Cooperative ligand-lattice binding. Approximate Gaussian binding distribution.
Nearest-neighbor cooperative binding of a ligand covering n sites and binding with equilibrium constant K and cooperativity factor omega to a large molecule with m binding sites (m much greater than n omega, n/omega) can be approximately described by a Gaussian distribution P(q-qmax), where q is the number of ligands bound and qmax the most probable value of q. The variance of the Gaussian is equal to the derivative dqmax/d ln(L), where L is the free ligand concentration. This variance, sigma 2, is a complicated function of qmax. However, in the limits of very large cooperativity, omega much greater than 1, very large anticooperativity, omega much less than 1, or noncooperativity, omega = 1, simpler expressions for sigma 2 can be given. For qmax = m/(n + 1), where the most probable number of bound ligands equals the number of free binding sites, sigma 2 has a particularly simple form: sigma 2 = 2m omega 1/2/(n + 1)3. The Gaussian and the infinite lattice approximations for the average number of ligands bound are good approximations only if sigma is much smaller than the number of binding sites. The variance may therefore provide an easy check on the validity of the infinite lattice approximation, which is commonly used to analyze experimental binding data.


Effects of selective monoamine oxidase inhibitors on the in vivo release and metabolism of dopamine in the rat striatum.
Brain microdialysis was used to examine the in vivo efflux and metabolism of dopamine (DA) in the rat striatum following monoamine oxidase (MAO) inhibition. Relevant catecholamines and indoleamines were quantified by HPLC coupled with a electrochemical detection system. The MAO-B inhibitor selegiline only affected DA deamination at a dose shown to inhibit partially type A MAO. Alterations in DA and metabolite efflux were not observed when using the MAO-B-selective dose of 1 mg/kg of selegiline. At 10 mg/kg, selegiline reduced the efflux of DA metabolites to approximately 70% of basal values without affecting DA efflux. K(+)- and veratrine-stimulated DA efflux was not affected by selegiline. Experiments using amphetamine and the DA uptake inhibitor nomifensine demonstrated that the effect of selegiline on DA metabolism was unlikely to be mediated either by inhibition of DA uptake or by an indirect effect of its metabolite amphetamine. The possibility that the effect of selegiline is mediated via a nonspecific inhibition of MAO is discussed. In contrast, the MAO-A inhibitor clorgyline inhibited basal DA metabolism and increased basal and depolarisation-induced DA efflux. A 1 mg/kg dose of clorgyline reduced basal DA metabolite efflux (40-60% of control values) without affecting DA efflux. At 10 mg/kg of clorgyline, DA efflux increased to 253 +/- 19% of basal values, whereas efflux of DA metabolites was reduced to between 15 and 26% of control values. The release of DA induced by K+ and veratrine was not affected by 1 mg/kg of clorgyline but was increased by approximately 200% following pretreatment with 10 mg/kg of clorgyline. The nonselective MAO inhibitor pargyline caused similar but more pronounced alterations in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation.
Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.


A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer.
Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.


Physiological and Psychological Effects of a Forest Therapy Program on Middle-Aged Females.
The natural environment is increasingly recognized as an effective counter to urban stress, and "Forest Therapy" has recently attracted attention as a relaxation and stress management activity with demonstrated clinical efficacy. The present study assessed the physiological and psychological effects of a forest therapy program on middle-aged females. Seventeen Japanese females (62.2 ± 9.4 years; mean ± standard deviation) participated in this experiment. Pulse rate, salivary cortisol level, and psychological indices were measured on the day before forest therapy and on the forest therapy day. Pulse rate and salivary cortisol were significantly lower than baseline following forest therapy, indicating that subjects were in a physiologically relaxed state. Subjects reported feeling significantly more "comfortable," "relaxed," and "natural" according to the semantic differential (SD) method. The Profile of Mood State (POMS) negative mood subscale score for "tension-anxiety" was significantly lower, while that for "vigor" was significantly higher following forest therapy. Our study revealed that forest therapy elicited a significant (1) decrease in pulse rate, (2) decrease in salivary cortisol levels, (3) increase in positive feelings, and (4) decrease in negative feelings. In conclusion, there are substantial physiological and psychological benefits of forest therapy on middle-aged females.


Crototropone, a new tropone derivative from Croton zehntneri.
Crototropone (3-hydroxy-5,6-dimethoxy-2-methylcyclohepta-2,4,6-trien-1-one) was isolated from roots of Croton zehntneri. The structure was established by spectroscopic methods.


Moving forward with interdisciplinary research on attractiveness-related biases.
In our response, we review and address the comments on our target article made in the 25 commentaries. First, we review and discuss the commentaries that recognized the value of our approach, accepted the main premises and conclusions of our target article, and suggested further avenues for research on attractiveness-related biases. We then respond to commentators who either misinterpreted some parts of our target article or made statements with which we disagree. These commentaries provided us with an opportunity to clarify some aspects of our target article, for example, the fact that we address both the functional significance of attractiveness-related biases and their underlying mechanisms. We provide a rebuttal to two commentaries, in which we are accused of poor scholarship. We conclude our response by addressing two commentaries that discussed the societal implications of the occurrence of attractiveness-related biases in the labor market by briefly discussing the relationship between scientific research and social policy.


Impact of switching virologically suppressed, HIV-1-infected patients from twice-daily fixed-dose zidovudine/lamivudine to once-daily fixed-dose tenofovir disoproxil fumarate/emtricitabine.
Evaluate the impact of switching from twice-daily zidovudine/lamivudine (AZT/3TC) to once-daily tenofovir DF plus emtricitabine (TDF/FTC) with efavirenz (EFV). Prospective, multicenter, single-arm 24-week trial. Patients on EFV + AZT/3TC for > or =8 weeks with HIV-1 RNA <400 copies/mL were switched to EFV + TDF/FTC and assessed for safety/tolerability, virologic and immunologic responses, adherence, and quality of life at 4, 12, and 24 weeks. Of 402 patients, 2% discontinued for an adverse event (AE) and 1 patient for virologic failure. At 24 weeks, 87% had HIV RNA <400 copies/mL, and 74% versus 71% at baseline had undetectable (HIV RNA <50 copies/mL) viral load (ITT; M=F). Treatment-emergent AEs were infrequent (< or = 5%) with gastrointestinal complaints being the most common. At 24 weeks compared to baseline, hemoglobin (Hb) increased by a median of 0.6 g/dL (p < .001), and a decrease in creatinine clearance of 7.6 mL/min (p < .001) was observed. Fasting lipids decreased slightly (p < .02) in a subset of patients studied (n = 160). A higher percentage of patients reported being "very satisfied" with treatment and the absence of regimen side effects at 24 weeks versus baseline (p < .001). At 24 weeks, 86% of patients took > or = 95% of doses versus 78% at baseline (p = .002). Patients switched to EFV + TDF/FTC maintained virologic suppression and the regimen was well tolerated. Patients reported increased satisfaction with treatment and fewer were bothered by side effects.


[Effects of lindane, an organochlorine insecticide, on the thyroid gland of larvae of Xenopus laevis Daudin in premetamorphosis].
The effects of 0.5 ppm of lindane were studied on the morphogenesis and the initial functioning of the thyroid gland. Some disturbances were observed: the formation of the first follicles were delayed and ultrastructural changes were noted: increase in the number of mitochondria, reduction of the endoplasmic reticulum. This demonstrates a noxious effect of lindane at the beginning of the functional maturation of the thyroid gland.


Generation of the integration-free induced pluripotent stem cell line (FHUSTCi001-A) from a patient with glomerulopathy with fibronectin deposits harboring FN1 mutation.
Glomerulopathy with fibronectin deposits (GFND) is an autosomal dominant kidney disease exhibiting microscopic hematuria, proteinuria, and hypertension that may lead to end-stage renal failure. In this study, using non-integrative episomal vectors an induced pluripotent stem cell (iPSC) line, FHUSTCi001-A, was derived from peripheral blood mononuclear cells of an 11-year-old boy with GFND carrying a heterozygous c.5602G > A (p.V1868M) mutation in the FN1 gene. The generated iPSC line has a normal karyotype, expresses pluripotency markers, and has the capacity to form all three germ layers in vivo. This iPSC line offers a useful cellular model to study the pathogenesis of GFND disease.


Elucidation of enterotoxigenic Bacillus cereus outbreaks in Austria by complementary epidemiological and microbiological investigations, 2013.
Identifying Bacillus cereus as the causative agent of a foodborne outbreak still poses a challenge. We report on the epidemiological and microbiological investigation of three outbreaks of food poisoning (A, B, and C) in Austria in 2013. A total of 44% among 32 hotel guests (A), 22% among 63 employees (B) and 29% among 362 residents of a rehab clinic (C) fell sick immediately after meal consumption. B. cereus isolated from left overs or retained samples from related foods were characterized by toxin gene profiling, and molecular typing using panC sequencing and M13-PCR typing (in outbreak A and C). We identified two B. cereus strains in outbreak A, and six B. cereus strains, each in outbreak B and C; we also found Staphylococcus aureus and staphylococcal enterotoxins in outbreak A. The panC sequence based phylogenetic affiliation of the B. cereus strains, together with findings of the retrospective cohort analyses, helped determining their etiological role. Consumption of a mashed potatoes dish in outbreak A (RR: ∞), a pancake strips soup in outbreak B (RR 13.0; 95% CI 1.8-93.0) and for outbreak C of a fruit salad (RR 1.50; 95% CI 1.09-2.00), deer ragout (RR: 1.99; 95% CI 1.23-3.22) and a cranberry/pear (RR 2.46; 95% CI 1.50-4.03)were associated with increased risk of falling sick. An enterotoxigenic strain affiliated to the phylogenetic group with the highest risk of food poisoning was isolated from the crème spinach and the strawberry buttermilk, and also from the stool samples of the one B. cereus positive outbreak case-patient, who ate both. Our investigation of three food poisoning outbreaks illustrates the added value of a combined approach by using epidemiological, microbiological and genotyping methods in identifying the likely outbreak sources and the etiological B. cereus strains.


