cell fractions. The cells were reacted with CD14 and CD68 for mononuclear phagocytes or with CD4 and CD14 for Th cells, then with anti-p24 MoAb. To detect HIV proviral sequences and intracellular p24 RNA sequences, genomic DNA and cellular RNA from leucocytes were extracted for semi-nested polymerase chain reaction (PCR) amplification. CD68+/p24+ and CD14+/CD68+/p24+ fractions were larger in GCF than in PB (P<0.0001; P < 0.003). CD14+/p24+ fraction was lower in GCF than in PB (P < 0.05). The fluorescence intensities (FI) for intracellular p24 in CD68+ and CD14+/CD68+ cells were higher in GCF than in PB (P < 0.003; P < 0.02), whereas those of CD14+ macrophages did not differ. The p24 FI of CD68+ macrophages in GCF correlated with CD4+ lymphocyte counts in PB (P < 0.005). p24 FI levels of CD14+ monocytes in GCF and PB significantly correlated (P < 0.02), whereas that of CD68+ macrophages did not. PCR and reverse transcriptase (RT)-PCR of cellular DNA and RNA yielded positive signals, demonstrating viral integration and production in GCF leucocytes. These results show that periodontitis lesions in AIDS patients can be characterized by a rapid macrophage turnover, and these HIV-infected macrophage exudates in GCF may be considered as a within-mouth source of virus.


Potassium and Zeolitic Structure Modified Ultra-microporous Adsorbent Materials from a Renewable Feedstock with Favorable Surface Chemistry for CO2 Capture.
Novel hierarchically structured microporous biocarbons with exceptionally high capacities for CO2 capture have been synthesized from the abundant agricultural waste of rice husk (RH), using a facile methodology that effectively integrated carbonization, activation, and potassium intercalation into a one-step process. Textural characterization demonstrates that the synthesized biocarbons exhibit exceedingly high ultra-microporosity accounting for up to 95% of total porosity mainly as a result of the naturally occurring silicon compounds within the RH molecular framework structures. With a modest surface area of up to 1035 m2/g and a total pore volume of 0.43 cm3/g, the best performing RH carbon has shown exceptionally high and fully reversible CO2 uptake capacity of 2.0 mmol/g at 25 °C and a CO2 partial pressure of 0.15 bar, which represents one of the highest uptakes ever reported for both carbon and MOF materials usually prepared from using cost-prohibitive precursor materials with cumbersome methodologies. It has been found that up to 50% of the total CO2 uptake is attributable to the unique surface chemistry of the RH carbons, which appears to be dominated by the enhanced formation of extra-framework potassium cations owing to the exceedingly high levels of ultra-microporosity and the presence of zeolitic structures incorporated within the carbon matrices. Characterizations by EDX element mapping, XPS, and heat of adsorption measurements confirm the existence of a range of zeolitic structures, which essentially transforms the RH carbons into a kind of zeolite-carbon nanocomposite material with strong surface affinity for CO2.


Tunable Electrical Conductivity and Magnetic Property of the Two Dimensional Metal Organic Framework [Cu(TPyP)Cu2(O2CCH3)4].
The coordination chemistry between copper acetate [Cu2(OAc)4] and 5,10,15,20-tetra-4-pyridyl-21H,23H-porphine (porphyrin, H2TPyP) is found to give rise to either a 2D metal-organic framework (MOF) [Cu(TPyP)Cu2(O2CCH3)4] or a 3D MOF [Cu(TPyP)CuCl2]·2.5TCE·7H2O], depending on the choice of solvent. The 2D MOF can be made into a film, which was doped with 7,7,8,8-tetracyanoquinodimethane (TCNQ), and the electrical conductivity of the thin film was increased by 3 orders of magnitude with respect to that of the undoped Cu-MOF. The formation of a charge-transfer complex between TCNQ and the 2D Cu-MOF also imparts stronger paramagnetic properties than for the undoped MOF.


[Increase in the concentration of alpha-fetoprotein in the blood of mice following a single dose of cyclophosphane].
Activation of extramedullar hemopoiesis in the liver together with an appreciable elevation of the alpha-fetoprotein (alpha-FP) level in the blood were observed in CBA, C3H/HeJ, DD, C57BL/6 and CC57BR/Mv mice after a single injection of cyclophosphane in a dose of 200 mg/kg bw. The alpha-FP concentration reached maximum days 2-4 after cyclophosphane administration, amounting of 290-560 ng/ml which surpasses 2-5-fold the basal level of the protein. In mice with an earlier serum alpha-FP elevation (CBA, C3H/HeJ and DD), the liver hemopoiesis also started earlier than in those with a delayed alpha-FP maximum (C57BL/6 and CC57BR/Mv).


A quantitative sequencing method using synthetic internal standards including functional and phylogenetic marker genes.
The method of spiking synthetic internal standard genes (ISGs) to samples for amplicon sequencing, generating sequences and converting absolute gene numbers from read counts has been used only for phylogenetic markers and has not been applied to functional markers. In this study, we developed ISGs, including gene sequences of the 16S rRNA, pmoA, encoding a subunit of particulate methane monooxygenase and amoA, encoding a subunit of ammonia monooxygenase. We added ISGs to the samples, amplified the target genes and performed amplicon sequencing. For the mock community, the copy numbers converted from read counts using ISGs were equivalent to those obtained by the quantitative real-time polymerase chain reaction (4.0 × 104 versus 4.1 × 104 and 3.0 × 103 versus 4.0 × 103 copies μL-DNA-1 for 16S rRNA and pmoA genes, respectively), but we also identified underestimation, possibly due to primer coverage (7.8 × 102 versus 3.7 × 103 μL-DNA-1 for amoA gene). We then applied this method to environmental samples and analysed phylogeny, functional diversity and absolute quantities. One Methylocystis population was most abundant in the sludge samples [16S rRNA gene (3.8 × 109 copies g-1 ) and the pmoA gene (2.3 × 109 copies g-1 )] and were potentially interrelated. This study demonstrates that ISG spiking is useful for evaluating sequencing data processing and quantifying functional markers.


Wnt-RhoA signaling pathways in fluoride-treated ameloblast-lineage cells.
This study examined the effect of sodium fluoride (NaF) on the Wnt and RhoA signaling pathways in murine ameloblast-lineage cells (ALCs) to better understand the developmental mechanisms of dental fluorosis. Wnt and Rho pathway activities were investigated when ALCs were treated with 1.5 mM NaF, dickkopf-related protein-1 (Dkk-1), secreted frizzled related-protein-2 (sFRP-2), β-catenin siRNA dominant negative RhoA (RhoA(DN)) plasmid and Y-27632. Wnt pathway activity was investigated via RT-PCR, Western blot and Topflash luciferase assay. The activity of the RhoA pathway was analyzed via Rho pull-down assay and immunoprecipitation. The differentiation of ALCs was analyzed by alkaline phosphatase assay. Western blot and Topflash luciferase assay results verified that both the Wnt and Rho pathways were upregulated by 1.5 mM NaF. Wnt was discovered to be located upstream from the Rho pathway, as confirmed by treatment with Wnt pathway cell receptor inhibitors Dkk-1 and sFRP-2, leading to a decrease in RhoA and ROCK activity. Inhibition of the Rho pathway with RhoA(DN) plasmid and Y-27632 caused upregulation of Wnt pathway activity which could be further increased by 1.5 mM NaF. The increased Wnt pathway activity was found to negatively regulate ALC differentiation. These data suggest that fluoride could induce the cross-talk between Wnt and RhoA signaling pathways, and these responses are predicted to contribute to the development of enamel fluorosis. © 2014 S. Karger AG, Basel.


Intraforaminal cervical gas cyst with vacuum disc treated by anterior cervical discectomy and fusion: illustrative case.
The authors report an extremely rare presentation of a patient with an intraforaminal cervical gas cyst with radiculopathy. The patient's condition was refractory to conservative treatment, and he was treated by anterior cervical discectomy and fusion (ACDF). Several intraspinal gas cysts with lumbar disc herniation have been treated surgically. However, no cases of intraforaminal cervical gas requiring ACDF have been reported. A 70-year-old male patient presented with right-sided neck and shoulder pain, aggravating in the supine position. Cervical radiography showed vacuum disc phenomenon at C4-5, and multiplanar computed tomography showed intraforaminal gas along the right C5 nerve root. The patient experienced severe pain with impaired sleep and daytime fatigue. After confirming C5 radiculopathy using an echo-guided technique using ultrasonography guidance, the authors performed C4-5 ACDF. Postoperatively, the patient's neck and shoulder pain disappeared immediately. There was no recurrence at the 2-year follow-up. This is the first case report of an intraspinal cervical gas cyst with radiculopathy treated by ACDF surgery. The vacuum disc had been implicated as the genesis of the intraforaminal cervical gas cyst, leading to radiculopathy. ACDF surgery provides favorable outcomes in cases of intraspinal gas refractory to conservative therapy.


Myosin heavy chain isoforms in single fibres from m. vastus lateralis of sprinters: influence of training.
The myosin heavy chain (MHC) composition of single fibres from m. vastus lateralis of a group of male sprint athletes (n = 6) was analysed, before and after a three months period of intensive strength- and interval-training, using a sensitive gel electrophoretic technique. Significant improvements were observed after training in almost all of a series of performance tests. After training the sprinters revealed a decrease in fibres containing only MHC isoform I (52.0 +/- 3.0% vs. 41.2 +/- 4.7% (mean +/- SE) (P < 0.05)) and an increase in the amount of fibres containing only MHC isoform IIA (34.7 +/- 6.1% vs. 52.3 +/- 3.6% (P < 0.05)). Fibres showing co-existence of MHC isoforms IIA and IIB decreased with training (12.9 +/- 5.0% vs. 5.1 +/- 3.1% (P < 0.05)). Only one out of 1000 fibres analysed contained only MHC isoform IIB. In contrast, a higher amount of type IIB fibres (18.8 +/- 3.6% vs. 10.5 +/- 3.9%, (P < 0.05)) was observed with myofibrillar ATPase histochemistry. The majority of histochemically determined type IIB fibres of sprinters seems therefore to contain both MHC isoforms IIA and IIB. Sprint-training appears to induce an increased expression of MHC isoform IIA in skeletal muscles. This seems related to a bi-directional transformation from both MHC isoforms I and IIB towards MHC isoform IIA.


