Quantitative analysis of the variation in angles of the carpal arch after open and endoscopic carpal tunnel release. Clinical article.
Previous studies have demonstrated that the volume of the carpal canal increases after open and endoscopic surgery in patients with carpal tunnel syndrome. There is some controversy regarding the contribution of the post operative widening of the carpal arch to the increment in carpal canal volume. The objectives of this study were to: 1) evaluate the degree of variation in the angles formed by the borders of the carpal arch following the surgical division of the transverse carpal ligament; and 2) determine if there are differences in the variation of these angles after the classical open surgery versus endoscopic carpal tunnel release.Methods. The authors prospectively studied 20 patients undergoing carpal tunnel syndrome surgery: 10 patients were treated via the standard open technique, and 10 underwent endoscopic carpal tunnel release. The angles of the carpal arch were measured on CT scans of the affected hand obtained before and immediately after the surgical procedures.Measurements were performed at the level of the pisiform-scaphoid hiatus and at the level of the hook of the hamate-trapezium hiatus. There was widening of the postoperative angles of the carpal arch after open and endoscopic division of the flexor retinaculum; however, the difference between pre- and postoperative angulations reached statistical significance only in those patients treated by means of the open procedure. The mean (+/- SD) values for the postoperative increase in the angles at the level of the pisiform-scaphoid hiatus were 5.1 +/- 0.4 degrees after open surgery and 2.5 +/- 0.3 degrees after the endoscopically assisted procedure (p < 0.05). At the level of the hook of the hamate-trapezium hiatus, the mean values for the widening of the angles were 6.2 +/- 0.6 degrees for the open surgery group and 1.2 +/- 0.4 degrees for those patients treated by means of the endoscopic technique (p < 0.05). The widening of the postoperative angles of the carpal arch is a phenomenon observed at the proximal and distal levels of the carpal canal, and it can be noted after both open and endoscopically assisted carpal tunnel release. The endoscopic procedure yielded less increase in these angles than the open surgery.


Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects.
This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL). Subjects homozygous for E3 converted approximately 50% of LVDL2 to LDL, the remainder being lost by direct catabolism. Those with the E2 phenotype produced less VLDL1, but converted more of it to VLDL2 (compared to E3 subjects). They displayed a characteristic dyslipidemia with the presence of slowly catabolized VLDL1 and VLDL2 remnants. LDL levels were low owing to increased direct catabolism of VLDL2 and IDL and a reduced efficiency of delipidation; only 25% of VLDL2 apo B was directed to LDL production. In contrast, E4 subjects converted more VLDL2 apo B to LDL than E3 subjects. About 70% of VLDL2 apo B was found in LDL; direct catabolism of VLDL and IDL was reduced as was the fractional catabolic rate of LDL (0.2 vs. 0.26 in E3 subjects). These changes in the VLDL----IDL----LDL metabolic cascade can in part be explained by alterations in hepatic LDL receptors with E2 subjects having higher and E4 subjects lower activities than those in E3 homozygotes.


Astrocyte elevated gene-1 overexpression in hepatocellular carcinoma: an independent prognostic factor.
Astrocyte elevated gene-1 (AEG-1) plays important roles in tumorigenesis such as proliferation, invasion, metastasis, angiogenesis, and chemoresistance. We examined the expression of AEG-1 in patients with hepatocellular carcinoma (HCC). Eighty-five samples were collected from patients with HCC who underwent surgery and were histopathologically confirmed to have HCC. Two independent pathologists, experienced in evaluating immunohistochemistry and blinded to the clinical outcomes of the patients, reviewed all samples. They determined AEG-1 expression semiquantitatively by assessing the percentage of positively stained immunoreactive cells and staining intensity. Clinicopathological data were analyzed in association with prognosis. The association was estimated by univariate and multivariate analyses with Cox regression. Tumor size (hazard ratio [HR], 2.285; 95% confidence interval [CI], 1.175-4.447; P = 0.015), microvascular invasion (HR, 6.754; 95% CI, 1.631-27.965; P = 0.008), and AEG-1 expression (HR, 4.756; 95% CI, 1.697-13.329; P = 0.003) were independent prognostic factors for overall survival. Those for disease-free survival rate were tumor size (HR, 2.245; 95% CI, 1.282-3.933; P = 0.005) and AEG-1 expression (HR, 1.916; 95% CI, 1.035-3.545; P = 0.038). The cumulative 5-year survival and recurrence rates were 89.2% and 50.0% in the low-expressing group and 24.5% and 82.4% in the high-expressing group, respectively. The results suggest that AEG-1 overexpression could serve as a valuable prognostic marker in patients with HCC.


Enzymatic activity of poliovirus RNA polymerase mutants with single amino acid changes in the conserved YGDD amino acid motif.
RNA-dependent RNA polymerases contain a highly conserved region of amino acids with a core segment composed of the amino acids YGDD which have been hypothesized to be at or near the catalytic active site of the molecule. Six mutations in this conserved YGDD region of the poliovirus RNA-dependent RNA polymerase were made by using oligonucleotide site-directed DNA mutagenesis of the poliovirus cDNA to substitute A, C, M, P, S, or V for the amino acid G. The mutant polymerase genes were expressed in Escherichia coli, and the purified RNA polymerases were tested for in vitro enzyme activity. Two of the mutant RNA polymerases (those in which the glycine residue was replaced with alanine or serine) exhibited in vitro enzymatic activity ranging from 5 to 20% of wild-type activity, while the remaining mutant RNA polymerases were inactive. Alterations in the in vitro reaction conditions by modification of temperature, metal ion concentration, or pH resulted in no significant differences in the activities of the mutant RNA polymerases relative to that of the wild-type enzyme. An antipeptide antibody directed against the wild-type core amino acid segment containing the YGDD region of the poliovirus polymerase reacted with the wild-type recombinant RNA polymerase and to a limited extent with the two enzymatically active mutant polymerases; the antipeptide antibody did not react with the mutant RNA polymerases which did not have in vitro enzyme activity. These results are discussed in the context of secondary-structure predictions for the core segment containing the conserved YGDD amino acids in the poliovirus RNA polymerase.


Interspecific Hybrids Between Pelargonium × hortorum and Species From P. Section Ciconium Reveal Biparental Plastid Inheritance and Multi-Locus Cyto-Nuclear Incompatibility.
The genetics underlying Cyto-Nuclear Incompatibility (CNI) was studied in Pelargonium interspecific hybrids. We created hybrids of 12 closely related crop wild relatives (CWR) with the ornamental P. × hortorum. Ten of the resulting 12 (F1) interspecific hybrids segregate for chlorosis suggesting biparental plastid inheritance. The segregation ratios of the interspecific F2 populations show nuclear interactions of one, two, or three nuclear genes regulating plastid function dependent on the parents. We further validated that biparental inheritance of plastids is common in section Ciconium, using diagnostic PCR primers. Our results pave the way for using the diverse species from section Ciconium, each with its own set of characteristics, as novel sources of desired breeding traits for P. × hortorum cultivars.


Translocation Frequency in Patients with Repeated CT Exposure: Comparison with CT-Naive Patients.
Epidemiologic studies using clinical indicators are limited in the assessment of the biological effects of low-dose ionizing radiation for medical purposes. We evaluated the biological effect of low-dose radiation by comparing translocation frequencies in patients with repeated computed tomography (CT) exposure and CT-naïve patients. The goal of this prospective case-control study was to determine whether repeated CT exposure is associated with increased frequency in chromosomal translocations. Two cohorts, comprised of case patients with a history of repeated CT exposure and age- and sex-matched CT-naïve control patients (n = 48 per cohort), were consecutively enrolled in this single-institution study. CT-radiation exposure was estimated using dose-length products, and translocation frequencies of peripheral blood lymphocytes were assessed using whole chromosome paints by fluorescence in situ hybridization (FISH). Comparison of translocation frequencies between cases and controls was performed using the Wilcoxon rank sum test (paired samples), and the relationship between cumulative radiation exposure and translocation frequency was assessed using a partial correlation analysis. Translocation frequencies were significantly different between cases and controls (P = 0.0003). The median translocation frequency was 7 [95% confidence interval (CI): 6, 8] for cases and 4 (95% CI: 3, 6) for controls. By using cumulative radiation exposure as the effect variable and translocation frequency as the response variable, we found a significant correlation between cumulative radiation exposure and translocation frequency (r = 0.6579, P < 0.0001). Chromosomal translocations were more frequent with repeated CT-exposed patients than in CT-naïve patients, and a positive dose-response relationship was present between cumulative radiation exposure and translocation frequency.


Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections.
Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.


