Patient Perspectives of Midlevel Providers in Orthopaedic Sports Medicine.
Midlevel providers (eg, nurse practitioners and physician assistants) have been integrated into orthopaedic systems of care in response to the increasing demand for musculoskeletal care. Few studies have examined patient perspectives toward midlevel providers in orthopaedic sports medicine. To identify perspectives of orthopaedic sports medicine patients regarding midlevel providers, including optimal scope of practice, reimbursement equity with physicians, and importance of the physician's midlevel provider to patients when initially selecting a physician. Cross-sectional study; Level of evidence, 3. A total of 690 consecutive new patients of 3 orthopaedic sports medicine physicians were prospectively administered an anonymous questionnaire prior to their first visit. Content included patient perspectives regarding midlevel provider importance in physician selection, optimal scope of practice, and reimbursement equity with physicians. Of the 690 consecutive patients who were administered the survey, 605 (87.7%) responded. Of these, 51.9% were men and 48.1% were women, with a mean age of 40.5 ± 15.7 years. More than half (51.2%) perceived no differences in training levels between physician assistants and nurse practitioners. A majority of patients (62.9%) reported that the physician's midlevel provider is an important consideration when choosing a new orthopaedic sports medicine physician. Patients had specific preferences regarding which services should be physician provided. Patients also reported specific preferences regarding those services that could be midlevel provided. There lacked a consensus on reimbursement equity for midlevel practitioners and physicians, despite 71.7% of patients responding that the physician provides a higher-quality consultation. As health care becomes value driven and consumer-centric, understanding patient perspectives on midlevel providers will allow orthopaedic sports medicine physicians to optimize efficiency and patient satisfaction. Physicians may consider these data in clinical workforce planning, as patients preferred specific services to be physician or midlevel provided. It may be worthwhile to consider midlevel providers in marketing efforts, given that patients considered the credentials of the physician's midlevel provider when initially selecting a new physician. Patients lacked consensus regarding reimbursement equity between physicians and midlevel providers, despite responding that the physician provides a higher-quality consultation. Our findings are important for understanding the midlevel workforce as it continues to grow in response to the increasing demand for orthopaedic sports care.


Protective effects of Brazilian propolis supplementation on capillary regression in the soleus muscle of hindlimb-unloaded rats.
The protective effects of Brazilian propolis on capillary regression induced by chronically neuromuscular inactivity were investigated in rat soleus muscle. Four groups of male Wistar rat were used in this study; control (CON), control plus Brazilian propolis supplementation (CON + PP), 2-week hindlimb unloading (HU), and 2-week hindlimb unloading plus Brazilian propolis supplementation (HU + PP). The rats in the CON + PP and HU + PP groups received two oral doses of 500 mg/kg Brazilian propolis daily (total daily dose 1000 mg/kg) for 2 weeks. Unloading resulted in a decrease in capillary number, luminal diameter, and capillary volume, and an increase in the expression of anti-angiogenic factors, such as p53 and TSP-1, within the soleus muscle. Brazilian propolis supplementation, however, prevented these changes in capillary structure due to unloading through the stimulation of pro-angiogenic factors and suppression of anti-angiogenic factors. These results suggest that Brazilian propolis is a potential non-drug therapeutic agent against capillary regression induced by chronic unloading.


Evaluation of HEMA released from four different adhesive systems by HPLC.
This study evaluated the elution of 2-hydroxyethyl methacrylate (HEMA) from 4 different adhesives, using high-performance liquid chromatography (HPLC). The adhesives were applied on a bovine dentin surface and polymerized using an LED curing unit (n=5). After polymerization, specimens were stored in 75% ethanol solution (6 mL). Residual HEMA that was eluted from adhesives (after 10 minutes, 1 hour, 24 hours, 7 days and 30 days) was analyzed using HPLC. Statistical analyses were performed using 1-way ANOVA, Tukey HSD test and paired 2-sample t-test. There were statistically significant differences among adhesive systems for the cumulative released HEMA and among the time periods (p<0.05). Clearfil SE Bond showed the highest amount of HEMA released, while Easy Bond showed the lowest. Among the time periods, the highest eluted HEMA value was detected in 10 minutes for all adhesives, and elution continued for up to 30 days. The HEMA eluted from adhesives was in different amounts, and the elution continued for a long time. The amount of eluted HEMA from adhesives used in this study was not viewed as critical for toxic reactions in biological tissues.


A novel multiple FISH array for the detection of genetic aberrations in cancer.
Interphase multicolor fluorescence in situ hybridization (IM-FISH) has great promise for improving cancer diagnosis because it can directly visualize multiple changes in chromosomes and gene copy number on a cell-to-cell basis. However, no more than four targets can be detected simultaneously by current commercially available IM-FISH protocols, and the DNA probes used are too large to detect the single-gene aberrations that characterize tumorigenesis. As a result, multiple FISH has a low sensitivity in detecting cancer cells. To overcome such limitations, we first developed specific genomic probes for the genes relevant to primary lung cancer. We next designed a multiple FISH array by arranging four different compositions of cocktails of four probes for each gene on a coverslip, which allowed four four-color FISH experiments to be performed in parallel on a single slide. We then tested the multiple FISH array on bronchial brushing samples from lung cancer patients to determine its ability to detect genetic abnormalities. A comparison of the data with the results of cytology and commercial four-color FISH suggested that the multiple FISH array had the highest sensitivity for cancer detection. The technique may thus be a powerful laboratory strategy for cancer prevention and early detection and for improved patient management.


Pregnancy-related cardiovascular conditions and outcomes in a United States Medicaid population.
This study aims to examine the incidence of pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes, and their relationship in US Medicaid-funded women. Medicaid is a government-sponsored health insurance programme for low-income families in the USA. We report the incidence of pregnancy-related cardiometabolic conditions (hypertensive disorders and diabetes in, or complicated by, pregnancy) and severe cardiovascular outcomes (myocardial infarction, stroke, acute heart failure, cardiomyopathy, cardiac arrest, ventricular fibrillation, ventricular tachycardia, aortic dissection/aneurysm and peripheral vascular disease) among Medicaid-funded women with a birth (International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code O80 or O82) over the period January 2015-June 2019, from the states of Georgia, Ohio and Indiana. In this cross-sectional cohort, we examined the relationship between pregnancy-related cardiometabolic conditions and severe cardiovascular outcomes from pregnancy through to 60 days after birth using multivariable models. Among 74 510 women, mean age 26.4 years (SD 5.5), the incidence per 1000 births of pregnancy-related cardiometabolic conditions was 224.3 (95% CI 221.3 to 227.3). The incidence per 1000 births of severe cardiovascular conditions was 10.8 (95% CI 10.1 to 11.6). Women with pregnancy-related cardiometabolic conditions were at greater risk of having a severe cardiovascular condition with an age-adjusted OR of 3.1 (95% CI 2.7 to 3.5). This US cohort of Medicaid-funded women have a high incidence of severe cardiovascular conditions during pregnancy. Cardiometabolic conditions of pregnancy conferred threefold higher odds of severe cardiovascular outcomes.


A new case of prenatally diagnosed pentasomy x: review of the literature.
Pentasomy X is a rare chromosomal abnormality probably due to a nondisjunction during the meiosis. Only four cases prenatally diagnosed were described until now. Our case is the fifth one prenatally diagnosed at 20 weeks of gestational age in a 39-years-old woman. She underwent invasive prenatal diagnosis for her advanced maternal age without any other known risk factor. Amniocentesis performed at 17 weeks showed a female 49, XXXXX karyotype. The ultrasonographic examination revealed nonspecific signs of a mild early fetal growth retardation and no significant increased nuchal fold. The fetal autopsy and the X-ray excluded major malformations. Prenatal diagnosis is often difficult due to the lack of indicative ultrasonographic findings and the rarity of described cases. The influence of the mother's age on the occurrence of penta-X syndrome has not been determined. Considering the lack of correlation between advanced maternal age and increased risk for pentasomy X, as well as the absence of typical echographic signs, evaluation of the inclusion of a noninvasive prenatal test (NIPT) that expands clinical coverage to include the X and Y chromosomes in routine prenatal diagnosis should be considered as well as three-dimensional ultrasound to detect any helpful indicative prognostic signs.


