Interrater Reliability in Analysis of Laryngoscopic Features for Unilateral Vocal Fold Paresis.
The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. In particular, laryngoscopy examination may result in significant disagreement in diagnosis among providers. We hypothesize that systematically evaluating for a standard set of clinical parameters will increase the diagnostic concordance among providers. Prospective case series conducted at a Tertiary referral Laryngology office. Two laryngologists (rater 1) and two trainees (rater 2) rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyogram. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A kappa coefficient was calculated for agreement in laryngoscopy findings and effectiveness in predicting the laterality of paresis. A substantial agreement (kappa coefficient > 0.61) existed between the raters for vocal fold length, vocal fold thickness, bowing, and reduction in movement. A moderate agreement (kappa coefficient > 0.41) existed between raters for piriform opening and reduced kinesis. The senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78, whereas the trainees correctly predicted the side of paresis in 63.1% for a kappa coefficient of 0.35. The raters agreed on the diagnosis in 73.7% of cases for a kappa coefficient of 0.50. Using a standard set of laryngoscopy findings may improve the provider's ability to identify the laterality of vocal fold paresis and increase interrater reliability compared with other series.


The structure of the linkage region of bovine nasal cartilage proteoglycan after beta-elimination and sulfite addition.
A method of peptide "fingerprinting" has been developed allowing the separation of the majority of the tryptic peptides of purified proteoglycan subunit from bovine nasal cartilage. When this preparation was reacted with 0.2 M sodium sulfite at pH 11.5, beta-elimination of the substituted glycosaminoglycans and O-linked oligosaccharides and the quantitative addition of sulfite occurred in the serine and threonine residues of the linkage region. After elimination-addition studies with sodium [35S] sulfite, 6 radiolabelled linkage peptides were isolated by 2-dimensional "fingerprinting." Five of these peptides were derived from a section of the protein core in which each [35S] cysteic acid residue was separated by an average of 6-10 amino acid residues. Apart from [35S] cysteic acid, the predominant amino acids in the attached peptides were glycine and glutamic acid (or glutamine), suggesting that a combination of these amino acids in the nascent protein core may be important for the initiation of glycosaminoglycan chains during proteoglycan biosynthesis.


Draft Genome Sequence of Streptomyces specialis Type Strain GW41-1564 (DSM 41924).
Here, we report the draft genome sequence of Streptomyces specialis type strain GW41-1564, which was isolated from soil. This 5.87-Mb genome exhibits a high G+C content of 72.72% and contains 5,486 protein-coding genes.


Immunoaffinity fractionation of Schistosoma mansoni worm antigens using human antibodies and its application for serodiagnosis.
A crude Schistosoma mansoni soluble worm antigen preparation (SWAP) was fractionated using an immunoaffinity column consisting of specific human anti-SWAP antibodies obtained from chronic S. mansoni-infected human sera and bound to CNBr-activated Sepharose 4B. The chromatographic separation resulted in three fractions: the unbound material (FW), and the eluted antigens with glycine-HCl (F1) and glycine-HCl-NaCl (F2). Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) showed that the purified antigens F1 and F2 consisted of several bands when stained with Coomassie blue and silver stain, with molecular weights between 20 X 10(3) and 200 X 10(3). The F1 and F2 fractions in addition to FW and SWAP were used in an enzyme-linked immunosorbent assay (ELISA) to measure antibody levels in sera from schistosomiasis patients. Each individual serum assessed with the purified F2 antigen gave 100% positivity and three to four times higher optical density in comparison to SWAP with only 88% positivity. No detectable cross-reactive antibodies against F2 were found when a limited number of sera from filariasis, fascioliasis and trichinellosis patients were screened. Furthermore, F2 was also used and found to be more sensitive generally in detecting anti-adult worm antibodies than SWAP in recently schistosomiasis-infected persons. Thus, F2 appears to be a highly sensitive and specific reagent for the serodiagnosis of schistosomiasis infection.


Preservative effects of some selected spice oleoresins to stabilize the sunflower oil in comparison to tertiary butylhydroquinone.
DPPH (1, 1-Diphenyl-2-Picrylhydrazyl) radical scavenging activity was performed to find out the antioxidant activity (AA) of all the antioxidants used at a concentration of 5, 10, and 15 μl/ml. Effect of spice oleoresins (clove, black pepper, and ginger) (200 ppm) and TBHQ (200 ppm) were incorporated in stabilizing refined, bleached, and deodorized (RBD) sunflower oil heating at frying temperature (170°C) and during accelerated oxidation storage (70°C) was studied in comparison to Tert-Butylhydroquinone (TBHQ). Antioxidant activity (AA) was found to be in the order TBHQ > clove > ginger > pepper at a concentration of 5; 10; 15 μl/ml. A direct correlation was found between AA and the effectiveness of oleoresins and TBHQ in controlling AV and PV of the sunflower oil. During both heating and storage, TBHQ was found most effective to control AV and PV followed by clove, pepper, and ginger.


[Evaluation of efficacy of immunosuppressive therapy plus recombinant human thrombopoietin for children with severe aplastic anemia].
Objective: To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients. Method: A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed. Among them, 15 patients were treated with the regimen of IST together with rhTPO and 30 patients were given IST treatment only. The variation characteristics of the peripheral blood routine as well as the transfusion of blood products was dynamically observed, and the therapeutic efficacy was assessed respectively after 3, 6 and 12 months after the treatment. In the meantime, adverse effects related to rhTPO application were recorded. Thereafter, the statistics of the two groups were compared by non-parametric rank sum test. Result: Among 45 pediatric patients, there were 26 male and 19 female, and the median age was 11 years (6-14). The number of patients received good hematological response(complete remission (CR) plus good partial response (GPR)) in the combinatory group versus vs. the IST group was 6 vs. 3 patients (χ(2)=3.906, P=0.048) at the 3rd month, 7 vs. 7 patients (χ(2)=1.568, P=0.210) at the 6th month, and 13 vs. 14 patients (χ(2)=6.667, P=0.01) at the 12th month respectively. For those achieved good hematological response at the 3rd month, the amount of platelets transfusion and red blood cells transfusion of the combined group were both less than that of the IST group during the period from the 10th to the 12th weeks (platelets transfusion: 1.4 U vs. 2.9 U, t=-3.523, P=0.002; red blood cells transfusion: 0.8 U vs. 2.6 U, t=-2.392, P=0.026). No serious adverse effect related to rhTPO application was observed in the IST combined with rhTPO group. Conclusion: Application of rhTPO can improve the short-term therapeutic efficacy of IST for pediatric SAA, alleviate transfusion dependence, and has a good safety profile.


Plasma microRNA signature is associated with risk stratification in prostate cancer patients.
The aim of this study was to establish a unique expression profile of circulating cell-free microRNAs (miRNAs) capable of differentiating between prostate cancer (PCa) patients with high-risk and intermediate-risk Gleason scores. MiRNA expression profiles were determined in plasma samples from 79 treatment-naïve PCa patients, 1-2 follow-up samples after radical prostatectomy (RP) from 51 out of the 79 PCa patients, and 33 healthy men, using a quantitative real-time PCR-based array containing 48 selected miRNAs. We identified 27 up- and 2 downregulated plasma miRNAs in PCa patients compared with healthy men. Most of the upregulated miRNA levels were also associated with increasing PSA levels and Gleason scores. Particularly, the levels of miR-16 (p = 0.002), miR-148a (p = 0.006) and miR-195 (p = 0.006) significantly correlated with high-risk Gleason scores, whereby miR-148a (p = 0.003) was also significantly associated with increasing PSA values. The high miRNA levels before RP remained increased in the postsurgical plasma samples. Our findings show a network of deregulated plasma miRNAs. In particular, miR-16, miR-148a and miR-195 are involved in the regulation of the PI3K/Akt signaling pathway. These miRNAs may be promising therapeutic targets for high-risk PCa stratification.


In situ pinning in slipped capital femoral epiphysis: long-term follow-up studies.
Management of moderately displaced slipped capital femoral epiphysis (SCFE) is debated, mostly because of the risks related to open reduction on one hand, and subsequent evolution toward femoroacetabular impingement (FAI) on the other. All SCFE cases treated with in situ fixation (ISF) and a minimum of ten years of follow-up beyond skeletal maturity were analysed in a retrospective multicentre study. Coxometry parameters were measured. Long-term results of ISF were meanwhile analysed at our Institution. A total of 222 patients were included. Patient reported outcome measurements were related to the severity of the initial slip. It suggested a 35.5° threshold for slip angle beyond which FAI was more frequent. Only slight remodelling at the head-neck junction is to be expected. Based on these findings, it seems reasonable to perform ISF only in SCFE with a slip angle below 35°.


Screening of the Filamin C Gene in a Large Cohort of Hypertrophic Cardiomyopathy Patients.
Recent exome sequencing studies identified filamin C (FLNC) as a candidate gene for hypertrophic cardiomyopathy (HCM). Our aim was to determine the rate of FLNC candidate variants in a large cohort of HCM patients who were also sequenced for the main sarcomere genes. A total of 448 HCM patients were next generation-sequenced (semiconductor chip technology) for the MYH7, MYBPC3, TNNT2, TNNI3, ACTC1, TNNC1, MYL2, MYL3, TPM1, and FLNC genes. We also sequenced 450 healthy controls from the same population. Based on the reported population frequencies, bioinformatic criteria, and familial segregation, we identified 20 FLNC candidate variants (13 new; 1 nonsense; and 19 missense) in 22 patients. Compared with the patients, only 1 of the control's missense variants was nonreported (P=0.007; Fisher exact probability test). Based on the familial segregation and the reported functional studies, 6 of the candidate variants (in 7 patients) were finally classified as likely pathogenic, 10 as variants of uncertain significance, and 4 as likely benign. We provide a compelling evidence of the involvement of FLNC in the development of HCM. Most of the FLNC variants were associated with mild forms of HCM and a reduced penetrance, with few affected in the families to confirm the segregation. Our work, together with others who found FLNC variants among patients with dilated and restrictive cardiomyopathies, pointed to this gene as an important cause of structural cardiomyopathies.


