Adverse events due to change in organization of problem drug users' treatment?
This study set out to identify any undesirable consequences of legislative change in the organization of the treatment of problem drug users (PDUs), which aimed to combine their social and medical care. The method used was a register-based three-year follow-up prevalent cohort study. On 1 January 1996, the law was changed to allocate unambiguous and undivided responsibility for the combined social and medical care of PDUs in Denmark. The main objective of the legislative change was to move PDUs from treatment by general practitioners (GPs) and at private clinics to treatment institutions under the control of the counties. The possibility remained that medical treatment could, however, continue to be given by GPs or private clinics, based on specific agreements. The study showed that at the end of the period, 31 December 1998, two-thirds remained in treatment at private clinics or at GP surgeries. During the period only 8% of users were at some time without methadone treatment; 2% remained without methadone treatment throughout the study period. The transition from GPs and private clinics to the county treatment centres went smoothly. The number of PDUs in MMT (methadone maintenance treatment) in the city of Copenhagen increased in the period 1995 to 1998. The average quantity of methadone given to the cohort increased during these years from 72 mg per day to 92 mg per day. The legislative change therefore did not result in a higher threshold for treatment or a more restrictive prescription of methadone. No adverse effect on crime, hospital admissions, or death could be attributed to the legislative change in treatment organization.


Modification of radiation damage in rat spinal cord by mitotane.
Modification of the paralytic response in rats after 6-MV photon irradiation of the spinal cord with either single or split exposures (two equal fractions given in a 24-hour period) by mitotane was investigated. Mitotane was administered as a suspension in physiologic saline (300 mg/kg/day) for either 5 days prior to or 5 days after irradiation. For rats receiving split doses of 6-MV photons, either the last two doses of mitotane were given 2 hours prior to each radiation fraction or mitotane was begun 2 hours after the second fraction and continued for 5 days. The data to 6 months after irradiation indicate that, in rats given mitotane for 5 days prior to single-dose photon irradiation, the paralytic response (as defined by the dose needed to produce paralysis in 50% of the irradiated groups of rats) was enhanced by a dose-enhancement factor (DEF) of 1.40. The DEF in the group of rats given mitotane after single doses of 6-MV photons was 1.15. In the split-dose irradiation experiments, the DEF for the groups of rats given mitotane prior to each radiation fraction was 1.36; while the DEF for the group of rats receiving mitotane beginning after the second fraction was 1.18. These data indicate that mitotane can potentiate the effects of 6-MV photon irradiation to the central nervous system, with mitotane administered prior to irradiation being the most effective sequence.


[Pearl and mother-of-pearl powder in health-care].
Based on pharmacological studies in files, mice and rats, the powder of sea pearl (Pteria martensii), mother-of-pearl and freshwater pearl has been proved to have tonic, anti-aging and anti-radiative actions. The effect of the sea pearl and mother-of-pearl powder is higher than that of freshwater pearl powder.


Analysis of the biosynthesis of HLA-DR glycoproteins in human malignant melanoma cell lines.
Human malignant melanoma cell line SK-MEL-37 expresses HLA-DR antigens having a characteristic 2-chain structure, with heavy chains (alpha) of approximately 32,000 daltons and light chains (beta) of approximately 28,000 daltons. Nonequilibrium pH-gradient electrophoresis (NEPHGE) on HLA-DR immunoprecipitated by rabbit anti-HLA-DR sera from [35S]-methionine-labeled, pulse-chased cells showed 2 closely spaced heavy-chain components (1, 2) and 4 light-chain spots (3-6). From nonchased samples, numerous more-basic components running in the heavy chain region were also precipitated. In particular, a very basic, 30,000 dalton component (pl approximately 8.5) was prominent (component 7); this spot probably corresponds to the invariant (Ii) peptide previously demonstrated in lymphoid cell HLA-DR precipitates (9) and the M-1 peptide of Shackelford and Strominger (10). None of these components (alpha, beta, or component 7) was precipitated from extracts of HLA-DR-negative melanoma cells. Pulse-chase experiments and the use of different labeled sugar precursors showed that component 7 is a partially glycosylated intracellular precursor, possibly of the HLA-DR alpha-chain. None of the immunoprecipitates, even from cells pulse-labeled for only 15 min, contained a peptide migrating in the 55,000 to 60,000 m.w. region. It was concluded that melanoma HLA-DR is not synthesized via a polyprotein precursor. In contrast to these results, obtained with rabbit anti-HLA-DR sera, a mouse monoclonal anti-HLA-DR was found to precipitate only biosynthetically completed alpha (1, 2) and beta (3-6) chains.


Effect of cell-wall skeleton of Mycobacterium bovis BCG on cell-mediated cytotoxicity in tumor-bearing mice.
Effect of oil-attached BCG cell-wall skeleton (BCG-CWS) on cell-mediated cytotoxicity in tumor-being mice was investigated using the allograft system. It was found that the treatment with oil-attached BCG-CWS was able to elevate the immunolgically depressed state of tumor-bearing mice to a normal level as determined by chromium release assay.


Acceleration of vacuolar regeneration and cell growth by overexpression of an aquaporin NtTIP1;1 in tobacco BY-2 cells.
Aquaporin is a water channel that increases water permeability through membranous structures. In plants, vacuoles are essential organelles that undergo dynamic volume changes during cell growth. To understand the contribution of aquaporins to plant cell growth, we developed a transgenic tobacco BY-2 cell line overexpressing the tonoplast intrinsic protein (TIP), gammaTIP. Vacuolar membranes of isolated vacuoles from gammaTIP-overexpressing cells showed higher water permeation activities than those from wild-type cells. We then examined the role of gammaTIP in vacuolar regeneration of evacuolated tobacco BY-2 protoplasts (miniprotoplasts). Vacuolar regeneration from thin to thick tube-network vacuoles and subsequent development of large vacuoles was accelerated in miniprotoplasts of this cell line. A parallel increase in the rate of cell expansion indicated a tight relationship between vacuolar development and cellular volume increases. Interestingly, overexpression of tobacco gammaTIP also enhanced cell division. Thus, increased vacuolar aquaporin activity may accelerate both cell expansion and cell division by increasing water permeability through the vacuolar membrane.


The prevalence of and risk factors for erosive oesophagitis and non-erosive reflux disease: a nationwide multicentre prospective study in Korea.
Prospective nationwide multicentre studies that have evaluated endoscopic findings and reflux symptoms using a well-designed questionnaire are very rare. To compare the prevalence rates of and risk factors for erosive oesophagitis and non-erosive reflux disease (NERD) in the Korean population. A gastroscopic examination was performed on 25 536 subjects who visited 40 Healthcare Centers for a health check-up. A gastro-oesophageal reflux questionnaire and multivariate analysis were used to determine the risk factors for erosive oesophagitis and NERD. 2019 (8%) and 996 subjects (4%) had erosive oesophagitis and non-erosive reflux disease, respectively; only 58% of subjects with erosive oesophagitis had reflux symptoms. Multivariate analysis showed that the risk factors for erosive oesophagitis and NERD differed, i.e. those of erosive oesophagitis were male, a Helicobacter pylori eradication history, alcohol, body mass index > or =25 and hiatal hernia. In contrast, the risk factors for NERD were female, age <40 and > or =60 vs. 40-59 years, body mass index <23 and a monthly income <$1000, glucose > or =126 mg/dL, smoking, a stooping posture at work and antibiotic usage. The prevalence rates of erosive oesophagitis and NERD were 8% and 4%, respectively, in Korean health check-up subjects. The risk factors for erosive oesophagitis and NERD were found to differ, which indicates that their underlying pathogeneses are distinct.


Tuning the acid/metal balance of carbon nanofiber-supported nickel catalysts for hydrolytic hydrogenation of cellulose.
Carbon nanofibers (CNFs) are a class of graphitic support materials with considerable potential for catalytic conversion of biomass. Earlier, we demonstrated the hydrolytic hydrogenation of cellulose over reshaped nickel particles attached at the tip of CNFs. The aim of this follow-up study was to find a relationship between the acid/metal balance of the Ni/CNFs and their performance in the catalytic conversion of cellulose. After oxidation and incipient wetness impregnation with Ni, the Ni/CNFs were characterized by various analytical methods. To prepare a selective Ni/CNF catalyst, the influences of the nature of oxidation agent, Ni activation, and Ni loading were investigated. Under the applied reaction conditions, the best result, that is, 76 % yield in hexitols with 69 % sorbitol selectivity at 93 % conversion of cellulose, was obtained on a 7.5 wt % Ni/CNF catalyst prepared by chemical vapor deposition of CH(4) on a Ni/γ-Al(2)O(3) catalyst, followed by oxidation in HNO(3) (twice for 1 h at 383 K), incipient wetness impregnation, and reduction at 773 K under H(2). This preparation method leads to a properly balanced Ni/CNF catalyst in terms of Ni dispersion and hydrogenation capacity on the one hand, and the number of acidic surface-oxygen groups responsible for the acid-catalyzed hydrolysis on the other.


6''-Azido-6''-deoxy-UDP-N-acetylglucosamine as a glycosyltransferase substrate.
6''-Azido-6''-deoxy-UDP-N-acetylglucosamine (UDP-6Az-GlcNAc) is a potential alternate substrate for N-acetylglucosaminyltransferases. This compound could be used to generate various glycoconjugates bearing an azide functionality that could in turn be subjected to further modification using Staudinger ligation or Huisgen cycloaddition. UDP-6Az-GlcNAc is synthesized from α-benzyl-N-acetylglucosaminoside in seven-steps with an overall yield of 6%. It is demonstrated to serve as a substrate donor for the glycosyl transfer reaction catalyzed by the human UDP-GlcNAc:polypeptidyltransferase (OGT) to the acceptor protein nucleoporin 62 (nup62).


The toxicity of human serum against Ehrlich cells--an attempt at characterizing responsible components.
A biochemical characterization of the toxic action of human serum on murine Ehrlich ascites tumor cells was attempted. Some observations are consistent, other inconsistent, with the hypothesis of complement dependent antibodies reacting with ubiquitous antigens on these cells. Studies using various serum fractions, and with pure preparations of human serum proteins, have not given consistent results. Of particular interest is the puzzling observation that the toxic action of human serum fractions sometimes only appears some time after the fractionation.