Clinical significance of STAT3 and MAPK phosphorylation, and the protein expression of cyclin D1 in skin squamous cell carcinoma tissues.
The present study aimed to investigate the significance of the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen‑activated protein kinase (MAPK), and the protein expression of cyclin D1, in skin squamous cell carcinoma (SCC) tissues. SCC specimens from the skin were collected from 30 patients, and normal skin tissues were collected from 10 individuals as a control. Immunohistochemistry was used to assess the protein expression levels of phosphorylated (p‑)STAT3, p‑MAPK and cyclin D1 in the SCC tissues. The levels of p‑STAT3 protein were abnormally increased in SCC (P<0.05); however, no significant differences in the protein expression of p‑MAPK were identified between the normal skin and the SCC specimens. The extent of the upregulation of the expression of p‑STAT3 and cyclin D1 correlated with the depth of tumor invasion (P<0.05). A positive correlation existed between the expression of p‑STAT3 and cyclin D1 in SCC. However, no association between the expression intensity of p‑MAPK and cyclin D1 was identified in SCC. It is postulated that the activation of STAT3 may induce the overexpression of cyclin D1, which results in the persistent proliferation of these tumor cells in SCC.


The regulation of ion channels and transporters by glycolytically derived ATP.
Glycolysis is an evolutionary conserved metabolic pathway that provides small amounts of energy in the form of ATP when compared to other pathways such as oxidative phosphorylation or fatty acid oxidation. The ATP levels inside metabolically active cells are not constant and the local ATP level will depend on the site of production as well as the respective rates of ATP production, diffusion and consumption. Membrane ion transporters (pumps, exchangers and channels) are located at sites distal to the major sources of ATP formation (the mitochondria). We review evidence that the glycolytic complex is associated with membranes; both at the plasmalemma and with membranes of the endo/sarcoplasmic reticular network. We examine the evidence for the concept that many of the ion transporters are regulated preferentially by the glycolytic process. These include the Na(+)/K(+)-ATPase, the H(+)-ATPase, various types of Ca(2+)-ATPases, the Na(+)/H(+) exchanger, the ATP-sensitive K(+) channel, cation channels, Na(+) channels, Ca(2+) channels and other channels involved in intracellular Ca(2+) homeostasis. Regulation of these pumps, exchangers and ion channels by the glycolytic process has important consequences in a variety of physiological and pathophysiological processes, and a better understanding of this mode of regulation may have important consequences for developing future strategies in combating disease and developing novel therapeutic approaches.


A prevalence study of xerophthalmia in the Philippines: implications for supplementation strategies.
In three provinces of the Philippines (Quezon, Northern Samar and Zamboanga del Sur), 11,378 children between 6 and 83 months of age were examined for signs of xerophthalmia and weighed to determine weight-for-age status. Xerophthalmia prevalence ranged from 1.6% to 4.4% for nightblindness and 0.6% to 2.7% for Bilot's spots in the three provinces indicating a serious vitamin A deficiency problem. These levels contrast sharply with the recent national xerophthalmia prevalence (0.7% for night blindness and 0.2% for Bitot's spots). There was a preponderance of mild xerophthalmia among males, and among children 4-6 years of age. No consistent association between weight-for-age status and xerophthalmia was found. The study recommends the universal distribution of vitamin A to children in high-prevalence regions, rather than the current practice of providing vitamin A supplements to moderately and severely underweight children identified through the annual village-based child weighing sessions, to ensure reaching children most at risk for xerophthalmia. The study also suggests the need for regional vitamin A assessments to identify areas endemic for vitamin A deficiency because the aggregate national prevalence may mask a more serious localized problem.


[Extrahospital pneumonias: the clinico-scintigraphic characterization and oxidative balance of cells].
Ventilation-perfusion pulmonary scintigraphy was carried out in 30 patients with a verified diagnosis of extra-hospital pneumonia (EHP) and 10 healthy subjects; ventilation-perfusion ratio (V/Q), apex-basis ventilation and perfusion gradient, and the condition of alveolar-capillary permeability (ACP) were analyzed. Clinical symptoms during the debut of EHP were more pronounced in patients with an alveolar type of pulmonary infiltrate (PI) vs. patients with interstitial one: they had pulmonary infiltration syndrome, pleural pain, tachypnoe, tachycardia, a fever of higher than 38 degrees C, and leucocytosis more often. During the acute period of EHP, elevated lipid peroxidation in the erythrocyte membrane as well as a decrease in the content of reduced glutathione and the activity of superoxide dismutase and catalase in erythrocytes did not depend on the type of PI. In EHP, independently of PI type, the study revealed an increase in V/Q of higher than 1.0 on the side of lesion and bilateral (including the healthy side) increase in ACP for radioactive aerosol.


Assessing alcohol consumption in general practice patients--a comparison between questionnaire and interview (findings of the Medical Research Council's general practice research framework study on lifestyle and health).
A self-administered questionnaire, the Health Survey Questionnaire (HSQ) was distributed to patients registered with 47 group general practices. The HSQ assesses alcohol consumption using a quantity frequency scale and includes the four CAGE questions and a question on whether respondents think they have an alcohol problem. A random stratified sample of those patients who returned an HSQ (2666 men and 1537 women) were subsequently invited to attend their general practice for an interview with the practice nurse, where weekly alcohol consumption was estimated using both a quantity frequency scale and a systematic enquiry about alcohol consumption for the week immediately preceding the interview. The latter method was taken as the 'gold standard'. Excessive drinkers were defined as men whose weekly consumption by this method was not less than 35 units per week and women drinking at least 21 units per week. After weighing the results to take account of the sampling bias in favour of the excessive drinkers, 11.7% of men and 2.9% of women were excessive drinkers according to the estimate of alcohol consumption at interview. This compares with the 7.6% of men and 2.7% of women who were heavy drinkers by the HSQ quantity frequency scale. The two interview estimates were comparable but in general the HSQ tended to underestimate consumption compared with these estimates. The questionnaire was found to be most effective in screening for excessive drinkers if all the patients who indicated concern about their drinking (i.e. those who were with CAGE positive or had a self-assessed drinking problem), as well as all of those who were above the limits for the trial on the quantity frequency scale, were selected as being potentially excessive drinkers. In the weighted sample, 14.8% of men and 6.9% of women were in this group. Using these selection criteria and taking the interview as the standard for determining the excessive drinkers a sensitivity of 58.6% and specificity of 91.08% was obtained for men, with a positive predictive value of 46.1% and a negative predictive value of 94.3%. For women the test was more sensitive (69.7%) and more specific (95.0%) and had a better negative predictive value (99.1%) than for men. The positive predictive value for women at 29.6% was not as good as that obtained for men. This analysis shows that the HSQ is a fairly effective tool for detecting excessive drinkers in general practices with a small proportion of false positive results. It is both economical and acceptable to patients in a wide range of practice settings.


Mean power frequency and amplitude of the mechanomyographic signal during maximal eccentric isokinetic muscle actions.
The purpose of the present investigation was to examine the effects of knee angular velocity on the mean power frequency (MPF) and amplitude of the mechanomyographic (MMG) signal during maximal eccentric (ECC) isokinetic muscle actions. Eleven adult subjects performed maximal ECC muscle actions of the leg extensors on a calibrated Cybex 6000 dynamometer at knee angular velocities of 60, 120, and 180 degrees.s-1. MMG was detected by a piezoelectric crystal contact sensor placed over the vastus lateralis muscle. There were no significant (p > 0.05) velocity-related changes in ECC peak torque (PT) or MMG MPF, however, the mean MMG amplitude value at 60 degrees.s-1 was significantly less (p < 0.05) than that at 180 degrees.s-1. These results did not support our previous hypothesis that the velocity-related increase in MMG amplitude for maximal ECC isokinetic muscle actions was due to selective recruitment of fast twitch fibers and derecruitment of slow twitch fibers with increasing velocity.


Micromonospora thermarum sp. nov., an actinobacterium isolated from hot spring soil.
An actinomycete, designated strain HSS6-12T, was isolated from hot spring sediment collected from Ranong province, Thailand. The strain showed taxonomic characteristics consistent with those of members of the genus Micromonospora. HSS6-12T produced a single spore directly on the substrate mycelium, and no aerial mycelium was detected. The isomer of diamino acid presented in cell wall peptidoglycan was meso-diaminopimelic acid. Arabinose, xylose, glucose, and ribose were detected in whole-cell hydrolysates. MK-10(H4), MK-9(H4), and MK-10(H6) were major menaquinones. Major cellular fatty acids were iso-C16:0, iso-C15:0, and iso-C17:0. Phospholipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, and phosphatidylinositolmannosides. 16S rRNA gene analysis revealed that HSS6-12T shared the highest 16S rRNA gene sequence similarity with Micromonospora inositola DSM 43819T (99.3%). In contrast, the genome analysis showed that HSS6-12T formed a tight taxonomic position in a phylogenomic tree with Micromonospora endolithica DSM 44398T. Moreover, the average nucleotide identity-blast, the digital DNA-DNA hybridization, and the average amino acid identity values between HSS6-12T and M. inositola DSM 43819T and M. endolithica DSM 44398T were 83.1-84.0%, 27.5-28.7%, and 80.4-82.2%, respectively, indicating that HSS6-12T was different species with both closely related Micromonospora-type strains. In addition, HSS6-12T could be discriminated from its closely related type strains by many physiological and biochemical characteristics. Thus, HSS6-12T could be considered a novel species of the genus Micromonospora, and the name Micromonospora thermarum is proposed for the strain. The type strain is HSS6-12T (= BCC 41915T = JCM 17127T).