Low prevalence of P. falciparum in-vivo resistance to chloroquine in northern Cameroon in 1986.
The response to chloroquine of 49 Plasmodium falciparum isolates from the Northern dry areas of Cameroon was assessed by 7 day in-vivo assays. Twenty seven patients were treated with the standard 25 mg/kg dose, and 22 received a reduced, but frequently used, 10 mg/kg dose. The results of these in vivo assays are in agreement with in-vitro data showing a low prevalence and a low degree of chloroquine resistance. In contrast with P. falciparum isolates from Southern Cameroon, no case of RII or RIII resistance was detected in the North. Clearance of parasite was delayed in 4 of the 22 patients treated with 10 mg/kg, and for one of them parasites remained up to day 7 despite subnormal but appropriate chloroquine blood concentrations.


Awareness and practice of dual contraception among female tertiary institution students in Ibadan, Nigeria.
To determine the knowledge, awareness, and factors associated with the practice of dual contraception among female undergraduates in Ibadan, Nigeria. This is a cross-sectional study using a semi-structured self-administered questionnaire to assess the knowledge and practice of dual contraception among female undergraduates in the University of Ibadan and The Polytechnic, Ibadan. A total of 1,200 undergraduate students were interviewed, and data obtained were analyzed with SPSS Version 18.0. The mean age of the respondents was 22.57±3.43 years. Among the respondents, 900 (84.6%) were unmarried, 871 (77.9%) have been sexually exposed, 793 (70.9%) had heard of dual contraception, and 659 (58.9%) had knowledge of dual contraception. Majority (66.8%) of the participants used effective contraception, of whom 423 (56.3%) used condom, while others used other short- or long-term reversible contraception. More than two-thirds (79.2%) of the sexually exposed respondents were aware of dual contraception, but only 465 (41.6%) had practiced it. The main sources of information about dual contraception were from friends and radio (45.3% and 36.1%, respectively). Those who had multiple sexual partners and early coitarche were more likely to use dual contraception (P<0.05). History of previous sexually transmitted infection (odds ratio =3.06, 95% confidence interval [CI] =2.03-4.62) and unwanted pregnancy (odds ratio =3.53, 95% CI =2.62-4.74) were strongly associated with the use of dual contraception. Uptake of dual contraception among the students was low. Efforts need to be concentrated on determining and addressing the challenges that are responsible for the lower uptake of dual contraception among female undergraduates who are at higher risk of unwanted pregnancy and sexually transmitted infections. Promotion of consistent use of dual contraception is pertinent in maximizing the benefits of dual contraception in our environment.


Behavioral treatment of dizziness secondary to benign positional vertigo following head trauma.
Benign positional vertigo (BPV) represents a challenge to rehabilitation due to the subjective nature of the complaint of dizziness, frequent failure of pharmacologic intervention, and complicating psychologic factors. Behavioral therapy was used to treat a 26-year-old woman who complained of debilitating dizzy spells after mild head injury sustained in a motor vehicle accident. During a three-week baseline period before treatment, the patient reported a weekly average of 48 dizzy spells, which prevented participation in independent activities and kept her homebound and psychologically distressed. Nine-week behavioral treatment included biofeedback-assisted relaxation training, psychologic counseling, gaze-fixation practice, desensitization exercise, and generalization training. This protocol has been used successfully to train aviators to combat vertigo and nausea in flight. Our regimen included hourly recording of physical activity, notation of frequency of dizzy spells, and use of behavioral methods during nine weeks. The patient reported 90% reduction in dizzy spells and full resumption of independent activities including driving and athletics. Results are discussed in the context of behavioral problems associated with BPV and application of behavioral methods to the complaint of dizziness.


Greenlandic patients with colorectal cancer: symptomatology, primary investigations and differences in diagnostic intervals between Nuuk and the rest of the country.
Colorectal cancer (CRC) is a potentially fatal disease, and expedited referral and treatment is needed to ensure early detection. We aimed to assess the symptomatology of Greenlandic patients with CRC and the primary investigations initiated before referral to Dronning Ingrids Hospital in Nuuk for further diagnostic workup. Primary care interval (first consultation until referral), hospital interval (referral until diagnosis) and diagnostic interval (first consultation until diagnosis) were calculated and compared between patients living in Nuuk and in other places in Greenland ("the Coast"). This was a retrospective, register-based study of all patients in Greenland diagnosed with CRC from 2008 through 2011. Medical history was obtained and investigated by reviewing the primary care charts. In total 113 patients were identified from the Greenlandic cancer database or pathology reports. About 80% of the patients were asked about blood in the stools and changes of bowel habits, and the majority responded positively to this. Abdominal examination was performed for 78%, 65% had a rectal examination performed, 22% a proctoscopy performed and 51% a haemoglobin level measured. The median primary care interval was 4 days in Nuuk vs. 55 days for patients from "the Coast" (p=0.01); the median diagnostic interval was 55 days in Nuuk vs. 95 days for patients from "the Coast" (p=0.04). Median hospital interval was similar for both groups (23 days vs 24 days; p=0.86). Women had a median primary care interval of 70 days vs. 15 days for men (p=0.06). Patients with CRC presented classic symptomatology of CRC. Primary care interval and diagnostic interval were significantly longer for patients from "the Coast" compared with Nuuk. Women tended to have longer primary care interval. A more standardised examination should be implemented and a national CRC screening programme should be considered to reduce the difference in diagnostic interval and ensure timely referral.


Health professional's social representation about ederly subject with mental health disorders: a pilot study on 790 health professionals.
The objective of the present study was to identify the structure and content of the Social Representation (SR) of health professionals regarding elderly subjects with mental health disorders and compare the latter to the lay Social Representation identified in the literature. The structure and content of the SR of health professionals was examined in 790 careproviders from the 'Grand Est' region of France through the use of the free and hierarchical associations methodology of Abric and Vergés. A prototypical and categorical analysis as well as a similarity analysis and factorial correspondence analysis were applied to the results. Analysis of the collated data revealed that the items 'chronic', 'dependent', 'behavior disorders', 'memory disorders', 'solitude' and 'social isolation' were the characteristic components of the central core of the social representation. Only the peripheral elements were more sensitive to the field of practice of each profession. These findings thus highlight that the SR of health professionals is substantially identical to that of the all-comer SR on several dimensions.


Acidification induces condensation of the adenovirus core.
The adenovirus (AdV) icosahedral capsid encloses a nucleoprotein core formed by the dsDNA genome bound to numerous copies of virus-encoded, positively charged proteins. For an efficient delivery of its genome, AdV must undergo a cascade of dismantling events from the plasma membrane to the nuclear pore. Throughout this uncoating process, the virion moves across potentially disruptive environments whose influence in particle stability is poorly understood. In this work we analyze the effect of acidic conditions on AdV particles by exploring their mechanical properties, genome accessibility and capsid disruption. Our results show that under short term acidification the AdV virion becomes softer and its genome less accessible to an intercalating dye, even in the presence of capsid openings. The AFM tip penetrates deeper in virions at neutral pH, and mechanical properties of genome-less particles are not altered upon acidification. Altogether, these results indicate that the main effect of acidification is the compaction of the nucleoproteic core, revealing a previously unknown role for chemical cues in AdV uncoating. STATEMENT OF SIGNIFICANCE: Studying the behavior of virus particles under changing environmental conditions is key to understand cell entry and propagation. One such change is the acidification undergone in certain cell compartments, which is thought to play a role in the programmed uncoating of virus genomes. Mild acidification in the early endosome has been proposed as a trigger signal for human AdV uncoating. However, the actual effect of low pH in AdV stability and entry is not well defined. Understanding the consequences of acidification in AdV structure and stability is also relevant to define storage conditions for therapeutic vectors, or design AdV variants resistant to intestinal conditions for oral administration of vaccines.


The relationship between smoking and convivial, intimate and negative coping alcohol consumption in young adults.
To explore the gender-specific associations of smoking with convivial, negative coping and intimate drinking contexts in young adults. Alcohol and cigarettes co-use is common and to be more effective in prevention activities, we need to understand the drinking contexts that facilitate their co-occurrence. Descriptive cross-sectional survey in the context of the LATO study (Lifestyle & Attitudes in a Student Population) in Greece. Of the 1,138 students who provided full data during November-December 2012, those who have smoked ≥1 cigarette/last month were defined as smokers. Based on the "Drinking Context Scale-9", we created low, moderate and high probabilities of drinking in each context and in total. Multivariate logistic regression analyses were performed. Participants reported higher probabilities to drink, in descending order, in the convivial (31.5%), negative coping (10.4%) and intimate (5.4%) contexts. Adjusted odds ratios for smoking were significantly higher for individuals who reported a moderate (OR = 2.15, 95% CI 1.51-3.05) to high (OR = 3.64, 95% CI 2.59-5.11) probability of drinking in any context. Moreover, female participants with high probabilities for drinking in convivial and negative coping contexts had higher odds ratios of engaging in smoking (convivial OR = 1.87, 95% CI = 1.23-2.85; coping OR = 2.66, 95% CI = 1.39-5.10) whereas this association was noticed only for convivial settings in male participants (OR = 2.88, 95% CI = 1.91-4.319). For women only, drinking in intimate contexts was protective against smoking (OR = 0.32, 95% CI = 0.10-0.98). Smoking is differentially related to drinking context based on gender. Prevention interventions targeting smoking and alcohol co-use in late adolescence may be more effective if employing a context and gender-specific approach. Nurses have a critical role in providing motivational interviewing in individuals and organise and execute health-promoting activities in larger groups for modifying their health risk behaviours. The social context should be carefully considered during assessments and prevention interventions.