Serum bromide measurements in infants below 1000 g, for determination of corrected bromide space.
We describe modifications to the gold colorimetric method for the measurement of serum bromide in the estimation of extracellular fluid volume. These modifications allow the application of the bromide dilution technique to small infants, below 1000 g birth weight, since sample volumes as small as 50 microliters may be assayed.


Development of an HL7 interface engine, based on tree structure and streaming algorithm, for large-size messages which include image data.
A basic assumption of Health Level Seven (HL7) protocol is 'No limitation of message length'. However, most existing commercial HL7 interface engines do limit message length because they use the string array method, which is run in the main memory for the HL7 message parsing process. Specifically, messages with image and multi-media data create a long string array and thus cause the computer system to raise critical and fatal problem. Consequently, HL7 messages cannot handle the image and multi-media data necessary in modern medical records. This study aims to solve this problem with the 'streaming algorithm' method. This new method for HL7 message parsing applies the character-stream object which process character by character between the main memory and hard disk device with the consequence that the processing load on main memory could be alleviated. The main functions of this new engine are generating, parsing, validating, browsing, sending, and receiving HL7 messages. Also, the engine can parse and generate XML-formatted HL7 messages. This new HL7 engine successfully exchanged HL7 messages with 10 megabyte size images and discharge summary information between two university hospitals.


Digest: Multiple factors influence mountain orchid diversity and distribution.
How have orchid species diversified in the campos rupestres, Brazil? Fiorini et al. (2023) use genomic data sets and multidisciplinary approaches, including phylogenetics and population genomics, to investigate the diversity of Bulbophyllum. They demonstrate that geographic isolation alone does not explain diversification patterns in Bulbophyllum species throughout the sky forests. Some taxa show considerable evidence of gene flow, and lineages not previously identified as closely related could present a novel source of their genetic diversity.


Lipase-catalyzed synthesis of antibacterial and antioxidative erythorbyl ricinoleate with high emulsifying activity.
Erythorbyl ricinoleate (ERO) was synthesized as a novel multi-functional emulsifier with antibacterial and antioxidative activities via lipase-catalyzed esterification between erythorbic acid and ricinoleic acid. Esterification regioselectively produced ERO (6-O-ricinoleoyl-erythorbate) of 238.67 mM at 48 h. ERO effectively reduced interfacial tension to 2.66 mN/m at its critical micelle concentration (0.73 mM), compared with other erythorbyl fatty acid esters (EFEs). Oil-in-water (O/W) emulsion stabilized by ERO remained stable for 15 days with a droplet size of 256.3 nm and polydispersity index of 0.22, whereas the emulsion stabilized by the other EFEs became unstable within six days. ERO had antibacterial activity against Gram-positive bacteria with minimum inhibitory concentrations from 0.2 to 0.6 mM. In O/W emulsion, ERO exhibited higher antioxidative activity than erythorbic acid against lipid oxidation. These findings suggest that ERO has high potential as multi-functional food additive to control lipid oxidation and bacterial contamination for O/W emulsion foods.


Nutrient signaling to mTOR and cell growth.
The mammalian target of rapamycin (mTOR) is a conserved protein kinase involved in a multitude of cellular processes including cell growth. Increased mTOR activation is observed in multiple human cancers and inhibition of mTOR has proven efficacious in numerous clinical trials. mTOR comprises two complexes, termed mTORC1 and mTORC2. Both complexes respond to growth factors, whereas only mTORC1 is controlled by nutrients, such as glucose and amino acids. Since the discovery of mTOR, extensive studies have intricately detailed the molecular mechanisms by which mTORC1 is regulated. Somewhat paradoxically, amino acid (AA)-induced mTORC1 activation -arguably the most essential stimulus leading to mTORC1 activation - is the least understood. Here we review the current knowledge of nutrient-dependent regulation of mTORC1.


Radiodensity of base, liner and luting dental materials.
The aim of this study was to determine the radiodensity of base, liner and luting dental materials and to compare them with human enamel and dentin. Four classes of materials were examined: conventional glass ionomers (CG)-Vitro Cem, Ketac Bond, Vidrion F, Vidrion C; resin-modified glass ionomers (RMGI)-Fuji II LC, Vitrebond; resinous cement (RC)-Rely-X ARC; and zinc phosphate cement (ZP)-Cimento LS. Five 2-mm-thick standard samples of each material and five 2-mm-thick enamel and dentin samples were produced. An aluminum step wedge served as control. Samples were positioned over a phosphor plate of Digora digital system, exposed to X-ray, and the radiodensity obtained in the software Digora for Windows 2.0. Data were submitted to Kruskal-Wallis and Dunnett multiple comparisons test (alpha=0.05). According to statistical analysis, the following sequence in degree of radiodensity could be seen among the groups: Cimento LS (ZP) > Vitro Cem (CG) = Fuji II LC (RMGI) = Rely-X ARC (RC) = Vitrebond (RMGI) > Ketac Bond (CG) > enamel = Vidrion F (CG) > Vidrion C (CG) = dentin. The presence of radiopaque fillers such as zinc, strontium, zirconium, barium, and lanthanium rather than material type seems to be the most important factor when analyzing material radiodensity. Almost all investigated materials presented an accepted radiodensity.


HLA class I homologous transcripts in the human embryonal carcinoma cell line Tera-2.
We have used the human teratocarcinoma-derived embryonal carcinoma cell line Tera-2 cl. 13 to explore the putative expression of novel HLA class I(-like) genes. Serological analyses revealed that Tera-2 cells do not express polymorphic HLA class I (-A, -B, -C) specificities, but do express HLA class I-like antigens. These phenotypic properties parallel those of certain mouse embryonal carcinoma cells. To study the expression of HLA class I(-like) genes in the Tera-2 cells two different approaches were used. Screening of a Tera-2 cDNA library with a full-length HLA class I cDNA probe under conditions that would allow for the identification of relatively distinct HLA class I-like sequences yielded 27 positive clones, all of which were of the regular HLA-A, -B, -C type. Reverse northern hybridizations of the restriction enzyme-digested Tlab region comprising cosmids with Tera-2 cDNA as the probe resulted in the identification of several putative human genes whose equivalents map within the mouse Tla region. However, none of these genes appeared to be structurally related to HLA class I. A putative H3.3 histone gene was identified in the proximal Tla region of the C57BL/10 mouse. It is concluded that no structural homologues of mouse Qa/Tla genes are expressed in the human developmental cell line Tera-2.


Properties of the crossover from nonclassical to classical chemical kinetics in a reversible A+B<-->C reaction diffusion process.
We study the properties of the reaction front formed in a reversible reaction diffusion process A+B<-->C, with initially separated reactants. The case of the mobile C component is considered. In accordance with Chopard et al. [Phys. Rev. E 47, R40 (1993)] the dynamics of the front is described as a crossover between the "irreversible" regime at short times and the "reversible" regime at long times. A refined definition for the rate of C production is suggested, taking into account both the forward and the backward reaction rates. By this definition within the framework of the mean-field equations it is shown that the reversible regime is characterized by scaling of the local rate of C production as R(local) approximately t(-1) and by scaling of the global rate of C production as R(global) approximately t(-1/2). It is also established that in the considered special case of equal diffusion coefficients and equal initial concentrations, the macroscopic properties of the reaction front, such as the global rate of the C production R(global) and the concentration profiles of the components outside the front reaction, are unchanged through this crossover.


Solvent-dehydrated cadaveric dermis: a new allograft for pubovaginal sling surgery.
The aim of this study was to evaluate the efficacy of solvent-dehydrated cadaveric dermis in pubovaginal sling surgery for the first time in the literature. Twenty-five women with stress urinary incontinence underwent pubovaginal sling surgery using 2 x 12 cm allograft dermis. Preoperatively, all patients were evaluated by a detailed urogynecologic evaluation, voiding diary, pelvic examination and urodynamic investigation. Outcome was assessed by the Urogenital Distress Inventory short form and standardized follow-up questionnaires. Twenty (80%) patients were cured of stress incontinence symptoms. Seventeen wore no pad and three reported occasional stress urinary incontinence and used no or one pad at a mean follow up of 12 months. Five (20%) patients in our series experienced the same amount of leakage as before the surgery. Seventy-six percent of the patients indicated that urinary incontinence was no longer negatively affecting their daily life and were satisfied with the procedure. Questionnaire-based assessment of outcome suggests that solvent-dehydrated cadaveric dermis is effective in the treatment of stress urinary incontinence. However, larger and comparative prospective studies with long-term results and randomized comparison of tissue preparation techniques are warranted.


Three Sgp loci act independently as well as synergistically to elevate the expression of specific endogenous retroviruses implicated in murine lupus.
Endogenous retroviruses are implicated in murine lupus nephritis. They provide a source of nephritogenic retroviral gp70-anti-gp70 immune complexes through the production of serum gp70 protein and anti-gp70 autoantibodies as a result of the activation of TLR7. The Sgp (serum gp70 production) loci identified in lupus-prone mice play distinct roles for the expression of different classes of endogenous retroviruses, as Sgp3 regulates the transcription of xenotropic, polytropic and modified polytropic (mPT) viruses, and Sgp4 the transcription of only xenotropic viruses. In the present study, we extended these analyses to a third locus, Sgp5, using BALB/c mice congenic for the NZW-derived Sgp5 allele and also explored the possible interaction of Sgp3 and Sgp4 loci to promote the expression of endogenous retroviruses and serum gp70. The analysis of Sgp5 BALB/c congenic mice demonstrated that the Sgp5 locus enhanced the expression of xenotropic and mPT viruses, thereby upregulating the production of serum gp70. These data indicate a distinct action of the Sgp5 locus on the expression of endogenous retroviruses, as compared with two other Sgp loci. Moreover, comparative analysis of C57BL/6 double congenic mice for Sgp3 and Sgp4 loci with single congenic mice revealed that Sgp3 and Sgp4 acted synergistically to elevate the transcription of the potentially replication-competent Xmv18 provirus and the production of serum gp70. This indicates that the combined effect of three different Sgp loci markedly enhance the expression of endogenous retroviruses and their gene product, serum gp70, thereby contributing to the formation of nephritogenic gp70-anti-gp70 immune complexes in murine lupus.


