The validity and reliability of the second korean working conditions survey.
The aim of this study was to evaluate the quality of the Second Korean Working Conditions Survey (KWCS), focusing on its validity and reliability. The external validity was evaluated by the assessment of sampling procedures and the response rate, in order to investigate the representativeness of the sample. The content validity was evaluated by the assessment of the development of the questionnaire, and the consistency of questions for the selected construct. The test-retest method was used to evaluate the reliability by means of a phone call survey of 30% of the respondents, who were randomly selected. The respondents' satisfaction regarding the survey procedures and interview time were analyzed to evaluate the quality of survey data. The external validity was assured by an acceptable sampling procedure, rigid multi-stage stratified cluster random sampling. The content validity was also guaranteed by a reasonable procedure for the development of the questionnaire with a pretest. The internal consistency of the questions for work autonomy was maintained, with 0.738 of Cronbach's alpha. The response rate of 36% was lower than that of the European Working Conditions Survey (EWCS), with a contact rate of 66%, compared to 76% for the EWCS. The matching rates of the five retested questions were more than 98% reliable. The quality of the second KWCS was assured by the high external and content validity and reliability. The rigid sampling procedure and development of the questionnaire contributed to quality assurance. The high level of reliability may be guaranteed by the sophisticated field survey procedures and the development of a technical manual for interviewers. The technical strategies for a high response rate should be developed for future surveys.


Syncatalytic modification of chicken liver xanthine dehydrogenase by hydrogen peroxide. The nature of the reaction.
Xanthine dehydrogenase engaged in catalyzing the oxidation of substrate by oxygen is repidly inactivated by the hydrogen peroxide generated during the reaction. Experimental evidence shows that peroxide reacts more readily with the reduced than with the oxidized form of the enzyme. Inactivation results from modification of the cyanolysable sulfur present at the molybdenum center.


Chronotropic response, safety, and accuracy of dobutamine stress echocardiography in patients with atrial fibrillation and known or suspected coronary artery disease.
Ninety-two consecutive patients with atrial fibrillation (AF) who underwent dobutamine stress echocardiography were compared with a control group of patients in sinus rhythm matched for age, sex, and resting heart rate. Patients with AF had an increased chronotropic response to dobutamine, but there were no adverse effects and no evidence that the lower doses of dobutamine typically given to patients with AF were insufficient to induce ischemia.


Real-world evidence of dupilumab efficacy and risk of adverse events: A systematic review and meta-analysis.
Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials. To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis. PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy. Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%. Limited data in terms of size and follow-up time were available. Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events.


BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing.
The tumour suppressor complex BRCA1-BARD1 functions in the repair of DNA double-stranded breaks by homologous recombination. During this process, BRCA1-BARD1 facilitates the nucleolytic resection of DNA ends to generate a single-stranded template for the recruitment of another tumour suppressor complex, BRCA2-PALB2, and the recombinase RAD51. Here, by examining purified wild-type and mutant BRCA1-BARD1, we show that both BRCA1 and BARD1 bind DNA and interact with RAD51, and that BRCA1-BARD1 enhances the recombinase activity of RAD51. Mechanistically, BRCA1-BARD1 promotes the assembly of the synaptic complex, an essential intermediate in RAD51-mediated DNA joint formation. We provide evidence that BRCA1 and BARD1 are indispensable for RAD51 stimulation. Notably, BRCA1-BARD1 mutants with weakened RAD51 interactions show compromised DNA joint formation and impaired mediation of homologous recombination and DNA repair in cells. Our results identify a late role of BRCA1-BARD1 in homologous recombination, an attribute of the tumour suppressor complex that could be targeted in cancer therapy.


Deciphering the impact of genetic variation on human polyadenylation using APARENT2.
3'-end processing by cleavage and polyadenylation is an important and finely tuned regulatory process during mRNA maturation. Numerous genetic variants are known to cause or contribute to human disorders by disrupting the cis-regulatory code of polyadenylation signals. Yet, due to the complexity of this code, variant interpretation remains challenging. We introduce a residual neural network model, APARENT2, that can infer 3'-cleavage and polyadenylation from DNA sequence more accurately than any previous model. This model generalizes to the case of alternative polyadenylation (APA) for a variable number of polyadenylation signals. We demonstrate APARENT2's performance on several variant datasets, including functional reporter data and human 3' aQTLs from GTEx. We apply neural network interpretation methods to gain insights into disrupted or protective higher-order features of polyadenylation. We fine-tune APARENT2 on human tissue-resolved transcriptomic data to elucidate tissue-specific variant effects. By combining APARENT2 with models of mRNA stability, we extend aQTL effect size predictions to the entire 3' untranslated region. Finally, we perform in silico saturation mutagenesis of all human polyadenylation signals and compare the predicted effects of [Formula: see text] million variants against gnomAD. While loss-of-function variants were generally selected against, we also find specific clinical conditions linked to gain-of-function mutations. For example, we detect an association between gain-of-function mutations in the 3'-end and autism spectrum disorder. To experimentally validate APARENT2's predictions, we assayed clinically relevant variants in multiple cell lines, including microglia-derived cells. A sequence-to-function model based on deep residual learning enables accurate functional interpretation of genetic variants in polyadenylation signals and, when coupled with large human variation databases, elucidates the link between functional 3'-end mutations and human health.


Successful endoscopic needle knife therapy combined with topical doxycycline injection of chronic sinus at ileal pouch-anal anastomosis.
Chronic presacral sinus at the anastomosis after restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) has been difficult to manage and results in a high rate of pouch failure. The aim was to present a novel technique with a combining endoscopic doxycycline injection and needle knife therapy for a sinus at the ileoanal anastomosis. We applied repeat Doppler ultrasound-guided endoscopic needle knife therapy to open the orifice of the anastomotic sinus followed by topical injection of doxycycline. After six sessions of the endoscopic therapy, the refractory sinus was completely healed. The Doppler ultrasound guided endoscopy therapy may provide an alternative treatment option for the patients with anastomotic sinus.


North-east Essex perinatal mortality survey--1971 to 1975.
A method of carrying out a Perinatal Mortality Survey in a non-academic district obstetric service is described. The results show a trend of improving perinatal mortality and the various factors that may be influencing this trend are discussed.


Five-week red cell storage with preservation of 2,3 DPG.
The 2,3 diphosphoglycerate (2,3 DPG) content of red cells stored in current anticoagulant-preservative products decreases rapidly after the first few days of storage, and by 3 weeks the red cells are essentially depleted of 2,3 DPG. Because ascorbic acid and ascorbate-2-phosphate (A-2-P) are effective in maintaining erythrocyte 2,3 DPG during liquid preservation, ascorbate was stabilized through autoclaving and subsequent storage by adding it as the trisodium salt of A-2-P to a phosphate-adenine-saline solution at a pH of 8.5 to 9.0. Red cell concentrates prepared from blood drawn into citrate-phosphate-double-dextrose were supplemented with the A-2-P additive solution (AS-4) and studied in vitro and in vivo. Mean 2,3 DPG values for 22 units were 147.6, 113.5, and 82.3 percent of initial value after storage for 3, 4, and 5 weeks, respectively. Maintenance of 2,3 DPG was at the expense of adenosine triphosphate (ATP), which fell to as low as 22.2 percent of initial value after 5 weeks. Despite the low ATP values, the 24 hour 51Cr-labeled red cell recoveries averaged 80.8 and 74.1 percent after 4 and 5 weeks of storage, respectively. The AS-4 system provides a red cell product with acceptable viability and improved oxygen off-loading function.


The effect of aging on hypothalamic function in oophorectomized women.
To detect age-related changes intrinsic to hypothalamic-pituitary function, we studied plasma gonadotropin levels in 12 oophorectomized women ages 27 to 64 years who were not undergoing hormone replacement therapy. Blood drawn from an indwelling catheter every 10 minutes for 5 hours was assayed for follicle-stimulating hormone, luteinizing hormone, estradiol, and prolactin concentrations. All estradiol levels were less than 20 pg/ml and prolactin values were normal. Mean gonadotropin concentrations, pulse frequency, and pulse amplitude were no different in women aged 27 to 49 years as compared with subjects 52 to 64 years old. When grouped according to gynecologic age (years since puberty) or years after oophorectomy, luteinizing hormone and follicle-stimulating hormone mean concentrations, mean pulse frequency, and mean pulse amplitude were comparable to those grouped according to chronologic age. On the basis of our findings, lack of response from postmenopausal ovaries to endogenous gonadotropin stimulation is a result of primary age-related change in the ovary, not in the hypothalamus.


Cancer follows chromosome missegregation when all endogenous repair mechanisms fail.
Almost all solid tumors consist of aneuploid cells with highly abnormal chromosome numbers. Such cancer cells could very well originate from chromosome missegregation which is a disturbingly common phenomenon, happening in 0.01 to 4 percent of cell divisions. Missegregated cells are aneuploid, typically lacking a chromosome or having one in surplus. Missegregated cells have mutation in the gene dose of the perhaps a thousand genes on a chromosome in one step. After missegregation cell division cannot be done right, as at least one daughter cell has a faulty chromosome number. At division in cells with surplus chromosomes the number will tend to increase due to mismatch in the division machinery. The organism has a number of repair mechanisms in place to prevent potential damage of accumulating aneuploidy. The first is the roll-back of the cell division itself, leading to tetraploidy or sometimes two nuclei in one cell; another is the prevention of further divisions. A very important one is induction of apoptosis, the cellular suicide. A special case is the elimination of the nucleus itself in the formation of red blood cells. Many aneuploid cells are probably eliminated by the immune system. A hypothetical mechanism would be the prevention of metastasis. Missegregation increases with age when the chromosomes lose their protective telomere ends at the Hayflick limit after about 50 divisions, and the unraveled chromosomes fuse and break. For cancer to develop all of these repair mechanisms must fail. The hypothesis offers a straightforward rationale for the multiple hit hypothesis of cancer development.


