[Modified Mollard procedure for congenital high anorectal malformations via rectal muscle sheath of blind bag out of previous sagittal approach].
To explore the efficacies of treating infants with congenital anorectal malformation by drawing from rectal muscle sheath of blind bag out of previous sagittal approach (modified Mollard procedure). Retrospective analyses of postoperative anus control and bowel movements were conducted for 172 patients with high anorectal malformation. The procedures included modified Mollard (n = 68, modified group), Pena (n = 64, Pena group) and abdominal perineal anus forming (n = 40, abdominoperineal group). The tensions of external sphincter and puborectalis were gauged by digital rectal examination and the perianal degree of fecal pollution was assessed by defecography. Among them, 28 boys and 18 girls had a good postoperative control of defecation in the modified group (P = 0.004). The ratios of postoperative external anal sphincter was strong were 73.5% (50/68) and 85.9% (55/64) respectively in the modified and Pena groups and they were higher than that of abdominal perineal group at 55.0% (22/40) (both P < 0.05). The difference in the former two groups was not statistically significant (P = 0.196). The incidence of constipation in the modified group was less than that in the Pena group (13.2% (9/68) vs 31.3% (20/64), P = 0.012). Modified Mollard procedure may avoid repeated operations, offer a better control of bowel function, ease patient suffering and improve their postoperative quality-of-life.


[Role of toxoplasmas in pathology of the vision organ].
The present paper presents data on the major clinical symptoms ofToxoplasma oculopathy in different forms of Toxoplasma infection. It also gives the results of the authors' own laboratory studies of specimens taken from individuals with pathology of the vision organ. They confirm the data available in the literature on that toxoplasmosis frequently occurs in combination with other infections, particularly with Herpes and Cytomegalovirus, Chlamydia, Ureaplasma, and Mycoplasma infections. The signs of eye lesions and a clinical case of an eleven-year-old girl diagnosed as having central recurrent multifocal exudative and hemorrhagic neurochoriorenitis of the right eye are given.


Effect of anti-inflammatory drugs on lipase in vitro.
Mefenamic acid, and to a lesser extent, flufenamic acid have a significant inhibitory effect on lipolysis as determined by the action of mouse pancreas lipase on the dilauric (didodecanoic) acid ester of fluorescein. Ibuprofen, fenoprofen calcium, phenylbutazone, oxyphenbutazone and alclofenac had comparatively little effect.


The law on compulsory vaccination in Italy: an update 2 years after the introduction.
Italy introduced a national law extending the number of compulsory vaccines from four to 10 in July 2017. The implementation placed a further burden on immunisation centres as they were required to cover the increased demand of vaccination by the parents of unvaccinated children. Vaccine coverage (VC) estimated 6 months and 1 year later, at 24 and 30 months (same birth cohort), had increased for all vaccines. At 24 months of age, measles VC increased from 87.3% in 2016 to 91.8% in 2017 and 94.1% at 30 months of age as at June 2018. In six of 21 regions and autonomous provinces, VC for measles was >95%. Despite the implementation of this law, vaccine hesitancy is still a problem in Italy and the political and social debate on mandatory vaccination is ongoing. Regardless of the policy to be adopted in the future, strategies to maintain high vaccination rates and the related herd immunity should be considered, including adequate communication to the population and the implementation of electronic immunisation registries.


An axonemal dynein particularly important for flagellar movement at high viscosity. Implications from a new Chlamydomonas mutant deficient in the dynein heavy chain gene DHC9.
Ciliary and flagellar axonemes contain multiple inner arm dyneins of which the functional difference is largely unknown. In this study, a Chlamydomonas mutant, ida9, lacking inner arm dynein c was isolated and shown to carry a mutation in the DHC9 dynein heavy chain gene. The cDNA sequence of DHC9 was determined, and its information was used to show that >80% of it is lost in the mutant. Electron microscopy and image analysis showed that the ida9 axoneme lacked electron density near the base of the S2 radial spoke, indicating that dynein c localizes to this site. The mutant ida9 swam only slightly slower than the wild type in normal media. However, swimming velocity was greatly reduced when medium viscosity was modestly increased. Thus, dynein c in wild type axonemes must produce a significant force when flagella are beating in viscous media. Because motility analyses in vitro have shown that dynein c is the fastest among all the inner arm dyneins, we can regard this dynein as a fast yet powerful motor.


A rapid single step staining technique for DNA analysis by flow microfluorimetry.
A new procedure is reported for the staining of DNA, for flow microfluorimetry. It allows the production of stained cell nuclei in a single step by incorporating the DNA stain with a solution of the nonionic detergent Triton-X-100. This method has been found to be applicable to all DNA fluorochromes tested (ethidium bromide, propidium iodide, mithramycin, DAPI, Hoechst 33342). DNA histograms obtained in this way are comparable to those using conventional staining techniques, e.g., ethanol fixation followed by staining. Using this procedure the DNA content distribution of solid tissue or cells from suspension or monolayer cultures can be generated in less than 5 min.


Isolation and characterization of polyhydroxyalkanoate-degrading bacteria in seawater at two different depths from Suruga Bay.
Polyhydroxyalkanoate (PHA) is a highly biodegradable microbial polyester, even in marine environments. In this study, we incorporated an enrichment culture-like approach in the process of isolating marine PHA-degrading bacteria. The resulting 91 isolates were suggested to fall into five genera (Alloalcanivorax, Alteromonas, Arenicella, Microbacterium, and Pseudoalteromonas) based on 16S rRNA analysis, including two novel genera (Arenicella and Microbacterium) as marine PHA-degrading bacteria. Microbacterium schleiferi (DSM 20489) and Alteromonas macleodii (NBRC 102226), the type strains closest to the several isolates, have an extracellular poly(3-hydroxybutyrate) [P(3HB)] depolymerase homolog that does not fit a marine-type domain composition. However, A. macleodii exhibited no PHA degradation ability, unlike M. schleiferi. This result demonstrates that the isolated Alteromonas spp. are different species from A. macleodii. P(3HB) depolymerase homologs in the genus Alteromonas should be scrutinized in the future, particularly about which ones work as the depolymerase.


A prospective study of sexual transmission of human T lymphotropic virus (HTLV)-I and HTLV-II.
Cross-sectional studies support sexual transmission of human T lymphotropic virus (HTLV)-I/II; however, prospective incidence data, particularly for HTLV-II, are limited. A cohort of 85 HTLV-positive (30 with HTLV-I and 55 with HTLV-II) blood donors and their stable (>or=6 months) heterosexual sex partners were followed biannually over the course of a 10-year period. Four of 85 initially seronegative sex partners of HTLV-I and -II carriers seroconverted, for an incidence rate (IR) of 0.6 transmissions/100 person-years (py) (95% confidence interval [CI], 0.2-1.6). This includes 2 HTLV-I transmissions/219 py (IR, 0.9 transmissions/100 py [95% CI, 0.1-3.3]) and 2 HTLV-II transmissions/411 py (IR, 0.5 transmissions/100 py [95% CI, 0.06-1.8]), with no significant difference by HTLV type. There were 2 male-to-female (IR, 1.2 transmissions/100 py [95% CI, 0.1-4.3]) and 2 female-to-male (IR, 0.4 transmissions/100 py [95% CI, 0.05-1.6) transmissions. HTLV-I or -II proviral load was 2 log10 lower in newly infected partners than in index positive partners who transmitted HTLV (P=.007). The incidence of sexual transmission of HTLV-II may be similar to that of HTLV-I, and female-to-male transmission may play a more important role than previously thought. HTLV-I and -II proviral load may be lower in sexually acquired infection, because of a small infectious dose.


Optic nerve decompression in benign intracranial hypertension.
Fourteen patients with benign intracranial hypertension who failed to respond to medical treatment, were treated with optic nerve decompression to prevent the sequelae of chronic unrelieved papilloedema. The mechanism by which optic nerve decompression protects the optic nerve is uncertain. These patients were reviewed to evaluate the efficacy of the procedure in the treatment of benign intracranial hypertension and to assess its mechanism of action. Preoperatively all patients had papilloedema, 11 patients had visual obscurations and 6 patients had evidence of visual failure. Postoperatively, visual obscurations and papilloedema resolved in all patients, and 5 of 6 patients had no further deterioration of visual function. Six patients had symptoms of raised intracranial pressure preoperatively and in 3 the symptoms resolved after surgery. Three patients had unilateral optic nerve decompression and papilloedema resolved in both eyes. In 1 patient intracranial pressure monitoring revealed raised pressure preoperatively with no significant change in the first 24 hours after surgery. We conclude that optic nerve decompression is effective in the treatment of benign intracranial hypertension, has its effect locally, and in some patients may lower the intracranial pressure.


Fibrinogen adsorption, platelet adhesion and thrombin generation at heparinized surfaces exposed to flowing blood.
Thrombus formation at an artificial surface in contact with blood is a complex process that encompasses accretion of platelets from flowing blood and fibrin deposition. Platelet adhesion and fibrin formation are intimately intertwined reactions that are triggered by different sets of surface adsorbed plasma proteins. To dissect the contribution of protein adsorption and platelet adhesion to thrombin formation, a coherent study was performed with non-coated (NC) and heparin-coated (HC) surfaces. Thrombin production in whole blood, platelet adhesion and protein adsorption were studied using an amidolytic thrombin assay, a dynamic platelet adhesion assay and ellipsometry, respectively. Thrombin generation in flowing whole blood exposed to HC surfaces was greatly diminished when compared with NC surfaces. However, separate platelet adhesion and protein adsorption studies with anticoagulated whole blood revealed that platelets do not adhere because fibrinogen is not available in the protein layer that was deposited during the perfusion. These findings indicate that the in vitro thrombogenicity of a material cannot be predicted from platelet adhesion and protein adsorption data when these measurements are performed with anti-coagulated blood or platelet rich plasma. Preincubation of NC and HC surfaces with fibrinogen or 2000-fold diluted plasma resulted in similar amounts of surface-bound fibrinogen and mediated massive platelet adhesion from flowing whole blood. These results indicate that a) platelet adhesion correlates with the availability of surface-bound fibrinogen and b) NC and HC surfaces are indistinguishable with respect to protein (fibrinogen) adsorption and platelet adhesion. It is apparent that the heparinized surface used in our studies exerts its anti-thrombogenic properties by neutralizing locally formed thrombin and not by reducing fibrinogen-dependent platelet adhesion.


