A mixed-methods study to evaluate a patient-designed tool to reduce harm from cancer-associated thrombosis: The EMPOWER study.
Venous thromboembolism (VTE) is a common and serious complication of systemic anticancer therapies. Delays in presentation increase risk of death or long-term morbidity. A patient charity developed an information video for patients receiving systemic anticancer therapy including what to do if they developed symptoms of VTE. This was introduced into clinical practice in a regional cancer center and its impact compared with a district general hospital where the video was not used. A mixed-methods approach was used, comprising clinical audit data, patient surveys, and key informant interviews. The time between development of VTE symptoms and seeking medical evaluation was routinely recorded on patients attending a regional cancer-associated thrombosis service with systemic anticancer therapy-provoked VTE. The video was then embedded into clinical practice at the regional cancer center for 3 months. The primary outcome was the difference in time to presentation with VTE symptoms, between patients attending the regional cancer center and the district general hospital (which acted as control). Other outcomes included impact on radiology resources, patient knowledge, and perspectives of chemotherapy nurses. Addition of the video was associated with a lower mean time to presentation from 8.9 to 2.9 days (0.33 hazard ratio; 95% confidence interval, 4.5-7.4; P < .0001). This may reflect greater awareness of VTE, resulting in earlier clinical presentation when they developed attributable symptoms. The video was associated with reduced delays in diagnosis of systemic anticancer therapy-associated VTE by 6 days, thereby reducing long-term complications.


Ceiling culture-derived proliferative adipocytes retain high adipogenic potential suitable for use as a vehicle for gene transduction therapy.
Adipose tissue is expected to provide a source of proliferative cells for regenerative medicine and cell-transplantation therapies using gene transfer manipulation. We have recently identified ceiling culture-derived proliferative adipocytes (ccdPAs) from the mature adipocyte fraction as cells suitable as a therapeutic gene vehicle because of their stable proliferative capacity. In this study, we examined the capability of adipogenic differentiation of the ccdPAs compared with stromal vascular fraction (SVF)-derived progenitor cells (adipose-derived stem cells, ASCs) with regard to their multipotential ability to be converted to another lineage and therefore their potential to be used for regenerative medicine research. After in vitro passaging, the surface antigen profile and the basal levels of adipogenic marker genes of the ccdPAs were not obviously different from those of the ASCs. However, the ccdPAs showed increased lipid-droplet accumulation accompanied with higher adipogenic marker gene expression after stimulation of differentiation compared with the ASCs. The higher adipogenic potential of the ccdPAs than the ASCs from the SVF was maintained for 42 days in culture. Furthermore, the difference in the adipogenic response was enhanced after partial stimulation without indomethacin. These results indicate that the ccdPAs retain a high adipogenic potential even after in vitro passaging, thus suggesting the commitment of ccdPAs to stable mature adipocytes after autotransplantation, indicating that they may have potential for use in regenerative and gene-manipulated medicine.


Tensile and shear bond strength of resin-reinforced glass ionomer cement to glazed porcelain.
The purpose of this study was to measure the tensile and shear bond strength of resin-reinforced glass ionomer cement (RGIC) to glazed porcelain, to evaluate the durability of RGIC by thermal cycling, and to examine the RGIC remaining on the surface of the porcelain after the bond strength test to evaluate bonding conditions. Three adhesives were used in this study: Concise (CO) as a chemically cured composite resin, Fuji ORTHO (FO) as a chemically cured RGIC, and Fuji ORTHO LC (FOLC) as a light-cured RGIC. Tensile and shear bond strengths were measured 24 hours after bonding orthodontic brackets and also after thermal cycling. Tensile bond strength after 24 hours was 6.6 +/- 3.2 MPa in CO, 7.3 +/- 1.4 MPa in FO, and 8.6 +/- 1.9 MPa in FOLC, and the strength significantly decreased after the thermal cycling test. Shear bond strength after 24 hours was 32.5 +/- 8.9 MPa in CO, 23.3 +/- 6.8 MPa in FO, and 24.7 +/- 6.5 MPa in FOLC, and in contrast to tensile bond strength, no decreases in the strength were detected after the thermal cycling test. CO showed significantly higher shear bond strength than did FO and FOLC. When using the shear bond strength test and CO, destruction of porcelain surfaces frequently occurred after 24 hours and was observed in every specimen after the thermal cycling. RGIC was found to be an advantageous alternative to resin adhesive for bracket bonding to porcelain and to enamel.


Alzheimer's genetics in the GWAS era: a continuing story of 'replications and refutations'.
After a decade of intensive investigation but only few replicable results, Alzheimer's disease (AD) genetics research is slowly picking up pace. This is mostly owing to the completion of several genome-wide association studies (GWAS), which have suggested the existence of over three dozen potential new AD susceptibility genes. Although only a handful of these could be confirmed in subsequent independent replication efforts to date, this success rate is still much higher than in the pre-GWAS era. This review provides a brief summary of the principal methodologic advances in genetics research of the past decade, followed by a description of the most compelling findings that these advances have unearthed in AD. The paper closes with a discussion of the persistent methodologic difficulties and challenges and an outlook on what we can expect to gain from the next 10 years of AD genetics research.


An immunoproteomics approach to identify Leishmania infantum proteins to be applied for the diagnosis of visceral leishmaniasis and human immunodeficiency virus co-infection.
The co-infection between visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) has increased in several countries in the world. The current serological tests are not suitable since they present low sensitivity to detect the most of VL/HIV cases, and a more precise diagnosis should be performed. In this context, in the present study, an immunoproteomics approach was performed using Leishmania infantum antigenic extracts and VL, HIV and VL/HIV patients sera, besides healthy subjects samples; aiming to identify antigenic markers for these clinical conditions. Results showed that 43 spots were recognized by antibodies in VL and VL/HIV sera, and 26 proteins were identified by mass spectrometry. Between them, β-tubulin was expressed, purified and tested in ELISA experiments as a proof of concept for validation of our immunoproteomics findings and results showed high sensitivity and specificity values to detect VL and VL/HIV patients. In conclusion, the identified proteins in the present work could be considered as candidates for future studies aiming to improvement of the diagnosis of VL and VL/HIV co-infection.


Estrogen potentiates constrictor prostanoid function in female rat aorta by upregulation of cyclooxygenase-2 and thromboxane pathway expression.
Estrogen potentiates vascular reactivity to vasopressin (VP) by enhancing constrictor prostanoid function. To determine the cellular and molecular mechanisms, the effects of estrogen on arachidonic acid metabolism and on the expression of constrictor prostanoid pathway enzymes and endoperoxide/thromboxane receptor (TP) were determined in the female rat aorta. The release of thromboxane A2 (TxA2) and prostacyclin (PGI2) was measured in male (M), intact-female (Int-F), ovariectomized-female (OvX-F), and OvX + 17beta-estradiol-replaced female (OvX + ER-F) rats. The expression of mRNA for cyclooxygenase (COX)-1, COX-2, thromboxane synthase (TxS), and TP by aortic endothelium (Endo) and vascular smooth muscle (VSM) of these four experimental groups was measured by RT-PCR. The expression of COX-1, COX-2, and TxS proteins by Endo and VSM was also estimated by immunohistochemistry (IHC). Basal release of TxA2 and PGI2 was similar in M (18.8 +/- 1.9 and 1,723 +/- 153 pg/mg ring wt/45 min, respectively) and Int-F (20.2 +/- 4.2 and 1,488 +/- 123 pg, respectively) rat aortas. VP stimulated the dose-dependent release of TxA2 and PGI2 from both male and female rat aorta. OvX markedly attenuated and ER therapy restored VP-stimulated release of TxA2 and PGI2 in female rats. No differences in COX-1 mRNA levels were detected in either Endo or VSM of the four experimental groups (P > 0.1). The expression of both COX-2 and TxS mRNA were significantly higher (P < 0.05) in both Endo and VSM of Int-F and OvX + ER-F, compared with M or OvX-F. Expression of TP mRNA was significantly higher in VSM of Int-F and OvX + ER-F compared with M or OvX-F. IHC revealed the uniform staining of COX-1 in VSM of the four experimental groups, whereas staining of COX-2 and TxS was greater in Endo and VSM of Int-F and OvX + ER-F than in OvX-F or M rats. These data reveal that estrogen enhances constrictor prostanoid function in female rat aorta by upregulating the expression of COX-2 and TxS in both Endo and VSM and by upregulating the expression of TP in VSM.


2020 Year in Review: Mechanical Ventilation During the First Year of the COVID-19 Pandemic.
Coronavirus disease 2019 (COVID-19) represents the greatest medical crisis encountered in the young history of critical care and respiratory care. During the early months of the pandemic, when little was known about the virus, the acute hypoxemic respiratory failure it caused did not appear to fit conveniently or consistently into our classification of ARDS. This not only re-ignited a half-century's long simmering debate over taxonomy, but also fueled similar debates over how PEEP and lung-protective ventilation should be titrated, as well as the appropriate role of noninvasive ventilation in ARDS. COVID-19 ignited other debates on emerging concepts such as ARDS phenotypes and patient self-inflicted lung injury from vigorous spontaneous breathing. Over a year later, these early perplexities have receded into the background without having been reviewed or resolved. With a full year of evidence having been published, this narrative review systematically analyzes whether COVID-19-associated respiratory failure is essentially ARDS, with perhaps a somewhat different course of presentation. This includes a review of the severity of hypoxemia and derangements in pulmonary mechanics, PEEP requirements, recruitment potential, ability to achieve lung-protective ventilation goals, duration of mechanical ventilation, associated mortality, and response to noninvasive ventilation. This paper also reviews the concepts of ARDS phenotypes and patient self-inflicted lung injury as these are crucial to understanding the contentious debate over the nature and management of COVID-19.