An adaptive two-scale biomedical image fusion method with statistical comparisons.
Two-scale image representation of base and detail in the spatial-domain is a well-known decomposition scheme for its lower computational complexity than that performed in the transform-domain in the field of image fusion. Unfortunately, for a pseudo-colour input image, the base and detail images in the spatial-domain obtained via image decomposition scheme always display in greyscale. In this paper, a two-scale image fusion method with adaptive threshold obtained by Otsu's method is proposed for pseudo-colour image in the colour space domain. For greyscale image, detail and base image are obtained using structural information extracted from the difference image between a global and a local patch size. Consequently, local edge-preserving filter for preserving luminance information and local energy with the discussed window size are adopted to combine base and detail image. Experimental results show that structural and luminance information has been better preserved in terms of subjective and objective evaluations for medical image and protein image fusion. Specially, a two-step non-parametric statistical test (Friedman test and Nemenyi post-hoc test) with p-values is adopted to analysis the statistical significant of the relative difference between the proposed and compared methods in terms of values of objective metrics including 30 co-registered pairs of imaging data.


Antenatal care in the European Union: a survey on guidelines in all 25 member states of the Community.
A comprehensive review of the content of national guidelines on antenatal care for normal pregnancies in the member states of the European Union was required to find out whether a common minimum guideline would be of benefit to complement national public health policies, and what this guideline might contain. A structured questionnaire was sent to the Ministries of Health and the societies of obstetricians and midwives. Descriptive analyses identified which and how many member states recommend a test, to how many people this applied, and whether there was a correlation between the gross national product and the number of tests recommended. Answers were obtained from all 25 member states. Twenty of them have a national guideline. Forty-seven tests were reported and 23 of these are recommended for routine care by more than 50% of the countries and apply to more than 50% of inhabitants. Those tests are also supported by scientific evidence. Countries with a GNP below EU-average recommend more tests than the others. For the first time it has been demonstrated what the member states of the EU recommend for antenatal care. Based on this, a common minimum guideline for antenatal care in the EU is recommended.


Insights into tissue-specific anthocyanin accumulation in Japanese plum (Prunus salicina L.) fruits: A comparative study of three cultivars.
In the present study, three matured Japanese plum cultivars with different colored peel and flesh were selected to mine the key transcription factors regulating anthocyanin formation in tissues. Results showed that PsMYB10 was correlated with structural genes C4H, F3H, and ANS. PsMYB6 could positively regulate C4H (r = 0.732) and accumulated anthocyanins in Sanhua plum's flesh. Sanhua plum has the highest phenolic and anthocyanin contents (10.24 ± 0.37 gallic acid equivalent mg g-1 dry weight (DW) and 68.95 ± 1.03 μg g-1 DW), resulting itself superior biological activity as 367.1 ± 42.9 Trolox equivalent mg g-1 DW in oxygen radical absorbance capacity value and 72.79 ± 4.34 quercetin equivalent mg g-1 DW in cellular antioxidant activity value. The present work provides new insights into the regulatory mechanism of tissue-specific anthocyanin biosynthesis, confirming the pivotal role of anthocyanins in the biological activity of plums, providing essential support for the development of horticultural products enriched with anthocyanins.


Novel benzothiazole‒urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA.
Novel benzothiazole‒urea hybrids were designed, synthesized and evaluated their anti-bacterial activity. They only exhibited anti-bacterial activity against Gram-positive bacteria, including clinical methicillin-resistant S. aureus (MRSA), compounds 5f, 5i, 8e, 8k and 8l exhibited potent activity (MIC = 0.39 and 0.39/0.78 μM against SA and MRSA, respectively). Crystal violet assay showed that compounds 5f, 8e and 8l not only inhibited the formation of biofilms but also eradicated preformed biofilms. Compound 8l had membrane disruption, little propensity to induce resistance, benign safety and in vivo anti-MRSA efficacy in a mouse model of abdominal infection. Therefore, our data demonstrated the potential to advance benzothiazole‒urea hybrids as a new class of antibiotics.


The impact of age and obesity on outcomes among patients hospitalized with COVID-19 in Denmark: A nationwide cohort study.
Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID-19). Age may impact the association between body weight and severity of COVID-19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19 in the initial wave of the pandemic. Based on data from the nationwide, clinical database: COVID-DK, risks of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality were compared among patients with and without obesity. Interaction with age was examined and we used Inverse Probability of Treatment Weighting regression for confounder adjustment. Among 524 patients, 142 (27%) were admitted to the ICU, 112 (21%) required IMV, and 109 (21%) died. Compared to COVID-19 patients without obesity, patients with obesity displayed a non-significant increased risk of ICU admission (Relative Risk [RR] 1.19, 95% Confidence Interval [CI] 0.88; 1.60), IMV (RR 1.23, CI 0.86; 1.75) and mortality (RR 1.21, CI 0.84; 1.75). COVID-19 patients with obesity, <60 years had highly increased risk of ICU admission (RR 1.92, CI 1.14; 3.24) and IMV (RR 1.95, CI 1.09; 3.49). In hospitalized COVID-19 patients, obesity conferred an approximately 20% increased risk for ICU admission, IMV, and death, although these relationships did not reach statistical significance. COVID-19 patients with obesity and <60 years had an almost doubled risk of ICU admission and IMV.


A combined method for measurement of cerebral blood flow and immunohistochemistry for investigation of cerebral ischemia.
A combined method was established where measurement of cerebral blood flow (CBF) by quantitative autoradiography and detection of morphologic ischemic damage by immunohistochemistry could be accomplished simultaneously with the same brain. The method was applied to the gerbil brain 15 min after occlusion of the right common carotid artery which demonstrated that the reduction of focal CBF can be heterogenous at an early ischemic period, that the residual focal CBF was below 8.0 ml/100 g/min in some areas with ischemic lesions but other areas were tolerant of severe hypoperfusion. The results also suggested that the pathophysiological mechanism of selective tissue vulnerability might be different from one site to another in cerebral ischemia. This method will be useful for autoradiographic measurement of other physiological and biochemical parameters in combination with the immunohistochemical method for demonstration of not only the structural damage, but also the alteration of cell-specific functions.


Prevalence of rectus diastasis is higher in patients with inguinal hernia.
To determine the prevalence of rectus diastasis (RD) in patients with inguinal hernia. Multicenter, cross-sectional study. Patients with inguinal hernia were included in the study group (IH) and those with benign proctologic complaints created the control group (CG). Age, gender, BMI, family history for inguinal hernias, comorbid diseases, alcohol use, smoking, constipation, malignancy, chemotherapy, number of births, multiple pregnancies and prostate hypertrophy history of all patients in both groups were recorded. All patients were evaluated for RD and umbilical hernias by physical examination. A total of 528 consecutive patients were included in the study (292 IH / 236 CG). Overall prevalence of RD was 35.6% and it was significantly higher in IH than in CG (46.9% vs 21.6%, p < 0.001). Also, umbilical hernia was more frequently detected in the patients with inguinal hernia. Other risk factors for RD were age, BMI, DM, BPH and smoking. The mean inter-rectus distance for 528 patients was 18.1 mm; it was 20.71 ± 10.68 mm in IH and 14.88 ± 8.82 in CG (p < 0.001). It was determined that the increase in age and BMI caused an increase in the inter-rectus distance, and that the presence of DM, inguinal hernia and umbilical hernia increased the inter-rectus distance quantitatively. The prevalence of RD seems to be higher in patients with inguinal hernia comparing to that in general population. Increased age, high BMI and DM were found to be independent risk factors for RD development.


A Collective Variable for the Efficient Exploration of Protein Beta-Sheet Structures: Application to SH3 and GB1.
We introduce a new class of collective variables which allow forming efficiently beta-sheet structures in all-atom explicit-solvent simulations of proteins. By this approach we are able to systematically fold a 16-residue beta hairpin using metadynamics on a single replica. Application to the 56-residue SH3 and GB1 proteins show that, starting from extended states, in ∼100 ns tens of structures containing more than 30% beta-sheet are obtained, including parts of the native fold. Using these variables may allow folding moderate size proteins with an accurate explicit solvent description. Moreover, it may allow investigating the presence of misfolded states that are relevant for diseases (e.g., prion and Alzheimer) and studying beta-aggregation (amyloid diseases).


A database with frailty, functional and inertial gait metrics for the research of fall causes in older adults.
The GSTRIDE database contains information of the health status assessment of 163 elderly adults. We provide socio-demographic data, functional and frailty variables, and the outcomes from tests commonly performed for the evaluation of elder people. The database contains gait parameters estimated from the measurements of an Inertial Measurement Unit (IMU) placed on the foot of volunteers. These parameters include the total walking distance, the number of strides and multiple spatio-temporal gait parameters, such as stride length, stride time, speed, foot angles and clearance, among others. The main processed database is stored, apart from MS Excel, in CSV format to ensure their usability. The database is complemented with the raw IMU recordings in TXT format, in order to let researchers test other algorithms of gait analysis. We include the Python programming codes as a base to reproduce or modify them. The database stores data to study the frailty-related parameters that distinguish faller and non-faller populations, and analyze the gait-related parameters in the frail subjects, which are essential topics for the elderly.


Correction to: European guidance for the diagnosis and management of osteoporosis in postmenopausal women.
The original version of this article, published on 15 October 2018, unfortunately, contained a mistake.


Flagellar regeneration of the trypanosome Crithidia fasciculata involves post-translational modification of cytoplasmic alpha tubulin.
Deflagellation of Crithidia fasciculata stimulated formation of new flagella and maximized production of alpha 3 tubulin. Continuous labeling during reflagellation revealed that alpha 1, 2, and 3 tubulins were formed, whereas the polyadenylated RNA translation products lacked alpha 3 isoform. Pulse-chase labeling experiments demonstrated that alpha 3 was a post-translational modification of cytoplasmic alpha tubulin.


