Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research Practice Guidelines.
The Depression Guideline Panel of the Agency for Health Care Policy and Research in 1993 published recommendations for treating major depression in primary care practice that were often based on studies of tertiary care psychiatric patients. We reviewed reports of randomized controlled trials in primary care settings published between 1992 and 1998. This evidence indicates that both antidepressant pharmacotherapy and time-limited depression-targeted psychotherapies are efficacious when transferred from psychiatric to primary care settings. In most cases, the choice between these treatments should depend on patient preference. Studies to date suggest that improving treatment of depression in primary care requires properly organized treatment programs, regular patient follow-up, monitoring of treatment adherence, and a prominent role for the mental health specialist as educator, consultant, and clinician for the more severely ill. Future research should focus on how guidelines are best implemented in routine practice, since conventional dissemination strategies have little impact.


Simultaneous quantification of glyphosate, glufosinate, and their major metabolites in rice and soybean sprouts by gas chromatography with pulsed flame photometric detector.
Procedures were developed for the simultaneous determination of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [dl-homoalanin-4-yl-(methyl)phosphinic acid] and their major metabolites, aminomethylphosphonic acid (AMPA) and 3-(methylphosphinico)propionic acid (3-MPPA), in rice and soybean sprouts by gas chromatography (GC) equipped with a pulsed flame photometric detector (PFPD). Herbicides and their major metabolites were previously derivatized with TMOA (trimethyl orthoacetate (TMOA) in the presence of acetic acid, and their GC responses versus heating temperature (70-90 degrees C) and heating time (30-120 min) were optimized. It was found that increases in heating temperature and heating time were unfavorable for the derivatization of glyphosate or glufosinate, whereas high temperature and extended reaction time remarkably facilitated that of AMPA and 3-MPPA except at 90 degrees C for an extended reaction time (120 min). Combination of AG1-X8 anion-exchange chromatography with a Florisil cartridge cleanup process was favorable for the GC-PFPD analysis. Four types of derivatives spiked in rice and soybean sprout matrices were eluted, reaching a baseline separation, in a sequence of 3-MPPA, AMPA, glyphosate, and glufosinate within 14 min using a DB-608 capillary column. Recoveries of glyphosate, AMPA, glufosinate, and 3-MPPA (0.5 ppm) spiked in both sample matrices were determined to be 72-81, 71-86, 101-119, and 83-90%, respectively, whereas the coefficient of variation was determined to be <10% in three repeated determinations. The instrumental limits of detection for glyphosate, AMPA, glufosinate, and 3-MPPA in sample matrices were 0.02, 0.03, 0.02, and 0.01 ppm, respectively. The limits of quantification for glyphosate, AMPA, glufosinate, and 3-MPPA in sample matrices were 0.06, 0.10, 0.06, and 0.04 ppm, respectively.


Identification of nonlinear fMRI models using Auxiliary Particle Filter and kernel smoothing method.
Hemodynamic models have a high potential in application to understanding the functional differences of the brain. However, full system identification with respect to model fitting to actual functional magnetic resonance imaging (fMRI) data is practically difficult and is still an active area of research. We present a simulation based Bayesian approach for nonlinear model based analysis of the fMRI data. The idea is to do a joint state and parameter estimation within a general filtering framework. One advantage of using Bayesian methods is that they provide a complete description of the posterior distribution, not just a single point estimate. We use an Auxiliary Particle Filter adjoined with a kernel smoothing approach to address this joint estimation problem.


Gender influence on treatment of chronic hepatitis C genotype 1.
Although various studies have been published regarding the treatment of chronic hepatitis C (CHC) with peginterferon (Peg-IFN) and ribavirin, little is known regarding the real impact of gender on the characteristics that influence the effectiveness and safety of antiviral treatment for CHC patients. The objective of this study was to evaluate the influence of gender on HCV treatment outcomes. A retrospective analytical study was conducted among selected carriers of CHC genotype 1, who were treated with Peg-IFN alpha-2b at a dose of 1.5 microg/kg or Peg-IFN alpha-2a at a dose of 180 microg/week plus a ribavirin dose of 1,000-1,250 mg/day, according to weight, between 2001 and 2007. Among 181 patients undergoing treatment, the mean age was 46.4 +/- 11.0 years and 46% were women. At baseline, 32% of the patients had advanced fibrosis (F3-F4 Scheuer), and 83% of the subjects had viral load > 400,000 IU/ml, without significant difference between the genders (p = 0.428 and p = 0.452, respectively). When compared with men, women had higher incidence of many adverse events such as anemia (p < 0.001) and higher need for dose reduction, for both Peg-IFN (p = 0.004) and ribavirin (p = 0.006). However, the rate of sustained virological response (SVR) did not differ between the genders: 45% (female) vs 41% (male); p=0.464. This study suggests that women and men react differently to combined therapy, especially in relation to the incidence of adverse events and the need for dose modification. Nevertheless, these differences do not influence the SVR rate.


Comparing acceptance- and control-based coping instructions on the cold-pressor pain experiences of healthy men and women.
The current study reflects recent developments in psychotherapy by examining the effect of acceptance-based coping instructions, when compared to the opposite, more control/distraction-based instructions, on cold-pressor pain. Since previous research indicates gender differences in how people cope with pain, we also sought to determine whether differences would be found between healthy men and women. As predicted, results indicated that women reported lower pain threshold and tolerance level than did men. Furthermore, the acceptance-based instruction resulted in lower sensory pain reports when compared to the opposite instructions. Finally, for affective pain, acceptance instructions only benefited women. These results suggest that acceptance-based coping may be particular useful in moderating the way in which individuals, especially women, cope with pain.


Correlates of support for a nicotine-reduction policy in smokers with 6-week exposure to very low nicotine cigarettes.
The US Food and Drug Administration recently issued an advanced notice of proposed rule-making for reducing the nicotine content in cigarettes to a minimally addictive level. Very little is known about whether use of very low nicotine content (VLNC) cigarettes affects support for a nicotine reduction policy. This study examined the effects of using VLNC versus usual brand (UB) cigarettes on support for a nicotine reduction policy and determined whether participant characteristics and responses to VLNC cigarettes were associated with policy support. Participants from a cigarette trial who were assigned to either 0.4 mg nicotine/g tobacco research cigarettes or their UB for 6 weeks were asked about their support for the policy. χ2 tests were used to compare support for the policy between cigarette conditions and logistic regression analyses were conducted to assess covariates associated with policy support. Policy support did not differ by condition. After 6 weeks of using VLNC cigarettes, 50% of participants supported the policy, 26% opposed and 24% responded 'Don't Know'. Support was higher among those adherent to smoking only VLNC cigarettes (65%) compared with those who were non-adherent (44%). Older participants and those interested in quitting had increased odds of support. Cigarette satisfaction, perceived harm and perceived nicotine content were not significantly associated with support. Smoking VLNC cigarettes did not affect support for a nicotine reduction policy. Understanding predictors of policy support and opposition will help public health officials to maximise the public health acceptance and impact of this policy (ClinicalTrials.gov Identifier: NCT01681875 Post-Results).


Harvest Time Optimization for Combustion Quality of Different Miscanthus Genotypes across Europe.
Delayed harvest can improve the quality of miscanthus biomass for combustion and enhance the long-term sustainability of the crop, despite accompanying yield losses. The aim of this study is to identify the optimal harvesting time, which can deliver improved biomass quality for combustion of novel miscanthus genotypes at various sites across Europe, without high yield losses and without compromising their environmental performance. The relevant field trials were established as part of the European project OPTIMISC with 15 genotypes at six sites across Europe. For this study, the five highest yielding genotypes from each germplasm group and three sites with contrasting climatic conditions (Stuttgart, Germany; Adana, Turkey; and Moscow, Russia) were selected for assessment. The biomass samples were collected between August and March (depending on site) and subjected to mineral and ash content analysis. At Stuttgart, the delay in harvesting time led to a significant variation in combustion quality characteristics, such as N content (0.64-0.21%), ash content (5.15-2.60%), and ash sintering index (1.30-0.20). At Adana, the delay in harvesting time decreased the N content from 0.62 to 0.23%, ash content from 10.63 to 3.84%, and sintering index from 0.54 to 0.07. At Moscow, the impact of delay in harvesting was not significant, except for N, Mg, and ash sintering index. Overall, a delay in harvesting time improved the combustion quality characteristics of each genotype, but at the expense of yield. Yield losses of up to 49% in Stuttgart and Adana and 21% for Moscow were recorded, with variations between genotypes and sites. The harvesting time also affected nutrient offtake, which in turn influences the long-term environmental performance of the crop. The highest N, P, and K offtakes were recorded at Stuttgart for each harvesting time except for final harvest (March), where Moscow had the highest N offtake. This study describes the three criteria (biomass quality, yield losses, nutrient offtake) for determining the ideal harvesting time, which gives the best compromise between dry matter yields and biomass quality characteristics without negatively affecting the environmental performance of the crop.


