Role of interferon-stimulated responsive element-like element in interleukin-8 promoter in Helicobacter pylori infection.
Gastric mucosal interleukin (IL)-8 levels are related to the presence of both the cag pathogenicity island (PAI) and OipA. We investigated the regions of the IL-8 promoter and the upstream signaling involved in IL-8 gene transcription. We cocultured parental Helicobacter pylori and isogenic oipA, hopZ, or cagE gene knockout mutants with gastric cancer cells. The regulatory sites in the IL-8 promoter were examined by luciferase reporter gene assay, electrophoretic mobility shift assays, and immunoblot analyses. Phosphorylated signal transducers and activators of transcription 1 (STAT1) levels in the antral gastric mucosa were measured by enzyme-linked immunosorbent assay. Maximal H. pylori -induced IL-8 gene transcription required the presence of the interferon-stimulated responsive element (ISRE)-like element, nuclear factor (NF)-kappa B and activator protein (AP)-1 binding sites. In vitro studies showed that OipA and the cag PAI were involved in inducing interferon regulatory factor (IRF)-1 to bind and activate the ISRE-like element and that the cag PAI, but not OipA, was involved in activating AP-1 and NF-kappa B. Both in vitro and in vivo studies showed that OipA, but not the cag PAI, was involved in STAT1 phosphorylation, as upstream signaling of IRF-1. OipA and the cag PAI are both necessary for full activation of the IL-8 promoter but act via different pathways that diverge upstream of IRF-1 where only OipA is involved in the STAT1-IRF1-ISRE pathway. The mucosal inflammatory response to H. pylori infection is complex and involves different pathways converging on the IL-8 promoter.


A population-based assessment of germline HOXB13 G84E mutation and prostate cancer risk.
A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 (HOXB13) was recently reported to be associated with hereditary prostate cancer. To explore the prevalence and penetrance of HOXB13 G84E in a general population. G84E and 14 additional HOXB13 polymorphisms were genotyped in two population-based, Swedish, case-control samples (Cancer of the Prostate in Sweden [CAPS] and Stockholm-1) comprising 4693 controls and 5003 prostate cancer cases. CAPS collected data on patients and population controls nationally between 2001 and 2003. Stockholm-1 collected data on biopsy-positive patients and biopsy-negative controls in the Stockholm area between 2005 and 2007. The outcome was pathologically verified prostate cancer. Relative and absolute risks among HOXB13 G84E mutation carriers were explored, as was the combined impact on disease risk of G84E and a polygenic score based on 33 established, common, low-risk variants. HOXB13 G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2-5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4-5.2). The strongest association was observed for young-onset (OR: 8.6; 95% CI, 5.1-14.0) and hereditary (OR: 6.6; 95% CI, 3.3-12.0) prostate cancer. Haplotype analyses supported that G84E is a founder mutation. G84E carriers have an estimated 33% (95% CI, 23-46) cumulative risk to age 80 yr of prostate cancer, compared to 12% (95% CI, 11-13) among noncarriers. For G84E carriers within the top quartile of a polygenic score of established susceptibility variants, the cumulative risk was estimated at 48% (95% CI, 36-64). HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer. One-third of G84E carriers will be diagnosed with prostate cancer, which has implications for surveillance in mutation carriers.


Medical evaluation, electrocardiographic analysis, and exercise testing of elite women distance runners.
Sixteen elite women runners and 14 good women runners underwent medical history and physical examinations. Resting ECGs were recorded in all and exercise ECGs in 28 of the 30 (two were injured). Women in both groups combined endurance with supplemental strength and flexibility workouts. They also tended to avoid potentially harmful substances such as excess dietary saturated fats, cigarettes, and alcohol. Their cardiac examinations were not unlike those of elite male runners. Several differences from the male runners were noted on both the resting and exercise ECGs.


Metal oxides for optoelectronic applications.
Metal oxides (MOs) are the most abundant materials in the Earth's crust and are ingredients in traditional ceramics. MO semiconductors are strikingly different from conventional inorganic semiconductors such as silicon and III-V compounds with respect to materials design concepts, electronic structure, charge transport mechanisms, defect states, thin-film processing and optoelectronic properties, thereby enabling both conventional and completely new functions. Recently, remarkable advances in MO semiconductors for electronics have been achieved, including the discovery and characterization of new transparent conducting oxides, realization of p-type along with traditional n-type MO semiconductors for transistors, p-n junctions and complementary circuits, formulations for printing MO electronics and, most importantly, commercialization of amorphous oxide semiconductors for flat panel displays. This Review surveys the uniqueness and universality of MOs versus other unconventional electronic materials in terms of materials chemistry and physics, electronic characteristics, thin-film fabrication strategies and selected applications in thin-film transistors, solar cells, diodes and memories.


Stochastic Model of T Cell Repolarization during Target Elimination I.
Cytotoxic T lymphocytes (T) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e., target cells). Once a natural killer or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a repolarization of the cell involving the rotation of the microtubule (MT) cytoskeleton and a movement of the MT organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly, a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules, and mitochondria. Because the mechanism of this relocation is still elusive, we devise a theoretical model for the molecular-motor-driven motion of the MT cytoskeleton confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and capture-shrinkage mechanisms, and compare quantitative predictions about the spatiotemporal evolution of MTOC position and MT cytoskeleton morphology with experimental observations. The model predicts the experimentally observed biphasic nature of the repositioning due to an interplay between MT cytoskeleton geometry and motor forces and confirms the dominance of the capture-shrinkage over the cortical sliding mechanism when the MTOC and IS are initially diametrically opposed. We also find that the two mechanisms act synergistically, thereby reducing the resources necessary for repositioning. Moreover, it turns out that the localization of dyneins in the peripheral supramolecular activation cluster facilitates their interaction with the MTs. Our model also opens a way to infer details of the dynein distribution from the experimentally observed features of the MT cytoskeleton dynamics. In a subsequent publication, we will address the issue of general initial configurations and situations in which the T cell established two ISs.


Analysis of first flush to improve the water quality in rainwater tanks.
Although most Australians receive their domestic supply from reticulated mains or town water, there are vast areas with very low population densities and few reticulated supplies. In many of these areas rainwater collected in tanks is the primary source of drinking water. Heavy metals have recently become a concern as their concentration in rain water tanks was found to exceed recommended levels suitable for human consumption. Rainwater storage tanks also accumulate contaminants and sediments that settle to the bottom. Although not widely acknowledged, small amounts of contaminants such as lead found in rain water (used as drinking water) may have a cumulative and poisonous effect on human health over a life time. This is true for certain factors that underlie many of the chronic illnesses that are becoming increasingly common in contemporary society. The paper reports on a study which is part of a project that aims to develop a cost effective in-line filtration system to improve water quality in rainwater tanks. To enable this, the characteristics of rainwater need to be known. One component of this characterization is to observe the effects of the first flush on a rainwater tank. Samples of the roof runoff collected from an urban residential roof located in the Sydney Metropolitan Area in the initial first few millimetres of rain were analysed. The results show that bypassing the first 2 mm of rainfall gives water with most water quality parameters compliant with the Australian Drinking Water Guidelines (ADWG) standards. The parameters that did not comply were lead and turbidity, which required bypassing approximately the first 5 mm of rainfall to meet ADWG standards. Molecular weight distribution (MWD) analysis showed that the concentration of rainwater organic matter (RWOM) decreased with increasing amount of roof runoff.


In-House Attending Trauma Surgeon Does Not Reduce Mortality in Patients Presented to a Level 1 Trauma Center.
Trauma is the leading cause of death in the Western world. Trauma systems have been paramount in opposing this problem. Commonly, Level 1 Trauma Centers are staffed by in-house (IH) attending trauma surgeons available 24/7, whereas other institutions function on an on-call (OC) basis with defined response times. There is on-going debate about the value of an IH attending trauma surgeon compared to OC trauma surgeons regarding clinical outcome. This study was performed at a tertiary care facility complying with all requirements to be a designated Level 1 Trauma Center as defined by the American College of Surgeons Committee on Trauma (ACSCOT). Inclusion occurred from January 1, 2012 through December 31, 2013. Patients were assigned an identifier for IH trauma surgeon attendance versus OC attendance. The primary outcome variable studied was overall mortality in relation to IH or OC attending trauma surgeons. Additionally, time to operating theater, hospital length-of-stay (HLOS), and intensive care unit (ICU) admittance were investigated. A total of 1,287 unique trauma cases in 1,285 patients were presented to the trauma team. Of all cases, 712 (55.3%) occurred between 1700h and 0800h. These 712 cases were treated by an IH attending in 66.3% (n = 472) and an OC attending in 33.7% (n = 240). In the group of patients treated by an IH attending trauma surgeon, the overall mortality rate was 5.5% (n = 26); in the group treated by an OC attending, the overall mortality rate was 4.6% (n = 11; P = .599). Cause of death was traumatic brain injury (TBI) in 57.6%. No significant difference was found in the time between initial presentation at the trauma room and arrival in the operating theater. In terms of trauma-related mortality during non-office hours, no benefit was demonstrated through IH trauma surgeons compared to OC trauma surgeons.