NRG1 gene rearrangements in clinical breast cancer: identification of an adjacent novel amplicon associated with poor prognosis.
Rearrangements of the neuregulin (NRG1) gene have been implicated in breast carcinoma oncogenesis. To determine the frequency and clinical significance of NRG1 aberrations in clinical breast tumors, a breast cancer tissue microarray was screened for NRG1 aberrations by fluorescent in situ hybridization (FISH) using a two-color split-apart probe combination flanking the NRG1 gene. Rearrangements of NRG1 were identified in 17/382 cases by FISH, and bacterial artificial chromosome array comparative genomic hybridization was applied to five of these cases to further map the chromosome 8p abnormalities. In all five cases, there was a novel amplicon centromeric to NRG1 with a minimum common region of amplification encompassing two genes, SPFH2 and FLJ14299. Subsequent FISH analysis for the novel amplicon revealed that it was present in 63/262 cases. Abnormalities of NRG1 did not correlate with patient outcome, but the novel amplicon was associated with poor prognosis in univariate analysis, and in multivariate analysis was of prognostic significance independent of nodal status, tumor grade, estrogen receptor status, and human epidermal growth factor receptor (HER)2 overexpression. Of the two genes in the novel amplicon, expression of SPFH2 correlated most significantly with amplification. This amplicon may emerge as a result of breakpoints and chromosomal rearrangements within the NRG1 locus.


Lack of evidence for transmission of human immunodeficiency virus through vaginal intercourse.
Research in determining risks for human immunodeficiency virus (HIV) transmission is confounded by many issues. They include lack of clarity or specificity in terminology used, respondents misunderstanding of questions, and lying. The base rate of lying (or social desirability responding) by itself is sufficient to account for the small percentage of Americans and Europeans claiming "heterosexual" transmission from partners not known to be intravenous drug users. This study integrates the physiological and epidemiological data on risk factors for HIV transmission with the psychological literature on the frequency of anal intercourse and of lying (in this case to researchers and clinicians about risk factors). When these factors are considered, intravenous and anal activities remain the only clear vectors for HIV transmission. Research suggesting that spermicidals are more effective at inactivating HIV than condoms are at physically containing HIV is also noted.


A case of CD10-negative angioimmunoblastic T cell lymphoma with leukemic change and increased plasma cells mimicking plasma cell leukemia: A case report.
Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma, known to express CD3 and CD4, and, frequently, also CD10 and c-Maf-1. Hypergammaglobulinemia is not particularly rare in patients with AITL. However, AITL in conjunction with plasmacytosis in the peripheral blood is rare. The current report presents a case of CD10-negative AITL demonstrating leukemic change and plasmacytosis in the peripheral blood mimicking plasma cell leukemia. A 78-year-old male was admitted to hospital due to systemic lymph node enlargement, high serum IgG and IgA, and increased counts of plasmacytoid cells and lymphoid cells with atypical nuclei in the peripheral blood. Initially, plasma cell leukemia was suspected, due to the extreme increase in the number of plasma cells in the peripheral blood. However, the plasma cells did not show clonal expansion on examination by flow cytometry. Based on histological analyses, following a biopsy of an enlarged lymph node, the patient was diagnosed with AITL. This case suggests that when hypergammaglobulinemia and increases in B-lineage cells are observed, AITL should be considered in addition to disorders of B-lineage cells.


Oral verrucous carcinoma. Treatment with radiotherapy.
Fifty-two cases of oral verrucous carcinoma treated with radiotherapy at the Regional Cancer Centre, Trivandrum, Kerala, India in 1982 were evaluated to determine the distribution within the oral cavity, clinical extent, and effectiveness of radiotherapy in controlling the disease. The most common site was the buccal mucosa. Fifty percent of the patients had clinically negative regional lymph nodes and 33% were in earlier stages (T1, T2, N0, and M0). The overall 3-year no evidence of disease (NED) survival rate was 44%. The 3-year NED survival rate with radium implant was 86%. We cannot comment on anaplastic transformation after radiotherapy because our treatment failures have not been subjected for biopsy concerning this matter. Because the results are comparable with those of well-differentiated squamous cell carcinoma, we think that the treatment policies advocated for oral squamous cell carcinoma are also applicable to oral verrucous carcinoma.


Administration of thyrotropin-releasing hormone into the central nucleus of the amygdala induces gastric lesions in rats.
Studies utilizing microinjections of thyrotropin-releasing hormone (TRH) were performed to determine potentially sensitive limbic brain sites to the ulcerogenic effect of TRH. Administration of TRH into the central nucleus of the amygdala (CEA) produced a high (80%) incidence of gastric lesions and also significantly stimulated acid secretion. Microinjections of TRH into other brain sites including superior colliculus, medial septum, substantia nigra and the hippocampus (CA1 area) were ineffective. Intra-CEA TRH-induced gastric lesions and acid secretion were prevented by vagotomy. These results indicate that the amygdala is of importance for mediating the ulcerogenic effect of brain TRH through peripheral vagal pathways.


Microtensile bond strength testing of luting cements to prefabricated CAD/CAM ceramic and composite blocks.
To investigate the Microtensile bond strength (microTBS) and failure mode of resin cements bonded to composite and ceramic CAD/CAM blocks following various surface treatments. Paradigm composite blocks and Cerec Vitablocs received three surface treatments following the control treatment of surface grinding with 600 SiC grit. (1) Application of adhesive resin (Adh), (2) etching with hydrofluoric acid and silanization (HF+S) or (3) combination of the previous two treatments (HF+S+Adh). Three resin cements (Tetric Flow, Nexus 2, RelyX ARC) were applied to these surfaces and built-up in layers. After 24 h water storage at 37 degrees C, the non-trimming version of microTBS test was used to produce 1 mm(2) microbars. The Microbars were subjected to a tensile load using a modified testing device. The broken specimens were examined with a stereomicroscope and SEM to determine the failure mode. All control and adhesive treated groups of the ceramic substrate showed premature debonding during cutting. The overall mean microTBS for the three resin cements bonded to ceramic following HF+S and HF+S+Adh surface treatment, was 27 and 29.2 MPa and for the resin cements bonded to composite substrate was 42.3 and 54.2 MPa, respectively. The mode of failure was 98% adhesive with composite as a substrate and 68% mixed failures with ceramic as a substrate. CAD/CAM restorations fabricated from processed composite blocks may have advantage over the ceramic blocks with regard to the higher bond strength with resin cements.


Childhood growth hormone treatment in women with Turner syndrome - benefits and adverse effects.
Turner syndrome (TS) is characterized by the partial or complete loss of one sex chromosome and results in growth failure, gonadal insufficiency and cardiac anomalies. Treatment with growth hormone (GH) during childhood has indisputable benefits when taking into account the low stature of TS women. Medical records and biochemical findings of 33 TS women treated with GH in childhood (GH+) were compared to those of 124 TS women who did not receive GH (GH-). It seems that the GH-treated group might have had a more severe initial phenotype than the untreated group, as evidenced by higher FSH, more feeding issues in infancy, more lymphedema cases and urinary system malformations. GH+ women were significantly taller and had a better lipid profile and lower prevalence of arterial hypertension than GH- . However, they also had lower thrombocyte counts, a greater prevalence of retrognathism and nail anomalies, especially when the GH treatment was delayed. Long-term GH use was not as effective for growth as GH treatment during the initial period and seemed to have resulted in elevated creatinine levels. GH treatment in childhood has benefits in adulthood; however, adverse effects may occur, especially in individuals with treatment that is delayed or is too long.


Co-expression of YieF and PhoN in Deinococcus radiodurans R1 improves uranium bioprecipitation by reducing chromium interference.
Overexpression of the enzyme phosphatase (PhoN/PhoK) in the radiation-resistant bacterium Deinococcus radiodurans could be an efficient strategy for uranium remediation. However, the presence of other metals in nuclear wastes often interferes with uranium bioprecipitation. In our study, the uranium-precipitating ability of the PhoN-expressing D. radiodurans strain (Deino-phoN) significantly decreased by 45.4% in 13 h in the presence of chromium (VI); however, it was partially recovered after supplementation with chromium (III). Therefore, the reduction of chromium (VI) to chromium (III) was obtained by the co-expression of the YieF protein and PhoN in D. radiodurans (Deino-phoN-yieF). As a result, an increase in the chromium (VI) reduction (25.1%) rate was observed in 24 h. Furthermore, uranium precipitation also increased by 28.0%. For the decontamination of groundwater, we immobilized Deino-phoN-yieF cells using Polyvinyl alcohol (PVA)-sodium alginate (SA) beads, followed by incubation in a bioreactor. Approximately 99% of chromium (VI) and uranium (VI) was removed after 4 continuous cycles operated for a period of over 20 days at room temperature (25 °C). Therefore, Deino-phoN-yieF could be used as a potential biological agent for mixed radioactive nuclear waste remediation.


Enalapril in the prevention of restenosis following intracoronary intervention in a swine model.
Restenosis following percutaneous transluminal coronary angioplasty continues to be a major limitation of the procedure. To test whether an angiotensin-converting enzyme inhibitor may reduce restenosis, this study utilized an atherosclerotic, stented, Hanford miniature swine model of restenosis. Each animal first was started on an atherogenic diet and had balloon abrasion of the left anterior descending and right coronary arteries. Four months later, balloon-mounted coil stents were placed into the abraded coronary arteries of each animal. Twenty-four animals then were randomly assigned to one of two groups: enalapril, and control. The enalapril group received 50 mg orally twice daily starting 1 week before intracoronary stenting. Follow-up 2 months later revealed angiographic stenosis in the control group of 30% +/- 13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/- 9%/20% +/- 11% in the enalapril group (P = not significant). The change in minimal lumen diameter from immediately after stenting to follow-up was not significantly different between control and enalapril groups. Area stenosis and maximal intimal thickness obtained by morphometric analysis were also compared, and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/- 16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns. There was no statistical difference. Enalapril fails to reduce restenosis in this animal model.


Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo.
Bax is a proapoptotic protein that is required for programmed cell death (PCD) of many neuronal populations. Here we show that, during an early period of retinal PCD and in naturally occurring sensory and motor neuron (MN) death in the spinal cord, Bax delivery results in enhanced death of these neural populations. In contrast, Bax overexpression fails to enhance an early phase of MN death that occurs in the cervical spinal cord, although overexpressed Bax appears to be activated in dying MNs. Bax overexpression does not also affect the survival of immature neurons prior to the PCD period. Taken together, these data provide the first in vivo evidence suggesting that Bax appears to act selectively as an executioner only in neurons undergoing PCD. Furthermore, although Bax appears to mediate the execution pathway for PCD, the effect of Bax overexpression on susceptibility to death differs between different neuronal populations.


Effects of 4-nonylphenol and 17alpha-ethynylestradiol exposure in the Sydney rock oyster, Saccostrea glomerata: Vitellogenin induction and gonadal development.
Adult Saccostrea glomerata were exposed to environmentally relevant concentrations of 4-nonylphenol (1microg/L and 100microg/L) and 17alpha-ethynylestradiol (5ng/L and 50ng/L) in seawater over 8 weeks. Exposures were performed to assess effects on vitellogenin induction and gonadal development during reproductive conditioning. Chronic direct estrogenicity within gonadal tissue was assessed via an estrogen receptor-mediated, chemical-activated luciferase reporter gene-expression assay (ER-CALUX). Estradiol equivalents (EEQ) were greatest in the 100microg/L 4-nonylphenol exposure (28.7+/-2.3ng/g tissue EEQ) while 17alpha-ethynylestradiol at concentrations of 50ng/L were 2.2+/-1.5ng/g tissue EEQ. Results suggest 4-nonylphenol may be accumulated in tissue and is partly resistant to biotransformation; maintaining its potential for chronic estrogenic action, while 17alpha-ethynylestradiol, although exhibiting greater estrogenic potency on biological endpoints possibly exerts its estrogenic action before being rapidly metabolised and/or excreted. A novel methodology was developed to assess vitellogenin using high-performance liquid chromatography (HPLC). Exposure to both 17alpha-ethynylestradiol (50ng/L) and 4-nonylphenol (100microg/L) produced increases in vitellogenin for females, whereas males exhibited increases in vitellogenin when exposed to 50ng/L 17alpha-ethynylestradiol only. Females exhibited greater vitellogenin responses than males at 50ng/L 17alpha-ethynylestradiol only. Histological examination of gonads revealed a number of individuals exhibiting intersex (ovotestis) in 50ng/L 17alpha-ethynylestradiol exposures. Male individuals in 1microg/L and 100microg/L 4-nonylphenol exposures and 5ng/L 17alpha-ethynylestradiol were at earlier stages of spermatogenic development than corresponding controls.


Synthesis and human/bacterial carbonic anhydrase inhibition with a series of sulfonamides incorporating phthalimido moieties.
A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 22.214.171.124) isoforms, the human (h) hCA I and II, and the α- and β-class CAs from the pathogenic bacterium Vibrio cholerae, VchCAα and VhcCAβ. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4.9-96.0nM. hCA II also showed high affinity for these compounds (KIs of 2.1-22.3nM), whereas the two bacterial enzymes were less effectively inhibited, with KIs of 281-3192nM for VchCAα, and 5.40-9.26µM for VhcCAβ. As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform.


Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.
The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.


Serial MR imaging with MS-325 for evaluating female sexual arousal response: determination of intrasubject reproducibility.
To determine if a similar sexual arousal response in normal, healthy women could be obtained and monitored by serial magnetic resonance (MR) imaging at two separate sessions. Serial imaging of the external genitalia was performed on nine healthy, sexually functional women at two separate MR sessions after administration of the contrast agent, MS-325. Images were obtained every three minutes during a 45-minute study period during each MR session. The second MR session began approximately 45 minutes after the end of the first MR session. While undergoing imaging, subjects viewed videotapes that contained neutral and sexually-explicit material through an audiovisual system. Analysis performed at each time point consisted of visual evaluation of the images, clitoral and femoral vein signal intensity measurements, relative regional blood volume calculations, and clitoral volume measurements. Statistical analysis of the results consisted of calculating correlation coefficients of the two MR sessions by using the least square fit method. All nine subjects reported sexual arousal on subjective questionnaires at each MR session. Post-contrast MS-325 MR images showed strong enhancement of the external genitalia at each session. There was excellent correlation between the two sessions for the clitoral volume measurements of all nine subjects. The correlation coefficient, r(2), was 0.95. The sexual arousal response in normal, healthy women can be monitored by serial imaging combined with the use of the contrast agent, MS-325, and similar results can be reproduced at two different MR sessions. This method holds promise for future studies of women with female sexual arousal dysfunction.


Regulating electron configuration of single Cu sites via unsaturated N,O-coordination for selective oxidation of benzene.
Developing highly efficient catalyst for selective oxidation of benzene to phenol (SOBP) with low H2O2 consumption is highly desirable for practical application, but challenge remains. Herein, we report unique single-atom Cu1-N1O2 coordination-structure on N/C material (Cu-N1O2 SA/CN), prepared by water molecule-mediated pre-assembly-pyrolysis method, can efficiently boost SOBP reaction at a 2:1 of low H2O2/benzene molar ratio, showing 83.7% of high benzene conversion with 98.1% of phenol selectivity. The Cu1-N1O2 sites can provide a preponderant reaction pathway for SOBP reaction with less steps and lower energy barrier. As a result, it shows an unexpectedly higher turnover frequency (435 h-1) than that of Cu1-N2 (190 h-1), Cu1-N3 (90 h-1) and Cu nanoparticle (58 h-1) catalysts, respectively. This work provides a facile and efficient method for regulating the electron configuration of single-atom catalyst and generates a highly active and selective non-precious metal catalyst for industrial production of phenol through selective oxidation of benzene.


Arrhythmias and Pregnancy: Management of Preexisting and New-Onset Maternal Arrhythmias.
Arrhythmias are the most common cardiovascular complication of pregnancy in women with and without structural heart disease. Appropriate maternal diagnosis and management is of utmost importance to optimize maternal and fetal outcomes. A multidisciplinary care approach with cardiology, maternal fetal medicine, anesthesia, and pediatrics is important for preconceptional, pregnancy, and delivery planning.


Long-term microglial phase-specific dynamics during single vessel occlusion and recanalization.
Vascular occlusion leading to brain dysfunctions is usually considered evoking microglia-induced inflammation response. However, it remains unclear how microglia interact with blood vessels in the development of vascular occlusion-related brain disorders. Here, we illuminate long-term spatiotemporal dynamics of microglia during single vessel occlusion and recanalization. Microglia display remarkable response characteristics in different phases, including acute reaction, rapid diffusion, transition and chronic effect. Fibrinogen-induced microglial cluster promotes major histocompatibility complex II (MHCII) expression. Microglial soma represents a unique filament-shape migration and has slower motility compared to the immediate reaction of processes to occlusion. We capture proliferative microglia redistribute territory. Microglial cluster resolves gradually and microglia recover to resting state both in the morphology and function in the chronic effect phase. Therefore, our study offers a comprehensive analysis of spatiotemporal dynamics of microglia and potential mechanisms to both vessel occlusion and recanalization. Microglial phase-specific response suggests the morphological feature-oriented phased intervention would be an attractive option for vascular occlusion-related diseases treatments.


Treatment of radioimmunoassay data: a computer program for curvefitting and dose interpolation using orthogonal polynomials.
We propose a method allowing the automatic exploitation of radioimmunoassay results. The standard curve is calculated according to two models; a linear model by Logit-Log transformation of data and another one using Fisher's orthogonal polynomials. The computer programs are written in FORTRAN IV.


Risk factors for acute esophagitis in non-small-cell lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy.
To determine the risk factors for acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemotherapy (CCT) and three-dimensional conformal radiotherapy (3D-CRT). Clinical data were retrospectively analyzed for 215 NSCLC patients treated with CCT and 3D-CRT during 2000-2003, 127 of whom also had induction chemotherapy (ICT). Carboplatin and paclitaxel were the most commonly used agents for both ICT and CCT. The median prescription dose of radiotherapy was 63.5 Gy in 35 fractions. AE was graded during each treatment week and 1-month follow-up visits. The factors related to clinical and disease characteristics, CCT and 3D-CRT treatments, and treatment planning were reviewed and analyzed for their association with Grade > or =3 AE using univariate and multivariate logistic tests. The rate of any grade AE was 93.0% and of Grade > or =3 was 20.5%. Univariate analyses showed that none of the clinical factors was significantly associated with Grade > or =3 AE. However, the mean radiation dose to the esophagus, the absolute esophageal volume treated above 15 Gy (aV15) through aV45 Gy, and the relative esophagus volume treated above 10 Gy (rV10) through rV45 Gy were significant risk factors for Grade > or =3 AE. Only rV20 was retained as the single risk factor in multivariate analyses. The risk of AE in the NSCLC patients treated with CCT and 3D-CRT was primarily determined by dosimetric factors. These factors should be carefully considered during treatment planning to minimize the incidence of AE.


Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.
We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation.


The journal of the future is here today.
Scientific publishing has undergone a complete transformation in the last two decades. While the process of peer review may differ little from what it was during the last 50 years, electronic indexing, electronic access, and now electronic submission of scientific manuscripts has transformed the surgical journal in the last decade. In fact, the editorial office of the journal has contracted to a workstation, a fax machine, a telephone, and a storage locker for the aging paper records.