Using PC12 cells to evaluate poly(caprolactone) and collagenous microcarriers for applications in nerve guide fabrication.
Tissue-engineered nerve guides can provide mechanical support as well as chemical stimulation for nerve regeneration. PC12 cells were used to test the novel combination of poly(caprolactone) (PCL) and macroporous collagen-based microcarriers (CultiSphers) as an initial phase in the fabrication of multichanneled nerve guides. Laminin-coated PCL was an effective matrix for the attachment, proliferation, and viability of PC12 cells, relative to uncoated PCL. PC12 cells attached to laminin-coated PCL and extended neurites when cultured in the presence of nerve growth factor (NGF). PC12 cells attached and proliferated on CultiSphers and extended neurites in response to NGF. A novel PCL/CultiSpher composite material also supported PC12 attachment and proliferation and provides a potentially useful material for the fabrication of synthetic nerve guides.


Management of acute coronary syndromes at hospital discharge: do targeted educational interventions improve practice quality?
Evidence-based guidelines exist for the management of patients with acute coronary syndromes (ACS), yet adherence is suboptimal. The Discharge Management of Acute Coronary Syndrome project used a quality improvement approach, with targeted intervention strategies to optimize: prescription of guideline-recommended medications; education regarding lifestyle modifications, including cardiac rehabilitation (CR); and communication between hospital staff, patients, and general practitioners. Hospitals across Australia participated in a quality improvement cycle of audit, feedback, intervention, and reaudit. Interventions involved educational meetings, academic detailing and point-of-care reminders, and feedback of baseline audit results. Outcome measures included prescription of guideline-recommended medications, referral to CR, and documentation and communication of management plan. At baseline, 49 hospitals recruited 1,545 patients, and postintervention, 45 hospitals remained active in the project and recruited 1,589 patients. Three thousand and thirty-four hospital staff attended group education or academic detailing sessions. Postintervention, there was a significant increase in the prescription of all four guideline-recommended medications (69% vs. 57%; p<.0001); short-acting nitrates (68% vs. 56%; p<.0001); and documented referral to CR (68% vs. 57%; p<.0001). There were significant increases in documented discharge medication counselling, smoking cessation counselling, and communication of management plans. Targeted educational interventions used as part of a quality improvement cycle can enhance adherence to evidence-based guidelines for the management of patients with ACS.


Composition-Thermometric Properties Correlations in Homodinuclear Eu3+ Luminescent Complexes.
A family of homodinuclear Ln3+ (Ln3+ = Gd3+, Eu3+) luminescent complexes with the general formula [Ln2(β-diketonato)6(N-oxide)y] has been developed to study the effect of the β-diketonato and N-oxide ligands on their thermometric properties. The investigated complexes are [Ln2(tta)6(pyrzMO)2] (Ln = Eu (1·C7H8), Gd (5)), [Ln2(dbm)6(pyrzMO)2] (Ln = Eu (2), Gd (6)), [Ln2(bta)6(pyrzMO)2] (Ln = Eu (3), Gd (7)), [Ln2(hfac)6(pyrzMO)3] (Ln = Eu (4), Gd (8)) (pyrzMO = pyrazine N-oxide, Htta = thenoyltrifluoroacetone, Hdbm = dibenzoylmethane, Hbta = benzoyltrifluoroacetone, Hhfac = hexafluoroacetylacetone, C7H8 = toluene), and their 4,4'-bipyridine N-oxide (bipyMO) analogues. Europium complexes emit a bright red light under UV radiation at room temperature, whose intensity displays a strong temperature (T) dependence between 223 and 373 K. This remarkable variation is exploited to develop a series of luminescent thermometers by using the integrated intensity of the 5D0 → 7F2 europium transition as the thermometric parameter (Δ). The effect of different β-diketonato and N-oxide ligands is investigated with particular regard to the shape of thermometer calibration (Δ vs T) and relative thermal sensitivity curves: i.e.. the change in Δ per degree of temperature variation usually indicated as Sr (% K-1). The thermometric properties are determined by the presence of two nonradiative deactivation channels, back energy transfer (BEnT) from Eu3+ to the ligand triplet levels and ligand to metal charge transfer (LMCT). In the complexes bearing tta and dbm ligands, whose triplet energy is ca. 20000 cm-1, both deactivation channels are active in the same temperature range, and both contribute to determine the thermometric properties. Conversely, with bta and hfac ligands the response of the europium luminescence to temperature variation is ruled by LMCT channels since the high triplet energy (>21400 cm-1) makes BEnT ineffective in the investigated temperature range.


Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice.
The in vivo engraftment of induced pluripotent stem cell (iPSC)-derived podocytes following allogeneic transplantation into host kidneys remains a challenge. Here we investigate the survival and engraftment of human dermal fibroblasts-derived differentiated iPSCs using a newborn mouse model, which represents a receptive immunoprivileged host environment. iPSCs were generated from skin biopsies of patients using Sendai virus reprogramming. Differentiation of nephrin (NPHS1)-green fluorescent protein (GFP) iPSCs into kidney podocytes (iPSC-PODs) was performed by the addition of Activin A, bone morphogenetic protein 7 (BMP7), and retinoic acid over 10 days of culture. To assess the in vivo incorporation of cells, undifferentiated iPSCs or day 10 iPSC-PODs, were labeled with either carboxyfluorescein succinimidyl ester (CFSE) or Qdot nanocrystals (Q705). Thereafter, 1 × 105 differentiated iPSC-PODs were injected directly into the kidneys of mouse pups at postnatal day one (P1). Using co-expression analysis of glomerular and podocyte-specific markers, Day 10 differentiated iPSC-PODs that were positive for podocin, were detected following direct kidney injection into newborn mice up to 1 week after transplantation. Undifferentiated iPSC-PODs were not detected at the same timepoint. The transplanted cells were viable and located in the outer nephrogenic zone where they were found to colocalize with, or sit adjacent to, cells positive for glomerular-specific markers including podocin, synaptopodin, and Wilms' tumor 1 (WT1). This study provides proof-of-principle that transplanted iPSC-POD can survive in recipient newborn mouse kidneys due to the immature and immunoprivileged nature of the developing postnatal kidneys.


Investigating the need for routine ultrasound screening to detect developmental dysplasia of the hip in infants born with breech presentation.
Breech presentation is a recognized risk factor for developmental dysplasia of the hip (DDH). Within North America, there is a lack of consensus on screening guidelines for DDH in infants with a negative physical examination of the hips. This study evaluates the need for ultrasound screening in all breech born infants to detect DDH and whether this is influenced by gender, gestational age and mode of delivery. A retrospective chart review was conducted to identify breech born infants who underwent routine hip ultrasound to detect DDH between 2010 and 2015. Patients were grouped by physical exam and ultrasound findings and compared based on gender, gestational age and mode of delivery. Three hundred and eighteen patients were identified (191 female, 127 male; 26 preterm, 57 late preterm, 235 term; 263 caesarean section delivery, 55 vaginal delivery). Three hundred and eight patients had a negative physical exam of which 27 were diagnosed with DDH based on screening ultrasound with females predominant (P<0.05). 12.50% of females with a negative physical exam had DDH compared to 3.23% of males (P<0.05). There was no difference in the rate of DDH detected by screening ultrasound based on gestational age (P=0.94) or mode of delivery (P=0.59). The diagnosis of DDH in breech born infants by screening ultrasound in those with a negative physical exam of the hips is more predominant in females, with no apparent association with gestational age or mode of delivery. Future analyses with larger sample sizes are needed before conclusions can be made on screening protocols.