Synthetic Data as a Strategy to Resolve Data Privacy and Confidentiality Concerns in the Sport Sciences: Practical Examples and an R Shiny Application.
There has been a proliferation in technologies in the sport performance environment that collect increasingly larger quantities of athlete data. These data have the potential to be personal, sensitive, and revealing and raise privacy and confidentiality concerns. A solution may be the use of synthetic data, which mimic the properties of the original data. The aim of this study was to provide examples of synthetic data generation to demonstrate its practical use and to deploy a freely available web-based R Shiny application to generate synthetic data. Openly available data from 2 previously published studies were obtained, representing typical data sets of (1) field- and gym-based team-sport external and internal load during a preseason period (n = 28) and (2) performance and subjective changes from before to after the posttraining intervention (n = 22). Synthetic data were generated using the synthpop package in R Studio software, and comparisons between the original and synthetic data sets were made through Welch t tests and the distributional similarity standardized propensity mean squared error statistic. There were no significant differences between the original and more synthetic data sets across all variables examined in both data sets (P > .05). Further, there was distributional similarity (ie, low standardized propensity mean squared error) between the original observed and synthetic data sets. These findings highlight the potential use of synthetic data as a practical solution to privacy and confidentiality issues. Synthetic data can unlock previously inaccessible data sets for exploratory analysis and facilitate multiteam or multicenter collaborations. Interested sport scientists, practitioners, and researchers should consider utilizing the shiny web application (SYNTHETIC DATA-available at https://assetlab.shinyapps.io/SyntheticData/).


Cross-frequency coherence and pulse propagation in a turbulent atmosphere.
Cross-frequency coherence of acoustic signals in a turbulent atmosphere is an important consideration for source localization with acoustic sensor arrays and for remote sensing of the atmosphere with sodars and tomography techniques. This paper takes as a starting point recently derived, closed-form equations for the spatial-temporal correlation function of a broadband acoustic signal propagating in a turbulent atmosphere with coupled spatial-temporal fluctuations in temperature and wind velocity. This theory is employed to calculate, based on the Rytov approximation, the two-point, two-time, two-frequency mutual coherence function of plane and spherical waves in the weak scattering regime. The cross-frequency coherence for these waveforms is then obtained and compared with that in the geometrical acoustics approximation. The coherence bandwidth is calculated and analyzed for typical meteorological regimes of the atmospheric surface layer and parameters of sound propagation. The results obtained are compared with available experimental data. The cross-frequency coherence is also used to study the effect of atmospheric turbulence on the mean intensity of an acoustic pulse propagating in a turbulent atmosphere.


Confirmation of EMIT cannabinoid assay results by bonded phase adsorption with thin layer chromatography.
Clinical urine specimens were screened for the presence of cannabinoids using the EMIT Cannabinoid Assay. Aliquots of these samples were also analyzed for 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THCA), the major cannabis metabolite in urine, by a technique which combines bonded phase adsorption (BPA) and thin layer chromatography (TLC). A 100% agreement between EMIT and BPA-TLC results was observed when at least 20 mL of urine was assayed by BPA-TLC. Bonded phase adsorption coupled with thin layer chromatography appears to be a suitable technique for the confirmation of positive EMIT Cannabinoid Assay results.


Breast Milk Is a Potential Reservoir for Livestock-Associated Staphylococcus aureus and Community-Associated Staphylococcus aureus in Shanghai, China.
Breast milk is the first choice in feeding newborn infants and provides multiple benefits for their growth and development. Staphylococcus aureus usually exists in breast milk and is considered one of the most important causative infective agents. To be effective in preventing and controlling S. aureus infections among infants, the aim of this study was to determine the occurrence and molecular characteristics of S. aureus isolated from 1102 samples of breast milk between 2015 and 2016 in Shanghai, China. Out of 71 S. aureus strains isolated, 15 (21.1%, 15/71) were MRSA and all the strains were characterized by spa typing, Multi-Locus Sequence Typing, SCCmec typing, antibiotic resistance testing and virulence-associated genes. A total of 18 distinct sequence types (STs) and 36 spa types were identified within the 71 isolates, among which the most frequently represented was ST398 (19.7%, 14/71), followed by ST7 (18.3%, 13/71), ST59 (16.9%, 12/71). The three predominant STs accounted for more than one half of all S. aureus isolates. The most prevalent spa types were t091 (12.7%, 9/71), followed by t571 (8.5%, 6/71), t189 (7.0%, 5/71), t034 (5.6%, 4/71), t437 (5.6%, 4/71), and t701 (4.2%, 3/71). All MRSA isolates belonged to SCCmec IV and V, accounting for 66.7 and 33.3% respectively. Notably, 23 (32.4%) S. aureus strains were multidrug resistance (MDR), including 4 (5.6%) MRSA and 19 (26.8%) MSSA strains, and MDR isolates were mostly resistant to penicillin, erythromycin and clindamycin. All isolates exhibited simultaneous carriage of at least 5 of 33 possible virulence genes and the most prevalent genes detected were icaA (100%), clfA (100%), hla (100%), sdrC (94.4%), hlg2 (88.7%), lukE (57.8%). 39 (54.9%, 39/71) isolates, including 9 (12.7%) of MRSA isolates, harbored ≥10 tested virulence genes evaluated in this study. The pvl gene was detected in 8 strains, which represented 5 different STs, with ST59 being the most one. Overall, our findings showed that S. aureus strains isolated from breast milk were mainly MSSA (78.9%, 56/71) and exhibited high genetic diversity in Shanghai area of China. Breast milk was a reservoir for LA-SA (ST398) and CA-SA (ST59), which was likely a vehicle for transmission of multidrug-resistant S. aureus and MRSA lineages. This is a potential public health risk and highlights the need for good hygiene practices to reduce the risk of infant infections.


Pubic osteomyelitis after surgery for perforated colonic diverticulitis with fecal peritonitis: A case report.
Pubic osteomyelitis is a rare type of suppurative osteomyelitis. Early diagnosis of pubic osteomyelitis is difficult, and prolonged inflammation results in progressive bone degradation, severe pelvic pain and a wide-based gait. We report the case of an 82-year-old woman who was admitted to a previous hospital with severe abdominal pain caused by a perforated colonic diverticulum with fecal peritonitis. She underwent an emergency operation and a postoperative wound infection occurred. Despite treatment of the infection, purulent exudate was discharged for three months and she gradually showed a gait disturbance. CT and MRI revealed that pubic symphysis showed osteolysis and there was severe inflammation around the wound. After administration of appropriate antibiotics, an operation, which included the removal of a fistula, debridement of sequestra and lavage of the abscess cavity, was performed. The inflammation improved promptly after the operation, and the patient was discharged on postoperative day 27 without any complications. Pubic osteomyelitis does not show the findings of typical acute suppurative osteomyelitis and hematological findings are nonspecific. It is important for early diagnosis to consider the risk factors of pubic osteomyelitis during examination. We would emphasize that a definitive diagnosis by CT and MRI and appropriate antimicrobial therapy combined with surgical treatment are important for pubic osteomyelitis.


[Regulatory Framework for Approval of PET Drug in Korea: A Survey Report].
To identify regulatory framework for approval of PET drugs in Korea. Interview and literature survey. In Korea Good Manufacturing Practice (GMP) regulation specific to radiopharmaceuticals, including PET (Positron Emission Tomography) drugs, under the Pharmaceutical Affairs Act was issued in August 2014, to be enforced on July 1, 2015, and its guidance was issued in December 2014. The new facilities to be established after July 1 of 2015 have to be compatible with this new regulation and already established facilities have two years grace period until June 30 of 2017. During this period, the regulatory authority will inspect all of the production sites which hold or submit approvals of radiopharmaceuticals. As of September 2015 in Korea, there are 7 commercial companies and 15 hospitals and institutes, which have approvals of PET drugs mainly FDG, and these companies and/or hospitals can supply PET drugs outside institutions. In this article we introduce the Korean regulations of development and approval of radiopharmaceuticals. The Korean regulatory authorization policy for radiopharmaceuticals are to some extent similar to the policy which the U.S. regulators set as the new regulations of PET drug. It is expected that the situations of production sites in Korea are to be improved through actual discussions among regulators and PET community through the process of actual inspection.


Prenatal PCB exposure, the corpus callosum, and response inhibition.
The present study reports the association between prenatal exposure to polychlorinated biphenyls (PCBs), the corpus callosum, and response inhibition in children who are 4.5 years old. Children (n = 189) enrolled in the Oswego study were tested using a continuous performance test. We measured (square millimeters) the splenium of the corpus callosum, a pathway implicated in the regulation of response inhibition, using magnetic resonance imaging. Results indicated a dose-dependent association between cord blood PCBs and errors of commission. Splenium size but not other brain areas predicted errors of commission (r(2) = 0.20), with smaller size associated with more errors of commission. There was an interaction between splenium size and PCB exposure. The smaller the splenium, the larger the association between PCBs and errors of commission. If the association between PCBs and response inhibition is indeed causal, then children with suboptimal development of the splenium are particularly vulnerable to these effects. These data await replication.


Effects of metoprolol and propranolol on glucose tolerance and insulin secretion in diabetes mellitus.
Twenty-two hypertensive diabetic patients were admitted to a double-blind, within-patient study, and treated with propranolol 80 mg and metoprolol 100 mg twice daily for 4 weeks according to a cross-over design. Dosages of the two drugs such as to induce comparable cardiovascular effects, did not induce relevant changes of fasting blood glucose levels in patients receiving the oral hypoglycaemic agent glibenclamide (group 1), insulin (group 2) or diet alone (group 3). Glucose tolerance, assessed with a 75 g oral load, was however decreased by propranolol, and not by metoprolol in the glibenclamide-treated group. Glucose-induced insulin secretion was reduced by propranolol and not by metoprolol both in the group treated by diet alone and in the glibenclamide-treated group. It is concluded that cardioselective metoprolol seems to be more suitable than the non-selective propranolol in the treatment of arterial hypertension in diabetic subjects, particularly when sulfonylureas are being used as hypoglycaemic agents.


