Isochores and tissue-specificity.
The housekeeping (ubiquitously expressed) genes in the mammal genome were shown here to be on average slightly GC-richer than tissue-specific genes. Both housekeeping and tissue-specific genes occupy similar ranges of GC content, but the former tend to concentrate in the upper part of the range. In the human genome, tissue-specific genes show two maxima, GC-poor and GC-rich. The strictly tissue-specific human genes tend to concentrate in the GC-poor region; their distribution is left-skewed and thus reciprocal to the distribution of housekeeping genes. The intermediately tissue-specific genes show an intermediate GC content and the right-skewed distribution. Both in the human and mouse, genes specific for some tissues (e.g., parts of the central nervous system) have a higher average GC content than housekeeping genes. Since they are not transcribed in the germ line (in contrast to housekeeping genes), and therefore have a lower probability of inheritable gene conversion, this finding contradicts the biased gene conversion (BGC) explanation for elevated GC content in the heavy isochores of mammal genome. Genes specific for germ-line tissues (ovary, testes) show a low average GC content, which is also in contradiction to the BGC explanation. Both for the total data set and for the most part of tissues taken separately, a weak positive correlation was found between gene GC content and expression level. The fraction of ubiquitously expressed genes is nearly 1.5-fold higher in the mouse than in the human. This suggests that mouse tissues are comparatively less differentiated (on the molecular level), which can be related to a less pronounced isochoric structure of the mouse genome. In each separate tissue (in both species), tissue-specific genes do not form a clear-cut frequency peak (in contrast to housekeeping genes), but constitute a continuum with a gradually increasing degree of tissue-specificity, which probably reflects the path of cell differentiation and/or an independent use of the same protein in several unrelated tissues.


A transposable element into the human long noncoding RNA CARMEN is a switch for cardiac precursor cell specification.
The major cardiac cell types composing the adult heart arise from common multipotent precursor cells. Cardiac lineage decisions are guided by extrinsic and cell-autonomous factors, including recently discovered long noncoding RNAs (lncRNAs). The human lncRNA CARMEN, which is known to dictate specification toward the cardiomyocyte (CM) and the smooth muscle cell (SMC) fates, generates a diversity of alternatively spliced isoforms. The CARMEN locus can be manipulated to direct human primary cardiac precursor cells (CPCs) into specific cardiovascular fates. Investigating CARMEN isoform usage in differentiating CPCs represents therefore a unique opportunity to uncover isoform-specific functions in lncRNAs. Here, we identify one CARMEN isoform, CARMEN-201, to be crucial for SMC commitment. CARMEN-201 activity is encoded within an alternatively spliced exon containing a MIRc short interspersed nuclear element. This element binds the transcriptional repressor REST (RE1 Silencing Transcription Factor), targets it to cardiogenic loci, including ISL1, IRX1, IRX5, and SFRP1, and thereby blocks the CM gene program. In turn, genes regulating SMC differentiation are induced. These data show how a critical physiological switch is wired by alternative splicing and functional transposable elements in a long noncoding RNA. They further demonstrated the crucial importance of the lncRNA isoform CARMEN-201 in SMC specification during heart development.


[Use of angle-stable implants for proximal humeral fractures: prospective study].
To evaluate and compare proximal humeral fractures treated either by plate osteosynthesis with angular-stable screws or by intramedullary nailing, and to define the indications optimal for use of either technique. The study comprised 97 patients. The proximal humeral internal locking system (PHILOS) plate was used in 49 patients (31 women and 18 men); with age average 57.4 years (women, 64.5 and men, 45.3 years). By the AO classification, 12 patients with type A, 15 with type B, and 22 with type C fractures. The Targon PH nail was used in 48 patients (32 women and 16 men) at an average age of 65.3 years (women, 72.2 and men, 51.4 years). Type A fractures were in 18, type B in 18 and type C in 12 patients. The patients were prospectively evaluated and placed into the two groups. The post-operative range of motion was assessed by the Constant-Murley (CM) score at 6 weeks, and at 3, 6 and 12 months. The CM value was related to the healthy collateral limb and recorded as a relative CM score. RESULTS In the PHILOS group, the average values were: operative time, 76.2 min; X-ray exposure, 4.2 min; and relative CM score, 74.5 points. The Targon PH group showed the average operative time of 50.2 min., X-ray exposure for 4 min. and the relative CM score 78.3 points. There were no significant differences between the groups, with the exception of shorter operative time in intramedullary nailing. Nailing is the method of choice for two-fragment fractures. In comminutive metaphyseal fractures particularly, the use of nailing is more effective than plate osteosynthesis that carries the risk of plate detachment from the diaphysis. In fractures with a long fracture line extending into the metaphysis, plate osteosynthesis with open reduction is a better option. The results in three-fragment fractures are comparable and the choice of an implant is the matter of surgeon's preference. The standard technique for four-fragment fractures involves the use of angular-stable plate fixation through the deltoid- pectoral approach. Intramedullary nailing is a borderline indication requiring a modified surgical procedure, with tubercles being fixed with osteosuture. No statistically significant differences in functional results occurred between the observed groups at one year of followup. In four-fragment proximal humerus fractures, the patients treated with Targon PH nails had more complications and worse relative CM scores than those treated with PHILOS plates; however, this was not statistically significant and the number of complications decreased after the technique of tubercle osteosuture had been introduced. Finally, the only significant difference between the groups was a shorter operative time with the use of intramedullary nailing.


Theoretical conditions for the stationary reproduction of model protocells.
In previous works we have explored the dynamics of chemically reacting proto-cellular systems, under different experimental conditions and kinetic parameters, by means of our stochastic simulation platform 'ENVIRONMENT'. In this paper we, somehow, turn the question around: accepting some broad modeling assumptions, we investigate the conditions under which simple protocells will spontaneously settle into a stationary reproducing regime, characterized by a regular growth/division cycle and the maintenance of a certain standard size and chemical composition across generations. In the first part, starting from purely geometric considerations, the condition for stationary reproduction of a protocell will be expressed in terms of a growth control coefficient (γ). Then, an explicit relationship, the osmotic synchronization condition, will be analytically derived under a set of kinetic simplifications and taking into account the osmotic pressure balance operating across the protocell membrane. In the second part of the paper, this general condition that constrains different molecular/kinetic parameters and features of the system (reaction rates, permeability coefficients, metabolite concentrations, system volume) will be applied to different cases of self-producing vesicles, predicting the stationary protocell size or lifetime. Finally, in order to test the validity of our analytic results and predictions, the case study is contrasted with data obtained through both stochastic and deterministic computational algorithms.


Chapter 13: Potentially (near) fatal asthma.
Potentially (near) fatal asthma (PFA) defines a subset of patients with asthma who are at increased risk for death from their disease. The diagnosis of PFA should motivate treating physicians, health professionals, and patients to be more aggressive in the monitoring, treatment, and control of this high-risk type of asthma. A diagnosis of PFA is made when any one of the following are present: (1) history of endotracheal intubation from asthma, (2) acute respiratory acidosis (pH < 7.35) or respiratory failure from acute severe asthma, (3) two or more episodes of acute pneumothorax or pneumomediastinum from asthma, (4) two or more episodes of acute severe asthma despite the use of long-term oral corticosteroids and other antiasthma medications. There are two predominant phenotypes of near fatal exacerbations, the "subacute" exacerbation and the "hyperacute" exacerbation. The best way to "treat" acute severe asthma is 3-7 days before it occurs (i.e., at the onset of symptoms or change in respiratory function) and to optimize control of asthma by decreasing the number of symptomatic days and days/nights requiring rescue therapy and increasing baseline respiratory status in "poor perceivers." PFA is treated with a multifaceted approach; physicians should appreciate limitations of pharmacotherapy including combination inhaled corticosteroid/long-acting beta-agonist products as well as addressing nonadherence, psychiatric, and socioeconomic issues that complicate care.


The origin of red cell fluorescence caused by hydrogen peroxide treatment.
Fluorescence in red cells following hydrogen peroxide treatment has been attributed to lipid peroxidation of the membrane. The putative relationship between lipid peroxidation and fluorescence was questioned by the finding that BHT and alpha-tocopherol, which are thought to inhibit lipid peroxidation, do not inhibit the fluorescence detected by flow cytometry. Furthermore, lipid peroxidation induced in red cells by the Fe(III)-ADP-ascorbate system did not produce fluorescence. These results require an alternative explanation for the hydrogen peroxide-induced fluorescence. A role for reduced hemoglobin is indicated by the inhibition of fluorescence by pretreatment of cells with CO that binds strongly to ferrohemoglobin and nitrite that oxidizes ferrohemoglobin. Our earlier studies have shown the formation of fluorescent heme degradation products during the reaction of purified hemoglobin with hydrogen peroxide, which was also inhibited by CO and nitrite pretreatment. The fluorescence produced in red cells after the addition of hydrogen peroxide can, therefore, be attributed to fluorescent heme degradation products.


[Salmonellosis in the horse].
Salmonellosis is a worldwide problem of both men and animals. Equine salmonellosis is an increasing problem and a review of the recent knowledge is given. Etiology, symptomatology, diagnostic procedures, therapy and prevention are discussed.


Merging In-Solution X-ray and Neutron Scattering Data Allows Fine Structural Analysis of Membrane-Protein Detergent Complexes.
In-solution small-angle X-ray and neutron scattering (SAXS/SANS) have become popular methods to characterize the structure of membrane proteins, solubilized by either detergents or nanodiscs. SANS studies of protein-detergent complexes usually require deuterium-labeled proteins or detergents, which in turn often lead to problems in their expression or purification. Here, we report an approach whose novelty is the combined analysis of SAXS and SANS data from an unlabeled membrane protein complex in solution in two complementary ways. First, an explicit atomic analysis, including both protein and detergent molecules, using the program WAXSiS, which has been adapted to predict SANS data. Second, the use of MONSA which allows one to discriminate between detergent head- and tail-groups in an ab initio approach. Our approach is readily applicable to any detergent-solubilized protein and provides more detailed structural information on protein-detergent complexes from unlabeled samples than SAXS or SANS alone.