Consensus-Based Recommendations for Advance Directives of People with Parkinson's Disease in Regard to Typical Complications by German Movement Disorder Specialists.
A huge proportion of people with Parkinson's disease (PwP) in Germany have written an advance directive (AD). However, the content of these forms in regard to specific Parkinson's disease (PD)-related complications is rather low. There is an urgent need to specify ADs of PwP and consequently to improve decision-making concerning end-of-life aspects for affected patients. Evidence- and consensus-based PD-specific recommendations for ADs might help to close this gap. A Delphi study with two online Delphi rounds was initiated. Initial recommendations were built on findings from previous studies and derived from evidence-based literature. Consensus on recommendations was defined as ≥80% concordance regarding clarity of formulated aspects and relevance for clinical practice. A total of 22 experts (15.2% response rate) predominantly from the workgroup 'neuro-palliative care' in Germany performed two Delphi rounds. Consensus was achieved for 14 of 24 initially presented recommendations. Recommendations relating to dopaminergic therapy as well as to non-oral therapy options were considered important by the expert panel. The recommendations should be taken into account when developing and giving advice on ADs for PwP. Health professionals should be trained in counselling ADs of PwP and in integrating these recommendations in ADs during the disease course of PD.


Development and validation of the Parents' Beliefs About Children's Emotions Questionnaire.
Parents' beliefs about children's emotions comprise an important aspect of parental emotion socialization and may relate to children's mental health and well-being. Thus, the goal of this study was to develop the multifaceted Parents' Beliefs About Children's Emotions (PBACE) questionnaire. Central to our work was inclusion of multiple ethnic groups throughout the questionnaire development process, from initial item creation through assessment of measurement invariance and validity. Participants included 1,080 African American, European American, and Lumbee American Indian parents of 4- to 10-year-old children who completed the initial item pool for the PBACE. Exploratory factor analyses were conducted with 720 of these parents to identify factor structure and reduce items. Confirmatory factor analysis was then conducted with a holdout sample of 360 parents to evaluate model fit and assess measurement invariance across ethnicity and across parent gender. Finally, validity of the PBACE scales was assessed via correlations with measures of parental emotional expressivity and reactions to children's emotions. The PBACE is composed of 33 items in 7 scales. All scales generally demonstrated measurement invariance across ethnic groups and parent gender, thereby allowing interpretations of differences across these ethnic groups and between mothers and fathers as true differences rather than by-products of measurement variance. Initial evidence of discriminant and construct validity for the scale interpretations was also obtained. Results suggest that the PBACE will be useful for researchers interested in emotion-related socialization processes in diverse ethnic groups and their impact on children's socioemotional outcomes and well-being. (PsycINFO Database Record (c) 2013 APA, all rights reserved).


Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation.
The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.


Severity of maternal depression and three types of mother-to-child aggression.
This study of low-income, single mothers suggests that severity of depression conditions the relationship between depression and three types of mother-to-child aggression. Compared to nondepressed mothers, moderately but not severely depressed women are more likely to be physically violent, and both moderately and severely depressed women are at increased risk for high frequencies of verbal/symbolic aggression.


Estimation of the average burst size of Phix174 am3, cs70 for use in mutation assays with transgenic mice.
In mutation assays using transgenic mice, with recoverable vectors such as PhiX174 am3, cs70, mutations originate from two sources: (1) in vivo mutations, that is, mutations that were fixed in the mouse, or (2) ex vivo mutations, that is, mutations that were fixed during recovery or plating. When a bacteriophage infects a bacterium, it multiplies and bursts the cell, releasing a number of phages referred to as the burst size. Our method for distinguishing between in vivo mutations and ex vivo mutations estimates the average number of bursts, the denominator of in vivo mutant frequencies, by dividing the total plaque-forming units (PFU) by the average number of phages in a burst. Herein, we outline a probability model relating observed plaque counts to the burst size and present the statistical method used to estimate the burst size. The average size of a single burst from nonrevertant phages was estimated in eight studies under the conditions of our mutation assay. The average burst size was stable across studies at 182.5 plaques per burst (standard error, 14.25). The probability that a burst is a specific size was approximated by a negative binomial distribution, which implies a Poisson-Pascal distribution for the observed plaque counts. The observed plaque counts were adequately fit by this approximation. Environ. Mol. Mutagen. 37:356-360, 2001 Published 2001 Wiley-Liss, Inc.


A Comparison of Attitudes Toward Suicide Among Individuals With and Without Suicidal Thoughts and Suicide Attempts in South Korea.
A suicidal person can go through different stages that include suicidal thoughts and suicide attempts. For a few individuals, these can end up with suicide. However, there have been no studies investigating any differences in attitudes toward suicides among individuals with no suicidal thoughts, those with suicidal thoughts, and those with suicide attempts. This study was carried out to compare attitudes toward suicide among three different groups: individuals with a history of no suicidal thoughts, those with a history of suicidal thoughts, and those with a history of suicide attempts. To examine Koreans' attitudes toward suicide, we analyzed the data from the 2013 National Suicide Survey involving 1,500 participants aged between 19 and 75 years. Different attitudes toward suicide were found among the three groups. Persons reporting that they had made a suicide attempt in their life showed the most permissive attitudes toward suicide. Since this research is based on cross-sectional data, it is difficult to eliminate the possibility of changes in attitude toward suicide completely after having a suicidal thought and suicide attempt. These results can be a useful source for constructing effective messages for suicide prevention campaigns and can ultimately contribute to an improvement in the public's perceptions of suicide in the future.


In vitro localization of bone growth factors in constructs of biodegradable scaffolds seeded with marrow stromal cells and cultured in a flow perfusion bioreactor.
Tissue engineering strategies aim at controlling the behavior of individual cells to stimulate tissue formation. This control is achieved by mimicking signals that manage natural tissue development or repair. Flow perfusion bioreactors that create culture environments with minimal diffusion constraints and provide cells with mechanical stimulation may closely resemble in vivo conditions for bone formation. Therefore, these culturing systems, in conjunction with an appropriate scaffold and cell type, may provide significant insight towards the development of in vitro tissue engineering models leading to improved strategies for the construction of bone tissue substitutes. The objective of this study was to investigate the in vitro localization of several bone growth factors that are usually associated with bone formation in vivo by culturing rat bone marrow stromal cells seeded onto starch-based biodegradable fiber meshes in a flow perfusion bioreactor. The localization of several bone-related growth factors-namely, transforming growth factor-beta1, platelet-derived growth factor- A, fibroblast growth factor-2, vascular endothelial growth factor, and bone morphogenetic protein- 2-was determined at two different time points in scaffolds cultured under perfusion conditions at two different flow rates using an immunohistochemistry technique. The results show the presence of regions positively stained for all the growth factors considered, except platelet-derived growth factor-A. Furthermore, the images obtained from the positively stained sections suggest an increase in the immunohistochemically stained area at the higher flow rate and culture time. These observations demonstrate that flow perfusion augments the functionality of scaffold/cell constructs grown in vitro as it combines both biological and mechanical factors to enhance cell differentiation and cell organization within the construct. This study also shows that flow perfusion bioreactor culture of marrow stromal cells, combined with the use of appropriate biodegradable fiber meshes, may constitute a useful model to study bone formation and assess bone tissue engineering strategies in vitro.


Perovskites and thin films-crystallography and chemistry.
We discuss the crystallographic and chemical basis of the perovskite family (ABX(3)) of oxides that are used in different thin film applications. Starting with the original structure we extend our scope to several modifications. Basic parameters like the ionic radii, the tolerance factor, the occupation of the oxygen sublattice and their effect on the structural parameters will be mentioned together with examples of relationships between structural and physical properties in the bulk and at interfaces.


Telemedicine and home monitoring for COPD - a narrative review of recent literature.
Home monitoring is one of the methods of using telemedical technologies aimed to provide care at home and maintain a connection between patients and healthcare providers. The purpose of this review is to describe recent advancements in the use of home monitoring for the care and management of chronic obstructive pulmonary disease (COPD) patients. Recent studies focused on remote monitoring for patients with COPD proved the positive effect of home monitoring interventions on the frequency of exacerbations and unscheduled healthcare visits, duration of patients' physical activity, proved sensitivity and overall specificity of such interventions and highlighted the effectiveness of self-management.Assessing end-user experience revealed high satisfaction levels among patients and healthcare staff who used home monitoring interventions. The majority of physicians and staff responded positively about the interventions' facilitation of communication with patients. Moreover, healthcare staff considered such technologies useful for their practice. Home monitoring for COPD patients improves medical care and disease management despite minor drawbacks and obstacles to its wide implementation. Involving end-users in evaluating and co-creating new telemonitoring interventions has the potential to improve the quality of remote monitoring for COPD patients in the near future.