The impact of prophylactic pancreatic stenting on post-ERCP pancreatitis: A nationwide, register-based study.
The role of prophylactic pancreatic stenting (PS) in preventing post-endoscopic retrograde cholangio-pancreatography (ERCP) pancreatitis (PEP) has yet to be determined. Most previous studies show beneficial effects in reducing PEP when prophylactic pancreatic stents are used, especially in high-risk ERCP procedures. The present study aimed to address the use of PS in a nationwide register-based study in which the primary outcome was the prophylactic effect of PS in reducing PEP. All ERCP-procedures registered in the nationwide Swedish Registry for Gallstone Surgery and ERCP (GallRiks) between 2006 and 2014 were studied. The primary outcome was PEP but we also studied other peri- and postoperative complication rates. Data from 43,595 ERCP procedures were analyzed. In the subgroup of patients who received PS with a total diameter ≤ 5 Fr, the risk of PEP increased nearly four times compared to those who received PS with a total diameter of >5 Fr (OR 3.58; 95% CI 1.40-11.07). Furthermore, patients who received PS of >5 Fr and >5 cm had a significantly lower pancreatitis frequency compared to those with shorter stents of the same diameter (1.39% vs 15.79%; p = 0.0033). PS with a diameter of >5 Fr and a length of >5 cm seems to have a better protective effect against PEP, compared to shorter and thinner stents. However, in the present version of GallRiks it is not possible to differentiate the exact type of pancreatic stent (apart from material, length and diameter) that has been introduced, so our conclusion must be interpreted with caution.


Uncovering the epidemic of HIV among men who have sex with men in Central Asia.
Research among people who inject drugs (PWID) in Central Asia has described same sex behavior among male PWID and may be associated with HIV and other infections. Little is known about the population of men who have sex with men (MSM) and the burden of HIV among MSM in Central Asian countries. We conducted a comprehensive search of peer-reviewed publications and gray literature on MSM and HIV in the region. Search strategies included terms for MSM combined with five Central Asian countries and neighbors, including Mongolia, Afghanistan, and Xinjiang Province, China. 230 sources were identified with 43 eligible for inclusion: 12 provided HIV prevalence and population size estimates for MSM, none provided incidence estimates, and no publications for Turkmenistan were identified. National reports estimate HIV prevalence among MSM to range from 1 to 2% in Kazakhstan, Kyrgyzstan, Tajikistan, Uzbekistan, Xinjiang, to 10% in Mongolia. Biobehavioral studies estimated HIV prevalence at 0.4% in Afghanistan and 20.2% in Kazakhstan. Sexual identities and behaviors vary across countries. Injection drug use was relatively low among MSM (<5% for most). Non-injection drugs, alcohol use prior to sex, and binge drinking were more common and potentially associated with violence. Criminalization of homosexuality (Afghanistan, Uzbekistan, and Turkmenistan) and stigma has limited research and HIV prevention. Improved understanding of risks, including potential linkages between sexual exposures and substance use, among MSM are important for response. The little known about HIV among MSM in Central Asia speaks to the urgency of improvements in HIV research, prevention, and care.


[The psychological reasons for the varying efficacy of suggestion in an experiment].
In 86 neurotic patients, judgements about TAT pictures were defined before a session of hypnosis. Later other judgments about the same pictures were suggested after the patients entered the hypnotic state. 34 patients who were in a deep enough hypnotic state manifested the lack of suggestion realization, which can be accounted for by image and intellectual activity that occurred at the moment of suggestion. Suggestibility increased whatever the depth of the hypnotic state, on condition that at the moment of suggestion the image and intellectual perception of TAT pictures could be rearranged. The given study made it possible to explain the occasionally occurring difference in suggestibility and hypnability which is of practical value.


Sex risk practices among HIV-positive individuals in Buenos Aires, Argentina.
We have limited information regarding the sexual risk behaviors of HIV-positive individuals in Argentina. It is important to understand these behaviors in order to develop strategies oriented at decreasing unsafe sex practices. A random sample of 140 HIV-positive individuals was recruited from an HIV primary care clinic in Buenos Aires, Argentina, between August and September 2005. Participants responded survey questions regarding their sexual behaviors in the previous three months. Logistic regression analysis was used to determine factors associated with inconsistent condom use during vaginal, anal, and oral sex. Of the 140 participants surveyed, 69% were male, the mean age was 38 years old, 29% reported having less than a high school education, and 84% reported having engaged in vaginal, anal, and/or oral sex in the past 3 months. Of 53 participants who reported engaging in anal sex, 60% were men who have sex with men, and 40% were heterosexuals. Inconsistent condom use was reported by 31% of participants engaging in anal sex, 39% of participants engaging in vaginal sex, and 71% of participants engaging in oral sex. When adjusting for other factors, participants reporting symptoms of depression were 5.2 times more likely to use condoms inconsistently during vaginal sex, and 4.3 times more likely to use condoms inconsistently during anal sex compared to participants reporting no depression symptoms. Providers should assess sexual risk practices of HIV-positive individuals reporting symptoms of depression, and provide counseling regarding the importance of consistent condom use to those patients who are engaging in unsafe sex practices.


[Met-enkephalin-Arg-Gly-Leu-like immunoreactivity-containing nerve fibers and cell bodies in the abdominal sympathetic ganglia of the rat--an immunohistochemical study].
The occurrence and localization of Met-enkephalin-Arg-Gly-Leu (Met-Enk-Arg-Gly-Leu)-like immunoreactivity in the lumbar paravertebral ganglion and the superior mesenteric ganglion in the rat were investigated by immunocytochemistry. Colchicine was employed as an axonal flow blocker to accumulate Met-Enk-Arg-Gly-Leu in the nerve cell bodies. The Met-Enk-Arg-Gly-Leu serum (R 0171) was produced by immunizing a mixed breed female rabbit with synthetic Met-Enk-Arg-Gly-Leu conjugated to ascaris protein by the glutaraldehyde method. Sections, 7 micron in thickness, of Bouin-fixed and paraffin-embedded tissues were immunostained by the peroxidase-antiperoxidase (PAP) method. Results obtained were summarized as follows: Colchicine-untreated rats possessed no strongly-immunoreactive nerve cell bodies for Met-Enk-Arg-Gly-Leu in the lumbar paravertebral ganglion, though a few of them were weakly immunopositive. Met-Enk-Arg-Gly-Leu-like immunoreactivity showing nerve fibers were occasionally seen in nerve fiber bundles of the lumbar paravertebral ganglion. In the superior mesenteric ganglion, a dense network of positively immunostained nerve fibers with a beaded appearance were seen around nerve cell bodies which were immunonegative for Met-Enk-Arg-Gly-Leu. In colchicine-treated rats, 55 percent of nerve cell bodies of the lumbar paravertebral ganglion showed various degrees of positive immunoreactivities for Met-Enk-Arg-Gly-Leu. Many strongly immunostained nerve terminals were seen in the lumbar paravertebral ganglion of colchicine-treated rats. In the superior mesenteric ganglion, the immunoreactivity for Met-Enk-Arg-Gly-Leu in the beaded nerve fibers around nerve cell bodies was intensified by the colchicine treatment, whereas the nerve cell bodies themselves remained immunonegative for Met-Enk-Arg-Gly-Leu.


OpenHelix: bioinformatics education outside of a different box.
The amount of biological data is increasing rapidly, and will continue to increase as new rapid technologies are developed. Professionals in every area of bioscience will have data management needs that require publicly available bioinformatics resources. Not all scientists desire a formal bioinformatics education but would benefit from more informal educational sources of learning. Effective bioinformatics education formats will address a broad range of scientific needs, will be aimed at a variety of user skill levels, and will be delivered in a number of different formats to address different learning styles. Informal sources of bioinformatics education that are effective are available, and will be explored in this review.


Changes in chromosomal localization of heterochromatin-binding proteins during the cell cycle in Drosophila.
We examined the heterochromatic binding of GAGA factor and proliferation disrupter (Prod) proteins during the cell cycle in Drosophila melanogaster and sibling species. GAGA factor binding to the brownDominant AG-rich satellite sequence insertion was seen at metaphase, however, no binding of GAGA factor to AG-rich sequences was observed at interphase in polytene or diploid nuclei. Comparable mitosis-specific binding was found for Prod protein to its target satellite in pericentric heterochromatin. At interphase, these proteins bind numerous dispersed sites in euchromatin, indicating that they move from euchromatin to heterochromatin and back every cell cycle. The presence of Prod in heterochromatin for a longer portion of the cell cycle than GAGA factor suggests that they cycle between euchromatin and heterochromatin independently. We propose that movement of GAGA factor and Prod from high affinity sites in euchromatin occurs upon condensation of metaphase chromosomes. Upon decondensation, GAGA factor and Prod shift from low affinity sites within satellite DNA back to euchromatic sites as a self-assembly process.


Generating Novel Materials Using the Intrinsically Disordered Protein Ubx.
The development of functionalized materials is needed to enable diverse applications. Protein-based materials are typically biocompatible and biodegradable and can exhibit a wide variety of useful mechanical properties. Most importantly, gene fusion enables facile incorporation of active proteins into the materials. However, many protocols rely on denaturing conditions to stimulate materials formation. These conditions would be expected to inactivate any appended functional proteins. This chapter describes methods to create protein fibers and films in a mild aqueous buffer near neutral pH. This facile, inexpensive single-pot approach to materials assembly does not require any special equipment. Also included in this chapter are methods to fuse fibers to form fiber bundles, and to use fibers for cell culture. Although these methods were developed to generate materials from the Drosophila Hox transcription factor Ultrabithorax, they may also work for other self-assembling proteins, many of which have sequence features in common with Ubx.