Theory of mind in patients with temporal lobe epilepsy.
Theory of mind (ToM) is a crucial aspect of social cognition and is mediated by a complex neural network. Studies on temporal lobe epilepsy (TLE) suggest that its neuropathological involvement includes several brain regions. Some regions seem to overlap the neural network responsible for ToM, and this overlap provides an opportunity to explore ToM in TLE patients. Another concern is psychosocial problems in TLE, and the study of ToM in TLE could serve as a basis for further understanding the nature of such psychosocial disturbances. Studies on whether TLE patients evidence ToM deficit, however, are scant and controversial. Consequently, we examine whether ToM deficit is evident in TLE. Thirty-one TLE patients and 24 matched controls were recruited and completed four tasks measuring different levels of ToM: false belief, faux pas recognition, processing of implied meanings, and cartoon ToM. The patients were impaired in both basic and advanced ToM. Right TLE had a more wide-ranging picture of deficit than left TLE. ToM appears to be vulnerable to TLE, especially on the right side. Since ToM might contribute to patients' psychosocial adjustment, we thus suggest that a ToM measure be included in regular neuropsychological assessments of such patients.


Long-term cancer patient survival in the United States.
Although survival rates are useful for monitoring progress in the early detection and treatment of cancer and are of particular interest to patients with new diagnoses, there are limited population-based estimates of long-term survival rates. We used data collected by the Surveillance, Epidemiology, and End Results Program for cases diagnosed during 1974-1991 and followed through 1992 to estimate relative survival at 5, 10, and 15 years after diagnosis of cancer of the breast, prostate, colon and rectum, and lung. Relative survival after diagnosis of breast and prostate cancer continued to decline up through 15 years after diagnosis, whereas survival after diagnosis of lung and colon or rectal cancer remained approximately constant after 5 and 10 years, respectively. Age-specific patterns of survival varied by site, stage, and demographics. Among patients with localized breast and prostate cancer, women who were younger than age 45 at breast cancer diagnosis and men who were 75 years and older at prostate cancer diagnosis had the poorest relative survival. Relative survival among lung cancer patients decreased with age at diagnosis, regardless of stage or demographics, and age-specific patterns of relative survival for patients with cancer of the colon and rectum differed according to race. Among white patients diagnosed with cancers of the colon and rectum, relative survival did not vary by age at diagnosis; among black patients older than 45 at diagnosis, relative survival decreased with age. This study provides population-based estimates of long-term survival and confirms black/white, male/female, and stage- and age-specific differences for the major cancers.


Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of osteoporosis.
Osteoporosis is a common bone disorder where the declined bone mass is far more than normal physiological status and usually associated with enhanced fracture risk, reduced bone strength and even deteriorated quality of life. Recent studies showed that statins could exert beneficial effects on bones via promoting osteoblastic activity mediated by increased expression of bone morphogenetic protein 2 and also by suppressing osteoclast proliferation. In this study, we developed atorvastatin-loaded tetracycline-poly (ethylene glycol)-poly(lactic-co-glycolic acid) (TC-PEG-PLGA/ATO) micelles for the targeted treatment of osteoporosis. The TC-PEG-PLGA was synthesized under the action of coupling reagents and then ATO was encapsulated through solvent diffusion method with encapsulation efficiency and drug loading of 89.32 ± 2.48% and 8.20 ± 0.53%, respectively. The release of ATO from micelles could be maintained for more than 48 h in pH 7.4 PBS. Pharmacokinetic results further demonstrated that TC-PEG-PLGA micelles could effectively shield ATO leakage from micelles and prolong their circulation time. Benefiting from TC specifically binding to hydroxyapatite (HAp), TC-PEG-PLGA/ATO micelles exerted good bone-targeted ability, as demonstrated by in vitro HAp affinity assay and biodistribution. Pharmacodynamic studies showed that TC-PEG-PLGA/ATO micelles could effectively improve bone mineral density and bone mechanical strength in osteoporotic rats. These results suggest that TC-PEG-PLGA/ATO micelles hold significant promise for the targeted treatment of osteoporosis.


[Anaerobic infection and its effect on the immune status of patients with acute destruction of the lungs].
From studying immunological reactivity in dynamics in 107 patients with acute destructions of the lungs, the authors proved that the severity and duration of the disorders are determined to a great extent by the presence of anaerobic infection in a pure form (18 patients) or in association with aerobic microflora (23 patients).


Implementation of a liquid chromatography tandem mass spectrometry assay for eight adrenal C-21 steroids and pediatric reference data.
Sensitive and accurate determination of steroids is essential for diagnosing congenital and acquired adrenal diseases. Since plasma concentrations change during childhood, age-specific reference ranges are the prerequisite for clinical interpretation. The objectives of this study were to develop a sensitive and reliable method for simultaneous detection and quantification of progesterone, 17-hydroxyprogesterone, deoxycorticosterone (DOC), 11-deoxycortisol, 21-deoxycortisol, corticosterone, cortisol (F) and cortisone (E) by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and to establish age- and sex-specific reference ranges from birth to adulthood. All eight steroids were measured simultaneously in 0.1 ml plasma by UPLC-MS/MS. Samples of 905 children were measured and grouped in five age groups. The assay was linear up to 70 ng/ml (700 ng/ml for F; r(2) > 0.992). The limit of detection ranged between 0.01 ng/ml for DOC and 0.07 ng/ml for E. Correlations with radioimmunoassays yielded a coefficient of determination between 0.82 and 0.99. Reference data are reported as a function of age and sex. The UPLC-MS/MS method presented here for the simultaneous detection of eight C-21 adrenal hormones together with the detailed reference ranges for children provides a valuable methodology for assessing adrenal steroids in clinical routine and research.


Experimental spinal cord repair (by means of direct connection of the above-the-lesion CNS with PNS).
There are no medical or surgical treatments able to repair traumatic paraplegia. Experiments done by connecting the above-the-lesion with the below-the-lesion cord by means of PNS grafts have always failed. The grafts are reinhabited by regrowing axons of the first motoneurons which however are not able to progress into the distal spinal cord. At the present state of knowledge no surgical treatment can cure paraplegia. Thousands of researchers are working all over the world in many different types of research ranging from molecular biology to embriology, and from biochemistry to pharmacology and surgery. None of these experiments have proved to be practically effective.


A field test of simple dispersal models as predictors of movement in a cohort of lake-dwelling brook charr.
1. Dispersal can be a major determinant of the distribution and abundance of animals, as well as a key mechanism linking behaviour to population dynamics, but progress in understanding dispersal has been hampered by the lack of a general framework for modelling dispersal. 2. This study tested the capacity of simple models to summarize and predict the lake-wide dispersal of an emerging cohort of young-of-the-year brook charr Salvelinus fontinalis, over 12 surveys conducted during a 2-month period. 3. The models are based on two types of dispersal kernel, the normal distribution from a simple diffusion process, and a Laplace distribution depicting exponential decay of the frequency of dispersers away from the point of origin. In all, four models were assessed: one-group diffusion (D1S) and exponential (E1S) models assuming homogeneous dispersal behaviour within the cohort, and two-group diffusion (D2S) and exponential (E2S) models accounting for intrapopulation differences in dispersal between sedentary and mobile individuals. 4. A rigorous cross-validation, based on calibrating the models to the distributions from the first two surveys only and then validating them on the remaining 10 distributions, was used to compare model predictions with observed values for five properties of the dispersal distributions: counts in individual shoreline sections; mean lateral displacement, variance and kurtosis of displacements; and the percentage of long-distance dispersers. 5. Substantial intrapopulation heterogeneity in dispersal behaviour was apparent: 83% of all individuals were estimated to be sedentary and the remainder mobile. Remarkably, the two-group exponential model E2S - calibrated to data from only two surveys conducted 3.5 and 8.5 days after the beginning of emergence - predicted reasonably well all properties of the spatial distribution of the cohort until the end of the study, 7 weeks later. 6. Standardized measures of mobility derived from simple models may lead to better understanding of population dynamics and improved management. Specifically, the ability to accurately predict long-distance dispersal may be critical to assessing population persistence and cohort strength whenever key habitats, such as refugia or productive areas supporting a large proportion of the cohort, are sparsely distributed or distant from the point of origin.


[Diagnosis and prognosis of neonatal cerebral infarction].
To analyze the relationship between clinical characteristics and prognosis of neonatal cerebral infarction and to draw attention to the disease to improve the long-term outcome through early diagnosis and intervention. The clinical characteristics of 6 confirmed cases were summarized. Perinatal conditions and other factors were analyzed for possible causes of the disease. The survived patients were followed-up for 6-8 months. The authors diagnosed 6 cases of neonatal cerebral infarction in one year, which accounted for 0.6% (6/969) of all the in-patients in the same time period. Among them 3 cases were confirmed as cerebrovascular malformations by magnetic resonance angiography (MRA), In 1 case the infarction was due to severe bilateral intraventricular hemorrhage, and in another case the disease was related to comprehensive factors such as prematurity, maternal pregnancy induced hypertension and respiratory failure secondary to bronchopulmonary dysplasia (BPD), and in 1 case the cause was undetermined. Four out of the 6 patients presented with varied forms of convulsions, which became the second leading cause for all the neonatal convulsive events (20%). None of the patients had localized neurological signs in the early course except for abnormal muscular tone of some extent. Cerebral ultrasound scanning in 5 out of 6 cases showed positive results. The diffusion-weighted magnetic resonance imaging (DW-MRI) was highly valuable for early confirmative diagnosis. Only one case was found normal within one year of follow-up and all the other 5 cases had unfavorable prognoses of varied severity. Neonatal cerebral infarction is not a rare condition and should be considered as one of the important causes for neonatal convulsion. Imaging study is the main technique for diagnosis. The prognoses were poor for those cases for whom early diagnosis and treatment can not be made or those with widespread cerebral lesions.


Gene therapy for liver disease.
With major advances in biomedical science over the last 2 decades, the possibility of treating human disease at a genetic level has become a tantalizing possibility. As a result, a growing number of investigators are focusing on the development of techniques to deliver therapeutic genes into cells. The liver has been a model organ in the development of this gene transfer technology. This review focuses on the attributes and limitations of the current gene delivery systems that have been explored in the context of liver disease and highlights the obstacles that must be addressed before hepatic gene therapy becomes a clinical reality.