A new sensitive method for the spectrophotometric determination of molybdenum using 3-hydroxy-2-(2'-thienyl)-4H-chromen-4-one.
A spectrophotometric method has been developed for the determination of Molybdenum (VI) using 3-hydroxy-2-(2'-thienyl)-4H-chromen-4-one as a complexing agent. The complex formed was dissolved in water in the presence of Triton X-100 and exhibits an absorption maximum at 410 nm. A large number of metal ions like Co(II), Ni(II), Mn(II), Cr(III), Zn(II), Cu(II), Hg(II), Bi(III), Fe(II), Fe(III), Zr(IV), V(V) can be tolerated at an appreciable concentrations. Molar absorptivity and Sandell's sensitivity of the method is 2.80 x 10(5) l mol-1cm-1 and 3.42 x 10(-4) micrograms cm-2, respectively. Beer's law is obeyed in the concentration range of 0.01-0.4 ppm Mo(VI). Aliquots containing 0.2 ppm of Mo(VI) give a mean absorbance of 0.56 with a relative standard deviation of 1.3%.


Qualities of daily life and suicide in old age: A comparative perspective.
The purpose of this article is to examine the incidence of suicide among older people from a crosscultural perspective. A review of the theories and the evidence relied on in studies of the relationship between age and suicide introduces a comparative study of suicide in old age. Age and gender aggregates in eleven countries are examined. Societal conditions, such as educational participation, pension expenditures, marital disruption among the aged, and qualities of daily life, like solitude and work absorption, are associated with late life suicide rates.


Compartment-specific modulation of GABAergic synaptic transmission by TRPV1 channels in the dentate gyrus.
The transient receptor potential TRPV1 or vanilloid receptor is a nonselective ligand-gated channel highly expressed in primary sensory neurons where it mediates nociception. TRPV1 is also expressed in the brain where its activation depresses excitatory synaptic transmission. Whether TRPV1 also regulates inhibitory synapses in the brain is unclear. Here, using a combination of pharmacology, electrophysiology, and an in vivo knockdown strategy, we report that TRPV1 activation by capsaicin or by the endocannabinoid anandamide depresses somatic, but not dendritic inhibitory transmission in both rat and mouse dentate gyrus. The effect on somatic inhibition was absent in TRPV1 knock-out mice and was also eliminated by two different TRPV1 shRNAs expressed in dentate granule cells, strongly supporting a functional role for TRPV1 in modulating GABAergic synaptic function. Moreover, TRPV1-mediated depression occurs independently of GABA release, requires postsynaptic Ca(2+) rise and activation of calcineurin, and is likely due to clathrin-dependent internalization of GABA receptors. Altogether, these findings reveal a novel form of compartment-specific regulation whereby TRPV1 channels can modify synaptic function in the brain.


Diamagnetic loop for the first plasma in the KSTAR machine.
The diamagnetic loop (DL) is installed for the plasma diamagnetic measurement at the first plasma in the Korea superconducting tokamak advanced research (KSTAR) machine. Experimental results from the position measurement of the DL inside the KSTAR vacuum vessel and the vacuum flux measurement by using the DL for the evaluation of the geometrical data and the balance coefficient of the DL for the compensation of the vacuum flux in the diamagnetic measurement are described. In addition, a preliminary work of an instrument for a hardware compensation of the vacuum flux is presented.


An ultrastructural study of the role of leucocytes and fibroblasts in the breakdown of Bruch's membrane.
Ultrastructural examination was performed on 30 eyes selected on the basis of a light microscopic classification as representing all stages of macular degeneration. The eyes belonged to 29 patients aged 40 to 91 years at death and all patients with the exception of the 40-year-old had been examined during life. The results indicate that monocytes, lymphocytes, fibroblasts and mast cells may play a role in the formation of breaks in Bruch's membrane at early and late stages of macular degeneration. The implications of these observations are discussed in the context of their possible role in choroidal neovascularization.


Fatal Caryospora bigenetica (Apicomplexa: Eimeriidae) infections in cotton rats, Sigmodon hispidus.
Four groups of cotton rats, Sigmodon hispidus, were shown to be suitable secondary hosts for the viperid coccidium, Caryospora bigenetica, following oral inoculation of a mixture of oocysts and sporocysts. Swelling of the face, ears, and scrota and hemorrhagic ears were the predominant clinical signs and some cotton rats died in 3 of 4 experiments. Developmental stages of C. bigenetica were found in connective tissue components of the ear, nose, cheeks, anal skin, scrotum, and penile sheath of all cotton rats in which these tissues were examined. Additionally, developmental stages of C. bigenetica were found in connective tissue components of the following tissues examined from some cotton rats: tongue, lung, testicle, epididymis, rectum, base of the tail, footpad, and bone marrow. The present study shows that C. bigenetica can be pathogenic for cotton rats and demonstrates many new anatomic sites for developmental stages of this parasite in the secondary host.


Autophagy as a macrophage response to bacterial infection.
The macrophage is a key component of host defense mechanisms against pathogens. In addition to the phagocytosis of bacteria and secretion of proinflammatory mediators by macrophages, autophagy, a process involved in turnover of cellular material, is a recently identified component of the immune response to bacterial infection. Despite the bactericidal effect of autophagy, some species of intracellular bacteria are able to survive by using one or more strategies to avoid host autophagic attack. Here, we review the latest findings on the interactions between bacteria and autophagy in macrophages.


Nucleic acid melting by Escherichia coli CspE.
Escherichia coli contains nine members of the CspA family. CspA and some of its homologues play critical role in cold acclimation of cells by acting as RNA chaperones, destabilizing nucleicacid secondary structures. Disruption of nucleic acid melting activity of CspE led to loss of its transcription antitermination activity and consequently its cold acclimation activity. To date, the melting activity of Csp proteins was studied using partially double-stranded model nucleic acids substrates forming stem-loop structures. Here, we studied the mechanism of nucleic acid melting by CspE. We show that CspE melts the stem region in two directions, that CspE-induced melting does not require the continuity of the substrate's loop region, and CspE can efficiently melt model substrates with single-stranded overhangs as short as 4 nt. We further show that preferential binding of CspE at the stem-loop junction site initiates melting; binding of additional CspE molecules that fully cover the single-stranded region of a melting substrate leads to complete melting of the stem.


Beneficial Effect of Dietary Fiber on the Upper Gastrointestinal Transit Time in Rats Suffering from a Toxic Dose of Amaranth.
Gobo dietary fiber (GDF) obtained from the roots of edible burdock (Arctium lappa L.) was examined for its protective role against amaranth (Food Red No. 2, Am) toxicity in the upper gastrointestinal tract (from the mouth to the ileal end) of rats. Ileorectostomized rats were examined for their growth response to feeding with a purified basal diet containing 4% Am with or without 7.5% GDF. The transit half-time (TT50) through the upper gastrointestinal tract was also examined with ileostomized rats by recovering the small intestinal contents from the ileal end, using Cr-EDTA as a nonabsorbable water-soluble marker. Although feeding Am to the ileorectostomized rats resulted in a 50% mortality, concurrent feeding of Am and GDF not only protected the rats from death but also significantly promoted their growth rate when compared to the effect on the survivors fed only with the Am-containing diet. The results of TT50 measurements on ileostomized rats showed that the TT50 was decreased by half in the presence of Am, but was restored to the value for the control without Am when the Am-containing diet was supplemented with GDF. These and previous rsults imply that Am toxicity develops mainly in the upper gastrointestinal tract as a result of decreased availability of nutrients that is produced by the rapid transit and inhibitory effect of Am on the digestion-absorption process. The beneficial effect of GDF appears to be in normalizing the rapid transit through the upper gastrointestinal tract of chyme containing Am and not in the cecum or colon.


Performance of multilayered particles: influence of a thin cushioning layer.
Nowadays, oral dosage forms with controlled release kinetics have known an increasing interest. The polymer coating of drug-loaded particles is one of the most common methods used for controlling drug delivery. Such multilayered particles could be either filled into capsules or compressed into tablets for their oral administration. However, many studies have noticed that coating films are damaged during the compression process, leading to significant changes in drug release profiles. The aims of this study were to investigate the effects of a thin cushioning layer [made of HydroxyPropylMethyl Cellulose (HPMC)] applied on coated theophylline particles upon particle characteristics, tablet properties, and then upon their dissolution performance. If no significant effect was shown with particles, this thin HPMC layer played an important role in the tablets. Tablet cohesiveness was decreased due to HPMC cushioning properties and moreover, the theophylline release rate was increased, as HPMC is a water-soluble polymer creating channels in polymer film for dissolution medium. Therefore, a cushioning layer helped to protect polymer coats from fracture during compression but could also affect drug release and so, both effects must be checked in such a drug delivery system.


Evaluation of elevated alanine aminotransferase and hepatitis B virus DNA in healthy seronegative blood donors.
Serum alanine transaminase (ALT) has been used as a surrogate marker for detection of hepatitis B and C in blood donors in Pakistan since 1985. Since the introduction of more sensitive assays the value of ALT became questionable but it was still used with subsequent wastage of blood units with raised ALT. We conducted a study for a period of one year to evaluate the usefulness of ALT. During the study period, 25117 subjects donated blood. Eight hundred and seventy two donors (3.4%) were positive for one or more serological tests. ALT of all donors ranged from 0-1501 U/L (Mean ± SD; 33.4 ± 25.45U/L). The donors seronegative for all disease markers were 24245 (96.6%). Of these, 21164 (84.2%) donors had their ALT within reference range while 2874 (11.4%) and 207 (0.8%) of donors had minimal and markedly elevated results respectively. Six hundred and twenty one blood units (including red cells, platelets and plasma) were discarded based on elevated ALT results alone at a cost of $39,123. Two hundred seronegative blood donors with normal ALT, minimally and markedly elevated ALT levels, were selected randomly and evaluated for hepatitis B deoxynucleic acid by individual PCR. None of the donors was found to be reactive. This work did not support a positive association between hepatitis B virus nucleic acid and elevated ALT in healthy serologically negative blood donors.