Simulation and Analysis of Tethering Behavior of Neutrophils with Pseudopods.
P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) play important roles in mediating the inflammatory cascade. Selectin kinetics, together with neutrophil hydrodynamics, regulate the fundamental adhesion cascade of cell tethering and rolling on the endothelium. The current study uses the Multiscale Adhesive Dynamics computational model to simulate, for the first time, the tethering and rolling behavior of pseudopod-containing neutrophils as mediated by P-selectin/PSGL-1 bonds. This paper looks at the effect of including P-selectin/PSGL-1 adhesion kinetics. The parameters examined included the shear rate, adhesion on-rate, initial neutrophil position, and receptor number sensitivity. The outcomes analyzed included types of adhesive behavior observed, tether rolling distance and time, number of bonds formed during an adhesive event, contact area, and contact time. In contrast to the hydrodynamic model, P-selectin/PSGL-1 binding slows the neutrophil's translation in the direction of flow and causes the neutrophil to swing around perpendicular to flow. Several behaviors were observed during the simulations, including tethering without firm adhesion, tethering with downstream firm adhesion, and firm adhesion upon first contact with the endothelium. These behaviors were qualitatively consistent with in vivo data of murine neutrophils with pseudopods. In the simulations, increasing shear rate, receptor count, and bond formation rate increased the incidence of firm adhesion upon first contact with the endothelium. Tethering was conserved across a range of physiological shear rates and was resistant to fluctuations in the number of surface PSGL-1 molecules. In simulations where bonding occurred, interaction with the side of the pseudopod, rather than the tip, afforded more surface area and greater contact time with the endothelial wall.


Is outpatient hysteroscopy accurate for the diagnosis of endometrial pathology among perimenopausal and postmenopausal women?
To assess the histological and visual accuracy of outpatient hysteroscopy. This was a retrospective analysis of all women referred to a tertiary center outpatient hysteroscopy clinic between March 2011 and October 2016 for the following indications: postmenopausal bleeding, suspected polyp, and/or thick endometrium. Histological accuracy was evaluated by comparing specimens obtained in hysteroscopy with those obtained by hysterectomy, and visual accuracy was evaluated by comparing visual findings with those obtained by biopsies. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were calculated to assess visual accuracy. The mean age of participants was 54.14 (interquartile range 43.0-64.0). A total of 408 pathological specimens were obtained from outpatient hysteroscopies during the 712 visits recorded in the clinic log. Histological accuracy was evaluated in 15 participants who eventually underwent hysterectomy. Total percent of agreement between hysteroscopy biopsies and final pathology obtained by hysterectomy was 73% (kappa = 0.47). Overall visual accuracy was calculated with a 93.1% sensitivity, 52.1% specificity, 90.4% positive predictive value, and 61.0% negative predictive value. Visual accuracy for benign pathology was generally higher compared with that for pre and malignant lesions. Visual accuracy was satisfactory for the diagnosis of endometrial carcinoma with sensitivity and specificity of 71.4% and 98.9%, respectively, but poor for diagnosing hyperplasia with sensitivity and specificity of 25.0% and 96.6%, respectively. Outpatient hysteroscopy is an adequate and reliable tool for the evaluation of benign pathology in the uterine cavity. Visual findings may not suffice, and directed biopsies may be required to improve diagnostic accuracy.


The effects of LAMP1 and LAMP3 on M180 amelogenin uptake, localization and amelogenin mRNA induction by amelogenin protein.
We previously demonstrated that the uptake of M180 amelogenin protein in dental epithelial cells (HAT-7) results in increased levels of amelogenin mRNA through enhanced mRNA stabilization. To determine the processes involved in the uptake of extracellular M180 amelogenin by cells and in amelogenin intracellular trafficking in the amelogenin protein-mediated amelogenin mRNA expression pathway, we investigated the effects of LAMP1 and LAMP3, which are candidate M180 amelogenin receptors, on M180 amelogenin uptake, localization and amelogenin mRNA induction by amelogenin protein, using anti-LAMP-1 and anti-LAMP-3 antibodies and siRNA analysis. The results indicate that LAMP3 blocking by anti-LAMP-3 decreases M180 amelogenin uptake, but does not affect amelogenin mRNA induction by amelogenin protein, suggesting that LAMP3 is related to amelogenin degradation. Down-regulation by siRNA of LAMP1, which is the receptor for small amelogenin protein (LRAP), does not affect M180 amelogenin uptake, localization or amelogenin mRNA induction by amelogenin protein. Thus, while LAMP1 is the specific receptor for LRAP, it is not a receptor for M180 amelogenin. These findings will aid further research into the understanding of M180 amelogenin function and expression.


Human-SARS-CoV-2 interactome and human genetic diversity: TMPRSS2-rs2070788, associated with severe influenza, and its population genetics caveats in Native Americans.
For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.


Amoxycillin in single oral dose for uncomplicated gonorrhoea.
One hundred and sixty-two cases of uncomplicated gonorrhoea were treated with 3g of amoxycillin swallowed in front of an observer. The failure rate of 2.1 percent was low, but did not reach the effectiveness of the standard gonopen probenecid regime, with which failures are a rarity. There were no side effects. It is suggested that 3g of amoxycillin be combined with 1g of probenecid as the treatment of choice, if an oral treatment regime is chosen.


Carpeting in hospitals: an epidemiological evaluation.
Epidemiological and microbiological studies were conducted in a hospital room with carpet (CR) and in one with carpet (NCR). Microbiological profiles were determined with specimens obtained from patients admitted to these rooms. Patient records were reviewed to note infection status and other case identities. Eleven-millimeter cylindrical core samples of carpet were obtained, and swab template techniques were used on the bare floor for subsequent enumeration and identification of contaminating microorganisms. In each sampling period, higher microbial counts per square inch (1 in(2) = ca 6.452 cm(2)) were measured for the carpet than for the bare floor. Recovery rates of Enterobacter spp., Klebsiella pneumoniae, and Escherichia coli were higher from carpet samples than from bare floor samples. Typable organisms (such as E. coli, Pseudomonas aeruginosa, K. pneumoniae, and Staphylococcus aureus) obtained from patients were also more frequently recovered from the carpet than from the bare flooring. Patients who stayed in the CR were shown to be colonized with the same types of organisms as those initially recovered from the carpet. However, no statistically significant differences were found in patients in the CR versus NCR in colonization with all typable and nontypable organisms first found on the floor. Disease in patients was found not to be associated with organisms found as contaminants of the carpet or the bare floor. Air above carpeting contained more consistent concentrations of organisms than air above the bare flooring.


Novel hemodynamic structures in the human glomerulus.
To investigate human glomerular structure under conditions of physiological perfusion, we have analyzed fresh and perfusion-fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton, and electron microscope imaging. Afferent and efferent arterioles (21.5 ± 1.2 µm and 15.9 ± 1.2 µm diameter), recognized from vascular origins, lead into previously undescribed wider regions (43.2 ± 2.8 µm and 38.4 ± 4.9 µm diameter) we have termed vascular chambers (VCs) embedded in the mesangium of the vascular pole. Afferent VC (AVC) volume was 1.6-fold greater than efferent VC (EVC) volume. From the AVC, long nonbranching high-capacity conduit vessels ( n = 7) (Con; 15.9 ± 0.7 µm diameter) led to the glomerular edge, where branching was more frequent. Conduit vessels have fewer podocytes than filtration capillaries. VCs were confirmed in fixed and unfixed specimens with a layer of banded collagen identified in AVC walls by multiphoton and electron microscopy. Thirteen highly branched efferent first-order vessels (E1; 9.9 ± 0.4 µm diameter) converge on the EVC, draining into the efferent arteriole (15.9 ± 1.2 µm diameter). Banded collagen was scarce around EVCs. This previously undescribed branching topology does not conform to the branching of minimum energy expenditure (Murray's law), suggesting that even distribution of pressure/flow to the filtration capillaries is more important than maintaining the minimum work required for blood flow. We propose that AVCs act as plenum manifolds possibly aided by vortical flow in distributing and balancing blood flow/pressure to conduit vessels supplying glomerular lobules. These major adaptations to glomerular capillary structure could regulate hemodynamic pressure and flow in human glomerular capillaries.


Cyberbullying perpetration and victimisation among junior and senior high school students in Guangzhou, China.
Cyberbullying research in China is in early stage. This study describes the cyberbullying experiences of junior and senior high school students in Guangzhou, China, and to examine the risk factors associated with cyberbullying perpetrators, victims and perpetrator-victims among students. We also investigated the frequency of cyberbullying and coping strategies of student victims. Participants were 2590 students in grades 7, 8, 9 and 10 from six junior and senior high schools in October 2015 in Guangzhou, in south China, who completed a questionnaire. Data on participants' experiences with cyberbullying perpetration and victimisation during the previous 6 months were collected. Multinomial logistic regression was used to analyse factors associated with being perpetrators, victims and perpetrator-victims. In this sample, 28.0% (725) of participants reported being a perpetrator and 44.5% (1150) reported being a victim in the previous 6 months. Specifically, 2.9% (74) reported being perpetrators only, 19.3% (499) reported being victims only and 25.2% (651) reported being perpetrator-victims (both perpetrator and victim). In addition, flaming was the most common form of cyberbullying in both perpetration and victimisation. Logistic regression analyses indicated that online game addiction in participants was associated with increased odds of being a perpetrator only; no democratic parenting style in the mother and physical discipline by parents were associated with increased odds of being a victim only; male students, students with low academic achievement, those spending over 2 hours a day online, experiencing physical discipline from parents and online game addiction were associated with increased odds of both perpetration and victimisation. Cyberbullying is a common experience among Chinese junior and senior high school students. These findings add to the empirical data on cyberbullying and reinforce the urgent need for cyberbullying prevention in China. Furthermore, from the perspective of practice, it is important to raise our awareness of cyerbullying and reduce the risk factors.