Anchoring effects on early autobiographical memories.
Studies of childhood memory typically show that our earliest memories come from between three and four years of age. This finding is not universal, however. The age estimate varies across cultures and is affected by social influences. Research from the judgments and decision-making literature suggests that these estimates might also involve a judgment under uncertainty. Therefore, they might be susceptible to less social influences such as heuristics and biases. To investigate this possibility, we conducted two experiments that used anchoring paradigms to influence participants' estimates of their age during early autobiographical memories. In Experiment 1, participants answered either a high-anchor or a low-anchor question, and were warned that the anchor was uninformative; they went on to estimate their age during their earliest autobiographical memory. In Experiment 2, we replicated Experiment 1 and extended the design to examine additional early autobiographical memories. In both experiments, participants in the low-anchor condition gave earlier age estimates than those in the high-anchor condition. These results provide new insights into the methods used to investigate autobiographical memory. Moreover, they show that reports of early autobiographical memories can be influenced by a relatively light touch - a change to a single digit in a single question.


Keratoacanthoma of the conjunctiva - case report and review of the literature.
Keratoacanthoma (KA) is a relatively common, benign, rapidly growing and self-limiting squamous proliferation, which appears most frequently on the sun-exposed skin. The nature of KA and its relationship to squamous cell carcinoma (SCC) still represent one of the major debates in dermatopathology, as it is the truthfulness of such a diagnosis outside the skin. However, the tumor is now known to originate from the pilosebaceous units of the skin or from ectopic sebaceous glands of squamous mucous membranes, and to differentiate onto follicular isthmus÷infundibulum-like epithelium. A 71-year-old man presented with a sore and red right eye, which on slit-lamp biomicroscopical examination revealed a dome-shaped lesion at the temporal inferior conjunctival limbus. After a thorough histopathological examination, a diagnosis of KA has been made, both after the initial tumor excision and after the relatively rapid recurrence. After the second intervention, no recurrence was observed over five years of follow-up, confirming the diagnosis. The peculiarity of the case stands in his exceptional rarity, being to our knowledge the first conjunctival KA reported in our country. In the light of current knowledge, the peculiar limbal location of all the conjunctival KAs reported in the literature raised the question of the possible role of limbal stem cells in the histogenesis of these tumors, similar to the pilosebaceous ones. The treatment of conjunctival KA remains the complete excision of the tumor, as it allows histopathological evaluation of the entire tumor and the exclusion of a KA-like SCCs or KAs with SCC component.


[Percutaneous biopsy (PB) of solid thoraco-abdominal formations with instrumental guidance. The authors' experience].
The results are reported of 283 percutaneous biopsies performed on solid thoracic and abdominal masses. Indications to biopsy are examined at first, which are relatively limited in number if compared to other authors' opinion on the subject--i.e., when the tumor cannot be characterized with any other methodology, or in case of neoplasms whose histological type is to be known in order to plan therapy. The techniques employed are then evaluated, with a special emphasis on the needle caliber and the guidance method (US, radioscopy and CT). Correct samplings have been obtained in more than 90% of cases. Minor complications were observed in less than 10% of cases, while major complications were totally absent. In conclusion, percutaneous biopsy proves useful in those cases where exam indication is respected and an accurate selection is previously performed.


Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor.
In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of a network of genes encoding erythropoietin, vascular endothelial growth factor, and several glycolytic enzymes. HIF-1 consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim) proteins, HIF-1alpha and Arnt. HIF-1alpha and Arnt mRNAs are constitutively expressed and were not altered upon exposure of HeLa or HepG2 cells to hypoxia, suggesting that the activity of the HIF-1alpha-Arnt complex may be regulated by some as yet unknown posttranscriptional mechanism. In support of this model, we demonstrate here that Arnt protein levels were not increased under conditions that induce an hypoxic response in HeLa and HepG2 cells. However, under identical conditions, HIF-1alpha protein levels were rapidly and dramatically up-regulated, as assessed by immunoblot analysis. In addition, HIF-1alpha acquired a new conformational state upon dimerization with Arnt, rendering HIF-1alpha more resistant to proteolytic digestion in vitro. Dimerization as such was not sufficient to elicit the conformational change in HIF-1alpha, since truncated forms of Arnt that are capable of dimerizing with HIF-1alpha did not induce this effect. Moreover, the high affinity DNA binding form of the HIF-1alpha-Arnt complex was only generated by forms of Arnt capable of eliciting the allosteric change in conformation. In conclusion, the combination of enhanced protein levels and allosteric change by dimerization defines a novel mechanism for modulation of transcription factor activity.


1,25-Dihydroxyvitamin D3 and its analog TX527 promote a stable regulatory T cell phenotype in T cells from type 1 diabetes patients.
The emergence of regulatory T cells (Tregs) as central mediators of peripheral tolerance in the immune system has led to an important area of clinical investigation to target these cells for the treatment of autoimmune diseases such as type 1 diabetes. We have demonstrated earlier that in vitro treatment of T cells from healthy individuals with TX527, a low-calcemic analog of bioactive vitamin D, can promote a CD4+ CD25high CD127low regulatory profile and imprint a migratory signature specific for homing to sites of inflammation. Towards clinical application of vitamin D-induced Tregs in autologous adoptive immunotherapy for type 1 diabetes, we show here that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and TX527 similarly imprint T cells from type 1 diabetes patients with a CD4+ CD25high CD127low regulatory profile, modulate surface expression of skin- and inflammation-homing receptors, and increase expression of CTLA-4 and OX-40. Also, 1,25(OH)2D3 and TX527 treatment inhibit the production of effector cytokines IFN-γ, IL-9, and IL-17. Importantly, 1,25(OH)2D3 and TX527 promote the induction of IL-10-producing CD4+ CD25high CD127low T cells with a stable phenotype and the functional capacity to suppress proliferation of autologous responder T cells in vitro. These findings warrant additional validation of vitamin D-induced Tregs in view of future autologous adoptive immunotherapy in type 1 diabetes.


Maternal influence on blood pressure suggests involvement of mitochondrial DNA in the pathogenesis of hypertension: the Framingham Heart Study.
To investigate the contribution of the mitochondrial genome to hypertension and quantitative blood pressure (BP) phenotypes in the Framingham Heart Study cohort, a randomly ascertained, community-based sample. Longitudinal BP values of 6421 participants (mean age, 53 years; 46% men) from 1593 extended families were used for analyses. In analyses of BP as a continuous trait, a variance components model with a variance component for maternal effects was used to estimate the mitochondrial heritability of the long-term average BP adjusted for age, sex, body mass index, and hypertension treatment. For analyses of BP as a categorical trait, a nonparametric test sensitive to excessive maternal inheritance was used to test for mitochondrial effect on long-term hypertension, defined as systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg or use of antihypertensive medication in one-half or more of qualifying examinations. This test was based on 353 pedigrees comprised of 403 individuals informative for mitochondrial DNA contribution. The estimated fraction of hypertensive pedigrees potentially due to mitochondrial effects was 35.2% (95% confidence interval, 27-43%, P < 10). The mitochondrial heritabilities for multivariable-adjusted long-term average systolic BP and diastolic BP were, respectively, 5% (P < 0.02) and 4% (P = 0.11). Our data provide support for a maternal effect on hypertension status and quantitative systolic BP, consistent with mitochondrial influence. Additional studies are warranted to identify mitochondrial DNA variant(s) affecting BP.


Current and Emerging Evidence for Toll-Like Receptor Activation in Sjögren's Syndrome.
While the importance of Toll-like receptor (TLR) signaling is well established in many autoimmune diseases, the role of TLR activation in Sjögren's syndrome (SS) is poorly understood. Studies in mice and humans reveal that TLRs are potent mediators of inflammation in SS. TLRs are expressed and functional in salivary tissue, and TLRs in peripheral blood cells of SS patients are also upregulated and hyperresponsive to ligation. In this review, we will detail observations in mouse models regarding the importance of TLR activation in both local and systemic disease. We will then discuss studies in SS patients that provide evidence of the importance of TLR-mediated signaling in disease. While the ligands that activate TLRs in the context of SS are unknown, emerging data suggest that damage-associated molecular patterns (DAMPs) may be significant drivers of the chronic and unremitting inflammation that is characteristic of SS. We will discuss putative DAMPs that may be of clinical significance in disease. Therapies that target TLR signaling cascades will likely reduce both exocrine-specific and systemic manifestations of SS.


Nuclear accumulation of the GATA factor AreA in response to complete nitrogen starvation by regulation of nuclear export.
Both the availability and the quality of nutrients affect cellular functions by controlling gene activity. AreA, a member of the GATA family of transcription factors, globally activates expression of genes involved in nitrogen source utilization in Aspergillus nidulans. The quality of the nitrogen source determines the level and activation capacity of AreA through controls at the level of areA mRNA stability and by interaction of AreA with the corepressor NmrA. The availability of potential nitrogen sources also affects the activation capacity of AreA. We show that the complete absence of a nitrogen source results in an enhanced level of AreA-dependent gene expression and that this response is independent of mechanisms regulating AreA activity in response to nitrogen source quality. During nitrogen starvation AreA accumulates in the nucleus, but the presence of a potential nitrogen source or carbon starvation prevents this accumulation. Furthermore, accumulated AreA is rapidly lost from the nuclei of nitrogen-starved cells when a nitrogen source is supplied or when a carbon source is absent, and this accompanies arrest of the AreA-dependent nitrogen starvation response on regulated gene expression. By the generation of a leptomycin B-sensitive mutant, we have been able to show that nuclear exit occurs via the CrmA exportin. We conclude that sensing mechanisms discriminate between starvation and the presence of potential nutrients that can signal to the AreA transcription factor. Nitrogen source availability, but not quality, affects nuclear accumulation by regulating nuclear exit of AreA, providing a rapid response to changes in the supply of nutrients.