Neck location of basal cell carcinomas: a new-significant variant?
Basal cell carcinoma of the neck has been suggested to have a distinct clinical, histological and prognostic significance. The aim of our study is to verify this assumption. Among 1,185 basal cell carcinomas, we have observed 42 tumors localized on the neck. The mean age did not differ from that of patients with basal cell carcinomas on other sites, and there was no difference in incidence between sexes. The frequence of recurrence was 4.76%, similar to the recurrence rate of basal cell carcinomas on other sites. The lesions were typed histologically according to accepted criteria. The patterns observed were: nodular (62.8%), superficial (21.1%), mixed (4.7%), micronodular (5.9%), and infiltrative (5.7%). These frequencies did not differ significantly from those observed in the basal cell carcinomas on other sites. Thus, in comparison with the overall basal cell carcinoma population, the tumors of the neck do not represent a particular clinical and histologic subtype and do not have a particular recurrence potential. We think that basal cell carcinomas localized on the neck do not represent a particular subtype of these tumors; their treatment can be the same as that of basal cell carcinomas on other regions.


How better availability of materials improved hand-hygiene compliance.
Hand hygiene is one of the most effective measures for preventing infections. The annual NHS staff survey in England provides national and local data on how staff feel about working in the NHS. It also provides staff with the opportunity to give their views on the availability of hand-washing materials. The infection prevention and control team at an NHS trust decided a review was required on this issue. This review assessed the availability of hand-washing materials and alcohol handrub on wards and at ward entrances. Three community buildings and 31 wards were reviewed. The audit results showed the availability of hand-washing materials was good in 30 out of 34 areas. Staff on both wards and in the community buildings highlighted what other materials were required for hand hygiene, and steps were made to provide these. The audit allowed hand-hygiene practices to be benchmarked across the trust and increased staff awareness of improving hand hygiene. As a result of this audit, the hand-hygiene compliance score increased from 80% to 95%.


An Organizational Commitment to Diversity, Equity, Inclusion, and Justice: A Multipronged Strategic Approach.
Cedars-Sinai is a sixth continuous Magnet organization in Southern California that embodies inclusive leadership in support of diversity, equity, inclusion, and justice (DEIJ) principles. The organization adheres to a strategic model prioritizing staff sense of belonging, empowerment, engagement, curiosity, and creativity. Employing inclusive leadership, we have implemented strong programs of professional development and continuous learning, innovation, and research. This leadership and these programs have fostered a culture of inquiry, support evidence-driven practice, quality improvement, and staff engagement. Our organization is committed to creating a caring and healing environment that promotes performance. We believe in practicing loving-kindness toward ourselves and others as a core value. Executive leadership support has been a key element in our successful implementation of DEIJ strategies, including employee resource groups, Shared Leadership Councils, transition to practice programs, health equity research, and innovative solutions. These strategies have been shown to yield a significant return on investment.


Effect of sleep state on the laryngeal chemoreflex in neonatal piglets.
The laryngeal chemoreflex (LCR) is a brain stem-mediated response that is a potential mechanism for sudden infant death syndrome. The vast majority of sudden infant death occurs during sleep, yet it remains to be established whether there is a particular sleep state that makes an infant animal more susceptible to apneic events via the LCR. The purpose of this study was to investigate the LCR during different sleep states in the neonatal piglet. In this study, continuous physiologic monitoring and electroencephalographic, electro-oculographic, and electromyographic techniques were utilized to study neonatal piglets during a hypnotic induced sleep model. Propofol drip anesthetic was utilized to provide an anesthetic state and was titrated for dose-dependent sedation. The LCR was initiated in 11 animals during quiet sleep, rapid eye movement sleep, and the anesthetic state. Baseline respiratory and cardiovascular responses were measured. Durations of apnea were recorded and compared. This study found that despite known physiologic differences in respiratory control during different sleep states as compared to the anesthetic state, there appears to be no increased risk of profound apnea in one state versus another in piglets 19 to 28 days old.


Dynamic Distribution of HIG2A between the Mitochondria and the Nucleus in Response to Hypoxia and Oxidative Stress.
Mitochondrial respiratory supercomplex formation requires HIG2A protein, which also has been associated with cell proliferation and cell survival under hypoxia. HIG2A protein localizes in mitochondria and nucleus. DNA methylation and mRNA expression of the HIGD2A gene show significant alterations in several cancers, suggesting a role for HIG2A in cancer biology. The present work aims to understand the dynamics of the HIG2A subcellular localization under cellular stress. We found that HIG2A protein levels increase under oxidative stress. H2O2 shifts HIG2A localization to the mitochondria, while rotenone shifts it to the nucleus. HIG2A protein colocalized at a higher level in the nucleus concerning the mitochondrial network under normoxia and hypoxia (2% O2). Hypoxia (2% O2) significantly increases HIG2A nuclear colocalization in C2C12 cells. In HEK293 cells, chemical hypoxia with CoCl2 (>1% O2) and FCCP mitochondrial uncoupling, the HIG2A protein decreased its nuclear localization and shifted to the mitochondria. This suggests that the HIG2A distribution pattern between the mitochondria and the nucleus depends on stress and cell type. HIG2A protein expression levels increase under cellular stresses such as hypoxia and oxidative stress. Its dynamic distribution between mitochondria and the nucleus in response to stress factors suggests a new communication system between the mitochondria and the nucleus.


EGFR signaling in the HGG-02 glioblastoma cell line with an unusual loss of EGFR gene copy.
Epidermal growth factor receptor (EGFR) gene amplification and the overexpression of EGFR are described as common features of glioblastoma multiforme (GBM). Nevertheless, we previously reported the loss of EGFR gene copy in a GBM specimen from a patient with an unusually favorable course of the disease, and the HGG-02 cell line with this aberration was successfully derived from this tumor. Here, we present a detailed analysis of changes in gene expression and cell signaling in the HGG-02 cell line; the GM7 reference cell line with a standard EGFR gene copy number derived from a very aggressive GBM was used as a control. We confirmed the downregulation of EGFR expression and signaling in HGG-02 cells using different methods (RTK analysis, gene profiling and RT-PCR). Other changes that may have contributed to the non-aggressive phenotype of the primary tumor were identified, including the downregulated phosphorylation of the Axl and Trk receptors, as well as increased activity of JNK and p38 kinases. Notably, differences in PDGF signaling were detected in both of these cell lines; HGG-02 cells preferentially expressed and signaled through PDGFRα, and PDGFRβ was strongly overexpressed and phosphorylated in the GM7 reference cell line. Using expression profiling of cancer-related genes, we revealed the specific profile of HGG-02 cells that included upregulated tumor-suppressors as well as downregulated genes associated with the extracellular matrix. This study represents the first comprehensive analysis of gene expression and cell signaling in glioblastoma cells with lower EGFR gene dosage. As indicated by our results, the TAM receptors, Trk receptors and PDGFRs need to be investigated further since their regulation appears to be important for glioblastoma biological features as well as the clinical course of the disease.


In vivo and in vitro effects of integration host factor at the DmpR-regulated sigma(54)-dependent Po promoter.
Transcription from the Pseudomonas CF600-derived sigma(54)-dependent promoter Po is controlled by the aromatic-responsive activator DmpR. Here we examine the mechanism(s) by which integration host factor (IHF) stimulates DmpR-activated transcriptional output of the Po promoter both in vivo and in vitro. In vivo, the Po promoter exhibits characteristics that typify many sigma(54)-dependent promoters, namely, a phasing-dependent tolerance with respect to the distance from the regulator binding sites to the distally located RNA polymerase binding site, and a strong dependence on IHF for optimal promoter output. IHF is shown to affect transcription via structural repercussions mediated through binding to a single DNA signature located between the regulator and RNA polymerase binding sites. In vitro, using DNA templates that lack the regulator binding sites and thus bypass a role of IHF in facilitating physical interaction between the regulator and the transcriptional apparatus, IHF still mediates a DNA binding-dependent stimulation of Po transcription. This stimulatory effect is shown to be independent of previously described mechanisms for the effects of IHF at sigma(54) promoters such as aiding binding of the regulator or recruitment of sigma(54)-RNA polymerase via UP element-like DNA. The effect of IHF could be traced to promotion and/or stabilization of open complexes within the nucleoprotein complex that may involve an A+T-rich region of the IHF binding site and promoter-upstream DNA. Mechanistic implications are discussed in the context of a model in which IHF binding results in transduction of DNA instability from an A+T-rich region to the melt region of the promoter.


Detection of Arcobacter spp. in Ground Pork by Modified Plating Methods.
A modified cefsulodin-irgasan-novobiocin (CIN) medium was developed for the recovery of Arcobacter spp. from meats. Modified CIN was compared to brain heart infusion agar supplemented with 10% bovine blood and cephalothin, vancomycin, and amphotericin B (CVA) as well as brain heart infusion agar supplemented with 10% bovine blood and no antibiotics. The three media were used to recover Arcobacter spp. in a survey of pork-processing plants. Examination of ground pork (149 samples) from one Iowa slaughter facility (Plant #1) revealed that 89 percent of the samples were positive for Arcobacter spp. In a second survey conducted 9 months later involving that same plant and four others, only 5% of the samples from the four plants were found to be positive for Arcobacter spp. Again, 90% of the samples were positive from Plant #1. It was not determined whether the sanitary practices during slaughter or the rearing of pigs on the source farms contributed to the prevalence of Arcobacter spp. in one plant versus another.


Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions. The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives. From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases. A total of 56 591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56 591 potential cases, we estimated 475-875 to be valid SJS/TEN cases. Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.


[Iron deficiency anemia in infants. Preliminary development results at five years].
Research, mostly conducted in developing countries, have suggested short and long term developmental delay in children who had iron-deficiency anemia (IDA) in their early life. This study aims to evaluate the development of 5-years old children who were diagnosed IDA at 9 months of age. 27 children with IDA diagnosed at 9 months of age and 28 non-anemic controls were followed-up until they were 5 years old. At 9 months of age and at 5 years of age, blood samples were collected for blood count, iron, transferrin and ferritin. Children with hemoglobin < 110 g/l and ferritin < 12 ng/ml were diagnosed with IDA and received iron treatment for IDA correction. C Reactive Protein and antibody to hepatitis A virus were also studied at 5 years of age. At this age, children's motor and cognitive development were accessed using Griffith's test. At 9 months of age, IDA children had [mean (SD)] 102.5 g/ l (5.9) g/l of hemoglobin and 5.6 ng/l (3.1) ng/ml of ferritin. At 5 years of age all children were healthy and without anemia. One child had positive antibody to hepatitis A virus. The results of Griffith's test at five years--anemic/non-anemic at 9 months of age. The mean (sd)-p: general coefficient--100.8 (6.6)/99.5 (7.1)-0.48; locomotor 110.2 (6.9)/109.3 (6.5)-0.62; personal-social--99.1 (11.4)/95.7(11.6)-0.28; hearing-speech--93.8 (9.1)/95.3 (13.7)-0.64; hand-eye--98.2 (13.2)/99.1 (14.3)-0.79; performance--97.5 (17.6)/96.9 (13.6)-0.88; practical reasoning--89.8 (9.1)/86.3(7.1)-0.21. As only one child had positive antibody to hepatitis A virus, the study population may be considered as belonging to a developed region. These results suggest that, at least in developed regions, infants who receive an early treatment for their mild IDA may not be affected in global development at the age of five.


Synthesis of DNA complementary to the mRNAs for milk proteins by E. coli DNA polymerase I.
E.Coli DNA polymerase I (Klenow subfragment) was used for the synthesis of complementary DNA with the mRNAs for rabbit milk proteins as templates. The cDNA formed, contained 200 nucleotides and represented about 20% of the mRNA template. The cDNA was hybridized specifically to the mRNA templates. The Klenow subfragment of the E.Coli DNA polymerase I was as efficient as the avian myeloblastosis virus reverse transcriptase in the synthesis of cDNA. The mean size of the cDNA fragments obtained with the Klenow enzyme proved to be 70% of the value obtained with the AMV reverse transcriptase and at least twice the value generally obtained with the complete E.Coli DNA polymerase I. The cDNA was used for the detection and the quantification of the mRNA template in various RNA fractions.


Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2 O exchange study.
Inversion recovery ultrashort echo time (IR-UTE) imaging holds the potential to directly characterize MR signals from ultrashort T2 tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR-UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T2 * signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D2 O exchange model and explored the potential of IR-UTE imaging for the quantification of ultrashort T2 * signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D2 O. Long T2 MR signals were measured using a clinical proton density-weighted fast spin echo (PD-FSE) sequence. IR-UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T2 signals (TInull ). Then, at this TInull , images with echo times (TEs) of 0.01-4 ms were acquired to measure the T2 * values of STCs. The PD-FSE signal dropped to near zero after 24 h of immersion in D2 O. A wide range of TInull values were used at different time points (240-330 ms for white matter and 320-350 ms for gray matter at TR = 1000 ms) because the T1 values of the long T2 tissue components changed significantly. The T2 * values of STCs were 200-300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D2 O or H2 O), and showed minimal changes after sequential immersion. The ultrashort T2 * signals seen on IR-UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D2 O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.


Detection of hepatocellular carcinoma: value of adding delayed phase imaging to dual-phase helical CT.
The purpose of our study was to determine the value of adding delayed phase imaging to dual-phase helical CT for the detection of hepatocellular carcinoma. One hundred thirteen patients with 131 hepatocellular carcinomas underwent triple-phase helical CT. The diagnosis was established by pathologic examination after surgical resection in all patients. For triple-phase helical CT, hepatic arterial, portal venous, and delayed phase scanning began 30, 60, and 180 sec, respectively, after the injection of 120 mL of iodinated contrast material. Dual-phase helical CT excluding delayed phase and triple-phase helical CT images were reviewed independently by three radiologists on a segment-by-segment basis. Diagnostic accuracy was assessed using receiver operating characteristic analysis in 330 resected segments. Sensitivities and specificities were calculated. The value of the delayed phase images in the characterization of hepatocellular carcinoma was also assessed. The diagnostic accuracy of triple-phase helical CT including delayed phase (area under the curve [A(z)], 0.973) was significantly higher than that of dual-phase helical CT (A(z), 0.954). The mean sensitivity of triple-phase CT (89%) was also significantly higher than that of dual-phase CT (86%). The mean specificities of triple-phase CT (99%) and dual-phase CT (99%) were equal. Delayed phase images were helpful in the characterization of hepatocellular carcinoma in 14% of patients. The addition of delayed phase imaging to dual-phase helical CT is valuable for the detection and characterization of hepatocellular carcinoma.


Improving Colorectal Cancer Screening Rates in Patients Referred to a Gastroenterology Clinic.
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the United States. Colonoscopy and fecal immunochemistry testing (FIT) are the primary recommended CRC screening modalities. The purpose of this study is to improve rates of CRC screening in Veterans and County hospital patients referred to gastroenterology fellow's clinics. A total of 717 patients between ages of 49 and 75 years were seen. Previous CRC screening was not performed in 109 patients (15.2%) because of not being offered (73.4%) or declining (26.6%) screening. Patients who received previous CRC screening compared with no previous screening were older (mean age 62.3 years vs. 60.3 years, p < .003), white (88.6% vs. 78.3%, p < .027), and more likely to be Veterans patients (90.8% vs. 77.5%, p < .001). After systematically discussing options for screening with 78 of the 109 unscreened patients, 56 of them (71.8%) underwent screening with either colonoscopy (32) or FIT (24). Patients seen by fellows in their last year of training agreed to undergo screening more often than those seen by other fellows (100% vs. 66.2%, p < .033). Systematic discussions about both colonoscopy and FIT can improve the overall rates of CRC screening.


Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.
The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus is worse than that of other staphylococci. Thus, it is clear that all peritonitis episodes cannot be considered equivalent in terms of outcome. The concept of peritonitis rate is only meaningful when specific organisms are considered.


Isotype-specific changes in the amount of beta-tubulin RNA in synchronized tobacco BY2 cells.
The 3'-ends of the beta-tubulin cDNA were amplified from tobacco BY2 polyA+ RNA. According to the differences in the predicted amino acid sequence at the extreme C-terminal, they were grouped into three different isotypes, NTB1 in which "EEGDYYEEDEEDLNEA", NTB2 in which "EEEYYEDEEEA QED" and NTB3 in which "DECEYEEEEEYDHEGN" follows the conservative "YQQYQDATAD" sequence. Using unique 3'-untranslated regions as probes, changes in the RNA levels of each beta-tubulin isotype were determined by dot-blot hybridization. The levels exhibited characteristic rhythms in the cell cycle. NTB1 RNA was highest in S phase in comparison to NTB2 RNA level which was highest in late G2. On the other hand, NTB3 RNA level was highest in early G2.


Trends in drug orientations and behavior: changes in a rural community, 1975-1982.
This paper examines trends in rural American rates of marijuana use and drug-related orientations over an 8-year period. The younger rural youths (13-year-olds) in our three surveys (1975, 1979, and 1982) reported significant declines in rates of use and expressed a general trend toward conservatism. The attitudes and orientations of older youths (16-year-olds) changed also, and in the same directions, but those changes were not statistically significant. Use rates for 16-year-olds, on the other hand, increased, but again the changes were not statistically significant. In at least one cohort we studied, attitudes changed prior to shifts in behavior. We also observed that the predictive ability of the selected attitudes and orientations increased considerably from 1975 to 1982. In the midst of a movement toward conservatism on drug issues, liberalness was even more closely linked to marijuana use than in the previous decade. Lastly, we evaluate the implications of these findings for drug prevention policy and future research.


Withdrawal from heroin in three or six weeks. Comparison of methadyl acetate and methadone.
A randomized clinical trial compared four methods of outpatient withdrawal from heroin. Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate. Within each drug group, subjects were assigned to detoxification programs either within the standard three-week period or in an extended six weeks of treatment. Outcome measures included retention to the end of the dosing schedule, use of illicit drugs during treatment, subjective discomfort, satisfaction, staff ratings of global progress, and durability of change at a three-month follow-up. Methadyl acetate performed similarly to methadone in most respects. Six-week withdrawal showed some temporary benefits over standard treatment, but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome.