Analysis of promoter activity of 5'-upstream regions of zebrafish olfactory receptor genes.
The vertebrate olfactory system receives and discriminates a great variety of odorants. Many lines of evidence suggest that individual olfactory neuron expresses a single type or limited types of the olfactory receptor genes. However, the mechanism of selection of a single gene in the olfactory receptor family remains unclear. In the present study, we utilized zebrafish to identify the promoter element of the olfactory receptor genes in their 5'-upstream regions. First, we isolated a number of zebrafish olfactory receptor genes. These olfactory receptor genes were specifically expressed in the olfactory tissue as visualized by whole mount in situ hybridization analysis. Time of onset of the expression of each receptor clone varied from 24 h to 48 h postfertilization. Then, we injected various constructs containing the 5'-upstream regions of the olfactory receptor genes connected to beta-galactosidase reporter gene into fertilized zebrafish embryos. Constructs from two independent olfactory receptor genes exerted beta-galactosidase (promoter) activity that is specifically upregulated in the olfactory tissue. Use of either longer or deleted constructs of these two genes diminished the promoter activity in the olfactory tissue. From these results we discuss the mechanism of the transcription of the olfactory receptor genes in the olfactory neurons.


Movement of genetically modified insects for research purposes.
Insects play a crucial role in research. Many laboratories are developing technologies to control insect vectors or agricultural pests by using genetic modifications that either reduce insect reproduction or increase refractoriness to disease transmission. Those tools include gene-drive elements that may spread such genetic traits in a selfsustaining and cost-effective manner. Since international research collaborations are nowadays routine, movement of genetically modified insects between laboratories under different regulatory jurisdictions is very common. This article describes the requirements and guidelines for transportation of genetically modified insects for research. The author draws upon the experience gained by an Italian laboratory, in its role as a research centre involved in shipments of wild and modified mosquitoes, within an international research consortium developing sustainable tools for malaria control.


Histopathologic study of uveitis in cats: 139 cases (1978-1988).
Histopathologic findings in 158 globes obtained from 139 cats by enucleation or at necropsy, with histopathologic diagnosis of uveitis, were compared, and morphology was correlated with clinical and/or histopathologic diagnosis. The most common morphologic feature was a lymphocytic-plasmacytic anterior uveal infiltrate that was either diffuse or nodular; specific cause could not be associated with this nongranulomatous anterior uveitis. In decreasing order of frequency, other common causes of uveitis in cats included feline infectious peritonitis; FeLV-associated lymphosarcoma; trauma; and lens-induced uveitis.


Parental Migration and Children's Exposure to Polyvictimization in Rural China.
The present study aims to investigate (1) the difference in polyvictimization rate between children left behind and those living with non-migrant parents in rural China, and (2) the social processes through which the effects of parental migration are conveyed through children's behaviors and interaction with the immediate external environment (e.g., family, school, and peers). The research hypotheses were tested by using a probability sample consisting of 1,681 middle school students in rural areas in Guizhou province (Mean age = 13.55, SD = 1.01; 50% of the participants were boys). Findings from multivariate logistic regression models and indirect effect analyses suggest that (1) overall, left-behind children are exposed to a higher level of polyvictimization than children living with both non-migrant parents in rural China and (2) whereas all left-behind children face similar challenges in school and family settings, each type of parental migration and caretaking arrangement entails unique protective or risk factors of polyvictimization. As one of the first studies to systematically investigate the rate and etiology of polyvictimization among children left behind in rural China, this study highlights the prominent role of parental migration in reproducing and reinforcing children's differential exposure to polyvictimization among China's rural families.


Postpartum stress urinary incontinence: a clinical study of 6,302 cases in Jiangsu Province.
To investigate the prevalence and influencing factors of stress urinary incontinence (SUI) within 6-8 weeks postpartum in Jiangsu Province. We designed a multi-center cross-sectional study involving seven hospitals in Jiangsu province, and enrolled women who underwent postpartum examination at 6-8 weeks in these hospitals between July 2019 and June 2021. According to the presence or absence of SUI, the enrolled patients were divided into two groups: the SUI group and the non-SUI group, respectively. We assessed the general health status, noted the details of delivery, and checked the pelvic floor electromyographic parameters of the postpartum women in both groups. Among 6,302 cases of postpartum women in Jiangsu province, there were 1,579 cases of SUI, with a prevalence of 25.06%. The prevalence of SUI increased significantly with age, BMI, increasing parity, coexisting constipation, organ prolapse, and diastasis recti abdominis. Compared to the non-SUI group, the SUI group had a lower mean value of the pre-baseline rest phase, shorter rise and fall times of fast muscle contractions, and a lower mean value of the endurance contraction phase. Multiple regression analysis revealed associations with weight (especially overweight and obesity), coexisting organ prolapse, constipation, parity, gestational week of delivery, mode of delivery, and mean value of endurance contraction phase. The prevalence of postpartum stress urinary incontinence in Jiangsu Province was 25.06%, and was linked to being overweight, parity > 2, coexisting organ prolapse, constipation, and a decrease in the mean value of the endurance contraction phase of the electromyograph. In this report, we offer a theoretical basis for the effective prevention of postpartum SUI clinically.


Indications and Techniques of Pediatric Keratoplasty in Eastern China From 2008 to 2017.
To explore the transition of indications and surgical techniques of pediatric keratoplasty in Eastern China in the past 10 years. Medical charts of 1026 pediatric patients (1059 eyes) who underwent keratoplasties at the Eye, Ear, Nose and Throat Hospital of Fudan University from 2008 to 2017 were retrospectively reviewed. The indications for keratoplasty and the surgical techniques were collected and analyzed. A total of 634 infants (≤3 years) (661 eyes), 207 toddlers and older children (4-12 years) (211 eyes), and 185 adolescents (13-18 years) (187 eyes) were included. The median age at the time of surgery was 2 years. The surgical indications were composed of congenital abnormalities (74.6%), acquired nontraumatic diseases (16.5%), acquired traumatic diseases (3.6%), and regraft (5.3%). Only congenital abnormality had a significant growing trend during this decade (P = 0.023). Keratoconus (67.2%) exceeded infectious keratitis (14.9%) and was the most common acquired nontraumatic cause in our study. The annual number of pediatric keratoplasties increased significantly from 40 cases in 2008 to 190 cases in 2017 (P < 0.001). Although penetrating keratoplasty was performed in 414 eyes (39.1%), its application in the treatment of keratoconus decreased significantly during this decade (P = 0.04). By contrast, deep anterior lamellar keratoplasty showed an increasing trend because of its popularization in the treatment of keratoconus (P = 0.003). Congenital abnormalities have replaced infectious keratitis and have been the leading indications of pediatric keratoplasty in the past 10 years. Although the using of penetrating keratoplasty was still the predominant procedure to treat pediatric corneal pathologies, the adoption of deep anterior lamellar keratoplasty showed a significant increasing trend during the past decade.


Primary malignant melanoma of the nasal cavity: report of two cases and review of the literature.
Primary malignant melanomas of the nasal cavity are rare, as only 400 cases have been reported to date. The present paper describes two cases recently seen in Caucasian women. The authors point out the difficult clinical diagnosis, as the symptoms are rather aspecific. From the histopathological point of view, diagnosis is easy in the melanotic cases while can show interpretating problems in the amelanotic ones, when melanoma is almost indistinguishable from other malignant neoplasms. A correlation between histological grading and prognosis was not detected, as both cases showed local recurrences within one year after surgery although they were, respectively, of epithelioid and undifferentiated type. While surgery appears to be the choice treatment of the primary lesion, the treatment of cervical metastasis is still disputable. On the whole, most authors think that the role played by radio- and mainly chemo-therapy is still limited and that cervical adenopathies should be treated by a simple lympho-adenectomy rather than by a neck dissection.


Mortality and re-revision following single-stage and two-stage revision surgery for the management of infected primary hip arthroplasty in England and Wales.
We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.