Resistance of activated human Th2 cells to NO-induced apoptosis is mediated by gamma-glutamyltranspeptidase.
Activation-induced death of inflammatory cells (AICD) has an important function in immune maintenance. Type 1 Th cells are known to be more susceptible to AICD than Th2 cells. In the current study we examined whether NO-induced apoptosis also preferentially eliminates Th1 cells over Th2 cells. Naive human Th lymphocytes (CD4(+)CD45RO(-)) were activated in vitro for 1 week in the presence of IL-12 plus anti-IL-4 or IL-4 plus anti-IL-12 to generate Th1- and Th2-polarized cultures respectively. Cultures were exposed to the NO donors Spermine-nonoate (Sper) and DPTA-nonoate to study NO-induced apoptosis. We found that NO preferentially induced apoptosis in Th1-polarized cells as demonstrated by Annexin staining in the presence of 10 microM Sper (70 +/- 16 versus 23 +/- 4.4% in Th2 cells P: < 0.01) and by DioC6 staining (38 +/- 10 versus 11 +/- 5% in Th2 cells, P: < 0.01). The mechanism of NO-induced apoptosis in Th1/Th2-polarized cells was distinct from AICD and Fas-induced apoptosis. Differential sensitivity between Th1- and Th2-polarized cultures originated at the level of intracellular glutathione (GSH) metabolism. GSH levels were higher in Th2 cells (1.6 +/- 0.2-fold Th1, P: < 0.01). High intracellular GSH in Th2-polarized cells did not account for reduced susceptibility to NO per se, since the inhibition of gamma-glutamyltrans-peptidase (gamma-GT), which is involved in GSH import, sensitized Th2 cells to NO-induced apoptosis without GSH depletion. Therefore, higher activity of gamma-GT in Th2 cells (2.1 +/- 0.4-fold Th1, P: < 0.001) specifically protects Th2 cells against NO-induced apoptosis. Preferential NO-induced elimination of human Th1 cells at sites of inflammation may thus select Th2 cells and contribute to immune deviation.


A hybrid perturbed-chain SAFT density functional theory for representing fluid behavior in nanopores.
A hybrid statistical mechanical model, which is fully consistent with the bulk perturbed-chain statistical associating fluid theory (PC-SAFT) in describing properties of fluids, was developed by coupling density functional theory with PC-SAFT for the description of the inhomogeneous behavior of real chain molecules in nanopores. In the developed model, the modified fundamental measure theory was used for the hard sphere contribution; the dispersion free energy functional was represented with weighted density approximation by averaging the density in the range of interaction, and the chain free energy functional from interfacial statistical associating fluid theory was used to account for the chain connectivity. Molecular simulation results of the density profile were compared with model prediction, and the considerable agreement reveals the reliability of the proposed model in representing the confined behaviors of chain molecules in an attractive slit. The developed model was further used to represent the adsorptions of methane and carbon dioxide on activated carbons, in which methane and carbon dioxide were modeled as chain molecules with the parameters taken from the bulk PC-SAFT, while the parameters of solid surface were obtained from the fitting of gas adsorption isotherms measured experimentally. The results show that the model can reliably reproduce the confined behaviors of physically existing substances in nanopores.


Age-related differences in patients admitted to a palliative home care service.
The aim of the study was to investigate possible differences in access to the service, symptomatology and therapy in relation to age among terminal cancer patients admitted to a home care program. We examined prospectively all 116 terminal cancer patients enrolled in a home care program in 1998, comparing those up to 70 years of age (48 patients) with those above 70 (68 patients). We also compared the age-related characteristics of this population with those of all 348 patients enrolled in the program in 1989-1991. There were no significant differences between the two age groups of the 1998 population in terms of symptoms, tumor site or medication, although NSAID use tended to be greater in older patients, and opioid and anti-emetic use greater in younger patients. Patients up to 70 years of age had significantly shorter survival from admission to home care than those over 70, and a greater proportion had metastases. There were no such significant age-related differences as regards survival and the presence of metastases in patients enrolled 10 years before. In conclusion, among terminally ill cancer patients referred to a palliative home care service in Milan, mostly treated at the National Cancer Institute, the 10-year admission trend showed that palliative care is made available increasingly later, particularly to those up to 70 years of age, in contrast to current recommendations.


Relationship of mammographic parenchymal patterns to breast cancer risk factors and smoking in Alaska Native women.
The purpose is to determine breast cancer risk factors and correlates of mammographic parenchymal patterns among Alaska Native women. A retrospective review was performed of mammograms and mammogram records among 528 sequential screening mammogram examinations performed in Anchorage, Alaska. Mammogram density was classified by American College of Radiology (Breast Imaging Reporting and Data System) density patterns 1-4 (fat-->dense) and by percent density. Clinical data, including risk factors, ethnic group (Indian, Aleut, or Eskimo), and smoking status were obtained. Results were analyzed by univariate and multivariate analyses. Of 528 women, 164 were Indian, 155 were Aleut, and 209 were Eskimo. Mean age at first birth was lower and parity higher compared with published data in white women. Breast cancer risk factors were similar across ethnic groups. In multivariate analysis, patient age, parity, hormone replacement therapy, hysterectomy, and history of biopsy were associated, and smoking was not associated with density scores. Aleut and Indian women were less likely to have high-density mammograms than were Eskimo women (P = 0.0448). No significant differences were found between ethnic group for conventional breast cancer risk factors. Mammogram density was associated with age at screening, parity, hormone replacement therapy, hysterectomy, history of biopsy, and ethnicity but not smoking status. Eskimo women had higher mammogram density than Aleuts or Indians.


Teaching Confirmatory Factor Analysis to Non-Statisticians: A Case Study for Estimating Composite Reliability of Psychometric Instruments.
Texts and software that we are currently using for teaching multivariate analysis to non-statisticians lack in the delivery of confirmatory factor analysis (CFA). The purpose of this paper is to provide educators with a complement to these resources that includes CFA and its computation. We focus on how to use CFA to estimate a "composite reliability" of a psychometric instrument. This paper provides guidance for introducing, via a case-study, the non-statistician to CFA. As a complement to our instruction about the more traditional SPSS, we successfully piloted the software R for estimating CFA on nine non-statisticians. This approach can be used with healthcare graduate students taking a multivariate course, as well as modified for community stakeholders of our Center for American Indian Community Health (e.g. community advisory boards, summer interns, & research team members). The placement of CFA at the end of the class is strategic and gives us an opportunity to do some innovative teaching: (1) build ideas for understanding the case study using previous course work (such as ANOVA); (2) incorporate multi-dimensional scaling (that students already learned) into the selection of a factor structure (new concept); (3) use interactive data from the students (active learning); (4) review matrix algebra and its importance to psychometric evaluation; (5) show students how to do the calculation on their own; and (6) give students access to an actual recent research project.


Prevalence of flat foot in preschool-aged children.
Our aim with this study was to establish the prevalence of flat foot in a population of 3- to 6-year-old children to evaluate cofactors such as age, weight, and gender and to estimate the number of unnecessary treatments performed. A total of 835 children (411 girls and 424 boys) were included in this study. The clinical diagnosis of flat foot was based on a valgus position of the heel and a poor formation of the arch. Feet of the children were scanned (while they were in a standing position) by using a laser surface scanner, and rearfoot angle was measured. Rearfoot angle was defined as the angle of the upper Achilles tendon and the distal extension of the rearfoot. Prevalence of flexible flat foot in the group of 3- to 6-year-old children was 44%. Prevalence of pathological flat foot was < 1%. Ten percent of the children were wearing arch supports. The prevalence of flat foot decreases significantly with age: in the group of 3-year-old children 54% showed a flat foot, whereas in the group of 6-year-old children only 24% had a flat foot. Average rearfoot angle was 5.5 degrees of valgus. Boys had a significant greater tendency for flat foot than girls: the prevalence of flat foot in boys was 52% and 36% in girls. Thirteen percent of the children were overweight or obese. Significant differences in prevalence of flat foot between overweight, obese, and normal-weight children were observed. This study is the first to use a three-dimensional laser surface scanner to measure the rearfoot valgus in preschool-aged children. The data demonstrate that the prevalence of flat foot is influenced by 3 factors: age, gender, and weight. In overweight children and in boys, a highly significant prevalence of flat foot was observed; in addition, a retarded development of the medial arch in the boys was discovered. At the time of the study, > 90% of the treatments were unnecessary.


Amblyopia in children (aged 7 years or less).
Amblyopia is reduced visual acuity not immediately correctable by glasses, in the absence of ocular pathology. It is commonly associated with squint (strabismus) or refractive errors resulting in different visual inputs to each eye during the sensitive period of visual development (aged <7-8 years). The cumulative incidence is estimated at 2% to 4% in children aged up to 7 years. We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of medical treatments for amblyopia in children aged 7 years or less? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 70 studies. After deduplication and removal of conference abstracts, 51 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 14 full publications. Of the 14 full articles evaluated, two systematic reviews were updated and three RCTs and two follow-up studies were added at this update. We performed a GRADE evaluation for nine PICO combinations. In this systematic overview we categorised the efficacy for three interventions, based on information about the effectiveness and safety of glasses, occlusion, or penalisation with atropine.


Metamaterial perfect absorber with unabated size-independent absorption.
Metamaterial absorbers open a new door for the design of optical harvesting devices ranging from the microwave to optical regimes. The top resonator in these structures is critical for the function of metamaterial absorbers. The resonant frequency, bandwidth, and maximum absorption mainly depend on the choice of material, shape, and size of the top resonator. The maximum absorption is generally impaired as the size of the resonator changes, due to the high sensitivity of impedance matching with the medium. In this paper, we experimentally demonstrate a metamaterial perfect absorber with unabated absorption as its resonator's size changes. The perfect absorber is based on an array of metal squares inscribed with a hollow square. The absorption maxima stay above 98% as the size changes from 600 to 1500 nm in the mid-infrared region, agreeing with simulated results yielding an absorption of ~100%. The unabated absorption properties can be interpreted by the equivalent circuit theory. Moreover, the experimental absorption remains above 91% for incident angles change up to 50°, both for TE and TM polarization. Our work offers a method for achieving stable perfect absorption in sensing, filtering, and selective thermal emission.