[Conservative endoscopic treatment for achalasia of the esophagus. Our experience].
The Authors report their experience in the endoscopic treatment using pneumatic dilatation for 18 patients with achalasia, seen in the period January 1992 August 1995 at the Laboratory of Digestive Endoscopy of the Institute of General Thoracic and Vascular Surgery of the University of Parma. Ten were males and 8 females, age range 23-79 years (average age 48 yrs.). The most common symptoms was dysphagia, all patients were radiologically and manometrically studied confirming the clinical and endoscopic diagnosis. All underwent pneumatic dilatation under endoscopic control. In all, 36 dilations were carried out without registering complications related to the method. A maximum follow-up of 30 months confirmed a good-excellent outcome in 89% of cases. In 3 cases a gastroesophageal reflux symptomatology was registered, but successfully treated medically. The Authors conclude that the pneumatic dilation for achalasia is to be considered the treatment of choice, leaving the surgical approach only for cases resistant to such treatment.


Grading by the Ki-67 Labeling Index of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Specimens of Pancreatic Neuroendocrine Tumors Can Be Underestimated.
There is an increasing need for grading with small endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) specimens for the proper diagnosis and therapy selection of patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, our understanding of EUS-FNAB specimen grading is limited compared with surgically resected specimens. We retrospectively determined Ki-67 labeling index (LI) of 33 matched EUS-FNAB and surgically resected PanNETs with digital image analyzer. Pairwise grades between the matched biopsy and surgically resected PanNET specimens were compared. The mean Ki-67 LI was higher in surgically resected PanNET specimens (5.5%) than in biopsy specimens (3.2%; P = 0.022). There was moderate agreement between the Ki-67 LI grades when individually evaluated matched biopsy and resected specimen pairs were compared (κ value = 0.62; P < 0.0001). However, discordance was noted in 6 cases (18%), and all of them were either grade 2 or 3 in resected PanNETs. Although Ki-67 LI grading of EUS-FNAB specimens may be concordant with that of matched surgically resected specimens in a large proportion of the PanNET cases, Ki-67 LI grading of EUS-FNAB specimens should be carefully applied in clinical practice because of the possibility of grading underestimation with grade 2 to 3 PanNET cases.


[Establishment of sleeve gastrectomy model in diet-induced obese Sprague-Dawley rats].
To establish sleeve gastrectomy(SG) rats model of obese type 2 diabetes mellitus(T2DM) for the research of hypoglycemic mechanism. Nine male Sprague-Dawley (6-week-old) rats were fed with high-sucrose and high-fat diet for 4 weeks, developing diet-induced obesity (DIO) rats model. The rats were then randomly divided into two groups. Six rats of them underwent sleeve gastrectomy(SG) as the sleeve gastrectomy group[SGG, body weight (471.8±17.9) g] and the other three rats underwent a laparotomy and stomach manipulation as the sham operative group[SOG, body weight (467.0±8.4) g]. The body weight, caloric intake and peripheral blood concentration of total ghrelin of rats were recorded after operation. The weight of all the rats declined progressively after operation. The weight of the rats in SOG began to rise on the 5th postoperative day(POD) and regain their preoperative levels on the average 22nd POD. However, the weight of the rats in SGG began to rise slowly from the 9th POD, but was still lower than that of SOG[(487.4±10.1) g] and preoperative levels[(471.8±17.9) g] on the 28th POD[(420.1±18.6) g](P=0.001). Average caloric intake of rats in SGG was significantly lower than that of SOG after operation, but there was no significant difference between the two groups(P=0.121). The ghrelin level of SGG showed a continuous decreasing trend after intervention, decreased by 17.4% compared with the preoperative level (1595.1±14.4 ng/L) on the 28th POD[(1316.8±14.8) ng/L]. The ghrelin level of SOG did not change obviously before and after operation and both groups differ statistically(P=0.000). A SG rat model is successfully established. This model can be used for the further study of mechanism analysis of T2DM resolution after surgery.


Stabilization of a ribosomal RNA tertiary structure by ribosomal protein L11.
Interactions between ribosomal protein L11 and a domain of large subunit rRNA have been highly conserved and are essential for efficient protein synthesis. To study the effects of L11 on rRNA folding, a homolog of the Escherichia coli L11 gene has been amplified from Bacillus stearothermophilus DNA and cloned into a phage T7 polymerase-based expression system. The expressed protein is 93% homologous to the L11 homolog from Bacillus subtilis, denatures at temperatures above 72 degrees C, and has nearly identical rRNA binding properties as the Escherichia coli L11 in terms of RNA affinity constants and their dependences on temperature, Mg2+ concentration, monovalent cation, and RNA mutations. Mg2+ and NH4+ are specifically bound by the RNA-protein complex, with apparent ion-RNA affinities of 1.6 mM-1 and 19 M-1, respectively, at 0 degree C. The effect of the thermostable L11 on the unfolding of a 60 nucleotide rRNA fragment containing its binding domain has been examined in melting experiments. The lowest temperature RNA transition, which is attributed to tertiary structure unfolding, is stabilized by approximately 25 degrees C, and the interaction has an intrinsic enthalpy of approximately 13 kcal/mol. The thermal stability of the protein-RNA complex is enhanced by increasing Mg2+ concentration and by NH4+ relative to Na+. Thus L11, NH4+, and Mg2+ all bind and stabilize the same rRNA tertiary interactions, which are conserved and presumably important for ribosome function.


[Classification and grading of tumors of the central nervous system--pathological analysis of 4,373 cases].
To research on the clinical application of the WHO 1979, 1993 and 2000 classifications of tumours of the central nervous system. With the analysis of 4 373 cases, problems were studied in applying the WHO classifications. (1) The 2000 classification used double criteria of WHO and ICD-O. The relationship between them was very confusing. (2) Opinions suggested for about 15 types of the tumours of meningothelial cells. (3) It was difficult to separate benign, atypical or anaplastic meningiomas. (4) The diagnostic criterion of anaplastic gliomas was not clear. (5) Practically, glioblastoma was a type of mixed gliomas. (6) More cases should be studied in order to recognize special types of the tumours of neuroepithelial tissue. Suggested to make out a criterion of classification and grading that is more applicable for clinical diagnosis.


Identification of calcium binding proteins in two-dimensional gel electrophoretic pattern of Drosophila thorax and their distribution in two types of muscles.
Ten Drosophila thorax proteins (six myosin light chains and four proteins called a, b, c, d) were found to have high affinities with Ca2+. This was proved after subjecting the total Drosophila thorax proteins to two-dimensional (2D) transblot, followed by 45Ca2+ autoradiography. Three proteins (a, c, d) showed Ca2+ dependent electrophoretic mobility changes. To know their tissue-specific localization, fibrillar and tubular type muscle fibers were individually dissected from freeze-dried flies and separately subjected to 2D gel electrophoresis. Fibrillar type muscle had protein b and a small amount of protein a. Tubular type muscle had proteins c, d and a very large amount of protein a. Protein d was characterized to be calmodulin.


Metal-free oxidative synthesis of quinazolinones via dual amination of sp3 C-H bonds.
A novel metal-free synthesis of quinazolinones via dual amination of sp(3) C-H bonds was developed. The sp(3) carbon in methylarenes or adjacent to a heteroatom in DMSO, DMF or DMA was used as the one carbon synthon.


Perioperative goal-setting consultations by surgical colleagues: a new model for supporting patients, families, and surgeons in shared decision making.
Patients with postoperative complications are often subjected to prolonged life-sustaining treatment based on erroneous assumptions about their goals of care. Shared decision making (SDM) is an evidence-based approach that helps ensure patients' wishes and values are honored in their course of treatment. Perioperative palliative care can help create goal-concordant trajectories of care for high risk, seriously ill, or complicated patients, through sophisticated prognostication, higher-level communication, and recommendations based on the best available evidence and patients' stated goals and priorities. Here, we present a surgeon-to-surgeon consultative model that surmounts many barriers to perioperative palliative care consultation and, as illustrated in the cases presented herein, offers profound and unique benefits for patients, families, and surgeons alike. While the support of a surgical colleague with palliative care skills can be helpful postoperatively in the setting of unanticipated outcomes or prolonged recovery, it is particularly beneficial when accessed preoperatively for the purposes of goal-concordant decision making and advance care planning. We encourage both individuals and professional societies to develop and expand the niche for surgeons interested in assisting with goal setting and SDM for patients on a consultative basis, particularly in the preoperative period.


Efficacy of scalp hair decontamination following exposure to vapours of sulphur mustard simulants 2-chloroethyl ethyl sulphide and methyl salicylate.
Chemical warfare agents are an actual threat and victims' decontamination is a main concern when mass exposure occurs. Skin decontamination with current protocols has been widely documented, as well as surface decontamination. However, considering hair ability to trap chemicals in vapour phase, we investigated hair decontamination after exposure to sulphur mustard simulants methyl salicylate and 2-chloroethyl ethyl sulphide. Four decontamination protocols were tested on hair, combining showering and emergency decontamination (use of Fuller's earth or Reactive Skin Decontamination Lotion RSDL®). Both simulants were recovered from hair after treatment, but contents were significantly reduced (42-85% content allowance). Showering alone was the least efficient protocol. Concerning 2-chloroethyl ethyl sulphide, protocols did not display significant differences in decontamination efficacy. For MeS, use of emergency decontaminants significantly increased showering efficacy (10-20% rise), underlining their usefulness before thorough decontamination. Our results highlighted the need to extensively decontaminate hair after chemical exposure. Residual amounts after decontamination are challenging, as their release from hair could lead to health issues.


Fe-doped cryptomelane synthesized by refluxing at atmosphere: Structure, properties and photocatalytic degradation of phenol.
Fe-doped cryptomelanes were synthesized by refluxing at ambient pressure, followed by characterization with multiple techniques and test in photocatalytic degradation of phenol. The introduction of Fe(III) into the structure of cryptomelane results in a decrease in particle size and the contents of Mn and K(+), and an increase in the Mn average oxidation state (AOS), specific surface area and UV-vis light absorption ability. Mn and Fe K-edge extended X-ray absorption fine structure spectroscopy analysis indicates that some Fe(III) is incorporated into the framework of cryptomelane by replacing Mn(III) while the remaining Fe(3+) is adsorbed in the tunnel cavity. These Fe-doped cryptomelanes have significantly improved the photocatalytic degradation rate of phenol, with the sample of ∼3.04 wt.% Fe doping being the most reactive and achieving a degradation rate of 36% higher than that of the un-doped one. The enhanced reactivity can be ascribed to the increase in the coherent scattering domain size of the crystals, Mn AOS and light absorption, as well as the presence of sufficient K(+) in the tunnel. The results imply that metal doping is an effective way to improve the performance of cryptomelane in pollutants removal and has the potential for modification of Mn oxide materials.