Large variability in plasma efavirenz concentration in Papua New Guinea HIV/AIDS patients associated with high frequency of CYP2B6 516T allele.
Papua New Guinea (PNG) has a high HIV/AIDS prevalence and very high frequency of the CYP2B6 c.516G>T (rs3745274) variant. We have conducted the first investigation of the impact of c.516G>T and patient demographics on plasma efavirenz (EFV) and 8-hydroxyefavirenz (8OH-EFV) concentrations, metabolic ratio (8OH-EFV/EFV) (MR), and their association with adverse effects, in PNG patients with HIV/AIDS. For 156 PNG patients with HIV/AIDS taking EFV 600 mg/day (for 3-156 months), plasma EFV and 8OH-EFV concentrations were quantified, CYP2B6 c.516G>T genotyped, and demographic and self-reported adverse effects data recorded. Genotype differences in EFV and 8OH-EFV concentrations, MR, and percent within therapeutic range (1000-4000 ng/ml) were examined, in addition to EFV and 8OH-EFV concentration differences between patients experiencing adverse effects. CYP2B6 c.516T allele frequency was 53%. Plasma EFV (p < 0.0001), 8OH-EFV (p < 0.01), and MR (p < 0.0001) differed significantly between genotypes, with genotype explaining 38%, 10%, and 50% of variability, respectively. Plasma EFV concentrations were significantly higher in T/T (median = 5168 ng/ml) than G/G (1036 ng/ml, post hoc p < 0.0001) and G/T (1502 ng/ml, p < 0.0001) genotypes, with all patients above therapeutic range (n = 23) being T/T genotype (p < 0.0001). EFV and 8OH-EFV concentrations were not significantly higher in patients experiencing adverse effects. In PNG HIV/AIDS population where the 516T frequency is very high, it explains a substantial portion of variability (38%) in EFV disposition; however, at least for the patients receiving EFV long term, this does not translate into significant side effects.


Strategic orientations of small multihospital systems.
Strategic behaviors of organizations can be classified along two dimensions--growth orientations, or patterns of evolution over time, and action orientations, or strategic aggressiveness in undertaking a particular growth orientation. We create measures of growth and action orientations for small multihospital systems and test the validity of the growth and action orientation typologies, using data from a sample of small multihospital systems. Growth and action orientations do appear to exist independently of each other, and they are related to the ownership status of the systems. Not-for-profit and church-other systems exhibit similar strategic orientations, unlike those of Catholic and investor-owned systems.


High prevalence of antibodies to core+1/ARF protein in HCV-infected patients with advanced cirrhosis.
Hepatitis C virus (HCV) possesses a second open reading frame (ORF) within the core gene encoding an additional protein, known as the alternative reading frame protein (ARFP), F or core+1. The biological significance of the core+1/ARF protein remains elusive. However, several independent studies have shown the presence of core+1/ARFP antibodies in chronically HCV-infected patients. Furthermore, a higher prevalence of core+1/ARFP antibodies was detected in patients with HCV-associated hepatocellular carcinoma (HCC). Here, we investigated the incidence of core+1/ARFPantibodies in chronically HCV-infected patients at different stages of cirrhosis in comparison to chronically HCV-infected patients at earlier stages of disease. Using ELISA, we assessed the prevalence of anti-core+1 antibodies in 30 patients with advanced cirrhosis [model for end-stage liver disease (MELD) ≥15] in comparison with 50 patients with mild cirrhosis (MELD <15) and 164 chronic HCV patients without cirrhosis. 28.7 % of HCV patients with cirrhosis were positive for anti-core+1 antibodies, in contrast with 16.5 % of non-cirrhotic HCV patients. Moreover, there was significantly higher positivity for anti-core+1 antibodies in HCV patients with advanced cirrhosis (36.7 %) compared to those with early cirrhosis (24 %) (P<0.05). These findings, together with the high prevalence of anti-core+1 antibodies in HCV patients with HCC, suggest that core+1 protein may have a role in virus-associated pathogenesis, and provide evidence to suggest that the levels of anti-core+1 antibodies may serve as a marker for disease progression.


Leptin enhances hypothalamic lactate dehydrogenase A (LDHA)-dependent glucose sensing to lower glucose production in high-fat-fed rats.
The responsiveness of glucose sensing per se to regulate whole-body glucose homeostasis is dependent on the ability of a rise in glucose to lower hepatic glucose production and increase peripheral glucose uptake in vivo In both rodents and humans, glucose sensing is lost in diabetes and obesity, but the site(s) of impairment remains elusive. Here, we first report that short-term high-fat feeding disrupts hypothalamic glucose sensing to lower glucose production in rats. Second, leptin administration into the hypothalamus of high-fat-fed rats restored hypothalamic glucose sensing to lower glucose production during a pancreatic (basal insulin)-euglycemic clamp and increased whole-body glucose tolerance during an intravenous glucose tolerance test. Finally, both chemical inhibition of hypothalamic lactate dehydrogenase (LDH) (achieved via hypothalamic LDH inhibitor oxamate infusion) and molecular knockdown of LDHA (achieved via hypothalamic lentiviral LDHA shRNA injection) negated the ability of hypothalamic leptin infusion to enhance glucose sensing to lower glucose production in high fat-fed rats. In summary, our findings illustrate that leptin enhances LDHA-dependent glucose sensing in the hypothalamus to lower glucose production in high-fat-fed rodents in vivo.


Retrosplenial and Hippocampal Synchrony during Retrieval of Old Memories in Macaques.
Memory for events from the distant past relies on multiple brain regions, but little is known about the underlying neural dynamics that give rise to such abilities. We recorded neural activity in the hippocampus and retrosplenial cortex of two female rhesus macaques as they visually selected targets in year-old and newly acquired object-scene associations. Whereas hippocampal activity was unchanging with memory age, the retrosplenial cortex responded with greater magnitude alpha oscillations (10-15 Hz) and greater phase locking to memory-guided eye movements during retrieval of old events. A similar old-memory enhancement was observed in the anterior cingulate cortex but in a beta2/gamma band (28-35 Hz). In contrast, remote retrieval was associated with decreased gamma-band synchrony between the hippocampus and each neocortical area. The increasing retrosplenial alpha oscillation and decreasing hippocampocortical synchrony with memory age may signify a shift in frank memory allocation or, alternatively, changes in selection among distributed memory representations in the primate brain.SIGNIFICANCE STATEMENT Memory depends on multiple brain regions, whose involvement is thought to change with time. Here, we recorded neuronal population activity from the hippocampus and retrosplenial cortex as nonhuman primates searched for objects embedded in scenes. These memoranda were either newly presented or a year old. Remembering old material drove stronger oscillations in the retrosplenial cortex and led to a greater locking of neural activity to search movements. Remembering new material revealed stronger oscillatory synchrony between the hippocampus and retrosplenial cortex. These results suggest that with age, memories may come to rely more exclusively on neocortical oscillations for retrieval and search guidance and less on long-range coupling with the hippocampus.


Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice.
Clematis mandshurica Ruprecht root has been used in Asia as a traditional anti-inflammatory, analgesic, and antitumor agent. Its main active component is hederagenin, a naturally occurring triterpene, and in this study, we examined the anti-inflammatory effects of hederagenin in lipopolysaccharide-stimulated RAW 264.7 cells using an enzyme-linked immunosorbent assay, Western blot, and RT-PCR. In addition, its effects on acute inflammation in vivo were observed using a carrageenan-induced mouse hind paw edema assay. Furthermore, the changes on the histopathology and histomorphometry of hind paw skins were examined using carrageenan-treated mice. Treatment with hederagenin (10, 30 and 100μM) resulted in inhibited levels of protein expression of lipopolysaccharide-stimulated iNOS, COX-2, and NF-κB as well as production of NO, PGE2, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide. Consistent with these results, hederagenin also dose-dependently reduced the lipopolysaccharide-induced mRNA levels of iNOS and COX-2, and of the above-mentioned cytokines. Interestingly, results of the carrageenan-induced mouse hind paw edema assay showed an anti-edema effect of hederagenin. Furthermore, hederagenin (30mg/kg) inhibited the carrageenan-induced increases in skin thicknesses, infiltrated inflammatory cells, and mast cell degranulation. These results suggest that hederagenin may possess anti-inflammatory activities.


Transient complete heart block complicating acute rheumatic fever.
First-degree heart block is a common electrocardiographic manifestation of acute rheumatic fever and is included in Jones' diagnostic criteria. Other electrocardiographic changes such as sinus tachycardia, bundle branch blocks. nonspecific ST-T wave changes, atrial and ventricular premature complexes have been reported with variable frequency. However, complete heart block is an exceptionally rare manifestation of acute rheumatic fever. We report the clinical course of a 16-year-old boy with acute rheumatic fever who had prolonged P-R interval in the electrocardiogram on admission which subsequently progressed to complete heart block. The patient regained normal sinus rhythm within a few minutes without any pharmacologic or electrical intervention.


New and Advanced Picosecond Lasers for Tattoo Removal.
Early methods of tattoo removal ultimately resulted in unacceptable cosmetic outcomes. While the introduction of laser technology was an improvement over the existing chemical, mechanical, and surgical procedures, the use of nonselective tattoo removal with carbon dioxide and argon lasers led to scarring. Q-switched lasers with nanosecond (10-9) pulse domains were considered to have revolutionized tattoo treatment, by selectively heating the tattoo particles, while reducing the adverse sequelae to adjacent normal skin. Theoretical considerations of restricting pulse duration, to heat tattoo particles to higher temperatures, proposed the use of sub-nanosecond pulses to target particles with thermal relaxation times lower than the nanosecond pulses in Q-switched lasers. Initial studies demonstrated that picosecond (10-12) pulses were more effective than nanosecond pulses in clearing black tattoos. Advances in picosecond technology led to the development of commercially available lasers, incorporating several different wavelengths, to further refine pigment targeting.