A case of antiepiligrin cicatricial pemphigoid with extensive cutaneous erosions mimicking pemphigus vulgaris.
Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepidermal blistering disease with predominant mucosal involvement. In this article, we report a young patient with mucosal and extensive cutaneous involvement in the form of large erosions mimicking those of pemphigus vulgaris thus leading to diagnostic dilemma. We were unable to find any other previous reports with such extensive cutaneous erosions mimicking those of pemphigus vulgaris. Laminin 5 was the antigen found on knockout substrate testing. Antiepiligrin CP is a distinct subtype of CP with antibodies against laminin 5. This subtype is mostly associated with malignancy but no underlying malignancy was found in our case. Present report also highlights the importance of knockout substrate testing when immunoblot is not available.


Unique Phenotypes and Functions of Follicular Helper T Cells and Regulatory T Cells in Sjögren's Syndrome.
Sjogren's syndrome (SS) is a T cell-mediated autoimmune disease of the systemic exocrine glands, such as salivary and lacrimal glands. A variety of T-cell subpopulations maintain immune tolerance in the thymus and periphery through complex immune responses including cellular and humoral immunity. The T-cell subpopulations exhibiting abnormal or unique phenotypes and impaired functionality have been reported to play important roles in the cellular mechanisms of autoimmunity in SS patients and animal models of SS. In this review, we focused on follicular helper T cells related to antibody production and regulatory T cells to control immune tolerance in the pathogenesis of SS. The unique roles of these T-cell subpopulations in the process of the onset or development of SS have been demonstrated in this review of recent publications. The clinical application of these T-cell subpopulations will be helpful for the development of new techniques for diagnosis or treatment of SS in the future.


Synthetic oxytocin and hastening labor: reflections on the synthesis and early use of oxytocin in Brazilian obstetrics.
This article reflects on the medicalization of childbirth, focusing on the development of synthetic oxytocin in 1953. Specifically addressed is the social life of oxytocin; in other words, its synthesis, stabilization, and use in obstetrics to hasten labor. Two Brazilian obstetrics journals of this era were surveyed to analyze the early use of synthetic oxytocin in Brazil in the late 1950s, along with obstetric arguments for or against its use. Notable in this period is the increasingly central role of the obstetrician in childbirth, as well as the recommendation to use different interventions linked together (particularly oxytocin) to shorten labor.


Modification at the 2'-Position of the 4,5-Series of 2-Deoxystreptamine Aminoglycoside Antibiotics To Resist Aminoglycoside Modifying Enzymes and Increase Ribosomal Target Selectivity.
A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, (ii) antibacterial activity against wild type Gram negative and positive pathogens, and (iii) overcoming resistance due to the presence of aminoacyl transferases acting at the 2'-position. The presence of five suitably positioned residual basic amino groups was found to be necessary for activity to be retained upon removal or alkylation of the 2'-position amine. As alkylation of the 2'-amino group overcomes the action of resistance determinants acting at that position and in addition results in increased selectivity for the prokaryotic over eukaryotic ribosomes, it constitutes an attractive modification for introduction into next generation aminoglycosides. In the neomycin series, the installation of small (formamide) or basic (glycinamide) amido groups on the 2'-amino group is tolerated.


A chemosensory-like histidine kinase is dispensable for chemotaxis in vitro but regulates the virulence of Borrelia burgdorferi through modulating the stability of RpoS.
As an enzootic pathogen, the Lyme disease bacterium Borrelia burgdorferi possesses multiple copies of chemotaxis proteins, including two chemotaxis histidine kinases (CHK), CheA1 and CheA2. Our previous study showed that CheA2 is a genuine CHK that is required for chemotaxis; however, the role of CheA1 remains mysterious. This report first compares the structural features that differentiate CheA1 and CheA2 and then provides evidence to show that CheA1 is an atypical CHK that controls the virulence of B. burgdorferi through modulating the stability of RpoS, a key transcriptional regulator of the spirochete. First, microscopic analyses using green-fluorescence-protein (GFP) tags reveal that CheA1 has a unique and dynamic cellular localization. Second, loss-of-function studies indicate that CheA1 is not required for chemotaxis in vitro despite sharing a high sequence and structural similarity to its counterparts from other bacteria. Third, mouse infection studies using needle inoculations show that a deletion mutant of CheA1 (cheA1mut) is able to establish systemic infection in immune-deficient mice but fails to do so in immune-competent mice albeit the mutant can survive at the inoculation site for up to 28 days. Tick and mouse infection studies further demonstrate that CheA1 is dispensable for tick colonization and acquisition but essential for tick transmission. Lastly, mechanistic studies combining immunoblotting, protein turnover, mutagenesis, and RNA-seq analyses reveal that depletion of CheA1 affects RpoS stability, leading to reduced expression of several RpoS-regulated virulence factors (i.e., OspC, BBK32, and DbpA), likely due to dysregulated clpX and lon protease expression. Bulk RNA-seq analysis of infected mouse skin tissues further show that cheA1mut fails to elicit mouse tnf-α, il-10, il-1β, and ccl2 expression, four important cytokines for Lyme disease development and B. burgdorferi transmigration. Collectively, these results reveal a unique role and regulatory mechanism of CheA1 in modulating virulence factor expression and add new insights into understanding the regulatory network of B. burgdorferi.


Comparison Between Two Pharmacologic Strategies to Alleviate Rewarming Shock: Vasodilation vs. Inodilation.
Rewarming from hypothermia is often challenged by coexisting cardiac dysfunction, depressed organ blood flow (OBF), and increased systemic vascular resistance. Previous research shows cardiovascular inotropic support and vasodilation during rewarming to elevate cardiac output (CO). The present study aims to compare the effects of inodilatation by levosimendan (LS) and vasodilation by nitroprusside (SNP) on OBF and global oxygen transport during rewarming from hypothermia. We used an in vivo experimental rat model of 4 h 15°C hypothermia and rewarming. A stable isotope-labeled microsphere technique was used to determine OBF. Cardiac and arterial pressures were monitored with fluid-filled pressure catheters, and CO was measured by thermodilution. Two groups were treated with either LS (n = 7) or SNP (n = 7) during the last hour of hypothermia and throughout rewarming. Two groups served as hypothermic (n = 7) and normothermic (n = 6) controls. All hypothermia groups had significantly reduced CO, oxygen delivery, and OBF after rewarming compared to their baseline values. After rewarming, LS had elevated CO significantly more than SNP (66.57 ± 5.6/+30% vs. 54.48 ± 5.2/+14%) compared to the control group (47.22 ± 3.9), but their ability to cause elevation of brain blood flow (BBF) was the same (0.554 ± 0.180/+81 vs. 0.535 ± 0.208/+75%) compared to the control group (0.305 ± 0.101). We interpret the vasodilator properties of LS and SNP to be the primary source to increase organ blood flow, superior to the increase in CO.


Varying Susceptibility of the Female Mammary Gland to In Utero Windows of BPA Exposure.
In utero exposure to the endocrine disrupting compound bisphenol A (BPA) is known to disrupt mammary gland development and increase tumor susceptibility in rodents. It is unclear whether different periods of in utero development might be more susceptible to BPA exposure. We exposed pregnant CD-1 mice to BPA at different times during gestation that correspond to specific milestones of in utero mammary gland development. The mammary glands of early-life and adult female mice, exposed in utero to BPA, were morphologically and molecularly (estrogen receptor-α and Ki67) evaluated for developmental abnormalities. We found that BPA treatment occurring before mammary bud invasion into the mesenchyme [embryonic day (E)12.5] incompletely resulted in the measured phenotypes of mammary gland defects. Exposing mice up to the point at which the epithelium extends into the precursor fat pad (E16.5) resulted in a nearly complete BPA phenotype and exposure during epithelial extension (E15.5 to E18.5) resulted in a partial phenotype. Furthermore, the relative differences in phenotypes between exposure windows highlight the substantial correlations between early-life molecular changes (estrogen receptor-α and Ki67) in the stroma and the epithelial elongation defects in mammary development. These data further implicate BPA action in the stroma as a critical mediator of epithelial phenotypes.


Electroconvulsive therapy in children and adolescents.
Electroconvulsive therapy (ECT) is a recognized and effective treatment in adults for several psychiatric and neurological conditions in which the use of pharmacotherapy is ineffective, untimely or contraindicated. It has been used with success in mood and psychotic disorders, catatonia, neuroleptic malignant syndrome, Parkinson's disease and intractable seizures. Its benefits have been recognized and its risks identified through an extensive body of research. The benefits of ECT are not limited to the adult population; research has been conducted on its use in child and adolescent populations for decades. In 2004, the American Academy of Child and Adolescent Psychiatry published practice parameters for the use of ECT in adolescent populations. However, ECT continues to be underused in cases where it is clearly indicated. In this article, we review the use of ECT in the adolescent population; its indications, administration, contraindications and risks, with emphasis on articles published after the American Academy of Child and Adolescent Psychiatry practice parameters were formulated. We also review reasons behind the underutilization of ECT in adolescents for whom this treatment modality is indicated.