New therapies: calcimimetics, phosphate binders and vitamin D receptor activators.
At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.


The role of nuclei and nucleoli in the control of cell proliferation.
A number of changes have been reported to occur in chromatin of quiescent cells stimulated to proliferate. These changes, indicative of increased transcriptional activity, occur in the early prereplicative phase, several hours before the onset of DNA replication, and are detectable not only in chromatin, but also in isolated nuclei and in whole cells. Most of the increased transcriptional activity can be attributed to an increased activity of the nucleolus; however, extranucleolar genes are also important in the regulation of the cell cycle flow, from G0 to S.


Synthesis and evaluation of aryl-substituted N-(arylethyl)-N-methyl-2-(1-pyrrolidinyl)ethylamines and corresponding arylacetamides for sigma receptor affinity.
A series of aryl-monosubstituted arylacetamides (4-9) and arylethylenediamine (10-18) compounds were synthesized based on the structure of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2). These compounds were prepared to evaluate the effect of aromatic substitution patterns on sigma-1 and sigma-2 receptor binding affinity and selectivity. The data indicate that 10-18 possessed higher affinity than 4-9 for both sigma sites, especially when substituted with an electron-withdrawing group. The diamine compounds 10-18 were selective for sigma-1 binding sites, whereas the arylacetamide compounds 4-9 generally exhibited an increased selectivity for sigma-2 sites compared to sigma-1. No clear pattern between the orientation of aromatic substituents and the sigma binding activity was observed.


Roles of the amino acid side chains in the actin-binding S-site of myosin heavy chain.
The heptapeptide Ile-Arg-Ile-Cys-Arg-Lys-Gly-OEt is the analog of the S-site, one of the actin-binding sites in myosin [Suzuki et al. (1987) J. Biol. Chem. 262, 11410-11412]. Various substituted heptapeptides were synthesized, and the dissociation constants of each acto-heptapeptide complex was measured. Comparison of the dissociation constants indicated that the hydrophobic side chain of Ile-1 was critical for the binding with F-actin, but not that of Ile-3. The positive charge and the side chain length of Arg-2 were also important. The presence of a sulfur atom in the Cys-4 was also necessary. The affinity of the N-terminal Ile-Arg-Ile part for F-actin was influenced by the kind of residues in the C-terminal tetrapeptide part. Based on these results, the side chains of Ile(702), Arg(703), and Cys(SH1)(705) in myosin subfragment-1 heavy chain were assigned to be critical for the binding with F-actin. The amino acid sequence of S-1 heavy chain containing these critical residues for the S-site from residue number 700 to 717 can be predicted as an analogue of the segment B of the ATP-binding site [Walker et al. (1982) EMBO J. 1, 945-951]. The actin-binding S-site possibly shares a part of the ATP-binding site in myosin. We discuss the possibility that the S-site is an inhibitory site of myosin ATPase and the so-called actin-activation of myosin ATPase is a deinhibition induced by transient binding of F-actin to the S-site.


KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition.
KRAS-mutant lung cancers have been recalcitrant to treatments including those targeting the MAPK pathway. Covalent inhibitors of KRAS p.G12C allele allow for direct and specific inhibition of mutant KRAS in cancer cells. However, as for other targeted therapies, the therapeutic potential of these inhibitors can be impaired by intrinsic resistance mechanisms. Therefore, combination strategies are likely needed to improve efficacy.Experimental Design: To identify strategies to maximally leverage direct KRAS inhibition we defined the response of a panel of NSCLC models bearing the KRAS G12C-activating mutation in vitro and in vivo. We used a second-generation KRAS G12C inhibitor, ARS1620 with improved bioavailability over the first generation. We analyzed KRAS downstream effectors signaling to identify mechanisms underlying differential response. To identify candidate combination strategies, we performed a high-throughput drug screening across 112 drugs in combination with ARS1620. We validated the top hits in vitro and in vivo including patient-derived xenograft models. Response to direct KRAS G12C inhibition was heterogeneous across models. Adaptive resistance mechanisms involving reactivation of MAPK pathway and failure to induce PI3K-AKT pathway inactivation were identified as likely resistance events. We identified several model-specific effective combinations as well as a broad-sensitizing effect of PI3K-AKT-mTOR pathway inhibitors. The G12Ci+PI3Ki combination was effective in vitro and in vivo on models resistant to single-agent ARS1620 including patient-derived xenografts models. Our findings suggest that signaling adaptation can in some instances limit the efficacy of ARS1620 but combination with PI3K inhibitors can overcome this resistance.


[Study of some neurohistologic objects by the method of scanning microscopy].
With the aid of a scanning measuring microscope (R. E. Bykov et al., 1972) different biological microobjects were measured in particular the nuclei of neurons and gliocytes at differnt levels of the spinal cord under normal and experimental conditions. The nuclei of the rabbit hypothalamus were stimulated by graded electrical current in order to induce neurogenic visceral dystrophies. Investigation of the square surfaces of cross sections of the neuron and gliocyte nuclie in different terms permitted establishment of progressing diminishing of the size of the square surface of the neuron nuclei against the background of a relatively steady state of steady state of wquare surfaces of the cross section of the nuclei of the adjacent glial cells. The obtained data are of interest not only for studying transneuronal changes in disturbed trophical function of the nervous system, but may be taken into consideration in clinical practice when elaborationg prerequistites for purposeful neurovegetative blocade in neurogenic dystrophies of the central genesis.


Clinical evaluation of a multifocal aspheric diffractive intraocular lens.
To evaluate the performance of an aspheric diffractive multifocal acrylic intraocular lens (IOL), ZMB00 1-Piece Tecnis. Five sites across Europe. Fifty-two patients with cataracts (average age 68.5±10.5 years, 35 female) were bilaterally implanted with the aspheric diffractive multifocal IOL after completing a questionnaire regarding their optical visual symptoms, use of visual correction and their visual satisfaction. The questionnaire was completed again 4-6 months after surgery along with measures of uncorrected and best-corrected distance and near visual acuity, under photopic and mesopic lighting, reading ability, defocus curve testing and ocular examination for adverse events. The residual refractive error was 0.01±0.47D with 56% of eyes within ±0.25D and 97% within ±1.0D. Uncorrected visual acuity was 0.02±0.10logMAR at distance and 0.15±0.30 logMAR at near, only reducing to 0.07±0.10logMAR at distance and 0.21±0.25logMAR at near in mesopic conditions.The defocus curve showed a near addition between 2.5-3.0 D allowing a reading acuity of 0.08±0.13 logMAR, with a range of clear vision <0.3 logMAR of ∼4.0 D. The average reading speed was 121.4±30.8 words per minute. Spectacle independence was 100% for distance and 88% for near, with high levels of satisfaction reported. Overall rating of vision without glasses could be explained (r=0.760) by preoperative best-corrected distance acuity, postoperative reading acuity and postoperative uncorrected distance acuity in photopic conditions (p<0.001). Only two minor adverse events occurred. The ZMB00 1-Piece Tecnis multifocal IOL provides a good visual outcome at distance and near with minimal adverse effects.


[Health-related quality of life of people with severe traumatic injury: a longitudinal study using the SF-36 health survey].
Even though 85 percent of those who have been severely injured in an accident in Germany survive, complex and serious long-term consequences are still a major problem not only for health and care insurance providers but also for the accident victims themselves because their quality of life is affected permanently. Therefore the aim of the current study is to identify factors that significantly improve the quality of life after a severe traumatic injury and to investigate whether the support by a reintegration service has a positive effect on the victims' quality of life. The sample consisted of severely injured accident victims who were supported by a reintegration service. The data collection comprised three data points. At every data point the SF-36 questionnaire was used to assess the participants' quality of life. The results indicate that an individual medical-vocational support by a reintegration service has the potential to significantly and stably improve the physical aspects of quality of life, even if the accident dates back several years. Furthermore it appears to be important to support the independence of the accident victims because assistance by a third person correlates with a lower degree of physical quality of life, regardless of severity or type of injury. Moreover it becomes clear that it is important to pay more attention to the treatment of psychological consequences of severe accidents.


Association of passive smoking with respiratory symptoms and clinical correlates, among married women, in a rural community in Islamabad.
To investigate the association of passive smoking with respiratory symptoms and clinical correlates in married women in a rural area of Pakistan. A Cross-sectional study was carried out on married women of Nurpur Shahan (rural Islamabad) by means of an Interviewer administered questionnaire. Systematic sampling of households was done. A total of 296 women were surveyed. The study period extended from January to July 2009. All data was entered and analyzed using SPSS v 10.0. The two major respiratory symptoms that were found to be associated with passive smoking were sinusitis [adjusted O.R(95% CI) 2.2 (1.3 - 3.5), p = 0.001] and cough [adjusted O.R (95% CI) 2.4 (1.2 - 4.8), p = 0.017]. Wood used as fuel for cooking purposes also contributed to one of the symptoms such as headache (p = 0.007). The pulse rate (79 +/- 11 beats/min) of the passive smoking women was statistically significantly higher than the pulse rate (76 +/- 9 beats/min) of the non-passive smoking women (p = 0.012). Passive smoking was found to be associated with respiratory symptoms among married women in this study. Higher pulse rate was associated with passive smoking.


In vitro assessment of immunocompetence in patients with malignant melanoma.
Ninety-four patients with malignant melanoma and 96 healthy controls were tested for lymphocyte proliferative capacity in a microblastogenesis assay. Each lymphocyte sample was assayed for incorporation of (3H)thymidine after stimulation with PHA, PWM, Con A (two doses), PPD, and allogeneic lymphocytes (MLC). MLC was the only assay that revealed a substantial and significant difference between the melanoma patients and controls. Almost all assays showed lower values in patients with more advanced disease. However, it was not possible to accurately predict clinical outcome from data obtained from in vitro immunocompetence tests. These results indicate the relatively limited clinical usefulness of assays of lymphocyte proliferative capacity in melanoma patients.