Association between use of hand hygiene products and rates of health care-associated infections in a large university hospital in Norway.
An association between use of hand hygiene products and health care-associated infection rates was investigated in a large Norwegian university hospital. We conducted an ecologic study by combining data from purchasing and admission systems with data from 32 point prevalence surveys (27,248 patients) in 1998-2005. Data on purchase of hand disinfectants and soap, and patient-days, were collected for 20 bed wards similar to those of the prevalence surveys. The prevalence of infections was 7.1%. We found no significant decline in overall infections (P = .19), but use of hand hygiene products significantly increased from 28.5 L per 1000 patients-days in 1998 to 43.3 L per 1000 patient-days in 2005 (P < .001). After examining a linear dose-response relation between use and infection rates, we observed a borderline significant decline in infections from 8% to 6% with increased use of hand hygiene products (P = .05). This association appeared stronger for wards that were registered with infections >9% at study start in 1998 (P < .001). These data suggests that infection rates may be reflected by amount of hand hygiene products used. Quantification of such products over time may serve as an indicator for hand hygiene performance in hospitals.


Continent urinary undiversion to modified ureterosigmoidostomy in bladder extrophy patients.
The objectives of urinary diversion are expanding from merely preserving kidney functions to enabling the patient to have a good quality of life while maintaining an acceptable certain body image. During the new era of continent urinary diversion the psychological drawbacks of noncontinent skin stoma in young adolescents cannot be overlooked. Ureterosigmoidostomy has been the technique of choice for continent urinary diversion in bladder extrophy patients when bladder reconstruction is not feasible or has failed. Although it provides a good daytime continence it is associated with a high rate of nighttime incontinence and delayed complications of pyelonephritis and hyperchloremic acidosis. We managed five male bladder extrophy patients with noncontinent skin stoma (sigmoid colon conduit in three and ileal conduit in two) including two patients who had previously had complicated classic ureterosigmoidostomy. They underwent urinary undiversion to the valved and augmented rectum (three patients) and the valved S-shaped rectosigmoid pouch (two patients) with some modifications. The conduit was used in the construction, and the ureters were implanted behind an isolated intussusception ileal nipple valve. Tube cecostomy and total parenteral nutrition was used for 7 to 10 days instead of a temporary defunctioning transverse colostomy. With a mean follow-up of 19.8 months (range 9-36 months) all the patients are fully continent during the day and night, with an emptying intervals of 3 to 6 hours. Follow-up intravenous pyelography and renal scans revealed improvement or stabilization of the function and configuration of the upper tracts in all renal units. No prophylactic alkali therapy was given. No clinical evidence of acidosis or symptomatic urinary tract infection was observed. Modified ureterosigmoidostomy is a good alternative for continent urinary undiversion even in those who have previously had complicated classic ureterosigmoidostomy. Our modification of using tube cecostomy and parenteral nutrition instead of a temporary transverse colostomy warrants attention; it made the technique simpler and more attractive.


The role of ultrasonography in the diagnosis and management of non-traumatic acute abdominal pain.
Our aim was to assess the effects of initial ultrasonography (US) evaluation on the diagnosis and management of non-traumatic acute abdominal pain in the emergency department. Three hundred patients with the complaint of non-traumatic acute abdominal pain who were sent for US examination with an initial clinical impression were included in the study. Pre-US and post-US surveys were designed for the clinicians who requested US. The percentage concordance of US findings with the discharge diagnosis made by clinical follow-up, imaging modalities and surgery was determined by calculating the confidence interval. The concordance of the initial clinical impression and the US diagnosis with the discharge diagnosis were compared using the McNemar test. US could not detect any pathology in 102 (34%; 95%CI, 28.6-39.3%) of the patients. The US revealed a different diagnosis than the clinical impression in 69 (23%; 95%CI, 18.2-27.7%), and confirmed the diagnosis in 121 (40%; 95%CI, 34.4-45.5%) patients. The US changed the treatment plans in 47% (95%CI, 41.3-52.6%) of the patients. The clinicians stated US helped them "very much" or "moderately" in making a diagnosis in 83% (95%CI, 78.7-87.2%). When US results were compared with the discharge diagnosis, there was concordance in 238 (79.3%; 95%CI, 74.3-83.6%) patients but not in 62 (20.6%; 95%CI, 16-25.1%). Among 121 patients the initial clinical impression agreed with the US diagnosis and there was concordance with the discharge diagnosis in 105 (86.7%; 95%CI, 80-92.7%). The concordance of US findings with the discharge diagnosis was significantly higher than that of the initial clinical impression statistically. In the initial evaluation of the patients with acute abdominal pain, US is considerably helpful in making the correct diagnosis, and that the concordance with the discharge diagnosis is high. When whole abdominal scanning is not performed, targeted US study according to the initial clinical impression decreases the clinical benefit of US.


Chronic unpredictable stress induces depression/anxiety-related behaviors and alterations of hippocampal monoamine receptor mRNA expression in female mice at different ages.
Depression and anxiety are the most common mental health disorders. Though they affect people at any age and occur more often in females, the pathophysiological changes under these conditions are less investigated. In the present study, we examined the effects of age and stress on depression- and anxiety-related behaviors in female mice. Saccharin preference and the open field test were carried out before and after chronic unpredictable stress in 4-, 14- and 25-month-old female mice. After behavioral tests, mRNA levels of monoamine receptors in the hippocampus were measured by real-time RT-PCR. Chronic unpredictable stress decreased saccharin preference in 4-, 14- and 25-month-old mice and the time spent in the center in the open field test in 25-month-old mice. For monoamine receptors, analysis of variance revealed significant effects of age on mRNA levels of Htr1a, Htr2a, Htr6, Adra1a, Adrb2, and Adrb3, significant effects of stress on mRNA levels of Htr4, Adra2c, Adrb1, and Adrb2, and interactions of age × stress on mRNA levels of Htr1a, Htr5b, Adra1d, Adra2a, Adra2c, and Adrb1. Chronic unpredictable stress decreased mRNA levels of Htr4, Htr5b, Adra2c, and Adrb1 in 4-month-old female mice. Correlations were observed between saccharin preference and mRNA levels of Htr4, Htr5b, Htr6, Adra1d, Adra2a, and Adra2c in 4-month-old mice and between the time spent in the center in the open field test and mRNA levels of Htr1b in 4-month-old mice, Htr3a, Htr7, and Adrb2 in 14-month-old mice, and Drd2 in 4- and 14-month-old mice. Our findings support that stress induces depression- and anxiety-related behaviors and the expression of hippocampal monoamine receptors in an age-dependent manner in female mice.


1H-NMR spectroscopy of the intracellular water of resting and rigor frog skeletal muscle.
The intracellular water of intact/relaxed and skinned/rigor fibers of frog skeletal muscle was studied at slack and stretched lengths by use of 1H-nuclear magnetic resonance (NMR) technique. The angular dependent changes of the NMR spectra of the water proton indicated that part of the intracellular water is aligned along the muscle fiber axis. The longitudinal and transverse proton-spin relaxation processes of the intracellular water were composed of a single- and multi-exponential processes respectively and the rate of both relaxations became slow as the water content of muscle fiber was increased. The longitudinal relaxation process was almost the same at slack and at stretched lengths for both intact/relaxed and skinned/rigor fibers. On the other hand, the transverse relaxation process was slightly but significantly faster at stretched than that at slack length for skinned/rigor fibers while it was almost the same at slack and at stretched lengths for intact/relaxed fibers. These results may be explained as the intracellular water located in the overlap region between actin and myosin filaments is less structured in rigor state than that in relaxed state, or that the rigor formation disrupts the structured water bound to myofilaments.


Fractionation using adsorptive macroporous resin HPD-600 enhances antioxidant activity of Gnetum gnemon L. seed hard shell extract.
In this study, antioxidant activities and identification of the bioactive substances in Gnetum gnemon L. (Gg) seed hard shell were evaluated. The seed of Gnetum gnemon L., an Indonesian native plant, is commonly consumed as a vegetable or further processed as cracker. Isolated substances from Gnetum gnemon seed are mainly stilbenoid derivatives which show potent antioxidant, tyrosinase inhibitor, and antimicrobial activities. Nevertheless, the antioxidant activity of its crude extract is still considered weak. In this study, an effort was made to improve antioxidant potency by fractionation using macroporous adsorptive resin (MAR). This fractionation successfully enhanced antioxidant activity of red Gg seed hard shell extract with efficient adsorption contact time within 30 min. Antioxidant activity of fractions 25-75% v/v ethanol increased three- to sevenfold as compared to crude extract and more importantly resulted in dry product which was easier for further processes. Identification of bioactive compounds in Gg seed hard shell extract with different degrees of ripeness was also performed by HPLC and confirmed the presence of Gnetin C, resveratrol, and other stilbenoid derivatives. These other stilbenoid derivatives could be the main substances contributing in antioxidant action with lower IC50 as compared to both Gnetin C and resveratrol. In summary, fractionation process using MAR HPD-600 reduced unnecessary sugar molecules from red Gg seed hard shell extract hence resulting to fraction with strong antioxidant activity.


Atrial fibrillation-related stroke in women: Evidence and inequalities in epidemiology, mechanisms, clinical presentation, and management.
Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. Despite substantial advances in (interventional) rhythm control treatment during the last decade, anticoagulation for stroke prevention remains a major component of AF treatment. There are important sex-specific differences in AF-related stroke, resulting from sex-specific mechanisms and therapeutic differences. This review summarizes available data on sex differences in risk assessment and prevention of stroke and highlights current knowledge gaps in AF-related stroke mechanisms, prevention and management that warrant further research. Increased thrombotic risk in women is multifactorial, involving hormonal changes after menopause, structural, endocrine and lifestyle/social factors and their interactions. It is clear from randomized studies that women benefit from anticoagulant treatment and that their bleeding risk is similar to men. Women should therefore receive equivalent treatment to men, based on the validated criteria for anticoagulation therapy. However, women are not represented equally in the large randomized studies and sex-related information in many fields is lacking. Female sex is an established risk factor for stroke in AF patients. The evidence for sex-specific differences in stroke risk assessment and stroke prevention is accumulating. However, the underlying biological mechanisms remain incompletely understood and further studies are required in order to decrease AF-related morbidity and mortality.