GrinLine identification using digital imaging and Adobe Photoshop.
The purpose of this study was to outline a method by which an antemortem photograph of a victim can be critically compared with a postmortem photograph in an effort to facilitate the identification process. Ten subjects, between 27 and 55 years old provided historical pictures of themselves exhibiting a broad smile showing anterior teeth to some extent (a grin). These photos were termed "antemortem" for the purpose of the study. A digital camera was used to take a current photo of each subject's grin. These photos represented the "postmortem" images. A single subject's "postmortem" photo set was randomly selected to be the "unknown victim." These combined data of the unknown and the 10 antemortem subjects were digitally stored and, using Adobe Photoshop software, the images were sized and oriented for comparative analysis. The goal was to devise a technique that could facilitate the accurate determination of which "antemortem" subject was the "unknown." The generation of antemortem digital overlays of the teeth visible in a grin and the comparison of those overlays to the images of the postmortem dentition is the foundation of the technique. The comparisons made using the GrinLine Identification Technique may assist medical examiners and coroners in making identifications or exclusions.


HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans.
To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown. One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes. Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI -1.66 to -0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05). In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.


Additional differentiating characters of the two subspecies of Staphylococcus hyicus.
Forty-five strains of Staphylococcus hyicus subsp. hyicus and 36 strains of S. hyicus subsp. chromogenes were examined for bacteriolytic activity with the same assay system previously used in taxonomic studies on staphylococci. The two subspecies differed from each other chiefly in that for optimal lytic activity S. hyicus subsp. hyicus strains required a higher salt concentration in the test medium than S. hyicus subsp. chromogenes strains. The lack of lytic activity on B15TP1 medium was a major difference between S. hyicus and S. aureus, and the lack of activity on TP2P medium was a major difference between S. hyicus and S. intermedius. Penicillin-binding proteins (PBPs) were studied in 40 S. hyicus strains. The S. hyicus subsp. hyicus strains had only one PBP (mol. wt 79 000) while the S. hyicus subsp. chromogenes strains had three distinct PBPs (mol. wts 84 000, 82 000 and 79 000).


Analyzing shifts in economic risks to providers in proposed payment and delivery system reforms.
A key consideration in implementing the Patient Protection and Affordable Care Act of 2010 will be changing Medicare payments to providers to slow the growth in costs and spur improvements in health care delivery. In addition to the technical feasibility of new payment models, a crucial issue will be the capacity of the health care system to assume more economic risk. This article analyzes some of the major models under consideration and assesses how feasible their implementation would be.


Molecular Characterization of Volatiles and Petrochemical Base Oils by Photo-Ionization GC×GC-TOF-MS.
The characterization of organic mixtures by comprehensive two-dimensional gas chromatography (GC×GC) coupled to electron impact (EI) ionization time-of-flight mass spectrometry (TOF-MS) allows the detection of thousands of compounds. However, owing to the exhaustive fragmentation following EI ionization, despite the use of mass spectral libraries, a majority of the compounds remains unidentified because of the lack of parent ion preservation. Thus, soft-ionization energies leading to organic compounds being ionized with limited or no fragmentation, retaining the molecular ion, has been of interest for many years. In this study, photoionization (PI) was evaluated as the ion source for GC×GC-TOF-MS measurements. First, capabilities and limitations of PI were tested using an authentic mixture of compounds of several chemical classes. Ionization energy exhibited by PI, equivalent to 10.8 eV, resulted in significant retention of molecular ion information; [M]+• for alkanes, ketones, FAMEs, aromatics, [M-H]+• for chloroalkanes, and [M-H2O]+• for alcohols. Second, considering the potential of PI for hydrocarbons, base oils, complex mixtures of saturated and unsaturated hydrocarbons blended for finished lubricant formulations, were extensively evaluated. Several chemical classes of hydrocarbons were positively identified including a large number of isomeric compounds, both aliphatics and cyclics. Interestingly, branched-alkanes were ionized with lower excess internal energy, not only retaining the molecular ions but also exhibiting unique fragmentation patterns. The results presented herein offer a unique perspective into the detailed molecular characterization of base oils. Such unprecedented identification power of PI coupled with GC×GC-TOF-MS is the first report covering volatiles to low-volatile organic mixtures.


In-hospital mortality among patients with type 2 diabetes mellitus and acute myocardial infarction: results from the national inpatient sample, 2000-2010.
Case-fatality rates in acute myocardial infarction (AMI) have significantly decreased; however, the prevalence of diabetes mellitus (DM), a risk factor for AMI, has increased. The purposes of the present study were to assess the prevalence and clinical impact of DM among patients hospitalized with AMI and to estimate the impact of important clinical characteristics associated with in-hospital mortality in patients with AMI and DM. We used the National Inpatient Sample to estimate trends in DM prevalence and in-hospital mortality among 1.5 million patients with AMI from 2000 to 2010, using survey data-analysis methods. Clinical characteristics associated with in-hospital mortality were identified using multivariable logistic regression. There was a significant increase in DM prevalence among AMI patients (year 2000, 22.2%; year 2010, 29.6%, Ptrend<0.0001). AMI patients with DM tended to be older and female and to have more cardiovascular risk factors. However, age-standardized mortality decreased significantly from 2000 (8.48%) to 2010 (4.95%) (Ptrend<0.0001). DM remained independently associated with mortality (adjusted odds ratio 1.069, 95% CI 1.051 to 1.087; P<0.0001). The adverse impact of DM on in-hospital mortality was unchanged over time. Decreased death risk over time was greatest among women and elderly patients. Among younger patients of both sexes, there was a leveling off of this decrease in more recent years. Despite increasing DM prevalence and disease burden among AMI patients, in-hospital mortality declined significantly from 2000 to 2010. The adverse impact of DM on mortality remained unchanged overall over time but was age and sex dependent.


Adolescents and school asthma knowledge and attitudes.
bronchial asthma is a chronic disease that affects a high percentage of adolescents, with a significant restriction of daily activities, and is a cause of school absenteeism. The relationships between adolescents and asthma disease in school were assessed, with a view to improving knowledge about the asthmatic adolescent. a survey was conducted in the Lisbon metropolitan area, covering urban (Lisbon) and rural (LourinhU a ) zones and including 1879 students and 81 teachers from the 7th to 9th high school years. The study groups were asthmatic students, their peers, and teachers. A self-administered questionnaire was applied to collect information. The results were compared with a reference group of 91 asthmatic students attending our Department of Immunoallergy-Hospital Dona Estefânia. Cotinine urinary measurements were made in a sample of asthmatics and a control group. the prevalence of current asthma among students was 10%. Estimates of asthma annual burden among 7th to 9th year students from Lisbon and LourinhUa high schools included 4,307 days missed from school, 4,148 medical consultations and a minimum of 351 hospital emergency care and 80 hospital admissions. Exposure to passive smoking was not significantly different between asthmatic students and theirs peers. Cotinine urinary measurements did not discriminate between exposed and non-exposed individuals. Cigarette smoking was almost as common among adolescent asthmatics (5.4%) as it was in non-asthmatic subjects (6.7%). However, 55% of asthmatics mentioned active and passive smoking as an asthma-exacerbating factor. Asthmatic students, theirs peers and teachers showed a deficient knowledge about asthma (mean group scores: 17.6; 14.2 and 17.7 of a possible 30), particularly in the areas related to asthma recognition and its management. Asthmatics attending our Allergy Department had the highest scores. All groups showed tolerance in the sense of a positive and understanding attitude toward a person with asthma. However, traditional beliefs about asthma disease (dependence, inferiority.) were confirmed. A positive correlation between knowledge levels and tolerance attitudes was found. in view of the dimension of the asthma problem in adolescence and its social and economic impact, it is justifiable to assess the need for the implementation of asthma education programs in schools in order to improve asthma management by the adolescents and their schools.


Health conditions and factors related to the work ability of teachers.
This is a cross-sectional study conducted with 258 teachers from nine state schools in two municipalities of São Paulo state with the purpose of assessing their work ability. A questionnaire with socio-demographic and health/work conditions data and the Work Ability Index (WAI) was performed. Most teachers were females, 41.9 yr old on average (SD 9.4), and with an undergraduate degree (95.7%). The work ability was considered good for 42.6% and moderate/low for 35.3%. In linear regressions models, which used the two domain model, the significant variables for a decrease in WAI were: individual perception of a worsening in the health situation (p<0001), having children (p=0.0003 / p=0.0001), difficulty in sleeping well at night (p=0.0009 / p=0.0014), history of physical pain in the previous six months (p<0.0001 / p<0.0001), being a teacher with a contract (p=0.0007) and working as a teacher for a longer time. (p=0.0183). Public investments on the work conditions of teachers are important to recover and to maintain their work ability.


A maize chromosome 3 addition line of oat exhibits expression of the maize homeobox gene liguleless3 and alteration of cell fates.
Maize chromosome addition lines of oat offer the opportunity to study maize gene expression in oat and the resulting phenotypes. Morphological examination of a maize chromosome 3 addition line of oat showed that this line exhibited several morphological abnormalities including a blade-to-sheath transformation at the midrib region of the leaf, a hook-shaped panicle, and abnormal outgrowth of aerial axillary buds. Dominant mutations in the maize liguleless3 (lg3) homeobox gene result in a blade (distal)-to-sheath (proximal) transformation at the midrib region of the leaf. Ectopic expression of the dominant mutant Lg3 allele is believed to cause the phenotype. Therefore, we suspected that the maize lg3 gene, which is located on maize chromosome 3, was involved in the phenotypes observed in the maize chromosome 3 addition line of oat. Genetic analyses of an oat BC1F2 family segregating for maize chromosome 3 showed that the presence of a stable maize chromosome 3 was required for the expression of these cell fate abnormalities. RNA expression analysis of leaf sheath tissue from oat plants carrying maize chromosome 3 demonstrated that maize LG3 transcripts accumulated in oat, indicating that this expression is associated with the blade-to-sheath transformation, hook-shaped panicle and outgrowth of aerial axillary bud phenotypes. Our results demonstrate that the maize chromosome addition lines of oat are useful genetic stocks to study expression of maize genes in oat.