Facial expression in male and female schizophrenia patients.
This study investigated gender differences in facial expression as a reaction to various emotional stimuli in two groups of schizophrenia patients. The first group consisted of hospitalized patients (22 men and 13 women) who were tested at three points in time. The second group consisted of outpatients (21 men, 8 women) who were tested at two points in time. In addition, the facial behaviour of two control groups was investigated (17 men and 12 women; 18 men and 14 women, respectively). Facial activity was videotaped, whilst participants watched emotion-eliciting video clips and participated in an emotion-inducing interview, and measured using the Facial Action Coding System. In agreement with our expectations, schizophrenia patients showed significantly less facial activity overall than healthy control participants. Contrary to expectations, however, female patients did not display more facial activity compared to male schizophrenia patients. This finding contrasts with those of healthy participants in previous studies where women tended to show more facial activity than men. It was further expected that in non-psychotic patients (i.e. outpatients), gender differences would be more clearly apparent and female schizophrenia patients would show considerably more facial activity than male patients, with findings more or less comparable to the gender differences found in healthy controls. However, no significant interaction was found between patient group (in- vs. outpatients) and gender. The different explanations for these findings are considered in this study.


Using routine healthcare data to determine the factors associated with hospital length of stay for hypertensive inpatients in Ghana, 2012-2017.
Hospitalisation for hypertension continues to rise in Ghana. It has been revealed that in Ghana, patients hospitalised for hypertension spend between 1 and 91 days on admission. This study therefore sought to estimate the hospital length of stay (LoS) of hypertensive patients and individual or health-related factors that may influence the hospitalisation duration in Ghana. We employed a retrospective study design that used routinely collected health data on hospitalised hypertensive patients in Ghana from the District Health Information Management System database between 2012 and 2017 to model LoS using survival analysis. The cumulative incidence function for discharge stratified by sex was computed. To investigate the factors that influence hospitalisation duration, multivariable Cox regression was used. Out of a total of 106 372 hypertension admissions, about 72 581 (68.2%) were women. The mean age of the patients was 55.3 (SD=17.5) years. Overall, the median LoS was 3 days with almost 90% of all patients being discharged by the 10th day of admission. Patients admitted in Volta region (HR: 0.89, p<0.001) and Eastern region (HR: 0.96, p=0.002) experienced late discharge as compared with patients admitted in Greater Accra. It was revealed that women (HR: 1.09, p<0.001) were discharged earlier than men. However, having a surgical procedure (HR: 1.07, p<0.001) and having comorbidities such as diabetes (HR: 0.76, p<0.001) and cardiovascular diseases other than hypertension (HR: 0.77, p<0.001) increased the LoS of patients. This study provides the first comprehensive assessment of factors influencing hospitalisation duration of admissions due to hypertension in Ghana. Female sex, all regions except Volta region and Eastern region, experienced early discharge. However, patients with a surgical intervention and comorbidity experienced late discharge.


Traumatic brain injury induced hypopituitarism: the need and hope of rehabilitation.
Traumatic brain injury is a leading cause of death and disability in developed countries. Damage caused by focal and diffuse lesions produces symptoms involving most major medical systems as well as symptoms of neurological and psychological origin. The severity of a traumatic brain injury is difficult to assess, and therefore, an initial accurate prognosis is difficult as well. Present treatments focus on relieving symptoms without adequately addressing the underlying cause of those symptoms. Recent studies have shown anterior pituitary deficiencies to be common amongst survivors of TBI. As many symptoms ascribed to a TBI are similar to the symptoms of hypopituitarism, it is possible that treatment of these deficiencies will improve functioning and the quality of life for survivors of traumatic brain injuries.


Papillomavirus infection of the lower genital tract: detection of viral DNA in gynecological swabs.
A total of 311 smears from the lower genital tract were examined by the filter in situ hybridization method to identify human papillomavirus (HPV) DNA. Of these 311 smears, 229 came from clinically and cytologically negative patients and served as a control group. In this group HPV-DNA was detected in 5 cases (2.2%). Of 82 cytologically positive cases (25 confirmed by histology) 56 (68%) contained HPV-DNA. A high prevalence of HPV 6/11 and absence of HPV 16/18 was found in cases with cytological signs of permissive HPV infection. In mild and moderate dysplasia all viruses occurred at almost the same frequency. In severe dysplasia/carcinoma in situ HPV 16/18 was found 5 times more frequently than HPV 6/11. HPV 16/18 was identified in all 4 invasive cancer cases. Cervical irrigation of colposcopically suspect areas was performed in 15 cytologically and HPV-DNA positive cases using the hydrodynamic filtration method. In 12 cases only the cells obtained from the colposcopically positive areas contained HPV-DNA. The sensitivity and reproducibility of the filter in situ hybridization was shown by: comparing the results obtained by HPV-DNA hybridization using Southern blot analysis of tumor biopsies; analysing the correlation of cytologic diagnosis and presence of HPV-DNA in follow-up examinations, and diagnosing presence or absence of HPV-DNA in parallel filters from the same patients.


[Comparative research of thrombosis animal model induced byendotoxin in combination with carrageenan in different animals].
To compare the development of thrombosis animal model induced by endotoxin(LPS) in combination with carrageenan (Ca) in different animals. Two species of rats (SD and Wistar) and three species of mice (Kunming, ICR and Balb/c mice) were employed in the study. The animals of each species were randomly divided into control group and model group (LPS/Ca treatment). The animals in the model group were pretreated with Ca ip at the doses of 25 mg x kg(-1) for rats and 150 mg x kg(-1) for mice, and then treated by LPS iv sixteen hours later, while in the control group were given normal saline (NS). Thrombosis in tails was observed at 24 h after LPS iv. Hematologic parameters were tested for all the animals from each species, and the blood concentration of TNFalpha and IL-6 at different time in SD and Wistar rats were measured. LPS/Ca combinatory treatment could induce thrombosis animal model in all five animal species, and the thrombus could be clearly observed on the tails. All species had the similar change in hematologic parameters characterized as the significant decrease of white blood cells and platlets. Inflammatory factors TNFalpha and IL-6 could be largely induced in blood of both SD and Wistar rats at 2 h after LPS iv, but both inflammatory factors only transitorily exist in blood at the early stage of thrombosis model formation. LPS/Ca combinatory treatment can successfully induce thrombosis animal model in all tested animal species, and thus this model has extensive animal candidates. The secretion of a large amount of inflammatory factors plays a crucial role in the formation of thrombosis animal model.


Diffusion-weighted MRI in abdominal oncology: clinical applications.
Diffusion-weighted magnetic resonance imaging (DWI) provides image contrast that is different from that obtained by conventional magnetic resonance techniques. Although previously, DWI has been used to evaluate various diseases of the central nervous system, several technical advances have expanded the clinical applications of DWI beyond the central nervous system. As a result, many reports have been published on the use of DWI in abdominal diseases. Particularly, abdominal DWI has now being focused on evaluation of patients with abdominal cancer. DWI can be used for pretreatment tumor detection, characterization including predicting tumor response to therapy, monitoring tumor response during therapy, and follow-up study after treatment to detect possible tumor recurrence.


From Desire to Dread-A Neurocircuitry Based Model for Food Avoidance in Anorexia Nervosa.
Anorexia nervosa is a severe psychiatric illness associated with food avoidance. Animal models from Berridge et al. over the past decade showed that environmental ambience, pleasant or fear inducing, can trigger either appetitive (desire) or avoidance (dread) behaviors in animals via frontal cortex, nucleus accumbens dopamine D1 and D2 receptors, and hypothalamus. Those mechanisms could be relevant for understanding anorexia nervosa. However, models that translate animal research to explain the psychopathology of anorexia nervosa are sparse. This article reviews animal and human research to find evidence for whether this model can explain food avoidance behaviors in anorexia nervosa. Research on anorexia nervosa suggests fear conditioning to food, activation of the corticostriatal brain circuitry, sensitization of ventral striatal dopamine response, and alterations in hypothalamic function. The results support the applicability of the animal neurocircuitry derived model and provide directions to further study the pathophysiology that underlies anorexia nervosa.