Assessing the nutritional status of hospitalized elderly.
The increasing number of elderly people worldwide throughout the years is concerning due to the health problems often faced by this population. This review aims to summarize the nutritional status among hospitalized elderly and the role of the nutritional assessment tools in this issue. A literature search was performed on six databases using the terms "malnutrition", "hospitalised elderly", "nutritional assessment", "Mini Nutritional Assessment (MNA)", "Geriatric Nutrition Risk Index (GNRI)", and "Subjective Global Assessment (SGA)". According to the previous studies, the prevalence of malnutrition among hospitalized elderly shows an increasing trend not only locally but also across the world. Under-recognition of malnutrition causes the number of malnourished hospitalized elderly to remain high throughout the years. Thus, the development of nutritional screening and assessment tools has been widely studied, and these tools are readily available nowadays. SGA, MNA, and GNRI are the nutritional assessment tools developed specifically for the elderly and are well validated in most countries. However, to date, there is no single tool that can be considered as the universal gold standard for the diagnosis of nutritional status in hospitalized patients. It is important to identify which nutritional assessment tool is suitable to be used in this group to ensure that a structured assessment and documentation of nutritional status can be established. An early and accurate identification of the appropriate treatment of malnutrition can be done as soon as possible, and thus, the malnutrition rate among this group can be minimized in the future.


Scapular positioning in overhead athletes with and without shoulder pain: a case-control study.
Abnormalities of scapular positioning are considered important risk factors for developing shoulder disorders. This study analyses the scapular positioning pattern in a group of overhead athletes with and without shoulder pain. In a multi-center blinded case-control study, 36 shoulder pain athletes (19 men, 17 women), were compared with 36 unimpaired athletes free of shoulder pain, matched for gender, age, hand dominance and body mass index. The blinded assessor performed visual observation, the measurement of the distance between the acromion and the table, inclinometry and the kinetic medial rotation test for dynamic scapular control in random order. Athletes with shoulder pain demonstrate scapular asymmetry in the sagittal plane, observed visually as anterior tilting on the painful side. Athletes with shoulder pain show a lack of scapular motor control on their painful side in contrast to their pain-free side. No scapular positioning or motor control differences were found in athletes with or without shoulder pain.


Quality of generalist vs. specialty care for people with HIV on antiretroviral treatment: a prospective cohort study.
To describe health-care use by persons with HIV in an urban area of Switzerland (Zurich). Further, to compare the different health-care settings. A 1-year prospective cohort study recruiting 60 patients at general practices and 60 patients at a specialized university outpatient clinic. Patients and their treating physicians were interviewed or answered questionnaires, respectively, at baseline, month 6 and 12. During the study period, five patient groups were identified among the 106 enrolled patients, of whom (i) 42% saw a general practitioner exclusively, (ii) 31% were treated at the specialized outpatient clinic, (iii) 8% were in shared care, (iv) 10% changed health-care model, and (v) 9% were lost to follow-up. Baseline demographic, psychosocial and clinical data were similar among patient groups. At study end, the proportion of patients with HIV-1 RNA < 400 copies/mL was 72%, 74%, 88%, 55% among groups (i) to (iv), respectively (ns), and 22% at month 6 among those lost to follow-up. Indicators for quality of care were similarly good among all patient groups. A well-working system offers high-quality healthcare to persons living with HIV, where existing teams of specialty and primary health-care professionals efficiently and effectively co-operate.


Premature mortality due to air pollution in European cities: a health impact assessment.
Ambient air pollution is a major environmental cause of morbidity and mortality worldwide. Cities are generally hotspots for air pollution and disease. However, the exact extent of the health effects of air pollution at the city level is still largely unknown. We aimed to estimate the proportion of annual preventable deaths due to air pollution in almost 1000 cities in Europe. We did a quantitative health impact assessment for the year 2015 to estimate the effect of air pollution exposure (PM2·5 and NO2) on natural-cause mortality for adult residents (aged ≥20 years) in 969 cities and 47 greater cities in Europe. We retrieved the cities and greater cities from the Urban Audit 2018 dataset and did the analysis at a 250 m grid cell level for 2015 data based on the global human settlement layer residential population. We estimated the annual premature mortality burden preventable if the WHO recommended values (ie, 10 μg/m3 for PM2·5 and 40 μg/m3 for NO2) were achieved and if air pollution concentrations were reduced to the lowest values measured in 2015 in European cities (ie, 3·7 μg/m3 for PM2·5 and 3·5 μg/m3 for NO2). We clustered and ranked the cities on the basis of population and age-standardised mortality burden associated with air pollution exposure. In addition, we did several uncertainty and sensitivity analyses to test the robustness of our estimates. Compliance with WHO air pollution guidelines could prevent 51 213 (95% CI 34 036-68 682) deaths per year for PM2·5 exposure and 900 (0-2476) deaths per year for NO2 exposure. The reduction of air pollution to the lowest measured concentrations could prevent 124 729 (83 332-166 535) deaths per year for PM2·5 exposure and 79 435 (0-215 165) deaths per year for NO2 exposure. A great variability in the preventable mortality burden was observed by city, ranging from 0 to 202 deaths per 100 000 population for PM2·5 and from 0 to 73 deaths for NO2 per 100 000 population when the lowest measured concentrations were considered. The highest PM2·5 mortality burden was estimated for cities in the Po Valley (northern Italy), Poland, and Czech Republic. The highest NO2 mortality burden was estimated for large cities and capital cities in western and southern Europe. Sensitivity analyses showed that the results were particularly sensitive to the choice of the exposure response function, but less so to the choice of baseline mortality values and exposure assessment method. A considerable proportion of premature deaths in European cities could be avoided annually by lowering air pollution concentrations, particularly below WHO guidelines. The mortality burden varied considerably between European cities, indicating where policy actions are more urgently needed to reduce air pollution and achieve sustainable, liveable, and healthy communities. Current guidelines should be revised and air pollution concentrations should be reduced further to achieve greater protection of health in cities. Spanish Ministry of Science and Innovation, Internal ISGlobal fund.


Prevalence and socio-demographic correlates of daily cigarette smoking in Poland: results from the Global Adult Tobacco Survey (2009-2010).
The aim of the study was to evaluate the prevalence and socio-demographic correlates of daily cigarette smoking among adults in Poland. A nationally representative household study was implemented between 2009 and 2010 to explore smoking pattern among the population aged 15 years and older. The smoking status and socio-demographic data were determined based on the Global Adult Tobacco Survey (GATS) questionnaire. Out of the 14000 households selected for the survey, 7840 sampled persons completed the interviews, including 2162 respondents who declared daily smoking of cigarettes. Logistic regression models were applied to assess factors related to daily cigarette smoking. Over 33% of men and 21% of women (p < 0.01) reported tobacco smoking on a daily basis. The significantly higher risk of smoking on a daily basis was observed among the male and female 20-59 years of age compared to the 60 or older population (p < 0.05). For men and women with the lower educational (primary/vocational/secondary) level, the risk of smoking was significantly higher than for the subjects with university degree (p < 0.05). The unemployed men smoked daily significantly more frequently than the employed ones (OR = 1.8; 95% CI: 1.4-2.4). This association was not observed among women (p > 0.05). The residents of urban areas smoked significantly more frequently than people living in rural settings (p < 0.05). Actions to tackle socio-economic inequalities in smoking need to be intensified. The antismoking efforts should be focused on the population of Poles at large and people with lower educational levels, unemployed men, and residents of large urban settings in particular. The tobacco control interventions should also address the population of women at reproductive age.


Coexpression and interaction of CXCL10 and CD26 in mesenchymal cells by synergising inflammatory cytokines: CXCL8 and CXCL10 are discriminative markers for autoimmune arthropathies.
Leukocyte infiltration during acute and chronic inflammation is regulated by exogenous and endogenous factors, including cytokines, chemokines and proteases. Stimulation of fibroblasts and human microvascular endothelial cells with the inflammatory cytokines interleukin-1beta (IL-1beta) or tumour necrosis factor alpha (TNF-alpha) combined with either interferon-alpha (IFN-alpha), IFN-beta or IFN-gamma resulted in a synergistic induction of the CXC chemokine CXCL10, but not of the neutrophil chemoattractant CXCL8. In contrast, simultaneous stimulation with different IFN types did not result in a synergistic CXCL10 protein induction. Purification of natural CXCL10 from the conditioned medium of fibroblasts led to the isolation of CD26/dipeptidyl peptidase IV-processed CXCL10 missing two NH2-terminal residues. In contrast to intact CXCL10, NH2-terminally truncated CXCL10(3-77) did not induce extracellular signal-regulated kinase 1/2 or Akt/protein kinase B phosphorylation in CXC chemokine receptor 3-transfected cells. Together with the expression of CXCL10, the expression of membrane-bound CD26/dipeptidyl peptidase IV was also upregulated in fibroblasts by IFN-gamma, by IFN-gamma plus IL-1beta or by IFN-gamma plus TNF-alpha. This provides a negative feedback for CXCL10-dependent chemotaxis of activated T cells and natural killer cells. Since TNF-alpha and IL-1beta are implicated in arthritis, synovial concentrations of CXCL8 and CXCL10 were compared in patients suffering from crystal arthritis, ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. All three groups of autoimmune arthritis patients (ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis) had significantly increased synovial CXCL10 levels compared with crystal arthritis patients. In contrast, compared with crystal arthritis, only rheumatoid arthritis patients, and not ankylosing spondylitis or psoriatic arthritis patients, had significantly higher synovial CXCL8 concentrations. Synovial concentrations of the neutrophil chemoattractant CXCL8 may therefore be useful to discriminate between autoimmune arthritis types.