An edge spread technique for measurement of the scatter-to-primary ratio in mammography.
An experimental measurement technique that directly measures the magnitude and spatial distribution of scatter in relation to primary radiation is presented in this work. The technique involves the acquisition of magnified edge spread function (ESF) images with and without scattering material present. The ESFs are normalized and subtracted to yield scatter-to-primary ratios (SPRs), along with the spatial distributions of scatter and primary radiation. Mammography is used as the modality to demonstrate the ESF method, which is applicable to all radiographic environments. Sets of three images were acquired with a modified clinical mammography system employing a flat panel detector for 2, 4, 6, and 8 cm thick breast tissue equivalent material phantoms composed of 0%, 43%, and 100% glandular tissue at four different kV settings. Beam stop measurements of scatter were used to validate the ESF methodology. There was good agreement of the mean SPRs between the beam stop and ESF methods. There was good precision in the ESF-determined SPRs with a coefficient of variation on the order of 5%. SPRs ranged from 0.2 to 2.0 and were effectively independent of energy for clinically realistic kVps. The measured SPRs for 2, 4, and 6 cm 0% glandular phantoms imaged at 28 kV were 0.21+/-0.01, 0.39+/-0.01, and 0.57+/-0.02, respectively. The measured SPRs for 2, 4, and 6 cm 43% glandular phantoms imaged at 28 kV were 0.20+/-0.01, 0.35+/-0.02, and 0.53+/-0.02, respectively. The measured SPRs for 2, 4, and 6 cm 100% glandular phantoms imaged at 28 kV were 0.22+/-0.02, 0.42+/-0.03, and 0.88+/-0.08, respectively.


Pig thyroid spectrin. A membrane-associated protein related in structure and function to brain spectrin.
Thyroid spectrin has been obtained pure from pig thyroid glands. This protein, composed of two non-identical polypeptide chains of 240 kDa and 235 kDa, appears to possess the same structural and immunological properties as well as the same calmodulin and actin-binding properties as brain spectrin. Through cross-linking of actin filaments it is a potent gelation factor for F-actin solutions. It represents one of the major protein of the cytoskeleton underlying the thyroid plasma membrane together with myosin, alpha-actinin and actin.


Lack of pharmacokinetic interaction after administration of lansoprazole or omeprazole with prednisone.
In a recently reported case, administration of omeprazole, a "proton pump" inhibitor, was temporally associated with the clinical relapse of pemphigus in a 44-year-old woman whose condition had been stabilized with a fixed dose of prednisone, suggesting the possibility of a drug interaction. This placebo-controlled, randomized, double-blind, three-period crossover study was conducted to evaluate and compare the pharmacokinetics of prednisolone after a single dose of prednisone given during multi-dose administration of lansoprazole or omeprazole. Lansoprazole (30 mg), omeprazole (40 mg), or placebo was administered once daily under fasted conditions for 7 days to healthy male volunteers. On the seventh day, a single dose of prednisone (40 mg) was administered concomitantly with the study medication, and plasma prednisolone concentrations were measured by high-performance liquid chromatography for 24 hours thereafter. Two weeks separated the first doses of each study period. Eighteen volunteers entered the study; pharmacokinetic data were evaluable for 15 participants. Safety data were evaluable for 16 participants in the lansoprazole/prednisone group; 17 in the omeprazole/ prednisone group; and 17 in the placebo/prednisone group. The pharmacokinetic parameters for prednisolone, including the maximum observed plasma concentration (Cmax), time to maximum plasma concentration (tmax), terminal-phase half-life (t1/2), and area under the concentration-time curve, were comparable for the three regimens. Adverse events (AEs) rated as possibly or probably drug related were reported by 50%, 24%, and 47% for subjects in the lansoprazole, omeprazole, and placebo treatment groups, respectively. Headache was the most common drug-related AE. No serious AEs were reported, and no subject withdrew from the study because of an AE. Concomitant administration of lansoprazole or omeprazole does not affect the absorption, biotransformation, or disposition of a single dose of prednisone. All three treatment regimens were well tolerated.


ACOG Committee Opinion No. 613: Increasing access to abortion.
Safe, legal abortion is a necessary component of women's health care. The American College of Obstetricians and Gynecologists supports the availability of high-quality reproductive health services for all women and is committed to improving access to abortion. Access to abortion is threatened by state and federal government restrictions, limitations on public funding for abortion services and training, stigma, violence against abortion providers, and a dearth of abortion providers. Legislative restrictions fundamentally interfere with the patient-provider relationship and decrease access to abortion for all women, and particularly for low-income women and those living long distances from health care providers. The American College of Obstetricians and Gynecologists calls for advocacy to oppose and overturn restrictions, improve access, and mainstream abortion as an integral component of women's health care.


Decontamination of biological agents from drinking water infrastructure: a literature review and summary.
This report summarizes the current state of knowledge on the persistence of biological agents on drinking water infrastructure (such as pipes) along with information on decontamination should persistence occur. Decontamination options for drinking water infrastructure have been explored for some biological agents, but data gaps remain. Data on bacterial spore persistence on common water infrastructure materials such as iron and cement-mortar lined iron show that spores can be persistent for weeks after contamination. Decontamination data show that common disinfectants such as free chlorine have limited effectiveness. Decontamination results with germinant and alternate disinfectants such as chlorine dioxide are more promising. Persistence and decontamination data were collected on vegetative bacteria, such as coliforms, Legionella and Salmonella. Vegetative bacteria are less persistent than spores and more susceptible to disinfection, but the surfaces and water quality conditions in many studies were only marginally related to drinking water systems. However, results of real-world case studies on accidental contamination of water systems with E. coli and Salmonella contamination show that flushing and chlorination can help return a water system to service. Some viral persistence data were found, but decontamination data were lacking. Future research suggestions focus on expanding the available biological persistence data to other common infrastructure materials. Further exploration of non-traditional drinking water disinfectants is recommended for future studies.


[Clinical and neuro electrophysiologic study of flail arm syndrome].
To explore the clinical and neuroelectrophysiological characteristics of flail arm syndrome (FAS). The clinical and neuroelectrophysiological characteristics were analyzed retrospectively from July 1, 2006 to July 1, 2012 in FAS patients (n = 56), those with upper limb onset amyotrophic lateral sclerosis (ALS) (n = 60) and those with upper brachial plexus neuropathy (n = 22) from our hospital. Nerve conduction study of musculocutaneous, axillary, median, ulnar, radial, tibial, peroneal and sural nerves and electromyogram (EMG) of bulbar, cervical, thoracic and lumbosacral regions were conducted. In FAS patients, the ratio of male-to-female was 5:1 and they were characterized by symmetric, proximal wasting and weakness of upper extremities, the involved muscles demonstrated neurogenic damage on EMG and the amplitude of compound muscle action potential (CMAP) of arms decreased. Compared with ALS patients, the amplitude of motor unit action potential (MUAP) of deltoid muscle and biceps muscle was higher in FAS patients ((1531 ± 76) vs (898 ± 57) µV; (1433 ± 57) vs (872 ± 75) µV) (F = 13.25, 6.33; P < 0.05). Compared with upper brachial plexus neuropathy patients, the amplitude of MUAP of first dorsal interosseous, deltoid and biceps muscles was higher in FAS patients ((1263 ± 24) vs (507 ± 42) µV; (1531 ± 76) vs (564 ± 27) µV; (1433 ± 57) vs (593 ± 36) µV) (F = 12.32, 16.71, 8.35; P < 0.05). The clinical manifestations of FAS are symmetric, proximal wasting and weakness of arms. And the involved muscles show denervation on EMG and the amplitudes of CMAPs decrease in motor nerves of upper extremities.


[Suitability of the practice of recording only the main health problem in primary care].
To analyse if recording only the main health problem (P) can reflect in a valid way the totality of health problems (P+S) cared for and all the actions generated by a consultation. Using a representative sample of the patients seen at the centre over a three-month period, information on P+S was gathered, P was identified and the actions generated by each one of the problems were recorded. Health problems were codified through CIPSAP-2-D and grouping diagnoses. SITE. General Medicine service in a Primary Care Centre. All the General Medical physicians at the Centre took part in the study by collecting data on the consultations established by the sampling. Frequency and order among the first 25 P+S and P problems were compared, as was the percentage of secondary problems encountered. Out of 559 consultations examined, Diabetes, Dislepemia and an irritated? Colon stood out as under-represented. Acute infections of the Upper Respiratory Tract, Conjunctivitis and ??Queratitis were over-represented. As for the activity generated, 83.1% corresponded to P, although there was great variability among the problems according to the percentage of secondary problems according to the percentage of secondary problems. Recording only the main health problem can be a valid instrument for providing an initial view of problems seen.


Spatio-temporal distribution of cell-bound and dissolved geosmin in Wahnbach Reservoir: Causes and potential odour nuisances in raw water.
In many lakes and reservoirs, problems caused by off-flavours are known to be particularly associated with the occurrence of planktonic and benthic cyanobacteria. Frequently observed objectionable taste and odorous products of cyanobacteria are geosmin and 2-methylisoborneol. Investigations focused on the littoral zone of Wahnbach Reservoir (Germany) revealed that benthic cyanobacteria were present in this oligotrophic drinking water reservoir. Benthic cyanobacteria were found in the depth horizon between 1.75 m and 11 m, particularly on south-exposed slopes. This spatial distribution indicates a possible key role of the underwater light climate. Moreover, cell-bound and dissolved geosmin were detected in corresponding littoral samples. Both fractions were subjected to spatial and primarily temporal variations with maximum concentrations at the end of summer. However, a substantial lowering of the water level caused a diminution of cyanobacterial growth. Due to the drawdown of the water level concentrations of cell-bound geosmin and pigments (as a proxy of cyanobacterial biomass) were remarkably reduced, and dissolved geosmin was never detected during this phase. Except for the influence of water level fluctuation no other abiotic variables had a significant influence on pigment and geosmin concentrations. From geosmin concentrations detected in the littoral zone, the probability of serious episodes of odour events in the raw water of the Wahnbach Reservoir was estimated. Hence, the probability that the raw water was affected by geosmin was minor, which was supported by routine flavour profiles. Nevertheless, the study shows that odorous episodes caused by benthic cyanobacteria are likely to develop even in an oligotrophic lake or reservoir when these cyanobacteria, and consequently odorous production, proliferate. In principle, such a proliferation cannot be excluded as nutrients are available from the sediment pore water, and underwater light at the sediment surface in the sub-littoral is sufficiently high due to very low phytoplankton-induced turbidity under oligotrophic conditions. Thus, management-induced fluctuations of the water level seem to be the main control variable to generate light conditions at the sediment surface fluctuating in a given depth horizon faster than cyanobacteria can develop there.