Structures, Stabilities, and Spectra Properties of Fused CH4 Endohedral Water Cage (CH4)m(H2O)n Clusters from DFT-D Methods.
In order to understand the cage fusion behavior during the nucleation processes of methane hydrate (MH), methane-encapsulated double-cage clusters (CH4)2(H2O)n (n = 30-43) and several multicage structures with three or more cages were studied employing DFT-D methods. We find that almost all the lowest-energy double-cage structures can be constructed by merging the most stable structures of the monocage clusters CH4(H2O)n (n = 18-24). Double-cage structures can achieve higher stability through sharing a hexagon than a pentagon, which may be applicable to larger fused cage clusters. The preference of hexagons during cage fusion should be favorable for the appearance of the cages including hexagons such as the 5(12)6(2), 5(12)6(4) cages during the MH nucleation process. The symmetric C-H stretching modes of methane molecules in the double-cage structures show a clear trend of red shift with increasing size of the composing monocages. Compared with the case of monocages, the stretching frequencies of methane molecules in double-cage structures shift slightly, indicating variation of monocage configuration when cage fusion occurs. The larger multicage structures are found to possess higher fusion energies through sharing more polygons. Their thermodynamic stabilities do not simply increase with the number of fused monocages and are affected by the spatial arrangement of the building cages.


[Circumcision with the Chinese Shang Ring in children: outcomes of 824 cases].
To observe the clinical effects of using the Chinese Shang Ring in circumcision children with either phimosis or redundant prepuce, and to investigate its superiority over the similar devices available. A total of 824 children with phimosis or redundant prepuce underwent circumcision with the Shang Ring. The clinical data were assessed concerning the duration of the procedure, incidence of post-operative complications, time of recovery and appearance of the penis. The procedure duration was (2.6 +/-1.2) min, and the complications included infection in 4 (0.6%), edema in 21 (3.2%), delayed removal of the ring in 10 (1.5%), redundant and asymmetric mucosa attributable to performance in 6 (0.9%) of the cases. The wounds healed and the rings were removed at 13.4 +/- 5.8 days after circumcision, with well-smoothed incision and good cosmetic results. Child circumcision with the Chinese Shang Ring is easy and simple in performance, with less operative time, fewer complications and better cosmetic results.


Chemical restraint as behavioural euthanasia: case studies from the Royal Commission into Aged Care Quality and Safety.
The prescription of psychotropic medication to older people living with dementia in residential aged care has become an increasing concern. The use of prescription medication is often prefaced as a way of preventing harm to self and others. However, the use of such medications has been considered a way of managing some of the behavioural and psychological symptoms of dementia. Using a large secondary data set, this study aimed to identify the precursors and mediating factors that influence the use of chemical restraint of older people in residential aged care. Publicly available documents from the Australian Royal Commission into Aged Care Quality and Safety were used as the data corpus for this study. Keywords were used to search over 7000 documents to extract a set of topic-related content. We identified the cases of seven people in respite or permanent residential aged care who had been prescribed or administered psychotropic medication under circumstances that appeared to demonstrate chemical restraint. All documents relating to the cases were collated for our data set. A descriptive case study approach to analysis was taken. Four key descriptive patterns were identified: labelling and limits to tolerance, pushing prescription as a solution, coverups and avoiding consent, and family's fight for liberty. Triangulation across the data and academic literature supports the findings. Our findings provide some insight into how chemical restrain happens. Featuring throughout the cases were reports of a lack of workforce capacity to care for and support residents exhibiting dementia behaviours. Prescription of psychotropic medications featured as a "first resort" care solution. Family and friends found such approaches to care unacceptable and frequently challenged the practice. Where consent for prescription was explicitly denied, more covert approaches are demonstrated. Family awareness, presence, and advocacy were key to challenging the practice of chemical restraint. Shortfalls in the capacity of the current workforce come into play here. However, workforce shortcomings can no longer mask this ubiquitous practice. Just as importantly the spotlight needs to be turned on the prescribers and the providers.


Homeoviscous Adaptation of the Acinetobacter baumannii Outer Membrane: Alteration of Lipooligosaccharide Structure during Cold Stress.
To maintain optimal membrane dynamics, cells from all domains of life must acclimate to various environmental signals in a process referred to as homeoviscous adaptation. Alteration of the lipid composition is critical for maintaining membrane fluidity, permeability of the lipid bilayer, and protein function under diverse conditions. It is well documented, for example, that glycerophospholipid content varies substantially in both Gram-negative and Gram-positive bacteria with changes in growth temperature. However, in the case of Gram-negative bacteria, far less is known concerning structural changes in lipopolysaccharide (LPS) or lipooligosaccharide (LOS) during temperature shifts. LPS/LOS is anchored at the cell surface by the highly conserved lipid A domain and localized in the outer leaflet of the outer membrane. Here, we identified a novel acyltransferase, termed LpxS, involved in the synthesis of the lipid A domain of Acinetobacter baumannii. A. baumannii is a significant, multidrug-resistant, opportunistic pathogen that is particularly difficult to clear from health care settings because of its ability to survive under diverse conditions. LpxS transfers an octanoate (C8:0) fatty acid, the shortest known secondary acyl chain reported to date, replacing a C12:0 fatty acid at the 2' position of lipid A. Expression of LpxS was highly upregulated under cold conditions and likely increases membrane fluidity. Furthermore, incorporation of a C8:0 acyl chain under cold conditions increased the effectiveness of the outer membrane permeability barrier. LpxS orthologs are found in several Acinetobacter species and may represent a common mechanism for adaptation to cold temperatures in these organisms. IMPORTANCE To maintain cellular fitness, the composition of biological membranes must change in response to shifts in temperature or other stresses. This process, known as homeoviscous adaptation, allows for maintenance of optimal fluidity and membrane permeability. Here, we describe an enzyme that alters the fatty acid content of A. baumannii LOS, a major structural feature and key component of the bacterial outer membrane. Although much is known regarding how glycerophospholipids are altered during temperature shifts, our understanding of LOS or LPS alterations under these conditions is lacking. Our work identifies a cold adaptation mechanism in A. baumannii, a highly adaptable and multidrug-resistant pathogen.


Concentration fluctuations in fluid mixtures.
The B matrix of the Kirkwood-Buff theory of solutions describes number fluctuations of the component species. We show how, when the eigenvalues of the B matrix are widely different in magnitude, the description of the fluctuations can be simplified by restriction to a lower dimensional subspace of composition space. This simplification entails a loss of accuracy, which is argued to be often acceptable. The development is illustrated by application to water-urea and water -2,2,2 trifluoroethanol solutions. It is concluded that in these cases, the fluctuations of the components are coupled primarily by keeping the amount of void space in the solution almost constant.


Dyslipidaemia in chronic kidney disease.
Chronic kidney disease (CKD) is associated with a highly atherogenic lipid profile, characterized by elevated triglycerides, low high-density lipoprotein (HDL) cholesterol and accumulation of small dense low-density lipoprotein (LDL) particles. Diverse mechanisms are responsible: uraemia, dialysis, immunosuppressive drugs and concomitant diseases exert their effect on the activity of key enzymes, transfer proteins and receptors involved in lipid metabolism. Post hoc analyses from large scale randomized controlled trials suggest a benefit of statin therapy with respect to cardiovascular and renal endpoints in patients with early CKD comparable to the effect in people without renal disease. Observational studies found a reduction in the risk of contrast media induced nephropathy and a reduction in the risk of hospitalization for sepsis in patients who had CKD and were treated with statins. In contrast, prospective, randomized, controlled statin trials in patients with diabetes on haemodialysis and in renal transplant recipients have not conclusively shown improvements in hard cardiovascular endpoints. This review will focus on lipid disturbances in renal disease, their impact on cardiovascular disease, existing endpoint studies and current treatment guidelines.


Leaving the Lecture Behind: Putting PubMed Instruction into the Hands of the Students.
This column describes the development of a one-shot PubMed instruction class for medical students at a health sciences library. Background information on the objective is presented and discussed in the context of educational practice literature. The new course design centers on a guided group method of instruction in order to integrate more active learning. Surveyed students reported that the method was an effective way to learn how to search PubMed and that they preferred it to a traditional lecture. Pros and cons of the method are offered for other health sciences libraries interested in presenting PubMed instruction in a similar manner.


[The evaluation of nutritional status of stable COPD patients and to investigate the effect of nutritional status on perception of dyspnea, exercise capacity, body composition, hospitalisation and life quality].
Malnutrition is a comorbidity oftenly seen in COPD patients who have progressive chronic inflammation and severity. In this prospective study, we aimed to determine the nutritional status of stable COPD patients and to investigate the impact of nutritional status on perception of dyspnoea, exercise capacity, body composition, hospitalisation and life quality. COPD patients were assessed using previous smoking story, physical examination and irreversible airway obstruction. This study was done with 50 COPD patients older than 65 years of age and 30 control subjects. Exclusion criteria were also the co-existance of malignancies, malabsorbtion, DM, neurological diseases, renal failure and unstable cardiac diseases known to influence the nutritional state. The obstruction degree was evaluated by spirometry, nutritional status was classified by the MNA questionnaire, perception of dyspnoea was assessed by the MMRC scale, exercise capacity was assessed by the 6MWT, life quality was assessed by the CAT scale. Body composition parameters FM, FFM and FMI were analyzed and hospitalisations during 6 months after discharge were recorded. The COPD patients were divided into three groups as without malnutrition (n= 25,%50), under risk of malnutrition (n= 19,%38) and malnourished (n= 6,%12). The COPD severity, MMRC dyspnoea score, CAT score and hospitalisations during 6 months following were higher among the malnourished patients. On the other hand, body mass index, 6MWT results, FM and FFM were lower in malnourished patients. A positive correlation between FFM and 6MWT and a negative correlation between FFM and hospitalisation were observed. MNA is a well-developed questionnaire which evaluates malnutrition in COPD patients. We determined that malnourished COPD patients have higher airway obstruction degree, perception of dyspnoea, CAT score and lower exercise capacity and FFM. FFM is an independent predictor of exercise capacity and rehospitalisation during 6 months.