Complaints against nurses: a reflection of 'the new managerialism' and consumerism in health care?
This paper discusses the effects of restructuring on nursing as a profession through an examination of the issue of complaints in Ontario. It argues that new managerialist techniques and associated changes in the nature of work are reducing the autonomy of nurses and making it difficult for them to meet the standards of their profession. Simultaneously, the Ontario government has increased the power of the public in the disciplinary process and the College of Nurses of Ontario is encouraging patients to register their complaints. The growth of consumerism in health care, coupled with the disciplinary process, individualizes complaints and deemphasizes their relationship to restructuring. Moreover, in response to the increasing number of complaints - complaints which more often come from the public - nursing organizations have encouraged the legalization of the disciplinary process, thus fostering the individualization of the issues.


Dapsone-associated fixed drug eruption.
Dapsone is a sulfone drug used to treat infectious conditions and also numerous dermatologic diseases. Fixed drug eruption is a distinctive adverse cutaneous reaction associated with the initial administration and subsequent delivery of a specific agent. Areas covered: The authors preformed a literature search using the following keywords: dapsone, fixed drug eruption, and adverse cutaneous drug reaction. Bibliographies were also reviewed for pertinent articles. The results were combed for relevant papers and reviewed. Articles pertaining to dapsone-associated fixed drug eruption were included. Expert commentary: The majority of cases of dapsone-associated fixed drug eruption in the literature come from Africa or India where there is a high prevalence of patients treated for leprosy. Characteristics of these cases are similar to fixed drug eruption described in the western literature, with differences in frequency of multiple versus solitary lesions. Dapsone-associated fixed drug eruption should be considered when reviewing the drug history of a patient with fixed drug eruption. In the case of darker pigmented individuals, multiple fixed drug eruption lesions may be more common. Multiple lesions may mimic Kaposi's sarcoma in human immunodeficiency virus positive patients. Dapsone-associated fixed drug eruption should be considered in the differential diagnosis of multiple hyperpigmented lesions.


Escitalopram in major depressive disorder: clinical benefits and cost effectiveness versus citalopram.
Objective. Escitalopram is the most selective of the serotonin reuptake inhibitors. Methods. We review all the clinical trials (three pivotal placebo-controlled trials with citalopram as an active reference, one long-term non-inferiority study and one head-to-head superiority study) that include citalopram as an active reference in major depressive disorder (MDD), and studies that evaluate the cost-effectiveness of the two drugs. Results. In two of the pivotal studies and in the long-term study, escitalopram was numerically better than citalopram in reducing Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline, with comparative tolerability. Meta-analyses of these studies showed statistically significant differences in favour of escitalopram in terms of reducing MADRS and increasing response. This effect was particularly apparent in patients with higher baseline MADRS scores. These trends were confirmed in a head-to-head study, which clearly demonstrated the superiority of escitalopram compared with citalopram on primary and secondary endpoints. The difference between treatments was clinically relevant. Cost-effectiveness analyses demonstrated that although escitalopram has a slightly higher unit cost than generic citalopram, expected direct medical and productivity- related costs were lower with escitalopram than citalopram. Conclusion. On the basis of these results, escitalopram was concluded to be more clinically effective and more cost-effective than citalopram for the treatment of MDD, with a similar tolerability profile.


Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years.
The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear. At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up. During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years. Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.


Heart health whispering: A randomized, controlled pilot study to promote nursing student perspective-taking on carers' health risk behaviors.
Lifestyle counseling is described as a "major breakthrough" in the control of chronic diseases. Counseling can be challenging to nurses due their lack of motivation to counsel, hesitancy to appear non-judgmental, lack of empathy, and lack of time. Nurses voice their need for more training in counseling communication skills. Our main objective was to engage in ongoing development and testing of a promising Heart Health Whispering perspective-taking intervention on nursing students' clinical empathy, perceptual understanding, and client readiness to alter health risk behaviors. In this randomized controlled pilot study, the full intervention (perspective-taking instructions, practice, and video-feedback) and partial intervention (video-feedback only) comprised 24 and 18 nursing students, respectively. Quantitative data were collected with a 10-item pre- and post-intervention clinical empathy tool, a one-item 'readiness to change' health risk behavior tool plus similarity ratings on students' empathic accuracy were calculated. Data were analyzed using Independent Samples t Tests and mixed model ANCOVA models. Students' and actors' evaluative responses toward the intervention phases were collected by handwritten notes, and analyzed using content analysis and constant comparison techniques. The main finding was that students in the full intervention group reported greater clinical empathy in the post versus baseline condition. Students underestimated their clinical empathy in comparison to carers' reports in the post-condition. In both intervention groups, carers reported more readiness to change in the post-condition. Carers identified favorable and unfavorable perceptions and outcomes of approaches taken by students. Students desired immediate and direct feedback after the video-dialogue and -tagging exercise. Heart Health Whispering is a promising intervention to help educators in basic and continuing education to bolster nurse confidence in empathic conversations on health risk behaviors. This intervention incorporates commonly used strategies to teach empathic communication along with a novel video-analysis application of a perspective-taking task. Student and carer actor comments highlighted the value in opportunities for students to engage in self-evaluation and practicing the empathic process of taking the client's perspective on health risk behaviors.


Cloning and sequencing of the gene for a Pseudomonas paucimobilis enzyme that cleaves beta-aryl ether.
We isolated Pseudomonas paucimobilis SYK-6, which was able to degrade various dimeric lignin compounds (Y. Katayama, S. Nishikawa, M. Nakamura, K. Yano, M. Yamasaki, N. Morohoshi, and T. Haraguchi, Mokuzai Gakkaishi 33:77-79, 1987). This metabolic process is a distinct characteristic of this bacterium, which is equipped with an enzymatic modification system for various dimeric lignin compounds involved in the tricarboxylic acid cycle. Cleavage of the beta-aryl ether linkage is essential in this process, because this linkage is the most abundant (approximately 50%) in lignin. Here, we report the isolation and characterization of the beta-etherase gene, which contains an open reading frame of 843 bp and which we call ligE. This gene was expressed in Escherichia coli, and the enzyme had the same kinetic properties as the P. paucimobilis SYK-6 enzyme.


Potential lactoferrin activity against pathogenic viruses.
Lactoferrin (LF) is an 80-kDa globular glycoprotein with high affinity for metal ions, particularly for iron. This protein possesses many biological functions, including the binding and release of iron and serves as one of the important components of the innate immune system, where it acts as a potent inhibitor of several pathogens. LF has efficacious antibacterial and antiviral activities against a wide range of Gram-positive and Gram-negative bacteria and against both naked and enveloped DNA and RNA viruses. In its antiviral pursuit, LF acts predominantly at the acute phase of the viral infection or even at the intracellular stage, as in hepatitis C virus infection. LF inhibits the entry of viral particles into host cells, either by direct attachment to the viral particles or by blocking their cellular receptors. This wide range of activities may be attributed to the capacity of LF to bind iron and its ability to interfere with the cellular receptors of both hosts and pathogenic microbes.


Functional and mechanistic analyses of biomimetic aminoacyl transfer reactions in de novo designed coiled coil peptides via rational active site engineering.
Ribosomes and nonribosomal peptide synthetases (NRPSs) carry out instructed peptide synthesis through a series of directed intermodular aminoacyl transfer reactions. We recently reported the design of coiled-coil assemblies that could functionally mimic the elementary aminoacyl loading and intermodular aminoacyl transfer steps of NRPSs. These peptides were designed initially to accelerate aminoacyl transfer mainly through catalysis by approximation by closely juxtaposing four active site moieties, two each from adjacent noncovalently associated helical modules. In our designs peptide self-assembly positions a cysteine residue that is used to covalently capture substrates from solution via transthiolesterification (substrate loading step to generate the aminoacyl donor site) adjacent to an aminoacyl acceptor site provided by a covalently tethered amino acid or modeled by the epsilon-amine of an active site lysine. However, through systematic functional analyses of 48 rationally designed peptide sequences, we have now determined that the substrate loading and intermodular aminoacyl transfer steps can be significantly influenced (up to approximately 103-fold) by engineering changes in the active site microenvironment through amino acid substitutions and variations in the inter-residue distances and geometry. Mechanistic studies based on 15N NMR and kinetic analysis further indicate that certain active site constellations furnish an unexpectedly large pK(a) depression (1.5 pH units) of the aminoacyl-acceptor moiety, helping to explain the observed high rates of aminoacyl transfer in those constructs. Taken together, our studies demonstrate the feasibility of engineering efficient de novo peptide sequences possessing active sites and functions reminiscent of those in natural enzymes.


Similarity in temperament between mother and offspring rhesus monkeys: sex differences and the role of monoamine oxidase-a and serotonin transporter promoter polymorphism genotypes.
Temperament is usually considered biologically based and largely inherited, however, the environment can shape the development of temperament. Allelic variation may confer differential sensitivity to early environment resulting in variations in temperament. Here we explore the relationship between measures of temperament in mothers and their first-born offspring and the role of genetic sensitivity in establishing the strength of these associations. Temperament ratings were conducted on 3- to 4-month-old rhesus monkeys after a 25-hr biobehavioral assessment. Factor analysis revealed a four-factor structure of temperament. Females assessed as infants have reproduced and their offspring have also been evaluated through the standardized testing paradigm. Canonical correlation analysis revealed statistically significant associations between factor scores of mothers and sons, but not mothers and daughters. Further, offspring possessing the high activity, "low risk," alleles of the rhMAOA-LPR or rh5-HTTLPR showed statistically significant canonical correlations, whereas those possessing other alleles did not, suggesting differential genetic sensitivity to the normative early experience of maternal temperament.