The influence of trees on the thermal environment and behaviour of grazing heifers in Brazilian Midwest.
The intensification of the livestock production system has gained prominence over the last decades. In addition to the reduction of grazing areas and increased productivity per hectare, the intercropping involving forest tree species and ruminants has been established as a sustainable production model, generating income and valuation of natural capital. Besides the social, economic, and environmental aspects, the animal welfare is a noteworthy factor. The objective of this study was to evaluate the microclimatic conditions in an open-pasture and in silvopastoral systems, considering the Temperature Humidity Index (THI) and alterations in animal behavior. Three different pasture arrangements were analyzed in this study: total absence of trees in an open-pasture (ArrA), presence of peripheral trees (Eucalyptus spp.) along the border fences (ArrB), and an intensive wooded area aggregated with pasture (ArrC). A herd of 24 crossbreed heifers (3/4 and 7/8 Holstein-Girolando breed) was evaluated. Behavior data were collected every 15 min starting at 08 h00 with readings ending at 16 h00. THI was used to evaluate the environmental comfort. The THI found in the system with open-pasture and in the two systems with silvopastoral arrangement reached critical levels. The two arrangements with eucalyptus rows were not capable of eliminating heat stress in the conditions found in the north region of Mato Grosso State although better conditions were obtained under the tree canopy. The differences between the microclimatic variables for the three arrangements modified the behavior of the animals regarding their location and activity, except for water consumption.


Automated three-dimensional analysis of particle measurements using an optical profilometer and image analysis software.
The automated collection of topographic images from an optical profilometer coupled with existing image analysis software offers the unique ability to quantify three-dimensional particle morphology. Optional software available with most optical profilers permits automated collection of adjacent topographic images of particles dispersed onto a suitable substrate. Particles are recognized in the image as a set of continuous pixels with grey-level values above the grey level assigned to the substrate, whereas particle height or thickness is represented in the numerical differences between these grey levels. These images are loaded into remote image analysis software where macros automate image processing, and then distinguish particles for feature analysis, including standard two-dimensional measurements (e.g. projected area, length, width, aspect ratios) and third-dimensional measurements (e.g. maximum height, mean height). Feature measurements from each calibrated image are automatically added to cumulative databases and exported to a commercial spreadsheet or statistical program for further data processing and presentation. An example is given that demonstrates the superiority of quantitative three-dimensional measurements by optical profilometry and image analysis in comparison with conventional two-dimensional measurements for the characterization of pharmaceutical powders with plate-like particles.


The treatment of sleep disorders of older people.
The National Institutes of Health Consensus Development Conference on the Treatment of Sleep Disorders of Older People brought together clinical specialists in pulmonology, psychiatry, psychology, geriatrics, internal medicine, other health care providers, and the public to address the cause, diagnosis, assessment, and specific treatments of sleep disorders of older people. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the scientific evidence and prepared a consensus statement. Among their findings, the panel concluded that although sleep patterns change during the aging process most older people with sleep disturbances suffer from any of a variety of medical and psychosocial disorders. The panel recommended that the diagnostic evaluation of sleep disorders begin with a careful clinical evaluation performed by an informed primary care physician. When necessary, referrals should be made to individuals or centers with specialized skills and tools for therapy. The panel recognized two types of disorders for which treatment may be beneficial: obstructive sleep apnea and insomnia. The mainstay for treatment for sleep apnea is the use of nasal continuous positive airway pressure. A thorough medical evaluation is essential prior to initiating treatment for insomnia, as its causes may be of psychiatric, pharmacological, or medical origin. The panel recommended that hypnotic medications not be the mainstay of treatment for insomnia as they may have habit forming potential if overused. The full text of the consensus panel's statement follows.


Investigation of neuropathic pain in treated leprosy patients in Ethiopia: a cross-sectional study.
Pain can be a significant problem for treated leprosy patients. It can be nociceptive due to tissue inflammation occurring during episodes of immune mediated reactions, or neuropathic due to leprosy affecting the somatosensory system. There are sparse epidemiological data on the prevalence and impact of neuropathic pain in treated leprosy patients. Tools for assessing neuropathic pain have not been validated in leprosy. We have examined nature of pain in a cross-sectional study to determine the prevalence of neuropathic pain (NP) in 80 recently treated leprosy patients in Ethiopia. Pain and depression were evaluated using the General Health Questionnaire (GHQ-12) and the Brief Pain Inventory (BPI) questionnaire. The Douleur Neuropathique en 4 Questions (DN4) and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used as screening tools for NP. Pain of any type was experienced by 60% of the patients. Pure nociceptive pain was experienced by 43%, pure NP by 11%, and mixed pain by 6%. Of the 14 patients who had NP either alone or in combination with nociceptive pain, 12 had high GHQ-12 scores, indicating possible depression. The DN4 had sensitivity and specificity of 100% and 45%, whereas the LANSS had 85% and 42%, respectively. This is the first study to differentiate nociceptive from NP in leprosy patients. The prevalence of NP is high in recently treated Ethiopian leprosy patients. We have validated the use of DN4 in leprosy and it is easier to use than LANSS. Depression is a common co-morbidity in patients with NP. The high prevalence and morbidity of NP in treated leprosy patients warrant clinical trials to assess the efficacy of pain therapies for leprosy-associated NP.


Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation.
This clinical study evaluated prospectively adverse events immediately following ultrasound-guided foam sclerotherapy (UGFS) for the treatment of lower extremity venous valvular insufficiency. Incidence of side effects associated with carbon dioxide (CO(2)) foam was compared with a historical control using air-based foam. The literature on the subject was reviewed. Vital signs were monitored during and immediately after UGFS, and adverse events were recorded for 24 hours following the procedure. The air-based foam group had 49 patients: 44 women and 5 men. The CO(2)-based foam group had 128 patients: 115 women and 13 men. CEAP class was C2EpAsPr, describing varicose veins, primary etiology, and saphenous reflux. UGFS followed thermal ablation of the great saphenous vein. Foam was prepared using the three-way tap technique to mix gas with 1% polidocanol in a 4:1 ratio. Segments of the great and small saphenous veins and their tributaries were treated with UGFS. Foam volumes injected were 27 +/- 10 (SD) (6-46 range) and 25 +/- 12 (6-57 range) mL for air- and CO(2)-based foams respectively (P = .39). Incidence of adverse events was compared by chi(2) statistics. Vital signs were compared by paired t test. During the procedure, the average heart rate decreased by less than 5 bpm for both groups (P < .001), and blood pressure decreased by less than 3 mm Hg in the CO(2) group (P < .02). Respiratory rate, electrocardiogram, and pulse oxymetry did not change significantly in both air- and CO(2)-foam series (P > .05). Visual disturbances were experienced by 3.1% (4/128) and 8.2% (4/49) patients in the CO(2) and air groups respectively (P = .15). Respiratory difficulties or circumoral paresthesia each occurred in 0.8% (n = 1) of the CO(2) patients. Incidence of chest tightness (3.1% vs 18%), dry cough (1.6% vs 16%), or dizziness (3.1% vs 12%) were significantly lower in the CO(2) vs air groups (P < .02). Nausea occurred in 2% and 4% of the CO(2) and air-based foam groups (P = .53). Overall, the proportion of patients describing side effects decreased from 39% (19/49) to 11% (14/128) as CO(2) replaced air for foam preparation (P < .001). Similar findings were described in the literature of air-based foam but data on the use of physiological gas were rare. Side effects decreased significantly if CO(2) rather than air was employed to make the sclerosing foam for chemical ablation of superficial veins of the lower extremity.


Analysis of new biomarkers for cholangiocarcinoma.
Cholangiocarcinoma is one of the most serious diseases in northeast Thailand, where its incidence is reported to be the highest in the world. We tried to develop a new method to detect cholangiocarcinoma in the early stages using serum proteins. We found that after fluorescent labeling of the sugar moiety of serum proteins, a new peak was identified, which might be a promising marker for cholangiocarcinoma.


Carriage of methicillin-resistant Staphylococcus aureus by veterinarians in Australia.
To estimate the prevalence of carriage of methicillin-resistant Staphylococcus aureus (MRSA) among Australian veterinarians. Individuals attending veterinary conferences in Australia in 2009 were recruited to provide nasal swabs and complete a questionnaire about their professional activities. Swabs were processed by standard methods for detecting MRSA and questionnaire responses were used to group veterinarians according to their areas of major work emphasis (species and practice type). Prevalence was estimated for each of these grouping and contingency tables and regression tree analysis used to explain the variation in MRSA carriage. Among the 771 respondents 'industry and government veterinarians' (controls) had the lowest prevalence of MRSA carriage at 0.9%. Veterinarians with horses as a major area of work emphasis had a prevalence of 11.8% (13-fold that of controls) and those whose only major emphasis was horses had a prevalence of 21.4% (23-fold that of controls). Veterinarians with dogs and cats as a major activity had a 4.9% prevalence (5-fold that of controls). Prevalence rates for other major activities (pigs, dairy and beef cattle, avian and wildlife) were also increased, but were estimated from smaller numbers of respondents. Regression tree analysis clearly isolated equine veterinarians and dog and cat practitioners as groups at increased risk of carriage of MRSA. Carriage of MRSA is a notable occupational health issue for veterinarians in clinical practice in Australia, particularly those who work with horses.