Current status of a mucosal vaccine against dental caries.
The evidence of a specific bacterial cause of dental caries and of the function of the salivary glands as an effector site of the mucosal immune system has provided a scientific basis for the development of a vaccine against this highly prevalent and costly oral disease. Research efforts towards developing an effective and safe caries vaccine have been facilitated by progress in molecular biology, with the cloning and functional characterization of virulence factors from mutans streptococci, the principal causative agent of dental caries, and advancements in mucosal immunology, including the development of sophisticated antigen delivery systems and adjuvants that stimulate the induction of salivary immunoglobulin A antibody responses. Cell-surface fibrillar proteins, which mediate adherence to the salivary pellicle, and glucosyltransferase enzymes, which synthesize adhesive glucans and allow microbial accumulation, are virulence components of mutans streptococci, and primary candidates for a human caries vaccine. Infants, representing the primary target population for a caries vaccine, become mucosally immunocompetent and secrete salivary immunoglobulin A antibodies during the first weeks after birth, whereas mutans streptococci colonize the tooth surfaces at a discrete time period that extends around 26 months of life. Therefore, immunization when infants are about one year old may establish effective immunity against an ensuing colonization attempts by mutans streptococci. The present review critically evaluates recent progress in this field of dental research and attempts to stress the protective potential as well as limitations of caries immunization.


A Two-Phase Improved Correlation Method for Automatic Particle Selection in Cryo-EM.
Particle selection from cryo-electron microscopy (Cryo-EM) images is very important for high-resolution reconstruction of macromolecular structure. The methods of particle selection can be roughly grouped into two classes, template-matching methods and feature-based methods. In general, template-matching methods usually generate better results than feature-based methods. However, the accuracy of template-matching methods is restricted by the noise and low contrast of Cryo-EM images. Moreover, the processing speed of template-matching methods, restricted by the random orientation of particles, further limits their practical applications. In this paper, combining the advantages of feature-based methods and template-matching methods, we present a two-phase improved correlation method for automatic, fast particle selection. In Phase I, we generate a preliminary particle set using rotation-invariant features of particles. In Phase II, we filter the preliminary particle set using a correlation method to reduce the interference of the high noise background and improve the precision of particle selection. We apply several optimization strategies, including a modified adaboost algorithm, Divide and Conquer technique, cascade strategy and graphics processing unit parallel technique, to improve feature recognition ability and reduce processing time. In addition, we developed two correlation score functions for different correlation situations. Experimental results on the benchmark of Cryo-EM images show that our method can improve the accuracy and processing speed of particle selection significantly.


Effects of Cholecalciferol Supplementation in Patients with stable heart failure and LOw vITamin D levels (ECSPLOIT-D): a double-blind, randomized, placebo-controlled pilot study.
The aim of this study was to investigate the effects of vitamin D (VD) on the interaction among functional, echocardiographic and hormonal parameters in patients with heart failure (HF) and VD deficiency. In a randomized, double blind trial, 35 patients with HF and VD<20 ng/mL, received either 300,000 U of oral cholecalciferol followed by 50,000 U/month for 6 months, or placebo treatment. Changes in the 6 Minute Walking Test (6MWT) assessed at 3 and 6 months in treatment group was the primary end point. Secondary endpoints were echocardiographic and hormonal changes. The same targets were compared in treated and placebo groups as secondary endpoints. In the treatment group the 6MWT improved at 3 (from 210±104 mt to 225±94 mt; P=0.033) but not at 6 months (from 210±104 mt to 217±94 mt; P=0.288) while PTH dropped at 3 (from 76.8±50.5 to 50.2±20.3 pg/mL; P=0.025), but not at 6 months. 6MWT improvement was negatively related to baseline VD levels. Variation in 6MWT did not significantly differ among groups at 3 (13.6±23.3 vs. 3.6±17.3; P 0.175) and 6 months (12.1±31.4 vs. 0.2±23.2; P 0.225). Left atrial size increased in the placebo group (from 50.8±20.7 to 61.7±36.0 mL/m2; P=0.010). Other hormonal parameters remained unchanged. In summary, the treatment of VD deficiency in patients with HF improved 6MWT after 3 months along with a decrease in PTH levels. However when compared with the placebo arm, treatment of VD deficiency did not influence the final outcomes.


The echogenicity of nerve blockade needles.
We performed a prospective, randomised study to evaluate the echogenicity of 11 regional block needles when inserted into a gel phantom at 45° in the ultrasound plane. Two hundred anaesthetists viewed in random sequence recordings of each needle as it was advanced into the phantom. Participants scored the needle for echogenicity on a scale of 0-10 and categorised the needle as 'hyperechoic' or 'standard'. The mean (95% CI) echogenicity score was 1.7 (1.4-2.0) units higher for three needles marketed as 'hyperechoic' compared with standard needles marketed by the same companies, p < 0.001. The odds ratios (95% CI) that an anaesthetist would categorise a needle as hyperechoic were: 5.3 (3.6-8.0) if the needle was marketed as hyperechoic, p < 0.001; and 1.7 (1.1-2.6) if regional anaesthetic experience was ≥ 1 year compared with < 1 year, p = 0.025.


Discovery of a new genus of anaerobic ammonium oxidizing bacteria with a mechanism for oxygen tolerance.
In the past 20 years, there has been a major stride in understanding the core mechanism of anaerobic ammonium-oxidizing (anammox) bacteria, but there are still several discussion points on their survival strategies. Here, we discovered a new genus of anammox bacteria in a full-scale wastewater-treating biofilm system, tentatively named "Candidatus Loosdrechtia aerotolerans". Next to genes of all core anammox metabolisms, it encoded and transcribed genes involved in the dissimilatory nitrate reduction to ammonium (DNRA), which coupled to oxidation of small organic acids, could be used to replenish ammonium and sustain their metabolism. Surprisingly, it uniquely harbored a new ferredoxin-dependent nitrate reductase, which has not yet been found in any other anammox genome and might confer a selective advantage to it in nitrate assimilation. Similar to many other microorganisms, superoxide dismutase and catalase related to oxidative stress resistance were encoded and transcribed by "Ca. Loosdrechtia aerotolerans". Interestingly, bilirubin oxidase (BOD), likely involved in oxygen resistance of anammox bacteria under fluctuating oxygen concentrations, was identified in "Ca. Loosdrechtia aerotolerans" and four Ca. Brocadia genomes, and its activity was demonstrated using purified heterologously expressed proteins. A following survey of oxygen-active proteins in anammox bacteria revealed the presence of other previously undetected oxygen defense systems. The novel cbb3-type cytochrome c oxidase and bifunctional catalase-peroxidase may confer a selective advantage to Ca. Kuenenia and Ca. Scalindua that face frequent changes in oxygen concentrations. The discovery of this new genus significantly broadens our understanding of the ecophysiology of anammox bacteria. Furthermore, the diverse oxygen tolerance strategies employed by distinct anammox bacteria advance our understanding of their niche adaptability and provide valuable insight for the operation of anammox-based wastewater treatment systems.


Visible-Light-Promoted Photoredox Syntheses of α,β-Epoxy Ketones from Styrenes and Benzaldehydes under Alkaline Conditions.
A range of styrenes and benzaldehydes were smoothly combined to form α,β-epoxy ketones under the synergistic actions of photocatalyst Ru(bpy)3Cl2, tert-butyl hydroperoxide (t-BuOOH), cesium carbonate (Cs2CO3), and visible light irradiation. The process likely proceeds through visible-light-enabled photocatalytic generations of acyl radicals as key intermediates.


Pressure dressings in mastoid and middle ear surgery: are they necessary? A retrospective review of patient outcomes.
The application of mastoid pressure dressings following mastoid and middle ear surgery is widely practised to reduce the risk of haematoma and seroma. There are a number of minor morbidities associated with use of the dressings, as well as a financial cost associated with an overnight stay in hospital or a return appointment for removal of the dressings. The benefit of having these dressings in situ overnight is questionable. A retrospective review of 133 patients who had their mastoid dressing removed 2 h after their procedure was undertaken at our Hospital. The patient records were scanned for procedure-related morbidities, and perioperative data were analysed. No haematomas or seromas occurred in any of the 133 patients studied. Minor morbidities associated with prolonged use of mastoid pressure dressings were avoided. Removal of mastoid pressure dressings 2 h following ear surgery is safe and effective. Furthermore, a mastoid dressing should not be a factor in the decision as to whether to treat a patient as a day case or overnight admission.


Effect of calcium and calmodulin antagonists on metamorphosis in the anuran tadpole, Rana tigerina.
The fact that calcium ions regulate the secretion of thyroid hormones could be extended to explore how the mechanisms of anuran metamorphosis is controlled by thyroid hormones. In the present study, an attempt was made to investigate the effects of both calcium channel blocker, Diltiazem (DT) and calmodulin inhibitor, Trifluoperazine (TFP) on metamorphosis and various developmental stages of the anuran tadpole, Rana tigerina. Both DT (25 microM) and TFP (2 microM) treatments caused total inhibition of the development and metamorphosis of the tadpole at premetamorphic stages. The metamorphosis was delayed by DT and totally inhibited by TFP when tadpoles were exposed at prometamorphic stages. Both drugs could not affect the tadpoles at climax stage. The findings suggest an active involvement of thyroid hormone in premetamorphic tadpoles. Calcium channel blockage with DT could not prevent the progression of tadpoles through prometamorphic stages which suggest that the change in calcium pool is not a determining factor mediating thyroid hormone release mechanism. The study suggests that in tadpole growth thyroid hormone secretion is modulated by calmodulin bound intracellular calcium.


Calcium signaling in invertebrate glial cells.
Calcium signaling studies in invertebrate glial cells have been performed mainly in the nervous systems of the medicinal leech (Hirudo medicinalis) and the sphinx moth Manduca sexta. The main advantages of studing glial cells in invertebrate nervous systems are the large size of invertebrate glial cells and their easy accessibility for optical and electrophysiological recordings. Glial cells in both insects and annelids express voltage-gated calcium channels and, in the case of leech glial cells, calcium-permeable neurotransmitter receptors, which allow calcium influx as one major source for cytosolic calcium transients. Calcium release from intracellular stores can be induced by metabotropic receptor activation in leech glial cells, but appears to play a minor role in calcium signaling. In glial cells of the antennal lobe of Manduca, voltage-gated calcium signaling changes during postembryonic development and is essential for the migration of the glial cells, a key step in axon guidance and in stabilization of the glomerular structures that are characteristic of primary olfactory centers.