Process evaluation of five tailored programs to improve the implementation of evidence-based recommendations for chronic conditions in primary care.
Although there is evidence that tailored implementation strategies can be effective, there is little evidence on which methods of tailoring improve the effect. We designed and evaluated five tailored programs (TPs) each consisting of various strategies. The aim of this study was to examine (a) how determinants of practice prioritized in the design phase of the TPs were perceived by health care professionals who had been exposed to the TPs and whether they suggested other important determinants of practice and (b) how professionals used the offered strategies and whether they suggested other strategies that might have been more effective. We conducted a mixed-method process evaluation linked to five cluster-randomized trials carried out in five European countries to implement recommendations for five chronic conditions in primary care settings. The five TPs used a total of 28 strategies which aimed to address 38 determinants of practice. Interviews of professionals in the intervention groups and a survey of professionals in the intervention and control groups were performed. Data collection was conducted by each research team in the respective national language. The interview data were first analyzed inductively by each research team, and subsequently, a meta-synthesis was conducted. The survey was analyzed descriptively. We conducted 71 interviews; 125 professionals completed the survey. The survey showed that 76 % (n = 29) of targeted determinants of practice were perceived as relevant and 95 % (n = 36) as being modified by the implementation interventions by 66 to 100 % of professionals. On average, 47 % of professionals reported using the strategies and 51 % considered them helpful, albeit with substantial variance between countries and strategies. In the interviews, 89 determinants of practice were identified, of which 70 % (n = 62) had been identified and 45 % (n = 40) had been prioritized in the design phase. The interviewees suggested 65 additional strategies, of which 54 % (n = 35) had been identified and 20 % (n = 13) had been prioritized, but not selected in the final programs. This study largely confirmed the perceived relevance of the targeted determinants of practice. This contrasts with the fact that no impact of the trials on the implementation of the recommendations could be observed. The findings suggest that better methods for prioritization of determinants and strategies are needed. Each of the five trials was registered separately in recognized trial registries. Details are given in the respective trial outcome papers.


European elk papillomavirus: characterization of the genome, induction of tumors in animals, and transformation in vitro.
The European elk papillomavirus (EEPV) genome was cloned in the BamHI cleavage site of the pBR322 vector. The cloned genome was used for construction of a physical map, employing restriction endonucleases BamHI, BglII, HindIII, PvuII, SacI, and XhoI. The sequence homology between the EEPV and bovine papillomavirus type 1 genomes was elucidated by performing hybridizations in different concentrations of formamide. Sequence homology could only be revealed under less stringent conditions, i.e., Tm - 43 degrees C. Nucleotide sequence information was also collected from the regions which lie adjacent to the three HindIII sites that are present in the EEPV genome. The results made it possible to align the EEPV and bovine papillomavirus type 1 genomes. Transformation by EEPV was demonstrated with the C127 mouse cell line, and fibrosarcomas were induced in young hamsters after subcutaneous injection. The transformed cells and the tumors contain multiple, nonintegrated copies of the EEPV genome. Virus particles could not be detected either in tumors or in transformed cells.


Effectiveness of intensive, group therapy for teenagers who stutter.
Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. A repeated-measures, single-subject experimental design was replicated across participants. The study consisted of a 5-week baseline phase, 2-week intensive treatment phase, 5-week consolidation phase and 10-month follow-up phase. Participants were asked to make ten video recordings at home during each phase, while completing a reading and a conversation task. Recordings were analysed in terms of the percentage of stuttered syllables using a simplified time-series analysis. Participants completed self-report questionnaires at predetermined times throughout the study. Data are presented for three males aged 17;7, 17;11 and 18;10. One participant completed all required recordings. Difficulties were encountered collecting follow-up data with the other two participants and data are available up to 5 months after the intensive therapy phase. A significant trend of reduced frequency of stuttering was found for all three participants during the intensive therapy phase. This trend continued throughout the consolidation phase and remained significant when available longer-term data were included in the analysis. Participants also reported increased self-efficacy about speaking and reduced overt and covert aspects of stammering. Findings show that this therapy programme for teenagers had a significant treatment effect for the participants studied in the short- and medium-term, however longer-term data were not available for all participants. Issues in conducting research with this client group are discussed.


Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement.
Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term.


Non-contact measurement of thermal diffusivity in tissue.
We demonstrate the application of an infrared (IR) imaging technique for non-contact determination of thermal diffusivity in biological materials. The proposed method utilizes pulsed laser excitation to produce an initial three-dimensional temperature distribution in tissue, and records IR images of subsequent heat diffusion. The theoretical model assumes that the time-dependent temperature increase following pulsed laser exposure is due to independent heat diffusion in longitudinal and lateral directions. A nonlinear least-squares algorithm is used to compute the lateral thermal point spread function from a pair of recorded IR images and to determine the thermal diffusivity of a test specimen. The recorded time-sequence of IR images is used to compute thermal diffusivity as a function of increasing time interval between two IR emission images. Experimental application of the method was demonstrated using tissue phantoms, ex vivo samples of hydrated cartilage and in vivo epidermis.


Head to head: the case for fighting behaviour in Megaloceros giganteus using finite-element analysis.
The largest antlers of any known deer species belonged to the extinct giant deer Megaloceros giganteus. It has been argued that their antlers were too large for use in fighting, instead being used only in ritualized displays to attract mates. Here, we used finite-element analysis to test whether the antlers of M. giganteus could have withstood forces generated during fighting. We compared the mechanical performance of antlers in M. giganteus with three extant deer species: red deer (Cervus elaphus), fallow deer (Dama dama) and elk (Alces alces). Von Mises stress results suggest that M. giganteus was capable of withstanding some fighting loads, provided that their antlers interlocked proximally, and that their antlers were best adapted for withstanding loads from twisting rather than pushing actions, as are other deer with palmate antlers. We conclude that fighting in M. giganteus was probably more constrained and predictable than in extant deer.


Resources and Recommendations for Using Transcriptomics to Address Grand Challenges in Comparative Biology.
High-throughput RNA sequencing (RNA-seq) technology has become an important tool for studying physiological responses of organisms to changes in their environment. De novo assembly of RNA-seq data has allowed researchers to create a comprehensive catalog of genes expressed in a tissue and to quantify their expression without a complete genome sequence. The contributions from the "Tapping the Power of Crustacean Transcriptomics to Address Grand Challenges in Comparative Biology" symposium in this issue show the successes and limitations of using RNA-seq in the study of crustaceans. In conjunction with the symposium, the Animal Genome to Phenome Research Coordination Network collated comments from participants at the meeting regarding the challenges encountered when using transcriptomics in their research. Input came from novices and experts ranging from graduate students to principal investigators. Many were unaware of the bioinformatics analysis resources currently available on the CyVerse platform. Our analysis of community responses led to three recommendations for advancing the field: (1) integration of genomic and RNA-seq sequence assemblies for crustacean gene annotation and comparative expression; (2) development of methodologies for the functional analysis of genes; and (3) information and training exchange among laboratories for transmission of best practices. The field lacks the methods for manipulating tissue-specific gene expression. The decapod crustacean research community should consider the cherry shrimp, Neocaridina denticulata, as a decapod model for the application of transgenic tools for functional genomics. This would require a multi-investigator effort.


Impacts of Natural Selection on Evolution of Core and Symbiotically Specialized (sym) Genes in the Polytypic Species Neorhizobium galegae.
Nodule bacteria (rhizobia) represent a suitable model to address a range of fundamental genetic problems, including the impacts of natural selection on the evolution of symbiotic microorganisms. Rhizobia possess multipartite genomes in which symbiotically specialized (sym) genes differ from core genes in their natural histories. Diversification of sym genes is responsible for rhizobia microevolution, which depends on host-induced natural selection. By contrast, diversification of core genes is responsible for rhizobia speciation, which occurs under the impacts of still unknown selective factors. In this paper, we demonstrate that in goat's rue rhizobia (Neorhizobium galegae) populations collected at North Caucasus, representing two host-specific biovars orientalis and officianalis (N2-fixing symbionts of Galega orientalis and G. officinalis), the evolutionary mechanisms are different for core and sym genes. In both N. galegae biovars, core genes are more polymorphic than sym genes. In bv. orientalis, the evolution of core genes occurs under the impacts of driving selection (dN/dS > 1), while the evolution of sym genes is close to neutral (dN/dS ≈ 1). In bv. officinalis, the evolution of core genes is neutral, while for sym genes, it is dependent on purifying selection (dN/dS < 1). A marked phylogenetic congruence of core and sym genes revealed using ANI analysis may be due to a low intensity of gene transfer within and between N. galegae biovars. Polymorphism in both gene groups and the impacts of driving selection on core gene evolution are more pronounced in bv. orientalis than in bv. officianalis, reflecting the diversities of their respective host plant species. In bv. orientalis, a highly significant (P0 < 0.001) positive correlation is revealed between the p-distance and dN/dS values for core genes, while in bv. officinalis, this correlation is of low significance (0.05 < P0 < 0.10). For sym genes, the correlation between p-distance and dN/dS values is negative in bv. officinalis but is not revealed in bv. orientalis. These data, along with the functional annotation of core genes implemented using Gene Ontology tools, suggest that the evolution of bv. officinalis is based mostly on adaptation for in planta niches while in bv. orientalis, evolution presumably depends on adaptation for soil niches. New insights into the tradeoff between natural selection and genetic diversity are presented, suggesting that gene nucleotide polymorphism may be extended by driving selection only in ecologically versatile organisms capable of supporting a broad spectrum of gene alleles in their gene pools.