STIMA: Submucosal Temporary Inferior Maxillary Antrostomy: A Cadaveric Controlled Study of a Modification of the Conventional Antrostomy.
Introduction: Inferior meatal antrostomy (IMA) is a safe and easy approach to the maxillary sinus. However, studies have shown disadvantages of conventional IMA, such as disruption of mucociliary transport and injury of the nasolacrimal duct (NLD). Endoscopic middle meatal antrostomy (MMA) has become the standard of care for addressing various maxillary pathologies. It is more functional and physiological but offers limited exposure to certain areas of the maxillary sinus, such as the prelacrimal recess, alveolar recess, and zygomatic recess. We proposed submucosal temporary inferior maxillary antrostomy (STIMA) to improve visualization and accessibility to such difficult-to-access locations. Objectives: To describe our proposed modification, to compare the degree of visualization and ease of accessibility between MMA and STIMA. Methods: This is a descriptive cadaveric study. It was performed on 4 fresh frozen human cadavers, and 8 maxillary sinuses were used to achieve the study's objectives. Different angled rigid nasal endoscopes and suction tubes were used to score the degree of visualization and ease of accessibility between the MMA and STIMA. Result: We demonstrated the superiority of the STIMA over the MMA in the degree of visualization and ease of accessibility in these difficult-to-access locations (P-value was significant, <.05). We did not encounter orbital injury or injury to the NLD in our specimens. Conclusion: STIMA is a relatively easy and safe modification of conventional IMA. It improves the degree of visualization and ease of accessibility to difficult-to-access maxillary sinus locations without the potential complications of conventional IMA.


Integrated and isolated impact of high-performance work practices on employee health and well-being: A comparative study.
We investigate the positive relationships between high-performance work practices (HPWP) and employee health and well-being and examine the conflicting assumption that high work intensification arising from HPWP might offset these positive relationships. We present new insights on whether the combined use (or integrated effects) of HPWP has greater explanatory power on employee health, well-being, and work intensification compared to their isolated or independent effects. We use data from the 2004 British Workplace Employment Relations Survey (22,451 employees nested within 1,733 workplaces) and the 2010 British National Health Service Staff survey (164,916 employees nested within 386 workplaces). The results show that HPWP have positive combined effects in both contexts, and work intensification has a mediating role in some of the linkages investigated. The results also indicate that the combined use of HPWP may be sensitive to particular organizational settings, and may operate in some sectors but not in others. (PsycINFO Database Record


Clinicopathologic Findings of Spontaneous Leukemia in 9 Pet African Hedgehogs (Atelerix Albiventris).
Previous reports of leukemia in hedgehogs are limited. We describe clinicopathologic features of leukemia in 9 hedgehogs, including eosinophilic leukemia (n = 3) and acute leukemia/leukemic phase of lymphoma (n = 6). All 3 hedgehogs with eosinophilic leukemia were older than 2 years of age; in contrast, 4 of 6 cases of acute leukemia/lymphoma were <2 years old. Hedgehogs presented for non-specific clinical signs of anorexia and lethargy. On hematologic testing, hedgehogs with eosinophilic leukemia had a marked leukocytosis, consisting mostly of eosinophilic precursors with fewer mature eosinophils, whereas there were 43-97% immature cells (blasts) in the blood of hedgehogs with acute leukemia/lymphoma. Anemia (n = 6) and/or thrombocytopenia (n = 6) were concurrent findings. Increased liver enzyme activities (alanine aminotransferase, alkaline phosphatase) and hypoalbuminemia were the common findings on biochemical panels. All cases of eosinophilic leukemia and 4 cases of acute leukemia/lymphoma died shortly after diagnosis (median 7 days, range 0-41 days), whereas 2 cases of acute leukemia/lymphoma lived for 94 or 101 days. Postmortem examination in 5 cases (1 eosinophilic leukemia, 4 acute leukemia/lymphoma) showed bone marrow infiltrates, confirming eosinophilic leukemia and acute leukemia in 1 and 3 cases, and bone marrow necrosis in 1 animal with acute leukemia/lymphoma. Immunohistochemical staining of bone marrow sections confirmed a T-cell acute leukemia in 1 case. Several hedgehogs had concurrent carcinomas. Hedgehogs suffer from eosinophilic leukemia and acute leukemia/lymphoma. However, classification of acute leukemia by lineage was not possible due to lack of hedgehog cross-reactive or species-specific reagents.


Immunity to EBV as revealed by immunedeficiencies.
Epstein-Barr virus infection is the most common viral latent infection in humans and represents one prototypical model to study immunity to viral infections. In that respect, inborn errors of immunity (IEIs) or primary immunodeficiencies (PIDs) predisposing to severe and chronic EBV infections provide peculiar examples to decipher-specific molecular and cellular components involved in the immune control of EBV-infected cells. Herein, we discuss the recent knowledge and concepts arising from these studies, with a particular focus on 'atypical' EBV infections when EBV enters T, NK and smooth muscle cells, instead of the common 'typical' infection of B cells.


[The practice of surgery in France. Current state, fears for the future].
After a study of the number of surgeons practising in France, the author presents data which may have a poor effect on the future of the specialty: increasing constraints, reduced numbers of interns, decreased income and disappearance of general surgery, etc. The discipline is poorly prepared for future technical innovations. In the near future the population may no longer be served by an adequate number of surgeons, due to lack of interest in the specialty.


The anatomical reduction of a moderate or severe stable slipped capital femoral epiphysis by modified Dunn subcapital osteotomy using the Ganz approach: functional and radiological outcomes.
This study analysed the clinical and radiological outcome of anatomical reduction of a moderate or severe stable slipped capital femoral epiphysis (SCFE) treated by subcapital osteotomy (a modified Dunn osteotomy) through the surgical approach described by Ganz. We prospectively studied 31 patients (32 hips; 16 females and five males; mean age 14.3 years) with SCFE. On the Southwick classification, ten were of moderate severity (head-shaft angle > 30° to 60°) and 22 were severe (head-shaft angle > 60°). Each underwent open reduction and internal fixation using an intracapsular osteotomy through the physeal growth plate after safe surgical hip dislocation. Unlike the conventional procedure, 25 hips did not need an osteotomy of the apophysis of the great trochanter and were managed using an extended retinacular posterior flap. Clinical outcome was assessed using the range of movement and the Harris Hip (HHS), Western Ontario and McMaster Universities Osteoarthritis (WOMAC), and Merle d'Aubigné scores, while radiological measurements included slip and alpha angles. The mean duration of follow-up was 24.1 months (12 to 40). There was a significant improvement in all clinical and radiological measurements after treatment (p < 0.001). Post-operative major complications were one deep infection and one case of femoral head collapse. These findings suggest that a modified Dunn osteotomy carried out through Ganz approach is a safe and effective method of treating the stable SCFE with a high degree of slip. Cite this article: Bone Joint J 2016;98-B:1283-8.


Isolation of intraflagellar transport trains.
The intraflagellar transport (IFT) system was first identified in situ by electron microscopy in thin sections of plastic-embedded flagella as linear arrays of electrondense particles, located between the B tubules of the outer doublets and the flagellar membrane. These arrays of particles are referred to as IFT trains. Upon membrane rupture, IFT trains are thought to easily dissociate to yield soluble IFT particles, which are commonly purified through sucrose gradients as ∼16-17S complexes. The latters easily dissociate into two subcomplexes, named A and B. We report here the isolation, visualization, and identification by immunolabeling of flexible strings of IFT particles, which are structurally similar to in situ IFT trains and appear to be formed by both complex A and complex B polypeptides. Moreover, the particles forming isolated IFT trains are structurally similar to the individual particles found in the ∼17S gradient peak. Our results provide the first direct evidence that ∼17S particles do indeed compose the IFT trains. The paper also represents the first isolation of the IFT trains, and opens new possibilities for higher resolution studies on their structure and how particles are attached to each other to form the particle trains.


Trust and distrust toward online health information in nurse-patient communication and implications for eHealth literacy.
In Norwegian hospitals, patients with newly diagnosed inflammatory joint disease are offered consultations with nurses, to address health issues related to their diagnosis and treatment. This study examines how issues of trust manifest in the communication between nurses and patients in clinical encounters; of particular interest are the accounts of trust and distrust toward online health information (OHI) linked to patients' eHealth literacy. Video-recorded observational data were collected from 16 primary nurse-patient consultations and 10 follow up consultations in a Norwegian hospital setting. Rhetorical discourse analysis was applied to examine the conversations, focusing on the rhetorical devices that were expressed by the nurses and the patients, such as justifications, contrasting, character work, and reported speech. The nurses acknowledged patients' references to online search activities related to health information while expressing their own reservations about OHI. The nurses explicitly and implicitly advised patients on specific eHealth literacy strategies, namely, to consult trustworthy sources, such as patient organizations; to trust the medical knowledge conveyed by health personnel; to distrust non-professional health advice online; and to avoid self-diagnosis based on health information sought on the Internet. Through the use of rhetorical devices, the nurses implicitly addressed eHealth literacy strategies in their communication with patients, including the importance of critically assessing the trustworthiness of health information. This complex communicative task requires a sensitivity toward patients' eHealth literacy levels.


Growth of Salmonella typhimurium in skim milk concentrates.
The influence of various levels of skim milk solids and temperature on the duration of lag phase, growth rate, and extent of growth of Salmonella typhimurium was investigated. The effect on growth of salmonellae (and a strain of Escherichia coli) of reduced pressure at a constant solids level and under conditions simulating vacuum condensation of skim milk was also studied. S. typhimurium grew when inoculated into skim milk solutions ranging from 10 to 60% solids and over a temperature range of 23 to 44 C. At 10 to 12 C, growth was evident only in the 10% skim milk. As the total solids level was increased or incubation temperature was deviated from the optimum, or both, there was an increase in the lag phase and generation time of salmonellae. A lower cell population also resulted. The generation time at 37 C of S. typhimurium incubated at atmospheric pressure was approximately one-half that in skim milk concentrates held under reduced pressure. In addition, a slightly longer lag phase and lower cell yield characterized the growth under reduced pressure. Concentration of skim milk had little or no effect on viability of salmonellae or E. coli when the vapor temperature in the vacuum pan was below the maximum growth temperature for salmonellae. Increasing the vapor temperature to 48 C caused a two-log reduction in viable organisms during the concentrating period (65 min).