Application of a surgical nursing cooperation program in laparoscopic pancreaticoduodenectomy.
To evaluate the value of programmed surgical nursing in laparoscopic pancreaticoduodenectomy (LPD) and summarize the experience. The clinical data of 80 patients who received LPD in Sun Yat-sen Memorial Hospital from January 2017 to December 2018 were analyzed retrospectively. A total of 40 patients were treated with traditional surgical nursing as the control group in the earlier stage. Afterwards, another 40 cases in the experimental group were treated using the surgical nursing program. Operation time, blood loss, and satisfaction of surgeons were analyzed. In all, 80 cases were successfully completed, and no significant difference was observed in the preoperative data statistics between these two groups (P>0.05). Compared with the control group, the average operation time and the average blood loss of the experimental group were significantly reduced (288.9±11.14 vs. 364.5±10.84 min, P<0.05; 135.3±20.12 vs. 364.8±77.39 mL, P<0.05), and the satisfaction of surgeons was significantly higher (95% vs. 80%, P<0.05). Skilled execution of nursing cooperation is crucial in LPD. Through appropriate preoperative preparation, gaining mastery operation steps, remaining in sync with surgeons, and perfecting the management details, the surgical nursing cooperation program can improve the satisfaction of the surgeons and make operations more efficient.


Determinants of low serum concentrations of salicylates in patients with Kawasaki disease.
The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose.


[Effect of stimulating the medial and lateral zones of the respiratory center on the electrical activity of the diaphragm, intercostal muscles and phrenic neurons].
Experiments on cats showed that the nucleus of the solitary tract displayed zones whose stimulation provoked separately stimulation or inhibition of the electrical activity of the phrenic neurons and the diaphragm. Stimulation in the nucleus ambiguus of such zones caused stimulation and inhibition of electrical activity of the intercostal inspiratory muscles. In stimulation of the corresponding zone in the giant cell nucleus the electrical activity of both groups of the inspiratory muscles proved to change. It is suggested that the action of stimulation of the giant cell nucleus zones on both groups of inspiratory muscles is mediated through the neurons of the solitary tract and the nucleus ambiguus.


Phase transitions in paradigm shift models.
Two general models for paradigm shifts, deterministic propagation model (DM) and stochastic propagation model (SM), are proposed to describe paradigm shifts and the adoption of new technological levels. By defining the order parameter m based on the diversity of ideas, Δ, it is studied when and how the phase transition or the disappearance of a dominant paradigm occurs as a cost C in DM or an innovation probability α in SM increases. In addition, we also investigate how the propagation processes affect the transition nature. From analytical calculations and numerical simulations m is shown to satisfy the scaling relation m=1-f(C/N) for DM with the number of agents N. In contrast, m in SM scales as m=1-f(α(a)N).


Electron microscopy of retinal tapetum (Caiman crocodilus).
The distribution and ultrastructure of the retinal tapetum lucidum in Caiman crocodilus is described. In the light adapted eye the tapetum is recognized in the superior half of the fundus. It consists of guanine containing crystalline platelets which are spread almost over the entire retinal pigment epithelial cells which can be divided into different layers: 1. The basal surface facing the choriocapillary vessels is differentiated into numerous densely packed true microfolds which are commonly described as "basal infoldings". 2. A remarkable high content of mitochondria as well as a great number of lipid droplet-like spherical bodies is observed. 3. In the nuclear zone a Golgi apparatus and all stages of phagocytosis are found. 4. Within the level of intercellular junctions, crystalline platelets are arranged mainly perpendicularly to the long axis of the neighbouring receptor cells, whereas 5. platelets in large pigment epithelial cell processes extending from the apical cell surface between the photoreceptors are oriented parallel to the receptor axis. 6. Heavy pigmentation of the apical tips of pigment cell processes by melanosomes is observed, but only within the lower half of the fundus. The functional significance of the tapetum of Caiman crocodilus is discussed.


Towards a non-living vaccine against Shigella flexneri: from the inactivation procedure to protection studies.
Shigellosis is one of the leading causes of diarrhea worldwide with more than 165 million cases annually. Hence, a vaccine against this disease is a priority, but no licensed vaccine is still available. Considering target population as well as intrinsic risks of live attenuated vaccines, non-living strategies appear as the most promising candidates. Remarkably, the preservation of antigenic properties is a major concern since inactivation methods of bacteria affect these qualities. We previously reported the use of a subcellular antigen complex for vaccination against shigellosis, based on outer membrane vesicles (OMVs) released from Shigella flexneri. Now, we describe in more detail the employment of binary ethylenimine (BEI) for inactivation of Shigella and its subsequent effect on the antigenic conservation of the vaccinal product. Results demonstrate the effectiveness of BEI treatment to completely inactivate Shigella cells without disturbing the antigenicity and immunogenicity of the OMVs. Thus, OMVs harvested after BEI inactivation were able to protect mice against an experimental infection with S. flexneri.


Office accreditation in dermatology.
Health care accreditation is a process of demonstrating compliance with nationally-recognized standards of excellence. Compliance with standards is verified during an on-site survey by specially-trained surveyors. Office-based surgery accreditation is available to dermatologists through the Accreditation Association for Ambulatory Health Care (AAAHC), and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO).


Delusional infestation and patient adherence to treatment: an observational study.
Delusional infestation (DI) is the persistent belief of pathogenic infestation of the skin or body, without objective medical evidence. Treatment for symptoms of delusions can be particularly challenging, especially when patients are difficult to engage and adverse to the possibility of a nonskin disorder. To date there has been no study to evaluate patient adherence to DI treatment. To assess the adherence of patients with DI to psychotropic and/or dermatological medication. Sixty-nine consecutive patients with DI receiving treatment from our psychodermatology clinic were identified from a departmental database. Patient adherence to treatment was assessed via medical records, patient letters and a telephone questionnaire. Eighteen of 69 patients were noncontactable, reducing the sample size to 51. Forty-nine of 51 patients were receiving psychotropic medication (96%). Psychotropic agents included second-generation antipsychotics and antidepressants. Twenty-nine of 49 patients were adherent to psychotropic medication. Secondary nonadherence was reported by 18 of 49 patients. Two patients were nonadherent to psychotropic medication. Adherence to dermatological medication was high (96%). This is the first study to assess the adherence of patients with DI to treatment. The majority of patients on psychotropic medication were compliant. Secondary nonadherence was mainly due to drug side-effects. The adherence to dermatological medications is high. Thorough counselling of patients with regard to indication, dosage and side-effects of psychotropic agents can improve adherence to medication and is an essential part of the treatment process for DI.


Six-month daily treatment of sheep with neurotoxic organophosphorus compounds.
The delayed neurotoxic effects of tri-o-cresyl-phosphate (TOCP), O-methyl-O-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (leptophos), and O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN) at 5, 5, and 1 mg/kg/day, respectively, on male sheep were studied during 6 months of daily oral treatment under field conditions. A vehicle-control group of sheep given corn oil (0.1 ml/kg/day) only was used for comparison. All sheep were killed 24 h after the 180th daily treatment. Blood, brain, spinal cord, and sciatic nerve tissues were taken for histological and/or biochemical examinations. The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment. TOCP produced either mild ataxia or lameness in two of four sheep during the last week of experiment. On the other hand, none of the EPN-treated sheep showed clinical signs of neurotoxicity during the course of the experiment at the dosage tested. These clinical results were supported by histological findings and also by biochemical results with neurotoxic esterase (NTE) measurements. In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains. Similar but somewhat less numerous lesions were noted in sheep treated with TOCP. No histological changes were observed in similar tissues taken from EPN-treated sheep. The results also indicated that, for chronic exposure to these neurotoxic organophosphorus compounds in sheep, a threshold in excess of 60-70% prolonged inhibition of brain NTE, or 50-60% inhibition of spinal cord NTE must be exceeded to initiate clinical and/or histological neurotoxic effects.


Characterisation of the vitreous proteome in proliferative diabetic retinopathy.
Diabetes can lead to serious microvascular complications such as proliferative diabetic retinopathy (PDR), which results in severe vision loss. The diabetes-induced alterations in the vitreous protein composition in diabetic patients with PDR may be responsible for the presence of PDR. The vitreous humour can be utilised in a variety of studies aimed toward the discovery of new targets for the treatment or prevention of PDR and the identification of novel disease mechanisms. The aim of this study was to compare the protein profile of vitreous humour from diabetic patients with PDR with that of vitreous humour from normal human eyes donated for corneal transplant. Vitreous humour from type 2 diabetic patients with PDR (n = 10) and from normal human eyes donated for corneal transplant (n = 10) were studied. The comparative proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Differentially produced proteins (abundance ratio > 2 or < -2, p < 0.01) were identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF tandem mass spectrometry. A total of 1242 protein spots were detected on the 2-D master gel of the samples, and 57 spots that exhibited statistically significant variations were successfully identified. The spots corresponded to peptide fragments of 29 proteins, including 8 proteins that increased and 21 proteins that decreased in PDR. Excluding the serum proteins from minor vitreous haemorrhage, 19 proteins were found to be differentially produced in PDR patients compared with normal subjects; 6 of these proteins have never been reported to be differentially expressed in PDR vitreous: N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH 1), tubulin alpha-1B chain, gamma-enolase, cytosolic acyl coenzyme A thioester hydrolase, malate dehydrogenase and phosphatidylethanolamine-binding protein 1 (PEBP 1). The differential production of pigment epithelium-derived factor (PEDF) and clusterin was confirmed by Western blot analysis. These data provide an in-depth analysis of the human vitreous proteome and reveal protein alterations that are possibly involved in the pathogenesis of PDR. Further investigation of these special proteins may provide potential new targets for the treatment or the prevention of PDR.