Clinical characteristics of asthmatic patients prescribed various beta-agonist metered-dose inhalers at Yamagata University Hospital.
To determine the prescription characteristics of beta-agonist metered-dose inhalers (MDI), we retrospectively investigated all prescriptions containing one of five types of beta-agonist MDIs available at Yamagata University Hospital in 1997, as well as patients' characteristics. The total number of asthmatic patients was 225 (age, 11-79, mean, 47.2) in 1997. Fenoterol MDI was prescribed to patients who visited the hospital at regular periods and had more severe asthma. Isoprenaline MDI also was not prescribed for first-time patients. Patients who were prescribed tulobuterol MDI had mild or moderate asthma and some of them were only occasional or first-time visitors. Salbutamol and procaterol MDIs were also prescribed for first-time patients; however, tulobuterol MDI was the most frequently prescribed for first-time patients. Patients prescribed fenoterol and isoprenaline MDIs had adequate knowledge of proper asthma management, because sufficient information had been provided about the use of MDIs in the past. Patients prescribed tulobuterol MDI should be provided with detailed instructions because they had little knowledge of handling MDIs and self-management of asthma as many of them were first or intermittent visitors. Patients prescribed salbutamol or procaterol MDIs should be evaluated regarding their past medications and some of them should be instructed regarding the use of the MDI. Although these clinical aspects might be applicable only to our hospital, the same or other prescription patterns will be found in other hospitals and/or by other physicians. Adequate instructions to individual patients who are prescribed a particular beta-agonist MDI should be provided by the medical staff, especially to outpatients, to reduce hospitalization and death from asthma.


Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta.
Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA2) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation.


Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters.
The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster was quantified by in situ hybridization. Hamsters housed in short days (SD) for 18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD) affected neither basal gene expression nor the induction of gene expression by food deprivation. Gene expression in juvenile LD hamsters similar in body weight to SD animals was relatively insensitive to food deprivation of either 24- or 48-h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for 24 but not 48 h decreased ob (obese) gene expression in inguinal but not epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All food-deprived hamsters had reduced plasma insulin concentrations, but plasma cortisol was only elevated in SD food-deprived animals. NPY gene expression was also increased after daily dexamethasone injections in adult LD hamsters. These results suggest that the neuroendocrine consequences of food deprivation in SD Djungarian hamsters are determined by some factor other than absolute body mass such as the size of adipose tissue reserves.


Identification of Resting-State Network Functional Connectivity and Brain Structural Signatures in Fibromyalgia Using a Machine Learning Approach.
Abnormal resting-state functional connectivity (rs-FC) and brain structure have emerged as pathological hallmarks of fibromyalgia (FM). This study investigated and compared the accuracy of network rs-FC and brain structural features in identifying FM with a machine learning (ML) approach. Twenty-six FM patients and thirty healthy controls were recruited. Clinical presentation was measured by questionnaires. After MRI acquisitions, network rs-FC z-score and network-based gray matter volume matrices were exacted and preprocessed. The performance of feature selection and classification methods was measured. Correlation analyses between predictive features in final models and clinical data were performed. The combination of the recursive feature elimination (RFE) selection method and support vector machine (rs-FC data) or logistic regression (structural data), after permutation importance feature selection, showed high performance in distinguishing FM patients from pain-free controls, in which the rs-FC ML model outperformed the structural ML model (accuracy: 0.91 vs. 0.86, AUC: 0.93 vs. 0.88). The combined rs-FC and structural ML model showed the best performance (accuracy: 0.95, AUC: 0.95). Additionally, several rs-FC features in the final ML model correlated with FM's clinical data. In conclusion, ML models based on rs-FC and brain structural MRI features could effectively differentiate FM patients from pain-free subjects.


Surgical treatment of acne scarring: non-linear scar revision.
Non-linear scar revision techniques involve levelling facial skin. Classification as to the nature of the pitting allows the surgeon to select techniques to improve the facial cosmetic appearance. The types of intradermal pitting and subcutaneous atrophy along with nodular scarring produce the lack of levelling and the depression that the patients want corrected. The useful modalities available to level facial skin are dermal levelling, injectable substances, dermal punch grafting, excision and facelifting. The selection of these techniques is dependent on the above classification and the patient's desire for improvement.


Disease-free survival as an end-point in the treatment of solid tumours--perspectives from clinical trials and clinical practice.
Disease-free survival (DFS) is an end-point for an increasing number of clinical trials in adjuvant and curative intent cancer treatment informing both regulatory bodies and clinical practice. DFS is seen both as a surrogate end-point and as an end-point in itself in clinical trials. Understanding the history of DFS, and some of the assumptions, limitations, and vulnerabilities for studies designed with this primary end-point are required. This commentary reviews recent drug approvals for anti-cancer agents in solid tumours in the adjuvant and curative settings, and considers the meaning of DFS from the perspectives of clinical trials and clinical practice.


[Clinical significance of elevated CEA values in the follow-up management of patients with breast cancer].
To evaluate the clinical significance of elevated CEA titers in primary breast cancer post-mastectomy 942 patients were followed up by means of clinical methods and CEA analysis according to a routine schedule. In 282 patients CEA in serum was found to be elevated (greater than or equal to 5 ng/ml) on at least one occasion. Recurrent disease became clinically evident in 255 patients (27%). CEA-positive patients had a significantly higher recurrence rate than CEA-negative patients (52% versus 16%, p less than 0.001). The mean lead time from first elevation of CEA to clinical diagnosis of recurrence was 5 months. The frequency of recurrent disease depended on the height of the CEA titer and the further course of CEA. With titers above 30 ng/ml 91% of patients developed recurrent disease, with constantly elevated or further increasing titers 74% and 100%, respectively. Regarding CEA and the type of metastases, no clear correlation was demonstrable. However, patients with soft tissue metastases exhibited a higher frequency of normal or low (less than 30 ng/ml) CEA titers as compared to patients with visceral or bone metastases. With respect to the criteria mentioned above, CEA is a valuable laboratory tool for early diagnosis of recurrence in breast cancer patients. However, the simple criterion much greater than CEA elevation much less than (5 ng/ml threshold) is of low prognostic significance. Despite intensive clinical searches for metastases and a mean observation time of 20 months, no recurrence became clinically evident in 48% of CEA-positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Yeast 18 S rRNA is directly involved in the ribosomal response to stringent AUG selection during translation initiation.
In eukaryotes, the 40 S ribosomal subunit serves as the platform of initiation factor assembly, to place itself precisely on the AUG start codon. Structural arrangement of the 18 S rRNA determines the overall shape of the 40 S subunit. Here, we present genetic evaluation of yeast 18 S rRNA function using 10 point mutations altering the polysome profile. All the mutants reduce the abundance of the mutant 40 S, making it limiting for translation initiation. Two of the isolated mutations, G875A, altering the core of the platform domain that binds eIF1 and eIF2, and A1193U, changing the h31 loop located below the P-site tRNA(i)(Met), show phenotypes indicating defective regulation of AUG selection. Evidence is provided that these mutations reduce the interaction with the components of the preinitiation complex, thereby inhibiting its function at different steps. These results indicate that the 18 S rRNA mutations impair the integrity of scanning-competent preinitiation complex, thereby altering the 40 S subunit response to stringent AUG selection. Interestingly, nine of the mutations alter the body/platform domains of 18 S rRNA, potentially affecting the bridges to the 60 S subunit, but they do not change the level of 18 S rRNA intermediates. Based on these results, we also discuss the mechanism of the selective degradation of the mutant 40 S subunits.


Disease resistance: incorporation into sexually incompatible somatic hybrids of the genus Nicotiana.
Somatic hybrid plants of Nicotiana nesophila and N. stocktonii with N. tabacum (cultivated tobacco) were produced by protoplast fusion. These combinations cannot be achieved with conventional sexual hybridization, yet are important in that the wild Nicotiana species are resistant to numerous diseases. Hybridity was verified by chromosome number, isoenzyme analysis, morphological characteristics, and genetic behavior. Local lesion-type resistance to tobacco mosaic virus has been observed in leaves of these somatic hybrid plants.


Association of BTG2, CYR61, ZFP36, and SCD gene polymorphisms with Graves' disease and ophthalmopathy.
Environmental and genetic factors predispose an individual to the development of Graves' disease (GD). In an expression study of intraorbital tissue, adipocyte-related immediate early genes (IEGs) and immunomodulatory genes were found to be overexpressed in patients with Graves' ophthalmopathy (GO). We hypothesized that genetic variations in these genes could be associated with GD and/or GO. A total of 98 single nucleotide polymorphisms (SNPs) in 12 genes were genotyped in 594 GD patients with (n=267) or without (n=327) GO and 1147 sex- and ethnicity-matched controls from Malmö, Sweden. Ten SNPs in four genes (BTG family, member 2 [BTG2], cysteine-rich, angiogenic inducer 61 [CYR61], zinc finger protein 36, C3H type, homolog mouse [ZFP36], and stearoyl-coenzyme A desaturase [SCD]) showed an association with GD and/or GO. SNPs rs12136280 (odds ratio [OR] 1.29, p=0.002), rs6663606 (OR 1.26, p=0.004), and rs17534202 (OR 1.21, p=0.02) in BTG2 and rs3753793 (OR 1.21, p=0.03) in CYR61 were associated with GD. An association with GO was shown for SNPs rs3753793 (OR 1.45, p=0.008), rs6682848 (OR 1.55, p=0.03), rs12756618 (OR 1.77, p=0.049), and rs1378228 (OR 1.29, p=0.049) in CYR61, rs1057745 (OR 1.56, p=0.03) and rs11083522 (OR 1.32, p=0.04) in ZFP36, and rs1393491 (OR 1.38, p=0,048) in SCD. Smoking and CYR61 rs12756618 interacted to increase the risk of GO. We found associations of SNPs in IEGs and SCD with GD and/or GO; however, confirmation in a different population is required.