Effects of exercise training on neurovascular control and skeletal myopathy in systolic heart failure.
Neurohormonal excitation and dyspnea are the hallmarks of heart failure (HF) and have long been associated with poor prognosis in HF patients. Sympathetic nerve activity (SNA) and ventilatory equivalent of carbon dioxide (VE/VO2) are elevated in moderate HF patients and increased even further in severe HF patients. The increase in SNA in HF patients is present regardless of age, sex, and etiology of systolic dysfunction. Neurohormonal activation is the major mediator of the peripheral vasoconstriction characteristic of HF patients. In addition, reduction in peripheral blood flow increases muscle inflammation, oxidative stress, and protein degradation, which is the essence of the skeletal myopathy and exercise intolerance in HF. Here we discuss the beneficial effects of exercise training on resting SNA in patients with systolic HF and its central and peripheral mechanisms of control. Furthermore, we discuss the exercise-mediated improvement in peripheral vasoconstriction in patients with HF. We will also focus on the effects of exercise training on ventilatory responses. Finally, we review the effects of exercise training on features of the skeletal myopathy in HF. In summary, exercise training plays an important role in HF, working synergistically with pharmacological therapies to ameliorate these abnormalities in clinical practice.


Defects of tyrosine289phenylalanine mutation on binding and functional properties of the human tachykinin NK2 receptor stably expressed in chinese hamster ovary cells.
A point mutation was made at position 289 in the transmembrane segment 7 of the human tachykinin NK2 receptor to yield a tyrosine/phenylalanine (Tyr/Phe) substitution. Chinese hamster ovary cells stably transfected with the wild-type or Tyr289Phe mutant NK2 receptor both bound neurokinin A (NKA) and the synthetic NK2 receptor-selective agonists, GR 64349 and [betaAla8]NKA(4-10), with high and even affinities. Neurokinin B (NKB) and substance P (SP) also displayed sizeable binding affinities, albeit with lower affinity as compared to NKA. In a functional assay (production of inositol-1,4,5-trisphosphate, IP3), NKA, GR 64349, and [betaAla8]INKA(4-10) stimulated IP3 accumulation via the wild-type and mutant receptors with similar potencies. On the other hand, NKB and SP exhibited a dramatic reduction in their agonist efficacies at the mutant receptor, NKB acting as a partial agonist (maximum effect = 50% of the response to NKA) and SP being totally inactive. The results obtained with phenoxybenzamine inactivation experiments indicated that a large and similar receptor reserve existed for both the wild-type and the mutant receptor. SP, which displayed sizeable binding affinity for the mutant receptor but did not stimulate IP3 accumulation, antagonized the agonist effect of NKA. The antagonist action of SP at the mutant NK2 receptor cannot be ascribed to receptor internalization. The Tyr/Phe replacement at position 289 markedly reduced the binding affinity and antagonist potency of the non-peptide ligand, SR 48968, without affecting the binding affinity and antagonist potency of the bicyclic peptide antagonist MEN 11420. The results indicate that the hydroxyl radical function of Tyr289 in transmembrane segment 7 of the human NK2 receptor is, directly or indirectly, involved in stimulus transduction when the NK2 receptor is occupied by NKB or SP, but not when using NKA or NK2 receptor-selective agonists.


Enhancement of isoleucine hydroxamate-mediated growth inhibition and improvement of isoleucine-producing strains of Serratia marcescens.
Growth inhibition by isoleucine hydroxamate in Serratia marcescens was significantly enhanced by adding valine plus leucine and by using glycerol as the carbon source. Isoleucine hydroxamate-resistant mutants were isolated under conditions in which growth inhibition was enhanced. One of the mutants, strain GIHVLr2179, lacked both feedback inhibition and repression of threonine deaminase. An alpha-aminobutyric acid-resistant mutant derived from strain GIHVLr2179, strain GIHVLAr2795, produced 12 mg of isoleucine per ml in the medium containing glucose and urea as carbon and nitrogen sources (a twofold increase over prior reports). This strain had increased activities of threonine deaminase, acetohydroxy acid synthase, aspartokinase, and homoserine dehydrogenase.


Patient Motivation to Reduce or Discontinue Opioids for Chronic Pain: Self-efficacy, Barriers, and Readiness to Change.
This study aimed to assess levels and predictors of self-efficacy and motivation to change opioid use among a community sample of patients using opioids for chronic pain, as well as patient-reported barriers to pursuing opioid discontinuation. Participants with a variety of chronic pain conditions, recruited from ResearchMatch.org , completed a battery of electronic, self-report questionnaires assessing demographic and medical characteristics, pain treatment history, and levels of readiness, self-efficacy, and other attitudes toward reducing or discontinuing opioid use. Multiple regression analyses and analyses of variance were conducted to examine predictors of readiness and self-efficacy to change opioid use. A modified version of rapid qualitative analysis was utilized to analyze themes in participant responses to an open-ended item about "what it would take" to consider opioid discontinuation. The final sample included N=119 participants, the majority of whom were female (78.2%), Caucasian (77.3%), and well-educated. Readiness and self-efficacy to decrease or stop opioid use were fairly low on a 0 to 10 Visual Analog Scale (2.6 to 3.8) and significantly higher to decrease than stop ( P <0.01). Higher readiness to change was predicted by lower pain severity and higher concern about opioids, whereas higher self-efficacy was predicted by shorter pain duration. Results from the qualitative analyses revealed that the availability of an alternative treatment option was the most commonly cited requirement to consider opioid discontinuation. Patients with lower pain severity, shorter duration of pain, and higher concerns about opioids may be a prime target from a motivation standpoint for interventions addressing opioid tapering and discontinuation.


History of Nonalcoholic Fatty Liver Disease.
Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig's seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of "NAFLD as a manifestation of the Metabolic Syndrome", to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.


Influences on Adolescents in an Ecosystem: Uniformed Groups.
The purpose of this study was to investigate whether participating in a uniformed group such as Boy Scouts, which can be seen as a meso-ecosystem, is likely to be beneficial for adolescents' psychosocial competence. The psychosocial competence of a representative sample of Hong Kong Chinese adolescents who were members of uniformed groups (N = 559) was compared with that of a corresponding sample of adolescents who were not members of uniformed groups (N = 834). Measures of psychosocial competence included social skills, helping attitudes, and leadership. Multiple regression analyses were used to examine how well participation in uniformed groups predicted the 3 measures of psychosocial competence concurrently. Results indicated that participation in uniformed groups was associated with higher levels of social skills, helping attitudes, and leadership. Results are discussed in relation to benefits of uniformed group participation.


Efficacy of weaning protocol in medical intensive care unit of tertiary care center.
To evaluate the efficacy of the protocol-directed weaning from a mechanical ventilator compared to physician-directed weaning. A comparative study between retrospective studies of physician-directed weaning as controls (N = 198) reviewed from July 2000 to July 2002 and the prospective studies of protocol-directed weaning as intervention (N = 196) enrolled from October 2002 to October 2003 in the medical ICU of Maharaj Nakorn Chiang Mai Hospital, tertiary care center of northern Thailand. Study results were concluded by Fisher's exact test. Baseline characteristics data of both groups including sex, age, illness severity which demonstrated by APACHE II score and PaO2/FiO2 ratio, causes of respiratory failure and mode of mechanical ventilation used were similar. The duration of mechanical ventilation before weaning was 5.89 +/- 3.71 days in the protocol-directed group and 7.41 +/- 5.54 days in the physician-directed group (p < 0.05). Weaning duration in the protocol-directed group was significantly shorter than the physician-directed group (14.58 +/- 16. 98 hours VS 47.09 +/- 38.23 hours; p < 0.05). Kaplan-Meire analysis demonstrated that patients in the protocol-directed group had significantly shorter durations of mechanical ventilation compared to patients in the physician-directed group (p = 0.001, log-rank test). The ICU LOS was significantly shorter in the protocol-directed group (7.91 +/- 4.71 vs 11.53 +/- 7.80 days; p < 0.05). The 28 days mortality rate and the incidence of hospital acquired pneumonia seemed to be less in the protocol-directed group (4.60% vs 6.10% and 5.60% vs 10.10% consecutively) and reintubation rate seemed to be higher in the protocol-directed group (6.1% vs 4.5%) than the physician-directed group but differences were not significant (p > 0. 05). Protocol-directed weaning proved to have more efficacy in weaning patients from a ventilator than physician-directed weaning in terms of weaning duration and ICU length of stay without a deteriorating effect to the patients.


Potential role of cellular miRNAs in coronavirus-host interplay.
Host miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses through several possible mechanisms including direct binding of viral RNA. Identification of human miRNAs involved in coronavirus-host interplay becomes important due to the ongoing COVID-19 pandemic. In this article we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. As a result, we identified six miRNAs (miR-21-3p, miR-195-5p, miR-16-5p, miR-3065-5p, miR-424-5p and miR-421) with high binding probability across all analyzed viruses. Further bioinformatic analysis of binding sites revealed high conservativity of miRNA binding regions within RNAs of human coronaviruses and their strains. In order to discover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV.