Differential expression of glypican-1 in ameloblastoma variants.
Although benign, ameloblastomas are locally invasive and destructive tumors of the jawbones. The glypicans comprise a family of glycosylphosphatidylinositol-anchored proteoglycans that, by virtue of their cell-surface localization and heparin sulfate chain composition, might regulate the response of cells to numerous heparin-binding growth factors, cell adhesion molecules, and extracellular matrix components. The expression of glypican-1 is differentially altered among different types of malignancies, suggesting a possible role in the tumorigenesis and biological behavior of these neoplasms. The aim of this study was to determine the expression of glypican-1 and then hypothesize the possible role that this protein may play in the biological behavior of ameloblastomas. We assessed the presence of glypican-1 by immunohistochemical staining analyses in a series of 80 cases of different types of ameloblastomas. Desmoplastic ameloblastomas exhibited the highest expression of glypican-1 (100%), followed by the peripheral (66%), solid/multicystic (51.2%), and unicystic (47.2%) types, showing statistically significant differences among them (P<0.001). Differences detected in glypican-1 expression among different subtypes of ameloblastomas, could be suggesting a possible association with their different biological behavior.


Bone markers in the management of metastatic bone disease.
Newer markers of bone formation and bone resorption are now available. Alone these new markers do not appear to be useful to diagnose metastatic bone disease. Several markers appear to be of prognostic importance and correlate with the extent of tumour in the skeleton. Serial monitoring of bone markers may be useful to monitor the efficacy of bisphosphonate and/or systemic therapy of both lytic and blastic bone metastases.


Antibacterial Activity of Emulsified Pomelo (Citrus grandis Osbeck) Peel Oil and Water-Soluble Chitosan on Staphylococcus aureus and Escherichia coli.
This study utilized pomelo steam distillation to isolate pomelo peel essential oil. The constituents were then analyzed through gas chromatography-mass spectrometry (GC-MS), and the antibacterial activity of the essential oil emulsions at different homogenizer speed conditions and concentrations of water-soluble chitosan (degree of acetylation, DA = 54.8%) against S. aureus and E. coli was examined. Analysis of the essential oil composition identified a total of 33 compounds with the main constituent, limonene accounting for 87.5% (940.07 mg/g) of the total. The pomelo peel oil was emulsified through homogenization at 24,000 rpm, resulting in a minimal inhibitory concentration (MIC) for E. coli that was 1.9 times lower than that of the essential oil without homogenization. In addition, a mixture of 0.4% essential oil emulsion and 0.03% water-soluble chitosan had the strongest synergetic antibacterial effect on S. aureus and E. coli at pH 7.4. In comparison with chitosan alone, the MIC value of this mixture was significantly 2.4 and 2.5 times lower. Hence, this study suggests using a mixture of emulsified pomelo peel oil and water-soluble chitosan to develop a novel natural food preservative, and that the processability of food, as well as the economic value of the byproducts of the Taiwan Matou pomelo and chitosan, could be increased.


Biodegradation by an arthrobacter species of hydrocarbons partitioned into an organic solvent.
An Arthrobacter strain mineralized naphthalene and n-hexadecane dissolved in 2,2,4,4,6,8,8-heptamethylnonane. The extent of mineralization increased with greater volumes of solvent. Measurements under aseptic conditions of the partitioning of naphthalene into the aqueous phase from the solid phase or from heptamethylnonane showed that the rates were rapid and did not limit mineralization. The rate of mineralization of hexadecane was rapid, although partitioning of the compound into aqueous solution was not detected. The Arthrobacter sp. grown in media with or without heptamethylnonane did not excrete products that increased the aqueous solubility of naphthalene and hexadecane. Measurements of the number of cells in the aqueous phase showed that the Arthrobacter sp. attached to the heptamethylnonane-water interface, but attachment was evident even without a substrate in the heptamethylnonane. Tests with small inocula of the Arthrobacter sp. demonstrated that at least a portion of naphthalene or hexadecane dissolved in heptamethylnonane was degraded by cells attached to the solvent-water interface. The cells did not adhere in the presence of 0.1% Triton X-100. The surfactant prevented mineralization of the hexadecane initially dissolved in heptamethylnonane, but it increased the rate and extent of mineralization of naphthalene initially dissolved in heptamethylnonane. The data show that organic solvents into which hydrophobic compounds partition affect the biodegradation of those compounds and that attachment of microorganisms to the organic solvent-water interface may be important in the transformation.


[Can surgery treat type 2 diabetes ? Yes, according to international companies].
Type 2 diabetes (DM2) and obesity are chronic diseases that often coexist with considerable morbidity and mortality. Approximately 85 % of all DM2 patients have a body mass index (BMI) ranking them as overweight (BMI 25‑29,9 kg/m2) or obese (BMI > 30 kg/m2). Metabolic surgery is the only treatment for diabetes that results in long-term remission in 23 to 60 % of patients in the office depending on the preoperative duration of diabetes and the severity of the disease. This review presents evidence for the use of metabolic surgery (CM) as a primary treatment for DM2, potential mechanisms of its effects, and recommendations for its use in expanded patient populations.


Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas.
Subependymal giant cell astrocytoma (SEGA) is a rare, benign brain tumour developing in patients with tuberous sclerosis complex (TSC). Typical histopathological findings of this neoplasm are solid sheets and perivascular pseudorosettes of large, gemistocytic, polygonal and occasionally ganglion-like cells within a fibrillated background, accompanied by spindle-shaped cells creating broad fascicles. Rich vascular stroma, and numerous calcifications are common. Mitoses, focal necrosis, and endothelial proliferation are rarely encountered. In this study we report 3 cases of SEGA out of 29 TSC patients, operated on in the Department of Neurosurgery, Children's Memorial Health Institute, from 1990 to 2011 and retrospectively reviewed. These 3 cases exhibited distinct anaplastic features that might mimic malignant glioma. Histologically, the tumours were composed of pleomorphic, gemistocytic, polygonal, ganglion-like or multinucleated cells arranged in sheets or forming perivascular pseudorosettes. Numerous foci of necrosis, microvascular proliferation and high mitotic activity with atypical mito-tic figures were documented. The Ki67 labelling index was about 15-20%. These tumours might be confused with high-grade gliomas and such a misleading diagnosis might result in aggressive radio- or chemotherapy. Despite the common statement that morphological features of anaplasia, i.e. pleomorphism, necrosis, microvascular proliferation and increased mitotic activity, are not of prognostic value, the tumour behaviour in our cases seems to be more aggressive and requires longer follow-up studies. We suggest recognizing such cases of subependymal giant cell astrocytoma as atypical SEGAs.


Aneurysmal Rupture of a Mesodiverticular Band to a Meckel's Diverticulum.
Aneurysmal rupture of a mesodiverticular band has not previously been reported in the clinical literature. We are reporting a case of hemoperitoneum in a 51-year-old male after an aneurysmal rupture of a mesodiverticular band. This case demonstrates that in rare instances, a rupture of the mesodiverticular band leading to Meckel's diverticulum can lead to significant hemoperitoneum. This is usually caused by a traumatic injury but in our case was apparently caused by an aneurysm of the mesodiverticular artery. Patients with known Meckel's diverticula should be aware of the possibility of rupture, as should clinicians treating those with a history of this usually benign congenital abnormality. Rapid surgical intervention is necessary to repair the source of bleeding, as massive blood loss was encountered in this case.


Alligator clips to molecular dimensions.
Techniques for fabricating nanospaced electrodes suitable for studying electron tunneling through metal-molecule-metal junctions are described. In one approach, top contacts are deposited/placed on a self-assembled monolayer or Langmuir-Blodgett film resting on a conducting substrate, the bottom contact. The molecular component serves as a permanent spacer that controls and limits the electrode separations. The top contact can be a thermally deposited metal film, liquid mercury drop, scanning probe tip, metallic wire or particle. Introduction of the top contact can greatly affect the electrical conductance of the intervening molecular film by chemical reaction, exerting pressure, or simply migrating through the organic layer. Alternatively, vacant nanogaps can be fabricated and the molecular component subsequently inserted. Strategies for constructing vacant nanogaps include mechanical break junction, electromigration, shadow mask lithography, focused ion beam deposition, chemical and electrochemical plating techniques, electron-beam lithography, and molecular and atomic rulers. The size of the nanogaps must be small enough to allow the molecule to connect both leads and large enough to keep the molecules in a relaxed and undistorted state. A significant advantage of using vacant nanogaps in the construction of metal-molecule-metal devices is that the junction can be characterized with and without the molecule in place. Any electrical artifacts introduced by the electrode fabrication process are more easily deconvoluted from the intrinsic properties of the molecule.