Type VI collagen expression is upregulated in the early events of chondrocyte differentiation.
Dedifferentiated chondrocytes cultured adherent to the substratum proliferate and synthesize large amounts of type I collagen but when transferred to suspension culture they decrease proliferation, resume the chondrogenic phenotype and the synthesis of type II collagen, and continue their maturation to hypertrophic chondrocyte (Castagnola et al., 1986, J. Cell Biol. 102, 2310-2317). In this report, we describe the developmentally regulated expression of type VI collagen in vitro in differentiating avian chondrocytes. Type VI collagen mRNA is barely detectable in dedifferentiated chondrocytes as long as the attachment to the substratum is maintained, but increases very rapidly upon passage of the cells into suspension culture reaching a peak after 48 hours and declining after 5-6 days of suspension culture. The first evidence of a rise in the mRNA steady-state levels is obtained already at 6 hours for the alpha 3(VI) chain. Immunoprecipitation of metabolically labeled cells with type VI collagen antibodies reveals that the early mRNA rise is paralleled by an increased secretion of type VI collagen in cell media. Induction of type VI collagen is not the consequence of trypsin treatment of dedifferentiated cells since exposure to the actin-disrupting drug cytochalasin or detachment of the cells by mechanical procedures has similar effects. In 13-day-old chicken embryo tibiae, where the full spectrum of the chondrogenic differentiation process is represented, expression of type VI collagen is restricted to the articular cartilage where chondrocytes developmental stage is comparable to stage I (high levels of type II collagen expression).(ABSTRACT TRUNCATED AT 250 WORDS)


Incorporating social media into dermatologic education.
In the current digital age, medical education has slowly evolved from the largely lecture-based teaching style of the past to incorporate more interactive pedagogical techniques, including use of social media. Already used readily by millennial trainees and clinicians, social media can also be used in innovative ways to teach trainees and facilitate continuing education among practicing clinicians. In this commentary, we discuss many learning benefits of social media and review potential pitfalls of employing social media in both trainee and physician dermatological education.


Validation of the human tissue factor/FVIIa complex as an antithrombotic target and the discovery of a synthetic peptide.
This review focuses on the validation of the principal initiator of human coagulation, the tissue factor (TF)/coagulation factor (F)VIIa complex, as an antithrombotic target, as well as on the discovery of a cyclic pentapeptide (PN7051), which dose-dependently inhibits TF/FVIIa-induced coagulation and thrombus formation. Target validation and studies of antithrombotic efficacy were performed with a human thrombosis model employing non-anticoagulated blood from severe homozygous FVII-deficient patients and healthy individuals at blood-flow conditions mimicking those in healthy and diseased vessels. Additional validation included an anti-TF monoclonal antibody, recombinant TF pathway inhibitor, recombinant inactivated-active site FVIIa and all-trans retinoic acid. Structural and biological characterization of PN7051 and other peptides from the same FVII domain indicate that PN7051 interferes with an essential interaction between the epidermal growth factor domain-2-like and the catalytic domains of FVIIa. A peptidomimetics approach is suggested to further improve the antithrombotic potency of PN7051.


The wound/burn guidelines - 6: Guidelines for the management of burns.
Burns are a common type of skin injury encountered at all levels of medical facilities from private clinics to core hospitals. Minor burns heal by topical treatment alone, but moderate to severe burns require systemic management, and skin grafting is often necessary also for topical treatment. Inappropriate initial treatment or delay of initial treatment may exert adverse effects on the subsequent treatment and course. Therefore, accurate evaluation of the severity and initiation of appropriate treatment are necessary. The Guidelines for the Management of Burn Injuries were issued in March 2009 from the Japanese Society for Burn Injuries as guidelines concerning burns, but they were focused on the treatment for extensive and severe burns in the acute period. Therefore, we prepared guidelines intended to support the appropriate diagnosis and initial treatment for patients with burns that are commonly encountered including minor as well as moderate and severe cases. Because of this intention of the present guidelines, there is no recommendation of individual surgical procedures.


A regional ultrasonic technique to measure left ventricular performance during coronary artery bypass.
Miniaturized, highly accurate pressure transducers and segment length measuring devices have been proven a safe, practical and stable method of analyzing cardiac performance in both acute and chronic animal experimentation. We have utilized a micromanometer-tipped intraventricular catheter and an ultrasonic segment length gauge implanted in the subendocardial layer of the left ventricle at the time of cardiac surgery to measure changes in systolic function and diastolic compliance prior to and after the completion of the operative procedure in man. No complications of this technique were encountered in the thirty patients studied. Continuous improvements in instrument design, data collection and data processing suggest future clinical applications are possible and desirable.


How is children's weight status assessed for early identification of overweight and obesity? - Narrative review of programs for weight status assessment.
Assessment of a child's weight status is the first step in the management of childhood overweight and obesity. We reviewed routine assessment programs to inform early and routine identification of childhood overweight and obesity to address this global health issue. Twelve electronic databases were searched (Scopus, Web of Science, Wiley, ScienceDirect, PsycINFO, PsycARTICLES, PsycEXTRA, CINAHL, Primary Search, MEDLINE, ERIC, Academic Search Elite) for universal programs for weight status assessment of children aged 4-12 in Organization for Economic Co-operation and Development - countries, which included more than one assessment and parents receiving feedback. Of 1638 papers found via database searches, and 18 additional records identified through other sources, 26 were included. Reference to five countries' programs for weight status assessment was found in the results: Australia, Sweden, the Netherlands, the United Kingdom and the United States. All of these programs were implemented in a school setting. Lack of services, stakeholder collaboration, parental awareness and engagement and government funding need to be improved for this health check to be undertaken as a part of an ongoing program. This review is about the implementation of similar programs. Early identification of risk for overweight and obesity allows families that require help to connect with available health services.


Effects of temperature and pretreatment conditions on mixed-acid fermentation of water hyacinths using a mixed culture of thermophilic microorganisms.
The MixAlco process biologically converts biomass to carboxylate salts that may be chemically converted to a wide variety of chemicals and fuels. This study investigated the use of water hyacinths as a feedstock, comparing digestibility after each of four different pretreatments at two fermentation temperatures (40 and 55 degrees C). Water hyacinths were treated with excess lime (0.3g Ca(OH)(2)/g dry biomass). Short-term treatment occurred for 1 and 2h at 100 degrees C. Long-term treatment occurred for 4 and 6 weeks at 50 degrees C. Treated water hyacinths were fermented with marine microorganisms for 28 days and acid concentration (g/L), conversion (g volatile solids (VS) digested/g VS fed), and selectivity (g acid/g VS digested) were measured. All pretreatments out performed fresh feedstock fermentations. The 40 degrees C fermentations exhibited greater acid yields and selectivity than the 55 degrees C. The 1-h hot-lime pretreatment exhibited the best overall outcomes at approximately 250%, 200%, and 125% increases relative to the fresh water hyacinths in total acid, conversion, and selectivity, respectively. The results show that with a gentle 1-h hot-lime pretreatment, water hyacinths can be fermented to produce liquid fuels, thus creating an economic value to water hyacinths that are cleared from choked waterways.


Nitric oxide induces apoptosis in spleen lymphocytes from MRL/lpr mice.
MRL/MpJ-Tnfrsf6lpr(MRL/lpr) mice, a murine model of systemic lupus erythematosus (SLE), have defective expression of Fas, substantially reducing signaling for apoptosis via this mechanism. However, it is known that MRL/lpr mice have increased spontaneous apoptosis of leukocytes. These conflicting observations have stimulated interest in apoptosis in this SLE model. MRL/lpr mice overproduce nitric oxide (NO) as autoimmune disease progresses. In vitro administration of NO may induce or decrease apoptosis depending on the cell type. Therefore, we hypothesized that NO induces MRL/lpr spleen lymphocyte apoptosis independent of Fas receptor engagement. Percentages of apoptotic spleen lymphocytes from MRL/lpr and BALB/cJ mice were determined ex vivo after in vivo treatment with NG-monomethyl-L-arginine (NMMA), a nitric oxide synthase (NOS) inhibitor. After culture in varying concentrations of a slow-acting NO donor, the following were determined in spleen lymphocytes: (1) levels of apoptosis, (2) the effect of phorbol myristate acid (PMA) on levels of NO-induced apoptosis, and (3) protein kinase C (PKC) activity. Spleen lymphocytes from MRL/lpr mice with active disease had increased levels of ex vivo apoptosis when compared with BALB/cJ controls. This increase was reduced by pharmacologic inhibition of NOS in MRL/lpr but not in BALB/cJ mice. Exogenous administration of NO in vitro reduced PKC activity and induced apoptosis in MRL/lpr spleen lymphocytes, an effect that could be reduced via coadministration of PMA in vitro. These results suggest that NO plays a role in spleen lymphocyte apoptosis in MRL/lpr mice, possibly via inhibition of PKC, despite a Fas defect.


Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor.
Recent evidence points to a relationship between the down-regulation of the calcium-sensing receptor (CaR) and parathyroid cell hyperplasia that is associated with chronic renal failure. It is not known, however, if down-regulation of the CaR precedes, and perhaps initiates, parathyroid cell proliferation, or if a decrease in the expression of the CaR occurs subsequently to hyperplasia or the conditions promoting it. The current study examined the temporal relationship of these two events. Rats were made uremic by subtotal nephrectomy and were (1) placed immediately on a high phosphate (HP) diet that promotes parathyroid gland hyperplasia, or (2) maintained on a low phosphate (LP) diet that inhibits development of secondary hyperparathyroidism before being switched to the HP diet. Serum chemistries and parathyroid gland (PTG) weights were examined; CaR content and parathyroid cell proliferation (PCNA/Ki-67) were analyzed by immunohistochemistry. When rats were nephrectomized and placed immediately on a HP diet, parathyroid cell proliferation was significantly increased by day 2 and continued to increase at day 4. CaR content was unchanged at 1 and 2 days post-nephrectomy, but fell by day 4. When nephrectomized rats were maintained for 1 week on a LP diet, then switched to a HP diet, an increase in parathyroid cell proliferation was again seen at day 2; down-regulation of the CaR did not occur until after 7 days of uremia and the HP diet. These data indicate that parathyroid cell hyperplasia precedes down-regulation of CaR expression in the uremic rat model.