Undetected Pancreatic Adenocarcinoma on Computed Tomography: Frequency According to Scan Protocol.
Computed tomography (CT) is the main diagnostic modality for detecting pancreatic adenocarcinoma. To assess the frequency of missed pancreatic adenocarcinoma on CT scans according to different CT protocols. The medical records of consecutive pancreatic adenocarcinoma patients were retrospectively collected (12/2011-12/2015). Patients with abdominal CT scans performed up to a year prior to cancer diagnosis were included. Two radiologists registered the presence of radiological signs of missed cancers. The frequency of missed cancers was compared between portal and pancreatic/triphasic CT protocols. Overall, 180 CT scans of pancreatic adenocarcinoma patients performed prior to cancer diagnosis were retrieved; 126/180 (70.0%) were conducted using pancreatic/triphasic protocols and 54/180 (30.0%) used portal protocols. The overall frequency of missed cancers was 6/180 (3.3%) in our study population. The frequency of missed cancers was higher with the portal CT protocols compared to the pancreatic/triphasic protocols: 5/54 (9.3%) vs. 1/126 (0.8%), P = 0.01. CT signs of missed cancers included small hypodense lesions, peri-pancreatic fat stranding, and dilated pancreatic duct with a cut-off sign. The frequency of missed pancreatic adenocarcinoma is higher on portal CT protocols. Physicians should consider the cancer miss rate on different CT protocols.


Well-being among Italian medical oncologists: an exploratory study.
Recently, attention has been focused on physicians' stress and quality-of-life improvement. Due to their relationship with patients, oncologists in particular are overloaded physically, emotionally and psychologically. Previous studies showed that training of communication skills improves the satisfaction and well-being of physicians and patients. Our research investigates the relationship between work stress and engagement and personal well-being in physicians working in Italian hospitals. 176 physicians were included. Doctors filled out self-report questionnaires to evaluate work stress and coping strategies, personal well-being, work engagement and two purpose-built scales to measure the degree of perceived organizational support and the level of specific training of social and relational skills. Descriptive statistics were used to analyze data, as well as correlation analysis (Pearson's r), hierarchical regression analysis (enter step) and analysis of variance (one-way ANOVA). Positive and significant correlations were found between variables. Moreover, physicians who obtained higher levels of specific training on social and relational skills reported lower levels of stress. Oncologists experienced greater stress than other physicians in terms of maladaptive coping and lack of additional training. The study suggests that physicians' well-being is mediated by professional aspects, such as social skills in relationships with patients.


Modified technique for combined liver-small bowel transplantation in pigs.
As the conventional combined liver-small bowel transplantation is complicated with many postoperative complications, the aim of this study was to describe a modified technique for the combined liver-small bowel transplantation with preservation of the duodenum, partial head of pancreas and hepatic biliary system in pigs. Composite liver/small bowel allotransplantations were undertaken in 30 long-white pigs. The graft included liver, about 3 to 4 m proximal jejunum, duodenum and partial pancreatic head. Vessels reconstructions included subhepatic vena cava-vena cava anastomosis, aorta-aorta anastomosis and portal-splenic vein anastomosis. Without immunosuppressive treatment, the median survival time of the animals was 6 days (2 to 12 days), and about 76.9 % (20/26) of the animals survived for more than 4 days after operation. The modified technique is feasible and safe for the composite liver/small bowel transplantation with duodenum and pancreas preserved in pigs. And also this technique can simplify the operation and decrease possible postoperative complications.


[Morphological reasoning of the resected tissue volume by the perforated ulcer of the duodenum].
102 tissue samples, resected during treatment of the perforated duodenal ulcers. The most pronounced fibroplastic and acute inflammatory tissue changes were registered in the immediate perforation zone and 0,5 sm above. At a distance of 1,0 sm these changes become less evident. Therefore, in patients with the perforated duodenal ulcer and palpable surrounding infiltrate less than 3,0 sm in diameter, the resection line should be no shorter than 1,0 sm away from the perforation.


Sodium chloride tolerance of terrestrial fungi.
A survey was made of the NaCl tolerance of 975 species of terrestrial fungi selected from the major taxonomic classes. The penicillia and aspergilli were notably the most resistant with the majority of their species able to grow in the presence of 20% or more of NaCl. The Basidiomycetes, as a class, were decidedly the least tolerant with over half the species unable to withstand more than 2% NaCl. Uniformity of tolerance by multiple strains of various species suggests that this may provide a useful taxonomic criterion.


Pregnancy-related strokes in southeast Turkey.
To evaluate the presentation, timing, etiology, risk factors, mortality, and outcome of ischemic stroke (IS), intracerebral hemorrhagic stroke (ICH/HS), and cerebral venous thrombosis (CVT) occurring during pregnancy and the postpartum period in southeast Turkey. The study was carried out from September 2003 to September 2005 at the emergency department of Dicle University Hospital in the southeast part of Turkey. Thirty-eight stroke patients, 18-42 years of age with a diagnosis of stroke during pregnancy or within 6 weeks of delivery were included. The records were retrospectively reviewed for presentation, gestational ages, strokes subtypes and time, stroke sort, stroke place, etiology, risk factors, hospital stay, mortality, and outcome. Thirty-eight patients were identified, including 18 with IS, 15 with ICH, and 5 patients with CVT. Most events (89.5%) occurred in the third trimester and the postpartum period. A definable cause was identified in 61.1% of IS and 60% of CHS. Causes of IS include pre-eclampsia or eclampsia (22.2%), hypercoagulable states (16.7%), and a diverse array of other causes, including cardio embolism (5.5%) and hypotension (16.7%). Pre-eclampsia/eclampsia (46.7%) and ruptured atriovenous malformation (6.7%) were the primary causes of ICH. The mortality rate for all patients was 34.2%. The etiology of stroke in pregnancy and the postpartum period is diverse. Strokes are most likely to occur in the third trimester and postpartum period and cluster in the first postpartum week. Mortality is high in patients with ICH. Pre-eclampsia and eclampsia are common causes of strokes.


Racial differences in acquisition of syringes from pharmacies under conditions of legal but restricted sales.
Injecting drug users (IDUs) are at increased risk of acquiring and transmitting HIV and other bloodborne pathogens through the multi-person use of syringes. Although research has shown that increased access to syringes through syringe exchange programs (SEPs) is an effective strategy to reduce risky injection practices many areas of the United States still do not have SEPs. In the absence of SEPs, legislation allowing pharmacies over-the-counter sales of syringes has also been shown to reduce syringe sharing. The success of pharmacy sales however is limited by other legal stipulations, such as drug paraphernalia laws, which in turn may contribute to fear among IDUs about being caught purchasing and carrying syringes. Between 2003 and 2006, 851 out-of-treatment IDUs were recruited using street outreach in the Raleigh-Durham (North Carolina) area. Data were collected using audio-computer assisted interview (ACASI) technology. Multiple logistic regression analyses were performed to assess factors associated with purchasing syringes from pharmacies. In our study sample, African-American IDUs were one-fifth as likely as white IDUs to report pharmacies as their primary source of syringes. Given the absence of syringe exchange programs and the relatively high prevalence of HCV and HIV among IDUs in the Raleigh-Durham area, the limited use of pharmacies as a source of syringes among African-American IDUs in this study sample is problematic. The study findings support the need for effective multilevel interventions to increase access to clean needles in this population, as well as for policy interventions, such as legalization of SEPs and elimination of penalties for carrying syringes, to reduce harm and eliminate the health threats posed by receptive syringe sharing.


Molecularly imprinted therapeutic contact lenses.
There exists a considerable unmet need for more efficacious delivery of ocular therapeutics. Contact lenses have been developed with high loading and controllable sustained release to overcome limited patient compliance and significant ocular transport limitations. This can best be achieved by extending and controlling the residence time of drugs on the eye surface and thereby limiting drug loss by lacrimation, drainage and non-productive absorption. Within hydrogels, molecular imprinting can be used to create memory for template molecules embedded within a flexible macromolecular network. Control in therapeutic loading and delay of release have been demonstrated with careful attention to the functional monomer/template ratio, the diversity of functional monomers, and the polymer backbone and network structure. Experimental work has also confirmed that macromolecular memory and not structural differences or phenomena are responsible for delayed drug release kinetics compared with non-imprinted systems. A therapeutically relevant amount of drug can be loaded for release to occur over multiple days, which allows the technique to be applied to daily-wear and extended-wear contact lenses. The focus of this article is to review the emerging field of molecularly imprinted contact lenses and highlight significant accomplishments, trends, as well as future strategies and directions. In the past 8 years, molecular imprinting has been used to produce therapeutic contact lenses with enhanced loading and delayed release. Progress in the field has mostly included low-molecular-weight therapeutics such as anti-glaucoma, antihistamine, antibiotic and anti-inflammatory therapeutics used to treat anterior eye disorders. Recently, high molecular weight comfort molecules have also been successfully demonstrated. Current methods can produce lenses of suitable thickness, water content, and mechanical and optical properties compared with commercial lenses on the market today.


The use of qualitative comparative analysis for critical event research in Alcohol and HIV in Mumbai, India.
In this paper we use Qualitative Comparative Analysis (QCA) in critical event analysis to identify under what conditions alcohol is necessary in contributing to unprotected sex. The paper is based on a set of in-depth interviews with 84 men aged 18 = 29 from three typical low income communities in Mumbai who reported using alcohol and having sex with at least one nonspousal partner once or more in the 30 days prior to the interview. The interviews included narratives of critical events defined as recent (past 30-60 day) events involving sexual behavior with or without alcohol. The paper identifies themes related to alcohol, sexuality and condom use, uses QCA to identify and explain configurations leading to protected and unprotected sex, and explains the differences. The analysis shows that alcohol alone is not sufficient to explain any cases involving unprotected sex but alcohol in combination with partner type and contextual factors does explain unprotected sex for subsets of married and unmarried men.