Downregulation of TLR7/9 leads to deficient production of IFN-α from plasmacytoid dendritic cells in chronic hepatitis B.
To investigate whether Toll-like receptor (TLR) 7 and TLR9-mediated interferon α (IFN-α) production in plasmacytoid dendritic cells (pDCs) is compromised in patients with chronic hepatitis B virus (HBV) infection. Peripheral blood mononuclear cells (PBMCs) were prepared from 32 chronic HBV patients and 13 healthy volunteers, and treated with loxoribine or cytidine phosphate guanosine (CpG) oligodeoxynucleotides (ODN). Interferon α in the supernatant was measured by sandwich ELISA. PDC frequency and the expression levels of TLR7 and TLR9 in pDCs were quantified by flow cytometry. The serum viral load of HBV was quantified using a highly sensitive real-time PCR kit. Compared to cells from healthy control group, PBMCs and pDCs from the HBV group showed significantly decreased production of IFN-α in response to ligand for TLR7 (loxoribine) and TLR9 (CpG ODN, P < 0.05). Mechanistically, the number of pDCs in peripheral blood, and the expression of pDC-associated TLR7 and TLR9 were significantly lower in HBV group than in the healthy control group (P < 0.05). In addition, the number of pDCs and the expression of TLR9 on pDCs were correlated inversely with the serum load of HBV. Impaired IFN-α production from pDC may contribute to the immunopathogenesis of chronic HBV infection, which may be the result of a reduced amount of pDCs as well as decreased expression of TLR7 and TLR9 on pDCs.


Chromatin accessibility profiling provides insights into larval cuticle color and adult longevity in butterflies.
Butterflies are diverse in virtually all aspects of their ontogeny, including morphology, life history, and behavior. However, the developmental regulatory mechanisms underlying the important phenotypic traits of butterflies at different developmental stages remain unknown. Here, we investigated the developmental regulatory profiles of butterflies based on transposase accessible chromatin sequencing (ATAC-seq) at three developmental stages in two representative species ( Papilio xuthus and Kallima inachus). Results indicated that 15%-47% of open chromatin peaks appeared in associated genes located 3 kb upstream (i.e., promoter region) of their transcription start site (TSS). Comparative analysis of the different developmental stages indicated that chromatin accessibility is a dynamic process and associated genes with differentially accessible (DA) peaks show functions corresponding to their phenotypic traits. Interestingly, the black color pattern in P. xuthus 4th instar larvae may be attributed to promoter peak-related genes involved in the melanogenesis pathway. Furthermore, many longevity genes in 5th instar larvae and pupae showed open peaks 3 kb upstream of their TSS, which may contribute to the overwintering diapause observed in K. inachus adults. Combined with RNA-seq analysis, our data demonstrated that several genes enriched in the melanogenesis and longevity pathways also exhibit higher expression, confirming that the expression of genes may be closely related to their phenotypic traits. This study offers new insights into larval cuticle color and adult longevity in butterflies and provides a resource for investigating the developmental regulatory mechanisms underlying butterfly ontogeny.


Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD.
Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O2) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WRmax) with phosphorus magnetic resonance spectroscopy (31P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; P < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; P > 0.05). The initial postexercise convective O2 delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD (P > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups (P > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O2 availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.


Pelvic sexual dimorphism among species monomorphic in body size: relationship to relative newborn body mass.
Females have larger pelves than males among eutherians to mitigate obstetrical difficulty. This study addresses 3 issues concerning pelvic sexual dimorphism using 8 species that are sexually monomorphic in nonpelvic size: Aotus azarae , Castor canadensis , Dasypus novemcinctus , Hylobates lar , Saguinus geoffroyi , Sciurus carolinensis , Sylvilagus floridanus , and Urocyon cinereoargenteus . Using published data to compute the index of relative newborn body mass (RNBM = [newborn body mass/adult female body mass]100%) for 266 eutherian species, A. azarae , H. lar , and S. geoffroyi are characterized as giving birth to relatively large newborns and the other 5 species as giving birth to relatively small newborns. The 3 issues are, compared to species giving birth to relatively small newborns, whether species that give birth to relatively large newborns have 1) higher magnitude of pelvic sexual size dimorphism (SSD), 2) lower prevalence of pelvic joint fusion, and 3) dissociation between pelvic and nonpelvic sizes. Nine measures of the pelvis were taken, and fusion of interpubic and sacroiliac joints was observed. Species grouped by high and low RNBM do not differ significantly in magnitude of SSD of pelvic inlet circumference. Species with high RNBM have significantly lower prevalence of interpubic joint fusion than those with low RNBM. Sexes do not differ in their multiple correlation coefficients between inlet circumference and nonpelvic body size in 7 of 8 species. Results suggest that 1) there are multiple anatomical pathways for pelvic obstetrical sufficiency, 2) an unfused interpubic joint is obstetrically advantageous, and 3) relative newborn size does not change the association between pelvic and nonpelvic size in females and males.


Familial cortical myoclonic tremor as a unique form of cortical reflex myoclonus.
Previously it was reported that some patients with tremor had the same electrophysiological findings as those seen in patients with cortical reflex myoclonus, and consequently the tremor was named "cortical tremor." In the present study, we examined six patients from three families with cortical tremor of relatively late onset. The inheritance pattern of cortical tremor was compatible with autosomal dominant trait. Those patients had relatively rhythmic involuntary movements (tremor) in the distal upper and lower limbs, especially during posture and/or fine movements. There was no cerebellar ataxia or dementia, and fits of loss of consciousness occurred only infrequently. Electrophysiologically, they had generalized spikes on electroencephalogram (EEG), giant cortical components of somatosensory evoked potential, an enhanced long-loop reflex (C-reflex), and cortical spikes preceding the rhythmic jerk demonstrable by the jerk-locked back averaging method, thus fulfilling the criteria of cortical reflex myoclonus. Furthermore, they had slow negative EEG shift starting 1-2 s prior to voluntary movements, suggesting that, as opposed to the conventional form of progressive myoclonus epilepsy (PME), the cerebellar efferent input to the motor cortices was normal. These clinical and electrophysiological pictures are distinct from those of familial essential tremor, familial essential myoclonus, or the conventional form of PME, and the term "familial cortical myoclonic tremor" will represent the clinical and electrophysiological features of this unique entity most appropriately.


[Hypoglycemia as a limitation to the treatment of diabetes mellitus].
In his paper, the author deals with hypoglycemia-related problems as the most frequent complication of the therapy for diabetes mellitus (DM). He points to threats that patients with hypoglycemia are exposed to, but also gives attention to risk groups of patients with regard to hypoglycemia development as well as different levels of the risk related to different antidiabetics.Key words: antidiabetics - diabetes mellitus - hypoglycemia.


[Relaxant effects of protopine on smooth muscles].
The relaxant effects of protopine (Pro) on smooth muscles were studied by recording isotonic contraction and radioimmunoassay. Pro relaxed the contraction of rabbit thoracic aorta, mesenteric artery, portal vein and guinea pig ileum and taenia colon induced by high K+ (70 mmol.L-1). Pro also inhibited the contraction of rabbit thoracic aorta, mesenteric artery, portal vein induced by NE (0.3 mumol.L-1) and guinea pig taenia colon induced by BaCl2 (1 mmol.L-1). Pro inhibited the intracellular Ca2+ release, but did not inhibit Ca2+ influx induced by NE. These results suggested that the smooth muscle relaxant mechanism of action of Pro may be the inhibition of intracellular Ca2+ release.


Studies on human thyroxine-binding globulin. VI. The nature of slow thyroxine-binding globulin.
A model system utilizing a highly purified partially desialylated thyroxine-(T(4)) binding protein (STBG) was studied. STBG was prepared by the same affinity chromatographic method we have reported for preparation of highly purified T(4)-binding globulin (TBG). The necessary prerequisite for preparation of STBG was the use of T(4)-substituted Sepharose which had been repeatedly exposed to large volumes of serum for purification of TBG. STBG moved more slowly on cellulose acetate electrophoresis than TBG but had the same molecular weight and antigenic determinants as TBG. It bound T(4) with a 1: 1 molar ratio but its affinity for T(4) was about 10 times less than that of TB. STBG had about onefourth the sialic acid content of TBG and the electrophoretic mobility of this protein was similar to that of a T(4)-binding protein with a mobility slower than that of TBG which has been seen in the electrophoretic patterns of some normal human serums and in serums of patients with hepatic cirrhosis and which does not appear to be an artifact caused by storage and freezing of serum. This fourth slowly migrating T(4)-binding region in electrophoretograms of cirrhotic serums is completely abolished by prior incubation with rabbit antiserum to TBG. The in vitro production of partially desialylated TBG from T(4)-Sepharose which had been previously exposed to large volumes of serum may be due to adsorption of neuraminidases to the Sepharose either directly from serum or as the result of bacterial contamination. Partial desialylation of TBG in vivo may be an early step in the catabolism of this protein.


Nutrient and sediment losses under simulated rainfall following manure incorporation by different methods.
Incorporation of manure into cultivated soils is generally recommended to minimize nutrient losses. A 3-yr study was conducted to evaluate sediment and nutrient losses with different tillage methods (moldboard plow, heavy-duty cultivator, double disk, and no-incorporation) for incorporation of beef cattle manure in a silage barley (Hordeum vulgare L.) cropping system. Runoff depths, sediment losses, and surface and subsurface nutrient transfers were determined from manured and unmanured field plots at Lethbridge, Alberta, Canada. A Guelph rainfall simulator was used to generate 30 min of runoff. Sediment losses among our tillage treatments (137.4-203.6 kg ha(-1)) were not significantly different due to compensating differences in runoff depths. Mass losses of total phosphorus (TP) and total nitrogen (TN) in surface runoff were greatest from the no-incorporation (NI) treatments, with reductions in TP loads of 14% for double disk (DD), 43% for cultivator (CU), and 79% for moldboard plow (MP) treatments. Total N load reductions in 2002 were 26% for DD, 70% for CU, and 95% for MP treatments compared to the NI treatments. Nutrient losses following incorporation of manure with the DD or CU methods were not significantly different from the NI treatments. Manure treatments generally had lower runoff depths and sediment losses, and higher phosphorus and nitrogen losses than the control treatments. Subsurface concentrations of NH4-N, NO3-N, and TN were greatest from the MP treatments, whereas subsurface phosphorus concentrations were not affected by tillage method. Tillage with a cultivator or double disk minimized combined surface and subsurface nutrient losses immediately after annual manure applications.