KIF3B gene silent variant leading to sperm morphology and motility defects and male infertility†.
Sperm structural and functi onal defects are leading causes of male infertility. Patients with immotile sperm disorders suffer from axoneme failure and show a significant reduction in sperm count. The kinesin family member 3B (KIF3B) is one of the genes involved in the proper formation of sperm with a critical role in intraflagellar and intramanchette transport. A part of exon 2 and exons 3-5 of the KIF3B encodes a protein coiled-coil domain that interacts with intraflagellar transport 20 (IFT20) from the intraflagellar transport protein complex. In the present study, the coding region of KIF3B coiled-coil domain was assessed in 88 oligoasthenoteratozoospermic (OAT) patients, and the protein expression was evaluated in the mature spermatozoa of the case and control groups using immunocytochemistry and western blotting. According to the results, there was no genetic variation in the exons 3-5 of the KIF3B, but a new A>T variant was identified within the exon 2 in 30 patients, where nothing was detected in the control group. In contrast to healthy individuals, significantly reduced protein expression was observable in oligoasthenoteratozoospermic patients carrying variation where protein organization was disarranged, especially in the principal piece and midpiece of the sperm tail. Besides, the protein expression level was lower in the patients' samples compared to that of the control group. According to the results of the present study the KIF3B gene variation as well as lower protein expression leads to defects in sperm morphology and motility and consequently to male infertility.


A new convexity measure for polygons.
Abstract-Convexity estimators are commonly used in the analysis of shape. In this paper, we define and evaluate a new convexity measure for planar regions bounded by polygons. The new convexity measure can be understood as a "boundary-based" measure and in accordance with this it is more sensitive to measured boundary defects than the so called "area-based" convexity measures. When compared with the convexity measure defined as the ratio between the Euclidean perimeter of the convex hull of the measured shape and the Euclidean perimeter of the measured shape then the new convexity measure also shows some advantages-particularly for shapes with holes. The new convexity measure has the following desirable properties: 1) the estimated convexity is always a number from (0, 1], 2) the estimated convexity is 1 if and only if the measured shape is convex, 3) there are shapes whose estimated convexity is arbitrarily close to 0, 4) the new convexity measure is invariant under similarity transformations, and 5) there is a simple and fast procedure for computing the new convexity measure.


Allocating scarce resources in real-time to reduce heart failure readmissions: a prospective, controlled study.
To test a multidisciplinary approach to reduce heart failure (HF) readmissions that tailors the intensity of care transition intervention to the risk of the patient using a suite of electronic medical record (EMR)-enabled programmes. A prospective controlled before and after study of adult inpatients admitted with HF and two concurrent control conditions (acute myocardial infarction (AMI) and pneumonia (PNA)) was performed between 1 December 2008 and 1 December 2010 at a large urban public teaching hospital. An EMR-based software platform stratified all patients admitted with HF on a daily basis by their 30-day readmission risk using a published electronic predictive model. Patients at highest risk received an intensive set of evidence-based interventions designed to reduce readmission using existing resources. The main outcome measure was readmission for any cause and to any hospital within 30 days of discharge. There were 834 HF admissions in the pre-intervention period and 913 in the post-intervention period. The unadjusted readmission rate declined from 26.2% in the pre-intervention period to 21.2% in the post-intervention period (p=0.01), a decline that persisted in adjusted analyses (adjusted OR (AOR)=0.73; 95% CI 0.58 to 0.93, p=0.01). In contrast, there was no significant change in the unadjusted and adjusted readmission rates for PNA and AMI over the same period. There were 45 fewer readmissions with 913 patients enrolled and 228 patients receiving intervention, resulting in a number needed to treat (NNT) ratio of 20. An EMR-enabled strategy that targeted scarce care transition resources to high-risk HF patients significantly reduced the risk-adjusted odds of readmission.


Building a common ground on the clinical case: design, implementation and evaluation of an information model for a Handover EHR.
Handovers need a common ground on the clinical cases between the members of the successive shifts to establish continuity of care. Conventional electronic patient record systems (EHR) proved to be only insufficiently suitable for supporting the grounding process. Against this background we proposed a basic concept for a handover EHR that extends general EHRs in particular openEHR based systems. The resulting handover information model was implemented in a database and evaluated based on 120 clinical cases. The information items of these cases could be mapped successfully to the model, however, the new class "anticipatory guidance" needed to be introduced. The evaluation also demonstrated the importance of highly aggregated information on the clinical case, opinions and meta-information such as the relevance of an item during handovers. Based on these findings, in particular the handover database, handover EHR applications are currently developed to support the grounding process.


Immunogenicity and Biodistribution of Anthrax DNA Vaccine Delivered by Intradermal Electroporation.
Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution. The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced. Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.


The plant 2-Cys peroxiredoxin BAS1 is a nuclear-encoded chloroplast protein: its expressional regulation, phylogenetic origin, and implications for its specific physiological function in plants.
2-Cys peroxiredoxins constitute a family of enzymes which catalyze the transfer of electrons from sulfhydryl residues to peroxides and are ubiquitously distributed among all organisms. This paper characterizes the higher plant 2-Cys-peroxiredoxin BAS1. (i) Escherichia coli over-expressing BAS1 exhibit increased tolerance for alkyl hydroperoxides in vivo. This result substantiates the peroxiredoxin function of BAS1. (ii) BAS1 protein is associated with the soluble chloroplast fraction of mesophyll protoplasts. Import and processing of in vitro-transcribed and cell-free translated BAS1 protein into isolated chloroplasts provides conclusive evidence that the plant-specific N-terminal extension of bas1 encodes the chloroplast import signal which targets the pre-form of BAS1 to the chloroplast stroma where it is cleaved to its mature size. (iii) Genomic analysis reveals that the targeting signal is encoded by a separate exon in Arabidopsis thalina. (iv) The amino acid sequence of the BAS1 core protein of higher plants has a higher degree of similarity to open reading frames in the genome of the bluegreen algae Synechochystis PCC sp. 6803 and in the plastome of the red algae Porphyra purpurea than to any other nuclear-encoded 2-Cys peroxiredoxin. Therefore, it is tempting to speculate that the chloroplast import signal was added to an ancestor gene of endosymbiotic origin in the course of plant evolution. (v) The bas1 gene expression is regulated under the control of the cellular redox state which is in accordance with the anti-oxidant function of the enzyme. While oxidative stressors increased expression only slightly, antioxidants such as reduced thiols strongly suppressed the transcript level. The implications of these findings are discussed with respect to the possible physiological functions of BAS1.


Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties.
Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia is known to be an underlying cause for the development of OA. Therefore, lipid and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA patients (n=29) and compared to those of rheumatoid arthritis (RA) patients (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1) was investigated in vitro on inflammatory parameters using human joint cells isolated from cartilage and synovial membrane obtained from OA patients after joint replacement. Cells were stimulated with ApoA1 in the presence or not of serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C and total cholesterol levels were strongly correlated to each other inside the OA joint cavity whereas same levels were not or weakly correlated to their corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1 induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast-like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients was observed and was correlated with inflammatory parameters in the OA joint cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.


Referral and diagnosis of common rheumatic diseases by primary care physicians.
To describe primary care patterns of referral and diagnoses of patients with rheumatic diseases referred to rheumatologists. The medical records of all consecutive patients referred in 1994 by >300 primary care physicians to two rheumatologists at an academic centre were reviewed. The referring physician diagnosis was compared with the rheumatologist's diagnosis. Sensitivity, specificity and predictive values of primary care diagnoses were estimated using the rheumatologist diagnosis as the 'gold standard'. University-based rheumatology out-patient clinic. Over half of the patients referred had a rheumatologist diagnosis of soft-tissue rheumatism or a spinal pain syndrome. Three hundred and forty-seven patients (49%) had a primary care diagnosis of a defined rheumatic disease. Of these, 142 (41%) of the primary care diagnoses were subsequently modified by the rheumatologist. The highest agreement between primary care physician and rheumatologist was observed for crystal-induced arthritis (kappa = 0.86), and the lowest agreement for polymyalgia rheumatica (kappa = 0.39) and systemic lupus (kappa = 0.46). Sensitivity was lowest for a primary care diagnosis of fibromyalgia (48%) and highest for ankylosing spondylitis (94%). Positive predictive values were generally low, in particular for systemic lupus erythematosus (33%) and polymyalgia rheumatica (30%). Most patients referred to an academic rheumatology centre had soft-tissue rheumatism or other pain syndromes. In general, diagnostic agreement between rheumatologists and primary care physicians was low. Increased emphasis on musculoskeletal disorders should be encouraged in medical education to increase the efficiency of rheumatology referrals.


Targeted mutagenesis of Medicago truncatula Nodule-specific Cysteine-Rich (NCR) genes using the Agrobacterium rhizogenes-mediated CRISPR/Cas9 system.
The host-produced nodule specific cysteine-rich (NCR) peptides control the terminal differentiation of endosymbiotic rhizobia in the nodules of IRLC legumes. Although the Medicago truncatula genome encodes about 700 NCR peptides, only few of them have been proven to be crucial for nitrogen-fixing symbiosis. In this study, we applied the CRISPR/Cas9 gene editing technology to generate knockout mutants of NCR genes for which no genetic or functional data were previously available. We have developed a workflow to analyse the mutation and the symbiotic phenotype of individual nodules formed on Agrobacterium rhizogenes-mediated transgenic hairy roots. The selected NCR genes were successfully edited by the CRISPR/Cas9 system and nodules formed on knockout hairy roots showed wild type phenotype indicating that peptides NCR068, NCR089, NCR128 and NCR161 are not essential for symbiosis between M. truncatula Jemalong and Sinorhizobium medicae WSM419. We regenerated stable mutants edited for the NCR068 from hairy roots obtained by A. rhizogenes-mediated transformation. The analysis of the symbiotic phenotype of stable ncr068 mutants showed that peptide NCR068 is not required for symbiosis with S. meliloti strains 2011 and FSM-MA either. Our study reports that gene editing can help to elicit the role of certain NCRs in symbiotic nitrogen fixation.