Intravenous RMP-7 increases delivery of ganciclovir into rat brain tumors and enhances the effects of herpes simplex virus thymidine kinase gene therapy.
Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increasing the BBTB delivery of GCV. In vitro, a significant bystander cytocidal effect of GCV was shown in mixed HSV-tk-transduced (HSV-tk+) and control vector-transduced (HSV-tk-) C6 glioma cultures. A dose-dependent cytotoxic effect of GCV on untransformed C6 cells was also shown. In vivo, rats with 100% HSV-tk+ or 100% HSV-tk- intracerebral C6 gliomas were treated for 7 days with intravenous infusions of GCV alone or with GCV and RMP-7 (2.5 microg/kg/day). The growth of HSV-tk+ and HSV-tk- gliomas decreased with increasing doses of GCV. A high dosage (100 mg of GCV/kg/day) eradicated all HSV-tk- and HSV-tk+ tumors. An intermediate dosage (5 mg of GCV/kg/day) reduced the growth of HSV-tk- gliomas by 42% if given alone, and by 88% in combination with RMP-7. A low dosage (0.5 mg of GCV/kg/day) in combination with RMP-7 enhanced the regression of HSV-tk+ gliomas by 87% compared with GCV alone. Low-dose GCV was ineffective in HSV-tk- tumors. RMP-7 increased [3H] GCV tumoral uptake by 2.6- and 1.7-fold in the tumor center and periphery, respectively. We conclude that RMP-7 could be an important adjunctive treatment for suicide gene therapy of brain tumors, while an RMP-7/GCV combination may also have a significant antitumor effect in untransfected gliomas.


Methotrexate for induction of remission in ulcerative colitis.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Corticosteroids and 5-aminosalicylates are the most commonly used therapies. However, many patients require immunosuppressive therapy for steroid-refractory and steroid-dependent disease. Methotrexate is a medication that is effective for treating a variety of inflammatory diseases, including Crohn's disease. This review was performed to determine the effectiveness of methotrexate treatment in UC patients. This review is an update of a previously published Cochrane review. To assess the efficacy and safety of methotrexate for induction of remission in patients with UC. MEDLINE, EMBASE, CENTRAL and the Cochrane IBD/FBD group specialized trials register were searched from from inception to June 26, 2014. Study references and review papers were also searched for additional trials. Abstracts from major gastroenterological meetings were searched to identify research published in abstract form only. Randomized controlled trials comparing methotrexate with placebo or an active comparator in patients with active ulcerative colitis were considered for inclusion. Two authors independently reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome measure was the proportion of patients who achieved clinical remission and withdrawal from steroids as defined by the studies and expressed as a percentage of the total number of patients randomized (intention-to-treat analysis). We calculated the risk ratio (RR) and corresponding 95% confidence intervals (95% CI) for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria. Two studies (n = 101 patients) were included in the review. One study (n = 67) compared oral methotrexate 12.5 mg/week) to placebo. The other study (n = 34) compared oral methotrexate (15 mg/week) to 6-mercaptopurine (1.5 mg/kg/day) and 5-aminosalicylic acid (3 g/day). The placebo-controlled study was judged to be at low risk of bias. The other study was judged to be at high risk of bias due to an open-label design. There was no statistically significant difference in clinical remission rates between methotrexate and placebo patients. Forty-seven per cent (14/30) of methotrexate patients achieved clinical remission and complete withdrawal from steroids during the study period compared to 49% (18/37) of placebo patients (RR 0.96, 95% CI 0.58 to 1.59. A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (32 events). There were no statistically significant differences in the proportion of patients who achieved clinical remission and withdrawal from steroids in the study comparing oral methotrexate to 6-mercaptopurine and 5-aminosalicylic acid. At 30 weeks, 58% (7/12) of methotrexate patients achieved clinical remission and withdrawal from steroids compared to 79% (11/14) of 6-mercaptopurine patients (RR 0.74, 95% CI 0.43 to 1.29) and 25% of 5-aminosalicylic acid patients (RR 2.33, 95% CI 0.64 to 8.49). GRADE analyses indicated that the overall quality of the evidence was very low due to very sparse data (18 and 9 events respectively) and and high risk of bias. In the placebo-controlled trial two patients (7%) were withdrawn from the methotrexate group due to adverse events (leucopenia, migraine) compared to one patient (3%) who had a rash in the placebo group (RR 2.47, 95% CI 0.23 to 25.91). Adverse events experienced by methotrexate patients in the active comparator study included nausea and dyspepsia, mild alopecia, mild increase in aspartate aminotransferase levels, peritoneal abscess, hypoalbuminemia, severe rash and atypical pneumonia. Although methotrexate was well-tolerated, the studies showed no benefit for methotrexate over placebo or active comparators. The results for efficacy outcomes between methotrexate and placebo, methotrexate and 6-mercaptopurine and methotrexate and 5-aminosalicylic acid were uncertain. Whether a higher dose or parenteral administration would be effective for induction therapy is unknown. At present there is no evidence supporting the use of methotrexate for induction of remission in active ulcerative colitis. A trial in which larger numbers of patients receive a higher dose of oral methotrexate should be considered. Currently there are two large ongoing placebo-controlled trials (METEOR and MERIT-UC) assessing the efficacy and safety of intramuscular or subcutaneous methotrexate in patients with active UC which may help resolve the evidence supporting the use of methotrexate as therapy for active of ulcerative colitis.


Enhanced platelet accumulation onto injured carotid arteries in rabbits after aspirin treatment.
Prostacyclin (PGI2) is a powerful inhibitor of platelet aggregation, but its role in the pathogenesis of arterial thrombosis is uncertain. We have studied the thrombogenic effect of inhibiting PGI2 production by aspirin (ASA) in carotid arteries of rabbits given 0, 3, 10, or 100 mg ASA/kg either 1, 3, 6, or 20 h beforehand. Platelet accumulation onto injured carotid arteries was enhanced with ASA in a dose of 10 mg/kg. A higher dose of ASA (100 mg/kg) had no further effect. The enhanced thrombogenic effect of ASA persisted for at least 20 h and was associated with a decrease in vessel wall PGI2 production. There was a strong inverse correlation (r = 0.55, P less than 0.01) between PGI2 production and platelet accumulation. The findings suggest that the margin of safety in obtaining an antithrombotic effect of ASA and producing a potential thrombotic effect in arteries may not be as large as predicted by studies using cultured endothelial cells or experimentally induced thrombosis in veins.


Measurable residual disease testing in acute myeloid leukaemia.
There is considerable interest in developing techniques to detect and/or quantify remaining leukaemia cells termed measurable or, less precisely, minimal residual disease (MRD) in persons with acute myeloid leukaemia (AML) in complete remission defined by cytomorphological criteria. An important reason for AML MRD-testing is the possibility of estimating the likelihood (and timing) of leukaemia relapse. A perfect MRD-test would precisely quantify leukaemia cells biologically able and likely to cause leukaemia relapse within a defined interval. AML is genetically diverse and there is currently no uniform approach to detecting such cells. Several technologies focused on immune phenotype or cytogenetic and/or molecular abnormalities have been developed, each with advantages and disadvantages. Many studies report a positive MRD-test at diverse time points during AML therapy identifies persons with a higher risk of leukaemia relapse compared with those with a negative MRD-test even after adjusting for other prognostic and predictive variables. No MRD-test in AML has perfect sensitivity and specificity for relapse prediction at the cohort- or subject levels and there are substantial rates of false-positive and -negative tests. Despite these limitations, correlations between MRD-test results and relapse risk have generated interest in MRD-test result-directed therapy interventions. However, convincing proof that a specific intervention will reduce relapse risk in persons with a positive MRD-test is lacking and needs testing in randomized trials. Routine clinical use of MRD-testing requires further refinements and standardization/harmonization of assay platforms and results reporting. Such data are needed to determine whether results of MRD-testing can be used as a surrogate end point in AML therapy trials. This could make drug-testing more efficient and accelerate regulatory approvals. Although MRD-testing in AML has advanced substantially, much remains to be done.


Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation.
Growing evidence points to the potential of agonistic anti-CD40 mAbs as adjuvants for vaccination against cancer. These appear to act by maturing dendritic cells (DCs) and allowing them to prime CD8 cytotoxic T lymphocytes (CTLs). Although it is well established that optimal T-cell priming requires costimulation via B7:CD28, recent studies emphasize the contribution of TNF receptors to this process. To understand how anti-CD40 mAbs trigger effective antitumor immunity, we investigated the role of TNFR superfamily members CD27 and 4-1BB in the generation of this immunity and showed that, although partially dependent on 4-1BB:4-1BBL engagement, it is completely reliant on CD27:CD70 interactions. Importantly, blocking CD70, and to some extent 4-1BBL, during anti-CD40 treatment prevented accumulation of tumor-reactive T cells and subsequent tumor protection. However, it did not influence changes in DC number, phenotype, nor the activity of CTLs once immunity was established. We conclude that CD27:CD70 and 4-1BB:4-1BBL interactions are needed for DC-driven accumulation of antitumor CTLs following anti-CD40 mAb treatment. Finally, in support of the critical role for CD70:CD27, we show for the first time that agonistic anti-CD27 mAbs given without a DC maturation signal completely protect tumor-bearing mice and provide a highly potent reagent for boosting antitumor T-cell immunity.


Quantitative characterization of rat tendinitis to evaluate the efficacy of therapeutic interventions.
Tendinitis is a painful soft tissue pathology that accounts for almost half of all occupational injuries in the United States. It is often caused by repeated movements and may result in loss of work and income. Current treatments for tendinitis are aimed at reducing inflammation, the major cause of the pain. Although anti-inflammatory drugs and various alternative therapies are capable of improving tendinitis, there are no quantitative scientific data available regarding their impact on inflammation. The objective of this study is to determine the time course for healing of rat tendinitis without intervention to be able to assess the efficacy of tendinitis treatments. We are interested in evaluating the therapeutic use of pulsed electromagnetic fields (PEMFs), a therapeutic modality that has been found to be beneficial for healing soft tissue injuries. Tendinitis was induced in Harlan Sprague Dawley rats by collagenase injections into the Achilles tendon, and tendons were collected for four weeks post-injury. To determine the amount of edema, we used caliper measurements of the rat ankles and quantified the tendon water content. To determine the extent of inflammation, we estimated the number of inflammatory cells on histological sections applying stereological methods. The data reveal that edema is maximal 24 hours after injury accompanied by a massive infiltration of inflammatory cells. Inflammatory cells are then gradually replaced by fibroblasts, which are responsible for correcting damage to the extracellular matrix. This natural time course of tendon healing will be used to evaluate the use of PEMFs as a possible therapeutic modality.