A decline in global CFC-11 emissions during 2018-2019.
The atmospheric concentration of trichlorofluoromethane (CFC-11) has been in decline since the production of ozone-depleting substances was phased out under the Montreal Protocol1,2. Since 2013, the concentration decline of CFC-11 slowed unexpectedly owing to increasing emissions, probably from unreported production, which, if sustained, would delay the recovery of the stratospheric ozone layer1-12. Here we report an accelerated decline in the global mean CFC-11 concentration during 2019 and 2020, derived from atmospheric concentration measurements at remote sites around the world. We find that global CFC-11 emissions decreased by 18 ± 6 gigagrams per year (26 ± 9 per cent; one standard deviation) from 2018 to 2019, to a 2019 value (52 ± 10 gigagrams per year) that is similar to the 2008-2012 mean. The decline in global emissions suggests a substantial decrease in unreported CFC-11 production. If the sharp decline in unexpected global emissions and unreported production is sustained, any associated future ozone depletion is likely to be limited, despite an increase in the CFC-11 bank (the amount of CFC-11 produced, but not yet emitted) by 90 to 725 gigagrams by the beginning of 2020.


Identification of two DNA helicases UvrD and DinG as suppressors for lethality caused by mutant cspA mRNAs.
CspA is a major cold shock-inducible protein (70 aa), and its major role in the cold shock response was shown to be as an RNA chaperone destabilizing secondary structure of mRNAs at low temperature. Previously, we showed that the overexpression of mutant cspA containing premature non-sense codons at various positions led to stalled ribosomes on mutant cspA transcripts, ultimately leading to cell death. This lethality is primarily due to the highly translatable cspA 5'-UTR that recruits most of the ribosomes from other mRNAs, which are then stalled at the abnormal stop codon. This was called the 'LACE' effect. We show here that non-sense mutation even at the 67th position as well as substitutions of aromatic amino acid residues present on the RNA-binding surface of CspA protein to alanine caused the LACE effect by trapping a substantial amount of ribosomes on cspA mRNAs. In an attempt to identify a suppressor(s), which may help the cells to recover from the inhibitory LACE effect, genetic screening of an Escherichia coli genomic library was performed. We isolated suppressors that contained the genomic fragments encoding uvrD and dinG, respectively, whose gene products are ATP-dependent DNA helicases. The nucleic acid-binding and ATPase activities of these two helicases were found to be essential for their suppression activity. This genomic screening offers an approach to shed light on the mechanistic of 5'-UTR of cspA mRNA and novel roles of E. coli helicases that function in DNA repair.


[Effects od iron supplementation on malaria infection].
An iron supplementation trial had been performed in a southern village of Togo during the rainy season when occurs malaria transmission. 241 infants from 6 to 36 months old were matched in two randomized groups. The first one (G1) received oral iron supplementation every day during three months. The second group (G2) received placebo. Tablet administration was double blind made. A third group (G3) had been created from two others with anaemic infants and received daily iron supplementation. Three biological and clinical surveys were done, i) before the trial (T0), ii) after supplementation (T3) and iii) six months later (T9). Several parameters were studied including malaria parasite density and titration of malaria antibodies. For each group the prevalence of Plasmodium falciparum was identical in the three surveys. Means of parasite density decreased during and after rainy season but variations were not significant. High parasitaemia frequency (i.e. greater than 10,000 parasitized red cells per mm3, considered as pyrogenic threshold) were identical in all groups and decreased after rainy season. Antibodies titers did not show any variation in the three groups. It seems that iron supplementation did not modify in 6 to 36 months infants the susceptibility to malaria nor the organism response.


[Features of speech dynamics in patients with different variants of motor aphasia in stroke].
Results of studying the peculiarities of speech restoration in patients with dynamic, efferent, afferent, and mixed motor aphasia are presented. These peculiarities were found to depend on the gravity of the speech disorder, time of the beginning and duration of the logopedic treatment, methods of the restorative training, relation between the impaired and preserved sides of the speech function. The studies of the peculiarities of the speech restoration process in various forms of motor aphasia have demonstrated that restorative training is necessary, has good prospects, and may contribute to a substantial social readaptation of the patients.


The intergenerational multiple deficit model and the case of dyslexia.
Which children go on to develop dyslexia? Since dyslexia has a multifactorial etiology, this question can be restated as: what are the factors that put children at high risk for developing dyslexia? It is argued that a useful theoretical framework to address this question is Pennington's (2006) multiple deficit model (MDM). This model replaces models that attribute dyslexia to a single underlying cause. Subsequently, the generalist genes hypothesis for learning (dis)abilities (Plomin and Kovas, 2005) is described and integrated with the MDM. Next, findings are presented from a longitudinal study with children at family risk for dyslexia. Such studies can contribute to testing and specifying the MDM. In this study, risk factors at both the child and family level were investigated. This led to the proposed intergenerational MDM, in which both parents confer liability via intertwined genetic and environmental pathways. Future scientific directions are discussed to investigate parent-offspring resemblance and transmission patterns, which will shed new light on disorder etiology.


Effects of Plyometric and Sprint Training on Physical and Technical Skill Performance in Adolescent Soccer Players.
To determine the influence of a short-term combined plyometric and sprint training (9 weeks) within regular soccer practice on explosive and technical actions of pubertal soccer players during the in-season. Twenty-six players were randomly assigned to 2 groups: control group (CG) (soccer training only) and combined group (CombG) (plyometric + acceleration + dribbling + shooting). All players trained soccer 4 times per week and the experimental groups supplemented the soccer training with a proposed plyometric-sprint training program for 40 minutes (2 days per weeks). Ten-meter sprint, 10-m agility with and without ball, CMJ and Abalakov vertical jump, ball-shooting speed, and Yo-Yo intermittent endurance test were measured before and after training. The experimental group followed a 9-week plyometric and sprint program (i.e., jumping, hurdling, bouncing, skipping, and footwork) implemented before the soccer training. Baseline-training results showed no significant differences between the groups in any of the variables tested. No improvement was found in the CG; however, meaningful improvement was found in all variables in the experimental group: CMJ (effect size [ES] = 0.9), Abalakov vertical jump (ES = 1.3), 10-m sprint (ES = 0.7-0.9), 10-m agility (ES = 0.8-1.2), and ball-shooting speed (ES = 0.7-0.8). A specific combined plyometric and sprint training within regular soccer practice improved explosive actions compared with conventional soccer training only. Therefore, the short-term combined program had a beneficial impact on explosive actions, such as sprinting, change of direction, jumping, and ball-shooting speed which are important determinants of match-winning actions in soccer performance. Therefore, we propose modifications to current training methodology for pubertal soccer players to include combined plyometric and speed training for athlete preparation in this sport.


Improved ethanol production by a xylose-fermenting recombinant yeast strain constructed through a modified genome shuffling method.
Xylose is the second most abundant carbohydrate in the lignocellulosic biomass hydrolysate. The fermentation of xylose is essential for the bioconversion of lignocelluloses to fuels and chemicals. However the wild-type strains of Saccharomyces cerevisiae are unable to utilize xylose. Many efforts have been made to construct recombinant yeast strains to enhance xylose fermentation over the past few decades. Xylose fermentation remains challenging due to the complexity of lignocellulosic biomass hydrolysate. In this study, a modified genome shuffling method was developed to improve xylose fermentation by S. cerevisiae. Recombinant yeast strains were constructed by recursive DNA shuffling with the recombination of entire genome of P. stipitis with that of S. cerevisiae. After two rounds of genome shuffling and screening, one potential recombinant yeast strain ScF2 was obtained. It was able to utilize high concentration of xylose (100 g/L to 250 g/L xylose) and produced ethanol. The recombinant yeast ScF2 produced ethanol more rapidly than the naturally occurring xylose-fermenting yeast, P. stipitis, with improved ethanol titre and much more enhanced xylose tolerance. The modified genome shuffling method developed in this study was more effective and easier to operate than the traditional protoplast-fusion-based method. Recombinant yeast strain ScF2 obtained in this study was a promising candidate for industrial cellulosic ethanol production. In order to further enhance its xylose fermentation performance, ScF2 needs to be additionally improved by metabolic engineering and directed evolution.


Hematopoietic cells regulate the angiogenic switch during tumorigenesis.
Hematopoietic cells (HCs) promote blood vessel formation by producing various proangiogenic cytokines and chemokines and matrix metalloproteinases. We injected mouse colon26 colon cancer cells or human PC3 prostate adenocarcinoma cells into mice and studied the localization of HCs during tumor development. HCs were distributed in the inner tumor mass in all of the tumor tissues examined; however, the localization of HCs in the tumor tissue differed depending on the tumor cell type. In the case of colon26 tumors, as the tumor grew, many mature HCs migrated into the tumor mass before fine capillary formation was observed. On the other hand, although very few HCs migrated into PC3 tumor tissue, c-Kit+ hematopoietic stem/progenitor cells accumulated around the edge of the tumor. Bone marrow suppression induced by injection of anti-c-Kit neutralizing antibody suppressed tumor angiogenesis by different mechanisms according to the tumor cell type: bone marrow suppression inhibited the initiation of sprouting angiogenesis in colon26 tumors, while it suppressed an increase in the caliber of newly developed blood vessels at the tumor edge in PC3 tumors. Our findings suggest that HCs are involved in tumor angiogenesis and regulate the angiogenic switch during tumorigenesis.