An (CA)n dinucleotide repeat polymorphism of the interleukin-6 (IL-6) gene is associated with metacarpal bone mineral density in hemodialysis patients.
Genetic factors may play an important role in the pathogenesis of reduced bone mineral density (BMD). IL-6 is a multifunctional cytokine and a candidate gene for regulation of bone mineral density (BMD). The relationship between a microsatellite polymorphism of the IL-6 gene and metacarpal BMD in Japanese hemodialysis patients was examined. We selected 165 patients (96 males and 69 females) with a mean age of 62.0 +/- 13.7 years (mean +/- standard deviation (SD) in this study. They were dialyzed for an average of 75.8 +/- 60.8 months (mean +/- SD). The microsatellite polymorphism in the IL-6 gene was examined. According to the number of cytosine-adenine repeats, varying from 13 to 18, 6 alleles could be distinguished. Patients were categorized based on the presence or absence of the allele with 126 bp (i.e. 14 CA repeats) (allele A, all others allele O). The frequencies of IL-6 gene genotypes in hemodialysis patients were 16.4% for OO, 52.1% for AO and 31.5% for AA. The BMD score adjusted for age and body weight (Z score) in the AA genotype group (-0.93 +/- 1.17) was significantly lower than that in the OO (-0.09 +/- 1.42, mean +/- SD, p < 0.005) or AO group (-0.48 +/- 1.15, mean +/- SD, p < 0.01). Serum intact PTH in the OO genotype group (79.3 +/- 84.6) was lower than that in the AA (120.8 +/- 113.6, mean +/- SD, p 0.10) or AO group (132.1 +/- 106.5, mean +/- SD, p < 0.05). These results suggest that polymorphism of the IL-6 gene may be a useful marker for reduced BMD.


DNA vaccines for transplantation.
DNA vaccination for transplantation has been less investigated compared with DNA vaccines for infectious disease, cancer and pathological autoimmunity. However, the emerging role of transplant-induced autoimmunity in allograft rejection may lead to the development of new DNA vaccination approaches where peripheral delivery of an antigen shared by recipient and allograft could be used to prevent rejection of a given organ for large numbers of individuals. In addition, apoptosis-inducing DNA vaccines could further minimize the need to identify specific donor antigens for induction of tolerance by generating apoptotic cells carrying donor or recipient antigens depending on site of vaccine delivery. The review covers DNA vaccination approaches that have been taken to prolong allograft survival in different animal model systems and their possible immune mechanisms and speculates on the future role of DNA vaccines for transplantation. The review gives insight into how new DNA vaccination strategies might be developed to take into account recent development in allotransplantation. DNA vaccination could reduce the need for systemic immunosuppressants and be applied to prevention of chronic rejection, which remains a major barrier to successful allotransplantation.


A two-state cell damage model under hyperthermic conditions: theory and in vitro experiments.
The ultimate goal of cancer treatment utilizing thermotherapy is to eradicate tumors and minimize damage to surrounding host tissues. To achieve this goal, it is important to develop an accurate cell damage model to characterize the population of cell death under various thermal conditions. The traditional Arrhenius model is often used to characterize the damaged cell population under the assumption that the rate of cell damage is proportional to exp(-EaRT), where Ea is the activation energy, R is the universal gas constant, and T is the absolute temperature. However, this model is unable to capture transition phenomena over the entire hyperthermia and ablation temperature range, particularly during the initial stage of heating. Inspired by classical statistical thermodynamic principles, we propose a general two-state model to characterize the entire cell population with two distinct and measurable subpopulations of cells, in which each cell is in one of the two microstates, viable (live) and damaged (dead), respectively. The resulting cell viability can be expressed as C(tau,T)=exp(-Phi(tau,T)kT)(1+exp(-Phi(tau,T)kT)), where k is a constant. The in vitro cell viability experiments revealed that the function Phi(tau,T) can be defined as a function that is linear in exposure time tau when the temperature T is fixed, and linear as well in terms of the reciprocal of temperature T when the variable tau is held as constant. To determine parameters in the function Phi(tau,T), we use in vitro cell viability data from the experiments conducted with human prostate cancerous (PC3) and normal (RWPE-1) cells exposed to thermotherapeutic protocols to correlate with the proposed cell damage model. Very good agreement between experimental data and the derived damage model is obtained. In addition, the new two-state model has the advantage that is less sensitive and more robust due to its well behaved model parameters.


Validation of the Delvotest SP NT. Performance Tested Methods(SM) 011102.
Delvotest SP NT is designed to test milk for the presence of antibacterial substances such as antibiotics. The test is made of an agar gel containing bacterial spores and a pH indicator. The milk sample is added onto the agar gel, and the test is placed for incubation at 64 degrees C. The principle of the test is based on the diffusion of possible inhibitory substances that may be present in the milk sample into the agar. This reduces growth and acid production by the test organism and delays or prevents the agar from changing color from purple to yellow. The present report includes all technical details about the Delvotest SP NT and the results of the validation study. The validation study demonstrates that the Delvotest SP NT conforms to the product performance claims and confirms the robustness of the test. The Delvotest SP NT is therefore granted Performance Tested Method(SM) certification.


Older adults' memory beliefs predict perceptions of memory strategy difficulty and effectiveness.
The current study investigated whether memory self-efficacy and beliefs about the controllability of memory abilities relate to older adults' perceptions of the difficulty and effectiveness of various strategies for improving their everyday memory. One hundred and fifteen older adults (ages 65-89) completed the Personal Beliefs about Memory Instrument to evaluate their beliefs about their own memory abilities and the Memory Strategies Questionnaire to assess perceptions of the difficulty and effectiveness of utilizing six different strategic approaches for optimizing memory function. Results showed that memory-self efficacy related to older adults' perceptions of how difficult various memory strategies are to implement, whereas control beliefs related to perceptions of memory strategy effectiveness. These results advance our understanding of how memory beliefs influence older adults' selection of approaches to improve their everyday memory abilities.


A Review of Surfactant Role in Soil Clogging Processes at Wastewater Exfiltration Locations in Sewers.
Wastewater contains significant sources of pollutants and contaminants. often the failure of a pipe, inadequate sealing or corrupt pipe-connections cause the loss of raw sewage, which percolates into the nearby soil. As a consequence, a colmation layer in conjunction with soil clogging is developing, which regulates the exfiltration rate. Recently, literature has emerged that offers findings about the effects of wastewater surfactants on the change of physical properties of the soil. A survey of published literature in this field provides information highlighting the influential mechanisms of surfactants in soil clogging through physical, chemical and biological processes. Therefore, to provide a comprehensive approach, this review describes the adsorption mechanisms of surfactants on organic and inorganic particles, at gas-bubbles and at biomass. We also provided our own input to the description of the adsorption of surfactants at fluid/fluid and fluid/solid interfaces in porous media associated with the clogging process.


Prostaglandin E1 increases oxygen extraction capabilities in experimental sepsis.
By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE1, fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE1 + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE1 alone than in the PGE1 + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054).(ABSTRACT TRUNCATED AT 400 WORDS)


A predictive model for alternative admission to dental education.
To compare academic progress and performance of students admitted through two admission systems and to analyse the predictive power of different components in an alternative admission. The subjects were students admitted to the dental programme at Malmö University, Sweden. The grade admission group was admitted on grades from secondary school (n = 126) and the alternative admission group via an alternative admission procedure (n = 157). The alternative admission procedure consisted of the following components: problem-solving matrices, spatial capacity tested with folding and tin models, manual dexterity, capacity for empathy and interview. Comparisons were made for academic progress (dropouts from the programme and study rate) and academic performance (examinations failed and outcomes of a comprehensive clinical examination). Spearman correlation was calculated for each component of the alternative admission procedure and academic progress as well as academic performance. Multivariate analyses were also carried out. Compared to the grade admission group, the alternative admission group presented lower rate of dropouts (3% vs. 20%, P < 0.001) and a larger proportion graduated within the expected time (88% vs. 60%, P < 0.01). There was no difference between the groups concerning academic performance. Capacity of empathy was correlated with study rate and outcomes of the clinical examination. The matrices predicted low proportion failed examinations and high students' self-assessments in the clinical examination. Predictive power of folding was limited and so was that of the interview. Manual dexterity was not correlated with academic progress or performance. Results support further development of admission selection criteria, particularly emphatic capacity that predicts important student academic achievements.


The Therapeutic Community: an international perspective.
The Therapeutic Community (TC) for drug-free substance abuse treatment can be found in more than 65 countries around the world, reflecting the global scope of substance abuse and addiction. This article describes some of the historical developments from an American-based to an international treatment model with professional associations on every continent. Possibly the two most important TC principles are outlined; i.e., the role of the treatment community as the primary agent of client change and the distinct therapeutic structure. While these two principles define the TC and can be found in programs around the world, the model leaves sufficient room to adapt practices and interventions to the respective culture. Examples of cultural adaptations are briefly described in this article.


The relationship between parity and overweight varies with household wealth and national development.
Recent studies support a positive relationship between parity and overweight among women of developing countries; however, it is unclear whether these effects vary by household wealth and national development. Our objective was to determine whether the association between parity and overweight [body mass index (BMI) > or =25 kg/m(2)] in women living in developing countries varies with levels of national human development and/or household wealth. We used data from 28 nationally representative, cross-sectional surveys conducted between 1996 and 2003 (n = 275 704 women, 15-49 years). The relationship between parity and overweight was modelled using logistic regression, controlling for several biological and sociodemographic factors and national development, as reflected by the United Nations' Human Development Index. We also modelled the interaction between parity and national development, and the three-way interaction between parity, household wealth and national development. Parity had a weak, positive association with overweight, which varied by household wealth and national development. Among the poorest women and women in the second tertile of household wealth, parity was positively related to overweight only in the most developed countries. Among the wealthiest women, parity was positively related to overweight regardless of the level of national development. As development increases, the burden of parity-related overweight shifts to include poor as well as wealthy women. In the least-developed countries, programmes to prevent parity-related overweight should target wealthy women, whereas such programmes should be provided to all women in more developed countries.