Didactic teaching conferences for IM residents: who attends, and is attendance related to medical certifying examination scores?
Didactic teaching conferences are a cornerstone of residents' training in internal medicine, yet these programs have received little formal evaluation. This study determines the factors associated with residents' attendance at didactic teaching conferences and the relationship of attendance to residents' scores on medical certification examinations. The attendance of 81 residents was recorded at 199 conferences at one university hospital's internal medicine residency program during the 1996-97 academic year. Characteristics of the conferences were recorded, including the date, whether lunch was provided, the daily census on the medicine general wards, daily ambient temperature, and conference type. Residents' scores on the United States Medical Licensing Examination (USMLE) Step 2 and American Board of Internal Medicine (ABIM) certification examination were collected. Residents' attendance at conferences was 34% overall or 54% excluding excused absences. Adjusting for the conferences' and residents' characteristics, attendance declined by one third as the year progressed. Providing lunch at noon conferences enhanced residents' attendance (odds ratio [OR] 1.26 overall and OR 1.64 for residents on inpatient rotations). Higher attendance was not associated with improvement in standardized medical knowledge test scores. Absenteeism and waning attendance through the year have important implications for structuring didactic internal medicine teaching. Providing lunch improves attendance, but this incentive should be weighed against the potential burdens of the pharmaceutical industry's funding of these lunches. The lack of relationship between attendance and residents' adjusted board scores calls for a better understanding of the value of this high-intensity medical education intervention.


[Anticonvulsant and neuroprotective effects of cyclopentyladenosine on the model of convulsive status in rats].
The neuroprotective and anticonvulsant effects of cyclopentyladenosine (CPA) have been studied on a new experimental model of the convulsive status in rats aged 3-4 months and 10 days. The convulsive status was modeled by intracerebroventricular injection of ferakril (water-soluble polymer of polyacrylic acid) solution. It is established that prophylactic administration of CPA results in a relatively lower degree of neurological deficit, both in the acute phase and on the next day, compared to the untreated control. Considering that adenosine receptor agonists are analogs of the natural metabolites that have minimal side effects and expressed neuroprotective properties, the use of agents of this group is perspective for both prevention and treatment of seizure conditions in neurology and neurosurgery.


Hydrogenation of C-C multiple bonds mediated by [Pd(NHC)(PCy(3))] (NHC=N-heterocyclic carbene) under mild reaction conditions.
N-Heterocyclic carbenes do it again! [Pd(SIPr)(PCy(3))] (1; SIPr=N,N'-(bis(2,6-diisopropylphenyl)imidazolidine), which is stable under H(2), was shown to be a highly active catalyst for the hydrogenation of a wide range of alkenes and alkynes. Reactions proceed under mild conditions (relatively low Pd loading, RT, low pressures of H(2)) even when sterically hindered alkenes (tri- and tetra-substituted) are used.


Analytical and numerical study on a vortex sheet in incompressible Richtmyer-Meshkov instability in cylindrical geometry.
Motion of a fluid interface in the Richtmyer-Meshkov instability in cylindrical geometry is examined analytically and numerically. Nonlinear stability analysis is performed in order to clarify the dependence of growth rates of a bubble and spike on the Atwood number and mode number n involved in the initial perturbations. We discuss differences of weakly and fully nonlinear evolution in cylindrical geometry from that in planar geometry. It is shown that the analytical growth rates coincide well with the numerical ones up to the neighborhood of the break down of numerical computations. Long-time behavior of the fluid interface as a vortex sheet is numerically investigated by using the vortex method and the roll up of the vortex sheet is discussed for different Atwood numbers. The temporal evolution of the curvature of a bubble and spike for several mode numbers is investigated and presented that the curvature of spikes is always larger than that of bubbles. The circulation and the strength of the vortex sheet at the fully nonlinear stage are discussed, and it is shown that their behavior is different for the cases that the inner fluid is heavier than the outer one and vice versa.


Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite.
Young adult male Sprague-Dawley rats were given 30 mumol/kg body weight [14C]methylamine hydrochloride and 700 mumol/kg body weight sodium nitrite by oral gavage. DNA isolated from the stomach and from the first 15 cm of the small intestine was methylated, containing 7-methylguanine (7mG) at a level of one 7mG molecule per 5 X 10(6) and 1 X 10(7) nucleotides, respectively. No 7mG was found in the liver at a limit of detection of one 7mG molecule per 2 X 10(8) nucleotides. In a second experiment, the excised stomachs were incubated with deoxyribonuclease before the isolation of the DNA in order to degrade DNA in the lumen and in the uppermost lining cells. This treatment resulted in a 30% decrease in the yield of DNA and a 90% reduction in the level of 7mG formation. The results show that nitrosation of a primary alkylamine yields a precursor of an alkylating agent which has a long enough lifetime to diffuse towards and react with intracellular DNA. A correlation of DNA methylation in the stomach with the corresponding tumor formation by the methylating carcinogen N-methyl-N'-nitro-N-nitroso-guanidine was used to estimate the role of DNA damage resulting from endogenous nitrosation of dietary methylamine in man. It was concluded that the risk resulting from this single amine must be negligible but that a similar evaluation of other primary amines is required before the over-all role of primary amine nitrosation in the etiology of human gastric cancer can be assessed.


Survivin and Bcl-2 expression in prostatic adenocarcinomas.
Dysregulated cell proliferation caused by inhibitors of programmed cell death (apoptosis) contributes to tumor progression and spread. Aberrant expression of Bcl-2, the most notable inhibitor of apoptosis, has been well characterized in several human malignancies. Recent studies have described a novel apoptosis inhibitor, survivin, in human carcinomas, although its exact role remains to be characterized. The purpose of this study was to evaluate the immunohistochemical expression of Bcl-2 and survivin proteins in prostate cancer and to correlate the results with clinicopathologic variables. Formalin-fixed, paraffin-embedded tissue sections from 138 cases of prostatic adenocarcinomas (PACs) were immunostained by an automated method using specific antibodies against survivin and Bcl-2. Staining was semiquantitatively scored based on both intensity and distribution, and results were correlated with morphologic and prognostic variables. Of the 138 PACs tested, 113 (82%) expressed survivin. We found no correlation between survivin expression and prognostic variables, including grade, stage, DNA content (ploidy), and recurrence. Bcl-2 expression was positive in 95 (69%) of these 138 cases and correlated with nondiploid DNA content. Fourteen (50%) of 28 nondiploid PACs expressed Bcl-2, compared to 17 (25%) of 68 diploid tumors (P =.02). A trend for association of Bcl-2 expression with tumor stage was noted as follows: 21 (39%) of 54 advanced-stage PACs expressed Bcl-2, in comparison with 20 (24%) of 84 low-stage tumors (P =.07). On univariate analysis, 25 (48%) of the 52 PACs that recurred expressed Bcl-2, as compared with 16 (19%) of the 86 nonrecurrent PACs (P <.001). No correlation was noted between survivin and Bcl-2 expression. Survivin is expressed in a majority of PACs and is not a prognosis-related marker, but may be a potential target for apoptosis-based therapy. Overexpression of Bcl-2 correlates with other prognostic variables and predicts disease recurrence of PACs. These data also suggest that survivin and Bcl-2 may regulate cell proliferation and cell death through different mechanisms.


The antiseptic effect of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution.
A quick drying rubbing type disinfectant of non-water non-towel type is an antiseptic method suitable for practical use in intensive care units where emergency situations are common. We determined the antiseptic efficacy and safety of a quick drying rubbing type povidone-iodine alcoholic disinfectant solution (HAD Hand Wash) in comparison with benzalkonium chloride alcoholic lotion. The bacterial reduction rate obtained by hand washing with a single 3 ml application was 93.8% for HAD Hand Wash and 94.1% for benzalkonium chloride alcoholic lotion. Thus, excellent antiseptic efficacy was obtained with both disinfectants. Roughening of hand skin which appeared in association with HAD Hand Wash solution was transient and mild in nature in all of the cases, indicating the high safety of this disinfectant. It is justified to say from these findings that HAD Hand Wash is useful as a hand and finger disinfectant.


Small interfering RNA targeting bovine papillomavirus type 1 E2 induces apoptosis in equine sarcoid transformed fibroblasts.
Equine sarcoids are skin tumours of horses caused by infection with BPV-1 or 2. Maintenance and replication of the viral genome depend upon the viral proteins E1 and E2. We examined the effects of an E2 specific siRNA on E2 and E1 viral gene expression, viral load and cell growth in BPV-1 transformed sarcoid-derived cells. Transfection with E2-siRNA caused a reduction in E2 and E1 mRNA expression as well as viral load, growth inhibition and decreased anchorage-independent growth. siRNA treated cells showed significantly higher apoptosis rates than control cells. Thus sequence specific targeting of E2 provides a powerful strategy to eliminate BPV-1 genomes and induce cell death in BPV-1 transformed cells.


The effect of timing of intravenous muscle relaxant on the quality of double-contrast barium enema.
To determine whether the timing of buscopan administration during double-contrast barium enema examination (DCBE) affects diagnostic quality. In a prospective setting, 100 consecutive adult out-patients referred for DCBE received 20 mg buscopan (hyoscine-N-butylbromide) intravenously, either before infusion of barium suspension (Group A) or after barium infusion and gas insufflation (Group B). A subjective assessment of ease of contrast medium infusion was made at the time of examination and the films subsequently analysed by two radiologists unaware of the mode of relaxant administration, who noted the quality of mucosal coating and made subjective and objective measurements of segmental distension. There was no significant difference in screening times, infusion difficulty or colonic contrast medium coating between the two groups. Subjective assessment of distension of the caecum, ascending colon, transverse colon and rectum were not significantly different. Patients receiving intravenous relaxant after barium and gas infusion had less subjective descending (P = 0. 05) and sigmoid (P = 0.04) colon distension, but there was no significant difference with respect to maximal bowel diameter in any of the segments measured. The timing of intravenous administration during DCBE is likely to have no significant effect on the diagnostic quality of the study.


Ultrastructural findings in experimental Creutzfeldt-Jakob disease in guinea pigs.
Brains from six clinically ill guinea pigs from various serial passages infected with brain homogenate from a patient with Creutzfeldt-Jakob disease were studied by light and electron microscopy. There were no appreciable morphologic differences among the animals at different passages. Light microscopy revealed clearing, swelling, and vacuolar changes in neurons and astrocytes. These changes occurred in both perikarya and cell processes. Large isolated vacuoles in the neuropil appeared to develop by progressive fusion between swollen cellular processes. By electron microscopy many neuronal processes contained degenerating organelles, osmiophilic bodies, membranous bodies and approximately 10 mm filamentous structures. In addition, vacuoles and membranous inclusions were seen in some neuronal nuclei, changes which have not been previously observed in spongiform encephalopathies.