Location of adrenal medullary pheochromocytoma by I-123 metaiodobenzylguanidine SPECT.
This is a retrospective study evaluating the efficacy of SPECT in the location of pheochromocytoma. Thirty patients with a suspected pheochromocytoma underwent I-123 metaiodobenzylguanidine (I-123 MIBG) SPECT 4 and 22 hours after intravenous injection of 370 MBq I-123 MIBG. SPECT was compared with planar scintigraphy, CT scanning, histology, and clinical course. Twenty-two-hour I-123 MIBG SPECT correctly identified 10 patients with adrenal medullary pheochromocytoma and correctly excluded pheochromocytoma in 19 patients. The sensitivity of the 22-hour MIBG SPECT was 1.00 and the specificity was 0.95. The positive predictive value was 0.95 and the negative predictive value was 1.00. In 16 patients, planar scintigraphy was compared with SPECT. SPECT located normal adrenal glands and tumors with greater confidence in three dimensions, but the patients with adrenal medullary pheochromocytoma were all correctly identified by planar scintigraphy. The results of SPECT and CT agreed in 29 of 30 patients (96.7%). I-123 MIBG SPECT for the location of pheochromocytoma has a high sensitivity, specificity, and positive and negative predictive values. I-123 MIBG SPECT or CT scanning alone were equally good for locating adrenal medullary pheochromocytoma but the combination of MIBG SPECT and CT makes it possible to distinguish between functioning and nonfunctioning adenomas. I-123 MIBG SPECT may be used alone or in combination with planar scintigraphy when three-dimensional location of a lesion is wanted.


Atomistic modeling of strain-controlled cyclic loading in TiAl crystalline nanowire.
In this paper, atomistic modeling of L10-TiAl nanowire has been performed utilizing the Embedded Atom Method (EAM) potential under strain-controlled cyclic loading. A nanowire oriented along the <100> axis with a cross-sectional dimension (D) of ~80 Å with a Length-to-width (L/D) ratio of 10.0 has been considered. Strain-controlled cyclic loading at room temperature has been performed by oscillating the nanowire length dimension sinusoidal with a specific amplitude and period. Tension-compression cyclic loading was employed with zero mean strain. Cyclic loading with percentage strains (%ε) of one to five percent have been considered. It has been observed that the cyclic stress in the nanowire continues to fluctuate during the initial loading cycles. However, once the nanowire becomes stable, a smooth variation of stresses with varying strain has been observed. The cause of initial fluctuations in the nanowire has been studied by varying (a) the amount of load (strain) applied, (b) the nanowire structure during cyclic loading, and (c) the rate at which the load has been applied. It has been identified that the rate of loading could be used for controlling the initial fluctuations of nanowire. Finally, a method for the calculation of cyclic stress versus cyclic strain for nanowires has been proposed. A cyclic stress versus cyclic strain curve has been plotted for a given L/D = 10 and a period of 10 ps. Results show that the TiAl nanowire is having 3/2 times higher stiffness in tension as compared to compression at a given strain under cyclic loading.


Digestive flexibility in females of the subterranean rodent ctenomys talarum in their natural habitat.
We studied the occurrence of digestive strategies at different levels in females of the subterranean herbivorous rodent Ctenomys talarum living in their natural habitat. We determined the dimensions of different parts of the gastrointestinal tract and organs along as the activity of key digestive enzymes(sucrase, maltase and N-aminopeptidase) in small intestine in females seasonally caught. Females of C. talarum did not show seasonal variations in the mass of the different parts of the gastrointestinal tract. In nonreproductive females large intestine was longer in autumn, whereas reproductive females did not show seasonal variations in the length of the different parts of the gut. Females of C. talarum exhibited a high sucrose, maltase and N-aminopeptidase activity in small intestine, although these activities were higher in small intestine of females caught in autumn (nonreproductive) than in females caught in winter (reproductive). The results show that C. talarum females exhibit characteristics in the gut at the morphological and biochemical level, which could represent digestive strategies to face the constraints imposed by their costly particular way of life.


Purification and properties of the P2 primary alkylsulphohydrolase of the detergent-degrading bacterium pseudomonas C12B.
The P2 primary alkylsulphohydrolase of the soil bacterium Pseudomonas C12B was purified to homogeneity (200-250-fold) by column chromatography on DEAE-cellulose, Sephadex G-100 and butyl-agarose. The intact protein is a dimer with a mol. wt. of 160 000. Activity towards primary alkyl sulphate esters was maximal at pH 8.3, varied little in the range pH 7.8-8.7, but decreased sharply at higher pH. For a homologous series of primary alkyl sulphate substrates (C6-C12), logKm decreased linearly with increasing chain length, corresponding to a contribution to the free energy of association between enzyme and substrate of -2.5kJ/mol for each additional CH2 group in the alkyl chain. logKi for the competitive inhibition by secondary alkyl 2-sulphate esters followed a similar pattern (-2.4kJ/mol for each additional CH2 group) except that only n-1 carbon atoms effectively participate in hydrophobic bonding, implying that the C-1 methyl group is not involved. logKi values for inhibition primary alkanesulphonates also depended linearly on chain length but with a diminished gradient, indicating a free-energy increment of -1.2kJ/mol per additional CH2 group. The collective results showed the presence of a hydrophobic site on the enzyme capable of accomodating an alkyl chain of considerable length. Cationic structures (in the form of arginine, lysine or histidine), whose presence might be expected for binding the anionic sulphate group, were not detectable at the active site.


Mitochondrial Deoxyguanosine Kinase Regulates NAD+ Biogenesis Independent of Mitochondria Complex I Activity.
Overexpression of DGUOK promotes mitochondria oxidative phosphorylation and lung adenocarcinoma progression. However, the role and mechanism of DGUOK in regulation of mitochondria function and lung cancer progression still poorly understood. Here we demonstrated that DGUOK regulated NAD+ biogenesis. Depletion of the DGUOK significantly decreased NAD+ level. Furthermore, knockout of the DGUOK considerably reduced expression of the NMNAT2, a key molecule controlling NAD+ synthesis, at both mRNA and protein levels. Ectopic expression of the NMNAT2 abrogated the effect of knockdown of DGUOK on NAD+. Notably, this regulation is independent of DGUOK -mediated mitochondria complex I activity. We also showed that NMNAT2 was highly expressed in lung adenocarcinoma and negatively correlated with the patient overall survival. Our study suggested that DGUOK regulates NAD+ in a NMNAT2 dependent manner and DGUOK-NMNAT2-NAD+ axis could be a potential therapeutic target in lung adenocarcinoma.


Atypical presentations of retroperitoneal giant schwannomas.
Schwannomas are usually benign rare tumors that originating from Schwann cells of peripheral nerve sheaths. Presentation is generally varied and changed in a non-specific range from abdominal mass, flank pain to incidental findings. Herein we report 2 cases of retroperitoneal giant schwannomas with different clinical presentations, of whom one presented with vague abdominal pain, palpable abdominal mass for 4 years, swelling and bilateral hydronephrosis that caused by giant abdominal mass; the other one presented with right flank pain, rectal hemorrhage and lower extremities edema. Two patients were treated by complete surgical excision of masses. The histological and immunohistochemical diagnosis was reported as benign schwannoma. Both of patients are doing well and had no recurrence in 9 years and 28 months follow-up, respectively.


Acid-base speciation of carboxylate ions in the surface region of aqueous solutions in the presence of ammonium and aminium ions.
The acid-base speciation of surface-active carboxylate ions in the surface region of aqueous solutions was studied with synchrotron-radiation-based photoelectron spectroscopy. The protonated form was found at an extraordinarily large fraction compared to that expected from the bulk pH. When adding salts containing the weak acid NH4(+) to the solution, the fraction of the acidic form at the surface increases, and to a much greater extent than expected from the bulk pH of the solution. We show that ammonium ions also are overrepresented in the surface region, and propose that the interaction between the surface-active anionic carboxylates and cationic ammonium ions creates a carboxylate-ammonium bilayer close to the surface, which increases the probability of the protonation of the carboxylate ions. By comparing the situation when a salt of the less volatile amine diethanolamine is used, we also show that the observed evaporation of ammonia that occurs after such an event only affects the equilibrium marginally.