Autophagy and redox status in carcinoma of an unknown primary.
The purpose of the study was to investigate the role and clinical implications of autophagy and reactive oxygen species-related proteins in carcinoma of an unknown primary (CUP). Tissue microarray was constructed for a total of 77 CUP cases. Immunohistochemical stains conducted were as follows: autophagy-related beclin-1, LC3A, LC3B, and p62; redox-related catalase, thioredoxin reductase, glutathione S-transferase π, thioredoxin-interacting protein, and manganese superoxide dismutase. Immunohistochemical results were then related to their clinicopathologic parameters. The degree of LC3A expression showed a difference according to histologic subtype. In undifferentiated carcinoma, LC3A had the highest expression and adenocarcinoma had the lowest expression (P = 0.021). According to clinical subtype, there was a significant difference between LC3A and glutathione S-transferase π in expression. LC3A had the highest expression in single-organ types and the lowest in intermediate and carcinomatosis types (P = 0.003). Glutathione S-transferase π showed the highest expression in nodal-type tumors and the lowest in carcinomatosis types (P = 0.010). In univariate analysis, shorter overall survival was related to tumor glutathione S-transferase π negativity (P = 0.030). Different expression levels of the autophagy and reactive oxygen species-related proteins, LC3A and glutathione S-transferase π, were observed according to histologic and/or clinical subtype of carcinoma of an unknown primary.


Temperature effects on development and fecundity of Brachmia macroscopa (Lepidoptera: Gelechiidae).
The current study investigated the impacts of temperature on the development and reproductivity of the sweet potato leaf folder, Brachmia macroscopa (Lepidoptera: Gelechiidae), in sweet potato leaves under laboratory conditions. We determined developmental time of B. macroscopa larval, pupal, and pre-adult stage at different temperatures. Male and female longevity, male and female lifespan, mortality of immature stages, oviposition period of B. macroscopa were also investigated under six constant temperatures (21°C, 24°C, 27°C, 30°C, 33°C, 36°C), based on age-stage, two-sex life tables. The results revealed that eggs in 36°C were unable to hatch. At temperatures between 21°C -33°C, the duration of the pre-adult period, as well as the adult lifespan both for males and females, were shortened by increasing temperatures. The lowest larval mortality rate (15.33%) occurred at 27°C. The age-stage-specific fecundity rates with the greatest number were, in order, 30°C, 27°C, 21°C, 24°C and 33°C. The results show that B. macroscopa population levels could reach highest at the temperature of 27℃.


Fe(II)-Catalyzed Isomerization of 4-Vinylisoxazoles into Pyrroles.
The first synthesis of pyrroles by Fe(II)-catalyzed isomerization of 4-vinylisoxazoles is reported. 5-Alkoxy, amino, and N,N-dialkylamino-3-aryl/alkyl-4-(2-R-vinyl)isoxazoles afford 2-aryl/alkyl-5-aryl/alkyl/methoxycarbonyl-1H-pyrrol-3-carboxylic acid derivatives typically under mild conditions with cheap and available FeCl2·4H2O as a catalyst. The isomerization of 5-alkoxy/amino-3-arylisoxazoles, bearing unsaturated carbo and heterocyclic substituents at the position 4, gives the corresponding fused pyrrolecarboxylic acid derivatives in high yields. DFT calculations were used to elucidate a probable mechanism of the isomerization and explain the influence of steric congestion of the vinyl moiety on the isomerization pathway.


Low prevalence of Helicobacter pylori infection in patients with hamartomatous fundic polyps.
Helicobacter pylori infection of the gastric mucosal surface was investigated in patients with hamartomatous fundic polyps or hyperplastic polyps and in patients without endoscopic evidence of disease (healthy subjects). Presence of H. pylori infection was determined by culture, histologic examination, and the endoscopic phenol red test. Adherence of H. pylori was evaluated with scanning electron microscopic examination of antral biopsy specimens. Both prevalence of H. pylori infection (P < 0.001) and H. pylori adherence (P < 0.05) were less in patients with hamartomatous fundic polyps than in healthy subjects and patients with hyperplastic polyps. However, the percentages of plasma cells in gastric mucosa that contained IgA and of gastric epithelial cells that expressed Lewis b did not differ significantly among the three groups. These findings suggest that defense mechanisms against the attachment of H. pylori other than IgA or Lewis b antigen are present in patients with hamartomarous fundic polyps.


Use of glycated albumin to distinguish occult diabetes mellitus from stress-induced hyperglycemia in Chinese orthopedic trauma patients.
Some nondiabetic trauma patients with hyperglycemia have been found to have occult diabetes mellitus (ODM). We studied whether glycated albumin (GA) was an effective tool for detecting ODM in orthopedic trauma patients with elevated glucose levels. A cross-sectional, sequential case series study of adult patients presenting to the Orthopedic Trauma Center between September 2009 and March 2010 with new limb fractures was performed. Hemoglobin A1c (HbA1c) and GA levels were measured in hyperglycemic patients with no prior diabetes mellitus. A receiver operating characteristic curve was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA in identifying occult diabetes in hospitalized patients with acute hyperglycemia. A total of 2,058 trauma patients were screened and 399 patients (19.4%) with no known diabetes mellitus were noted to be hyperglycemic. Of these 399 patients, 38.3% (n = 153) had ODM according to the HbA1c diagnosis cutoff point. GA level was strongly correlated with HbA1c using Pearson's correlation analysis (r = 0.887, p < 0.01). Using logistic regression analysis, GA (odds ratio [OR] = 1.60, p < 0.001) and fasting plasma glucose (OR = 1.974, p < 0.001) were identified as significant risk factors for the diagnosis of ODM. Receiver operating characteristic curve analysis showed that a GA value of 17.5% gave an optimal sensitivity of 73.20% and specificity of 99.12% for distinguishing ODM from stress-induced hyperglycemia. Almost 40% of nondiabetic orthopedic trauma patients presenting with hyperglycemia were found to have ODM. A GA value of 17.5%, the optimal cutoff point, could distinguish between ODM and stress-induced hyperglycemia in Chinese orthopedic trauma subjects. II, diagnostic study.


Evaluation of patients with previous coronary stent implantation with 64-section CT.
To prospectively evaluate the diagnostic accuracy of 64-section computed tomography (CT) for the assessment of in-stent or peristent restenosis, with conventional coronary angiography as the reference standard. The study was approved by the medical ethics committee, and informed consent was obtained in all 50 enrolled patients (40 men, 10 women; mean age, 60 years +/- 11 [standard deviation]). In addition to conventional coronary angiography with quantitative coronary angiography, 64-section CT was performed. For each stent, assessability was determined and was related to stent characteristics and heart rate by using a chi(2) test. On the interpretable images of stents and peristent lumina (5.00 mm proximal and distal to the stent), the presence of significant (> or =50%) restenosis was determined. For this analysis, partially overlapping stents were considered to represent a single stent. Of 76 stents, 65 (86%) were determined to be assessable. Increased heart rate and overlapping positioning were associated with increased uninterpretability of the images of stents (P < .05), whereas location of the stent and thickness of the strut were not. In seven patients, stents were placed in an overlapping manner, resulting in 58 stents available for the evaluation of significant (> or =50%) in-stent restenosis. All six significant (> or =50%) in-stent restenoses were detected, and the absence of significant (> or =50%) restenosis was correctly identified in the 52 remaining stents, resulting in sensitivity and specificity of 100%. Sensitivity and specificity for the detection of significant (> or =50%) peristent stenosis were 100% and 98%, respectively. In selected patients with previous stent implantation, 64-section CT can be used to evaluate in-stent restenosis with high accuracy. Accordingly, the technique may be useful for noninvasive exclusion of in-stent or peristent restenosis, thereby avoiding invasive imaging in a considerable number of patients.


An allelopathic competition model with quorum sensing and delayed toxicant production.
The dynamics of a differential functional equation system representing an allelopathic competition is analyzed. The delayed allelochemical production process is represented by means of a distributed delay term in a linear quorum-sensing model. Sufficient conditions for local asymptotic stability properties of biologically meaningful steady-state solutions are given in terms of the parameters of the system. A global asymptotic stability result is also proved by constructing a suitable Lyapunov functional. Some simulations confirm the analytical results.


Stigmatization as a Barrier to Urologic Care: A Review.
Heavy societal stigma of certain conditions has created an environment where individuals may be hesitant to seek professional care. Urology is a specialized field that focuses on many of these conditions that society has deemed taboo to discuss. In this review, we address barriers that have prevented patients from seeking urologic care in order to better understand and elucidate important concerns within development of the physician-patient relationship. Recognizing these concerns can also assist in public health outreach approaches to motivate patients for seeking urologic care. The scope of this review was limited to three highly prevalent conditions affecting both men and women, including urinary incontinence, erectile dysfunction, and genitourinary syndrome of menopause.


[The effect of HLA-DRB4 on the clinical picture of chronic polyarthritis].
61 patients suffering from classic erosive rheumatoid arthritis (RA) with a condition persisting for more than 5 years, were examined together with 69 healthy control subjects with regard to associations to "supertypic" HLA-D specificities. We found a significant increase of HLA-DRw53 in patients with seropositive RA (SPRA) (31/42 patients = 73.8%, Chi 2 = 18.4, p less than 0.01, RR = 7.3). Our results confirm the hypothesis, that the HLA-DRB4 gene is closer related to the disease susceptibility genes of SPRA than of DR4 (DRB1).


Fabrication of digital rainbow holograms and 3-D imaging using SEM based e-beam lithography.
Here we present an approach for creating full-color digital rainbow holograms based on mixing three basic colors. Much like in a color TV with three luminescent points per single screen pixel, each color pixel of initial image is presented by three (R, G, B) distinct diffractive gratings in a hologram structure. Change of either duty cycle or area of the gratings are used to provide proper R, G, B intensities. Special algorithms allow one to design rather complicated 3D images (that might even be replacing each other with hologram rotation). The software developed ("RainBow") provides stability of colorization of rotated image by means of equalizing of angular blur from gratings responsible for R, G, B basic colors. The approach based on R, G, B color synthesis allows one to fabricate gray-tone rainbow hologram containing white color what is hardly possible in traditional dot-matrix technology. Budgetary electron beam lithography based on SEM column was used to fabricate practical examples of digital rainbow hologram. The results of fabrication of large rainbow holograms from design to imprinting are presented. Advantages of the EBL in comparison to traditional optical (dot-matrix) technology is considered.