Functional brain networks in never-treated and treated long-term Ill schizophrenia patients.
This study compared the topological organization of brain function in never-treated and treated long-term schizophrenia patients. In a cross-sectional study, 21 never-treated schizophrenia patients with illness duration over 5 years, 26 illness duration-matched antipsychotic-treated patients and 24 demographically-matched healthy controls underwent a resting-state functional magnetic resonance imaging (MRI) scan. The topological properties of brain functional networks were compared across groups, and then we tested for differential age-related effects in regions with significant group differences. Both never-treated and antipsychotic-treated schizophrenia patient groups showed altered nodal centralities in left pre-/postcentral gyri relative to controls. Never-treated patients demonstrated reduced global efficacy, decreased nodal centralities in right amygdala/hippocampus and bilateral putamen/caudate relative to antipsychotic-treated patients and controls. No significant relationships of age and altered functional metrics were seen in either patient group, and no alterations were greater in the treated group. These findings provide insight into brain function deficits over the longer-term course of schizophrenia independent from potential effects of antipsychotic medication. The presence of greater alterations in never-treated than treated patients suggests that long-term antipsychotic treatment may partially protect or enhance brain global and nodal topological function over the course of schizophrenia, notably involving the amygdala, hippocampus, and striatum that have long been associated with the disorder.


Multi-wavelength imaging with the adaptive optics scanning laser Ophthalmoscope.
The adaptive optics scanning laser ophthalmoscope has been fitted with three light sources of different wavelengths to allow simultaneous or separate imaging with one, two or three wavelength combinations. The source wavelengths used are 532 nm, 658 nm and 840 nm. Typically the instrument is used in dual-frame mode, performing imaging at 840 nm and precisely coincident retinal stimulation in one of the visible wavelengths. Instrument set-up and single-detector image capture are described. Simultaneous multi-wavelength imaging in the living human retina is demonstrated. The chromatic aberrations of the human eye lead to lateral and axial shifts, as well as magnification differences in the image, from one wavelength to another. Measurement of these chromatic effects is described for instrument characterization purposes.


The role of lysine 532 in the catalytic mechanism of human topoisomerase I.
Based on co-crystal structures of human topoisomerase I with bound DNA, Lys(532) makes a minor groove contact with the strongly preferred thymidine residue at the site of covalent attachment (-1 position). Replacement of Lys(532) with either arginine or alanine has essentially no effect on the sequence preference of the enzyme, indicating that this interaction is not required for the preference for a T at the -1 position. Although both the cleavage and religation activities of the K532R mutant enzyme are reduced, cleavage is reduced to a greater extent than religation. The reverse is true for the K532A mutant enzyme with religation so impaired that the nicked intermediate accumulates during plasmid relaxation assays. Consistent with the shift in the cleavage religation equilibrium toward cleavage for the K532A mutant enzyme, expression of the mutant enzyme in Saccharomyces cerevisiae is cytotoxic, and thus this mutant enzyme mimics the effects of the anticancer drug camptothecin. Cleavage assays with the mutant enzymes using an oligonucleotide containing a 5'-bridging phosphorothiolate indicate that Lys(532) functions as a general acid during cleavage to protonate the leaving 5'-oxygen. It is possible that the contact with the -1 base is important during catalysis to provide positional rigidity to the active site. The corresponding residues in the vaccinia virus topoisomerase and the tyrosine recombinases may have similar critical roles in catalysis.


Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection.
Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters vp , K(trans) , and ve for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not. DCE-MRI studies were performed on nine Fisher 344 rats inoculated intracerebrally with 9L gliosarcoma cells using both gadofosveset and gadopentetate. The parameters vp , K(trans) , and ve were estimated using NMS. K(trans) estimates using gadofosveset, compared to gadopentetate, differed in their means (gadofosveset 0.025 ± 0.008 min(-1) vs. gadopentetate 0.046 ± 0.011 min(-1) ; P = 0.0039). This difference notwithstanding, the intraclass correlation coefficient (ICC) for the two estimates of K(trans) showed nearly perfect linear dependence (ICC = 0.8479 by Pearson's r). Other estimates, ve (gadofosveset 22.7 ± 4.7% vs. gadopentetate 23.6 ± 5.6%; P = 0.4258) and vp (gadofosveset 1.5 ± 0.5% vs. gadopentetate 1.6 ± 0.4%; P = 0.25), were not different in their means between the two CAs, and there was almost perfect agreement for ve (ICC = 0.8798) and substantial agreement for vp (ICC = 0.7981) between the two CAs. Estimates of K(trans) were statistically different using gadofosveset and gadopentetate, whereas ve and vp were similar with two CAs. NMS produced robust estimates of pharmacokinetic parameters using DCE-MRI that show promise as important measures of tumor physiology and microenvironment.


Investigating the role of cardiovascular biomarkers in children with pre-dialysis chronic kidney disease: a substitute to echocardiography to detect increased left ventricular mass?
Children with chronic kidney disease (CKD) are at increased risk of future cardiovascular (CV) events. Our aim in this prospective single-centre cross-sectional analysis was to assess the relationship of a novel panel of CV biomarkers with left ventricular hypertrophy (LVH). A panel of five CV biomarkers (asymmetric dimethyl arginine, high sensitivity C-reactive protein, homocysteine, N-terminal pro-B type natriuretic peptide and uric acid) were measured on the same day as an echocardiogram assessment, in paediatric patients with pre-dialysis stages 3-5 of CKD. Of 73 children aged 5-18 years, LVH, all eccentric, was identified in 38%. Systolic blood pressure (BP), glomerular filtration rate (GFR) and higher intake of calcium-based phosphate binders were significantly worse in children with LVH. In multivariate models analysing each biomarker one at a time with confounders [GFR, systolic BP z-score, anti-hypertensive medication (yes/no) and elemental calcium intake], clinic systolic BP z-score and elemental calcium intake consistently displayed a significant relationship with indexed left ventricular mass (LVMI). None of the evaluated CV biomarkers displayed a significant relationship with LVMI. In our cohort of children with moderately severe pre-dialysis CKD we have identified no suitable biomarkers to detect LVH. We would therefore recommend that echocardiographic determination of LVMI remains the technique of choice for detection of LVH in children with CKD.


A Prospective Randomized Trial Comparing Sirolimus-Coated Balloon With Paclitaxel-Coated Balloon in De Novo Small Vessels.
There are no data comparing sirolimus-coated balloons (SCBs [MagicTouch, Concept Medical]) to paclitaxel-coated balloons (PCBs [SeQuent Please Neo, B. Braun]) for the treatment of de novo small vessel disease (SVD). This study sought to compare quantitative coronary angiographic outcomes at 6 months after treatment of de novo SVD with a PCB or SCB. This prospective, multicenter, noninferiority trial randomized 121 patients (129 SVD lesions) to treatment with an SCB or PCB, with balloon sizing determined using optical coherence tomography. The primary endpoint was noninferiority for the 6-month angiographic net lumen gain. Angiographic follow-up was completed in 109 (90.1%) patients in the per-protocol analysis. The mean ± SD angiographic net gains were 0.25 ± 0.40 mm with SCBs vs 0.48 ± 0.37 mm with PCBs, resulting in SCBs failing to meet the 0.30 mm criterion for noninferiority (Pnoninferiority = 0.173), with an absolute difference of -0.23 mm (95% CI: -0.37 to -0.09) secondary to a smaller late loss (0.00 ± 0.32 mm vs 0.32 ± 0.47 mm; P < 0.001) and more frequent late lumen enlargement (53.7% vs 30.0%; OR: 2.60; 95% CI: 1.22-5.67; P = 0.014) with PCBs. Binary restenosis rates were 32.8% and 12.5% following treatment with SCBs and PCBs, respectively (OR: 3.41; 95% CI: 1.36-9.44; P = 0.012). The mean angiography-derived fractional flow ratio at follow-up was 0.86 ± 0.15 following treatment with SCBs and 0.91 ± 0.09 following PCBs (P = 0.026); a fractional flow ratio ≤0.80 occurred in 13 and 5 vessels after treatment with SCBs and PCBs, respectively. The SCB MagicTouch failed to demonstrate noninferiority for angiographic net lumen gain at 6 months compared to the PCB SeQuent Please Neo.


Association Between Sensorimotor Impairments and Functional Brain Changes in Patients With Low Back Pain: A Critical Review.
Low back pain (LBP) coincides with sensorimotor impairments, for example, reduced lumbosacral tactile and proprioceptive acuity and postural control deficits. Recent functional magnetic resonance imaging studies suggest that sensorimotor impairments in LBP may be associated with brain changes. However, no consensus exists regarding the relationship between functional brain changes and sensorimotor behavior in LBP. Therefore, this review critically discusses the available functional magnetic resonance imaging studies on brain activation related to nonnociceptive somatosensory stimulation and motor performance in individuals with LBP. Four electronic databases were searched, yielding nine relevant studies. Patients with LBP showed reduced sensorimotor-related brain activation and a reorganized lumbar spine representation in higher-order (multi)sensory processing and motor regions, including primary and secondary somatosensory cortices, supplementary motor area, and superior temporal gyrus. These results may support behavioral findings of sensorimotor impairments in LBP. In addition, patients with LBP displayed widespread increased sensorimotor-evoked brain activation in regions often associated with abnormal pain processing. Overactivation in these regions could indicate an overresponsiveness to sensory inputs that signal potential harm to the spine, thereby inducing overgeneralized protective responses. Hence, functional brain changes could contribute to the development and recurrence of LBP. However, future studies investigating the causality between sensorimotor-related brain function and LBP are imperative.