Surgery for deep venous incompetence.
Chronic deep venous incompetence (DVI) is caused by incompetent vein valves and/or blockage of large-calibre leg veins and causes a range of symptoms including recurrent ulcers, pain and swelling. Most surgeons accept that well-fitted graduated compression stockings (GCS) and local care of wounds serve as adequate treatment for most patients, but sometimes symptoms are not controlled and ulcers recur frequently, or they do not heal despite compliance with conservative measures. In these situations, in the presence of severe venous dysfunction, surgery has been advocated by some vascular surgeons. This is an update of the review first published in 2000. To assess the effects of surgical management of deep venous incompetence in terms of ulcer healing, ulcer recurrence and alleviation of symptoms. For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 9). Randomised controlled trials of surgical treatment for patients with DVI. For this update, two review authors (RRG and SCH) extracted data independently. All included studies required full risk of bias assessment in line with current procedures of The Cochrane Collaboration. Two review authors (RRG and SCH) independently assessed risk of bias and consulted with a third review author (AA) when necessary. Four studies with 273 participants were included. All included studies reported clinical outcomes following valvuloplasty. We found no studies investigating other surgical procedures for the treatment of patients with DVI. All included studies investigated primary valve incompetence. We found no trials that investigated the results of surgery for secondary valvular incompetence or the obstructive form of DVI. Because different outcome measures were used, it was not possible to pool the results of included studies. The methodological quality of the included studies was low, mainly because information regarding randomisation and blinding was missing, or because data were incomplete or were presented poorly. Ulcer healing and ulcer recurrence were not reported in one study, and the remaining three studies did not include participants with ulcers or with active ulceration. Three studies reported no significant complications of surgery and no incidence of DVT during follow-up. One study did not report on the occurrence of complications. Clinical changes were assessed by subjective and objective measurements, as specified in the clinical, aetiological, anatomical, and pathophysiological (CEAP) classification score. This requires vascular laboratory measurements of lower limb haemodynamics before and after surgery. Tests include an overall evaluation of venous function with venous refilling time (VRT) or ambulatory venous pressure (AVP). Two small trials comparing external valvuloplasty using limited anterior plication in combination with ligation of incompetent superficial veins against ligation alone (L) showed that ligation plus limited anterior plication produced significant improvement in AVP: The mean difference was -15 mm Hg (95% confidence interval (CI) -20.9 to -9.0) at one year and -15 mm Hg (95% CI -21 to -8.9) at two years. Sustainable statistically significant improvement in AVP and VRT was achieved by ligation and limited anterior plication at 10 years in one study. However, AVP values after surgery remained relatively high, causing its benefit to be questioned. Similarly, another study including participants who were deteriorating preoperatively showed sustained mild clinical improvement for seven years in those subjected to valvuloplasty compared with participants undergoing superficial venous surgery alone. However, this benefit was lost when the condition of participants was stable preoperatively. One small study (n = 40) with grade 3 reflux and no participants with ulcers reported that external valvuloplasty of the femoral vein combined with surgical repair of the superficial venous system improved the haemodynamic status of the lower limbs, restored valvular function more effectively and achieved better outcomes than surgical repair of the superficial venous system alone. No evidence was found for benefit or harm of valvuloplasty in the treatment of patients with DVI secondary to primary valvular incompetence. The individual trials included in this review were small; they used different methods of assessment and overall were of poor quality. They did not include participants with severe DVI. Trials investigating the effects of other surgical procedures on deep veins are needed. Until the findings of such trials become available, the benefit of valvuloplasty remains uncertain.


Implicit memory effects when using pictures with children and adults: hypermnesia too?
Pictorial stimuli were used to investigate implicit- and explicit-memory phenomena in 3 experiments. The general procedure involved the presentation of a series of pictures during a study phase, followed by an implicit-memory test and an explicit-memory test. In the implicit-memory test, participants were presented with picture fragments and were instructed to write down what the fragment looked like. In the explicit-memory test, participants were asked to make a yes/no recognition decision regarding each picture. For children, implicit memory for pictures was robust when they were tested after a 48-hr interval, but that effect declined after 1 week; a similar implicit-memory effect for pictures was seen with college students; and the time course of the implicit-memory effect for pictures among college students (all short intervals of less than 1 week-1, 2, 3, 4, and 5 days) produced a more elevated implicit-memory performance than during the immediate testing condition. Hypermnesia may have been the cause of the increase in memory performance over the short intervals.


Production of the siderophore 2,3-dihydroxybenzoic acid is required for wild-type growth of Brucella abortus in the presence of erythritol under low-iron conditions in vitro.
Production of the siderophore 2,3-dihyroxybenzoic acid (2,3-DHBA) is required for the wild-type virulence of Brucella abortus in cattle. A possible explanation for this requirement was uncovered when it was determined that a B. abortus dhbC mutant (BHB1) defective in 2,3-DHBA production displays marked growth restriction in comparison to its parent strain, B. abortus 2308, when cultured in the presence of erythritol under low-iron conditions. This phenotype is not displayed when these strains are cultured under low-iron conditions in the presence of other readily utilizable carbon and energy sources. The addition of either exogenous 2,3-DHBA or FeCl(3) relieves this growth defect, suggesting that the inability of the B. abortus dhbC mutant to display wild-type growth in the presence of erythritol under iron-limiting conditions is due to a defect in iron acquisition. Restoring 2,3-DHBA production to the B. abortus dhbC mutant by genetic complementation abolished the erythritol-specific growth defect exhibited by this strain in low-iron medium, verifying the relationship between 2,3-DHBA production and efficient growth in the presence of erythritol under low-iron conditions. The positive correlation between 2,3-DHBA production and growth in the presence of erythritol was further substantiated by the observation that the addition of erythritol to low-iron cultures of B. abortus 2308 stimulated the production of 2,3-DHBA by increasing the transcription of the dhbCEBA operon. Correspondingly, the level of exogenous iron needed to repress dhbCEBA expression in B. abortus 2308 was also greater when this strain was cultured in the presence of erythritol than that required when it was cultured in the presence of any of the other readily utilizable carbon and energy sources tested. The tissues of the bovine reproductive tract are rich in erythritol during the latter stages of pregnancy, and the ability to metabolize erythritol is thought to be important to the virulence of B. abortus in pregnant ruminants. Consequently, the experimental findings presented here offer a plausible explanation for the attenuation of the B. abortus 2,3-DHBA-deficient mutant BHB1 in pregnant ruminants.


The antigenic structure of the human glycoprotein hormone alpha-subunit: II. Cross-species comparisons.
Eight monoclonal antibodies, specific for the glycoprotein hormone alpha-subunit, were raised against human free alpha-subunit, human FSH, or human CG. All of these antihuman monoclonal antibodies were tested for cross-reactivity with alpha-subunits derived from bovine, porcine, equine, bull frog, sea turtle, turkey, and ostrich glycoprotein hormones. All showed cross-reactivity with affinities ranging from 10(-4) to 10(-8) depending upon the antibody and the species of alpha-subunit. Cyanogen bromide fragments of bovine and equine alpha, when tested with selected antibodies indicated that antigenic determinants could be localized in two regions: alpha 9-33 and alpha 76-92. Comparison of amino acid sequences, and relative potencies, suggest that major antigenic determinants involve residues 21, 22, and 23 (F-F-S in human alpha) and 76-85 (G-G-F-K-V-E-N-H-T-A in human alpha). As part of this study the N-terminal amino acid sequences of bull frog, sea turtle, turkey, and ostrich alpha-subunits were determined and reported for the first time.


Some limits to evidence-based medicine: a case study from elective orthopaedics.
There has been growing interest in recent years in the application of the principles of evidence-based medicine (EBM), although implementation is complex. Scientific, organisational, and behavioural factors all combine to shape clinical behaviour change. Case study based qualitative data are presented which illuminate such processes within one clinical setting (elective orthopaedics), drawn from a larger study. It is suggested that (1) there are alternative models of what constitutes "evidence" in use; (2) scientific knowledge is in part socially constructed; and (3) clinical professionals retain a monopoly of technical knowledge. The implication is that there may be severe obstacles to the rapid or broad implementation of EBM.


A validation of the Croatian version of Zarit Burden Interview and clinical predictors of caregiver burden in informal caregivers of patients with dementia: a cross-sectional study.
To validate the Croatian version of the Zarit Burden Interview (ZBI) and to investigate the predictors of perceived burden. This cross-sectional study involved 131 dyads of one informal caregiver family member and one patient with dementia visiting primary care practices (Health Care Center Zagreb-West; 10/2017-9/2018). Patient-related data were collected with the Mini-Mental-State-Examination, Barthel-index, and Neuropsychiatric-Inventory-Questionnaire (NPI-Q); caregiver-related data with the ZBI, and general information on caregivers and patients with a structured questionnaire. Principal-axis-factoring with varimax-rotation was used for factor analysis. The caregivers' mean age was 62.1±13 years. They were mostly women (67.9%) and patients' children (51.1%). Four dimensions of ZBI corresponding to personal strain, frustration, embarrassment, and guilt were assessed and explained 56% variance of burden. Internal consistency of ZBI (α=0.87) and its dimensions (α1=0.88, α2=0.83, α3=0.72, α4=0.75) was good. Stronger cognitive and functional impairment of patients was associated only with personal strain, whereas more pronounced neuropsychiatric symptoms and the need for daily care were associated with more dimensions. Longer caregiver education suppressed embarrassment and promoted guilt. Guilt was higher in younger caregivers, caregivers of female patients, patients' children, and non-retired caregivers. In multivariate analysis significant predictors of higher overall burden were male sex of the patient, higher NPI-Q, the need for daily-care services, shorter duration of caregiving, non-spouse relationship, higher number of hours caring per-week, and anxious-depressive symptoms in a caregiver. The Croatian version of ZBI is reliable and valid. Our data confirm that ZBI is a multidimensional construct. Caregivers may benefit from individually tailored interventions.