Evolving conceptualizations of cocaine dependence.
Cocaine was considered incapable of producing dependence in 1980 but was proclaimed the "drug of greatest national public health concern" by 1984. Clinical consensus in 1980 held that cocaine did not produce a withdrawal syndrome, but recent clinical investigations demonstrate that cocaine produces unique abuse and withdrawal patterns that differ from other major abused drugs. Evolving pre-clinical research over the past two decades now suggests that chronic cocaine abuse produces neurophysiological alterations in specific central nervous system systems that regulate the capacity to experience pleasure. These evolving clinical and pre-clinical constructs have led to applications of promising experimental pharmacological treatments for cocaine abuse.


The RBS1 domain of Gemin5 is intrinsically unstructured and interacts with RNA through conserved Arg and aromatic residues.
Gemin5 is a multifaceted RNA-binding protein that comprises distinct structural domains, including a WD40 and TPR-like for which the X-ray structure is known. In addition, the protein contains a non-canonical RNA-binding domain (RBS1) towards the C-terminus. To understand the RNA binding features of the RBS1 domain, we have characterized its structural characteristics by solution NMR linked to RNA-binding activity. Here we show that a short version of the RBS1 domain that retains the ability to interact with RNA is predominantly unfolded even in the presence of RNA. Furthermore, an exhaustive mutational analysis indicates the presence of an evolutionarily conserved motif enriched in R, S, W, and H residues, necessary to promote RNA-binding via π-π interactions. The combined results of NMR and RNA-binding on wild-type and mutant proteins highlight the importance of aromatic and arginine residues for RNA recognition by RBS1, revealing that the net charge and the π-amino acid density of this region of Gemin5 are key factors for RNA recognition.


Post-surgical Euglycemic Diabetic Ketoacidosis in a Patient on Empagliflozin in the Intensive Care Unit.
Euglycemic diabetic ketoacidosis (EDKA) is a rare variant of diabetic ketoacidosis which has been recently reported in association with sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Empagliflozin, an agent belonging to this therapeutic class, was approved by the U.S. Food and Drug Administration (FDA) in 2014 for management of type 2 diabetes. Since then, sparse reports of its association with EDKA are emerging, similarly to its predecessors in the class. We report the case of a 58-year-old female who developed EDKA in the intensive care unit (ICU) 48 hours after her last intake of empagliflozin and a day after neurosurgery. Though expected to improve in the post-operative period, she developed a rapidly worsening and unexplained anion gap metabolic acidosis. She was eventually diagnosed with EDKA which was successfully treated with intravenous insulin infusion, dextrose-containing fluids and discontinuation of the offending drug. Metabolic abnormalities improved in less than 24 hours and patient recovered without complications. This report highlights the importance of recognizing EDKA as a complication of oral anti-diabetics and discontinuing SGLT-2 inhibitors days prior to surgery and ICU admission. Care should be applied to providing patient with low-dose ketogenesis-inhibiting basal insulin and close observation of laboratory values in order to minimize delays in diagnosis, prolonged hospital stays and complications of EDKA.


Estimating nonnegative matrix model activations with deep neural networks to increase perceptual speech quality.
As a means of speech separation, time-frequency masking applies a gain function to the time-frequency representation of noisy speech. On the other hand, nonnegative matrix factorization (NMF) addresses separation by linearly combining basis vectors from speech and noise models to approximate noisy speech. This paper presents an approach for improving the perceptual quality of speech separated from background noise at low signal-to-noise ratios. An ideal ratio mask is estimated, which separates speech from noise with reasonable sound quality. A deep neural network then approximates clean speech by estimating activation weights from the ratio-masked speech, where the weights linearly combine elements from a NMF speech model. Systematic comparisons using objective metrics, including the perceptual evaluation of speech quality, show that the proposed algorithm achieves higher speech quality than related masking and NMF methods. In addition, a listening test was performed and its results show that the output of the proposed algorithm is preferred over the comparison systems in terms of speech quality.


Hydrogen bond competition in the ethanol-methanol dimer.
Previous theoretical work on the ethanol-methanol dimer has been inconclusive in predicting the preferred hydrogen bond donor/acceptor configuration. Here, we report the microwave spectrum of the dimer using a chirped pulse Fourier transform microwave spectrometer from 8-18 GHz. In an argon-backed expansion, 50 transitions have been assigned to a trans-ethanol-acceptor/methanol-donor structure that is likely stabilized by a secondary weak C-HO hydrogen bond. A higher energy conformer was observed in a helium-backed expansion and tentatively assigned to a gauche-ethanol-acceptor/methanol-donor structure. No ethanol-donor/methanol-acceptor dimers have been found, suggesting such interactions are energetically disfavored. A preliminary analysis of the A-E splitting due to the internal rotation of the methanol methyl group in the ground state species is also presented. We find evidence of the Ubbelohde effect in the measured A-E splittings of three deuterated isotopologues and the normal species of this conformer.


Is hypergastrinaemia dangerous to man?
Achlorhydria has been discussed as a possibly dangerous consequence of therapeutic inhibition of gastric acid secretion since the introduction of H2-receptor antagonists. The risk of long-term hypergastrinaemia has only been considered for about 5 years. The reason for this was the demonstration that gastric carcinoids (ECLomas) observed after life-long treatment of rats with the proton pump inhibitor omeprazole could also be produced in rats by other methods leading to long-lasting profound hypergastrinaemia. Such methods were the 80% resection of the oxyntic mucosa or feeding of ranitidine (2000 mg/day) for 2 years. The endocrine tumours corresponded to the gastric carcinoids found in patients with long-lasting hypergastrinaemia due to pernicious anaemia or with a gastrinoma as part of the MEN I syndrome. Neither in animals nor in man could other endocrine tumours or adenocarcinomas of the gastrointestinal tract be related to hypergastrinaemia. Epidemiologic data do not support gastrin dependence of adenocarcinoma of the stomach or the colon. Experimental findings of gastrin effects on tumour growth in vivo and in vitro have been contradictory and may be explained by the presence of gastrin receptors on tumour cells and the role of gastrin as an autocrine growth factor in some of these tumours. Since acid blockade by proton pump inhibitors or H2-receptor blockers dose-dependently increase serum gastrin levels, patients with ranitidine-resistant peptic ulceration receiving long-term treatment with high-dose omeprazole have been followed up with serial gastric biopsy specimens for up to 5 years. Complete healing, moderate hypergastrinaemia, and a slight hyperplasia but no dysplasia of the ECL cells in the oxyntic mucosa have been observed, which seemed to be correlated to chronic gastritis progressing over the years. Despite these negative findings excessive hypergastrinaemia by overdosage of potent drugs for inhibition of gastric secretion should be avoided and monitoring of plasma gastrin levels is recommended in case of long-term treatment.


[Levels and distribution of the dioxin-like polychlorinated biphenyls (PCBs) in the surface sediment of the Yellow River ].
The levels of DL-PCBs in the surface sediments collected in 15 different sampling sites from the Tibetan Plateau to the Yellow River estuary along the Yellow River were measured using the GC-MS. The concentrations of ∑DL-PCBs ranged from 2. 3 to 14.8 pg.g-1 and the TEQs of DL-PCBs were between 0. 001 4 and 0. 023 1 pgg-1 , with an average of 0. 007 3 pg.g-1. Compared with other domestic and foreign rivers, the DL-PCBs and TEQ levels of the Yellow River were at low levels. The main DL-PCBs congeners in the Yellow River sediments were tetra and penta chlorinated biphenyls. The DL-PCBs congener composition of rural and underdeveloped areas was similar, and there was similar congeners composition between the industry developed areas and the populous areas. Petrochemical industries and hydropower facilities may affect the distribution of DL-PCBs congener in the sediments. A significant correlation between concentrations of DL-PCBs and GDP per capita was found. It indicated that the contamination extent of DL-PCBs in the Yellow River was related with the local economic development, DL-PCBs levels in developed areas were higher than those in remote rural areas.


Airway emergency from spontaneous haemorrhagic thyroid cancer.
Spontaneous thyroid haemorrhages are rare. There are reported cases occurring in thyroid nodules and cysts but none in thyroid malignancies. We describe a 48 year old who presented to the on-call ENT team with a rapidly progressing neck swelling that was interfering with his airway. After resuscitation, the patient underwent a right lobectomy to stop the bleeding. Histology showed a thyroid follicular carcinoma. As per the regional multidisciplinary team discussion, he underwent a completion thyroidectomy followed by radioactive iodine treatment. We conclude that spontaneous haemorrhages of the thyroid gland can occur in malignancies and stress the importance of early histological diagnosis.


The Tattle About Tongue-Ties.
Ankyloglossia, commonly called "tongue-tie," has been increasingly diagnosed in the breast-feeding infant, with growing numbers of surgical interventions in the last 2 decades. As more practitioners have become involved in the diagnosis and treatment, there has not been a consensus on terminology and indications for intervention. In 2020, the American Academy of Otolaryngology - Head and Neck Surgery Foundation reviewed the bodies of lactation, dental, pediatric, and otolaryngology literature to seek professional consensus and note areas requiring more definitive evidence. This article highlights the findings for the general pediatrician seeking to support breast-feeding dyads. [Pediatr Ann. 2021;50(8):e310-e312.].


Design, Synthesis, Cytotoxic Activity and Apoptosis-inducing Action of Novel Cinnoline Derivatives as Anticancer Agents.
Tyrosine kinases and topoisomerase I are common target enzymes for the majority of the anticancer agents. In contrast to quinazolines and quinolines, kinase inhibitors and topoisomerase inhibitors incorporating cinnoline scaffold are relatively infrequent. Thus the aim of this work was to replace the former scaffolds with the latter one. Eighteen novel cinnoline derivatives were designed, synthesized and characterized using both microanalytical and spectral data. The cytotoxic activity of the new compounds was screened in vitro against both human breast cancer cells and normal breast cells. The enzymatic inhibition activity of promising candidates against both epidermal growth factor receptor tyrosine kinase and topoisomerase I was accomplished. Cell cycle profiles were observed at IC50 doses of representative biologically active compounds. Compound 7 represented a new scaffold incorporating triazepinocinnoline ring system and showed outstanding cytotoxic activity against MCF-7 (0.049 µM), tyrosine kinase inhibition (0.22 µM), apoptosis percentage and the highest selectivity index.