Syndrome of progressive deforming non-inflammatory arthritis of childhood: two patients of camptodactyly-arthropathy-coxa vara-pericarditis syndrome.
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare familial arthropathy of childhood, commonly misdiagnosed as juvenile idiopathic arthritis. It is characterized by non-inflammatory arthropathy, coxa vara deformity, and sterile pericarditis. We describe two children with CACP syndrome who were referred to the rheumatology clinic for the suspicion of inflammatory arthritis. A literature search was carried out using PubMed/ Medline and Embase databases. English language reports of mutation-proven cases of CACP syndrome reported until 31 March 2020 were retrieved and analysed. Both the children had a delay in diagnosis (age at diagnosis- 12 and 13 years, respectively) and had received immunomodulatory therapy for suspected inflammatory arthritis. Presence of symmetrical arthropathy of large joints, camptodactyly, and normal inflammatory parameters are clues that indicated CACP syndrome. One child with a novel variant in PRG4 also had associated mitral valve prolapse and regurgitation. Both had severe constrictive pericarditis requiring pericardiectomy. On literature review, a total of 98 mutation-proven cases of CACP syndrome have been reported till date. Arthropathy in CACP syndrome mainly involves knees, wrists, ankles, and hips. Pericarditis is usually mild, however, can present rarely with severe symptoms requiring surgical intervention. CACP syndrome can closely mimic inflammatory arthritis and early clinical recognition is important to avoid misdiagnosis. Molecular confirmation is essential for early diagnosis and future genetic counselling for affected families.


Tendon elongation with bovine pericardium (Tutopatch®) when conventional strabismus surgery is not possible.
Sometimes, a conventional recess-resect surgery may not be sufficient to obtain satisfactory ocular alignment. Patients who have previously undergone surgery and/or have a large difference in visual acuity between both eyes and do not wish to undergo surgery on the sound eye provide a surgical challenge. In these cases, tendon elongation with bovine pericardium may be an option. We retrospectively reviewed the charts of 38 patients who underwent strabismus surgery with tendon elongation. Before surgery, 31 had exotropia (angle -21.8 ± 5.7 degrees) and 7 esotropia (angle +19.1 ± 5.4 degrees). Reasons for tendon elongation included the following: 15 patients refused surgery on their sound eye; in 15 patients, conventional recess-resect was not possible; and in 7 patients, the elongation best fitted the motility pattern. In one patient, tendon elongation was preferred over conventional recession because of a thin sclera. Follow-up was 0.5 to 4 years. At last follow-up visit, in patients with previous exotropia, the angle was -3.3 ± 5.9 degrees; in patients with previous esotropia, +0.2 ± 0.5 degrees. Most had some duction limitation in the direction of the elongated muscle. All patients but one were satisfied with the result. In the patients with previous exotropia, there was a small but nonsignificant regression to recurrence of the exodeviation (on average 0.5 degree per year). Tendon elongation is a valuable addition to our strabismus surgery repertoire. However, because of duction limitations after surgery, it should be reserved for those cases in which conventional surgery is not an option.


Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys.
A cluster of trigeminal nociceptive neurons was located in the lateral sulcus on the upper bank of the frontoparietal operculum in a region bordering between cortical areas SII and 7b. These neurons were isolated in cortical cell layers IV and V-VI. All nociceptive neurons responded exclusively to noxious mechanical stimulation of cutaneous receptive fields on the face/head or intraoral tissue. Sustained noxious mechanical stimulation elicited slowly adapting responses that accurately encoded the duration of the stimulation. Prolonged discharges following removal of noxious stimulation were not observed. These nociceptive specific neurons poorly encoded graded noxious stimuli. Trigeminal somatosensory neurons within and surrounding the SII-7b cluster were not topographically organized according to divisions of the trigeminal nerve, laterality of receptive fields, or division of face/head and intraoral receptive fields. The thalamocortical, corticocortical and indirect corticolimbic connectivities of SII and area 7b and the possible role of SII-7b nociceptive neurons in learning, memory and avoidance behaviors are discussed.


In Vivo Fluorescence Reflectance Imaging with Subcutaneous Mouse Tumor Models.
Optical imaging is undoubtedly one of the most versatile and widely used imaging techniques in both research and clinical practice. Among optical imaging technologies, fluorescence imaging is the most popularly used and has become an essential tool in biomedical science. A key component of fluorescence imaging is fluorescence-producing reporters, including fluorescent dyes and conjugates, as well as fluorescent proteins. For in vivo imaging applications, fluorophores with long emission at the near-infrared (NIR) region are generally preferred to overcome the photon attenuation in living tissue. Here, we describe the in vivo fluorescence imaging of an integrin αυβ3 targeted NIR fluorescent probe (cRGD-ICG-Der-02) using subcutaneous mouse tumor models.


Anomalous pulmonary venous drainage of the right lung.
An unusual case of anomalous drainage of the right lung is described. The right superior pulmonary vein drained into the superior vena cava, and the middle and lower pulmonary veins drained into the inferior vena cava. Repair was achieved by creating a pericardial baffle that drained the inferior vein and the orifice of the superior vena cava through a surgically created atrial septal defect. The superior vena cava was transected and the distal portion anastomosed to the right atrial appendage.


Lung specific expression of a human mutant p53 affects cell proliferation in transgenic mice.
The human mutant p53(273H) has been shown in vitro to have both dominant-negative and gain-of-function properties, as well as to retain partial DNA-binding and transcriptional activation functions. We have developed a line of transgenic mice in which the human mutant p53(273H) is expressed in a lung specific manner (p53 (+/+/TG)). Crossing of the transgenic mice with p53 knockout mice led to generate mice with various genetic backgrounds. To evaluate the influence of p53 mutants in cell proliferation in mice lung tissue, we analyzed cell proliferation rate by Bromodeoxyuridine (BrdU) labeling and by expression of proliferating cell nuclear antigen (PCNA). BrdU analysis showed a 3.7-fold increase in the number of BrdU positive cells in the (p53 (-/+/TG)) mice compared to the (p53 (-/+)) mice, whereas no difference was observed in proliferation rate in the p53 (-/-/TG) lungs as compared to p53 (-/-) lungs. After the mice were treated with gamma-irradiation, BrdU positive cells were absent from both the p53 (-/+/TG) and p53 (-/+) mice, whereas a decrease in the rate of cell proliferation occurred in p53 (-/-/TG) lungs as compared to p53 (-/-) lungs. Real time PCR results indicated that the p53(273H) mutant did not retain the function to activate expression of p21 (WAF1/CIP1) in the transgenic mice. The above results indicate that overexpression of the human mutant p53(273H) in vivo results in an increase in basal proliferation rate which requires the presence of wild type p53. Mutant p53(273H) may affect cell proliferation by interrupting murine endogenous p53 function.


The deep history of imaginary worlds.
If recent exploratory traditions tap into evolved psychological dispositions to explore, wouldn't humans be expected to have drawn on such dispositions long before the written word? Trickster oral traditions fill this role in all levels of society, affluence, and on all continents, inverting the boundaries of social worlds and those between humans and animals, fostering cultural innovation.


Effects of source leukocyte collection on the immune system.
This study was initiated in order to assess any immunologic effects that source leukocyte concentrate collection might have on double-bag plasmapheresis donors. Previous studies have shown that surveillance parameters, such as T versus non-T lymphocyte subpopulations, showed no abnormal values in donors with as many as 500 visits over a 12-year period. The present study demonstrates that the frequency and the total number of leukocyte donations do not effect the lymphocyte subpopulations and functions observed. No significant changes were noted for specific and nonspecific stimulation, natural killer (NK) cell activity, lymphocyte surface markers and a variety of functional parameters. For example, the apheresis donors manifested no differences in NK cell activity, human leukocyte interferon production, IgG synthesis by B cells and percent suppression of both IgG synthesis and mixed lymphocyte cultures, when compared to non-apheresed donors.


Interleukin-1alpha secreted by pancreatic cancer cells promotes angiogenesis and its therapeutic implications.
Previously we reported the critical role of interleukin (IL)-1alpha in liver metastasis from pancreatic cancer (PaCa). However, its role in angiogenesis and metastasis, particularly as it relates to the interaction between tumor and stromal cells, was not clearly elucidated. To further investigate, we initially compared vascular endothelial cell migration and tube formation in human PaCa cell lines that differed in metastatic potential. We then compared the effects of IL-1alpha derived from PaCa cells on the same processes. Expression of IL-1alpha mRNA and protein in PaCa cells was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IL-1alpha mRNA and protein were detected only in predominantly liver-metastatic PaCa cells. Next, we examined differences in migration and tube formation by human umbilical vein endothelial cells (HUVECs) in the various PaCa cells using invasion and angiogenesis assays, respectively. Furthermore, we determined the effects of IL-1alpha secreted by PaCa cells on migration and tube formation by HUVECs using coculture experiments. Expression of IL-1alpha mRNA and protein was observed only by the highly liver-metastatic PaCa cell lines BxPC-3 and SW 1990. Both HUVEC migration and tube formation were significantly enhanced by coculture with metastatic PaCa cells and IL-1alpha (P < 0.01). Similarly, blockade of IL-1alpha by its antagonist inhibited HUVEC migration and tube formation (P < 0.01). Our results indicate that IL-1alpha secreted by PaCa cells plays an important role in metastasis through vascular endothelial cell invasion and angiogenesis. Thus, blocking IL-1alpha is a potential novel therapeutic strategy in PaCa.


Phenomenology of neurophysiologic changes during surgical treatment of carotid stenosis using signal analysis.
To describe the changes in the shape and topology of the somatosensory evoked potential (SSEP) during carotid endarterectomy, with particular reference to the time of clamping. Routine intraoperative monitoring was performed on 30 patients undergoing carotid endarterectomy (15) or undergoing stenting (15) using median nerve SSEPs. Post-operatively the first and second derivatives of the potential were examined. Separate analysis of the SSEP using wavelets was also performed. In no instances did changes in the SSEP reach clinical significance. The first derivative showed significant changes that were temporally related to the clamp period. After clamping the 'velocity' was higher than baseline. There were changes in the wavelets related to the clamp period with more marked spectral edges at the conclusion of the procedure than baseline. In all instances the patient had a good clinical outcome. Wavelet and derivative analysis of evoked potentials show changes that are not apparent with measures of amplitude and latency. The clinical relevance of these changes remains uncertain and await larger studies. Increased velocity and spectral edges may be markers of increased cerebral blood flow, at least in the setting of pre-existing carotid stenosis.