Cicerin and arietin, novel chickpea peptides with different antifungal potencies.
Two antifungal peptides with novel N-terminal sequences, designated cicerin and arietin were isolated from seeds of the chickpea (Cicer arietinum), respectively. Both peptides were adsorbed on Affi-gel blue gel and CM-Sepharose and exhibited a molecular weight of approximately 8.2 and 5.6 kDa, respectively. Arietin was more strongly adsorbed on CM-Sepharose than cicerin and manifested a higher translation-inhibiting activity in a rabbit reticulocyte lysate system and a higher antifungal potency toward Mycosphaerella arachidicola, Fusarium oxysporum and Botrytis cinerea. Both were devoid of mitogenic and anti-HIV-1 reverse transcriptase activities.


Prolonged high-frequency oscillatory ventilation in tubercular multifocal cystic lung disease.
Multifocal cystic lung disease in infants is most commonly congenital, and is managed surgically with perioperative mechanical ventilation. Multifocal cystic lung disease in infants may be due to tuberculosis. We report a young infant with tubercular multifocal cystic lung disease and respiratory failure. The initial chest imaging revealed diffuse nodular infiltrates. Soon after admission he required conventional mechanical ventilation for respiratory failure. The bronchoalveolar lavage fluid grew Mycobacterium tuberculosis in culture. Subsequent chest imaging showed progression to multifocal cystic lung disease. The ventilation mode was changed to high-frequency oscillatory ventilation (HFOV) due to persistent CO(2) retention in the presence of cystic lung disease. The cystic lung disease reversed with antitubercular treatment and prolonged HFOV with slow wean.


Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model.
Biallelic CEBPA mutations and FMS-like tyrosine kinase receptor 3 (FLT3) length mutations are frequently identified in human acute myeloid leukemia (AML) with normal cytogenetics. However, the molecular and cellular mechanisms of oncogene cooperation remain unclear because of a lack of disease models. We have generated an AML mouse model using knockin mouse strains to study cooperation of an internal tandem duplication (ITD) mutation in the Flt3 gene with commonly observed CCAAT/enhancer binding protein alpha (C/EBPα) mutations. This study provides evidence that FLT3 ITD cooperates in leukemogenesis by enhancing the generation of leukemia-initiating granulocyte-monocyte progenitors (GMPs) otherwise prevented by a block in differentiation and skewed lineage priming induced by biallelic C/EBPα mutations. These cellular changes are accompanied by an upregulation of hematopoietic stem cell and STAT5 target genes. By gene expression analysis in premalignant populations, we further show a role of FLT3 ITD in activating genes involved in survival/transformation and chemoresistance. Both multipotent progenitors and GMP cells contain the potential to induce AML similar to corresponding cells in human AML samples showing that this model resembles human disease.


Can a retro-polypeptide fold into a globule?
Communicated by Ramaswamy H. Sarma.


Histone chaperone CAF-1: essential roles in multi-cellular organism development.
More and more studies have shown chromatin remodelers and histone modifiers play essential roles in regulating developmental patterns by organizing specific chromosomal architecture to establish programmed transcriptional profiles, with implications that histone chaperones execute a coordinating role in these processes. Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved three-subunit protein complex, was identified as a histone chaperone coupled with DNA replication and repair in cultured mammalian cells and yeasts. Interestingly, recent findings indicate CAF-1 may have important regulatory roles during development by interacting with specific transcription factors and epigenetic regulators. In this review, we focus on the essential roles of CAF-1 in regulating heterochromatin organization, asymmetric cell division, and specific signal transduction through epigenetic modulations of the chromatin. In the end, we aim at providing a current image of facets of CAF-1 as a histone chaperone to orchestrate cell proliferation and differentiation during multi-cellular organism development.


[Evaluation of the mental state of elderly diabetic patients in education].
Maintaining to good glycemic control is necessary to treat diabetes effectively and it is also necessary to understand the mental characteristics of elderly patients with diabetes. We investigated evaluation of the mental state, using self-depressive scale (SDS) and the Tokyo university egogram form (TEG), of 356 asymptomatic diabetic patients (254 non-elderly, 102 elderly) admitted for educational about diabetes. On TEG, we studied evaluation of five ego states for the following showing: critical parent (CP), nurturing parent (NP), adult (A), free child (FC) and adapted child (AC). First of all, we studied evaluation of mental characteristics of the elderly, NP and A of TEG were higher in the elderly than in the non-elderly (p < 0.01). Furthermore, the SDS was lower on discharge than on admission in both groups (p < 0.01). The group showing improvement had a significantly higher SDS score on admission than the group showing aggravation (p < 0.01). We classified the group with an SDS score 50 or more SDS as the depressed group; those with a 40 to 49 score as the slight distress group; and a score of 39 or less score was considered normal. The depressed group had significantly lower A and FC, and a higher AC on TEG, than other groups (p < 0.01). Therefore, elderly diabetic patients seem to be rational and obliging. This study revealed the mental effects of diabetic education to be similar in elderly and non-elderly diabetic patients.


Antifungal Sesquiterpenoids, Rhodocoranes, from Submerged Cultures of the Wrinkled Peach Mushroom, Rhodotus palmatus.
Seven previously unknown sesquiterpenoids and norsesquiterpenoids, rhodocoranes F-L (1-7), were isolated from the fermentation broth of the basidiomycete Rhodotus palmatus. Their structures were elucidated utilizing 1D and 2D NMR techniques as well as HRESIMS; they are unusual noracorane, spiro[4.4]nonene, and acorane-type sesquiterpenoids. They include the first naturally occurring cyclopentylidenefuranones (3-5) and the new tricyclic scaffold of 7. Metabolites 1-7 exhibited a general mild antimycotic activity, while 1-3 also displayed cytotoxic effects.


Knowledge about preventing and managing lymphedema: a survey of recently diagnosed and treated breast cancer patients.
Physical therapists, books and oncologist's staff were the most frequently cited sources of lymphedema prevention and management information in a telephone survey of 148 recently treated breast cancer patients. Awareness, current practice and intention to practice 13 recommended prevention behaviors were low, and variations in these indices and in information sources were observed between those reporting any swelling and those who did not. Citing radiation oncologists as an information source reflected significantly higher levels of awareness, practice and intention as compared to not citing them. Also, citing oncologists reflected lower scores on the three indices as compared to not citing them. The results suggest that lymphedema prevention and management information is not getting to breast cancer survivors in a timely fashion and underscore the urgent need to develop and implement appropriate educational strategies. Additionally, research into factors that could motivate survivors to practice the recommended behaviors is warranted.


Use of the acridine orange staining on smears of human spermatozoa after heat-treatment: evaluation of the chromatin condensation.
A simple, rapid procedure was described to evaluate the degree of chromatin compactness in human spermatozoa. Smears of fixed spermatozoa were heat-treated and stained with acridine orange. Smears from the same sperm samples were also stained with acidic aniline blue. Three groups of semen could be distinguished according to the percentage of red sperm heads observed under fluorescence microscope. 1) Semens with spermatozoa whose chromatin appeared normal before and after heat-treatment. 2) Semens with spermatozoa whose chromatin appeared normal before and abnormal after heat-treatment. 3) Semens with spermatozoa whose chromatin appeared abnormal before and after heat-treatment. The positive correlation between the percentages of red heads and the percentages of blue stained heads suggests that modifications in the biochemical composition of the basic protein component associated with DNA are responsible for the denaturation process.


EWGLI: a European surveillance scheme for travel associated legionnaire s disease.
The European Working Group for Legionella Infections (EWGLI) was set up in 1986 and introduced the European Surveillance Scheme for Travel Associated Legionnaires Disease in 1987. The microbiologists working in reference laborat-ories and the epidemiolog


Rapid and validated fluorometric HPLC method for determination of gabapentin in human plasma and urine for clinical application.
A rapid derivatization and validated HPLC method for gabapentin in human plasma and urine is needed for clinical use. The objective of this study was to establish a rapid and validated analytical method for the determination of gabapentin in human plasma and urine using isocratic fluorometric HPLC for clinical application. This analytical method is based on precolumn fluorescent derivatization using 4-fluoro-7-nitro-benzofurazan. The derivatization was coupled to fast HPLC separation using a 2·3 μm-particle size ODS column (100 × 4·6 mm i.d.). The derivatization of gabapentin was optimized and HPLC separation was achieved over an ODS column with a run time of 3·5 min. Calibration curves in human plasma and urine were linear over the concentration ranges of 0·05-10 and 10-1000 μg/mL, respectively. Intra- and inter-assay precision and accuracy values of plasma were within 8·0% and 101-109% and within 8·3% and 94-108%, respectively. Those of urine were within 8·5% and 97-106% and within 9·5% and 97-105%, respectively. This validated method was applied to a pharmacokinetic study in healthy subjects. Interindividual variations in plasma disposition and urinary excretion of gabapentin were observed. A rapid and validated isocratic fluorometric HPLC method for the determination of gabapentin in human plasma and urine for clinical application has been established. This method can be utilized to evaluate the pharmacokinetic disposition of gabapentin in humans.


A trial to determine the role of placental extract in the treatment of chronic non-healing wounds.
To investigate the effect of topical placental extract in the treatment of non-healing wounds. One hundred patients attending the wound clinic at University Hospital, Varanasi, India, with wounds of more than six weeks' duration were recruited. Fifty patients were treated with placental extract, and 50 were controls. Wound biopsy and swab culture and sensitivity were performed and the area surrounding the wound was X-rayed. Wound size was measured and the rate of epithelialisation assessed at weekly follow-ups. In nine cases biopsies were repeated after two weeks of treatment and sent for histopathological examination, including angiogenesis. Thirty patients dropped out, leaving 40 cases in the treatment group and 30 in the control group. Over an eight-week period, 27 patients (67.5%) in the treatment group showed more than 50% epithelialisation, compared with only seven patients (23.3%) in the control group. Placental extract has a beneficial role to play as a topical agent in the management of chronic non-healing wounds.