Glucocorticoid receptor signaling contributes to constitutive activation of the noncanonical NF-κB pathway in term human placenta.
Our recent study demonstrated that constitutively activated RelB/NF-κB2 positively regulates the CRH in the human placenta. In the current study, we explored the role of the glucocorticoid receptor (GR) signaling in constitutive activation of the noncanonical NF-κB pathway. A glucocorticoid response element (GRE) motif search suggests that both NF-κB inducing kinase (NIK) and RelB genes, which are key regulators of the noncanonical NF-κB pathway, have a putative GRE within their promoter, approximately 1 kb upstream from the transcription start site. By using chromatin immunoprecipitation assay we identified that the GR and phosphorylated GR at Ser211 were associated with the GREs of both NIK and RelB. Dexamethasone stimulated expression of NIK, RelB, NF-κB2 as well as CRH and cyclooxygenase-2 (COX-2). Repression of GR by short interfering RNA resulted in inhibition of NIK, RelB, NF-κB2, CRH, and COX-2. In addition, depletion of GR attenuated glucocorticoid-mediated up-regulation of NIK, RelB, NF-κB2, CRH, and COX-2. Furthermore, siRNA specifically targeting NIK down-regulated CRH and COX-2. Taken together, these results suggest that constitutive activation of the noncanonical NF-κB pathway in term human placenta is driven by the GR signaling, which in turn up-regulates placental CRH and other NF-κB-responsive genes.


Vaccination behaviour influences self-report of influenza vaccination status: a cross-sectional study among health care workers.
Published influenza vaccination coverage in health care workers (HCW) are calculated using two sources: self-report and vaccination records. The objective of this study was to determine whether self-report is a good proxy for recorded vaccination in HCW, as the degree of the relationship is not known, and whether vaccine behaviour influences self-reporting. A cross-sectional study was conducted using a self-administered survey during September 2010. Considering the vaccination record as the gold standard of vaccination, the properties of self-report as a proxy of the record (sensitivity, specificity, positive predictive value, negative predictive value) were calculated. Concordance between the vaccination campaigns studied (2007-2010) was made using the Kappa index, and discordance was analyzed using McNemar's test. 248 HCW responded. The 95% confidence intervals of coverage according to the vaccination record and to self-report overlapped, except for 2007, and the Kappa index showed a substantial concordance, except for 2007. McNemar's test suggested that differences between discordant cases were not due to chance and it was found that the proportion of unvaccinated discordant cases was higher than that of vaccinated discordant cases. In our study population, self-reported influenza vaccination coverage in HCW in the previous two years is a good proxy of the vaccination record. However, vaccination behaviour influences the self-report and explains a trend to overestimate coverage in self-reporting compared to the vaccination record. The sources of coverage should be taken into account whenever comparisons are made.


Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats.
Membrane mechanics is an important biological factor regulating many cellular functions including cell motility, intercellular and intracellular signaling, gene expression, and membrane ion channel activity. Primary afferent neurons transduce sensory information about temperature, touch, and pain. These sensory functions may be profoundly affected by the states of primary afferent neuron mechanics. However, membrane mechanics of primary afferent neurons is largely unknown. In this study, we established the optical trapping technique for determining membrane mechanics of cultured primary afferent neurons of the dorsal root ganglia (DRG). We further determined the roles of cytoskeleton and membrane lipids in DRG neuron mechanics. We found that DRG neurons had a plasma membrane tension of ∼54 pN/μm, and the tension was significantly decreased to ∼29 pN/μm by cytochalasin D treatment to disrupt actin cytoskeleton and increased to ∼79 pN/μm by methyl-β-cyclodextrin treatment to sequester membrane cholesterol. DRG neuron membrane stiffness was not significantly affected by the cytoskeleton disruption but was significantly increased after cholesterol sequestration. Our findings elucidate membrane mechanical properties of primary afferent neurons, which provide, to our knowledge, a new perspective on their sensory functions.


A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.
Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.


Melatonin and cell death: differential actions on apoptosis in normal and cancer cells.
Melatonin is a natural compound synthesized by a variety of organs. It has been shown to function as a cell-protective agent. Since 1994, when the first paper was published documenting the role of melatonin in apoptosis, the number of reports in this area has increased rapidly. Much of the research conducted falls into three major categories: first, the role of melatonin in inhibiting apoptosis in immune cells; second, the role of melatonin in preventing neuronal apoptosis and finally, the role of melatonin in increasing apoptotic cell death in cancer cells. The mechanisms whereby melatonin influences apoptosis have not clarified, although a number of mechanistic options have been suggested. Apoptotic cell death is a physiological phenomenon related to homeostasis and proper functioning of tissues and organs; however, a failure in the apoptotic program is related to a number of diseases. The participation of melatonin in apoptosis in numerous cell types and its potential importance in a variety of diseases such as immunodeficiency, neurodegeneration and cancer is summarized in this review.


Accumulation and perchlorate exposure potential of lettuce produced in the Lower Colorado River region.
The Colorado River is contaminated with perchlorate concentrations of 1.5-8 microg/L, an anion linked to thyroid dysfunction. Over 90% of the lettuce (Lactuca sativa L.) consumed during the winter months in the United States is produced in the Lower Colorado River region. Studies were conducted in this region to survey the potential for lettuce perchlorate accumulation and estimate potential human exposure to perchlorate from lettuce. Total uptake of perchlorate in the above-ground plant of iceberg lettuce was approximately 5 g/ha. Exposure estimates ranged from 0.45 to 1.8 microg/day depending on lettuce types and trimming. For all lettuce types, hypothetical exposures were less than 4% of the reference dose recommended by the National Academy of Sciences. Results show the relative iodide uptake inhibition potential because of lettuce nitrate was 2 orders of magnitude greater than that associated with the corresponding trace levels of perchlorate. These data support the conclusion that potential perchlorate exposures from lettuce irrigated with Colorado River water are negligible relative to acute or long-term harmful amounts.


Two general methods for the isolation of enzyme activities by colony filter screening.
We describe two general methodologies, based on filter-sandwich assays, for isolating enzymatic activities from a large repertoire of protein variants expressed in the cytoplasm of E. coli cells. The enzymes are released by the freezing and thawing of bacterial colonies grown on a porous master filter and diffuse to a second "reaction" filter that closely contacts the master filter. Reaction substrates can be immobilized either on the filter or on the enzyme itself (which is then, in turn, captured on the reaction filter). The resulting products are detected with suitable affinity reagents. We used biotin ligase as a model enzyme to assess the performance of the two methodologies. Active enzymes were released by the bacteria, locally biotinylated the immobilized target substrate peptide, and allowed the sensitive and specific detection of individual catalytically active colonies.


Viscosity sensor utilizing a piezoelectric thickness shear sandwich resonator.
This paper describes a novel quartz crystal sensor for measurement of the density-viscosity product of Newtonian liquids. The sensor element consists of two piano-convex AT-cut quartz crystals vibrating in a thickness-shear mode with the liquid sample in between. This special set-up allows suppression of disturbing resonances in the liquid layer. Such resonances are generated in the common single-plate arrangements due to compressional waves caused by spurious out-of-plane displacements of the shear vibrating finite plate. The primary measurands of the sensor are the fundamental resonance frequency and the associated resonance Q-value, which are influenced by the viscously entrained liquid contacting the quartz surface. The sensor allows the measurement of samples with viscosities from almost zero (air!) up to 200 cP with a sample volume of 130 microl.


Molecular implementation of sequential and reversible logic through photochromic energy transfer switching.
Photochromic spiropyrans modified with fluorophores were investigated as molecular platforms for the achievement of fluorescence switching through modulation of energy transfer. The dyads were designed in such a way that energy transfer is only observed for the open forms of the photochrome (merocyanine and protonated merocyanine), whereas the closed spiropyran is inactive as an energy acceptor. This was made possible through a deliberate choice of fluorophores (4-amino-1,8-naphthalimide, dansyl, and perylene) that produce zero spectral overlap with the spiro form and considerable overlap for the merocyanine forms. From the Förster theory, energy transfer is predicted to be highly efficient and in some cases of 100% efficiency. The combined switching by photonic (light of λ>530 nm) and chemical (base) inputs enabled the creation of a sequential logic device, which is the basic element of a keypad lock. Furthermore, in combination with an anthracene-based acidochromic fluorescence switch, a reversible logic device was designed. This enables the unambiguous coding of different input combinations through multicolour fluorescence signalling. All devices can be conveniently reset to their initial states and repeatedly cycled.