Vitamin D receptor agonists induce prostatic acid phosphatase to reduce cell growth and HER-2 signaling in LNCaP-derived human prostate cancer cells.
We have previously shown that concentrations of 1alpha,25-dihydroxyvitamin D(3) (1,25D) that induce G(0)/G(1) cell cycle arrest in androgen-dependent LNCaP prostate cancer cells also decrease expression of c-Myc, a proto-oncogene that stimulates progression from G(1) to S phase of the cell cycle. Since both c-Myc expression and cell cycle progression are regulated by tyrosine kinase activation, we examined the ability of 1,25D to alter tyrosine kinase signaling in LNCaP cells and the androgen-independent LNCaP C81 (C81 LN) cell line. 1,25D selectively reduced protein tyrosine phosphorylation within both the LNCaP and C81 LN cells. This reduction in tyrosine kinase signaling appears to result from elevated levels of cellular prostatic acid phosphatase (PAcP). Western blots and biochemical assays revealed 1,25D increases the level of active PAcP in both cell lines. In addition, 1,25D decreased tyrosine phosphorylation of HER-2, an EGFR family member inactivated by PAcP, and the HER-2 downstream adaptor protein p52 Shc in C81 LN cells. Inhibition of HER-2 signaling by AG825 reduces growth of C81 LN cells and the parental LNCaP cells. These data therefore suggest that 1,25D-mediated decreases in LNCaP and C81 LN cell growth are in part due to decreases in tyrosine kinase signaling that result from up-regulation of PAcP.


Biological activities of extracts from Chinese bayberry (Myrica rubra Sieb. et Zucc.): a review.
Chinese bayberry (Myrica rubra Sieb. et Zucc.) is a subtropical fruit tree native to China and other Asian countries, and culture of this Myricaceae plant has been recorded in Chinese history for more than 2000 years. Bayberry fruit is delicious with attractive color, flavor, and high economic value. Compared with other berries, bayberry fruit is a rich source of cyanidin-3-glucoside (C3G, e.g., 64.8 mg/100 g fresh weight in 'Biqi' cultivar), which accounts for at least 85 % of the anthocyanins in the fruit. Bayberry is also a plant with high medicinal value since different organs have been used historically as folk medicines. Research efforts suggest bayberry extracts contain antioxidants that exhibit bioactivities counteracting inflammation, allergens, diabetes, cancer, bacterial infection, diarrhea and other health issues. Bayberry compounds have been isolated and characterized to provide a better understanding of the chemical mechanisms underlying the biological activities of bayberry extracts and to elaborate the structure-activity relationships. As the identification of compounds progresses, studies investigating the in vivo metabolism and bioavailability as well as potential toxicity of bayberry extracts in animal models are receiving more attention. In addition, breeding and genetic studies of bayberry with high accumulation of health-benefiting compounds may provide new insight for the bayberry research and industry. This review is focused on the main medicinal properties reported and the possible pharmaceutically active compounds identified in different bayberry extracts.


Letter to the editor: Comment on a case report of thermal injury to spinal cord, a rare complication of percutaneous microwave spine tumour ablation.
Microwave ablation of the spine is an effective treatment option for patients with symptomatic osseous metastases. It is an increasingly common procedure in clinical practice and can be performed in conjunction with other procedures such as vertebroplasty and nerve root blocks. Multiple studies have demonstrated the safety and efficacy of the percutaneous ablation; however potential complications can arise. Thermal injury to the spinal cord is a rare but serious known complication which has severe consequences to the patient. Multiple strategies can be adopted to reduce the rate of complications. We aim to discuss the various technical considerations when performing percutaneous ablation of spinal tumours to decrease the risks of complications.


Preservation of single-flash visual evoked potentials at very low cerebral oxygen delivery in preterm infants.
Single-flash visual evoked potentials (VEPs) were recorded in 32 preterm infants (mean gestational age: 29 weeks) during extreme physiologic conditions within the first day of life. The VEP configuration was normal in all patients at the onset of the investigation. Hypoxic episodes (PaO2 less than 3 kPa) caused rapid and consistent attenuation of the VEP mostly with an instantaneous recovery after normalization of PaO2. In contrast, VEP amplitude and latency were unaffected during episodes with low cerebral blood flow (4.5 ml/100 gm/min) and correspondingly low oxygen delivery to the brain (1 ml/100 gm/min), severe hypocapnia (PaCO2 1.6 kPa), and severe arterial hypotension (MABP 10 mm Hg), provided that the arterial oxygen tension was greater than 5 kPa. Absence of N1 was observed soon after the development of severe intracranial hemorrhage; however, this abnormality was short in duration. We conclude that the neurons generating VEPs are supported sufficiently during extreme physiologic episodes, except during severe hypoxia. The recovery time may be proportional to the cerebral insult.


Stroke, Physical Function, and Death Over a 15-Year Period in Older Australian Women.
As populations age, an increasing number of older women are living with stroke. This study looks at long-term outcomes for women with stroke, comparing mortality rates for women with poor physical function (PF) and those with higher levels of function. The purpose is to understand not only how long women might live after a stroke, but also how long they live with physical disability. The study uses 15 years of data on women from the Australian Longitudinal Study on Women's Health 1921 to 1926 cohort. The risk of stroke and the risk of stroke and poor PF were estimated using Cox proportional hazard model. Among women who reported a stroke during the study period, mortality risk was compared according to their physical functioning level after that stroke. Almost half of the women who had a stroke and poor PF survived past 10 years. The 10-year mortality rate was 37% for women with stroke and adequate PF and 51% for women with stroke and poor PF at the time of the stroke (hazard rate ratio, 1.52; 95% CI, 1.18-1.95; P=0.0015 adjusting for demographic and health covariates). This study provides evidence of the long-term outcomes of stroke among older women, with women living for many years with poor PF. This outcome has important implications for the women's quality of life during their later years and in understanding the burden of disability associated with stroke.


Ultrasensitive and visible light-responsive photoelectrochemical aptasensor for edifenphos based on Zinc phthalocyanine sensitized MoS2 nanosheets.
Developing a simple, rapid detection method for the analysis of edifenphos (EDI) is crucial due to its residue is harmful to acetylcholinesterase on the human cellular system, and cause a lot of complications. Herein, we synthesized visible light-responsive MoS2 nanosheets decorated with Zinc phthalocyanine (ZnPc) nanoparticles (ZnPc/n-MoS2). Due to the sensitization of ZnPc nanoparticles, the resulting ZnPc/n-MoS2 exhibited narrower energy bandgap and efficient charge transfer. Especially, the carrier lifetime of ZnPc/n-MoS2 is 2 more times longer than n-MoS2, and the photocurrent intensity of ZnPc/n-MoS2 is 24 times of n-MoS2 and 22 times of ZnPc nanoparticles under visible light irradiation. Further, a visible light-responsive ultrasensitive photoelectrochemical (PEC) aptasensor for selectivity recognition of EDI was triumphantly established by using EDI aptamer as a biorecognition element, which exhibited a wide linear ranking from 5 ng L-1 to 10 μg L-1 (R2 = 0.996) and a low detection limit of 1.667 ng L-1 (S/N = 3). The splendid performance of the ZnPc/n-MoS2 nanosheet ultrasensitive sensing platform can be applied to detect the concentration of EDI in food, biomedical and environmental analysis.


The role of computed tomography in evaluation of skeletal metastases.
Computed tomography was performed in 100 patients for additional evaluation of suspected skeletal metastases following radionuclide bone scanning in 86 patients and conventional radiography in all. A retrospective review of these cases revealed that the majority (78%) involved the spine and pelvis. Computed tomography contributed to the diagnosis of a malignancy by revealing a definite destructive lesion of bone in 27 patients who had an abnormal radionuclide bone scan, a normal or inconclusive radiograph, or both. It excluded a malignant lesion in 19 patients. In 38 patients, computed tomography provided additional information that contributed to such aspects of patient care as obtaining tissue diagnosis, determining the extent of lesions, and evaluating the response to treatment. False diagnoses were made in two patients. Detection by computed tomography of a skeletal lesion and histologic documentation, frequently by computed tomography-guided percutaneous needle aspiration biopsy, greatly curtailed an otherwise extensive search for the primary site. Furthermore, this information altered the treatment plan by obviating the need for radical resection or biopsy of the primary tumor and by directing the choice of an appropriate chemotherapeutic regimen.


Astragulus polysaccharide-loaded fibrous mats promote the restoration of microcirculation in/around skin wounds to accelerate wound healing in a diabetic rat model.
Tissue engineering scaffolds (TES) can carry numerous biomacromolecules and cells, and they have been widely used in diabetic skin wound healing with positive effects. However, the bioactive retention of biomacromolecules and cells during fabrication and storage is still a factor restricting their use. Moreover, impaired blood supply in/around poorly healing diabetic skin wounds has not been considered. In the present study, a bioactive natural substance of Astragalus polysaccharide (APS), which has stable and confirmed effects on endothelial protection, was embedded into fibrous TES by electrospinning. The administration of APS-loaded TES on the skin wound in a diabetic rat model led to a dose-dependent promotion in skin blood flow around wounds and an increase in endoglin expression and microvessel density in regenerated skin tissues. Furthermore, the higher loading of APS in TES led to faster collagen synthesis, appendage and epidermal differentiation, and wound closure. In summary, the combination of APS with TES is a potentially novel therapeutic strategy for diabetic skin wound healing, as it not only mimics the ultrastructure of extracellular matrixes but also restores skin microcirculation.