Management of Heart Failure in Patients with Chronic Kidney Disease.
Chronic kidney disease (CKD) is increasingly prevalent in patients with heart failure (HF) and HF is one of the leading causes of hospitalisation, morbidity and mortality in patients with impaired renal function. Currently, there is strong evidence to support the symptomatic and prognostic benefits of β-blockers, renin-angiotensin-aldosterone inhibitors (RAASis), angiotensin receptor-neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRA) in patients with HF and CKD stages 1-3. However, ARNIs, RAASis and MRAs are often suboptimally prescribed for patients with CKD owing to concerns about hyperkalaemia and worsening renal function. There is growing evidence for the use of sodium-glucose co-transporter 2 inhibitors and IV iron therapy in the management of HF in patients with CKD. However, few studies have included patients with CKD stages 4-5 and patients receiving dialysis, limiting the assessment of the safety and efficacy of these therapies in advanced CKD. Interdisciplinary input from HF and renal specialists is required to provide integrated care for the growing number of patients with HF and CKD.


Epidemiology of cerebrovascular diseases in cuba, 1970 to 2006.
Cerebrovascular diseases (CD) are a global health problem. They are the second and third causes of death in the world and in Cuba, respectively. Projections for year 2020 suggest they will continue to be among the main causes of death and disability, both in developed and developing countries. In 2006, the National Health System (NHS) presented its Public Health Projections in Cuba for Year 2015, which set the following specific goals for CD mortality reduction: overall mortality by 25%, female mortality by 30%, and hospital mortality by 30%. Analyze CD mortality in Cuba from 1970 to 2006, before and after implementation of the National Program for Cerebrovascular Disease Prevention and Control (NPCD-PC) to obtain a better understanding of the current situation, which may serve as the basis to meet the goals set for year 2015. CD mortality databases from the National Statistical Division of the Cuban Ministry of Public Health were used. The following variables were applied: sex, CD-related causes, and place of death. Crude and age-adjusted mortality rates were determined. Overall mortality, mortality by sex, years of potential life lost, hospital mortality, incidence, and prevalence were calculated. Crude mortality rates showed a sustained increase within the time series under study; conversely, age-adjusted rates showed a decrease in mortality during the 1970s, were stable in the 1980s and 1990s and, finally, decreased since year 2000, when the NPCD-PC program was started in the country. The male/female ratio increased slightly from the late 1990s until 2005; yet female mortality has shown a tendency to increase. Between 1993 and 2002, cerebral hemorrhage caused more deaths than the cerebral infarction; since then, this profile has reversed. CD-related years of potential life lost (YPLL) showed a decrease from 1970 to 1975, followed by a sustained increase through 1985, and a gradual decrease since 1990. Hospital mortality diminished steadily from 1990 to 1999 and has remained stable since year 2000. Even though there was greater CD incidence from 2000 to 2001, it has decreased since then. However, prevalence has increased slightly every year from 2000 to 2005. Although overall mortality and female mortality rates, in particular, increased following implementation of the NPCD-PC program, age-adjusted mortality, hospital mortality, and incidence diminished during the same period. Further study is recommended to determine specific actions required to achieve CD mortality reduction goals by 2015.


Acyl-CoA dehydrogenase substrate promiscuity: Challenges and opportunities for development of substrate reduction therapy in disorders of valine and isoleucine metabolism.
Toxicity of accumulating substrates is a significant problem in several disorders of valine and isoleucine degradation notably short-chain enoyl-CoA hydratase (ECHS1 or crotonase) deficiency, 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, propionic acidemia (PA), and methylmalonic aciduria (MMA). Isobutyryl-CoA dehydrogenase (ACAD8) and short/branched-chain acyl-CoA dehydrogenase (SBCAD, ACADSB) function in the valine and isoleucine degradation pathways, respectively. Deficiencies of these acyl-CoA dehydrogenase (ACAD) enzymes are considered biochemical abnormalities with limited or no clinical consequences. We investigated whether substrate reduction therapy through inhibition of ACAD8 and SBCAD can limit the accumulation of toxic metabolic intermediates in disorders of valine and isoleucine metabolism. Using analysis of acylcarnitine isomers, we show that 2-methylenecyclopropaneacetic acid (MCPA) inhibited SBCAD, isovaleryl-CoA dehydrogenase, short-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase, but not ACAD8. MCPA treatment of wild-type and PA HEK-293 cells caused a pronounced decrease in C3-carnitine. Furthermore, deletion of ACADSB in HEK-293 cells led to an equally strong decrease in C3-carnitine when compared to wild-type cells. Deletion of ECHS1 in HEK-293 cells caused a defect in lipoylation of the E2 component of the pyruvate dehydrogenase complex, which was not rescued by ACAD8 deletion. MCPA was able to rescue lipoylation in ECHS1 KO cells, but only in cells with prior ACAD8 deletion. SBCAD was not the sole ACAD responsible for this compensation, which indicates substantial promiscuity of ACADs in HEK-293 cells for the isobutyryl-CoA substrate. Substrate promiscuity appeared less prominent for 2-methylbutyryl-CoA at least in HEK-293 cells. We suggest that pharmacological inhibition of SBCAD to treat PA should be investigated further.


Insulin-like growth factor binding proteins in femoral and vertebral bone marrow stromal cells: expression and regulation by thyroid hormone and dexamethasone.
Insulin-like growth factor (IGF)-I is an important regulator of bone metabolism. Clinical observations suggest that different anatomic sites within the adult skeleton respond differently to hormonal and therapeutic treatment, and recent studies on bone marrow stromal cells in culture show that there are skeletal site-dependent differences in the gene expression of IGF-I. The actions of IGF-I and -II on bone cells are known to be modulated by the IGF binding proteins (IGFBP)-1 through -6 and the Type I and Type II IGF receptors. Therefore, we compared the expression of IGFBP-1 through -6 in adult female rat bone marrow stromal cell cultures derived from two separate skeletal sites: vertebrae and femurs. The cultures were maintained simultaneously under conditions that support osteoblast differentiation from osteoprogenitors present in the femoral and vertebral marrow cell populations. We also addressed whether IGFBP messenger RNA levels are regulated by thyroid hormone (T(3)) and dexamethasone (dex) treatment in femoral vs. vertebral marrow stromal cells in vitro, since steroid hormones play an important role in skeletal function. Northern blot analyses revealed that there are distinct skeletal site differences in the gene expression of IGFBPs. The vertebral marrow cultures express IGFBP-2 through -6 mRNAs, with IGFBP-2, IGFBP-4, and IGFBP-6 mRNAs predominating. The femoral marrow stromal cell cultures express only IGFBP-4 and IGFBP-6. Importantly, vertebral marrow cultures have much higher IGFBP mRNA steady-state levels than femoral cultures for all the detected IGFBP transcripts. IGFBP-1 is not detected in either femoral or vertebral cultures. In addition to a skeletal site difference, we show that T(3) and dex regulate the expression of specific IGFBP mRNAs. T(3) treatment also upregulates IGF-I protein secretion by vertebral marrow stromal cell cultures. Interestingly, the type I receptor for IGF-I was expressed equivalently in cultures from the two skeletal sites. These findings have important implications for the anatomical site specificities of hormonal responses that are noted in the skeleton.


A novel cell culture model for studying ischemia-reperfusion injury in lung transplantation.
Many cell culture models have been developed to study ischemia-reperfusion injury; however, none is specific to the conditions of lung preservation and transplantation. The objective of this study was to design a cell culture model that mimics clinical lung transplantation, in which preservation is aerobic and hypothermic. A549 cells, a human pulmonary epithelial cell line, were preserved in 100% O(2) at 4 degrees C for varying periods in low-potassium dextran glucose solution, simulating ischemia, followed by the introduction of warm (37 degrees C) DMEM plus 10% fetal bovine serum to simulate reperfusion. Cultures were assayed for cell attachment and viability. Sequential extension of ischemic times to 24 h showed a time-dependent loss of cells. There was a further decrease in cell number after simulated reperfusion. Cell detachment was due mainly to cell death, as determined by cell viability. The effects of chemical components such as dextran 40 and calcium in the preservation solution and various preservation gas mixtures were examined by use of this model system. With its design and validation, this model could be used to study mechanisms related to ischemia-reperfusion injury at the cellular and molecular level.


Guidelines and realities of asthma management. The Philadelphia story.
Guidelines from the National Heart, Lung, and Blood Institute, Bethesda, Md, have encouraged more frequent use of inhaled steroids in asthma management. To determine (1) whether prescription rates for inhaled steroids have increased compared with prescriptions for bronchodilators and (2) significant associations of demographic factors with bronchodilator-inhaled steroid prescription ratios and with rates of inhaled steroid prescriptions. Cross-sectional analysis of monthly bronchodilator and inhaled steroid prescription rates, numbers and types of asthma care providers, and demographic factors. Philadelphia, Pa. Using univariate and multivariate analyses, bronchodilator and inhaled steroid prescription rates were determined for 45 ZIP codes and studied for associations with race and ethnicity, poverty, educational attainment, marital status, gender, total numbers of asthma drug prescriptions, and numbers and types of asthma care providers. Monthly bronchodilator-inhaled steroid prescription ratios increased from July 1991 to June 1993 (P < .001). Prescription rates for inhaled steroids and inhaled bronchodilators declined, but rates for oral bronchodilators (beta-agonists and theophylline) increased. By stepwise multiple regression, higher bronchodilator-inhaled steroid prescription ratios and lower inhaled steroid prescription rates were each significantly associated with ZIP codes in which greater proportions of residents lacked a high school diploma (P < .001); associations that approached statistical significance were found for higher bronchodilator-inhaled steroid ratios and fewer asthma care providers (P = .05) and for lower inhaled steroid prescription rates and lower proportions of asthma specialists (P = .04). In Philadelphia, a gap exists between optimal asthma drug prescribing and actual prescribing patterns that has widened from July 1991 to June 1993. Underuse of inhaled steroids is most closely associated with lower educational attainment, suggesting that interventions that include addressing the special asthma care needs of a low-literacy population will be required to achieve the goals of the National Asthma Education Program.