Rapid selection of tetracycline-controlled inducible cell lines using a green fluorescent-transactivator fusion protein.
We describe a modification of the tetracycline-controlled expression system that facilitates the rapid identification of tetracycline-sensitive clones. The TetR/VP16 transactivator protein was tagged with the green fluorescent protein (GFP) at its N-terminus. This results in a functional transactivator which allows cells expressing high levels of the modified transactivator to be selected by fluorescent-activated cell sorting. After expansion, single cell clones that maintain a high level of GFP fluorescence can be tested for their ability to transactivate a luciferase gene under control of the Tet operator, leading to the rapid identification of clones with strong inducibility.


[Dimensions of parental rearing styles in alcohol dependent patients: first results of the questionnaire on parental attitudes and rearing practices (FEPS)].
To date no instrument for the assessment of parenting styles is available in the German -language area that has been validated in patients with addictive disorders. Therefore the aim of this study was the confirmatory evaluation of the factor structure of the Questionnaire on Parental Attitudes and Rearing Practices (FEPS) in 186 alcohol dependent patients. The model as proposed by the test developers with the 4 factors Care, Autonomy, Low Punishment, and Low Material Reinforcement showed acceptable fit when residual correlations were allowed (mother: χ(2)/df=1,92, RMSEA=0,07, TLI=0,79; father: χ(2)/df=1,75, RMSEA=0,07, TLI=0,82). All factors showed sufficient factor reliabilities as well as good to very good internal consistencies. Factor loadings, discriminations and difficulties of the indicators could be regarded as good, with the exception of 2 items. These results indicate the factorial validity of the FEPS in patients with alcohol dependence.


The competitiveness of solvent adsorption on polar-embedded stationary phases.
Solvation processes on polar embedded stationary phases were investigated by determination of excess isotherms in binary acetonitrile/water mobile phase. The obtained results indicate the competitiveness of acetonitrile and water adsorption on heterogeneous surfaces of chemically bonded stationary phases. The calculation of excess isotherm as a volume of excessively accumulated solvent confirms the competitiveness of solvents' adsorption in qualitative and quantitative meaning. Corresponding excess isotherms of water and acetonitrile are symmetrical with respect to the x-axis. It confirms that the displaced volume of acetonitrile is replaced by an equal volume of water and vice versa. Additionally, fitting the two-site adsorption model to experimental data provides quantitative values with low experimental errors. The obtained results confirm the advantage of volumetric assumption of excess adsorption over direct adsorption layers of solvents, which is commonly postulated.


Vinyl polymers based on L-histidine residues. Part 1. The thermodynamics of poly(ampholyte)s in the free and in the cross-linked gel form.
Amphiphilic vinyl polymers (in the free and cross-linked forms), carrying carboxyl and imidazole groups, were prepared by a radical polymerization of the purposely synthesized N-acryloyl-L-histidine. The protonation thermodynamic studies (at 25 degrees C in 0.15 M NaCl) showed high polyelectrolyte character of the soluble polymer. Unlike the linear decreasing trend of the basicity constant, over the whole range of alpha (degree of protonation), the enthalpy changes for the protonation of the imidazole nitrogen in the polymer showed a decreasing pattern only at alpha > 0.5. This was ascribed to the formation of hydrogen bonds between protonated and free neighboring monomer units. Viscometric data revealed a minimum hydrodynamic volume of the polymer at its isoelectric point (pH 5), whereas at higher or lower pHs, the macromolecule expanded greatly as a consequence of the charged sites formation. This produced a preferential solvation of the protonated imidazole and carboxylate ions, the latter being surrounded by more water molecules in the hydration shell. The peculiar hydration behavior was confirmed in the cross-linked polymer. The hydrogel showed an equilibrium degree of swelling (EDS), strongly dependent on pH, in a similar manner as viscometric data of the soluble polymer. A linear relationship between the reduced viscosity and the EDS was found. The polymer was non toxic against the RAW264 cell line.


Track detection in railway sidings based on MEMS gyroscope sensors.
The paper presents a two-step technique for real-time track detection in single-track railway sidings using low-cost MEMS gyroscopes. The objective is to reliably know the path the train has taken in a switch, diverted or main road, immediately after the train head leaves the switch. The signal delivered by the gyroscope is first processed by an adaptive low-pass filter that rejects noise and converts the temporal turn rate data in degree/second units into spatial turn rate data in degree/meter. The conversion is based on the travelled distance taken from odometer data. The filter is implemented to achieve a speed-dependent cut-off frequency to maximize the signal-to-noise ratio. Although direct comparison of the filtered turn rate signal with a predetermined threshold is possible, the paper shows that better detection performance can be achieved by processing the turn rate signal with a filter matched to the rail switch curvature parameters. Implementation aspects of the track detector have been optimized for real-time operation. The detector has been tested with both simulated data and real data acquired in railway campaigns.


Removal of cyanide from water by means of plasma discharge technology.
Two different nonthermal plasma reactors at atmospheric pressure were assessed for the first time for cyanide removal (1 mg L(-1)) from aqueous solutions (0.025 M NaHCO(3)/NaOH buffer, pH 11) at laboratory scale. Both devices were dielectric barrier discharge (DBD) reactors; one of them was a conventional batch reactor (R1) and the other one was a coaxial thin falling water film reactor (R2). A first-order degradation kinetics was proposed for both experiments, obtaining k(R1) = 0.5553 min(-1) and k(R2) = 0.7482 min(-1). The coaxial reactor R2 yielded a removal of 99% within only 3 min. Energy efficiencies (G) were calculated, yielding 1.74 mg kW(-1) h(-1) for R1 and 127.9 mg kW(-1) h(-1) for R2. When the treatment was applied to industrial wastewaters, cyanide elimination was confirmed, although at a lower rate (above 92% removal in 90 min with R2). Therefore, plasma reactors could be a relevant alternative to established advanced oxidation techniques (UV, H(2)O(2), ozonation, etc.) for the removal of cyanide from wastewaters with low organic loads or even drinking waters.


Morphine after tubal ligation with bupivacaine: dosage versus body weight.
We investigated whether there was a statistically significant difference in patient need for postoperative analgesia based on adjusted body weight between heavier and lighter women who underwent laparoscopic tubal ligation with bupivacaine injection at the skin incision. We examined 49 records of women who underwent laparoscopic tubal ligation at Oklahoma State University Medical Center between 2000 and 2005 and received an injection of bupivacaine at the surgical site during the procedure. Postsurgical morphine was measured as doses per kilogram of body weight against total body weight and as total milligrams per kilogram of body weight against total body weight. A regression was performed for each measurement. Heavier women required significantly fewer total milligrams of morphine per kilogram of body weight and fewer total doses of morphine per kilogram of body weight than lighter women (2-tailed P = .0035 and P = .0018, respectively). Our data may suggest that lipophilic bupivacaine injected at a surgical site is held in place better and works for a longer period when more fat is present.


Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in Myelodysplasia.
Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized by genetic heterogeneity, different clinical behaviors and prognoses. Some of this group of bone marrow failure conditions have known external causes, some are of unknown origin. Within marrow, intracellular, and extracellular elements of the innate immune system are activated and contribute to creation of multiple cytogenetic abnormalities and are central to the mode of hematopoietic cell failure. Basiorka et al. showed that NLRP3 inflammasome activity is essential to the innate immune system's destruction of marrow hematopoietic cells commonly in myelodysplasia. In April 2018 Hao et al. reported that methylene blue inhibits rat NLRP3 inflammasome function. Methylene blue has been in continuous use in humans for over a century. It is associated with an eminently benign side effect profile in human use. If as in rodents, methylene blue also inhibits NLRP3 inflammasome function in human myelodysplasia a trial of adjunctive methylene blue treatment in transfusion dependent, low risk myelodysplasia where marrow inflammation and apoptosis predominates, would be worth trying. HIGHLIGHTS - Cytogenetic abnormalities and innate immune activation are seen in myelodysplasia- The NLRP3 inflammasome is a core element generating marrow failure of myelodysplasia- In April 2018 methylene blue was reported to potently inhibit NLRP3 inflammasome function- Methylene blue has benign side effects and has been in human use for a century- Study of methylene blue treatment of myelodysplasia would be a low-risk intervention.


Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy.
All cytokines belonging to the interleukin-6 (IL-6)-type family of cytokines utilize receptors that have a modular build of several immunoglobulin-like and fibronectin type III-like domains. Characteristic of these receptors is a cytokine receptor homology region consisting of two such fibronectin domains defined by a set of four conserved cysteines and a tryptophan-serine-X-tryptophan-serine sequence motif. On target cells, interleukin-6 first binds to its specific receptor and subsequently to a homodimer of the signal transducer protein gp130. The interleukin-6 receptor consists of three extracellular domains. The N-terminal immunoglobulin-like domain is not involved in ligand binding, whereas the third membrane proximal fibronectin-like domain accounts for more than 90% of the binding energy to IL-6. Here, the key residues of this fibronectin-like domain involved in the interaction with IL-6 are described. Chemical shift mapping data with 15N-labeled IL-6R-D3 and unlabeled IL-6 coupled with recent structural data clearly reveal the epitope within the IL-6R-D3 responsible for mediating the high affinity interaction with its cognate cytokine.


Evaluation and management of patients after implantable cardioverter-defibrillator shock.
There has been a tremendous increase in the use of implantable cardioverter-defibrillators (ICDs) after several large clinical trials demonstrated their ability to effectively reduce mortality in selected populations of patients with cardiac disease. Thus, the nonelectrophysiologist will often encounter patients who have received an ICD shock. To assess options for the evaluation and management of patients who have received an ICD shock. Literature search using the PubMed and MEDLINE databases to identify articles published from January 1990 to September 2006, using the Medical Subject Headings defibrillators, implantable; defibrillators, implantable/adverse effects; anti-arrhythmic agents; electric countershock; quality of life; tachycardia therapy; algorithm; ventricular tachycardia/diagnosis; and supraventricular tachycardia/diagnosis. Case reports were excluded and articles were limited to those published in English. Scientific statements and guidelines from the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society were also reviewed, as were the reference lists of retrieved articles, to identify any additional articles for inclusion. There are multiple causes of both appropriate and inappropriate ICD shocks. Irrespective of appropriateness, receiving ICD shocks substantially impairs a patient's quality of life. A variety of techniques are available using ICD programming to reliably limit the occurrence of appropriate or inappropriate ICD shocks. Antiarrhythmic medications can also effectively reduce the occurrence of shocks. Through the use of effective ICD programming and antiarrhythmic medications, the occurrence of ICD shocks can be reduced while maintaining the lifesaving ability of the ICD. A basic understanding of the range of available options is fundamental for evaluation and management of the patient who has received an ICD shock.