Palmitate increases musclin gene expression through activation of PERK signaling pathway in C2C12 myotubes.
Musclin is a type of muscle-secreted cytokine and its increased gene expression induces insulin resistance in type 2 diabetes. However, the mechanism underlying increased musclin gene expression is currently unclear. Excessive saturated fatty acids (SFA) can activate the secretion of several muscle-secreted cytokines as well as endoplasmic reticulum (ER) stress pathway, thereby contributing to the development of type 2 diabetes. The purpose of this study was to investigate the mechanisms responsible for the effect of palmitate, the most abundant SFA in the plasma, on the gene expression of musclin in C2C12 myotubes. Treatment of C2C12 myotubes with palmitate or tunicamycin significantly increased the expression of musclin as well as ER stress-related genes, but treatment with oleate did not. Pre-treatment of C2C12 myotubes with 4-phenyl butyrate suppressed the expression of ER stress-related genes, simultaneously, resulting in decreased expression of the musclin gene induced by palmitate or tunicamycin. These results indicate that ER stress is related to palmitate-induced musclin gene expression. Moreover, palmitate-induced musclin gene expression was significantly inhibited in C2C12 myotubes when PERK pathway signaling was suppressed by knockdown of the PERK gene or treatment with GSK2656157, a PERK autophosphorylation inhibitor. However, there was no difference in the palmitate-induced musclin gene expression when IRE1 and ATF6 signaling pathways were suppressed by knockdown of the IRE1 and ATF6 genes. These findings suggest that palmitate increases musclin gene expression via the activation of the PERK signaling pathway in C2C12 myotubes.


1,1'-Methyl-enebis(4-tert-butyl-pyridinium) dichloride hemihydrate.
The structure of the title hydrated salt, C19H28N2 2+·2Cl-·0.5H2O, at 150 K has monoclinic (C2/c) symmetry. The water mol-ecule is located on a twofold rotation axis.


QA/QI and nursing competence: a combined model.
A Quality Assessment/Improvement/Competency Model, developed at Norwalk Hospital, provides objective data which fulfills Joint Commission QA/QI requirements. Simultaneously, this monitoring system provides for evaluation of clinical competence.


Inequalities in cause-specific mortality in children and adolescents in the Moramanga health survey, Madagascar.
One child or young adolescent dies every 10 min in Madagascar and large disparities in survival persist. We estimated cause-specific mortality in a cohort of children aged 0-14 in the Moramanga district and explored how causes of death shape these inequalities. Children were followed prospectively between 2012 and 2017. Causes of death were established based on verbal autopsies. Incidence rate ratios were estimated in Poisson regression models. The risk of dying before age 15 was 68.1 per thousand live births. Risks of dying were highest in the first year of life (31.2‰) and lowest in children aged 10-14 (6.4‰). The male-to-female sex ratios of mortality increased with age and reached 2.3 among adolescents aged 10-14. Communicable, nutritional and neonatal causes accounted for 79.5% of deaths below age 5 and 47.0% above age 5. Mortality was positively associated with household poverty, lack of education of the household head, and rural residence. Interventions should be designed with an equity lens to reduce large disparities in survival and be tailored to the needs of each age-group.


A survey of cancer morbidity and mortality in vaccinees seven to 12 years after the administration of live vaccine propagated in human diploid cells.
Using record linkage, cancer morbidity and mortality were examined in 2973 recipients of RA 27/3 strain rubella vaccine propagated in WI 38 cells. During the follow-up reported (mean duration 9.8 years; range seven to 12 years) the rate of cancer notifications and of deaths from cancer were similar to those observed in the equivalent age range of the general population.


[A method of recording the gastric secretory function in mice].
The technique of simultaneous study of stomach functions and the secretory levels of its glands was developed on the CC57W/MvY mice using morphological, bio- and histochemical methods. Protein RNA, DNA contents and levels of gastric tissue SDH activity as well as the composition of the gastric juice were studied. The correlation of gastric secretion with the activity of its tissue SDH was demonstrated.


Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in long evans rats.
Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1β, IL-6, IL-10, TNF-α, and TGF-β genes. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-β, IL-1 β, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.


An acetylcholinesterase biosensor based on platinum nanoparticles-carboxylic graphene-nafion-modified electrode for detection of pesticides.
A sensitive amperometric acetylcholinesterase (AChE) biosensor based on platinum nanoparticles (Pt NPs), carboxylic graphene (CGR), and nafion (NF)-modified glassy carbon electrode (GCE) has been developed. The Pt NPs-CGR-NF nanocomposites with excellent conductivity, catalysis, and biocompatibility offered an extremely hydrophilic surface for AChE adhesion. Chitosan (CS) was used as cross-linker to immobilize the AChE on Pt-CGR-NF-modified GCE. NF was used as a protective membrane of the AChE biosensors. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl with an apparent Michaelis-Menten constant value of 148μM. Under optimum conditions, the biosensor detected methyl parathion in the linear range from 1.0×10(-13) to 1×10(-10)M and from 1.0×10(-10) to 1×10(-8)M with a detection limit of 5×10(-14)M and detected carbofuran in the linear range from 1.0×10(-12) to 1×10(-10)M and from 1.0×10(-10) to 1×10(-8)M with a detection limit of 5×10(-13)M. The biosensor exhibited good sensitivity, acceptable stability, and reproducibility, thus providing a promising tool for analysis of enzyme inhibitors.


The HPV response is different with constant pressure vs constant flow perfusion.
Hypoxic pulmonary vasoconstriction (HPV) may be manifest in one of two ways: either an increase in the pulmonary artery pressure, or flow diversion away from the portion of the pulmonary bed with reduced conductance. We tested the hypothesis that the magnitude of the HPV response differs under conditions of constant flow perfusion, where pulmonary artery pressure (Ppa) rises during hypoxia, vs conditions of constant pressure perfusion, where Ppa remains constant and flow (Q) is diverted away from the lungs during hypoxia. In isolated, perfused rabbit lungs, the HPV response to four levels of hypoxia (12, 6, 3 and 0% oxygen) was of greater magnitude and more sustained under conditions of constant pressure perfusion as compared to constant flow perfusion. The possible significance of these findings as they relate to interpretation of studies in both the perinatal and mature pulmonary circulation is discussed.


Targeting the B cell in vasculitis.
The treatment of severe vasculitides, such as antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis, is associated with both short- and long-term toxicities that limit its use in paediatric patients and is complicated by refractory and relapsing disease that requires increased exposure to these toxic therapies. B cells have been implicated in the pathogenesis of autoimmune diseases, including vasculitis, and represent a potential target for new therapies that may have a more acceptable toxicity profile. The use of rituximab, a biologic therapy directed against B cells, has provided valuable insight into the potential role of B-cell targeted therapies for vasculitis. Rituximab appears to be a potentially useful treatment for vasculitis in adult patients, but randomized evidence comparing it to cyclophosphamide in terms of both efficacy and toxicity is lacking, as is long-term safety data. Several other B-cell-directed therapies are in development and may offer rational alternatives or adjunctives to traditional treatments.


Arterial desaturation in healthy children during transfer to the recovery room.
The oxygen saturation in 71 healthy paediatric patients (3.5 months to 16.7 years) was measured by pulse oximetry during transfer from the operating room to the recovery room. These measurements were recorded continuously while the patients breathed room air. Of the patients studied, 28.1 per cent exhibited significant arterial desaturation of less than or equal to 90 per cent. The corresponding PO2 for this saturation level is less than or equal to 58 mmHg. In only 45 per cent of these desaturated patients was the desaturation recognized clinically by the presence of cyanosis. Age, type of anaesthetic, the use or avoidance of narcotics, and the use of controlled or spontaneous respiration had no significant relationship to the incidence of desaturation. Since more than a one quarter of all patients studied desaturated significantly, and since cyanosis can be difficult to detect clinically during the transfer period, the use of supplemental oxygen during transfer should be considered by the anaesthetist at the end of every paediatric general anaesthetic.


Cross-Validation of Age-Predicted Maximal Heart Rate Equations Among Female Collegiate Athletes.
The purpose of this study was to determine the accuracy of 3 general and 2 female-specific age-predicted maximal heart rate (HRmax) prediction equations in female collegiate athletes. Thirty female collegiate athletes (age = 21.5 ± 1.9 years, height = 164.7 ± 6.6 cm, weight = 61.3 ± 8.2 kg) participated. HRmax was determined with a maximal graded exercise test and predicted with 3 general equations (Fox et al., Astrand, and Tanaka et al.) and 2 female-specific equations (Fairbarn et al. and Gulati et al.). There was no significant difference between observed HRmax (185.9 ± 5.0 b·min) and the Fairbarn (187.5 ± 1.2 b·min) and Gulati (187.1 ± 1.7 b·min) equations (p = 0.11 and 0.23, respectively). The Fox (198.5 ± 1.9 b·min), Astrand (198.1 ± 1.6 b·min), and Tanaka (193.0 ± 1.4 b·min) equations provided significantly higher estimates compared with observed HRmax (p < 0.001 for each). The standard error of the estimate was similar for all the prediction equations (between 5.0 and 5.4 b·min), but the total error was smallest for Fairbarn and Gulati (5.3 b·min for each) and largest for Fox and Astrand (13.9 and 13.3 b·min, respectively). The 95% limits of agreement of the mean error were similar for all of the prediction equations, with values varying between 9.9 and 10.5 b·min. Because of the wide limits of agreement displayed by each equation, the use of age-predicted methods for estimating HRmax in collegiate female athletes should be performed only with caution.


Reevaluating the Sensory Account of Visual Working Memory Storage.
Recent human fMRI pattern-decoding studies have highlighted the involvement of sensory areas in visual working memory (VWM) tasks and argue for a sensory account of VWM storage. In this review, evidence is examined from human behavior, fMRI decoding, and transcranial magnetic stimulation (TMS) studies, as well as from monkey neurophysiology studies. Contrary to the prevalent view, the available evidence provides little support for the sensory account of VWM storage. Instead, when the ability to resist distraction and the existence of top-down feedback are taken into account, VWM-related activities in sensory areas seem to reflect feedback signals indicative of VWM storage elsewhere in the brain. Collectively, the evidence shows that prefrontal and parietal regions, rather than sensory areas, play more significant roles in VWM storage.