Noncanonical autophagy inhibits the autoinflammatory, lupus-like response to dying cells.
Defects in clearance of dying cells have been proposed to underlie the pathogenesis of systemic lupus erythematosus (SLE). Mice lacking molecules associated with dying cell clearance develop SLE-like disease, and phagocytes from patients with SLE often display defective clearance and increased inflammatory cytokine production when exposed to dying cells in vitro. Previously, we and others described a form of noncanonical autophagy known as LC3-associated phagocytosis (LAP), in which phagosomes containing engulfed particles, including dying cells, recruit elements of the autophagy pathway to facilitate maturation of phagosomes and digestion of their contents. Genome-wide association studies have identified polymorphisms in the Atg5 (ref. 8) and possibly Atg7 (ref. 9) genes, involved in both canonical autophagy and LAP, as markers of a predisposition for SLE. Here we describe the consequences of defective LAP in vivo. Mice lacking any of several components of the LAP pathway show increased serum levels of inflammatory cytokines and autoantibodies, glomerular immune complex deposition, and evidence of kidney damage. When dying cells are injected into LAP-deficient mice, they are engulfed but not efficiently degraded and trigger acute elevation of pro-inflammatory cytokines but not anti-inflammatory interleukin (IL)-10. Repeated injection of dying cells into LAP-deficient, but not LAP-sufficient, mice accelerated the development of SLE-like disease, including increased serum levels of autoantibodies. By contrast, mice deficient in genes required for canonical autophagy but not LAP do not display defective dying cell clearance, inflammatory cytokine production, or SLE-like disease, and, like wild-type mice, produce IL-10 in response to dying cells. Therefore, defects in LAP, rather than canonical autophagy, can cause SLE-like phenomena, and may contribute to the pathogenesis of SLE.


A Fuzzy-Based Context-Aware Misbehavior Detecting Scheme for Detecting Rogue Nodes in Vehicular Ad Hoc Network.
A vehicular ad hoc network (VANET) is an emerging technology that improves road safety, traffic efficiency, and passenger comfort. VANETs' applications rely on co-operativeness among vehicles by periodically sharing their context information, such as position speed and acceleration, among others, at a high rate due to high vehicles mobility. However, rogue nodes, which exploit the co-operativeness feature and share false messages, can disrupt the fundamental operations of any potential application and cause the loss of people's lives and properties. Unfortunately, most of the current solutions cannot effectively detect rogue nodes due to the continuous context change and the inconsideration of dynamic data uncertainty during the identification. Although there are few context-aware solutions proposed for VANET, most of these solutions are data-centric. A vehicle is considered malicious if it shares false or inaccurate messages. Such a rule is fuzzy and not consistently accurate due to the dynamic uncertainty of the vehicular context, which leads to a poor detection rate. To this end, this study proposed a fuzzy-based context-aware detection model to improve the overall detection performance. A fuzzy inference system is constructed to evaluate the vehicles based on their generated information. The output of the proposed fuzzy inference system is used to build a dynamic context reference based on the proposed fuzzy inference system. Vehicles are classified into either honest or rogue nodes based on the deviation of their evaluation scores calculated using the proposed fuzzy inference system from the context reference. Extensive experiments were carried out to evaluate the proposed model. Results show that the proposed model outperforms the state-of-the-art models. It achieves a 7.88% improvement in the overall performance, while a 16.46% improvement is attained for detection rate compared to the state-of-the-art model. The proposed model can be used to evict the rogue nodes, and thus improve the safety and traffic efficiency of crewed or uncrewed vehicles designed for different environments, land, naval, or air.


Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions.
Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.


Patterns of whole-body muscle activations following vertical perturbations during standing and walking.
Falls commonly occur due to losses of balance associated with vertical body movements (e.g. reacting to uneven ground, street curbs). Research, however, has focused on horizontal perturbations, such as forward and backward translations of the standing surface. This study describes and compares muscle activation patterns following vertical and horizontal perturbations during standing and walking, and investigates the role of vision during standing postural responses. Fourteen healthy participants (ten males; 27±4 years-old) responded to downward, upward, forward, and backward perturbations while standing and walking in a virtual reality (VR) facility containing a moveable platform with an embedded treadmill; participants were also exposed to visual perturbations in which only the virtual scenery moved. We collected bilateral surface electromyography (EMG) signals from 8 muscles (tibialis anterior, rectus femoris, rectus abdominis, external oblique, gastrocnemius, biceps femoris, paraspinals, deltoids). Parameters included onset latency, duration of activation, and activation magnitude. Standing perturbations comprised dynamic-camera (congruent), static-camera (incongruent) and eyes-closed sensory conditions. ANOVAs were used to compare the effects of perturbation direction and sensory condition across muscles. Vertical perturbations induced longer onset latencies and shorter durations of activation with lower activation magnitudes in comparison to horizontal perturbations (p<0.0001). Downward perturbations while standing generated earlier activation of anterior muscles to facilitate flexion (for example, p=0.0005 and p=0.0021 when comparing the early activators, rectus femoris and tibialis anterior, to a late activator, the paraspinals), whereas upward perturbations generated earlier activation of posterior muscles to facilitate extension (for example, p<0.0001 and p=0.0004, when comparing the early activators, biceps femoris and gastrocnemius, to a late activator, the rectus abdominis). Static-camera conditions induced longer onset latencies (p=0.0085 and p<0.0001 compared to eyes-closed and dynamic-camera conditions, respectively), whereas eyes-closed conditions induced longer durations of activation (p=0.0001 and p=0.0008 compared to static-camera and dynamic-camera, respectively) and larger activation magnitudes. During walking, downward perturbations promptly activated contralateral trunk and deltoid muscles (e.g., p=0.0036 for contralateral deltoid versus a late activator, the ipsilateral tibialis anterior), and upward perturbations triggered early activation of trunk flexors (e.g., p=0.0308 for contralateral rectus abdominis versus a late activator, the ipsilateral gastrocnemius). Visual perturbations elicited muscle activation in 67.7% of trials. Our results demonstrate that vertical (vs. horizontal) perturbations generate unique balance-correcting muscle activations, which were consistent with counteracting vertical body extension induced by downward perturbations and vertical body flexion induced by upward perturbations. Availability of visual input appears to affect response efficiency, and incongruent visual input can adversely affect response triggering. Our findings have clinical implications for the design of robotic exoskeletons (to ensure user safety in dynamic balance environments) and for perturbation-based balance and gait rehabilitation.


Survey of dermatological conditions in a population of domestic dogs in Mashhad, northeast of Iran (2007-2011).
university small animal clinic, 1299 Iranian domestic dogs presented from September 2007 through March 2011 to the Ferdowsi University of Mashhad Veterinary Teaching Hospital, were examined. Dermatological disorders were noted in 17.00% (221/1299) of all the dogs examined. Pruritus was the most common presenting sign, accounting for 25.35% of the dermatological consultations. It was followed by erythema, maculo-papular-pustular eruptions (16.97%), erosive or ulcerative lesions (16.74%), scaling or crusting (13.02%), alopecia (8.84%) and visible ectoparasites (7.44%). The most common primary final diagnoses were superficial pyoderma, cutaneous manifestations of canine leishmaniasis, flea infestation and allergy, tick infestation, atopic dermatitis, scabies, unspecified dermatoses, otitis, furunculosis and food allergy. There were no apparent age or sex predilections for dermatological disease as a whole. Spitz (odds ratio = 3.38; p = 0.001), Terriers (odds ratio = 2.52; p < 0.001) and German Shepherds (odds ratio = 1.90; p = 0.001) appeared to be at increased risk for dermatological disease. In addition, Khorasani large cross breed dogs (odds ratio = 0.36; p = 0.003) and mixed breed dogs (odds ratio = 0.33; p < 0.001) showed decreased risk for dermatological conditions. To the best of our knowledge, this is the first survey study on canine dermatological conditions carried out in Iran.


In Vivo 2-Hydroxyglutarate Monitoring With Edited MR Spectroscopy for the Follow-up of IDH-Mutant Diffuse Gliomas: The IDASPE Prospective Study.
D-2-hydroxyglutarate (2HG) characterizes IDH-mutant gliomas and can be detected and quantified with edited MRS (MEGA-PRESS). In this study, we investigated the clinical, radiologic, and molecular parameters affecting 2HG levels. MEGA-PRESS data were acquired in 71 patients with glioma (24 untreated, 47 treated) on a 3 T system. Eighteen patients were followed during cytotoxic (n = 12) or targeted (n = 6) therapy. 2HG was measured in tumor samples using gas chromatography coupled to mass spectrometry (GCMS). MEGA-PRESS detected 2HG with a sensitivity of 95% in untreated patients and 62% in treated patients. Sensitivity depended on tumor volume (>27 cm3; p = 0.02), voxel coverage (>75%; p = 0.002), and expansive presentation (defined by equal size of T1 and FLAIR abnormalities, p = 0.04). 2HG levels were positively correlated with IDH-mutant allelic fraction (p = 0.03) and total choline levels (p < 0.001) and were higher in IDH2-mutant compared with IDH1 R132H-mutant and non-R132H IDH1-mutant patients (p = 0.002). In patients receiving IDH inhibitors, 2HG levels decreased within a few days, demonstrating the on-target effect of the drug, but 2HG level decrease did not predict tumor response. Patients receiving cytotoxic treatments showed a slower decrease in 2HG levels, consistent with tumor response and occurring before any tumor volume change on conventional MRI. At progression, 1p/19q codeleted gliomas, but not the non-codeleted, showed detectable in vivo 2HG levels, pointing out to different modes of progression characterizing these 2 entities. MEGA-PRESS edited MRS allows in vivo monitoring of 2-hydroxyglutarate, confirming efficacy of IDH inhibition and suggests different patterns of tumor progression in astrocytomas compared with oligodendrogliomas.