Plasma fatty acid changes and increased lipid peroxidation in patients with adult respiratory distress syndrome.
There is a strong evidence that adult patients with acute respiratory distress syndrome (ARDS) are under severe oxidative stress, which leads to molecular damage. Using gas chromatography-mass spectrometry, our objective was to sequentially monitor changes, in intensive care unit (ICU) patients, characteristic of the oxidative loss of plasma unsaturated fatty acids and formation of the highly specific oxidation product of linoleic acid, 4-hydroxy-2-nonenal. Prospective, nonintervention, descriptive study. Limited statistics were applied to facilitate interpretation of the data. ICU of a postgraduate teaching hospital. Eighteen critically ill patients with an established diagnosis of ARDS requiring high FIO2 administered by mechanical ventilation were compared with ten normal, healthy controls and ten patients pre- and postcardiopulmonary bypass surgery at risk for developing ARDS. None. Sixty percent of the patients with ARDS included in this study survived. Major changes in the plasma concentrations of fatty acids occurred in all patients during their stay in the ICU. Percentage decreases in plasma linoleic acid concentrations were accompanied by increases in plasma oleic and palmitoleic acid concentrations. Circulating linoleic acid concentrations were significantly (p = .0001) lower in patients with ARDS than in the two control groups. The patients with ARDS who did not survive had lower (p = .0056) plasma oleic acid values than normal healthy controls and patients at risk for ARDs as a consequence of undergoing cardiopulmonary bypass surgery. Changes in palmitoleic acid, however, did not reach significance within the different groups studied. Patients with ARDS showed higher plasma concentrations of 4-hydroxy-2-nonenal (0.433 +/- 0.048 vs. 0.523 +/- 0.069 nmol/mL plasma for survivors and nonsurvivors, respectively) when compared with normal healthy controls (0.205 +/- 0.03 nmol/mL, p = 0.0001) and cardiopulmonary bypass patients at risk for developing ARDS (0.279 +/- 0.027 nmol/mL, p = .034 prebypass). During intensive care treatment, patients with ARDS decrease their percentage plasma concentrations of total plasma linoleic acid, but increase their percentage concentrations of oleic and palmitoleic acids. As plasma linoleic acid concentrations decreased, there was usually an increase in plasma 4-hydroxy-2-nonenal values, one of its specific peroxidation products, suggestive of severe oxidative stress leading to molecular damage to lipids.


Smart green spectrophotometric assay of the ternary mixture of drotaverine, caffeine and paracetamol in their pharmaceutical dosage form.
Three green and facile spectrophotometric methods were developed for the assay of Petro® components; drotaverine HCl (DRT), caffeine (CAFF), and paracetamol (PAR). The three methods depend on measuring the absorbance of the studied drugs through their ethanolic solution. The first derivative spectrophotometry (FDS) at (Δλ = 10) were good parameters for DRT and CAFF resolution; DRT and CAFF could be well calibrated using FDS at 320 and 285 nm, respectively. PAR could be estimated at 308 nm utilizing the second derivative spectrophotometry (SDS). Method II relies on the double divisor ratio derivative spectroscopy (DDRDS). The first derivative was applied on each drug where they would be assayed at 309, 288, and 255 nm for DRT, CAFF, and PAR, respectively. Method III depends on the mean centering (MCR) technique. DRT, CAFF, and PAR could be determined at 309, 214, and 248 nm, respectively. The concentrations were rectilinear in the ranges of 2-20 µg/mL for DRT, 1.5-15 µg/mL for CAFF, and 2-40 µg/mL for PAR in double devisor and mean centering but PAR from 5 to 40 µg/mL in derivative method. Method validation was performed according to ICH guidelines assured by the agreement with the comparison method. In addition, greenness assessment of the proposed methods was investigated. The application of the proposed method was extended to analyse tablet dosage form and performing invitro dissolution testing.


11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice.
11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11β-HSD1-deficient mice. 11β-HSD1-deficiency resulted in elevated circulating unconjugated BAs, an effect more pronounced in global than liver-specific knockout mice. Gene expression analyses revealed decreased expression of the BA-CoA ligase Fatp5, suggesting impaired BA amidation. Reduced organic anion-transporting polypeptide-1A1 (Oatp1a1) and enhanced organic solute-transporter-β (Ostb) mRNA expression were observed in livers from global 11β-HSD1-deficient mice. The impact of 11β-HSD1-deficiency on BA homeostasis seems to be GR-independent because intrahepatic corticosterone and GR target gene expression were not substantially decreased in livers from global knockout mice. Moreover, Fatp5 expression in livers from hepatocyte-specific GR knockout mice was unchanged. The results revealed a role for 11β-HSD1 in BA homeostasis.


Improving early detection of exotic or emergent oyster diseases in France: identifying factors associated with shellfish farmer reporting behaviour of oyster mortality.
Farmers' vigilance is essential for the detection of epidemics, including potential emerging diseases, in marine shellfish. A field study was conducted to investigate oyster farmers' reporting practices and behaviour, and to identify factors influencing the reporting process of oyster mortality, with the ultimate aim of improving early detection of unexplained oyster mortality outbreaks. A retrospective case-control study of oyster farmers from Charente-Maritime (France) was designed, based on interviews with 27 non-reporting and 89 reporting farmers, further split into 40 formerly-reporting and 49 currently-reporting farmers. Information about farmer and farm characteristics, farming practices, farm health history and related financial compensation on the farm, knowledge of the mortality reporting system and reporting behaviour was collected. Sampling design was considered in the calculations and farmers' reporting behaviour was modelled using an ordinal logistic regression (continuation-ratio model). Notification procedures were fairly well known among farmers and the reporting system was well accepted overall. Nevertheless, a lack of awareness of the aims of the reporting system was revealed, which contributed to late reporting. Factors identified as driving a farmer's decision to report oyster mortality concerned their lack of awareness of mortality reporting (production type, farm size, location of the production cycle, accessibility of the leasing grounds) and willingness to report (possibility and extent of financial compensation, a feeling of not being involved, whether it was first year of reporting). Overall classification performance of the model built in this study was 64%. In particular, financial compensation for oyster production losses appeared to be a clear incentive for reporting, but was countered by a habituation effect combined with a lack of awareness of the aims of the reporting system: oyster farmers looking for benefits for themselves in reporting, rather than early detection of a disease outbreak. Both economic compensation and the farmers' non-economic values and perceptions should be considered to improve oyster farmers' reporting compliance and sustainability of the reporting system. Education and participatory approaches could help to change these attitudes and thus improve oyster farmers' compliance with reporting duties, resulting in improved early detection of epidemics and emerging or exotic oyster diseases.


Effects of vasopressin on the circulation and its baroreflex control in healthy men.
Information on the hemodynamic effects of vasopressin (AVP) in healthy humans is very limited despite its known importance in body fluid homeostasis and release in pathologic states such as hemorrhage and trauma. Although it is a potent vasoconstrictor in vitro, it does not cause the expected rise in arterial pressure when given systemically to animals with intact baroreflexes. It has been proposed that this is because AVP facilitates baroreflex control of the circulation. In this study, we assessed the effect of infusion of AVP on resting circulatory variables and on the baroreflex control of forearm vascular resistance and heart rate in healthy men. AVP in a dose of 0.4 ng/kg/min, which raised plasma level of AVP to 24 +/- 4 pg/ml, a value known to have a significant antidiuretic effect, had little hemodynamic effect, producing only mild bradycardia and a slight increase in central venous pressure. Reflex changes in heart rate during neck suction (-15 and -30 mm Hg) and neck pressure (+15 and +30 mm Hg) were not altered. Reflex responses to lower body negative pressure and to its release were also unchanged by this dose of AVP. In contrast, a higher dose of AVP (4 ng/kg/min), which raised plasma levels to 290 +/- 41 pg/ml, a concentration known to occur as a result of hemorrhagic hypotension and circulatory stresses, did cause hemodynamic changes. There was tachycardia (from 63 +/- 2 to 68 +/- 2 beats/min), a decrease in pulse pressure (from 62 +/- 2 to 53 +/- 2 mm Hg), an increase in central venous pressure (from 2.6 +/- 0.5 to 4.1 +/- 0.4 mm Hg), and surprisingly in view of the known vasoconstrictor effect of AVP, an increase in forearm flow (from 4.4 +/- 0.7 to 5.9 +/- 1.2 ml/min/100 ml tissue) and a decrease in forearm vascular resistance (from 24 +/- 4 to 18 +/- 3 U); there was no significant change in mean arterial pressure (from 83 +/- 2 to 83 +/- 3 mm Hg). Reflex changes in heart rate were unaltered. The maximal vasoconstrictor response in the forearm attained during lower body negative pressure was not influenced by AVP, but the reflex vasodilator response to the sudden release of lower body negative pressure was significantly augmented, vascular resistance falling to 23 +/- 4 U before and 13 +/- 2 U during AVP. The unanticipated findings in this study include the biphasic changes in heart rate with increasing doses of AVP, the absence of a pressor response, and the vasodilatation in forearm vessels.(ABSTRACT TRUNCATED AT 400 WORDS)


Microbiological analysis in three diverse natural geothermal bathing pools in Iceland.
Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000-40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria.


Volume, characteristics and consequences of internal migration in Colombia.
More than one-third of the Colombian population can be classified as migrants. The prevailing direction of movements is urbanwards, yet it is significant that better than a third of all movements are to rural destinations. Nationwide comparisons of migrants and residents on demographic characteristics would indicate that all streams are selective of the younger and unmarried population, with women predominating in urbanwards movements and men in those to rural areas. However, when compared in terms of socioeconomic characteristics, migrants are more sharply differentiated among themselves than they are from the resident population at each of their respective destinations. Within the migrant population, a natural funneling of the more able migrants to the largest centers suggests itself. Migrants have consistently higher activity rates than the remainder of the population and, in the case of men at least, appear capable of competing for jobs on an equal basis with residents at their respective destinations. Female migrants, however, are consistently overrepresented in lower-status activities, particularly in domestic services.