Timing and Degree of Acute Kidney Injury in Patients Requiring Non-Surgical Intensive Care.
The degree and timing of acute kidney injury (AKI) on admission and during hospitalization in patients requiring non-surgical intensive care remain unclear.Methods and Results: In this study, 3,758 patients requiring intensive care were analyzed retrospectively. AKI was defined based on the ratio of serum creatinine concentrations recorded at each time point (i.e., on admission and during the first 5 days in the intensive care unit and during hospitalization) to those measured at baseline. Patients were grouped by combining AKI severity (RIFLE class) and timing (i.e., from admission to 5 days [A-5D]; from 5 days to hospital discharge [5D-HD]) as follows: No-AKI; New-AKI (no AKI to Class R [risk; ≥1.5-fold increase in serum creatinine], I [injury; ≥2.0-fold increase in serum creatinine], and F [failure; ≥3.0-fold increase in serum creatinine or receiving dialysis during hospitalization]); Stable-AKI (Class R to R; Class I to I); and Worsening-AKI (Class R to I or F; Class I to F). Multivariate logistic regression analysis indicated that 730-day mortality was independently associated with Class R, I, and F on admission; Class I and F during the 5D-H period; and New-AKI and Worsening-AKI during A-5D and 5D-HD. AKI on admission, even Class R, was associated with a poor prognosis. An increase in RIFLE class during hospitalization was identified as an important factor for poor prognosis in patients requiring intensive care.


Handheld computers and paper diaries for documenting the use of factor concentrates used in haemophilia home therapy: a qualitative study.
A recently published randomized controlled trial (RCT) showed that adherence to infusion diary record keeping was improved by the use of handheld computers. In this study, attitudes to record keeping were explored and patient preferences regarding the method of recording determined for the patients who participated in the trial. Qualitative study consisting of individual semi-structured interviews with 20 severely affected patients with haemophilia who participated in an RCT. Individuals were purposefully sampled based on their recent method of record keeping and whether child or adult. Analysis employed a constant comparative method to identify key themes from the data. Most individuals (19 of 20, 95%) considered record keeping to be important. They readily identified reasons to keep records: to benefit themselves, their families, clinical staff, product distributors and manufacturers. Keeping records helps them: feel a part of the health care team; have confidence they would be notified of product recalls; review their past history; improve their ability to advocate for themselves and improve communication among all parties. Record keeping, particularly when using paper diaries, can be burdensome and a challenge to maintain consistently. All 10 individuals (100%) who had used both paper diaries and handheld computers preferred the latter. Most patients understand that record keeping can be of benefit to them. Clinics can use this knowledge to inspire other patients by developing educational programmes that de-emphasize authority. In addition, given the evidence of both patients' preference for handheld computers, and the effectiveness of this approach documented in an RCT, switching to handheld computers is likely to improve record keeping.


[Dental caries prevalence survey in children and teenagers].
To identify the prevalence of caries in affiliated children and teenagers at Instituto Mexicano del Seguro Social (IMSS). The survey was carried out according to the World Health Organization indexes. The studied was carried out in 1545 boys and girls aged three, five, six, and twelve years and selected by stratified random sampling in seven places of Mexican Republic (Guanajuato, East and West Estado de México, Northwest 1, Northeast 2, Southwest 3, and Southeast 4 DF). The prevalence of caries was 66.9 %. Rates were higher in temporary dentition than in permanent teeth (p < 3.07). The mean of caries index per tooth in primary dentition in children of six years of age was 3.57 +/- 2.8. In the 12 years of age group the average per tooth was 1.97 +/- 1.4. The main component in both primary and permanent dentition was caries with 2.49 and 1.56 respectively. The results of this survey showed slight changes in prevalence and high levels of caries in children.


Usefulness of Noncontrast-Enhanced Silent Magnetic Resonance Angiography (MRA) for Treated Intracranial Aneurysm Follow-up in Comparison with Time-of-Flight MRA.
Flow visualization in time-of-flight magnetic resonance angiography (TOF MRA) is limited for treated intracranial aneurysms owing to magnetic susceptibility and radiofrequency shielding. To assess the clinical usefulness of noncontrast-enhanced magnetic resonance angiography (MRA) using a silent scan (silent MRA) as a follow-up imaging modality in patients with treated intracranial aneurysms. A total of 119 patients with 126 treated aneurysms underwent silent MRA and TOF MRA during the same scan session. Two neuroradiologists independently assessed overall image quality and visualization of the treated site using a 5-point Likert scale to compare the 2 image sets. We used receiver operating characteristic (ROC) curve analysis to investigate the diagnostic performance of the 2 MRA methods in evaluating aneurysm occlusion. Interobserver reliability was also assessed using weighted kappa statistics. The overall image quality scores of silent MRA and TOF MRA were 4.04 ± 0.22 and 4.64 ± 0.48, respectively (P < .001), and interobserver agreement was substantial (P < .001). For the treated site, the score of flow visualization on silent MRA was higher than that on TOF MRA, 3.94 ± 0.94 vs 2.59 ± 1.37 (P < .001), with substantial interobserver agreement (P < .001). ROC curve analysis showed that silent MRA was superior to TOF MRA in diagnostic performance (area under the curve [AUC] = 0.962; 95% CI: 0.931-0.982 vs AUC = 0.843; 95% CI: 0.792-0.886; P < .001). Silent MRA can be useful to evaluate treated intracranial aneurysms during follow-up without radiation exposure and use of contrast material. It is characterized by higher diagnostic performance and superior visualization for the treated site.


Variability of the transporter gene complement in ammonia-oxidizing archaea.
Ammonia-oxidizing archaea (AOA) are a widespread and abundant component of microbial communities in many different ecosystems. The extent of physiological differences between individual AOA is, however, unknown. Here, we compare the transporter gene complements of six AOA, from four different environments and two major clades, to assess their potential for substrate uptake and efflux. Each of the corresponding AOA genomes encode a unique set of transporters and although the composition of AOA transporter complements follows a phylogenetic pattern, few transporter families are conserved in all investigated genomes. A comparison of ammonia transporters encoded by archaeal and bacterial ammonia oxidizers highlights the variance among AOA lineages as well as their distinction from the ammonia-oxidizing bacteria, and suggests differential ecological adaptations.


Taxonomic re-evaluation of the South African fish haemogregarine, Desseria fragilis.
Development stages of a haemogregarine were found in Giemsa-stained heart blood smears of 3 of the 4 horned blennies (Parablennius cornmutus) captured at De Hoop Nature Reserve, South Africa. Gamonts of this haemogregarine conformed to an existing description of Desseria (Haemogregarina) fragilis from P. cornmutus, but intraerythrocytic trophozoites, as well as meronts undergoing division, were reported for the first time for this species. A detailed redescription of D. fragilis allowed its taxonomic re-evaluation. Intraerythrocytic division excluded D. fragilis from Desseria, whereas morphometric similarities and identical patterns of development lead to the conclusion that D. fragilis is the cosmopolitan haemogregarine, Haemogregarina bigemina. Nomenclatural correction synonymizing the 2 species is recommended.


Directed assembly of the thylakoid membrane on nanostructured TiO2 for a photo-electrochemical cell.
The thylakoid membrane mainly consists of photosystem I (PSI), photosystem II (PSII) and the cytochrome b6f embedded in a lipid bilayer. PSI and PSII have the ability to capture sunlight and create an electron-hole pair. The study aims at utilizing these properties by using the thylakoid membrane to construct a photo-electrochemical cell. A controlled aerosol technique, electrohydrodynamic atomization, allows a systematic study by the fabrication of different cell configurations based on the surfactant concentration without any linker, sacrificial electron donor and mediator. The maximum photocurrent density observed is 6.7 mA cm(-2) under UV and visible light, and 12 μA cm(-2) under visible light illumination. The electron transfer occurs from PSII to PSI via cytochrome b6f and the electron at PSII is regenerated by water oxidation, similar to the z-scheme of photosynthesis. This work shows that re-engineering the natural photosynthesis circuit by the novel technique of electrospray deposition can result in an environmentally friendly method of harvesting sunlight.


Video telemetry and behavioral analysis discriminate between compulsive cleaning and compulsive checking in obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) patients exhibit compulsive acts that share key characteristics that discriminate them from normal behaviors. In OCD, factor analysis of symptomatology has identified separate clusters (contamination/cleaning; harming/checking; symmetry/ordering; hoarding). Here we used video analysis of the motor characteristics of OCD compulsions derived from two separate clusters, checking and cleaning, in order to determine whether behavioral differences exist in the way these two compulsions are performed. We compared 22 behavioral components (acts) of 12 OC-cleaning rituals and 25 OC-checking rituals. A normal activity with the identical theme was matched for each OC ritual as a control. For each ritual and control, we measured 22 parameters (such as the duration and frequency of act performance), and the levels of functionality, by evaluating the degree to which the act appears to contribute toward achieving its goal. We found that both OC-cleaning and OC-checking rituals differed from their respective control activity, and that they also differ between themselves in seven out of the 22 parameters. OC-cleaning involved increased repetition of functional activity whereas OC-checking involved a relatively increased non-functional activity. These results suggest that OCD cleaning and checking rituals are sufficiently different to justify their division into different subtypes and presumably are sub-served by different mechanisms. A better understanding of the relationship between those behavioral parameters derived from video-telemetry, and the parameters assessed by means of clinical and neurobiological tools, would improve our understanding of the nosological significance of compulsive symptoms and contribute to advancing endophenotypic exploration of the heterogeneity of OCD.