Suspect and non-target screening of semi-volatile emerging contaminants in indoor dust from Danish kindergartens.
Indoor dust is a sink of hundreds of organic chemicals, and humans may potentially be exposed to these via indoor activities. This study investigated potentially harmful semi-volatile organic contaminants in indoor dust from Danish kindergartens using suspect and non-target screening on gas chromatography (GC)-Orbitrap, supported by target analyses using GC-low resolution mass spectrometry (LRMS). A suspect list of 41 chemicals with one or more toxicological endpoints, i.e. endocrine disruption, carcinogenicity, neurotoxicity and allergenicity, known or suspected to be present in indoor dust, was established including phthalate and non-phthalate plasticizers, flame retardants, bisphenols, biocides, UV filters and other plastic additives. Of these, 29 contaminants were detected in the indoor dust samples, also including several compounds that had been banned or restricted for years. In addition, 22 chemicals were tentatively identified via non-target screening. Several chemicals have not previously been detected in Danish indoor dust. Most of the detected chemicals are known to be potentially harmful for human health while hazard assessment of the remaining compounds indicated limited risks to human. However, children were not specifically considered in this hazard assessment.


Effect of dosage regimen on natriuretic response to furosemide.
We have examined the differences in urinary excretion of water, sodium, potassium, chloride, urea, and creatinine produced by different dosage regimens offurosemide in normal volunteers. Three oral dosage regimens were compared: 20 mg daily, 20 mg twice daily, and 40 mg daily. Furosemide, 20 mg, did not produce a significant weight loss, diuresis, or natriuresis in 12 normal subjects. With 40 there was a significant weight loss, diuresis, natriuresis, and chloruresis over 24 hr. Comparison of the divided regimen with 40 mg daily revealed significantly greater sodium excretion, and chloride excretion with 20 mg twice daily. The divided dosage regimen produced a different pattern of diuresis with most of the sodium and water excretion occurring after the second dose. These differences in response to different regimens are predictable from pharmacokinetic considerations and may have clinical significance.


Maltodextrin Consumption Impairs the Intestinal Mucus Barrier and Accelerates Colitis Through Direct Actions on the Epithelium.
Food additives are common components of processed foods consumed in a Western diet. In inflammatory bowel disease patients, some diets that exclude food additives improved clinical disease parameters, suggesting a link between food additives and disease pathogenesis. Food additives also enhanced disease severity in mouse colitis models through incompletely described mechanisms. This study examined the mechanisms by which the food additive maltodextrin (MDX) alters the development of colitis in a murine model. Interleukin-10 knockout (IL10KO) mice were fed diets supplemented with MDX or carboxymethyl cellulose (CMC) to determine their impact on colitis onset and severity; microbiome composition, function, and location; colonic immune cell infiltrates; and mucus layer integrity. Primary IL10KO colonic epithelial monolayers were used to dissect the impact of MDX directly on epithelial differentiation and mucus production. MDX or CMC consumption increased the incidence and severity of colitis, as well as decreased microbiome diversity, altered microbial composition, and decreased fecal acetic acid levels. The number of mucus producing cells were decreased in food additive fed mice and resulted in increased microbial proximity to the intestinal epithelium. Additionally, MDX supplementation resulted in crypt hyperplasia and expansion of the HopX+ injury renewal stem cell niche. In primary intestinal epithelial-derived monolayers devoid of microbes and immune cells, MDX exposure decreased goblet cell number and mucus production in association with downregulated expression of the transcription factor Klf4, a marker of terminally differentiated goblet cells. These results suggest MDX disrupts the balance of epithelial cell differentiation and proliferation to contribute to disease pathogenesis through direct and indirect actions on the intestinal epithelial barrier.


On Arrival High Blood Glucose Level is Associated With Detrimental and Fatal Hospitalization Outcomes for Acute Coronary Syndrome.
High blood glucose level is frequently encountered in acute coronary syndrome. We investigated the effects of high blood glucose measured on arrival on hospitalization adverse events in acute coronary syndrome. Our study patients were Javanese in ethnicity, which constitute half of population in Indonesia. We hypothesized that elevated blood glucose has detrimental effects on hospitalization for acute coronary syndrome. We designed an observasional cohort study and recruited 148 consecutive patients with acute coronary syndrome. Venous blood was collected on hospital arrival. High blood glucose level was determined as plasma glucose > 140 mg/dL. Adverse hospitalization events were recorded, i.e. mortality, acute heart failure, cardiogenic shock and heart rhythm disorders. Echocardiography examination was performed to determine left ventricular function. The prevalence of on arrival high blood glucose among Javanese patients with acute coronary syndrome was considerably high (36%). On arrival high blood glucose was associated with acute heart failure (P < 0.001) and shock cardiogenic (P = 0.02). Heart rhythm disorders were higher in high blood glucose patients (P = 0.004). Left ventricular dysfunction was more prevalent in high blood glucose patients (P = 0.001) and ejection fraction was lower (P = 0.001). On arrival high blood glucose was independently associated with hospitalization adverse events (adjusted odds ratio = 2.3, 95% confidence interval: 1.1-4.9, P = 0.03) and hospital mortality (adjusted odds ratio = 6.9, 95% confidence interval: 1.2-38.6, P = 0.03). Our study suggests that on arrival high blood glucose among Javanese patients with acute coronary syndrome is considerably high and is associated with detrimental and fatal hospitalization outcomes.


Membrane active 7-thiazoxime quinolones as novel DNA binding agents to decrease the genes expression and exert potent anti-methicillin-resistant Staphylococcus aureus activity.
A novel class of 7-thiazoxime quinolones was developed as potential antimicrobial agents for the sake of bypassing resistance of quinolones. Biological assays revealed that some constructed 7-thiazoxime quinolones possessed effective antibacterial efficiency. Methyl acetate oxime derivative 6l exhibited 32-fold more active than ciprofloxacin against MRSA, which also possessed rapidly bactericidal ability and low toxicity towards mammalian cells. The combination use of 7-thiazoxime quinolone 6l and ciprofloxacin was able to improve antibacterial potency and effectively alleviate bacterial resistance. The preliminarily mechanism exploration revealed that compound 6l could destroy the cell membrane and insert into MRSA DNA to bind with DNA gyrase, then decrease the expression of gyrB and femB genes. The above results strongly suggested that methyl acetate oxime derivative 6l held a promise for combating MRSA infection.


Discovering innate immunity genes using differential display: a story of RNA helicases.
In this review we discuss the current literature for RNA helicases in response to RNA virus infection. We show the use of Differential Display Reverse Transcription PCR methodology (DD) to analyze virus-host interactions and we present current findings in dengue virus-induced gene expression of RNA helicases.


Schism and Synthesis at the Royal Society.
November 7-9, 2016 witnessed a joint discussion meeting of the Royal Society and the British Academy (the UK national academies for the sciences and social sciences, respectively) entitled 'New Trends in Evolutionary Biology: Biological, Philosophical and Social Science Perspectives'. The meeting, anticipated with a mix of feverish enthusiasm and dread, sold out months in advance, the eager audience perhaps expecting radical and traditional evolutionists to go toe to toe, rather than the constructive dialogue among biologists, social scientists, and researchers in the humanities that the academies advertised. One issue under discussion was whether or not the explanatory core of evolutionary biology requires updating in the light on recent advances in evo-devo, epigenetics, ecosystem ecology, and elsewhere.


New Sesquiterpene Lactones and Other Constituents from Helianthuspetiolaris
Three new sesquiterpene lactones, 11alpha,13-dihydroxydehidrocostuslactone (1), the unusual 5, 10-epoxygermacranolide 4,15-anhydrohelivypolide (2), and 3-methoxy-1,2-anhydridoniveusin A (4), together with the 5,10-epoxygermacranolide helivypolide, four known 3,10-furanoheliangolides, and five known kaurane- and trachylobane-type diterpenes, have been isolated from Helianthus petiolaris.


Gene variants of coagulation related proteins that interact with SARS-CoV-2.
Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches.


Depression and Perceived Stress After Spontaneous Coronary Artery Dissection and Comparison With Other Acute Myocardial Infarction (the VIRGO Experience).
Data on depression and stress among patients with spontaneous coronary artery dissection (SCAD) are limited. Using data from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study, which prospectively enrolled 3,572 acute myocardial infarction (AMI) patients between 18 and 55 years of age, we identified 67 SCAD cases. We compared Patient Health Questionnaire-9 (PHQ-9) and 14-item Perceived Stress Scale (PSS-14) scores obtained at baseline, 1 month, and 12 months between SCAD and AMI of all other causes. Using longitudinal linear mixed-effects analysis, we compared depression and stress scores between SCAD and other AMI, adjusting for time and selected covariates. Patients with SCAD had lower baseline PHQ-9 scores (6.1 ± 6.0 vs 7.7 ± 6.4 for other patients with AMI, p = 0.03), similar 1-month scores, and lower 12-month scores (3.2 ± 4.3 vs 4.9 ± 5.5, p = 0.004). At baseline and 1 month, patients with SCAD had similar PSS-14 scores to those of other patients with AMI. At 12 months, patients with SCAD had lower scores (18.4 ± 8.8 vs 21.5 ± 9.3 for other patients with AMI, p = 0.009). After adjustment for cardiovascular risk factors, co-morbidities, and clinical acuity, no differences in PHQ-9 or PSS-14 scores remained between SCAD and other AMI. Similar results were obtained in a subgroup analysis of only women with SCAD and other AMI. In conclusion, patients with SCAD had a relatively lower burden of depression and perceived stress than other patients with AMI, potentially because of fewer co-morbidities and favorable socioeconomic factors. However, given high depression and stress burden in both SCAD and other patients with AMI, routine screening can help identify and treat these patients.