Effect of radiation-induced xerostomia on human oral microflora.
A longitudinal study was performed to assess the effects of radiation-induced xerostomia on the human oral microflora. Pronounced microbial population shifts were found in each of five intraoral sites tested. Cariogenic microorganisms gained prominence at the expense of noncariogenic microorganisms in concert with the saliva shutdown. These changes occurred before the onset of clinical caries irrespective of whether or not a topical fluoride gel was used as a caries preventive.


Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients.
To evaluate quantitative hepatitis B surface antigen (qHBsAg) as a diagnostic marker for inactive carriers (ICs) and hepatitis B surface antigen (HBsAg) seroclearance in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. We retrospectively studied 300 HBeAg-negative CHB patients with initial serum hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) levels <2000 IU/mL. Serum HBV DNA and alanine aminotransferase (ALT) levels were monitored every 6 months for 24 months. ICs were identified as having persistent HBV DNA levels <2000 IU/mL and normal ALT levels, whereas active carriers (ACs) were identified as having HBV DNA levels ≥2000 IU/mL, with or without elevated ALT levels. The serum qHBsAg level was defined at baseline and evaluated as a diagnostic predictor using a receiver-operating characteristic curve. The study group comprised 134 men and 166 women with a median age of 41.5 years. At baseline, 200 ICs displayed lower levels of qHBsAg (1492 IU/mL) compared with 100 ACs (2936 IU/mL) (P = 0.005). The qHBsAg level was independently associated with the IC state and HBsAg seroclearance. Baseline qHBsAg levels <1000 IU/mL and HBV DNA levels <2000 IU/mL, when detected simultaneously, allowed for identification of ICs with 41% sensitivity and 72% specificity. Fifteen patients (5%) displayed HBsAg seroclearance after 24 months. A qHBsAg cutoff value of <50 IU/mL provided 100% sensitivity and 92% specificity in predicting HBsAg seroclearance. The qHBsAg level at a single timepoint among HBeAg-negative CHB patients with low HBV DNA levels at baseline was not a predictive marker for ICs; however, it accurately predicted spontaneous HBsAg seroclearance at 24 months.


Ultrastructure of Lingual Papillae in Common Chimpanzee (Pan troglodytes) Foetus, Newborn and Adult Specimens.
Among primates, the two recognized species of chimpanzees (common chimpanzee, Pan troglodytes; pygmy chimpanzee, Pan paniscus) are considered to be the most similar to humans. Importantly, in mammals, the food intake behaviour largely determines the tongue morphology, including the type, proportion and distribution of gustatory and non-gustatory tongue papillae. The lingual papillae form during its development and mature in post-natal life depending on the different feeding. In this study, we have used scanning electron microscopy to analyse the age-related changes in the lingual papillae of foetal, newborn and adult P. troglodytes. Four main types of lingual papillae, denominated filiform, fungiform, foliate and vallate, and one subtype of filiform papillae called conical papillae, were found. The main age-related changes observed in all kinds of papillae were a progressive keratinization and morphological complexity along the lifespan. During the foetal period, there was scarce keratinization, which progressively increases in young animals to adulthood. The number of filiform increased with ageing, and both filiform and fungiform papillae in adult tongues are divided into pseudopapillae. On the other hand, the vallate papillae vary from smooth simple surfaces in foetal tongues to irregular surfaces with grooves and pseudopapillae (microscopic papilla-shaped formations within the papilla itself) in adults. These results describe for the first time the age-related variations in the three-dimensional aspect of lingual papillae of the chimpanzee tongue and provide new data to characterize more precisely these structures in the human closest specie.


In vitro effects of doxorubicin and mitomycin C on human Tenon's capsule fibroblasts.
Doxorubicin is an antiproliferative agent, that also inhibits prolyl 4-hydroxylase in vitro. We evaluated the effects of doxorubicin and mitomycin C (MMC) on the proliferation of human Tenon's capsule fibroblasts and the secretion of type I collagen in these cells to explore the potential use of doxorubicin as an antifibrotic agent after glaucoma filtering surgery. Standard immunoassays were used to determine the concentrations of type I procollagen COOH-terminal peptide (PIP), laminin and vitronectin receptor in conditioned media and cell lysates in the presence or absence of doxorubicin or MMC. The mitotic activity and viability of these cells were also determined. Cellular ultrastructure was evaluated by transmission electron microscopy. Doxorubicin and MMC decreased the cellular viability, the mitotic activity, and the production of the peptides measured. The inhibition of PIP secretion into the culture medium was higher in doxorubicin-treated cultures than in MMC-treated cultures at the tested concentrations (5-100 microM). The decrease in PIP levels in cell lysates was less in doxorubicin-treated culture (25 microM) than in MMC-treated culture (25 microM), suggesting that procollagen synthesis and secretion might be attenuated by doxorubicin. Ultrastructural studies revealed increased numbers of lysosomes in the cytoplasm of doxorubicin-treated cells relative to MMC-treated cells. Doxorubicin and MMC reduced cell viability and inhibited the proliferation and synthesis of PIP, laminin, and vitronectin receptor peptide. Inhibitory effects of doxorubicin on PIP secretion were more potent than those of MMC. Doxorubicin may be useful for inhibiting the fibrotic response at the site of ocular filtering surgery.


Susceptibility to DDT and some other insecticides of head lice (Pediculus capitis De Geer) in Czechoslovakia.
For testing the susceptibility of the head louse to insecticides impregnated bunches of polyamide fibres, whose diameter resembled that of human hair (0.1 mm) were used. In this manner a low mortality of control lice collected from infected persons was obtained (2.9% after 16 hours of exposure). Even after 25 years of DDT use no apparent resistance could be demonstrated in 25 tested louse populations and cross resistance to permethrin in 7 tested populations. The diagnostic concentration for resistance to pp'-DDT was established at 1%. Of the tested insecticides the highest toxicity was shown by malathion (LC50 = 0.000 018%), pirimiphos-methyl had on average a twice lower toxicity, trichlorphon 104 times lower, tetramethrin 1220 times lower, permethrin 2.5 times lower and pp'-DDT 630 times lower toxicity.


Supportive Versus Immunosuppressive Therapy of Progressive IgA nephropathy (STOP) IgAN trial: rationale and study protocol.
The best treatment of IgA nephropathy (IgAN) is currently not well defined. The Supportive Versus Immunosuppressive Therapy of Progressive IgA Nephropathy (STOP IgAN) trial aims to answer if, in IgAN patients, an immunosuppressive treatment is more effective than a supportive treatment. In a randomized prospective multicenter study (www.clinicaltrials.gov, NCT00554502), we will treat 148 patients at risk for progressive IgA nephropathy following a 6-month run-in phase, in 2 groups: (group a) supportive treatment: patients with a persistent proteinuria >0.75 g/day will receive a maximized therapy to reduce blood pressure and urinary protein loss using angiotensin-converting enzyme inhibitors and AT1 blockers, statins, dietary counseling for a low-sodium and low-protein diet and education/intervention programs to stop smoking. (group b) immunosuppressive treatment: in addition to the identical treatment of group a, patients will receive treatment with steroids (glomerular filtration rate [GFR] > or =60 ml/min) or steroids plus cyclophosphamide/azathioprine (GFR <60 ml/min). Study end points are the complete remission of the disease and the individual degree of renal functional loss. If the immunosuppressive therapy shows a superior efficacy with respect to prevention of renal failure, the potentially higher therapy cost and risk might be justified. Finally, our trial can serve as a model for various other types of glomerulonephritis, for which such trials are very difficult to perform, given their infrequency.


Evaluation of the Mean Cost and Activity Based Cost in the Diagnosis of Pulmonary Tuberculosis in the Laboratory Routine of a High-Complexity Hospital in Brazil.
At a global level, with the increase in healthcare costs, there is a need to assess the economic impact of the incorporation of new technologies in different health disorders in different countries. There is scarce information regarding costs incurred with the use of current or new diagnostic tests for tuberculosis or from the vantage point of their incorporation within the healthcare systems of high-burden countries. The present study aimed to assess the mean cost and the activity based cost of the laboratory diagnosis for tuberculosis by means of conventional techniques and from the Detect TB®LabTest molecular test kit in a general high-complexity hospital of the public health system in Brazil. Cost analysis was performed by means of primary data, collected in the Mycobacteria and Molecular Biology Laboratory in 2013. The mean cost and activity based cost were, respectively, U$10.06/U$5.61 for centrifuged bacilloscopy by Ziehl Neelsen (ZN) and Auramine (AU); U$7.42/U$4.15 for direct bacilloscopy by ZN; U$27.38/U$16.50 for culture in a Loweinstein-Jensen solid medium; and U$115.74/U$73.46 for the Detect TB®LabTest Kit. The calculation of the ABC should be used in making decisions by administrators to be the best method of assessing the costs of conventional techniques and molecular method for providing the real value of the tests. So it is need to calculate the ABC, and not of the mean cost, in various scenarios before incorporating new technologies in health institutions.