Antibiotic prophylaxis for transurethral urological surgeries: Systematic review.
The use of antibiotic prophylaxis to prevent urinary tract infection and bacteremia (sepsis) following endoscopic urologic procedures is a controversial topic. Evidence in the literature revealed that urological instrumentation is associated with increased incidence of urinary tract infection and bacteremia. The aim of this review is to evaluate the effectiveness of antibiotic prophylaxis in reducing the risk of urinary tract infection in patients who had transurethral urological surgeries. We have selected all RCTs of adult population who underwent all different types of transurethral urological surgery, including cystoscopy, transurethral resection of prostate and transurethral resection of bladder tumor, and received prophylactic antibiotics or placebo/no treatment. At first, more than 3000 references were identified and reviewed; of which 42 studies with a total of 7496 patients were included in the final analysis. All those trials were analyzing antibiotic prophylaxis versus placebo/no treatment, and they were significantly favoring antibiotic use in reducing all outcomes, including bacteriuria (RR 0.36, 95% CI 0.29 to 0.46, P < 0.0001) with moderate heterogeneity detected (I(2) 48%), symptomatic UTI (RR 0.38, 95% CI 0.28 to 0.51, P < 0.0001) with no significant heterogeneity was detected (I(2)= 17%), bacteremia (RR 0.43, 95% CI 0.23 to 0.82, P < 0.0001) with no noted heterogeneity (I(2) = 0%), and fever ≥38.5 Celsius (RR 0.41, 95% CI 0.23 to 0.73, P = 0.003); also, there was no noted heterogeneity (I(2) = 0%). However, using antibiotic prophylaxis did not reduce the incidence of low grade temperature (RR 0.82, 95% CI 0.61 to 1.11, P = 0.20) or in moderate grade temperature (RR 1.03, 95% CI 0.71 to 1.48, P = 0.89). Antibiotic prophylaxis appears to be an effective intervention in preventing urinary tract infections and its sequels following transurethral urological surgeries in patients with preoperative sterile urine.


[Esophageal wall structure in people of elderly and senile age].
Using histological methods, the esophageal wall structure and the cytoarchitectonics of mucous membrane were studied in the individuals of elderly (n = 5) and senile (n = 10) age. The control group included the individuals of I (n = 3) and II (n = 3) periods of mature age. It was demonstrated that with advancing age in most cases the destructive processes took place in the epithelium (delamination of the layer, separation of large fragments, formation of microerosions etc.) in most of the studied cases. Lymphocytes, neutrophils and eosinophils were found between the epithelial cells; the numbers of infiltrating cells was increased 2-3 times during aging. Mucosal lamina propria and the submucosa, in particular, were characterized by the thickening of the bundles of collagen fibers. A two-fold increase in the number of the cells of the fibroblast lineage was found. The number of leukocytes in the lamina propria was increased by the eldery age in the upper and lower parts of the esophagus (3.5 and 1.75 times respectively). The changes in lamina muscularis were manifested by its thinning, delamination and myocyte dissociation. Remodeling of the muscular tunic was less pronounced. The degree of changes increased distally and varied widely depending on the individual peculiarities.


Evaluation of quinacrine treatment for prion diseases.
Based on in vitro observations in scrapie-infected neuroblastoma cells, quinacrine has recently been proposed as a treatment for Creutzfeldt-Jakob disease (CJD), including a new variant CJD which is linked to contamination of food by the bovine spongiform encephalopathy (BSE) agent. The present study investigated possible mechanisms of action of quinacrine on prions. The ability of quinacrine to interact with and to reduce the protease resistance of PrP peptide aggregates and PrPres of human and animal origin were analyzed, together with its ability to inhibit the in vitro conversion of the normal prion protein (PrPc) to the abnormal form (PrPres). Furthermore, the efficiencies of quinacrine and chlorpromazine, another tricyclic compound, were examined in different in vitro models and in an experimental murine model of BSE. Quinacrine efficiently hampered de novo generation of fibrillogenic prion protein and PrPres accumulation in ScN2a cells. However, it was unable to affect the protease resistance of preexisting PrP fibrils and PrPres from brain homogenates, and a "curing" effect was obtained in ScGT1 cells only after lengthy treatment. In vivo, no detectable effect was observed in the animal model used, consistent with other recent studies and preliminary observations in humans. Despite its ability to cross the blood-brain barrier, the use of quinacrine for the treatment of CJD is questionable, at least as a monotherapy. The multistep experimental approach employed here could be used to test new therapeutic regimes before their use in human trials.


Computation of transient flow rates in passive pumping micro-fluidic systems.
Motion in micro-channels of passive flow micro-fluidic systems can be controlled by proper design and estimated by careful modeling. We report on methods to describe the flow rate as function of time in a passive pump driven micro-fluidic system. The model considers the surface energy present in small droplets, which prompts their shrinkage and induces flow. The droplet geometries are controlled by the micro-fluidic system geometry and hydrophilicity of the droplet channel contact area so that the chord of the droplet's cross section is restrained as the fluid is pumped. The model uses interfacial thermodynamics and the Hagen-Poiseuille equation for calculating the flow rate in micro-channels. Existing analyses consider the theoretical relationships among sample volume and induced flow rate, surface energy of the drops at the entrance and exit ports, and the resistance to flow. This model provides more specific information on the influence of the experimental conditions in computations of the flow rate. The model was validated in four sets of experiments. Passive pumps with 1.8 mm diameter, hydrophobic or hydrophilic entry ports, 5.0 or 10.0 mm channel length, and 2.5 or 3.3 mm diameter reservoir ports provided initial flow rates between 85 nL s(-1) and 196 nL s(-1).


Lab on a tip: Applications of functional atomic force microscopy for the study of electrical properties in biology.
Electrical properties, such as charge propagation, dielectrics, surface potentials, conductivity, and piezoelectricity, play crucial roles in biomolecules, biomembranes, cells, tissues, and other biological samples. However, characterizing these electrical properties in delicate biosamples is challenging. Atomic Force Microscopy (AFM), the so called "Lab on a Tip" is a powerful and multifunctional approach to quantitatively study the electrical properties of biological samples at the nanometer level. Herein, the principles, theories, and achievements of various modes of AFM in this area have been reviewed and summarized. STATEMENT OF SIGNIFICANCE: Electrical properties such as dielectric and piezoelectric forces, charge propagation behaviors play important structural and functional roles in biosystems from the single molecule level, to cells and tissues. Atomic force microscopy (AFM) has emerged as an ideal toolkit to study electrical property of biology. Herein, the basic principles of AFM are described. We then discuss the multiple modes of AFM to study the electrical properties of biological samples, including Electrostatic Force Microscopy (EFM), Kelvin Probe Force Microscopy (KPFM), Conductive Atomic Force Microscopy (CAFM), Piezoresponse Force Microscopy (PFM) and Scanning ElectroChemical Microscopy (SECM). Finally, the outlook, prospects, and challenges of the various AFM modes when studying the electrical behaviour of the samples are discussed.


Correlates of Hookah Smoking among Arab Adults in Israel Identified by a Machine Learning Algorithm.
Hookah smoking is a common activity around the world and has recently become a trend among youth. Studies have indicated a relationship between hookah smoking and a high prevalence of chronic diseases, cancer, cardiovascular, and infectious diseases. In Israel, there has been a sharp increase in hookah smoking among the Arabs. Most studies have focused mainly on hookah smoking among young people. To examine the association between hookah smoking and socioeconomic characteristics, health status and behaviors, and knowledge in the adult Arab population and to build a prediction model using machine learning methods. This quantitative study based is on data from the Health and Environment Survey conducted by the Galilee Society in 2015-2016. The data were collected through face-to-face interviews with 2046 adults aged 18 years and older. Using machine learning, a prediction model was built based on eight features. Of the total study population, 13.0% smoked hookah. In the 18-34 age group, 19.5% smoked. Men, people with lower level of health knowledge, heavy consumers of energy drinks and alcohol, and unemployed people were more likely to smoke hookah. Younger and more educated people were more likely to smoke hookah. Hookah smoking is a widespread behavior among adult Arabs in Israel. The model generated by our study is intended to help health organizations reach people at risk for smoking hookah and to suggest different approaches to eliminate this phenomenon.


Membrane receptor sites for the identification of lymphoreticular cells in benign and malignant conditions.
The cells of the lymphoreticular system are heterogeneous both morphologically and functionally. The bone marrow derived (B) lymphocyte can be identified by the presence of easily detectable surface immunoglobulin and a receptor for antigen-antibody-complement (EAC) complexes. Monocytes and histiocytes also bear a receptor for EAC and in addition possess a receptor for cytophilic antibody detected with red cell--IgG complexes (IgGEA). In man, thymus derived (T) lymphocytes form non-immune rosettes with sheep red blood cells (E). We have examined a number of malignant lymphoreticular populations for the presence of the EAC, EA, and E receptors on suspensions of cells and have adapted the technique to demonstrate the EAC and EA receptors on frozen tissue sections. Rosetted malignant cells can also be cytologically examined on Millipore filters. The malignant cells both in section and suspension from the spleens and lymph nodes of 6 patients with nodular lymphoma bound EAC but not IgGEA or E; by these criteria these malignant cells are of B lymphocytic origin. The malignant cells from the spleens of 2 patients with leukaemic reticuloendotheliosis and 1 patient with malignant histiocytosis could be classified as being of histiocytic origin by the selective binding of IgGEA. In 3 cases of diffuse lymphocytic lymphoma the malignant cells bound only E and are therefore of T lymphocytic origin. The application of these techniques to the classification of malignant lymphoma may lead to important theoretical and therapeutic advances.