Argania spinosa var. mutica and var. apiculata: variation of fatty-acid composition, phenolic content, and antioxidant and α-amylase-inhibitory activities among varieties, organs, and development stages.
Argania spinosa includes two varieties, var. apiculata and var. mutica. These argan varieties were introduced into Tunisia in ancient times and are actually cultivated in some botanic gardens. Little is known about the chemical differentiation among these argan varieties. Hence, the aim of this study was to determine the fatty-acid composition, the total phenolic and flavonoid contents, and the antioxidant and α-amylase-inhibitory activities of leaf, seed, and pulp extracts of both argan varieties harvested during the months of January to April. The fatty-acid distribution was found to depend on the argan variety, the plant organ, and the harvest time. Significant variations in the phenolic contents were observed between the investigated varieties as well as between leaves, pulps, and seeds of each variety. As expected, phenolic compounds were found to be contributors to the antioxidant and α-amylase-inhibitory activities of both argan varieties. The chemical differentiation observed among the two argan varieties, based mainly on the fatty-acid composition, might have some chemotaxonomic value.


Naproxen sodium in dysmenorrhea secondary to endometriosis.
Twenty patients with moderate to very severe painful menstrual periods secondary to endometriosis were treated in a double-blind, four-period, crossover clinical trial with naproxen sodium and placebo. Complete or substantial pain relief was obtained in 83% of the cases of painful menstruation with naproxen sodium and in 41% with placebo (P = .008). Only 5% of the naproxen sodium-treated women needed supplemental analgesics compared with 36% of the placebo-treated women (P = .002). There was a trend towards diminished interference of dysmenorrhea with normal patient activities during naproxen sodium treatment compared with placebo (P = .069). No significant side effects occurred with either treatment. These results indicated that naproxen sodium is efficacious and safe for the treatment of menstrual distress in patients with endometriosis.


Blinding and Randomization.
Most, if not all, guidelines, recommendations, and other texts on Good Research Practice emphasize the importance of blinding and randomization. There is, however, very limited specific guidance on when and how to apply blinding and randomization. This chapter aims to disambiguate these two terms by discussing what they mean, why they are applied, and how to conduct the acts of randomization and blinding. We discuss the use of blinding and randomization as the means against existing and potential risks of bias rather than a mandatory practice that is to be followed under all circumstances and at any cost. We argue that, in general, experiments should be blinded and randomized if (a) this is a confirmatory research that has a major impact on decision-making and that cannot be readily repeated (for ethical or resource-related reasons) and/or (b) no other measures can be applied to protect against existing and potential risks of bias.


Exploration of Sleep as a Specific Risk Factor for Poor Metabolic and Mental Health: A UK Biobank Study of 84,404 Participants.
Short and long sleep durations have adverse effects on physical and mental health. However, most studies are based on self-reported sleep duration and health status. Therefore, this longitudinal study aims to investigate objectively measured sleep duration and subsequent primary health care records in older adults to investigate the impact of sleep duration and fragmentation on physical and mental health. Data on objective sleep duration were measured using accelerometry. Primary care health records were then obtained from the UK Biobank (n=84,404). Participants (mean age, 62.4 years) were divided into five groups according to their sleep duration derived from the accelerometry data: <5 hours, 5-6 hours, 6-7 hours, 7-8 hours and >8 hours. ICD-10 codes were used for the analysis of primary care data. Wake after sleep onset, activity level during the least active 5 hours and episodes of movement during sleep were analysed as an indication for sleep fragmentation. Binary regression models were adjusted for age, gender and Townsend deprivation score. A "U-shaped" relationship was found between sleep duration and diseases including diabetes, hypertension and heart disease and depression. Short and long sleep durations and fragmented sleep were associated with increased odds of disease. Six to eight hours of sleep, as well as less fragmented sleep, predicted better long-term metabolic and mental health.


Hexafluoroisopropanol induces self-assembly of β-amyloid peptides into highly ordered nanostructures.
Deposition of insoluble fibrillar aggregates of β-amyloid (Aβ) peptides in the brain is a hallmark of Alzheimer's disease. Apart from forming fibrils, these peptides also exist as soluble aggregates. Fibrillar and a variety of nonfibrillar aggregates of Aβ have also been obtained in vitro. Hexafluoroisopropanol (HFIP) has been widely used to dissolve Aβ and other amyloidogenic peptides. In this study, we show that the dissolution of Aβ40, 42, and 43 in HFIP followed by drying results in highly ordered aggregates. Although α-helical conformation is observed, it is not stable for prolonged periods. Drying after prolonged incubation of Aβ40, 42, and 43 peptides in HFIP leads to structural transition from α-helical to β-conformation. The peptides form short fibrous aggregates that further assemble giving rise to highly ordered ring-like structures. Aβ16-22, a highly amyloidogenic peptide stretch from Aβ, also formed very similar rings when dissolved in HFIP and dried. HFIP could not induce α-helical conformation in Aβ16-22, and rings were obtained from freshly dissolved peptide. The rings formed by Aβ40, 42, 43, and Aβ16-22 are composed of the peptides in β-conformation and cause enhancement in thioflavin T fluorescence, suggesting that the molecular architecture of these structures is amyloid-like. Our results clearly indicate that dissolution of Aβ40, 42 and 43 and the amyloidogenic fragment Aβ16-22 in HFIP results in the formation of annular amyloid-like structures.


Thifluzamide induces the toxic effects on zebrafish (Danio rerio) via inhibition of succinate dehydrogenase (SDH).
Thifluzamide is widely used in treatment of rice diseases and has potential toxicity on aquatic organism. Although previous studies have focused on the toxic effect of thifluzamide in zebrafish, no consistent conclusions have been reached. To help to elucidate the toxic mechanism, qualities of liver and mitochondria were evaluated. The global changes in the transcriptome of zebrafish after exposure to thifluzamide were measured. Based on this, the expression and activities of chitinase and succinate dehydrogenase (SDH) were further assayed. And the targeted site of thifluzamide in zebrafish was confirmed by dock study and co-exposure study. Here we report that developmental inhibition was observed along with presence of liver and mitochondrial damage. The expression of SDHa-d and genes related to mitochondrial DNA (mtDNA) replicate and mitochondrial complexes were significantly altered. And, as the top differentially expressed genes, the expression of chia.1-6 did show apparent changes, but differences of chitinase activity between exposure groups and the controls did not reach significance. In line with that, dock study showed that the binding potentials of thifluzamide toward zebrafish chitinase and SDH exhibited in the following order: SDH> chitinase. And sdhb-sdhc-sdhd (Qp site) showed the highest binding activity toward thifluzamide. The joint exposure (thifluzamide + Q10) significantly improved the survival of zebrafish compared with single thifluzamide exposure. These results indicate that SDH, especially Qp-site, may be the target of thifluzamide in zebrafish and inhibition of SDH activity may be at least in partial responsible for the toxicity of thifluzamide in zebrafish. In addition, the antagonistic effect of Q10 on thifluzamide toxicity in zebrafish suggests that Q10 may be a useful adjunct to detoxification.


Comparative effects of particulate and soluble glucan on macrophages of C3H/HeN and C3H/HeJ mice.
In order to compare both the actions of soluble glucan (glucan-F) and particulate glucan (glucan-P) on macrophages and the responsiveness of macrophages from C3H/HeJ and C3H/HeN mice to these immunomodulators, interleukin-1 (IL-1) levels, phagocytosis and superoxide production were monitored after an in vitro exposure to glucan-F or glucan-P. A 2 or 20 h exposure to either glucan preparation decreased the ability of both C3H/HeJ and C3H/HeN macrophages to ingest zymosan. In contrast, glucan-P, but not glucan-F, decreased (after a 20 h exposure) the uptake of both IgG opsonized erythrocytes and latex beads. Furthermore, glucan-P, but not glucan-F was as effective as zymosan (after a 1 h exposure) in inducing superoxide release by macrophages isolated from both C3H/HeN and C3H/HeJ mice. While the effects of glucan-P on PMA-induced superoxide release and IL-1 levels were similar in macrophages from C3H/HeJ and C3H/HeN mice, glucan-F was ineffective at enhancing PMA-induced superoxide release or increasing IL-1 levels in C3H/HeJ mice. Thus (1) the effects of glucan-P on phagocytosis of opsonized erythrocytes and latex beads are not mimicked by glucan-F and (2) while macrophages from C3H/HeJ mice respond normally (as compared with C3H/HeN macrophages) to glucan-P, they are hyporesponders to glucan-F. These findings indicate that the activation of macrophages by glucan-P involves different (or additional) pathways from those activated by glucan-F.


Necrotizing myopathy: clinicoserologic associations.
Necrotizing myopathy (NM) is distinguished from idiopathic inflammatory myositis (IIM) by dominance of myofiber necrosis, lack of mononuclear inflammatory infiltrates, and presence of antibodies to signal recognition particle (SRP). The clinical features of 64 cases of NM were determined. Measurement of autoantibodies was undertaken on stored sera from 23 patients with NM. The incidence of malignancy was determined from the South Australian Cancer Registry. NM patients showed male predominance (61%), more frequent myalgias, and higher creatine kinase (CK) levels compared with IIM patients. Patients with NM had a high incidence of systemic lupus erythematosus (SLE) (21%), hypertension (11 of 17, 65%), and diabetes mellitus (3 of 13, 23%). No patient had antibodies to SRP. NM patients showed no altered risk for malignancy compared with the South Australian population (P = 0.86). NM is associated with SLE, hypertension, and diabetes mellitus. Comprehensive assessment of cardiovascular risk is indicated in NM, which raises the possibility of targeted interventions.


Growth, structure, morphology, and magnetic properties of Ni ferrite films.
The morphology, structure, and magnetic properties of nickel ferrite (NiFe2O4) films fabricated by radio frequency magnetron sputtering on Si(111) substrate have been investigated as functions of film thickness. Prepared films that have not undergone post-annealing show the better spinel crystal structure with increasing growth time. Meanwhile, the size of grain also increases, which induces the change of magnetic properties: saturation magnetization increased and coercivity increased at first and then decreased. Note that the sample of 10-nm thickness is the superparamagnetic property. Transmission electron microscopy displays that the film grew with a disorder structure at initial growth, then forms spinel crystal structure as its thickness increases, which is relative to lattice matching between substrate Si and NiFe2O4.