Influence of Ward Environments on External Ventricular Drain Infections: A Retrospective Risk Factor Analysis.
Background: Ventriculostomy-related infection (VRI) is one of the most severe and common complications of external ventricular drains (EVD). Ward environment is closely related to hospital-acquired infection, but its role in EVD infection is unclear. For some other recognized risk factors, clinical evidence also remains complicated and undetermined. We aimed to evaluate ward environment including multi-bed accommodation and intensive care unit (ICU) stay as potential risk factors for VRI, as well as to confirm those already known factors. Methods: We reviewed EVDs retrospectively in our center between January 2012 and January 2017. Univariable and logistic regression analysis were performed to identify risk factors for EVD-related infection. Results: A total of 284 patients who underwent EVD procedure were included. Thirty-six (12.7%) developed EVD-related infection. Univariable analysis revealed that the infection group had longer intensive care unit (ICU) stay (6.81 vs. 3.65 days, p = 0.045) but multi-bed accommodation showed no statistical difference between the two groups (p = 0.404). Univariable analysis also showed VRI patients had lower pre-operational Glasgow Coma Scale (6.89 vs. 9.32, p = 0.001), longer drainage placement duration (11.4 vs. 8.30 days, p < 0.001), greater numbers of cerebrospinal fluid (CSF) sampling (3.89 vs. 1.73, p < 0.001), higher percentage of pre-operational artificial airway status (50.0% vs. 18.1%, p < 0.001), and higher percentage of intracranial hemorrhage diagnosis (88.9% vs. 73.8%, p = 0.048). Logistic regression analysis demonstrated longer post-operational ICU stay (>5 days, odds ratio [OR] = 3.21, p = 0.026) as independent risk factor for EVD-related infection. Other independent risk factors included CSF sampling counts (>3, OR = 5.14, p <0.001), EVD duration (>7 days, OR = 3.85, p = 0.028), and pre-operational artificial airway status (OR = 2.85, p = 0.038). Conclusions: Longer post-operational ICU stay, frequent CSF sampling, longer duration of EVD placement, and pre-operational intubation are independent risk factors for EVD infection. Multi-bed accommodation and bilateral EVD placement have no substantial influence on VRI risk.


Centrality of positive and negative deployment memories predicts posttraumatic growth in danish veterans.
The purpose of the present study was to examine theoretically motivated predictors for the development of positive changes following potentially traumatic experiences (i.e., posttraumatic growth). Specifically, we wanted to examine the prediction that memories of highly negative and positive deployment events predict subsequent posttraumatic growth. A total of 251 Danish soldiers (7% female, mean age 26.4) deployed to forward operating bases in Afghanistan filled out questionnaires before, during, and after deployment. This allowed us to perform prospective as well as cross-sectional analyses of the data. The main findings were that the centrality of highly emotional memories from deployment predicted growth alongside openness to experience, combat exposure, and social support. Importantly, the centrality of both positive and negative memories predicted growth equally well. The perceived importance of both negative and positive events may play an important part in the development of posttraumatic growth.


Outcomes of ST Segment Elevation Myocardial Infarction without Standard Modifiable Cardiovascular Risk Factors - Newer Insights from a Prospective Registry in India.
Patients with ST elevation myocardial infarction (STEMI) without standard modifiable cardiovascular risk factors (SMuRFs; dyslipidaemia, hypertension, diabetes mellitus and smoking) are reported to have a worse clinical outcome compared to those with SMuRFs. However, robust prospective data and low-and middle-income country perspective are lacking. We aimed to study the patients with first STEMI and assess the influence of SMuRFs on clinical outcomes by comparing the patients with and without SMuRFs. We included all consecutive STEMI patients without prior coronary artery disease enrolled in the Madras Medical College STEMI Registry from September 2018 to October 2019. We collected baseline clinical characteristics, revascularisation strategies and clinical outcome. We analysed suboptimal self-reported sleep duration as a 5th extended SMuRF (eSMuRF). Primary outcome was in-hospital mortality. Secondary outcomes included in-hospital complications and one-year all-cause mortality. Among 2,379 patients, 605 patients (25.4%) were SMuRF-less. More women were SMuRF-less than men (27.1% vs 22.1%; P = 0.012). SMuRF-less patients were older (57.44 ± 13.95 vs 55.68 ± 11.74; P < 0.001), more often former tobacco users (10.4% vs 5.0%; P < 0.001), with more anterior wall MI (62.6% vs 52.1%; P = 0.032). The primary outcome [in-hospital mortality (10.7% vs 11.3%; P = 0.72)] and secondary outcomes [in-hospital complications (29.1% vs 31.7%; P = 0.23) and one-year all-cause mortality (22.3% vs 22.7%; P = 0.85)] were similar in both groups. Addition of suboptimal self-reported sleep duration as a 5th eSMuRF yielded similar results. 25% of first STEMI patients were SMuRF-less. Clinical outcomes of patients without SMuRFs were similar to those with SMuRFs. Suboptimal sleep duration did not account for the risk associated with the SMuRF-less status.


Fetopathological examination for the fetuses with Down syndrome in Tunisia: Epidemiological study and associated malformations.
For Down syndrome (DS), traditional epidemiological studies to determine the prevalence, cause, and clinical significance of the syndrome have been conducted over the last 100 years. In Tunisia, the current work is the first in-depth study in epidemiology of DS from fetopathological data. The aim of this epidemiological study was to determine the impact of some feto-maternal characteristics in occurrence of DS and to search the frequency of associated congenital malformations with this syndrome. Our retrospective study was realized for 144 fetuses with DS among 9321 autopsied fetuses in embryo-fetopathological service between 1994 and 2011. In our study, the majority of mothers (72.91%) were 35 years and older, with a statistically significant difference (p<10-6, OR=16.7, CI=8.7-32.4). The abnormalities of extremities (31%) were the most common fetal abnormalities followed by facial (23.51%) and digestive abnormalities (19.63%). One of the main conclusions of this research is that the most common risk factor for DS is maternal age. On the other hand, the type and the frequency of associated congenital anomalies with DS are still controversial.


Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy.
Cerebral phosphorus-31 magnetic resonance spectroscopy was undertaken in 33 patients with biopsy-proven cirrhosis: 6 had no evidence of neuropsychiatric impairment on standard clinical, psychometric and electrophysiological testing; 8 had evidence of subclinical hepatic encephalopathy; and 19 were classified as having overt hepatic encephalopathy. The reference population comprised 15 healthy volunteers. Unlocalized spectra were acquired from the entire head with a 45-degree pulse angle and repetition times of 1 and 5 sec. Spectra localized to the basal ganglia were acquired with a 45-degree pulse angle and a repetition time of 1 sec. Peak area ratios of phosphomonoesters, inorganic phosphate, phosphodiesters and phosphocreatine relative to beta-ATP were measured in the spectra acquired. We noted no consistent change in the ratios of inorganic phosphate to ATP and phosphocreatine to ATP. Mean values of the ratios of phosphomonoesters to ATP and phosphodiesters to ATP were significantly lower in the total patient population than in the reference population, and they correlated with the patients' neuropsychiatric status. Thus we found no significant reductions in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients who were neuropsychiatrically unimpaired, but significant reductions were observed in the mean ratios of phosphomonoesters to ATP and phosphodiesters to ATP in patients with both subclinical and overt hepatic encephalopathy. The most marked reductions in these metabolite ratios were observed in patients with overt encephalopathy.


Media framing of complex issues: The case of endangered languages.
This study investigates how media frame a global trend that is complex in nature, emergent in terms of scientific understanding, and has public policy implications: the rapid disappearance of languages. It analyzes how English-language media from 15 western, industrialized countries frame the causes and implications of endangered languages over 35 years (1971-2006) - a time period notable for growing, interdisciplinary concerns over the potential negative impacts of losing the world's linguistic diversity. The results reveal a media discourse characterized by three complementary frames that are sympathetic to the plight of endangered languages, but that present the problem, its cause, and societal implications in a logical structure that would promote public complacency.


A technique for using CT images in attenuation correction and quantification in SPECT.
A technique is described for using computed tomography (CT) images for attenuation correction and quantification in SPECT. The CT images are aligned with the corresponding SPECT slices and the Hounsfield units are converted to linear attenuation coefficient values for the SPECT radionuclide. The attenuation coefficient map thus produced is used to provide the attenuation correction required in the SPECT reconstruction. The technique has been evaluated in both a non-anatomical and an anatomical phantom giving a mean accuracy in quantifying activity of various features in the phantoms of 2.6% (range 0.3%-4.0%). The value of performing scatter correction prior to attenuation correction in obtaining accurate quantification is demonstrated. The practicalities of applying the technique in patient studies are discussed.


[Surgical treatment of infective endocarditis in childhood--report of 3 cases].
This is the case report of 3 surgical patients with infective endocarditis in childhood. Case 1: A 8 year-old boy was admitted with high fever and congestive heart failure. Aureus staphylococci were identified by blood culture. Echocardiogram showed a vegetating mass on the posterior mitral leaflet. This patient was cured by emergency mitral valve replacement during the active phase of infection. Case 2: A 3 year-old girl was admitted with infective endocarditis related to VSD. Viridans streptococci were identified by blood culture. Echocardiogram showed a vegetating mass on the septal tricuspid leaflet. After successful antibiotic therapy, this patient underwent the closure of VSD and tricuspid valvuloplasty. Case 3: A 7 year-old boy was admitted with infective endocarditis related to VSD. Aureus staphylococci were identified with blood culture. Echocardiogram showed a vegetating mass on the anterior tricuspid leaflet and moderate tricuspid regurgitation. After successful antibiotic therapy, this patient underwent the closure of VSD and tricuspid valvuloplasty. We believe that echocardiography plays an important role in the diagnosis and management of infective endocarditis and that tricuspid valvuloplasty is the method of first choice in treatment of the patient with regional tricuspid infective endocarditis.


Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release.
Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a role in regulation of collagen fibrillogenesis and function as a reservoir of transforming growth factor beta (TGF-beta) in the extracellular milieu. We have examined the susceptibility of DCN to five different matrix metalloproteinases (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern. The N-terminal sequence of the two fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The values of Km for the MMPs capable of degrading DCN are very similar (10-12 microM), but the kcat/Km value for MMP-7 (30.5 microM-1.h-1) is 4.5-fold higher than those for MMP-2 and MMP-3. Incubation of a DCN-TGF-beta1 complex with MMP-2, -3 or -7 results in release of TGF-beta1 from the complex. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues.