Preparation and characterization of cross-linked phospholipid bilayer capillary coatings for protein separations.
Analysis of protein and peptide mixtures via capillary electrophoresis is hindered by nonspecific adsorption of analytes to the capillary walls, resulting in poor separations and quantitative reproducibility. Phospholipid bilayer (PLB) coatings are very promising for improving protein and peptide separations due to the native resistance to nonspecific protein adsorption offered by PLBs; however, these coatings display limited chemical and temporal stability. Here, we show the preparation and characterization of a highly cross-linked, polymerized phospholipid capillary coating prepared using bis-SorbPC. Poly(bis-SorbPC) PLB coatings are prepared in situ within fully enclosed fused silica capillaries via self-assembly and radical polymerization. Polymerization of the PLB coating stabilizes the membrane against desorption from the surface and migration in an electric field, improves the temporal and chemical stability, and allows for the separation of both cationic and anionic proteins, while preserving the native resistance to nonspecific protein adsorption of natural PLBs.


Polymorphism of growth-correlated genes associated with fatness and muscle fiber traits in chickens.
Thirty single nucleotide polymorphisms (SNP) and one 6-bp insertion-deletion (indel) from 8 genes of somatotropic axis were used to study the association with chicken fatness and muscle fibers. The allele frequency difference between Xinghua and White Plymouth Rock chickens was observed, and their effects on fatness and muscle fiber traits were also evaluated by linkage analyses. The G143831A (G+1705A) SNP of the growth hormone (GH) gene was related to fat width, and the G144762A (G+119A) SNP of the GH gene was significantly associated with abdominal fat pad weight, abdominal fat pad ratio, and crude fatty content of the breast muscle. The 6-bp indel of the growth hormone secretagogue receptor (GHSR) gene was significantly linked with the fat traits. The C51978309T SNP of the insulin-like factor-I (IGF-I) gene was significantly linked with the transversal area of the leg muscle fiber and transversal area of the breast muscle fiber. There was significant linkage between the insulin (INS) gene and 2 traits of the transversal area of transversal area of the leg muscle fiber and transversal area of the breast muscle fiber. Association of 30 SNP and one 6-bp indel from 8 genes of somatotropic axis with chicken fatness and muscle fiber traits was analyzed in the present study. The GH, GHSR, and leptin receptor genes were significantly related to chicken fatness. The INS and IGF-I genes were linked with muscle fiber density. Therefore, the genes of somatotropic axis not only affected chicken growth and body composition but also were associated with fatness and muscle fiber traits.


Reactive neuromuscular training for the anterior cruciate ligament-deficient knee: a case report.
To demonstrate the response to a proprioceptive training model during a 1-week rehabilitation regime. The techniques were demonstrated on a college-aged female basketball player who had injured her anterior cruciate ligament (ACL) several weeks earlier. The athlete was tested, trained, and then retested during her semester break. The ACL injury has become a fairly common occurrence in the world of athletics. Knowing this, the athletic trainer is constantly searching for ways to improve the rehabilitative process. New research demonstrates that rehabilitation should be based on proprioception. The ACL not only serves a mechanical role by limiting passive knee mobility but also serves a sensory role through the mechanoreceptors deep in its tissue, which communicate with the neuromuscular system to provide proprioceptive feedback during training and competition. Partial or complete tear of the ACL. The athlete was treated with a rehabilitation protocol based on proprioception, which uses reactive neuromuscular training. Our rehabilitation focused on the muscular imbalances about the hip, knee, and ankle. The athlete achieved dramatic decreases in muscular imbalances about the hip and knee in only 1 week of rehabilitation through reactive neuromuscular training. The athlete had significant gains in strength over her brief period of therapy. However, these gains can be viewed only as neuromuscular changes and not strictly as gains in strength. The athlete returned to postseason competition under the supervision of her surgeon, who later recommended surgical reconstruction at the completion of the basketball season with rehabilitation during the offseason.


Long-term performance of homografts versus stented bioprosthetic valves in the pulmonary position in patients aged 10-20 years.
We aimed to compare the long-term performance of pulmonary homografts and stented bioprosthetic valves in the pulmonary position in patients aged 10-20 years. Between January 1995 and December 2015, 188 patients aged 10-20 years undergoing pulmonary valve replacement were identified retrospectively from hospital databases in both congenital cardiac centres in Brisbane. Valve performance was evaluated using previously described standard criteria. Propensity score matching was used to balance the 2 treatment groups. Freedom from structural valve degeneration in homografts (n = 131) was 97%, 92% and 85% at 3, 5 and 10 years, respectively, and 91% and 53% at 3 and 5 years, respectively, in the bioprosthesis group (n = 57). Freedom from reintervention in homografts was 96%, 93% and 88% at 3, 5 and 10 years, respectively, and 93% and 68% at 3 and 5 years, respectively, in the bioprosthesis group. The unadjusted Cox regression analysis demonstrated that a bioprosthesis was at 5.64 times the risk of structural valve degeneration and 3.89 times the risk of reintervention. The Cox regression analysis performed on the propensity matched sample (45 pairs of patients) revealed that a bioprosthesis was at almost 10 times the risk of experiencing structural valve degeneration [hazard ratio (HR) = 9.18] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34). In our patient population, pulmonary homografts outperformed stented bioprosthetic valves within 5 years when implanted in the pulmonary position in patients aged 10-20 years. We recommend the use of a pulmonary homograft for pulmonary valve replacement in this age group in patients undergoing surgery for congenital heart disease.


Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial.
To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. The duration of objective oral mucositis > or = Grade 1 (p = 0.0097), Grade 2 (p = 0.0232), and Grade 3 (p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) (p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration > or = Grade 3 (p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference (p = 0.5374) between the two arms. Mean body weight change was also not significantly different (p = 0.8070). Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of > or = Grade 3 subjective mucositis.


Dentoalveolar and Airway Changes Following En Masse Distal Movement of the Maxillary Dentition with Infrazygomatic Crest Anchorage: A Prospective Study.
Mini screws placed buccal to the maxillary first or second molars in the infra zygomatic crest (IZC) region can be used as anchors for various types of tooth movement. En masse distal movement of the maxillary dentition with IZC anchorage is routinely practiced nowadays as more patients demand a non-extraction treatment and it should be evaluated. The goal of this study was to assess dentoalveolar and airway changes in individuals with class II malocclusion after en masse distal movement of the maxillary dentition utilizing infrazygomatic anchorage. This prospective study included patients who required en masse distal movement of the maxillary dentition. Following initial leveling and aligning, mini screws were placed in the IZC region, and the maxillary arch was distalized en-masse. Pre (T0) and post distalization (T1) lateral cephalograms were traced for dentoalveolar and airway changes. Statistical tests were done with SPSS software. Shapiro-Wilk test for normality and paired T test for comparison between before and after en masse distalization were done. The changes in dental angular and linear measurements such as U1 to N-A, L1 to N-B and interincisal angle, U1 to N-A and U1 to point A distance, U1 to palatal plane, L1 to N-B, L1 to Apo line distance, U6 to PtV were statistically significant (P > 0.05). Linear parameters such as L1 to ApO line, upper airway, and lower airway were not statistically significant (<0.05). Class II div I malocclusions can be efficiently corrected without extractions using IZC anchorage by en masse distal movement of the maxillary dentition. Significant reduction in upper anterior inclination, intrusion of maxillary anterior teeth, and distal movement of the posterior teeth were noted. No changes in airway dimensions were noted.