Early morning executive functioning during sleep deprivation is compromised by a PERIOD3 polymorphism.
To contrast the effects of total sleep deprivation (TSD) on executive and non-executive function in volunteers homozygous for either the short or long variant of a variable number tandem repeat polymorphism in PERIODS, which is a genetic marker for susceptibility to the negative effect of sleep loss on waking performance. Following two laboratory nights of baseline sleep, both groups underwent an approximately 40-hour constant routine, performing brief tests of executive, memory, attention, and motor function every 2 hours. Clinical Research Centre. Fourteen PER3(4/4) (homozygotes for shorter variant of the gene) and 10 PER3(5/5) (homozygotes for longer variant) healthy, young adults (mean 25.0 +/- 1.0 years). Total sleep deprivation (approximately 40 hours) following baseline sleep. Hormonal assays established that melatonin levels, which reflect circadian phase, reached their midpoint around 04:00 in both genotypes. Cognitive performance deteriorated across the night, and was similar for both genotypes throughout, except 2-4 h after the midpoint of the melatonin rhythm. Only at this time-point and only on tests of executive function (e.g., 3-back, paced visual serial addition task) did PER3(5/5) participants perform reliably worse. Covariance analyses controlling for genotype dependent differences in homeostatic sleep pressure derived from principal component analysis of baseline sleep latency, slow wave sleep and wake after sleep onset largely removed these early morning differences in executive function. This PER3 polymorphism differentially influences the effects of sleep deprivation on executive and non-executive function in the early morning. These effects appear to be mediated through homeostatic sleep pressure.


Monitoring apple flavor by use of quartz microbalances.
"Electronic noses", i.e. arrays of differently coated quartz microbalances (QMB), have been used for selective detection of, and discrimination between, volatile organic compounds (VOC) formed during the post-harvest ripening of apples. The flavor components to be differentiated are chemically rather similar carbonyl compounds, chiefly aldehydes and esters. Because their relative ratios change during the post-harvest ripening period, appropriately selected sensor-active layers lead to characteristic patterns of the sensor responses which can be analyzed via pattern-recognition methods. This enables qualitative and quantitative identification of individual components whereby the post-harvest ripening of apples and other fruits can be monitored. Different kinds of apple differ in type and concentration of individual carbonyl compounds.


An emerging disease causes regional population collapse of a common North American bat species.
White-nose syndrome (WNS) is an emerging disease affecting hibernating bats in eastern North America that causes mass mortality and precipitous population declines in winter hibernacula. First discovered in 2006 in New York State, WNS is spreading rapidly across eastern North America and currently affects seven species. Mortality associated with WNS is causing a regional population collapse and is predicted to lead to regional extinction of the little brown myotis (Myotis lucifugus), previously one of the most common bat species in North America. Novel diseases can have serious impacts on naïve wildlife populations, which in turn can have substantial impacts on ecosystem integrity.


Clients' and nurses' perspectives on caring as related to nursing leadership--the Hellenic dimension. Part One.
Public perceptions of caring are vital to the future of the nursing profession. Literature indicates that patients conceive caring in a traditional manner which contrasts with that of nurses. This paper addresses the culturally determined complex and interactive personal, historical and sociopolitical factors that account for the development of clients' and nurses' perceptions of caring and explains the differences observed in research between the two groups. It also discusses the high cost that society and nursing pay today for the poor public image of nurse caring. Finally, it identifies strategies that nurses, especially those in leadership positions, can use to improve the consumer's view of caring and to reduce the gap existing between clients' and professionals' perceptions of the concept. The Hellenic perspective is used as a reference point to present the relevance of the issue to the broader context of nursing in the world. The paper is based upon primary and secondary data including research findings, legislation, the authors' observations and experiences with their domestic health care system, and available literature on the subject.


Environmental Modifications and Supports for Participation Among Adults Aging With Intellectual and Developmental Disabilities: A Scoping Review.
Adults aging with intellectual and developmental disabilities (IDD) continue to face barriers to participation in meaningful occupation; moreover, the increased life expectancy of adults with IDD intensifies the need for age- and environment-specific support. To map and categorize transdisciplinary literature on environmental modifications and supports for adults aging with IDD. Studies published between January 1, 2000, and January 1, 2019, identified through PubMed and Scopus. Study Selection and Data Collection: Eleven articles met the inclusion criteria and contained information specific to occupational participation based on environmental modification (e.g., physical space, technology, universal design, type of living setting), social supports (e.g., family members, caretakers, peer groups, health care professionals, policies, organizational infrastructure), or both and adults age ≥35 yr with IDD. Eleven studies met the criteria for this scoping review. Thematic coding was used to examine the articles within one or more themes: definition of need, environmental risk and assessment, environmental setting, intervention and program planning, use of technology, and bureaucracy. This review highlights collective and individual outcomes in the areas of assessment, intervention, and advocacy. Further research is needed within the scope of occupational therapy and disability studies that examines environmental factors and participation outcomes in this population. What This Article Adds: The authors define the interconnectedness of adults aging with IDD and environmental factors, identify barriers to participation, and guide occupational therapy practitioners' logic on how to positively affect environmental change and supports through intervention.


Effects of dexamethasone on antigen expression and virus production in avian sarcoma virus-transformed cells.
We studied the effects of dexamethasone on virus production and antigen expression in avian retrovirus-infected chick embryo fibroblast (CEF) cells. The presence of specific receptors for this hormone in both normal and infected CEF cells could only be demonstrated using cultures that were at or near confluence. Dexamethasone, while not toxic to the cells, exerted a growth-retarding influence when employed at concentrations of 10(-8) or 10(-9) M. These same concentrations of hormone were inhibitory to virus production, elaboration of plasminogen activator activity, and antigen expression as determined in a sensitized lymphocyte stimulation assay. In contrast, infected cells that had been treated with hormone displayed enhanced reactivity in a specific immunofluorescence test.


Homocystine-induced arteriosclerosis. The role of endothelial cell injury and platelet response in its genesis.
The atherogenic mechanism of homocystinemia has been defined by measuring endothelial cell loss and regeneration, platelet consumption, and intimal lesion formation in a primate model. Three groups of baboons were studied: (a) 8 control animals; (b) 15 animals after 3 mo of continuous homocystinemia; and (c) 11 animals after 3 mo of combined homocystinemia and oral treatment with dipyridamole. Experimental homocystinemia caused patchy endothelial desquamation comprising about 10% of the aortic surface despite a 25-fold increase in endothelial cell regeneration. Neither endothelial cell loss nor regeneration was changed significantly by dipyridamole. Homocystine-induced vascular deendothelialization produced a threefold increase in platelet consumption that was interrupted by dipyridamole inhibition of platelet function. All homocystinemic animals developed typical arteriosclerotic or preatherosclerotic intimal lesions composed of proliferating smooth muscle cells averaging 10-15 cell layers surrounded by large amounts of collagen, elastic fibers, glycosaminoglycans, and sometimes lipid. Intimal lesion formation was prevented by dipyridamole therapy. We conclude that homocystine-induced endothelial cell injury resulted in arteriosclerosis through platelet-mediated intimal proliferation of smooth muscle cells that can be prevented by drug-induced platelet dysfunction.


Anatomy, function, and pathophysiology of the posterior tibial tendon.
The posterior tibial tendon is vital for the structure and function of the foot and ankle. Dysfunction of the tendon can be debilitating and devastating. In recent years, much attention had been directed toward the diagnosis and treatment of PTTD. To properly diagnose and devise an appropriate treatment regimen, the anatomy, function, and pathophysiology associated with PTTD need to be thoroughly understood.


The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.
5-Fluorouracil (5-FU) is the most widely used cytotoxic drug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. Twenty-six patients were treated with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007). MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue metabolism of a fluorinated drug is of interest.


Human pulmonary infections with bovine and atypical mycobacteria in Lagos, Nigeria.
A total of 2784 cases with persistent symptoms of lower respiratory tract infections were seen in four of the chest clinics in Lagos between January and June of 1983. Of these, 668 were randomly selected and screened for pulmonary tuberculosis. Repeated sputum samples from the 668 patients were cultured on Lowenstein-Jenseen slopes and 102 pure mycobacterial isolates were obtained. The isolates were differentiated into tubercle bacilli, bovine or atypical mycobacteria on the basis of results obtained from nine identification tests. Of the 102 mycobacterial isolates obtained, 87 (85%) were identified as Mycobacterium tuberculosis, four (4%) as M. bovis and 11 (11%) as atypical mycobacteria. Among this atypical group, six were classified as M. avium, four as M. kansasii and one as M. fortuitum. The study showed the involvement of bovine and atypical mycobacteria in pulmonary infections in Lagos. Tuberculosis-like diseases produced by some of the atypical group are resistant to most of the conventionally used anti-tuberculosis drugs. The need for adequate bacteriological analysis in current-day diagnosis and treatment of pulmonary tuberculosis is therefore highlighted since the 11 atypical cases seen in this study would otherwise have been diagnosed and treated as cases of classical tuberculosis.