Socioeconomic status and barriers to the use of free antiretroviral treatment for HIV/AIDS in Enugu State, south-eastern Nigeria.
With about 3 million people living with HIV, Nigeria has approximately 8% of the global burden of HIV cases. In 2009, only about 34% of those in need of antiretroviral treatment (ART) were able to access care, which means that Nigeria was far from achieving the United Nations target of 'universal access' by 2010. This study aimed to describe the barriers to accessibility and the coping strategies employed to overcome these barriers among users of free ART services overall and by socioeconomic status (SES). Data were collected from 240 people receiving ART at one urban and one peri-urban health facility in Enugu State, south-eastern Nigeria. Information on SES, demographic characteristics, and barriers and coping mechanisms for accessing ART were elicited from the respondents. The high cost of transportation, HIV stigma, and long waiting hours were found to be key barriers to the use of ART services. On average, ART clients spent just under four hours at the clinic during their monthly appointments. The use of personal savings and financial support from relatives were the main means to access treatment. When the data were analysed according to clients' SES, transportation costs were a chief concern among the poorest while those who were better off were more likely to be concerned about stigma and discrimination. These findings should be borne in mind when designing and locating services to maximise ongoing accessibility to ART.


The extracellular polysaccharide Pel makes the attachment of P. aeruginosa to surfaces symmetric and short-ranged.
Biofilms are surface-mounted, multicellular communities of microbes. Biofilms are often associated with chronic infections that resist treatment, evade the immune system, and damage host tissue. An essential characteristic of the biofilm state is that constituent organisms are bound in a polymeric matrix. This matrix gives the system spatial structure and clusters bacteria near each other, facilitating intercellular interactions. The Pseudomonas aeruginosa strain PAO1 is widely studied as a model biofilm-forming organism. The polymeric matrix of PAO1 biofilms is dominated by two bacteria-produced extracellular polymers, Pel and Psl. We use a combination of optical and atomic force microscopy to examine the roles of these polymers in very early biofilm development. In agreement with other researchers, we find that Psl mediates strong attachment to a glass surface. We find that Pel alone can mediate some attachment, but not as permanent as that mediated by Psl. Unexpectedly, we find that Pel promotes symmetric attachment, in the form of rod-shaped bacteria lying down flat on the surface, and that the presence of Pel makes attachment forces more short-ranged than they are with Psl alone. We suggest that these effects may result from synergistic interactions of Pel with the Psl polymeric matrix.


Influence of statin use on the incidence of recurrent venous thromboembolism and major bleeding in patients receiving rivaroxaban or standard anticoagulant therapy.
Statins may reduce the risk of first and recurrent venous thromboembolism (VTE). No data are available on their potential benefit in patients treated with the oral anticoagulant rivaroxaban. The EINSTEIN DVT/PE and EINSTEIN Extension studies compared rivaroxaban with standard of care (n=8280) and placebo (n=1188), respectively. The incidences of recurrent VTE and major bleeding per 100 patient-years for exposure (or not) to statins were calculated. A Cox proportional hazards model was constructed, stratified by index event and intended treatment duration, with statin use as a time-dependent variable, for each treatment group (rivaroxaban vs enoxaparin/vitamin K antagonist or placebo) and adjusted for relevant variables. In EINSTEIN DVT/PE, 1509 (18.3%) patients used statins during the at-risk period, and 6731 (81.7%) did not. Overall, 2.6 recurrent VTEs occurred per 100 patient-years with statin use compared with 3.8 per 100 patient-years without statins (adjusted hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.46-1.25). HRs for recurrent VTE were similar for concomitant use of rivaroxaban-statin and enoxaparin/VKA-statin. Major bleeding events occurred in 3.0 per 100 patient-years with statin use compared with 2.3 per 100 patient-years without statins (adjusted HR 0.77; 95% CI 0.46-1.29). Due to adjustments in the Cox regression model, the direction of this HR is in contrast to the crude comparison. In EINSTEIN Extension, no recurrent VTEs occurred with statin use in the rivaroxaban group compared with 1.6 per 100 patient-years without statins. In the placebo group, 12.2 recurrent VTEs occurred per 100 patient-years with statin use compared with 13.2 per 100 patient-years without (adjusted HR 0.81; 95% CI 0.35-1.86). The effect of statins in this secondary analysis of the EINSTEIN VTE treatment program is consistent with other studies that suggest a reduced risk of recurrent VTE, but conclusive evidence of this benefit is lacking. Statins are simple to use, inexpensive, very safe and do not cause bleeding. Therefore, the potential effect on reducing recurrent VTE, which is in the range of that of acetylsalicylic acid, deserves evaluation in a large randomized trial. ClinicalTrials.gov: EINSTEIN PE, NCT00439777; EINSTEIN DVT, NCT00440193; EINSTEIN Extension, NCT00439725.


Systemic loxoscelism in the age of community-acquired methicillin-resistant Staphylococcus aureus.
The increase in cases of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), as well as its isolation from the majority of skin and soft tissue abscesses in the emergency department, requires the emergency physician to consider this diagnosis in all skin or soft tissue infections. However, making the diagnosis of MRSA when the wound is actually a cutaneous lesion of a brown recluse spider bite may have untoward consequences. Furthermore, the clinical manifestations of systemic loxoscelism may be misdiagnosed as a systemic staphylococcal infection. We present a patient with systemic loxoscelism who was diagnosed with a systemic infection and received an unnecessary surgical procedure.


Using performance reference compounds in polyethylene passive samplers to deduce sediment porewater concentrations for numerous target chemicals.
Polymeric passive samplers are useful for assessing hydrophobic organic chemical contamination in sediment beds. Here, an improved method is described for measuring concentrations of contaminants in porewater by using performance reference compounds (deuterated phenanthrene, pyrene, and chrysene) to calibrate sampler/site-specific mass transfer behavior. The method employs a one-dimensional diffusion model of chemical exchange between a polymer sheet of finite thickness and an unmixed sediment bed. The model is parametrized by diffusivities and partition coefficients for both the sampler and sediment. This method was applied to estimate porewater concentrations for seventeen PAHs from polymeric samplers deployed for 3-10 days in homogenized sediment from a coal-tar contaminated site. The accuracy of the method was verified by comparing the passive sampler results to concentrations measured through liquid-liquid extraction of physically separated porewaters, with corrections for sorption to colloidal organic carbon. The measurements made using the two methods matched within about a factor of 2.0 (+/-0.9) for the 17 target PAHs.


Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA.
A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.


Strategies From 11 U.S. Medical Schools for Integrating Basic Science Into Core Clerkships.
Calls for curricular reform in medical schools and enhanced integration of basic and clinical science have resulted in a shift toward preclerkship curricula that enhance the clinical relevance of foundational science instruction and provide students with earlier immersion in the clinical environment. These reforms have resulted in shortened preclerkship curricula, yet the promise of integrated basic science education into clerkships has not been sufficiently realized because of barriers such as the nature of clinical practice, time constraints, and limited faculty knowledge. As personalized medicine requires that physicians have a more nuanced understanding of basic science, this is cause for alarm. To address this problem, several schools have developed instructional and assessment strategies to better integrate basic science into the clinical curriculum. In this article, faculty and deans from 11 U.S. medical schools discuss the strategies they implemented and the lessons they learned to provide guidance to other schools seeking to enhance basic science education during clerkships. The strategies include program-level interventions (e.g., longitudinal sessions dedicated to basic science during clerkships, weeks of lessons dedicated to basic science interspersed in clerkships), clerkship-level interventions (e.g., case-based learning with online modules, multidisciplinary clerkship dedicated to applied science), bedside-level interventions (e.g., basic science teaching scripts, self-directed learning), and changes to formative and summative assessments (e.g., spaced repetition/leveraging test-enhanced learning, developing customized examinations). The authors discovered that: interventions were more successful when buy-in from faculty and students was considered, central oversight by curricular committees collaborating with faculty was key, and some integration efforts may require schools to provide significant resources. All schools administered the United States Medical Licensing Examination Step 1 exam to students after clerkship, with positive outcomes. The authors have demonstrated that it is feasible to incorporate basic science into clinical clerkships, but certain challenges remain.


Learning professional ethics: Student experiences in a health mentor program.
The use of patient centred approaches to healthcare education is evolving, yet the effectiveness of these approaches in relation to professional ethics education is not well understood. The aim of this study was to explore the experiences and learning of health profession students engaged in an ethics module as part of a Health Mentor Program at the University of Toronto. Students were assigned to interprofessional groups representing seven professional programs and matched with a health mentor. The health mentors, individuals living with chronic health conditions, shared their experiences of the healthcare system through 90 minute semi-structured interviews with the students. Following the interviews, students completed self-reflective papers and engaged in facilitated asynchronous online discussions. Thematic analysis of reflections and discussions was used to uncover pertaining to student experiences and learning regarding professional ethics. Five major themes emerged from the data: (1) Patient autonomy and expertise in care; (2) ethical complexity and its inevitable reality in the clinical practice setting; (3) patient advocacy as an essential component of day-to-day practice; (4) qualities of remarkable clinicians that informed personal ideals for future practice; (5) patients' perspectives on clinician error and how they enabled suggestions for improving future practice. The findings of a study in one university context suggest that engagement with the health mentor narratives facilitated students' critical reflection related to their understanding of the principles of healthcare ethics.