Restoration of thrombosed Brescia-Cimino dialysis fistulas by using percutaneous transluminal angioplasty.
To evaluate the authors' experience with a technique for management of thrombosed Brescia-Cimino arteriovenous fistula. Forty patients with 42 thrombosed arteriovenous fistulas were percutaneously treated. Thrombosis occurred within 24 hours of attempted angioplasty in five fistulas, between 24 and 72 hours in 27, and longer than 72 hours in 10. Thrombosed fistulas were approached in a retrograde fashion followed by direct balloon dilation with 5-8-mm balloon catheters. If retrograde catheterization failed to cross the arterial anastomosis, an antegrade puncture directly into the thrombosed drainage vein close to the anastomosis was performed with ultrasonographic guidance, as an aid to catheterize the arterial inflow. Thrombolytic therapy with infusion of urokinase directly into the thrombus was performed in selected patients with visible thrombus that had compromised blood flow in the partially restored vascular access. Postintervention primary and secondary patency was calculated by using Kaplan-Meier analysis. Patency rates between patients without and with urokinase infusion were examined by using the log-rank test. Anatomic success was achieved in 39 (93%) of 42 fistulas; and clinical patency, in 38 (90%) of 42 fistulas. Postintervention primary and secondary patencies (including initial technical failure) at 6, 12, and 18 months were 81% and 84%, 70% and 80%, and 63% and 80%, respectively. No significance of patency rate between patients without and with urokinase infusion was found (P =.912). Three patients died of unrelated causes at 1, 2, and 5 months after the procedures. No major complications were encountered. High anatomic success and excellent clinical patency can be achieved in the salvage of thrombosed arteriovenous fistulas. Percutaneous restoration of arteriovenous fistulas should be attempted before surgical recreation to optimize outcome in patients undergoing hemodialysis.


Seroprevalence of Hepatitis A and E Virus Infections Among Healthy Population in Shiraz, Southern Iran.
Enterically-transmitted acute viral hepatitis is caused predominantly by hepatitis A virus (HAV) and hepatitis E virus (HEV). The prevalence of HEV and HAV infections varies in different geographical regions. This study was conducted to determine the prevalence of HEV and HAV infections among Iranian healthy individuals in southern Iran. Totally, 1030 samples were collected from healthy subjects in schools, those referred to tertiary outpatient clinics and health centers in Shiraz between November 2011 and May 2012. Their ages ranged between six months and 95 years. The presence of total anti-HAV and anti-HEV immunoglobulin M (IgM) in plasma was assessed by ELISA. The results showed that 66.2% and 0.6% of the general population in this area were positive for total anti-HAV and IgM antibodies by ELISA, respectively. As seen, 13.4% and 0.9% were positive for total anti-HEV and IgM antibodies, respectively. The difference in total anti-HAV and anti-HEV antibodies was significant among the age groups (P < 0.001). This study showed that the prevalence rates of HAV and HEV antibodies were positively correlated with age. The results demonstrated that the infection with these two viruses in the region was high and some high-risk individuals including females at child-bearing age were more susceptible. HAV vaccination could be recommended for antibody-negative adults.


Bacteriophage N3 of Haemophilus influenzae. IV. Intracellular events during infection by Haemophilus influenzae phage and transfection by its DNA.
Intracellular events following infection of competent Haemophilus influenzae cells by N3 phage or transfection by DNA from phage were examined. After infection by whole phage three forms of intracellular phage DNA were observed by sedimentation velocity analysis. These forms are probably twisted circles, open circles and linear duplexes. In transfection only about 15% of the phage DNA is efficiently taken up by the competent cells. After entry of phage DNA into wild-type cells in transfection the DNA is degraded at early times, but later some of the fragments are reassembled, resulting in molecules that sediment faster than the monomer length of phage DNA. These presumably concatamer forms are generated by recombination. In strain rec-1 the fast-sedimenting molecules do not appear and degradation of phage DNA is even more pronounced than in the wild-type cells. Since rec-1 is transfected with much lower efficiency than the wild-type our hypothesis is that both fragmentation and generation of fast-sedimenting phage DNA by recombination are required for efficient transfection. These results also show that although phage N3 codes for its own recombination system it cannot operate in the early stages of transfection and succesful transfection is entirely dependent upon the host recombination system.


Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian Carcinoma Patients Treated with Chemotherapy.
Single nucleotide polymorphic variants of DNA repair genes may improve drug efficacy through altering expression levels of the encoded proteins. This study evaluated the influence of genetic polymorphism GSTP1 Ile105Val, GSTM1 (null/non-null) and 2 XRCC1 polymorphisms (Arg194Trp and Arg399Gln) on the survival of ovarian carcinoma patients treated with chemotherapy. 106 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms were genotyped by pyrosequencing. The genotypes XRCC1 194Arg/Trp and XRCC1 194Trp/Trp conferred no significant risk of death when compared to 194Arg/Arg (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.33-3.09, and HR 0.89, 95% CI 0.31-2.57, respectively). Similarly, those carrying the XRCC1 399Arg/Gln genotype had no increased risk of death compared to the XRCC1 399Arg/Arg (HR 0.85, 95% CI 0.39-1.86); no homozygous carriers of the glutamine allele (XRCC1 399 Gln/Gln) were detected. The GSTP1 105Ile/Val had no increased risk of death compared to the GSTP1 105Ile/Ile (HR = 1.20, 95% CI = 0.55-2.63) and no homozygous carriers of the valine allele (GSTP1 105Val/Val) were detected in the study. Compared to the non-null genotype of GSTM1, the mortality rate was nonsignificantly reduced in patients with the null genotype (HR 1.07, 95% CI 0.48-2.42). However, overall survival of the patients treated with the carboplatin-based regimen was significantly longer than for those treated with alternative chemotherapy (plog-rank = 0.006). The present findings suggest that there are no correlations between genotypes and survival.


Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin- refractory colorectal cancer: a phase I/II study of the Arbeitsgemeinschaft für Internistische Onkologie (AIO).
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer. Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/ 500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/ 80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy. 13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease. Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRIAIO alone.


A three-dimensional model of intercellular calcium signaling in epithelial cells.
We have developed a fully three-dimensional (3D) model of calcium signaling in epithelial cells based on a set of reaction diffusion equations that are solved on a large-scale finite-element code in three dimensions. We have explicitly included the cellular compartments including the cell nucleus, cytoplasm, and gap junctions. The model allows for buffering of free Ca2+, calcium-induced calcium release, and the explicit inclusion of mobile buffers. To make quantitative comparisons to experimental results, we used fluorescence microscopy images of cells to generate an accurate mesh describing cell morphology. We found that Ca2+ wave propagation through the tissue is a function of both initial conditions used to start the wave and various geometrical parameters that affect propagation such as gap junction density and distribution, and the presence of nuclei. The exogenous dyes used in experimental imaging also affect wave propagation.


Point-of-Care Ultrasound for Jugular Venous Pressure Assessment: Live and Online Learning Compared.
Point-of-care ultrasound (POCUS) is a novel technique for the assessment of jugular venous pressure. Distance education may allow for efficient dissemination of this technique. We compared online learning to a live course for teaching ultrasonography jugular venous pressure (u-JVP) to determine if these teaching methods yielded different levels of comfort with and use of u-JVP. This was an interventional trial of Canadian emergency physicians who had taken a basic POCUS course. The participants were in one of three Groups: online learning (Group OL), live teaching (Group LT), control (Group C). Group LT participants also took an advanced course prior to the study that included instruction in u-JVP. The participants who took the basic course were randomized to Group OL or Group C. Group OL was subject to the intervention, online learning. Group C only received an article citation regarding u-JVP. Questionnaires were completed before and after the intervention. The primary outcome was physician self-reported use and comfort with the technique of u-JVP after online learning compared to live teaching. Of the 287 advanced course participants, 42 completed the questionnaires (Group LT). Of the 3303 basic course participants, 47 who were assigned to Group OL completed the questionnaires and 47 from Group C completed the questionnaires. Use of u-JVP increased significantly in Group OL (from 15% to 55%) and Group C (from 21% to 47%) with the intervention. The comfort with use did not differ between Group LT and Group OL (p=0.14). The frequency of use remained higher in Group LT than Group OL (p=0.07). Online learning increases the use and comfort with performing u-JVP for emergency physicians with prior POCUS experience. Although the comfort with use of u-JVP was similar in Groups LT and OL, online learning appears to yield levels of use that are less than those of a live course.


Association between hyper-pronated foot and the degree of severity of disability in patients with non-specific low back pain.
It has been established that Hyper-pronation of the foot may lead to postural changes in the lower limbs, with a resultant pelvic ante-version, and a subsequent risk of development of low back pain. However, the association between the presence of a hyper-pronated foot and the severity of disability in low back pain is currently not known. The purpose of this study was to examine whether the presence of a hyper-pronated foot has any impact on the degree of severity of disability (functional status) in patients with non-specific low back pain. An observational study was conducted in an outpatient setting, where patients diagnosed as having non-specific low back pain were included. The degree of severity of disability was measured using the Modified Oswestry Low Back Pain Disability Questionnaire, and the foot hyper-pronation was assessed with the execution of the Navicular Drop test. Descriptive statistics and Linear regression analyses were conducted. Of the 71 patients included, 14 demonstrated having a unilateral hyper-pronation of the foot. The mean scores for the functional status and hyper-pronation of the foot were 37.15 (SD = 10.40) and 6.06 (SD = 3.42) respectively. An association was not found between the severity of disability and the presence of foot hyper-pronation (B = .87, p = .78). Hyper-pronation of the foot could lead to the development of non-specific low back pain, but the degree of severity of the disability is not influenced by the presence of a hyper-pronated foot. The alterations in lower limb mechanics leading to back pain are a complex issue, and thus needs further research.