Ethanol-derived acetaldehyde: pleasure and pain of alcohol mechanism of action.
Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), has been implicated in several actions of alcohol, including its reinforcing effects. Previously considered an aversive compound, ACD was useful in alcoholic's pharmacological treatment aimed at discouraging alcohol drinking. However, it has recently been shown that EtOH-derived ACD is necessary for EtOH-induced place preference and self-administration, thereby suggesting a possible involvement of ACD in EtOH motivational properties. In addition, EtOH-stimulating properties on DA neurons are prevented by pharmacological blockade of local catalase H2O2 system, the main metabolic step for biotransformation of EtOH into ACD within the central nervous system. It was further shown that pretreatment with thiol compounds, like L-Cysteine or D-Penicillamine, reduced EtOH and ACD-induced motivational effects, in fact preventing self-administration of both EtOH and ACD, thus suggesting a possible role for ACD as a biomarker useful in evaluating potential innovative treatments of alcohol abuse. These findings suggest a key role of ACD in the EtOH reinforcing effects. In the present paper we review the role of EtOH-derived ACD in the reinforcing effects of EtOH and the possibility that ACD may serve as a therapeutically targetable biomarker in the search for novel treatments in alcohol abuse and alcoholism.


Synthesis and characterization of beta-cyclodextrin-conjugated magnetic nanoparticles and their uses as solid-phase artificial chaperones in refolding of carbonic anhydrase bovine.
Surface-functionalized magnetic nanoparticles are widely used in various fields of biotechnology. In this study, beta-cyclodextrin-conjugated magnetic nanoparticles (CD-APES-MNPs) are synthesized and the use of CD-APES-MNPs as a solid-phase artificial chaperone to assist protein refolding in vitro is demonstrated using carbonic anhydrase bovine (CA) as model protein. CD-APES-MNPs are fabricated by grafting mono-tosyl-beta-cyclodextrin (Ts-beta-CD) onto 3-aminopropyltriethoxysilane (APES)-modified magnetic nanoparticles (APES-MNPs). Results obtained from transmission electron microscopy (TEM) and vibrating sample magnetometery (VSM) show that the synthesized magnetic nanoparticles are superparamagnetic with a mean diameter of 11.5 nm. The beta-CD grafting is confirmed by Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The amount of beta-CD grafted on the APES-MNPs is found to be 0.042 mmol g(-1) from elemental analysis. Our refolding results show that a maximum of 85% CA refolding yield can be achieved using these beta-CD-conjugated magnetic nanoparticles which is at the same level as that using liquid-phase artificial chaperone-assisted refolding. In addition, the secondary and tertiary structures of the refolded CA are the same as those of native protein under optimal conditions. These results indicate that CD-APES-MNPs are suitable and efficient stripping agents for solid-phase artificial chaperone-assisted refolding due to easier and faster separation of these nanoparticles from the refolded samples and also due to recycling of the stripping agents.


SKIN FEATURES IMPORTANT FOR THE OCCURRENCE OF CONTACT DERMATITIS IN HEALTHCARE WORKERS.
The occurrence of skin lesions in healthcare workers is associated with a negative impact on important skin functions, including protection from mechanical injuries, sunlight, dehydration, and penetration of chemical substances or pathogenic microorganisms. In healthcare professionals, the most common occupational skin disease is contact dermatitis (CD), either irritant (ICD) or allergic (ACD), and typically on the hands. ICD accounts for about 80% of occupational CD, making it the most frequent cause. According to the literature, CD frequency is higher among healthcare professionals than other occupations, with critical occupational risk factors including contact with irritants and allergens at the workplace. Furthermore, ICD is a multifactorial disorder influenced by many constituent and environmental factors. Constituent factors include age, gender, body location, atopy, and genetic factors, while environmental factors include temperature, airflow, humidity, and occlusion. Commonly encountered irritants are water, detergents and surfactants, solvents, oxidizing agents, acids, and alkalis; however, use of protective gloves or equipment, hand-washing habits, use of cleansers and creams, active inflammatory skin diseases, and daily activities are also important for ICD onset. Additionally, ICD is known to predispose to ACD. Important risk factors for ACD development include occupation, age, history of atopic dermatitis, genetics, female gender, and fair skin phototype. In summary, numerous skin features and other occupation-related factors contribute to CD among healthcare practitioners. Given the high level of exposure to contact irritants/allergens in the healthcare setting, implementation of preventive measures is crucial for a safer work environment.


Improving acceptance of computerized prescribing alerts in ambulatory care.
Computerized drug prescribing alerts can improve patient safety, but are often overridden because of poor specificity and alert overload. Our objective was to improve clinician acceptance of drug alerts by designing a selective set of drug alerts for the ambulatory care setting and minimizing workflow disruptions by designating only critical to high-severity alerts to be interruptive to clinician workflow. The alerts were presented to clinicians using computerized prescribing within an electronic medical record in 31 Boston-area practices. There were 18,115 drug alerts generated during our six-month study period. Of these, 12,933 (71%) were noninterruptive and 5,182 (29%) interruptive. Of the 5,182 interruptive alerts, 67% were accepted. Reasons for overrides varied for each drug alert category and provided potentially useful information for future alert improvement. These data suggest that it is possible to design computerized prescribing decision support with high rates of alert recommendation acceptance by clinicians.


Longitudinal changes in maternal corin and mid-regional proatrial natriuretic peptide in women at risk of pre-eclampsia.
Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Yet, elevated maternal plasma atrial natriuretic peptide (ANP) and corin levels have been reported in pregnancies complicated by pre-eclampsia (PE). The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and mid-regional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop PE and gestational hypertension (GH). This was a nested case-control study drawn from a larger prospective longitudinal study in singleton pregnancies identified as being at high risk for PE by screening at 11 + 0 to 13 + 6 weeks' gestation. Blood samples were taken every 4 weeks until delivery. Values were compared in pregnancies that developed preterm PE (requiring delivery before 37 weeks' gestation), term PE, GH and those that remained normotensive. A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term PE and 12 preterm PE. In the normotensive group, log10 corin levels were associated with gestational age (P < 0.01), whereas log10 MR-PANP levels were not. In the preterm-PE group, compared with the normotensive group, corin was significantly lower until 20 weeks' gestation (P = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group (P = 0.637 and P = 0.161, respectively). Compared with the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm PE and GH (P = 0.046 and P = 0.019, respectively), but not term PE (P = 0.467). Maternal-plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm PE.


Calcified amorphous tumour of the heart: presentation of a rare case operated using minimal access cardiac surgery.
Calcified amorphous tumour (CAT) of the heart is a rarely reported non-neoplastic cardiac mass. The authors report a 69-year-old female with long-standing severe asthma and on home oxygen, who presented with a 2 cm mobile mass in the left ventricular outflow tract and symptoms of left heart failure and stroke. During minimal access cardiac surgery, a CAT was found attached to the base of the mitral valve. The tumour was removed and the patient had an uneventful postoperative course. The authors present their experience with this patient and review the current literature on this rare kind of tumour.


Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells.
Hepatocellular carcinoma (HCC) is a common malignancy and often resistant to chemotherapy. Many chemotherapy regimens have been tried to control advanced HCC, but have produced a low response rate and no clear impact. CPT-11, a derivative of camptothecin, works as type-I DNA topoisomerase inhibitor and showed a major objective response rate in patients with metastatic colorectal cancer. In this study, the mechanism underlying chemo-resistance to SN-38, an active form of CPT-11, in HCC was investigated in relation to anti-apoptotic pathways NF-kappaB and PI3K/Akt. Hep3B was the most resistant to SN-38 among three hepatoma cell lines. NF-kappaB was constitutively activated in Hep3B, and SN-38 further enhanced the nuclear translocation of NF-kappaB. However, inactivation of NF-kappaB by adenovirus expressing IkappaB super-repressor or MG-132, proteasome inhibitor, did not sensitize Hep3B to SN-38-induced apoptosis. On the other hand, SN-38 phosphorylated Akt and pretreatment with PI3K inhibitors increased SN-38-induced apoptosis, indicating that resistance to SN-38 in Hep3B occurs partly through the PI3K/Akt not the NF-kappaB pathway. Blocking of PI3K/Akt may thus be helpful for overcoming chemo-resistance of HCC.


BRM270 Suppresses Cervical Cancer Stem Cell Characteristics and Progression by Inhibiting SOX2.
Cervical cancer is one of the leading causes of cancer death in women worldwide. BRM270 (BRMLife) has therapeutic potential for cancer treatment owing to its ability to inhibit cell proliferation, and expression of cluster of differentiation (CD) 133 in CD133+ cancer cells. This study was designed to evaluate the therapeutic effects of plant extract formulation BRM270 against cervical cancer progression. The expression of sex-determining region Y-box 2 (SOX2) was tested in four different cervical cancer cell lines, HeLA, SiHa, Caski and C33A. SOX2-expressing SiHa and C33A cell lines were selected for further experiments on the in vitro and in vivo effects of BRM270 on cervical cancer progression using western blotting, flow cytometry, sphere-formation assay, magnetic-activated cell sorting of CD133+ cervical cancer cells, and xenografts in female athymic BALB/c nude mice. In the present study, in cervical cancer stem cells (CSCs), we found that BRM270 inhibited expression of SOX2, which is associated with cervical cancer initiation and metastasis. BRM270 also inhibited CD133 expression and induced apoptosis of CSCs and suppressed CD133+ CSC proliferation and sphere formation in vitro as well as SiHa and C33A cell xenograft tumor growth in vivo. This was accompanied by down-regulation of markers of epithelial-to-mesenchymal transition. BRM270 might be an effective agent for cervical cancer treatment.