Oxygen-related processes in red blood cells exposed to tert-butyl hydroperoxide.
The correlation between the oxidative processes in tert-butyl hydroperoxide (tBHP)-exposed red blood cells and the reactions of oxygen consumption and release were investigated. Red blood cell exposure to tBHP resulted in transient oxygen release followed by oxygen consumption. The oxygen release in red blood cells was associated with intracellular oxyhaemoglobin oxidation. The oxygen consumption proceeded in parallel with free radical generation, as registered by chemiluminescence, but not to membrane lipid peroxidation. The oxygen consumption was also observed in membrane-free haemolyzates. The order of the organic hydroperoxide-induced reaction of oxygen release with respect to the oxidant (tBHP) was estimated to be 0.9 +/- 0.1 and that of the oxygen consumption reaction was determined to be 2.4 +/- 0.2. The apparent activation energy values of the oxygen release and oxygen consumption were found to be 107.5 +/- 18.5 kJ/mol and 71.0 +/- 12.5 kJ/mol, respectively. The apparent pKa value for the functional group(s) regulating the cellular oxyHb interaction with the oxidant in tBHP-treated red blood cells was estimated to be 6.7 +/- 0.2 and corresponded to that of distal histidine protonation in haemoprotein. A strong dependence of tBHP-induced lipid peroxidation on the oxygen concentration in a red blood cell suspension was observed (P50 = 32 +/- 3 mmHg). This dependence correlated with the oxygen dissociation curve of cellular haemoglobin. The order of the membrane lipid peroxidation reaction with respect to oxygen was found to be 0.5 +/- 0.1. We can conclude that the intensity of the biochemical process of membrane lipid peroxidation in tBHP-exposed erythrocytes is controlled by small changes in such physiological parameters as the oxygen pressure and oxygen affinity of cellular haemoglobin. Neither GSH nor oxyhaemoglobin oxidation depended on oxygen pressure.


New psychotropic drug developments in German speaking countries.
Since the rediscovery of lithium salts as a prophylactic against depression and the introduction of long-term neuroleptic drugs, Europe has experienced a stagnation in the development of new psychotropic drugs of new structure and influence radius. In the past two years, only one new antidepressant, three neuroleptic drugs and three tranquilizers with a particular activity spectrum and range of indication have been developed. The antidepressant maprotilin (Ludiomil) of the substance group of dibenzo-bicyclo-octadiene shows-contrary to the previously used antidepressants-an incentive-increasing and mood-elevating but also an anxiolytic effect, nearly no influence on the circulation, insignificant side effects and a prompt onset of effect after administration. Therefore, it may also be administered for people suffering from heart disease and old age. Its main ranges of indication are for anxious and retarded endogenous as well as involutional depressive states. In the field of neuroleptics, the trend goes to development of long-term neuroleptics and also to neuroleptic drugs with prompt efficacy. Concerning tranquilizers, one is searching for anxiolytic drugs with slight sedative effects. The chemical structure related to influence radii, the ranges of indication and the side effects of these recently developed drugs are presented.


Factors affecting the outcome of extracorporeal shock wave lithotripsy for unilateral urinary stones in children: a 17-year single-institute experience.
Extracorporeal shock wave lithotripsy (ESWL) is a first-line treatment for pediatric urinary stone disease. We aimed to determine the factors affecting the outcome of ESWL for unilateral urinary stones in children. A total of 81 pediatric patients aged 0 to 16 years with urinary stones treated by ESWL from January 1995 through May 2012 were retrospectively reviewed. All patients were required to have unilateral urinary stone disease. Children who underwent other surgical procedures before ESWL were excluded. Outcomes evaluated after ESWL were the stone-free rate at 3 months after ESWL, success within a single session, and success within three sessions. Factors affecting the success within three sessions were also analyzed. The final analysis was for 42 boys and 22 girls (mean age, 9.2±5.2 years). Of these 64 patients, 58 (90.6%) were treated by ESWL without other surgical procedures and 54 (84.4%) were successfully treated within three ESWL sessions. In the multivariate analysis, multiplicity (odds ratio [OR], 0.080; 95% confidence interval [CI], 0.012 to 0.534; p=0.009) and large stone size (>10 mm; OR, 0.112; 95% CI, 0.018 to 0.707; p=0.020) were significant factors that decreased the success rate within three ESWL sessions. Most of the pediatric urinary stone patients in our study (90.6%) were successfully treated by ESWL alone without additional procedures. If a child has a large urinary stone (>10 mm) or multiplicity, clinicians should consider that several ESWL sessions might be needed for successful stone fragmentation.


Clearance of retroviremia and regression of malignancy in cats with leukemia-lymphoma during treatment with staphylococcal protein A.
Cats persistently infected with a type C retrovirus (feline leukemia virus; FeLV) were treated either by the extracorporeal perfusion of their plasma through filter columns containing staphylococcal protein A (SPA) or by the intraperitoneal injection of SPA for up to 32 treatments. The clearance of evidence of viral infection occurred during treatment with SPA in 67% of the treated cats with chronic viral infection that had FeLV-related abnormalities other than overt malignancy. This rate of viral clearance is more than 30 times greater than the incidence of spontaneous clearance of persistent FeLV viremia in the untreated cat. Actual clearance of viremia occurred in 28% of all cats treated. Regression of malignancy, which occurred in four of 12 (33%) treated cats, was demonstrated by reductions in tumor size and bone marrow neoplastic cell populations. Immediately preceding or concurrent with these remissions from viral infection and malignant disease, a marked though transient elevation in the plasma level of circulating gamma-like interferon occurred in some responding cats and was followed by the appearance and rising titer of a complement-dependent cytotoxic antibody that reacted with FeLV-infected cells. This IgG antibody was shown by several analyses to be specific for the major viral envelope glycoprotein gp70. Further investigations demonstrated that high levels of FeLV at the cellular level might be responsible for the reduced ability of normal feline lymphocytes to secrete gamma-interferon in response to mitogenic stimuli in vitro. These findings may provide some clue to the variation in the responsiveness of individual cats to immunotherapy with staphylococcal protein A.


Early experience with the Evolut FX self-expanding valve vs. Evolut PRO+ for patients with aortic stenosis undergoing TAVR.
The Evolut FX system is the most recent generation of self-expandable transcatheter heart valve (THV) technology. This study aims to report the early experience and outcomes associated with this system. Our analysis included 200 consecutive patients who underwent transcatheter aortic valve replacement at our center from 2022 to 2023. The first cohort comprised the last 100 patients who received the Evolut PRO+ THV, while the second cohort included the first 100 patients who received the Evolut FX THV. The primary endpoints of the study were defined according to the Valve Academic Research Consortium-3 (VARC-3) criteria, which included technical success (at exit from procedure), device success (at discharge or at 30 days), and early safety (at 30 days). The study groups demonstrated no significant differences in baseline characteristics, including co-morbidities, pre-procedural imaging, and echocardiography. VARC-3 technical success rate was 99 % for both valves. The VARC-3 device success rate for the Evolut FX was 92 % compared to 97 % for the Evolut PRO+ (p = 0.12), and VARC-3 early safety rate was 80.1 % for the Evolut PRO+ vs. 81.5 % for the Evolut FX (p = 0.82). The in-hospital permanent pacemaker implantation rate for the Evolut FX was 12 % compared to 9 % for the Evolut PRO+ (p = 0.21). There were no differences in clinical outcomes, such as mortality or stroke, between the two groups. The Evolut FX THV performed well when used for patients with severe aortic stenosis, demonstrating high success with low complication rates when compared to an earlier generation of self-expanding THV.


In-use testing and interpretation of chemical-resistant glove performance.
Issuing gloves to workers is the most common approach to protecting against skin contact with hazardous chemicals. Typically, glove materials are selected and duration of wear is estimated based on comparisons of laboratory test data. Those who select the glove materials often fail to verify their selections by testing the glove during actual use. This failure poses a common but potentially serious hazard to workers. Although methods are available for assessing permeation rates during actual use, such testing is unlikely without acceptable exposure guidance criteria for decision making. This document reviews methods for testing glove performance during actual use and suggests an approach for estimating acceptable exposure guidance criteria for evaluation of chemicals that are systemically absorbed. It is the authors' opinion that as of now an approach to estimating exposure criteria for chemical irritants and sensitizers may not be feasible. With available data resources, acceptable glove exposure criteria could be generated for use in assessing the risk of using specific gloves for handling many compounds in occupational settings.


Unplanned surgical reoperations in a tertiary hospital: perioperative mortality and associated risk factors.
The aim of the study was to estimate the rate of unplanned surgical reoperations in a tertiary hospital and the mortality in reoperated patients and to determine factors associated with risk of mortality in these patients. Unplanned surgical reoperations in our hospital were recorded from 1 May 2006 to 31 March 2008. Unplanned reoperation was defined as any surgical procedure required to treat a complication of a prior procedure within the first 30 days of the initial operation. Patients were followed until hospital discharge. Of 11,468 patients who underwent surgery, 381 (3.3%) required reoperation. The main indications for the second or subsequent procedure were postsurgical bleeding (26.3%) and infection (31.2%). Mortality was higher in reoperated patients (21.7 vs. 2.9% in nonreoperated patients, P<0.05). Age, number of reoperations, reoperation of patients before discharge from the postoperative care unit, acute abdomen as the indication for reoperation and reoperation in the thoracic cavity were independently associated with mortality. Unplanned reoperations have important implications for patient outcomes and are related to high mortality. Certain patient-related and procedure-related factors increase risk.