Evaluation of a batched-extraction method for measurement of sirolimus, tacrolimus, and cyclosporine on the Architect i2000SR.
Manual extraction of immunosuppressants is required before measurement on the Architect immunoassay analyzer. The individual extraction of samples places clinical laboratory staff at risk for ergonomic injury. We evaluated the analytical performance of a batched extraction method for measuring sirolimus, tacrolimus, and cyclosporine using the Architect i2000SR. Residual whole blood samples from patients receiving immunosuppressant therapy were used for evaluation. The analytical evaluation included imprecision, linearity, and method comparison. Technologist-to-technologist variation was also assessed. Total imprecision ranged from 2.58 to 3.13% for sirolimus, 2.70-3.77% for tacrolimus, and 7.82-12.41% for cyclosporine. Linearity was verified from 0.44-19.49 μg/l for sirolimus, 0.05-26.15 μg/l for tacrolimus, and 0.15-991.55 μg/l for cyclosporine. Deming regression analysis showed slope and intercept were not significant for either technologist-to-technologist comparison or for batched vs. individual processing comparison. Bland-Altman analysis of individual vs. batched processing revealed a mean bias of 1.29% (LLOA: -14.63%, ULOA: 17.21%) for sirolimus, 2.07% (LLOA: -10.87%, ULOA: 15%) for tacrolimus, and -1.56% (LLOA: -20.05%, ULOA: 16.94%) for cyclosporine. The values were not significantly different from the bias and LLOAs observed for technologist-to-technologist comparison. The imprecision and linearity of batched methods met analytical goals. The batched method also correlated well with the individual extraction methods. The ULOA and LLOA for all drugs tested exceeded a TAE or ± 15%. However, similar range of differences was observed between technologists, suggesting that batch processing did not increase or reduce variability due to manual preparation steps.


Structural mechanisms of trabecular bone loss in man.
The relationship between trabecular thinning and loss of connectedness of the trabecular bone pattern has been studied in iliac crest bone samples from 89 normal subjects in order to determine the structural mechanisms underlying age-related bone loss. Trabecular width and structure were quantitatively assessed using computerized techniques. Highly significant negative correlations were found between the mean trabecular plate thickness and number of free ends/mm2 both in males (r = -0.571) and in females (r = -0.667) (P less than 0.001). Mean trabecular plate thickness also showed significant negative correlations with other structural indices indicating reduced connectedness, whereas positive correlations were found with those indices representing preservation of connectedness. Examination of the relative frequency of trabecular widths less than 100 microns revealed that only 2-5% of the trabecular surface would be susceptible to erosion by a resorption cavity of normal depth. These results indicate that trabecular thinning and erosion are interdependent processes in age-related bone loss. Since only a small percentage of the trabecular surface is susceptible to erosion, and resorption cavities normally occupy only 1-5% of the total trabecular surface, these findings imply that the site of activation of new BMUs may not be randomly distributed but may instead be preferentially located at sites of lower trabecular width.


Imaging characteristics of two subtypes of congenital hemangiomas: rapidly involuting congenital hemangiomas and non-involuting congenital hemangiomas.
Common infantile hemangiomas (COMMON) occur in approximately 10% of infants by the age of 1 year, with a female predominance. Some hemangiomas can be fully developed at birth and are thus called congenital hemangiomas (CH). Within this population, two courses have been identified: rapidly involuting CH (RICH) and non-involuting CH (NICH). Little has been reported on the clinical prognosis and imaging features of these entities. To describe the imaging characteristics of two subtypes of CH, i.e. RICH and NICH, and to compare them with COMMON. We retrospectively gathered data on 26 children presenting with CH, i.e. lesions fully developed at birth. These lesions were divided into two groups according to the clinical course: suspected RICH (n=8) and suspected NICH (n=18). We used US, CT or MRI and angiography to identify the gross anatomy and structure and the vascularization. Imaging findings were compared with the clinical course and pathology results, when available. The imaging findings in these patients were compared retrospectively with those in 26 patients with COMMON randomly chosen from the database of our multidisciplinary clinic. When compared with COMMON imaging characteristics, NICH and RICH had distinctive features on US such as being heterogeneous (72% of NICH and 62.5% of RICH vs 42.3% of COMMON), visible vessels (72% of NICH and 62.5% of RICH vs 15.4% of COMMON), calcifications (17% of NICH and 37.5% of RICH vs no case of COMMON). On CT and/or MRI, we compared imaging features such as well-defined limits (67% of NICH and 60% of RICH vs 100% of COMMON), and fat stranding (29.4% of NICH and RICH vs 7.7% of COMMON). Distinctive imaging characteristics are observed in cases of CH with US findings of visible vessels and calcifications statistically significant.


[Religion and spirituality, definitions and challenges].
Understanding religious teachings and the religious dimension in our societies is not made any easier with a discourse that is often lacking in rigor for dealing with this reality. Some basic notions need to be clarified to better define the religious and the spiritual.


A glucose biosensor based on microporous polyacrylonitrile synthesized by single rare-earth catalyst.
A glucose biosensor was constructed by electrochemical adsorption of glucose oxidase (GOD) in microporous polyacrylonitrile (PAN), which was synthesized by single rare-earth catalyst-Y(OAr)(3.) The biosensor shows a fast response, good operational stability and reproducibility. The influences of molecular weight of polymer, pH, operating potential and temperature on the biosensor response were explored by amperometric method. The apparent activation energy and optimum pH of enzyme-catalyzed reaction are 35.9 kJ mol(-1) and 6.2, respectively.


The pivot fracture: an unusual tibial plateau fracture found in association with acute ACL injury.
Tibial plateau fractures are common fractures which are often associated with concurrent soft tissue injury and for which accurate preoperative diagnosis is important for development of an appropriate treatment plan and outcome prediction. Here, we present an extreme manifestation of the pivot shift phenomenon with an unusual tibial plateau fracture with flipped component not described by any existing tibial plateau fracture classification system and never reported previously in conjunction with an anterior cruciate ligament injury. We describe the utilization of advanced imaging not typically utilized in the management of tibial plateau fractures in combination with clinical suspicion to diagnose the associated soft tissue injuries and develop an appropriate management plan.


The Nitric Oxide Prodrug JS-K Induces Ca(2+)-Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.
Hepatocellular carcinoma is one of the most common and deadly forms of human malignancies. JS-K, O(2)-(2, 4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1, 2-diolate, has the ability to induce apoptosis of tumor cell lines. In the present study, JS-K inhibited the proliferation of HepG2 cells in a time- and concentration-dependent manner and significantly induced apoptosis. JS-K enhanced the ratio of Bax-to-Bcl-2, released of cytochrome c (Cyt c) from mitochondria and the activated caspase-9/3. JS-K caused an increasing cytosolic Ca(2+) and the loss of mitochondrial membrane potential. Carboxy-PTIO (a NO scavenger) and BAPTA-AM (an intracellular Ca(2+) chelator) significantly blocked an increasing cytosolic Ca(2+) in JS-K-induced HepG2 cells apoptosis, especially Carboxy-PTIO. Meanwhile, Carboxy-PTIO and BAPTA-AM treatment both attenuate JS-K-induced apoptosis through upregulation of Bcl-2, downregulation of Bax, reduction of Cyt c release from mitochondria to cytoplasm and inactivation of caspase-9/3. In summary, JS-K induced HepG2 cells apoptosis via Ca(2+)/caspase-3-mediated mitochondrial pathway.


Change processes during intensive day programme treatment for adolescent anorexia nervosa: a dyadic interview analysis of adolescent and parent views.
Day programmes for adolescent anorexia nervosa (AN) can function as an alternative to inpatient admissions and/or an increase in outpatient treatment intensity. Processes of change during treatment for AN are currently poorly understood. This study aimed to explore how adolescents with AN and their parents understood the helpful and unhelpful factors and processes that impacted them during day programme treatment. A critical realist paradigm was used to qualitatively explore the views of 16 participants. Participants were recruited from the Intensive Treatment Programme (ITP) at the Maudsley Center for Child and Adolescent Eating Disorders (MCCAED) at the end of treatment. Dyadic Interview Analysis (DIA) was used to compare and contrast the narratives of the seven adolescent-parent pairs after two inductive reflexive thematic analyses were conducted for the group of eight adolescents and the group of eight parents separately. Eight subthemes across three themes were identified: 1) "Like me she didn't feel so alone anymore"-families connect with staff, peers, and each other; 2) "You have to eat because ITP say so"-the programme provides families with containment through its structure and authority; and 3) "I found that I was using the skills I learnt there like in multiple aspects of my life, not just around food"-families take in new ideas and generalize these into their lives. These interconnected themes generated hope and change. However, helpful elements individually could be unhelpful if one or more of the other factors were missing. For example, staff firmness, which participants often found helpful (theme two), could be experienced as harshness when adolescents did not feel related to as individuals (theme one). The findings can be conceptualized within recent descriptions regarding the therapeutic change, including epistemic trust and mentalization. Treatment characteristics, such as intensity and containment, as well as illness-specific factors and processes, such as control and collaboration, the role of peer support, and the potential for family members to experience the impact of the adolescent's AN and treatment non-response as traumatic, are equally important to consider.


The cytoplasmic tail substitution increases the assembly efficiency of Ebola virus glycoprotein on the budded virus of Bombyx mori nucleopolyhedrovirus.
Glycoprotein (GP1,2) of the Ebola virus (EBOV) is the key membrane fusion protein, which is a key candidate protein for vaccine preparations. Previously, GP1,2 was expressed by Bombyx mori nucleopolyhedrovirus (BmNPV) expression vector system; however, few GP1,2 was incorporated into budded virus (BV) of BmNPV. To improve the incorporation efficiency of GP1,2 into the virion, the GP1,2 fusion with the cytoplasmic tail of GP64 of BmNPV was expressed in BmN cells by the BmNPV expression system. The BV was purified by ultracentrifugation, and GP1,2 expression in BV was detected by the antibody. The result indicated that a 532% increase in the relative GP1,2 densitometry signal was observed in constructs utilizing the GP64 C-terminal domain; moreover, the substitution of GP1,2 native signal peptide with GP64 signal peptide increased the incorporation efficiency by 34.6% in the relative GP1,2 densitometry signal. We revealed that the application of the cytoplasmic tail of BmNPV GP64 significantly increased the incorporation rate of GP1,2 into the BV envelope. This study lays a foundation for GP1,2 vaccine development.