Synergistic effects of compost, cow bile and bacterial culture on bioremediation of hydrocarbon-contaminated drill mud waste.
Bioremediation has gained global prominence as an effective method for treating hydrocarbon-contaminated drill mud waste (HCDW). However, the problem of low nutrient content, bioavailability and microbial presence remain largely unresolved. In this study, the synergistic effects of compost, cow bile and bacterial culture on the degradation rate of HCDW was investigated. A homogenized HCDW sample (80 kg) obtained from 25 different drill mud tanks was divided into 20 portions (4 kg each) and each adjusted to 1.4% nitrogen content + 20 ml cow bile (i.e., basic treatment). Pure cultures of Brevibacterium casei (Bc) and Bacillus zhangzhouensi (Bz) and their mixture (BcBz) were subsequently added to 12 of the amended HCDW (basic) to undergo a 6-week incubation. A portion of the unamended HCDW (2 kg) was used as control. Initial pH, electrical conductivity and surface tension values of the HCDW were 8.83, 2.34 mS/cm and 36.5 mN/m, respectively. Corresponding values for total petroleum hydrocarbon (TPH), total nitrogen and total plate count bacteria were 165 g/kg, 0.04% and 4.4 × 102 cfu/ml. The treatments led to a substantial reduction in TPH (p < 0.05) while the control had no significant effect (p > 0.05). TPH reduction after the experimental period occurred in the order: basic + BcBz (99.7%) > basic + Bz (99.5%) > basic + Bc (99.2%) > basic (95.2%) > control (0.06%). Multiple regression analysis revealed significant effect of total plate count, pH, CN ratio and electrical conductivity (R2 = 0.87, p = 0.05) on the degradation of TPH in the HCDW. The study demonstrates strong interactive effects of compost, cow bile and bacteria culture on the remediation of HCDW, which can be applied to boost the efficiency of the bioremediation technique.


Prevalence and Clinical Determinants of Left Atrial Appendage Thrombus in Patients With Atrial Fibrillation Before Pulmonary Vein Isolation.
The CHADS2 score is considered a reliable predictor of stroke/thromboembolism risk in patients with atrial fibrillation (AF). However, thromboembolism can occasionally occur even in patients with AF with low CHADS2 score (CHADS2 score = 0 or 1). To investigate the incidence and predictors of left atrial appendage (LAA) thrombus (LAAT) formation in patients with AF, we studied consecutive 543 Japanese patients with AF who underwent transesophageal echocardiography before pulmonary vein isolation from 2008 to 2012. All patients were treated with anticoagulation therapy with warfarin, and their clinical and echocardiographic characteristics were evaluated. LAATs were observed in 35 (6.4%) of 543 patients, and the prevalence was clearly correlated with the patient's CHADS2 scores. Of 338 patients with low CHADS2 score, LAATs were observed in 7 patients (2.1%). By multivariate analysis, increased left atrial volume (≥50 ml), decreased ejection fraction (<56%), and increased brain natriuretic peptide level (>75 pg/ml) were significantly associated with increased prevalence of LAATs, even in patients with low CHADS2 score. Accordingly, we proposed a new scoring system to predict LAAT (left atrial volume ≥50 ml: score 2; ejection fraction <56%: score 1; brain natriuretic peptide >75 pg/ml: score 1). Patients with a score ≥2 have a greater risk of LAAT, whereas all patients with score ≤1 have no LAATs. Our scoring system is useful for evaluation of the risk of LAAT in patients with AF even with low CHADS2 score.


Patient experience, pain, and quality of life after lower limb angioplasty: a multisite prospective cohort study.
To explore the experience of patients undergoing endovascular lower limb angioplasty and evaluate the improvements in quality of life and disease-related symptoms after the procedure. Patients completed a questionnaire before treatment and three questionnaires after the procedure (immediately after the procedure, and again 4 weeks and 3 months later). Anxiety, patient understanding, procedure-related pain, and disease-related pain were assessed by a visual analog score (VAS). Complications, analgesic requirements, and satisfaction were recorded. Changes to quality of life were assessed by the validated SF36 questionnaire. A total of 88 patients (41%) responded. Overall, disease-related pain decreased over 3 months after the procedure. Smokers had more pain both before and after the procedure (P < 0.05). Explanation was considered better if provided by radiologist (P < 0.05). Sixty-nine percent of patients found the procedures less painful (mean VAS 2.5) than they had anticipated (VAS 5.5). Fifty percent of patients experienced adverse effects related to their puncture site, but this was highest among patients who had undergone the procedure before and smokers. The greatest quality-of-life improvements were in emotional and general health. Higher levels of disease-related pain were associated with worse general, emotional, and physical health (P < 0.05). Lower limb angioplasty provides symptomatic and quality-of-life improvements. Implementation of simple measures could improve patient satisfaction-for example, treatment should be explained by the radiologist in advance. Routine prescription of analgesics with particular attention to smokers and those undergoing repeat interventions is suggested.


Time to recovery after general anesthesia at hospitals with and without a phase I post-anesthesia care unit: a historical cohort study.
There is little knowledge about how hospitals can best handle disruptions that reduce post-anesthesia care unit (PACU) capacity. Few hospitals in Japan have any PACU beds and instead have the anesthesiologists recover their patients in the operating room. We compared postoperative recovery times between a hospital with (University of Iowa) and without (Shin-yurigaoka General Hospital) a PACU. This historical cohort study included 16 successive patients undergoing laparoscopic gynecologic surgery with endotracheal intubation for general anesthesia, at each of the hospitals, and with the hours from OR entrance until the last surgical dressing applied ≥ two hours. Postoperative recovery times, defined as the end of surgery until leaving for the surgical ward, were compared between the hospitals. The median [interquartile range] of recovery times was 112 [94-140] min at the University of Iowa and 22 [18-29] min at the Shin-yurigaoka General Hospital. Every studied patient at the University of Iowa had a longer recovery time than every such patient at Shin-yurigaoka General Hospital (Wilcoxon-Mann-Whitney, P < 0.001). The ratio of the mean recovery times was 4.90 (95% confidence interval [CI], 4.05 to 5.91; P < 0.001) and remained comparable after controlling for surgical duration (5.33; 95% CI, 3.66 to 7.76; P < 0.001). The anesthetics used in the Iowa hospital were a volatile agent, hydromorphone, ketorolac, and neostigmine compared with the Japanese hospital where bispectral index monitoring and target-controlled infusions of propofol, remifentanil, acetaminophen, and sugammadex were used. This knowledge can be generally applied in situations at hospitals with regular PACU use when there are such large disruptions to PACU capacity that it is known before a case begins that the anesthesiologist likely will need to recover the patient (i.e., when there will not be an available PACU bed and/or nurse). The Japanese anesthesiologists have no PACU labour costs but likely greater anesthesia drug/monitor costs.


Kinetic equivalence of transmembrane pH and electrical potential differences in ATP synthesis.
ATP synthase is the key player of Mitchell's chemiosmotic theory, converting the energy of transmembrane proton flow into the high energy bond between ADP and phosphate. The proton motive force that drives this reaction consists of two components, the pH difference (ΔpH) across the membrane and transmembrane electrical potential (Δψ). The two are considered thermodynamically equivalent, but kinetic equivalence in the actual ATP synthesis is not warranted, and previous experimental results vary. Here, we show that with the thermophilic Bacillus PS3 ATP synthase that lacks an inhibitory domain of the ε subunit, ΔpH imposed by acid-base transition and Δψ produced by valinomycin-mediated K(+) diffusion potential contribute equally to the rate of ATP synthesis within the experimental range examined (ΔpH -0.3 to 2.2, Δψ -30 to 140 mV, pH around the catalytic domain 8.0). Either ΔpH or Δψ alone can drive synthesis, even when the other slightly opposes. Δψ was estimated from the Nernst equation, which appeared valid down to 1 mm K(+) inside the proteoliposomes, due to careful removal of K(+) from the lipid.


Hospital rates of maternal and neonatal infection in a low-risk population.
In 2003, the Agency for Healthcare Quality and Research (AHRQ) published its Quality Indicators for healthcare, and set out methodological criteria for the evaluation of potential candidates. Because perinatal infections may result from poor obstetrical practices, we intended to describe the variability of maternal and congenital neonatal infections across different types of hospital ownership (e.g., not for profit, government), and to assess whether rates of these infections meet criteria as quality indicators. Population-based cohort study. All laboring women without maternal, fetal, or placental complications who delivered in California in 1997, and their neonates, as reported through hospital discharge data. A Bayesian hierarchical logistic regression model was used to quantify the effects of both "patient-level" risk factors such as parity and prior cesarean history, and "hospital-level" risk factors such as ownership and teaching status. The 308,841 mother-newborn pairs in this low-risk study population delivered at 281 hospitals; 0.39% had uterine infections and 1.3% had neonatal infections. Hospital ownership and teaching status were strongly associated with perinatal infection. Secondly, methods used to estimate and analyze hospital-specific infection rates identified hospitals with exceptionally high rates. Twenty-eight hospitals had neonatal infection rates that ranged from 3% to 28%. The methods presented here were consistent with AHRQ methods and criteria for potential Quality Indicators. They also identified hospitals with exceptionally high rates of infectious morbidity. The relationship between hospital ownership and obstetrical practice patterns, and the feasibility of practice improvement, remain to be studied.


Immunomodulation by Gut Microbiome on Gastrointestinal Cancers: Focusing on Colorectal Cancer.
Gastrointestinal cancer (GI) is a global health disease with a huge burden on a patient's physical and psychological aspects of life and on health care providers. It is associated with multiple disease related challenges which can alter the patient's quality of life and well-being. GI cancer development is influenced by multiple factors such as diet, infection, environment, and genetics. Although activating immune pathways and components during cancer is critical for the host's survival, cancerous cells can target those pathways to escape and survive. As the gut microbiome influences the development and function of the immune system, research is conducted to investigate the gut microbiome-immune interactions, the underlying mechanisms, and how they reduce the risk of GI cancer. This review addresses and summarizes the current knowledge on the major immune cells and gut microbiome interactions. Additionally, it highlights the underlying mechanisms of immune dysregulation caused by gut microbiota on four major cancerous pathways, inflammation, cellular proliferation, apoptosis, and metastasis. Overall, gut-immune interactions might be a key to understanding GI cancer development, but further research is needed for more detailed clarification.