Vaccines for emerging infections.
Emerging infectious diseases represent a grave threat to animal and human populations in terms of their impact on global health, agriculture and the economy. Vaccines developed for emerging infections in animals can protect animal health and prevent transmission of zoonotic diseases to humans. Examples in this paper illustrate how industry and public health can collaborate to develop a vaccine to prevent an emerging disease in horses (West Nile virus vaccine), how poultry vaccination can protect animals and prevent transmission to people (avian influenza vaccine), how regulatory changes can pave the way for vaccines that will control the carrier state in animals and thus prevent infection in humans (Bartonella henselae vaccine in cats) and how novel technologies could be applied to vaccinate wildlife reservoir species for rabies. Stemming from the realisation that zoonotic diseases are the predominant source of human emerging infectious diseases, it behoves academic, public health, and animal health agencies to consider creative constructive approaches to combat serious public health challenges. Vaccination of vector/reservoir species, when efficacious vaccines are available, offers significant advantages to combating zoonotic human disease.


Adult Bronchoscopy Training: Current State and Suggestions for the Future: CHEST Expert Panel Report.
The determination of competency of trainees in programs performing bronchoscopy is quite variable. Some programs provide didactic lectures with hands-on supervision, other programs incorporate advanced simulation centers, whereas others have a checklist approach. Although no single method has been proven best, the variability alone suggests that outcomes are variable. Program directors and certifying bodies need guidance to create standards for training programs. Little well-developed literature on the topic exists. To provide credible and trustworthy guidance, rigorous methodology has been applied to create this bronchoscopy consensus training statement. All panelists were vetted and approved by the CHEST Guidelines Oversight Committee. Each topic group drafted questions in a PICO (population, intervention, comparator, outcome) format. MEDLINE data through PubMed and the Cochrane Library were systematically searched. Manual searches also supplemented the searches. All gathered references were screened for consideration based on inclusion criteria, and all statements were designated as an Ungraded Consensus-Based Statement. We suggest that professional societies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. Bronchoscopy training programs should incorporate multiple tools, including simulation. We suggest that ongoing quality and process improvement systems be introduced and that certifying agencies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. We also suggest that assessment of skill maintenance and improvement in practice be evaluated regularly with ongoing quality and process improvement systems after initial skill acquisition. The current methods used for bronchoscopy competency in training programs are variable. We suggest that professional societies and certifying agencies move from a volume- based certification system to a standardized skill acquisition and knowledge-based competency assessment for pulmonary and thoracic surgery trainees.


Isolation.
This comic tells the true story of a hospitalist physician learning from a patient how to slow down. It is a commentary on the isolating experience of hospitalization-magnified for patients by infection control precautions and hospital restrictions and for clinicians by long hours away from family and friends, particularly during peaks of the COVID-19 pandemic.


Virus-specific splicing inhibitor in extracts from cells infected with HIV-1.
Human immunodeficiency virus type 1 (HIV-1), in contrast with most other retroviruses, encodes trans-regulatory proteins for virus gene expression. It is shown in this study, by means of an in vitro splicing system, that nuclear extracts obtained from cells infected with HIV-1 contain a factor (or factors) that specifically inhibits splicing of a synthetic SP6/HIV pre-messenger RNA (pre-mRNA)-containing donor and acceptor splice sites in the coding region for the envelope protein. It is also shown that the SP6/HIV pre-mRNA is not capable of assembly in a ribonucleoprotein complex, spliceosome, in extracts from infected cells. These findings raise the possibility that specific inhibition of pre-mRNA splicing in the envelope protein coding region by HIV-1 trans-regulatory factors might be one control mechanism for efficient production of structural viral proteins and virion assembly.


Neuroimaging and neurocircuitry in post-traumatic stress disorder: what is currently known?
Neurobiologic, psychologic, and social factors interact jointly to create and perpetuate the symptoms of post-traumatic stress disorder (PTSD). The fear conditioning paradigm in animal research helped researchers gather preclinical evidence for the possible contribution of several brain areas to PTSD symptoms. In the past 10 years, highly sophisticated neuroimaging techniques made it possible for researchers to look at the brain of patients with PTSD and draw conclusions about the neurocircuitry underlying PTSD symptoms. In this article, the author will review the evidence from neuroimaging studies for the involvement of the following brain areas in PTSD neurocircuitry: the amygdala, the anterior cingulate cortex and subcallosal gyrus, the inferior frontal gyrus, the posterior cingulate cortex, and the hippocampus. Neuroimaging studies have shown these areas as altered in structure or function in patients with PTSD. The author also presents the normal functions that these areas subserve and, whenever possible based on the evidence, infer how their dysfunction may contribute importantly to the symptomatology of PTSD.


[Cortical positive potentials in the period of eye fixation prior to saccades and antisaccades].
The EEG of 10 right-handed healthy subjects preceding saccade and antisaccade with mean values of latency in the eye fixations period were selected and averaged. The positive potential P2 appearing on the fixation stimuly switching on and slow positive wave following after it were more prominent before antisaccades than normal saccades. Space-temporal analyses of presaccadic potentials showed that right frontal cortex was activated more before antisaccades. These findings suggest that right cortical hemisphere dominate in spatial attention and inhibition of automatic saccades to visual stimuli in the period of antisaccades preparing. During the period of central fixations "intermediate" positivity potentials, developing in 600-400 ms prior to saccade or antisaccade onset, were find out. These potentials were predominantly recorded in the left frontal and frontosagittal cortical areas. The obtained evidence suggest that "intermediate" positive potentials a period related to the process of motor attention, anticipation and decision making in the period of eyes fixation.


Intra-hepatic and extra-hepatic cholangiocarcinoma: New insight into epidemiology and risk factors.
Cholangiocarcinoma (CCA) is a malignant tumour that arises from biliary epithelium at any portion of the biliary tree. CCA is currently classified as intra-hepatic or extra-hepatic CCA (EH-CCA). Recent evidences suggest that intra-hepatic CCA (IH-CCA) and EH-CCA are biologically different cancers, giving further support to a number of recent epidemiological studies showing large differences in terms of incidence, mortality and risk factors. The purpose of this manuscript is to review recent literature dealing with the descriptive epidemiology and risk factors of CCA with a special effort to compare IH- with EH-CCA.


DTI correlates of cognition in conventional MRI of normal-appearing brain in patients with clinical features of subacute combined degeneration and biochemically proven vitamin B(12) deficiency.
Vitamin B12 deficiency may cause neural injury that results in cognitive deficits. The main purpose of our study was to evaluate morphometric and microstructural changes in the brain and relate them to cognition in subacute combined degeneration of the spinal cord and patients with biochemically deficient vitamin B12. Fifty-one patients were recruited and underwent nerve-conduction velocity tests and routine hematologic examinations. Serum vitamin B12 and homocystine levels were also measured. All patients and 46 age- and sex-matched controls underwent cervical spine and brain MR imaging along with cognition tests. MR imaging included conventional scans and DTI. Voxel-based morphometry was performed for determining the WM and GM volumes, based on T1-weighted images. DTI measures that included fractional anisotropy, ADC, radial diffusivity, and axial diffusivity were determined by using tract-based statistics. None of the patients showed any abnormality on conventional MR imaging. No significant changes in GM and WM volumes were observed in patients compared with controls. Significant reductions in the fractional anisotropy and an increase in ADC and radial diffusivity values were observed in multiple brain regions in patients compared with controls. These changes were confirmed on the region-of-interest analysis. Neuropsychological scores were significantly different in patients compared with controls and showed significant correlation with fractional anisotropy and radial diffusivity in a few brain regions. Microstructural changes are seen in WM regions on DTI in patients with vitamin B12 deficiency and correlate with cognition scores. DTI can be used for objective assessment of microstructural changes in the brain in vitamin B12 deficiency.


Are all outcomes in chronic heart failure rated equally? An argument for a patient-centred approach to outcome assessment.
Chronic heart failure (CHF) is a multi-dimensional and complex syndrome. Outcome measures are important for determining both the efficacy and quality of care and capturing the patient's perspective in evaluating the outcomes of health care delivery. Capturing the patient's perspective via patient-reported outcomes is increasingly important; however, including objective measures such as mortality would provide more complete account of outcomes important to patients. Currently, no single measure for CHF outcomes captures all dimensions of the quality of care from the patient's perspective. To describe the role of outcome measures in CHF from the perspective of patients, a structured literature review was undertaken. This review discusses the concepts and methodological issues related to measurement of CHF outcomes. Outcome assessment at the level of the patient, provider and health care system were identified as being important. The perspectives of all stakeholders should be considered when developing an outcomes measurement suite to inform CHF health care. This paper recommends that choice of outcome measures should depend on their ability to provide a comprehensive, comparable, meaningful and accurate assessment that are important to patient.


Training paramedics: emergency care for children with special health care needs.
To enhance knowledge and comfort related to the emergency care of children with special health care needs (CSHCN) through an innovative continuing education program for paramedics. A self-study program presenting in-depth information about common problems that affect the assessment and management of a child's airway, breathing, circulation, disability, and environment (ABCDEs), regardless of the child's diagnosis, was developed. This program used a manual, a video, practice mannequins, and skills evaluations to teach skills to paramedics employed at a municipal fire department. Pre- and posttraining surveys found that the paramedics were significantly more comfortable with the assessment and management of CSHCN after the completion of the self-study program, with a pretraining average of 2.83 and posttraining average of 4.20 on a five-point Likert-type scale, t(37) = 12.87, p < 0.001. A skills evaluation showed that skills performance varied widely across 21 skills, ranging from skills mastery to low skills knowledge. On the posttraining survey, between 74% and 94% of the paramedics rated each topic (tracheostomies, indwelling central venous catheters, cerebrospinal fluid shunts, gastrostomies, child abuse, and latex allergy) as applicable to their practices as paramedics. Given the growing population of CSHCN, it is important to provide specialized education to increase an EMS provider's preparedness to respond to emergency situations involving children with special health care needs.