Piceatannol attenuates fat accumulation and oxidative stress in steatosis-induced HepG2 cells.
Non-alcoholic fatty liver disease (NAFLD), which affects over 20% of the adult population, is the most common liver disease worldwide and can progress to inflammatory hepatitis, cirrhosis and liver cancer. The need to alleviate NAFLD is imperative, but there are limited pharmacological therapies available. Based on previous reports that piceatannol, a stilbenoid metabolite of resveratrol, exhibits anti-obesity, antioxidant and anti-inflammatory effects, the goal of this study was to determine the efficacy of piceatannol on prevention and/or treatment of NAFLD. The results showed that piceatannol significantly decreased fat accumulation and suppressed lipogenesis and fatty acids (FAs) uptake by decreasing sterol regulatory element-binding protein 1 (SREBP1) and cluster of differentiation 36 (CD36) in steatosis-induced HepG2 hepatocytes. Piceatannol treatment also promoted FAs β-oxidation by increasing farnesoid X receptor (FXR), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyltransferase 1α (CPT1α) under steatosis conditions. Moreover, piceatannol significantly suppressed FA-induced oxidative stress and inhibited phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (ERK1/2). Overall, it is suggested that piceatannol reduced fat accumulation in steatosis-induced HepG2 cells by suppressing lipogenesis (SREBP1 and ACC) and FA uptake (CD36), and promoting FAs oxidation (FXR, PPARα and CPT1α).


Isolation and purification of a rat liver 3-hydroxy-3-methylglutaryl-coenzyme reductase activating protein (RAP).
A protein with an estimated subunit mass of 19 kDa was isolated and purified from perfused rat liver cytosol. This protein activates hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (NADPH) (EC 220.127.116.11), the rate-limiting enzyme in the cholesterol biosynthetic pathway. The activation process by this HMG-CoA reductase activating protein (RAP) is time-dependent and requires NADPH. Maximal activity of HMG-CoA reductase induced by RAP is comparable to that obtained in the presence of thiols, such as GSH, and can exceed 100-fold the activity obtained when thiols are omitted. Purified RAP lacks ability to reduce 5,5'-dithiobis-(2-nitrobenzoic acid). RAP was purified to homogeneity utilizing DEAE- and phenyl-Sepharose CL-4B column chromatography. The purified RAP migrates as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and shows multiple interconvertible aggregational forms on native polyacrylamide gel electrophoresis. A monospecific antibody against RAP was prepared by immunization of hens and extracted from either their egg yolks or serum. The catalytic activity of RAP might be responsible for the physiological activation of HMG-CoA reductase and regulation of its activity.


Thyroid surgery for differentiated thyroid cancer - recent advances and future directions.
Population-based studies have demonstrated that an increasing number of incidental thyroid nodules are being identified. The corresponding increase in thyroid-based diagnostic procedures, such as fine-needle aspiration biopsy, has in part led to an increase in the diagnoses of thyroid cancers and to more thyroid surgeries being performed. Small papillary thyroid cancers account for most of this increase in diagnoses. These cancers are considered to be low risk because of the excellent patient outcomes, with a 5-year disease-specific survival of >98%. As a result, controversy remains regarding the optimal management of newly diagnosed differentiated thyroid cancer, as the complications related to thyroidectomy (primarily recurrent laryngeal nerve injury and hypoparathyroidism) have considerable effects on patient quality of life. This Review highlights current debates, including undertaking active surveillance versus thyroid surgery for papillary thyroid microcarcinoma, the extent of thyroid surgery and lymphadenectomy for low-risk differentiated thyroid cancer, and the use of molecular testing to guide decision-making about whether surgery is required and the extent of the initial operation. This Review includes a discussion of current consensus guideline recommendations regarding these topics in patients with differentiated thyroid cancer. Additionally, innovative thyroidectomy techniques (including robotic and transoral approaches) are discussed, with an emphasis on patient preferences around decision-making and outcomes following thyroidectomy.


Citizen scientist lepidopterists exposed to potential carcinogens.
Lepidopterists use substantial volumes of solvents, such as chloroform, 1,1,2,2-tetrachloroethane and xylene, in their traps when collecting faunistic and phenological data. A majority of them are citizen scientists and thus in part not identified by occupational healthcare as being at risk due to solvent handling. We surveyed the extent of solvent use, the frequency and extent of potential exposure and the safety precautions taken in trapping and catch handling by Finnish lepidopterists. Chloroform and 1,1,2,2-tetrachloroethane were the most frequently used anaesthetics. Potential for exposure prevailed during trap maintenance and exploration and catch sorting. Adequate protection against vapours or spills was worn by 17% during trap exploration. Subjects completed a median of 100 trap explorations per season. Dermal or mucosal spills were recorded at a median rate of one spill per ten (chloroform) to 20 (1,1,2,2-tetrachloroethane and xylene) trap explorations. Median annual cumulative durations of 8 and 20 h of exposure to chloroform and 1,1,2,2-tetrachloroethane at levels above odour detection threshold were reported. Subjective adverse findings possibly related solvents had been noticed by 24 (9.8%) lepidopterists. All the events had been mild to moderate. No factor predicting unsafe procedures or adverse reactions was recorded despite thorough statistical testing.


Cytogenetic effects of inhaled ozone.
We have repeated as closely as possible the experiments of Zelac et al., who observed significantly elevated levels of chromosome aberrations in short-term cultures of peripheral lymphocytes from Chinese hamsters that had inhaled ozone. Unlike Zelac et al., we observed no increase in chromosome-type aberration levels, though a small increase in chromatid-aberration levels similar to that reported for exposed human subjects by Merz et al. was seen. No increase in the levels of any chromosomal aberration type was seen in parallel direct bone-marrow preparations. Sister-chromatid exchange (SCE) levels and cell-replication rates, which were determined in the Chinese hamster peripheral lymphocyte cultures and also in bone-marrow samples from similarly treated mice, failed to show any ozone-induced changes.


A tricky and rare cause of pulmonary eosinophilia: myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA.
Eosinophilic lung diseases represent a heterogeneous group of disorders with prominent infiltrate of eosinophils in lung interstitium and alveolar spaces. Peripheral blood eosinophilia is often present. Infections, drugs, allergens, toxic agents have to be evaluated as possible causes of eosinophilic lung infiltrates. The category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 represents an uncommon cause of eosinophilic lung infiltrate. We report the case of a 70-year old man complaining of dry cough and dyspnea. Ground glass-opacities were seen on imaging studies and peripheral blood eosinophilia was present. A thorough step-wise patient's evaluation led to identify the clonal nature of eosinophilia and the diagnosis of myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA was made. Correlation with clinical history, laboratory tests and imaging studies is essential to achieve the correct diagnosis when facing with eosinophilic lung infiltrates. A prolonged eosinophilia can cause life-threatening organ damage. Identification of PDGFRA rearrangement, as in the present case, is particularly critical given the sensitivity and excellent response to imatinib, which has completely changed the natural history of this neoplasm.


NADPH-cytochrome P-450 reductase. Physical properties and redox behavior in the absence of the FAD moiety.
NADPH-cytochrome P-450 reductase contains one molecule each of FMN and FAD. The FAD moiety has been selectively removed, producing the FMN reductase. The FMN reductase is stable and enzymatic activity is reconstituted with either FAD or FMN. FMN remains tightly bound, but can both dissociate from the FMN site and bind to the vacant FAD site. The amount of FMN bound in the FAD site is minimal under specific experimental conditions. There are at least two conformational subpopulations of the FMN reductase; NADP dissociates readily from one but extremely slowly from the other. Rapid dissociation of NADP is regained upon reconstitution with FAD. The one-electron redox state of the FMN reductase is thermodynamically stabilized, though to a lesser degree than in the holoreductase. When two-electron reduced FMN reductase is exposed to oxygen, a stable species with an absorbance peak at 580 nm forms rapidly and quantitatively. This species has been identified by electron paramagnetic resonance spectroscopy as the neutral radical of FMN and is indistinguishable from the air-stable radical of the holoreductase. The redox behavior of the FMN reductase is in agreement with properties proposed previously for the FMN site.


Role of mitochondria in ciprofloxacin induced apoptosis in bladder cancer cells.
In our earlier series we showed that ciprofloxacin inhibits bladder tumor cell growth with concomitant S/G2M cell cycle arrest and reported an increased Bax-to-Bcl-2 ratio in cells undergoing cell death. In the current series we elucidated the molecular mechanisms by which ciprofloxacin induces apoptotic processes. Ciprofloxacin mediated mitochondrial depolarization was detected by flow cytometry in HTB9 cells. Mitochondrial permeability transition was measured by spectrophotometry in isolated mitochondria treated with ciprofloxacin in the presence and absence of cyclosporin. The consequential decrease in mitochondrial calcium, cytochrome c release and Bax translocation to mitochondria, which resulted in the activation of caspase 3 leading to apoptotic cell death, was measured by biochemical and confocal microscopy. Mitochondrial depolarization was observed during ciprofloxacin induced apoptotic processes. Cyclosporin A, a known inhibitor of the mitochondrial permeability transition pore, protected cells against decreased mitochondrial potential. Also, ciprofloxacin induced an alteration of mitochondrial calcium as early as 5 minutes and this disruption of intracellular calcium homeostasis was prevented by cyclosporin. Ciprofloxacin also had a direct effect on swelling of isolated mitochondria, which was absent in the presence of cyclosporin. Mitochondrial changes were accompanied by cytochrome c release and caspase 3 activation. Our findings also showed Bcl-2 dependent subcellular redistribution of Bax to the mitochondrial membrane in ciprofloxacin treated bladder tumor cells. The disruption of calcium homeostasis, mitochondrial swelling and redistribution of Bax to the mitochondrial membrane are key events in the initiation of apoptotic processes in ciprofloxacin treated bladder cancer cells.