Higher Lipoprotein (a) Levels Are Associated with Better Pulmonary Function in Community-Dwelling Older People - Data from the Berlin Aging Study II.
Reduced pulmonary function and elevated serum cholesterol levels are recognized risk factors for cardiovascular disease. Currently, there is some controversy concerning relationships between cholesterol, LDL-cholesterol, HDL-cholesterol, serum triglycerides and lung function. However, most previous studies compared patients suffering from chronic obstructive pulmonary disease (COPD) with healthy controls, and only a small number examined this relationship in population-based cohorts. Moreover, lipoprotein a [Lp(a)], another lipid parameter independently associated with cardiovascular diseases, appears not to have been addressed at all in studies of lung function at the population level. Here, we determined relationships between lung function and several lipid parameters including Lp(a) in 606 older community-dwelling participants (55.1% women, 68±4 years old) from the Berlin Aging Study II (BASE-II). We found a significantly lower forced expiration volume in 1 second (FEV1) in men with low Lp(a) concentrations (t-test). This finding was further substantiated by linear regression models adjusting for known covariates, showing that these associations are statistically significant in both men and women. According to the highest adjusted model, men and women with Lp(a) levels below the 20th percentile had 217.3ml and 124.2ml less FEV1 and 239.0ml and 135.2ml less FVC, respectively, compared to participants with higher Lp(a) levels. The adjusted models also suggest that the known strong correlation between pro-inflammatory parameters and lung function has only a marginal impact on the Lp(a)-pulmonary function association. Our results do not support the hypothesis that higher Lp(a) levels are responsible for the increased CVD risk in people with reduced lung function, at least not in the group of community-dwelling older people studied here.


Conditional Reprogramming of Pediatric Human Esophageal Epithelial Cells for Use in Tissue Engineering and Disease Investigation.
Identifying and expanding patient-specific cells in culture for use in tissue engineering and disease investigation can be very challenging. Utilizing various types of stem cells to derive cell types of interest is often costly, time consuming and highly inefficient. Furthermore, undesired cell types must be removed prior to using this cell source, which requires another step in the process. In order to obtain enough esophageal epithelial cells to engineer the lumen of an esophageal construct or to screen therapeutic approaches for treating esophageal disease, native esophageal epithelial cells must be expanded without altering their gene expression or phenotype. Conditional reprogramming of esophageal epithelial tissue offers a promising approach to expanding patient-specific esophageal epithelial cells. Furthermore, these cells do not need to be sorted or purified and will return to a mature epithelial state after removing them from conditional reprogramming culture. This technique has been described in many cancer screening studies and allows for indefinite expansion of these cells over multiple passages. The ability to perform esophageal screening assays would help revolutionize the treatment of pediatric esophageal diseases like eosinophilic esophagitis by identifying the trigger mechanism causing the patient's symptoms. For those patients who suffer from congenital defect, disease or injury of the esophagus, this cell source could be used as a means to seed a synthetic construct for implantation to repair or replace the affected region.


Molecular cloning of plasmolipin. Characterization of a novel proteolipid restricted to brain and kidney.
Plasmolipin is an 18-kDa proteolipid protein found in kidney and brain, where it is restricted to the apical surface of tubular epithelial cells and to mammalian myelinated tracts, respectively (Sapirstein, V.S., Nolan, C. E., Stadler, I.I., and Fischer, I. (1992) J. Neurosci. Res. 31, 96-102; Cochary, E. F., Bizzozero, O. A., Sapirstein, V. S., Nolan, C. E., and Fischer, I. (1990) J. Neurochem. 55, 602-610). Addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K(+)-selective (Tosteson, M. T., and Sapirstein, V. S. (1981) J. Membr. Biol 63, 77-84). The present study describes the isolation and cloning of plasmolipin cDNA that includes the sequence of the complete coding region of the protein, the analysis of plasmolipin mRNA expression and a proposed model for its membrane structure. Northern blot analysis 1) shows that plasmolipin is encoded by a 1.7-kilobase mRNA, 2) confirms that the distribution of plasmolipin is restricted to kidney and brain, and 3) indicates that the expression of plasmolipin mRNA in cultured oligodendrocytes increases with cell maturation consistent with changes in the level of the protein. Restriction enzyme digestion of DNA followed by Southern blot analysis indicates that plasmolipin is encoded by a single gene. Sequence analysis of plasmolipin cDNA shows an open reading frame encoding a 157-amino acid protein of 17.4 kDa. The deduced amino acid sequence confirms the hydrophobic nature and high helical content of the protein and predicts a structure with four transmembrane domains similar to several other small hydrophobic proteins implicated in ion movement. The proposed model for membrane topology shows an enrichment of hydroxyl groups within two of the transmembrane domains and places cysteine residues near the extracellular membrane surface. Examination of protein sequence data bases reveals little overall homology with other proteins including proteolipids; however, three of the four transmembrane segments of plasmolipin show strong similarity with known membrane transport proteins. These results indicate that plasmolipin is an unique proteolipid protein that may participate in ion transport events specific to select membrane domains.


Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis.
Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by adoptive transfer of MBP-reactive T cells in order to investigate the role of astrocytes in pathology. GFAP protein and mRNA expression (analyzed using semiquantitative Western blot and RT-PCR techniques) were upregulated in the spinal cord of mice, which had developed a complete paralysis of hind- and fore-limbs and tail (grade 4 EAE), thus establishing that reactive gliosis occurred under these experimental conditions. Within the same samples and using similar techniques, we found that glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes to metabolize glutamate may contribute to EAE pathology.


Ultrafast nucleation and growth of high-quality monolayer MoSe2 crystals via vapor-liquid-solid mechanism.
The controlled production of two-dimensional atomically thin transition metal dichalcogenides (TMDs) is fundamentally important for their device applications. However, the synthesis of large-area and high-quality TMD monolayers remains a challenge due to the lack of sufficient understanding of growth mechanisms, especially for the chemical vapor deposition (CVD). Here we report molten-salt assisted CVD growth of highly crystalline MoSe2 monolayers via a novel vapor-liquid-solid (VLS) mechanism. Our results show that the growth rate of the VLS-grown monolayer MoSe2 is about 40 times faster than that of MoSe2 grown via the vapor-solid (VS) mechanism, which makes the fabrication of 100 μm domains for ∼2 min and a uniform monolayer film within 5 min. The ultrafast growth of monolayer MoSe2 crystals benefits from the synergic effect of one-dimensional VLS growth and two-dimensional VS edge expansion. Moreover, these MoSe2 monolayers exhibit high crystal quality and enhanced photoluminescence due to efficient Se-vacancy repairing by the doping of halogen atoms. These findings provide a new understanding of MoSe2 growth and open up an opportunity for the rapid synthesis of high-quality TMD monolayers and heterostructures.


Osteoporosis and the Marfan syndrome.
Fourteen patients with Marfan syndrome, defined according to present criteria, had bone mineral content of the distal forearm measured by single photon absorptiometry. Patients were matched for age and sex with a large local group of healthy volunteers. While further work is needed with other methods of densitometry with measurements at other sites, our results provide no evidence that there is an increased incidence of osteoporosis in Marfan syndrome. Previous reports of an association were probably due to incorrect clinical diagnosis or confusion with clinically similar syndromes known to cause osteoporosis.


Present approach to the severely involved rheumatoid wrist.
The wrist is a common target for rheumatoid arthritis, with the radiocarpal joint being involved more often than the midcarpal joint. The authors discuss the treatment modalities available for patients with advanced disease: total wrist fusion, flexible implant arthroplasty, and partial wrist fusion. The last procedure, utilized only since 1982 and limited to patients with only radiocarpal joint involvement, eliminates pain and corrects deformity while maintaining a significant range of motion. The indications and techniques for each procedure are described.


Higher visuo-Attentional Demands of Multiple Object Tracking (MOT) Lead to A Lower Precision in Pointing Movements.
Multiple object tracking (MOT) requires visually attending to dynamically moving targets and distractors. This cognitive ability is based on perceptual-attentional processes that are also involved in goal-directed movements. This study aimed to test the hypothesis that MOT affects the motor performance of aiming movements. Therefore, the participants performed pointing movements using their fingers or a computer mouse that controlled the movements of a cursor directed at the targets in the MOT task. The precision of the pointing movements was measured, and it was predicted that a higher number of targets and distractors in the MOT task would result in a lower pointing precision. The results confirmed this hypothesis, indicating that MOT might influence the performance of motor actions. The potential factors underlying this influence are discussed.


Sinus histiocytosis with massive lymphadenopathy: response to cyclophosphamide therapy.
A patient with sinus histiocytosis with massive lymphadenopathy is described. After attempts to control lymph node size and constitutional symptoms with corticosteroids were unsuccessful with radiation therapy and nonsteroidal anti-inflammatory drugs, the patient was treated with two courses of low doses of oral cyclophosphamide therapy. He remains in complete remission 15 months after therapy was discontinued.


Anal-rectal cytology: correlation with human papillomavirus status and biopsy diagnoses in a population of HIV-positive patients.
We describe the cytological distribution of disease, correlate cytological diagnoses with human papillomavirus (HPV) DNA status and surgical biopsy diagnoses, determine if CD4 counts correlate with lesion severity, and compare anal-rectal data of HIV-infected patients (primarily men) with cervical data. A retrospective search of the computerized database identified 118 HIV-positive patients who had anal-rectal cytology. Cytology results were compared with available follow-up data including repeat anal-rectal cytology tests, surgical biopsy, CD4 counts, and HPV DNA polymerase chain reaction-based genotyping. Cytological diagnoses included 3% unsatisfactory for diagnosis, 41% negative for intraepithelial lesion or malignancy (NILM), 23% atypical squamous cells of undermined significance (ASC-US), 31% low-grade squamous intraepithelial lesion (LSIL), and 2% high-grade squamous intraepithelial lesion (HSIL) (ASC-US/squamous intraepithelial lesion, 0.7:1). Two anal intraepithelial neoplasia (AIN) II, 10 AIN III, and 1 invasive squamous cell carcinoma were histologically detected (11%). The majority of AIN II was preceded by LSIL, 54%; ASC-US, 15%; and HSIL, 8%. The false-negative fraction was 23%. Sensitivity, specificity, negative predictive value, and positive predictive value were 92%, 8%, 33%, and 67%, respectively. Of those HPV tested concurrent with the first cytology specimen, 48% NILM, 78% ASC-US, and 100% LSIL were HPV positive. Mean CD4 counts (per microliter) were lower in patients with HSIL (243 [SD, 65]) compared with LSIL (400 [SD, 261]) and NILM (428 [SD, 232]). Anal-rectal cytology is a useful screening test. A high percentage of AIN II lesions were detected in this at-risk population, and the majority was detected following cytological abnormality.