Genetic analysis of the population structure of socially organized oystercatchers (Haematopus ostralegus) using microsatellites.
On the island of Schiermonnikoog (The Netherlands), the breeding population of oystercatchers can be divided into two groups: 'residents' and 'leapfrogs', based on their distinct social characteristics and limited probabilities of status change between breeding seasons. In order to investigate whether this social organization has caused local genetic differentiation, leapfrogs and residents were compared at eight polymorphic microsatellite loci. No significant genetic subdivision between residents and leapfrogs was observed (theta = 0.0000; 95% confidence interval (CI), -0.0027-0.0033), indicating that the oystercatcher population on the island of Schiermonnikoog has to be considered as one panmictic unit. Investigation of three additional locations in the northern part of The Netherlands did not reveal significant genetic population subdivision either (theta = -0.0005; 95% CI, -0.0045-0.0037), despite the fact that adult osytercatchers show extreme fidelity to their breeding localities. These results indicate panmixis and considerable levels of gene flow within the northern part of The Netherlands. Thus, the results from genetical analyses do not seem to be in agreement with observational data on the dispersal behaviour of breeding individuals. It is argued that the lack of population structure, locally on Schiermonnikoog as well as across larger geographical distances, is to be attributed to high levels of gene flow through dispersal of juvenile birds.


Demographic and behavioural risk factors associated with Trichomonas vaginalis among South African HIV-positive men with genital ulcer disease: a cross-sectional study.
Demographic and risky sexual behaviours may increase the risk for Trichomonas vaginalis (TV) infection and, thus, enhance HIV transmission to uninfected partners. We assessed the demographic and behavioural risk factors associated with TV among South African HIV-positive men with genital ulcer disease. We conducted a cross-sectional study with data from a randomised controlled trial conducted by the Centers for Disease Control and Prevention and the London School of Hygiene and Tropical Medicine. The data were obtained from three primary healthcare clinics in South Africa. At baseline (n=387), participants reported on demographics, sexual behaviour, history of sexually transmitted infections and clinical ulcers. The outcome TV was measured using real-time multiplex PCR assays and a Rotor-gene 3000 platform from the first and past urine samples of all participants. Logistic regression model estimated ORs and 95% CIs adjusted for demographics, sexual risk behaviours and ulcer conditions. An estimated 11.4% of TV was detected among the men. The odds of TV infection were significantly associated with high blister counts (OR 4.0, 95% CI 1.6 to 28, p=0.01), ulcer pain (OR 0.4, 95% CI 0.2 to 0.7, p=0.003), number of days with ulcers (OR 0.4, 95% CI 0.2 to 0.8, p=0.006), sought treatment before coming into clinics (OR 0.07, 95% CI 0.002 to 0.7, p=0.005) and being unqualified worker (OR 2.5, 95% CI 0.9 to 6.7 p=0.05). Multivariate analyses revealed that increased days with ulcers (OR 0.1, 95% CI 0.04 to 0.5, p=0.002) and ulcer pain intensity (OR 0.08, 95% CI 0.007 to 1.1, p=0.05) remained significantly associated with decreased odds of TV infection. Men from the Sotho ethnic group were eight times more likely to have TV infection (OR 8.6, 95% CI 1.3 to 55.7, p<0.02) than men from the other ethnic groups. HIV-positive men with severe ulceration should be screened and treated for TV to minimise HIV transmission to uninfected partners.


[Surveillance study on use of over-the-counter drug and health food by school pharmacist for grade-schooler, junior high school student, and high school students].
In recent years, it is necessary to acquire knowledge not only about medicine but also over-the-counter (OTC) drugs and health food for children, because lowering trend in the age of the health hazard by improper use of health food is reported. Therefore, in order to estimate the extent of use of OTC drugs and health food, the school pharmacists administered a questionnaire to students in grade-school (n=123), junior high school (n=303), and high school (n=115) in Fukuyama city. As a result of the questionnaire survey, surprisingly, the usage ratio of OTC drugs and health food showed the most increase in grade-schooler. The trigger of use of health food is "parents' recommendations" in the lower grades, otherwise the ratio of "use by themselves" was increased in the higher grades. Moreover, a remarkable difference was observed by the kinds of use in students with or without exercise. Interestingly, exercise group expected "physical strength" effects than no exercise group. In addition, the ratio of consultation to the pharmacist at the time of purchase of OTC drugs and health food was low in all grade students. In particular, the ratio of consultation to the pharmacist at the time of purchase of health food was very low in high school students. Therefore, to provide accurate information of medicine and health food for students, the school pharmacist should engage not only in routine work but also in positive guidance about OTC drugs and health food in the future.


Phylogeography of two European newt species--discordance between mtDNA and morphology.
The newts Triturus vulgaris and Triturus montandoni are sister species that exhibit contrasting levels of intraspecific morphological variation. Triturus vulgaris has a broad Eurasiatic distribution encompassing both formerly glaciated and unglaciated areas and shows substantial morphological differentiation in the southern part of its range, while T. montandoni, confined to the Carpathians, is morphologically uniform. We analysed sequence variation of two mtDNA fragments of the total length of c. 1850 bp in 285 individuals of both species collected from 103 localities. Phylogenetic analysis of 200 unique haplotypes defined 12 major clades, their age estimated at c. 4.5-1.0 million years (Myr). Most of the older clades were found in the southern part of the range, and also in central Europe, mainly in Romania. The distribution of mtDNA clades points to the existence of several glacial refugia, located in the Caucasus region, Anatolia, the Balkan Peninsula, Italy, and more to the north in central Europe. The concordance between mtDNA based phylogeny and the distribution of T. vulgaris subspecies was weak. Triturus montandoni haplotypes did not form a monophyletic group. Instead they were found in six clades, in five of them mixed with T. vulgaris haplotypes, most likely as a result of past or ongoing hybridization and multiple introgression of mtDNA from T. vulgaris to T. montandoni. Patterns of sequence variation within clades suggested long-term demographic stability in the southern groups, moderate and relatively old demographic growth in the populations inhabiting central Europe, and high growth in some of the groups that colonized northern parts of Europe after the last glacial maximum.


Prevalence of delayed hypersensitivity to the European standard series in a self-selected population.
There are limited reports of the prevalence of positive reactions in healthy adults to patch tests with standard allergens; there are no recent comprehensive studies from Australia. Healthy adult volunteers (n = 219) from the Western Australian community were patch tested using the European standard series of allergens. Seventy-seven (35%) reacted to at least one allergen, positive patch tests being most prevalent to nickel sulfate (20%), potassium dichromate (9%), cobalt chloride (6%) and fragrance mix (4%). Prevalence of positive patch tests to nickel and chromate was higher than that reported for another healthy population, which may stem from self-selection of volunteers or geographical differences, including extent of exposure to allergens.


Diffusion, Interactions, and Disparate Kinetic Trapping of Water-Hydrocarbon Mixtures in Nanoporous Solids.
Mixed fluids confined in porous solid hosts present challenges for the accurate characterization of individual-component behavior. NMR diffusometry with chemical resolution is used to identify unexpected loading- and composition-dependent anomalous diffusion in water/cyclohexane mixtures confined to solid nanoporous glass (NPG) hosts. Diffusion NMR results indicate that data obtained on pure-component liquids in confinement cannot be extrapolated to their nonideal liquid mixtures confined in the same solid host. Loading-dependent data must be obtained on each component in the confined mixture in order to determine which of the liquid components exhibits chemical affinity for the host and, conversely, which of the components exhibits anomalous diffusivity. Most notably, NMR diffusometry revealed that cyclohexane diffusivity varied by 2 orders of magnitude in a water-rich mixture depending on the total fluid loading in the NPG host, ranging from anomalously high diffusivities that significantly exceeded that for pure cyclohexane in NPG at low fluid loadings to kinetically trapped sequestration at high fluid loadings. NMR diffusometry indicates that nonideal solution behavior in fluids confined within nanoporous hosts may have practical implications for enhanced oil recovery methods. Specifically, kinetic trapping of hydrocarbons in water-flooding regimes can result from complex liquid-vapor equilibrium that is significantly perturbed from that which exists in bulk or microporous confinement.


Neural circuit-dependent odor adaptation in C. elegans is regulated by the Ras-MAPK pathway.
The molecular machinery that mediates odor adaptation in the olfactory neurons is well documented in various animal species. However, types of adaptation that depend on neural circuits are mostly unexplored. We report here that the Ras-MAPK pathway is essential for such a type of odor adaptation, called early adaptation, in C. elegans. Early adaptation requires a pair of AIY interneurons, which receive synaptic inputs from olfactory neurons. Mutants of the Ras-MAPK pathway show defects in early adaptation. Continued exposure to an odorant causes activation of MAP kinase not only in the olfactory neurons, but also in the AIY interneurons. While activity of the Ras-MAPK pathway in the olfactory neurons is important for odor perception, its activity in the AIY interneurons is important for odor adaptation. Our results thus reveal a dual role of the Ras-MAPK pathway in sensory processing in the nervous system of C. elegans.