Fractures of the scapula.
One hundred thirty-seven fractures of the scapula in 121 patients were reviewed. The average age at the time of injury was 35 years, with fractures predominant in males (64%). The majority of cases (43%) involved fractures of the body of the scapula, with fractures of the scapular neck being second most common (26%). Automobile accidents produced the most injuries (52%), followed by auto-pedestrian (18%), falls (12%), and motorcycle accidents (11%). Associated bony or major soft-tissue trauma was present in all but 15 of the 121 patients, the most common being fractured ribs in 44%. Other associated injuries included fractures of the clavicle (26%), fractured skull (24%), cerebral contusion (20%), neurologic deficit (13%), and pulmonary contusion or hemo-pneumothorax (16%). Patients with injuries involving the acromion process or acromioclavicular joint had a significantly higher incidence of associated peripheral nerve injuries than those with other fractures of the scapula, indicating that special attention should be given to the neurologic examination of patients with these fractures. Careful neurovascular examination is mandatory. Treatment was usually conservative, independent of the location of the fracture, with satisfactory long-term results. We recommend simple immobilization followed by early active range of motion exercise.


Time sensing by NAADP receptors.
NAADP (nicotinic acid-adenine dinucleotide phosphate) is a newly described intracellular messenger molecule that mediates Ca2+ increases in a variety of cells. However, little is known of the mechanism whereby ligand binding regulates the target protein. We report in the present paper that NAADP receptors from sea urchin eggs undergo an unusual stabilization process that appears to be dependent upon the time during which receptors are exposed to their ligand. We demonstrate that receptors 'tagged' with NAADP for short periods were more readily dissociated following subsequent delipidation than those labelled for longer. Stabilization of NAADP receptors by their ligand was delayed relative to ligand association taking on the order of minutes to develop at picomolar concentrations. The stabilizing effects of NAADP did not require cytosolic factors or the continued presence of NAADP and persisted upon solubilization. NAADP receptors, however, failed to stabilize at reduced temperature. We conclude that NAADP receptors possess a simple molecular memory endowing them with the remarkable ability to detect the duration of their activation.


Langerhans cells, orthotopic corneal allografts, and direct and indirect pathways of T-cell allorecognition.
To determine after orthotopic corneal allografting the role of Langerhans cells in activation of T cells via the direct and indirect pathways of allorecognition and the relationship between these pathways and the rapidity of graft rejection. Corneas from eyes of normal mice and from eyes after superficial cauterization were grafted to eyes of major histocompatibility complex (MHC) and/or minor histocompatibility (H)-disparate recipient mice. The grafts were analyzed through time for content of class 1 MHC- bearing Langerhans cells and for rejection or acceptance. Graft recipients were evaluated for acquisition of delayed hypersensitivity (DH) and cytotoxic T cells (Tc) directed at donor MHC and minor H alloantigens. Langerhans cells migrated more rapidly into epithelium of cauterized grafts than normal grafts. Unlike normal grafts, the vast majority of cauterized allografts were rejected within 2 weeks. Normal grafts induced neither DH nor Tc directed at donor MHC antigens, whereas cauterized grafts induced both DH and Tc specific for donor MHC. All grafts induced DH directed at donor minor H antigens, but only rejected grafts correlated with acquisition of Tc directed at donor minor H antigens. CONCLUSIONS. The rapidity of orthotopic corneal allograft rejection correlated with density of Langerhans cells within epithelium and with acquisition of donor-specific DH and Tc. Although recipient-derived Langerhans cells promoted minor H-specific, self-MHC-restricted T cells (indirect pathway) and subacute graft rejection, donor-derived Langerhans cells promoted early, acute rejection in conjunction with allogeneic MHC-specific Tc (direct pathway).


Microfluidic capture and release of bacteria in a conical nanopore array.
We present a simple and inexpensive method for the capture and release of bacteria contained in an array of conical nanopores on a membrane inside a microfluidic device. As an example, we demonstrate that cyanobacteria can be captured, one bacterium per pore, in a defined orientation with over 500 bacteria per membrane with viabilities as high as 100%. The device can also specifically capture cyanobacteria from a mixed suspension of cyanobacteria and chlamydomonas with a selectivity as high as 90%.


Predicting the completion of an integrative and intensive outpatient chronic pain treatment with the personality assessment inventory.
The effects of intensive, integrative treatments for chronic pain are affected by patient compliance, and in many cases, selecting noncompliant individuals adversely impacts the cost-effectiveness of such programs. The pretreatment identification of individuals who are at risk for dropout could assist clinicians in augmenting treatments with motivational enhancement strategies for high-risk patients or using such information to select individuals who are most likely to complete a given intervention program. In this study, we tested the ability of indicators from the Personality Assessment Inventory (PAI; Morey, 1991), administered prior to treatment, to identify individuals who dropped out of a 20-day chronic pain program. Results replicate findings from outpatient psychotherapy research in finding that PAI Mean Clinical Elevation and Treatment Process Index significantly differentiated dropouts from graduates, particularly when the Treatment Rejection scale suggested patients were motivated for treatment. We discuss these results and offer recommendations for the prediction of treatment dropout in pain settings.


Deguelin action involves c-Met and EGFR signaling pathways in triple negative breast cancer cells.
Treatment of breast cancer patients with antiestrogens and aromatase inhibitor(s) or Herceptin have shown significant success in steroid receptor positive or Her-2+ breast cancers respectively. However, choice of treatments for breast cancer patients with negative status for estrogen, progesterone receptors and HER2/neu is limited. As a result, search for appropriate therapy regimen for these triple negative breast cancers (TNBC) has become a major focus of investigations for many laboratories. Recently, Deguelin, a natural product isolated from African plant Mundulea sericea (Leguminossae) has shown both antiproliferative actions in various cancers including breast as well as chemoprenventive activity against carcinogen induced experimental cancers. In this report we evaluated efficacy and mechanism of action of Deguelin in triple negative breast cancer cell lines. In vitro, Deguelin in a dose and time dependent manner inhibited the growth of MDA-MB-231, MDA-MB-468, BT-549 and BT-20 cells. Deguelin (2 or 4 mg/kg body weight), when injected intraperitoneally, reduced the in vivo tumor growth of MDA-MB-231 cells transplanted subcutaneously in athymic mice. Moreover it was nontoxic as evident from daily observations on mobility, food and water consumption and comparison of bodyweight and other visceral organ weights with those in control animals at the termination of the study. The western blot analyses and immunostaining studies indicated that the deguelin effects may be mediated through EGFR-PAKT/c-Met p-ERK and NF-κB by down regulating their downstream targets such as p-STAT3, c-Myc, Survivin. These results suggest that Deguelin may have a significant therapeutic value for the treatment of TNBC patients.


Management of mass casualty events: the Israeli experience.
Among all the emergency scenarios, the most common medical emergency event in Israel is the conventional mass casualty event (MCE). This article describes the Israeli model of emergency preparedness and management at the national level, step-by-step emergency management at the hospital level, and nursing roles in emergency events. Israel has a unique national and local model of organizing and managing an emergency event, characterized by a central national organization that is responsible for emergency policy, management, coordination, quality control, and ongoing improvement. Well-planned emergency preparedness training for a multidisciplinary staff is crucial. Nurses play significant roles both clinically and managerially in leading and organizing emergency events on all levels. Lessons gained from the special model of management of MCEs in Israel, particularly regarding unique nursing roles, may be considered for applicability in other countries.


Interaction of the N-methyl-D-aspartate receptor complex with a novel synapse-associated protein, SAP102.
Ionotropic glutamate receptors are known to cluster at high concentration on the postsynaptic membrane of excitatory synapses, but the mechanism by which this occurs is poorly understood. Studies on the neuromuscular junction and central inhibitory synapses suggest that clustering of neurotransmitter receptors requires its interaction with a cytoplasmic protein. Recently, in vitro studies have shown that members of the N-methyl--aspartate (NMDA) class of glutamate receptors interact with a synapse-associated protein, SAP90 (PSD-95). However, evidence for the in vivo interaction of NMDA receptors with SAPs is still lacking. In the present study, we demonstrate the specific interaction between SAP102, a novel synapse-associated protein, and the NMDA receptor complex from the rat cortical synaptic plasma membranes using co-immunoprecipitation techniques. No association was observed between SAP102 and GluR1, a member of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate class of glutamate receptors. To identify the domain on the NMDA receptor responsible for this interaction, we constructed hexahistidine fusion proteins from different regions of the NR1a and NR2 subunits of the NMDA receptor. Immunoblot overlay experiments showed that while the C-terminal domain of the NR2 subunit displayed strong binding, the NR1a intracellular C-terminal tail did not interact with SAP102. The site of interaction was more precisely located to the last 20 amino acids of the NR2 subunit as indicated by the interaction of the synthetic peptide with SAP102. In summary, we demonstrate here for the first time an in vivo interaction between the native NMDA receptor complex and a synapse-associated protein. These results suggest that SAP102 may play an important role in NMDA receptor clustering and immobilization at excitatory synapses.


Hierarchical Ti3C2Tx MXene/Carbon Nanotubes for Low Overpotential and Long-Life Li-CO2 Batteries.
Electrochemical carbon dioxide conversion at ambient temperature is an efficient route to synchronously provide a continuous power supply and produce useful chemicals such as carbonates. Rigid catalysts with rational morphological and structural design are used to overcome the sluggish reaction kinetics and contribute to a better cycle life in Li-CO2 batteries. In this report, a two-dimensional Ti3C2Tx MXene/carbon heterostructure assembled parallel-aligned tubular architecture was delicately synthesized through a self-sacrificial templating method and delivered an ultralow overpotential of 1.38 V at 0.2 A·g-1. The heterostructure that inherited the high catalytic performance of Ti3C2Tx MXene and the outstanding stability of carbon material promoted the adsorption of CO2 and accelerated the decomposition of lithium carbonate, which was proved by in situ and ex situ characterizations and density functional theory calculations. The tubular architecture with large surface area was demonstrated to provide a high durability for long cycle life and ensure good contacts among gas, electrolyte, and electrode.