Method of pacing does not affect the recurrence of syncope in carotid sinus syndrome.
Pacemaker therapy is effective in reducing recurrent syncope in patients with symptomatic carotid sinus hypersensitivity (CSH), yet the optimal pacing modality for this syndrome is not known. The objective of this study is to prospectively investigate the impact of three pacing methods (DDDR vs DDDR with sudden bradycardia response [SBR] vs VVI) on recurrent syncope and quality of life. Twenty-one patients with symptomatic CSH (syncope or near syncope) were randomized to VVI, DDDR, or DDDR with SBR on a double-blinded basis in a sequential crossover fashion with 6 months in each mode. The primary endpoints were recurrent events and quality of life (assessed by SF-36). The mean number of events and SF-36 scores were compared. At baseline, over the preceding 6 months, there were a total of 29 syncopal events and 258 presyncopal events among 21 patients. Following pacing in any mode, the total number of these syncopal events reduced to two in two patients (P < 0.001) and 17 presyncopal events (P < 0.001) in 12 patients. The mean number of events was not significantly different between the three pacing methods. SF-36 scores revealed some minor benefits of DDDR pacing versus baseline in the categories, but no pacing method was found to be superior. The study was unable to confirm the initial study hypothesis of a superiority of one pacing modality over another. Quality of life measures allude to potential benefit from DDDR pacing alone.


Radioxenon monitoring in Beijing following the Fukushima Daiichi NPP accident.
This paper reports the brief process and results of radioxenon monitoring and analysis in Beijing following the Fukushima Daiichi nuclear power plant accident. The accident and release of volatile radionuclides were caused by 9.0 magnitude earthquake and tsunami on March 11, 2011. The maximum concentrations of (133)Xe and (131 m)Xe were in excess of 0.90 Bq.m(-3) and 0.047 Bq.m(-3), respectively. The activity ratio of (131 m)Xe to (133)Xe and the dynamic trend of (133)Xe activity concentration were analyzed.


Estimating prevalence of early Alzheimer's disease in the United States, accounting for racial and ethnic diversity.
Updated estimates of the US Alzheimer's disease (AD) population, including under-represented populations, are needed to improve clinical trial diversity. A step-wise approach calculating prevalent numbers from clinical syndrome to biomarker-positive mild cognitive impairment (MCI) due to AD and mild AD was developed, using age-and-race/ethnicity-stratified data where available. The estimated percentage of Americans aged ≥ 65 years with MCI due to AD was 9.2% of non-Hispanic Whites, 13.6% of non-Hispanic Blacks, 11.1% Hispanics, and 9.7% other race/ethnicities. The estimated percentage of Americans aged ≥ 65 years with mild dementia due to AD among non-Hispanic Whites was 3.7%, non-Hispanic Blacks 7.0%, Hispanics 5.3%, and 3.9% other race/ethnicities. Of these early-stage AD cases, few are likely diagnosed, ranging from 13% of prevalent non-Hispanic Black cases to 27% of non-Hispanic White cases. Under-representation in clinical trials may be improved by setting recruitment goals reflecting the diversity of the AD patient population and supporting efforts toward timely diagnosis.


Natural intragenotypic and intergenotypic HCV recombinants are rare in southwest China even among patients with multiple exposures.
Both intragenotypic and intergenotypic hepatitis C virus (HCV) recombinants were recently identified, whereas the frequency of HCV recombinants in circulation in certain parts of the world remains uncertain. To assess the frequency of natural intragenotypic and intergenotypic HCV recombinants in southwest China and that of multitypic HCV infection, which is the prerequisite factor for recombination. Comparison of the genotyping results based on core-envelope 1 and non-structural 5B sequence phylogenetic analyses to detect the possible recombinants. Multitypic HCV infection was detected by colony analysis of the core-envelope 1 region. There was no discrepancy between genotyping results based on the core-envelope 1 and non-structural 5B regions in 243 sera from 222 patients, including 107 samples from 92 intravenous drug users, 26 samples from 20 hemodialysis patients, and 110 samples from 110 other patients. Multitypic HCV carriage was identified in 9 (47.4%) of the 19 patients with multiple exposures who were randomly selected, and 11 (45.8%) of the 24 specimens. There were 26 repeatedly exposed patients who had more than one HCV RNA positive sera at different time points, but neither of their HCV subtypes had switched over time. Although the high frequency of multitypic HCV infection was identified in patients with multiple exposures, intergenotypic or intragenotypic recombination remains an infrequent event in southwest China; thus, routine genotyping with more than one subgenomic region for clinical use is not warranted.


Coupled Mach-Zehnder interferometer memory element.
Two active Mach-Zehnder interferometers are integrated in a monolithic InP/InGaAsP photonic integrated circuit. Together they form a crucial component for optical signal processing: an optical memory element or set-reset flip-flop. The switching time for this initial device is approximately 200 ps. The photonic integrated circuit contains active and passive optical components, including electro-optic phase shifters.


A versatile assay for gelatinases using succinylated gelatin.
A spectrophotometric assay using succinylated gelatin as substrate is described for measuring the catalytic activity of gelatinases. The assay is based on measurement of primary amines exposed as a result of hydrolysis of the substrate by gelatinases. Comparison of hydrolysis by matrix metalloproteinase (MMP) 1, 2, 3, 7, 9 indicated that succinylated gelatin was primarily digested by MMP-2 and -9. The assay is rapid (<60 min), specific, suitable for measuring gelatinolytic activity of enzymes and high volume screening of MMP-2 and -9 inhibitors. Sensitivity of the assay is comparable to that of gelatin zymography, under similar experimental conditions. Thus, the assay combines ease and rapidity of assays based on synthetic peptide substrates with specificity of the gelatin zymography technique.


Ca2+ channels: diversity of form and function.
The past year has seen some significant advances in our understanding of the structural and functional properties of neuronal voltage-gated Ca2+ channels. Molecular cloning and protein purification studies have identified structural components, and expression studies are beginning to define the biophysical and pharmacological properties of the cloned channels. A number of studies of native Ca2+ channels show that the concept of channel modulation includes gating by both voltage and ligands.


Serum β-carotene concentrations and the risk of congestive heart failure in men: a population-based study.
Fruit and vegetable intake has been associated with lower risk for cardiovascular diseases, but data on congestive heart failure (CHF) are inconsistent. The association of serum carotenoids, biomarkers reflecting fruit and vegetable intake, with the risk of CHF has not been well documented in previous studies. We therefore examined the association between carotenoid levels and the risk of CHF. Data were available for 1031 males aged 46 to 65 years participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (Finland). Baseline data for the present study were collected between 1991 and 1993. The association between serum concentrations of carotenoids and the risk of CHF was examined by using Cox proportional hazard models. During the median of 17.8 follow-up years, CHF occurred in 72 patients. Age and examination year adjusted risk (hazard ratio, HR) for CHF among men within the lowest quartile of serum β-carotene was 4.08 (95% CI, 1.90-8.78, p<0.001) as compared to men in the highest quartile of serum β-carotene. After further adjustment for many potential confounders, men with the lowest quartile of β-carotene had almost 3-fold increased risk of CHF (HR=2.78, 95% CI, 1.23-6.25, p=0.014). However, serum concentrations of lycopene and α-carotene were not related to the risk of CHF. The present study suggests that low concentrations of serum β-carotene may be associated with an increased risk of CHF.


Detection of bacterial antigens in cerebrospinal fluid by a latex agglutination test in 'septic unknown' meningitis and serogroup B meningococcal meningitis.
The latex agglutination test (Wellcogen) was evaluated specifically in cases of 'septic unknown' meningitis, with CSF findings characteristic of bacterial meningitis but with no bacterial organisms grown on CSF culture or seen on microscopy after Gram staining. In only 4 (12%) of 33 cases of 'septic unknown' meningitis were antigens identified in the CSF. This kit contains for the first time reagents for the detection of serogroup B Neisseria meningitidis antigens and was also evaluated for this bacteria. Only 6 (27%) of 22 serogroup B N. meningitidis cases were identified.


An immunoinformatics approach to epitope-based vaccine design against PspA in Streptococcus pneumoniae.
Streptococcus pneumoniae (SPN) is the agent responsible for causing respiratory diseases, including pneumonia, which causes severe health hazards and child deaths globally. Antibiotics are used to treat SPN as a first-line treatment, but nowadays, SPN is showing resistance to several antibiotics. A vaccine can overcome this global problem by preventing this deadly pathogen. The conventional methods of wet-laboratory vaccine design and development are an intense, lengthy, and costly procedure. In contrast, epitope-based in silico vaccine designing can save time, money, and energy. In this study, pneumococcal surface protein A (PspA), one of the major virulence factors of SPN, is used to design a multi-epitope vaccine. For designing the vaccine, the sequence of PspA was retrieved, and then, phylogenetic analysis was performed. Several CTL epitopes, HTL epitopes, and LBL epitopes of PspA were all predicted by using several bioinformatics tools. After checking the antigenicity, allergenicity, and toxicity scores, the best epitopes were selected for the vaccine construction, and then, physicochemical and immunological properties were analyzed. Subsequently, vaccine 3D structure prediction, refinement, and validation were performed. Molecular docking, molecular dynamic simulation, and immune simulation were performed to ensure the binding between HLA and TLR4. Finally, codon adaptation and in silico cloning were performed to transfer into a suitable vector. The constructed multi-epitope vaccine showed a strong binding affinity with the receptor molecule TLR4. Analysis of molecular dynamic simulation, C-immune simulation, codon adaptation, and in silico cloning validated that our designed vaccine is a suitable candidate against SPN. The in silico analysis has proven the vaccine as an alternative medication to combat against S. pneumoniae. The designated vaccine can be further tested in the wet lab, and a novel vaccine can be developed.