Silver(I)-N-heterocyclic carbene complexes challenge cancer; evaluation of their anticancer properties and in silico studies.
Because of the continuous need for efficient therapeutic agents against various kinds of cancers and infectious diseases, the pharmaceutical industry has to find new candidates and strategies to develop novel and efficient drugs. They increasingly use computational tools in R&D stages for screening extensive sets of drug candidates before starting pre-clinical and clinical trials. N-Heterocyclic carbenes (NHCs) can be evaluated as good drug candidates because they offer both anti-cancer and anti-inflammatory features with their general low-toxicity profiles. To date, different kinds of NHCs (Cu, Co, Ni, Au, Ag, Ru, etc.) have been synthesized and their therapeutic uses has been shown. Here, we have reviewed the recent studies focused on Ag(I)-NHC complexes and their anti-cancer activities. Also, existing examples of the usage of density functional theory and structure-activity relationship have been evaluated.


Precocious development of glucuronidating and hydroxylating enzymes in chick embryos treated with pituitary grafts.
1. Initiation of precocious development of UDP-glucuronyltransferase by an endogenous factor is reported for the first time. 2. This development occurs in chick embryo liver and kidney after grafting of the cephalic lobe of chicken pars-distalis pituitary tissue on to the chorioallantoic membrane, and in liver results in a rise in the enzyme activity from virtually zero to ;adult' values. Aniline hydroxylase also precociously develops in the liver of grafted embryos, its activity rising from one-third to the full adult value. Specific activities of glucose 6-phosphatase, cytochrome P-450 and NADPH-cytochrome c reductase did not significantly change. 3. The response of the transferase does not require the presence of host pituitary gland nor, apart from 1 day's necessary initiation, the presence of the graft itself. 4. The host becomes competent to respond on the 14th day of incubation; response continues for at least 3 days after removal of the graft, and for 2 days in the isolated liver. Grafting of embryonic pars distalis younger than 17 days does not evoke a response in the host liver. 5. Secretion of the pituitary factor increases suddenly some 24-48h before the naturally developing surge in liver UDP-glucuronyltransferase activity and may be responsible for initiating this rise in vivo. 6. The factor is probably not a growth or luteinizing hormone; its nature and the likelihood of a secondary hormone acting directly on the liver are discussed.


The Effect of Process Variables and Binder Concentration on Tabletability of Metformin Hydrochloride and Acetaminophen Granules Produced by Twin Screw Melt Granulation with Different Polymeric Binders.
In twin screw melt granulation, granules are produced by passing mixtures of drug substances and polymeric binders through twin screw extruder such that temperatures are maintained below melting point of drugs but above glass transition of polymers used, whereby the polymers coat surfaces of drug particles and cause their agglomeration into granules. Since various formulation factors, such as binder type and concentration, and processing variables like extrusion temperature, screw configuration, and screw speed, can influence the granulation process, the present investigation was undertaken to study their effects on tabletability of granules produced. Three different types of polymeric binders, Klucel® EXF (hydroxypropyl cellulose), Eudragit® EPO (polyacrylate binder), and Soluplus® (polyvinyl caprolactam-co-vinyl acetate-ethylene glycol graft polymer), were used at 2, 5, and 10% concentrations. Metformin hydrochloride (HCl) (mp: 222°C) and acetaminophen (mp: 169°C) were used as model drugs, and drug-polymer mixtures with metformin HCl were extruded at 180, 160, and 130°C, while those with acetaminophen were extruded at 130 and 110°C. Other process variables included screw configurations: low, medium, and high shear for metformin HCl, and low and medium shear for acetaminophen; feed rates: 20 and 60 g/min; and screw speed of 100 and 300 RPM. Formulation and process variables had significant impact on tabletability. The target tensile strength of ≥2 MPa could be obtained with all polymers and at all processing temperatures when metformin HCl was granulated at 180°C and acetaminophen at 130°C. At other temperatures, the target tensile strength could be achieved at certain specific sets of processing conditions.


Outcomes of suture button repair of the distal tibiofibular syndesmosis.
Recently, a suture button device has been advocated as a simple and effective method of repairing the syndesmosis. Proponents of the device have cited earlier weightbearing and elimination of the need for device removal as potential advantages over metallic screws. However, the available reports generally have short followup. With longer followup, some concerns about the suture button device have surfaced. We reviewed the clinical and radiographic results of 24 patients with acute injuries to the distal tibiofibular syndesmosis who were treated with suture button fixation. Average followup was 20 months. The primary outcomes measure was the AOFAS ankle hindfoot score. Secondary outcomes measures included a calibrated measurement of the tibiofibular clear space and tibiofibular overlap. The average AOFAS score was 94 points. Syndesmotic parameters returned to normal after surgery and remained normal throughout the followup period. One in four patients required removal of the suture endobutton device due to local irritation or lack of motion. Osteolysis of the bone and subsidence of the device into the bone was observed in four patients. Three patients developed heterotopic ossification within the syndesmotic ligament, one mild, one moderate, and one who had a nearly complete syndesmotic fusion. The suture button device is an effective way to repair the syndesmosis. In our series, the reduction of the syndesmosis was maintained throughout the followup period. However, reoperation for device removal was more common than anticipated. Osteolysis of the bone near the implant and subsidence of the device may occur.


Vascular complications of severe hyperhomocysteinemia in patients with homocystinuria due to cystathionine beta-synthase deficiency: effects of homocysteine-lowering therapy.
Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency leads to severe hyperhomocysteinemia (HHcy). Vascular events (VE) remain the major cause of morbidity and mortality in the untreated patients with HCU. The study on the natural history of untreated HCU disclosed that, at the time of maximal risk, in other words beyond 10 years old, there was one event per 25 years. Recent studies from Australia (n = 32), The Netherlands (n = 28), and Ireland (n = 24) have documented the effects of long-term treatment on the vascular outcome of a total of 84 patients with 1314 patient-years of treatment for HCU. The mean (range) age was 27.8 (2.5 to 70) years. Five VE were recorded during treatment; one pulmonary embolism, two myocardial infarctions, and two abdominal aneurysms. All five VE occurred in B6-responsive patients at a mean (range) age of 48.8 (30 to 60) years. In 1314 patient-years of treatment, 53 VE would have been expected if they remained untreated; instead only 5 were documented, relative risk = 0.091 (95% confidence interval [CI] 0.043 to 0.190; p < 0.001). Appropriate homocysteine-lowering therapy for severe HHcy significantly reduced the vascular risk in patients with HCU. VE were rare with treatment despite the fact that the post-treatment homocysteine levels were several times higher than the cutoff point for homocysteine in the normal population. The present findings may have relevance to the current concept of "mild HHcy" as a risk factor for vascular disease, with elevated plasma homocysteine levels considerably lower than that of the post-treatment levels in this group of reported patients.


Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.
Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.


High incidence of acute full-thickness rotator cuff tears.
Epidemiological studies of full-thickness rotator cuff tears (FTRCTs) have mainly investigated degenerative lesions. We estimated the population-based incidence of acute FTRCT using a new diagnostic model. During the period November 2010 through October 2012, we prospectively studied all patients aged 18-75 years with acute onset of pain after shoulder trauma, with limited active abduction, and with normal conventional radiographs. 259 consecutive patients met these inclusion criteria. The patients had a median age of 51 (18-75) years. 65% were males. The patients were divided into 3 groups according to the clinical findings: group I, suspected FTRCT; group II, other specific diagnoses; and group III, sprain. Semi-acute MRI was performed in all patients in group I and in patients in group III who did not recover functionally. We identified 60 patients with FTRCTs. The estimated annual incidence of MRI-verified acute FTRCT was 16 (95% CI: 11-23) per 10(5) inhabitants for the population aged 18-75 years and 25 (CI: 18-36) per 10(5) inhabitants for the population aged 40-75 years. The prevalence of acute FTRCT in the study group was 60/259 (23%, CI: 18-28). The tears were usually large and affected more than 1 tendon in 36 of these 60 patients. The subscapularis was involved in 38 of the 60 patients. Acute FTRCTs are common shoulder injuries, especially in men. They are usually large and often involve the subscapularis tendon.


Emergence of KPC-producing Klebsiella pneumoniae in Italy.
The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed. Klebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all beta-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-beta-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test. This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.


Reorganizing nursing work on surgical units: a time-and-motion study.
A time-and-motion study was conducted in response to perceptions that the surgical nursing staff at a Montreal hospital was spending an excessive amount of time on non-nursing care. A sample of 30 nurse shifts was observed by trained observers who timed nurses' activities for their entire working shift using a hand-held Personal Digital Assistant. Activities were grouped into four main categories: direct patient care, indirect patient care, non-nursing and personal activities. Break and meal times were excluded from the denominator of total worked hours. A total of 201 working hours were observed, an average of 6 hours, 42 minutes per nurse shift. The mean proportions of each nurse shift spent on the main activity categories were: direct care 32.8%, indirect care 55.7%, non-nursing tasks 9.0% and personal 2.5%. Three activities (communication among health professionals, medication verification/preparation and documentation) comprised 78.9% of indirect care time. Greater time on indirect care was associated with work on night shifts and on the short-stay surgical unit. Subsequent work reorganization focused on reducing time spent on communication and medications. The authors conclude that time-and-motion studies are a useful method of monitoring appropriate use of nursing staff, and may provide results that assist in restructuring nursing tasks.