Revision total hip replacement with cement.
This article outlines the author's perspectives on the use of cement in revision total hip replacement. The results reported in the literature are briefly described and a follow-up of the author's personal results using cement the second time on the femoral side will be outlined. Specifically, 110 revisions were performed between 1974 and 1989 and only four of those have required revision for aseptic loosening. Three have been noted to be radiologically loose without sufficient symptoms to warrant revision. Specific cement techniques and prosthetic choices are described. Several clinical examples using cement will illustrate its versatility for treating significant femoral anatomical deficiencies.


Influence of Subclinical Corneal Edema on Contrast Sensitivity in Fuchs Endothelial Corneal Dystrophy.
The aim of this study was to compare visual function, with a focus on contrast sensitivity, between patients with Fuchs endothelial corneal dystrophy (FECD) with and without subclinical corneal edema. In this cross-sectional, observational, single-center study, 46 pseudophakic eyes of 31 patients with FECD were divided into 2 groups depending on the presence of subclinical corneal edema. All eyes presented with a Krachmer grade of 5 and no clinical corneal edema. The criteria for subclinical corneal edema were loss of regular isopachs, displacement of the thinnest point, and focal posterior surface depression in Scheimpflug tomography. If more than 1 criterion was present, subclinical corneal edema was diagnosed. The corrected distance visual acuity, contrast sensitivity (Pelli-Robson chart and CSV-1000 test with optional glare), and straylight were measured. The differences between both groups were analyzed using clustered Wilcoxon rank-sum tests. The corrected distance visual acuity and the contrast sensitivity, measured with a Pelli-Robson chart, were significantly inferior in eyes with subclinical corneal edema compared with eyes without subclinical edema ( P < 0.05). At all spatial frequencies, eyes with subclinical edema demonstrated lower contrast sensitivity with a statistically significantly reduction in total contrast sensitivity when tested with ( P = 0.005) and without ( P = 0.002) glare. The straylight did not significantly differ between both groups ( P > 0.05). The corrected distance visual acuity and contrast sensitivity were significantly reduced in FECD eyes with subclinical corneal edema compared with those with no subclinical edema. This decrease in visual quality may be considered when evaluating the need for surgical intervention at earlier stages of FECD.


High-resolution intravascular magnetic resonance quantification of atherosclerotic plaque at 3T.
The thickness of fibrous caps (FCT) of atherosclerotic lesions is a critical factor affecting plaque vulnerability to rupture. This study tests whether 3 Tesla high-resolution intravascular cardiovascular magnetic resonance (CMR) employing tiny loopless detectors can identify lesions and accurately measure FCT in human arterial specimens, and whether such an approach is feasible in vivo using animal models. Receive-only 2.2 mm and 0.8 mm diameter intravascular loopless CMR detectors were fabricated for a clinical 3 Tesla MR scanner, and the absolute signal-to-noise ratio determined. The detectors were applied in a two-step protocol comprised of CMR angiography to identify atherosclerotic lesions, followed by high-resolution CMR to characterize FCT, lesion size, and/or vessel wall thickness. The protocol was applied in fresh human iliac and carotid artery specimens in a human-equivalent saline bath. Mean FCT measured by 80 μm intravascular CMR was compared with histology of the same sections. In vivo studies compared aortic wall thickness and plaque size in healthy and hyperlipidemic rabbit models, with post-mortem histology. Histology confirmed plaques in human specimens, with calcifications appearing as signal voids. Mean FCT agreed with histological measurements within 13% on average (correlation coefficient, R = 0.98; Bland-Altman analysis, -1.3 ± 68.9 μm). In vivo aortic wall and plaque size measured by 80 μm intravascular CMR agreed with histology. Intravascular 3T CMR with loopless detectors can both locate atherosclerotic lesions, and accurately measure FCT at high-resolution in a strategy that appears feasible in vivo. The approach shows promise for quantifying vulnerable plaque for evaluating experimental therapies.


Molecular Mechanisms of the Regulation of Liver Cytochrome P450 by Brain NMDA Receptors and via the Neuroendocrine Pathway-A Significance for New Psychotropic Therapies.
Recent investigations have highlighted the potential utility of the selective antagonist of the NMDA receptor GluN2B subunit for addressing major depressive disorders. Our previous study showed that the systemic administration of the antagonist of the GluN2B subunit of the NMDA receptor, the compound CP-101,606, affected liver cytochrome P450 expression and activity. To discern between the central and peripheral mechanisms of enzyme regulation, our current study aimed to explore whether the intracerebral administration of CP-101,606 could impact cytochrome P450. The injection of CP-101,606 to brain lateral ventricles (6, 15, or 30 µg/brain) exerted dose-dependent effects on liver cytochrome P450 enzymes and hypothalamic or pituitary hormones. The lowest dose led to an increase in the activity, protein, and mRNA level of CYP2C11 compared to the control. The activities of CYP2A, CYP2B, CYP2C11, CYP2C6, CYP2D, and protein levels of CYP2B, CYP2C11 were enhanced compared to the highest dose. Moreover, CP-101,606 increased the CYP1A protein level coupled with elevated CYP1A1 and CYP1A2 mRNA levels, but not activity. The antagonist decreased the pituitary somatostatin level and increased the serum growth hormone concentration after the lowest dose, while independently decreasing the serum corticosterone concentration of the dose. The findings presented here unveil a novel physiological regulatory mechanism whereby the brain glutamatergic system, via the NMDA receptor, influences liver cytochrome P450. This regulatory process appears to involve the endocrine system. These results may have practical applications in predicting alterations in cytochrome P450 activity and endogenous metabolism, and potential metabolic drug-drug interactions elicited by drugs that cross the blood-brain barrier and affect NMDA receptors.


Major infection after pediatric cardiac surgery: a risk estimation model.
In pediatric cardiac surgery, infection is a leading cause of morbidity and mortality. We created a model to predict risk of major infection in this population. Using the Society of Thoracic Surgeons Congenital Heart Surgery Database, we created a multivariable model in which the primary outcome was major infection (septicemia, mediastinitis, or endocarditis). Candidate-independent variables included demographic characteristics, comorbid conditions, preoperative factors, and cardiac surgical procedures. We created a reduced model by backward selection and then created an integer scoring system using a scaling factor with scores corresponding to percent risk of infection. Of 30,078 children from 48 centers, 2.8% had major infection (2.6% septicemia, 0.3% mediastinitis, and 0.09% endocarditis). Mortality and postoperative length of stay were greater in those with major infection (mortality, 22.2% versus 3.0%; length of stay >21 days, 69.9% versus 10.7%). Young age, high complexity, previous cardiothoracic operation, preoperative length of stay more than 1 day, preoperative ventilator support, and presence of a genetic abnormality were associated with major infection after backward selection (p < 0.001). Estimated infection risk ranged from less than 0.1% to 13.3%; the model discrimination was good (c index, 0.79). We created a simple bedside tool to identify children at high risk for major infection after cardiac surgery. These patients may be targeted for interventions to reduce the risk of infection and for inclusion in future clinical trials.


Identification and characterization of guanosine 5'-monophosphate reductase of Trypanosoma congolense as a drug target.
Trypanosoma congolense is one of the most prevalent pathogens which causes trypanosomosis in African animals, resulting in a significant economic loss. In its life cycle, T. congolense is incapable of synthesizing purine nucleotides via a de novo pathway, and thus relies on a salvage pathway to survive. In this study, we identified a gene from T. congolense, TcIL3000_5_1940, as a guanosine 5'-monophosphate reductase (GMPR), an enzyme that modulates the concentration of intracellular guanosine in the pathogen. The recombinant protein was expressed in Escherichia coli, and the gene product was enzymatically confirmed as a unique GMPR, designated as rTcGMPR. This enzyme was constitutively expressed in glycosomes at all of the parasite's developmental stages similar to other purine nucleotide metabolic enzymes. Mycophenolic acid (MPA) was found to inhibit rTcGMPR activity. Hence, it is a potential lead compound for the design of trypanocidal agents, specifically GMPR inhibitor.


High density SNP and SSR-based genetic maps of two independent oil palm hybrids.
Oil palm is an important perennial oil crop with an extremely long selection cycle of 10 to 12 years. As such, any tool that speeds up its genetic improvement process, such as marker-assisted breeding is invaluable. Previously, genetic linkage maps based on AFLP, RFLP and SSR markers were developed and QTLs for fatty acid composition and yield components identified. High density genetic maps of crosses of different genetic backgrounds are indispensable tools for investigating oil palm genetics. They are also useful for comparative mapping analyses to identify markers closely linked to traits of interest. A 4.5 K customized oil palm SNP array was developed using the Illumina Infinium platform. The SNPs and 252 SSRs were genotyped on two mapping populations, an intraspecific cross with 87 palms and an interspecific cross with 108 palms. Parental maps with 16 linkage groups (LGs), were constructed for the three fruit forms of E. guineensis (dura, pisifera and tenera). Map resolution was further increased by integrating the dura and pisifera maps into an intraspecific integrated map with 1,331 markers spanning 1,867 cM. We also report the first map of a Colombian E. oleifera, comprising 10 LGs with 65 markers spanning 471 cM. Although not very dense due to the high level of homozygosity in E. oleifera, the LGs were successfully integrated with the LGs of the tenera map. Direct comparison between the parental maps identified 603 transferable markers polymorphic in at least two of the parents. Further analysis revealed a high degree of marker transferability covering 1,075 cM, between the intra- and interspecific integrated maps. The interspecific cross displayed higher segregation distortion than the intraspecific cross. However, inclusion of distorted markers in the genetic maps did not disrupt the marker order and no map expansion was observed. The high density SNP and SSR-based genetic maps reported in this paper have greatly improved marker density and genome coverage in comparison with the first reference map based on AFLP and SSR markers. Therefore, it is foreseen that they will be more useful for fine mapping of QTLs and whole genome association mapping studies in oil palm.