What Would Justice Blackmun Say? A Response to Dobbs.
Dobbs appears more extreme when juxtaposed against Roe's hidden history. Justice Blackmun was the author of Roe, but the opinion was the product of a remarkable collaboration that incorporated the suggestions of many Justices. Thus, Roe's medical framing embodied the vision of the Court as a whole, not one individual.


[A validated questionnaire for measuring patient satisfaction in general and specialist ambulatory medical care: the Qualiskope-A].
To develop a reliable and valid questionnaire to measure patient satisfaction in ambulatory care, enabling a detailed analysis of the determinants of patient satisfaction that is applicable in GP and specialist outpatient care. Questionnaire with 27 single items subdivided into four categories: "professional competence", "physician-patient interaction", "information", and "practice organisation". Survey of 3,487 patients in 123 medical practices. 1,151 patients were in specialist care and 2,336 patients in general medical care. Qualiskope-A is a reliable and valid instrument for measuring patient satisfaction in ambulatory care. All item-total correlations for single items were greater than r = 0.40. Coefficients for Cronbach's alpha for the four dimensions ranged between 0.87 and 0.94. The increasing political importance of patients' attitudes and satisfaction for the development of policy measures to ensure and improve the quality of care is beyond doubt. To make sure that the measurement of patient satisfaction does not only serve to meet regulatory requirements but helps to improve the quality of care and provides reliable data for health services research, a high standard is required for the questionnaires to be used. The Qualiskope-A and only few other instruments meet this high standard.


Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia.
Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited eye disease characterized by progressive degeneration of photoreceptors. Recently, immune cells, including microglia, Müller cells and astrocytes, in degenerative retina are demonstrated to play key roles in the development of RD and can be used as potential therapeutic targets. Liver X receptors (LXRs) are important immuno-inflammatory response transcription factors that have been reported to be a new potential therapeutic drug target for neurodegenerative diseases. However, the potential therapeutic utility of LXRs for RP has not been evaluated. In the present study, Pde6β (rd1) mice received intraperitoneal injections of T0901317 (T0, 50 mg/kg/d) or vehicle (2% DMSO) for 7 days with age-matched C57/BL6 mice as controls. The effect of T0 was examined by quantitating photoreceptor apoptosis, microglial density and the expression of inflammatory mediators; the underlying mechanisms were then explored with a microarray assay. T0 markedly delayed apoptosis of the photoreceptors, partially through suppressing the activation of microglia and the gliosis of Müller cells, and decreased the expression levels of IL-6, iNOS, COX-2 and ENG in rd1 mice; as a result, the visual function of T0-treated rd1 mice measured with electroretinograms (ERG) was preserved for a longer time than that of vehicle-treated rd1 mice. The microarray assay showed that the Janus kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway was significantly affected in the retina of rd1 mice with T0 treatment. Our data suggested that T0 modulated the immunologic function of glia cells in the degenerative retina through the JAK3/STAT pathway and delayed the apoptosis of photoreceptors.


Effects of two fungicide formulations on microbial and macroinvertebrate leaf decomposition under laboratory conditions.
Aquatic fungi contribute significantly to the decomposition of leaves in streams, a key ecosystem service. Little is known, however, about the effects of fungicides on aquatic fungi and macroinvertebrates involved with leaf decomposition. Red maple (Acer rubrum) leaves were conditioned in a stream to acquire microbes (bacteria and fungi) or leached in tap water (unconditioned) to simulate potential reduction of microbial biomass by fungicides. Conditioned leaves were exposed to fungicide formulations QUILT (azoxystrobin + propiconazole) or PRISTINE (boscalid + pyraclostrobin) in the presence and absence of the leaf shredder, Hyalella azteca (amphipods; 7-d old at start of exposures) for 14 d at 23 °C. The QUILT formulations (∼0.3 μg/L, 1.8 μg/L, and 8 μg/L) tended to increase leaf decomposition by amphipods (not significant) without a concomitant increase in amphipod biomass, indicating potential increased consumption of leaves with reduced nutritional value. The PRISTINE formulation (∼33 μg/L) significantly reduced amphipod growth and biomass (p < 0.05), effects similar to those observed with unconditioned controls. The significant suppressive effects of PRISTINE on amphipod growth and the trend toward increased leaf decomposition with increasing QUILT concentration indicate the potential for altered leaf decay in streams exposed to fungicides. Further work is needed to evaluate fungicide effects on leaf decomposition under conditions relevant to stream ecosystems, including temperature shifts and pulsed exposures to pesticide mixtures. Environ Toxicol Chem 2016;35:2834-2844. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America.


Urban transmission of Chagas disease in Cochabamba, Bolivia.
Chagas disease is a major public health problem in Bolivia. In the city of Cochabamba, 58% of the population lives in peripheral urban districts ("popular zones") where the infection prevalence is extremely high. From 1995 to 1999, we studied the demographics of Chagas infections in children from five to 13 years old (n = 2218) from the South zone (SZ) and North zone (NZ) districts, which differ in social, environmental, and agricultural conditions. Information gathered from these districts demonstrates qualitative and quantitative evidence for the active transmission of Trypanosoma cruzi in urban Cochabamba. Seropositivity was high in both zones (25% in SZ and 19% in NZ). We observed a high risk of infection in children from five to nine years old in SZ, but in NZ, a higher risk occurred in children aged 10-13, with odds ratio for infection three times higher in NZ than in SZ. This difference was not due to triatomine density, since more than 1,000 Triatoma infestans were captured in both zones, but was possibly secondary to the vector infection rate (79% in SZ and 37% in NZ). Electrocardiogram abnormalities were found to be prevalent in children and pre-adolescents (SZ = 40%, NZ = 17%), indicating that under continuous exposure to infection and re-infection, a severe form of the disease may develop early in life. This work demonstrates that T. cruzi infection should also be considered an urban health problem and is not restricted to the rural areas and small villages of Bolivia.


Alterations in empathic responding among women with posttraumatic stress disorder associated with childhood trauma.
Although studies increasingly point toward problems with social cognition among individuals with posttraumatic stress disorder (PTSD), few studies have assessed empathic responding. The aim of the current study was to investigate empathic responding in women with PTSD related to childhood trauma, and the contribution of parental bonding to empathic abilities in this sample. Participants with PTSD (n = 29) and sex- and age-matched healthy controls (n = 20) completed two self-report empathy measures, the Interpersonal Reactivity Index (IRI) and the Toronto Empathy Questionnaire (TEQ), and a self-report measure of attachment, the Parental Bonding Instrument (PBI). Women with PTSD, relative to controls, reported significantly lower levels of empathic concern (r = 0.29) and perspective taking (r = 0.30), yet significantly higher levels of personal distress (r = 0.45) on the IRI. Women with PTSD also reported elevated scores on the TEQ (η (2) = 0.13). Levels of paternal care on the PBI, rather than childhood trauma severity or PTSD symptom severity best predicted perspective taking scores on the IRI in the PTSD sample (R (2) = 0.20). Women with PTSD associated with childhood trauma reported alterations among different domains of empathic functioning that may be related to low levels of paternal care.


Recruitment and retention in an SMS-based health education program: Lessons learned from Text2BHealthy.
While text messages or short messaging service programs are increasingly utilized for delivering health education, few studies have explored the unique challenges of recruiting and retaining participants in such programs. This study utilizes survey and focus group data from Text2BHealthy, a short messaging service-based nutrition and physical activity promotion program, to examine barriers to enrollment and facilitators of retention among parents of elementary school students. Results show that participants were hard to reach with recruitment materials, had difficulty with self-enrollment, and were apprehensive about program costs. However, 89-90 percent of participants were retained. Results suggest that providing manual enrollment options, alternative program delivery methods (e.g. email messages), and opportunities to reenroll may facilitate participation in short messaging service-based health education and promotion programs.


Effects of the US Food and Drug Administration Boxed Warning of Erythropoietin-Stimulating Agents on Utilization and Adverse Outcome.
Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.


Immunity to melanin and to tyrosinase in melanoma patients, and in people with vitiligo.
The aim of this study was to determine the presence and the intensity of humoral immunity to melanoma-associated antigens: tyrosinase and melanin, in patients with melanoma, in persons with vitiligo and in control healthy people. The study involved 63 patients with melanoma and 19 persons with vitiligo. Control group consisted up to 41 healthy volunteers. Mushroom tyrosinase and synthetic melanin were used as the antigens. ELISA test showed significantly (p < 0.0000004 and p < 0.04) lower levels of IgM anti-tyrosinase autoantibodies, in melanoma and vitiligo patients respectively, compared to controls.Although there was no significant difference between the levels of IgA anti-melanin autoantibodies in melanoma or vitiligo patients in comparison with controls, the enhanced concentrations of anti-melanin IgA autoantibodies were preferentially found in melanoma patients with metastatic disease. Significantly high percentage in the Fc alphaRI (CD89) positive cells was determined in melanoma patients (p < 0.002 and p < 0.008) in comparison to that found in healthy people or in patients with vitiligo, in the already mentioned order, pointing that IgA dependent cellular cytotoxicity is not important for the immune action against melanoma, even more that it is included in some immune suppression.Levels of IgG autoantibodies to mentioned antigens in melanoma patients although low were not significantly lower from controls. These findings analyzed together with the statistically significant low percentage of FcgammaRIII, (CD16) positive immunocompetent cells (p < 0.0007 and p < 0.003), which was found in patients with melanoma compared with healthy or vitiligo people respectively, and statistically significant low percentage of (CD16 + CD56+) natural killer (NK) cells (p < 0.005) found in melanoma patients in comparison to healthy controls pointed to the low probability for anti-melanoma IgG mediated, antibody mediated cellular cytotoxicity, (ADCC) and NK cytotoxicity. Moreover the ratio of the percentages of granulocytes and percentage of lymphocytes was statistically higher in patients with melanoma in relation to healthy people as well as to people with vitiligo (p < 0.0007 and p < 0.05 respectively). Autoantibodies to tyrosinase and to melanin which are found even in healthy people, point that consummation of edible mushrooms that carry the antigen tyrosinase and melanin, could influence the humoral anti-melanoma immune response.Levels of different immunoglobulin classes of anti-melanin and anti-tyrosinase antibodies varied depending on the presence and the stage of studied diseases. Besides, the statistically enhanced ratio of the percentages of granulocytes and percentage of lymphocytes, together with statistically decreased percentage of NK cells is found in analyzed melanoma patients.


A genome-wide map of adeno-associated virus-mediated human gene targeting.
To determine which genomic features promote homologous recombination, we created a genome-wide map of gene targeting sites. We used an adeno-associated virus vector to target identical loci introduced as transcriptionally active retroviral vectors. A comparison of ~2,000 targeted and untargeted sites showed that targeting occurred throughout the human genome and was not influenced by the presence of nearby CpG islands, sequence repeats or DNase I-hypersensitive sites. Targeted sites were preferentially located within transcription units, especially when the target loci were transcribed in the opposite orientation to their surrounding chromosomal genes. We determined the impact of DNA replication by mapping replication forks, which revealed a preference for recombination at target loci transcribed toward an incoming fork. Our results constitute the first genome-wide screen of gene targeting in mammalian cells and demonstrate a strong recombinogenic effect of colliding polymerases.


Horizontal partial laryngectomy for supraglottic squamous cell carcinoma.
Between 1981-1999, 75 patients treated for supraglottic SCC with horizontal supraglottic laryngectomy (HSL) at the Otolaryngology Head and Neck Surgery Department of Lausanne University Hospital were retrospectively studied. There were 16 patients with T1, 46 with T2 and 13 with T3 tumors. Among these, 16 patients (21%) had clinical neck disease corresponding to stage I, II, III and IV in 12, 39, 18 and 6 patients, respectively. All patients had HSL. Most patients had either elective or therapeutic bilateral level II-IV selective neck dissection. Six patients (8%) with advanced neck disease had ipsilateral radical and controlateral elective II-IV selective neck dissections. Adjuvant radiotherapy was given to 25 patients (30%) for either positive surgical margins (n=8), pathological nodal status (n=14) or both (n=3). Median follow-up was 48 months (range, 24-199). Five-year disease-specific survival and locoregional and local control were 92, 90 and 92.5%, respectively. Among five patients who were diagnosed with local recurrence, one had a total laryngectomy (1.4%); the others were treated by endoscopic laser surgery. Two patients had both a local and regional recurrence. They were salvaged with combined surgery and radiotherapy, but eventually died of their disease. Cartilage infiltration seems to influence both local control (P=0.03) and disease-specific survival (P=0.06). There was a trend for worse survival with pathological node involvement (P=0.15) and extralaryngeal extension of the cancer (P=0.1). All patients except one recovered a close to normal function after the treatment. Aspiration was present in 16 patients (26%) in the early postoperative period. A median of 16 days (7-9) was necessary to recover a close to normal diet. Decannulation took a median of 17 days (8-93). Seven patients kept a tracheotomy tube for up to 3 months because of persistent aspiration. There was no permanent tracheostomy or total laryngectomy for functional purposes. Horizontal supraglottic laryngectomy remains an adequate therapeutic alternative for supraglottic squamous cell carcinoma, offering an excellent oncological outcome. The postoperative functional morbidity is substantial, indicating the need for careful patient selection, but good laryngeal function recovery is the rule. The surgical alternative is endoscopic laser surgery, which may offer comparable oncological results with less functional morbidity. Nevertheless, these two different techniques need to be compared prospectively.


A report of human papilloma virus-16 associated vaginal carcinoma after thirty-two years of successful radiation therapy for cervical cancer.
Once the recommended 5-year recurrence-free follow-up is achieved for cervical cancers regular annual pelvic examination is mandatory. The main aim of presenting this short report is to emphasize the difficulties in the collection and interpretation of cytology samples from stenosed cervix or vault after pelvic irradiation. Radiotherapy can induce changes in the cellular morphology which may persist for many years. A 64-year old post-menopausal lady who had received radiation therapy 32 years back for cervical carcinoma stage IIb presented to the Gynecology outpatient department with vaginal spotting. Even though the patient was under regular follow-up for the initial 2 years, she was lost to further follow-ups. The patient was symptom-free except for one episode of spotting in August 2016 and the histopathological examination of the vault smear had ruled out malignancy. However, 1 month later she again presented with spotting and pelvic examination revealed a warty growth at the lateral vaginal wall. The tissue excision biopsy was tested positive for HPV-16 DNA and the histopathology confirmed vaginal squamous cell carcinoma. The association of human papilloma virus (HPV) in cervical cancers was well established and these patients manifest a higher risk of HPV-induced vaginal cancers. HPV DNA testing during follow-up may facilitate early recognition of HPV-related lower genital tract cancers.


Exploring Patterns of the Use of Electronic Nicotine Delivery Systems among Adolescents in High-Risk Appalachian (U.S.A) Communities.
Background: Electronic nicotine delivery systems (ENDS) use among adolescents in the United States (U.S.) has surpassed conventional tobacco products (CTPs), including cigarettes. Increasingly, ENDS are used concurrently with CTPs and substances such as cannabis. However, few studies involve Central Appalachia, a region with historically high rates of tobacco and other substance use. Objective: To examine prevalence of concurrent use of ENDS and cannabis among school-going adolescents in Appalachian Tennessee and delineate associations between ENDS use and substance-related risk behavior (cannabis use), social relations (peer use), and school-related risk behavior (academic performance). Methods: Data were obtained from a survey conducted with youth aged 13-17 years in 2018 in a county in Appalachian Tennessee (n = 280). A multivariable logistic regression model was fit to evaluate associations between ENDS and cannabis use, and other factors. Results: Overall, lifetime ENDS and cannabis prevalence estimates were 31.1% and 18.6%, respectively. Lifetime ENDS users had increased odds of also being lifetime cannabis users [OR = 9.22, 95% confidence interval (CI): 3.44-24.75]. Lifetime ENDS users had increased odds of reporting ENDS use among peers [OR = 12.11; 95% CI: 5.40-27.12] and lower academic performance (OR associated with mostly C or D vs. A grades was 4.28, 95% CI: 1.68-10.90). Conclusion: This study found an association between ENDS and cannabis use among adolescents in Appalachian Tennessee exists. Additionally, peer use and academic performance were associated with ENDS use. The findings have implications for public health intervention planning to address not only ENDS but also substance use among Appalachian youth.


Tegumental ultrastructure of adult Gynaecotyla squatarolae (Digenea: Microphallidae).
Gynaecotyla squatarolae (Digenea: Microphallidae) adult flukes were recovered from experimental chicks at day 4-6 post-infection and their tegumental ultrastructure was observed with a scanning electron microscopy. They were pyriform in shape, and their anterior halves were concaved ventrally. The whole body surface was covered with tegumental spines, which were wide and 16-17 digitated between oral and ventral suckers. The density of spines and number of digits decreased posteriorly. The oral sucker was subterminal and the excretory pore was at the posterior end of the worm. Two ventral suckers were similar in appearance and protruded near midline of the worm. The genital atrium was dextral to the small ventral sucker. The dorsal surface was covered with tegumental spines, but the spines were sparser than on the ventral surface. On the middle portion of the dorsal surface, a small opening presumed to be the Laurer's canal was seen. From these findings, it has been confirmed that the adult G. squatarolae has unique characteristics in the surface ultrastructure.


Clearance of Neutrophils From ICH-Affected Brain by Macrophages Is Beneficial and Is Assisted by Lactoferrin and CD91.
Within hours after intracerebral hemorrhage (ICH) onset, masses of polymorphonuclear neutrophils (PMNs) infiltrate the ICH-affected brain. After degranulation involving controlled release of many toxic antimicrobial molecules, the PMNs undergo rapid apoptosis and then are removed by phagocytic microglia/macrophages (MΦ) through a process called efferocytosis. Effective removal of PMNs may limit secondary brain damage and inflammation; however, the molecular mechanisms governing these cleanup activities are not well understood. We propose that scavenger receptor CD91 on myeloid phagocytes especially in presence of CD91 ligand, LTF (lactoferrin, protein abundant in PMNs), plays an important role in clearance of dead apoptotic PMNs (ANs). Mice/rats were subjected to an autologous blood injection model of ICH. Primary cultured microglia were used to assess phagocytosis of ANs. Immunohistochemistry was employed to assess CD91 expression and PMN infiltration. CD91 knockout mice selectively in myeloid phagocytes (Mac-CD91-KO) were used to establish the CD91/LTF function in phagocytosis and in reducing ICH-induced injury, as assessed using behavioral tests, hematoma resolution, and oxidative stress. Masses of PMNs are found in ICH-affected brain, and they contain LTF. MΦ at the outer border of hematoma are densely packed, expressing CD91 and phagocytosing ANs. Microglia deficient in CD91 demonstrate defective phagocytosis of ANs, and mice deficient in CD91 (Mac-CD91-KO) subjected to ICH injury have increased neurological dysfunction that is associated with impaired hematoma resolution (hemoglobin and iron clearance) and elevated oxidative stress. LTF that normally ameliorates ICH injury in CD91-proficient control mice shows reduced therapeutic effects in Mac-CD91-KO mice. Our study suggests that CD91 plays a beneficial role in improving ANs phagocytosis and ultimately post-ICH outcome and that the beneficial effect of LTF in ICH is in part dependent on presence of CD91 on MΦ.