Benign Metastasizing Leiomyoma to the Lung and Spine: A Case Report and Literature Review.
Benign metastasizing leiomyomas (BML) represent a rare phenomenon consisting of the extra-uterine spread of smooth muscle cells with similar histological, immunological, and molecular patterns to those of benign uterine leiomyomas. They are considered benign based off their low mitotic activity, lack of anaplasia or necrosis, and limited vascularization. This condition represents an interesting diagnostic and treatment challenge based on their rarity and indolent nature. Our case represents a unique finding of BML in the thoracic spine in a postmenopausal woman many years after hysterectomy and partial oophorectomy. There are currently no standard guidelines for treatment of BML, given the rare nature of this condition, with most patients treated with a combination of surgical resection and radiotherapy, followed by hormonal treatment and radiological surveillance serving as the primary backbone of current management plans. Given that these patients present a unique clinical challenge in terms of diagnosis and management, it is important to delineate and further examine these rare entities.


Effect of dietary crude protein and energy on gosling growth performance and carcass trait.
The study was undertaken to assess dietary CP and ME concentrations for optimum growth performance and carcass characteristics of goslings. In a 5 x 3 factorial arrangement, 360 one-day-old commercial generation Huoyan goslings were randomly assigned to experimental diets with 10.87, 11.37, 11.87, 12.37, and 12.87 MJ of ME/kg of diet; each contained 15.0, 17.5, and 20.0% CP, respectively, from 0 to 4 wk of age (WOA). Each dietary treatment was replicated 6 times. Body weight and feed consumption were measured, and carcass characteristics were evaluated at 4 WOA. The result showed that birds on a diet with 11.87, 12.37, and 12.87 MJ of ME/kg at 0 to 4 WOA exhibited greater BW gain than those on a diet with 10.87 and 11.37 MJ of ME/kg (P < 0.01), though BW gain was not different among 11.87, 12.37, and 12.87 MJ of ME/kg of diet. Mean BW gain of birds fed 17.5 and 20.0% CP diets was not different (P > 0.05), but they were higher than those on 15.0% dietary CP concentration (P < 0.001). Feed intake was not influenced by dietary ME levels (P > 0.05). Feed intake of birds fed 17.5 and 20.0% CP diets was higher than those of birds on 15.0% CP diets (P < 0.01). Feed conversion ratios of birds fed on 11.87, 12.37, and 12.87 MJ of ME/kg of diet were better than those fed on 10.87 and 11.37 MJ of ME/kg (P < 0.001). Feed conversion ratios of birds fed on 17.5 and 20.0% CP diets were better than those fed on 15.0% CP diets. Moreover, there were no significant interactions between CP and ME on growth performance. There was a direct relationship between dietary ME levels and eviscerated carcass percentage, abdominal fat percentage, and liver relative weight (P < 0.01). Breast and leg meat percentage were influenced by dietary CP concentrations significantly (P < 0.001). Thus, diets with 11.87 MJ of ME/kg and 17.5 to 20.0% CP were used more efficiently from 0 to 4 WOA by Huoyan goslings.


Bone secondaries in breast cancer: the solitary metastasis.
The bone scan findings of 160 consecutive cases of breast cancer metastatic to bone presenting to Guy's Hospital between 1982-1987 were retrospectively assessed for number and distribution of lesions. Twenty-one percent of patients relapsed with a solitary bone metastasis. The spine was the commonest site for both solitary (52% of cases) and multiple (87%) metastases. Solitary bone metastases are more common than previously thought.


Visual acuity and behavior of monocularly deprived monkeys after retinal lesions.
One eyelid of each of three Macaca nemestrina monkeys was sutured shut at 3 weeks of age. One animal had the central 10 degrees of the open eye retina lesioned at 3 weeks of age (EL1), a second at 9 months of age (LL1), and the third had no lesion (MD1). After a reverse suture at 9 months of age, the deprived eye was tested for grating acuity, visual behavior, and visual field. EL1 tested positively on all behavioral tasks by 1 month and showed good visual ability to negotiate a playroom but never performed better than 20/1,250 on grating acuity. MD1 showed little visual behavior in the playroom but tested at 20/400 acuity. LL1 rapidly recovered all aspects of visual behavior and tested at 20/80 visual acuity. Perimetry shows that LL1 and EL1 respond mainly in the central portion of the deprived eye visual field but not to the periphery or the monocular segment. We conclude that removal of the open eye retina after the critical period allows much visual recovery by the deprived eye but that removal of the open eye retina within the critical period does not prevent many of the effects of monocular deprivation.


Racial Differences in Patient-Reported Post-Stroke Disability in Older Adults.
Longstanding disparities have been reported in stroke-related outcomes with blacks experiencing more post-stroke disabilities. Little is known about long-term disability outcomes among older stroke survivors. This study was a retrospective analysis of data from the 2015 National Health Interview Survey (NHIS). A group of 655 stroke survivors (541 white and 114 black) age 65 and older were asked to rate their ability to complete 10 functional tasks without special equipment. Univariate comparisons were completed using t-tests and chi-square statistics for racial comparisons of disability reports. Multinomial logistic regression was used to determine odds of reporting disability after controlling for relevant covariates. The mean age of the sample was 76.6 years. After controlling for relevant covariates, white stroke survivors were less likely to report the following tasks being "very difficult/can't do at all" without using special equipment compared to blacks: reach overhead (OR = 0.39, 95% CI 0.23⁻0.65; p = 0.000) and grasp small objects (OR = 0.42, 95% CI 0.25⁻0.73; p = 0.002). Both black and white older stroke survivors experience significant post-stroke disability across a range of functional tasks. Slightly greater long term post-stroke disability appears to exist among older blacks.


Postoperative surface deposits on intraocular lenses in children.
To report the clinicopathologic features of 4 intraocular lenses (IOLs) composed of 3 different hydrophilic biomaterials explanted from children who had postoperative opacification of the IOL optic. David J Apple, MD, Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah, USA. The IOLs were explanted 20, 11, 22, and 25 months postoperatively from children aged 10, 3, 36, and 20 months old, respectively, at IOL implantation. Clinical data were obtained to correlate the findings with possible associated risk factors. The explanted IOLs were examined by gross and light microscopy. They were further analyzed with a stain for calcium, alizarin red 1%. Scanning electron microscopy and energy dispersive X-ray spectroscopy (EDS) were also performed. The primary reason for cataract surgery in Case 1 and Case 2 was persistent hyperplastic primary vitreous (PHPV); 1 patient received a B-Lens IOL (Hanita) and the other a Centerflex IOL (Rayner). The primary reason in Case 3 was familial bilateral congenital cataract and in Case 4, rubella cataract; both patients received a Hydroview IOL (Bausch & Lomb). All 4 IOLs had surface deposits on the optic, but the morphology of the deposits on the B-Lens and Centerflex IOLs was different than that in previously reported cases. The deposits in all four cases stained positive with alizarin red and consisted of calcium and phosphorus when imaged with EDS. Calcified deposits on 2 Hydroview IOLs explanted from children were similar to those seen in adults with the same IOL. The deposits on the B-Lens and Centerflex IOLs were probably secondary to a breakdown of the blood-aqueous barrier caused by preexisting PHPV.


Apoptotic, Anti-Inflammatory Activities and Interference with the Glucocorticoid Receptor Signaling of Fractions from Pistacia lentiscus L. var. chia Leaves.
In this study acetonic extracts of leaves of Pistacia lentiscus L. var. chia (mastiha tree) grown in the south as well as in the north Chios Greek island were isolated and further fractionated to give three different polarity fractions: apolar, medium-polar, and polar. The isolated fractions were assessed as regards their main composition, cytotoxic, anti-inflammatory activities, and interference with the glucocorticoid receptor (GR) signaling, applying cytotoxic assay, luciferase assays, and Western blot analysis of apoptosis-, energy-, and inflammation-associated molecules. Differences in cell viability have been detected among different polarity leaf fractions as well as among fractions of different plant origin with polar fractions showing the highest cytotoxicity. Fractions-induced anti-inflammatory activities and suppressive effects on the dexamethasone (DEX)-induced GR transcriptional activation were unveiled. The partition protocol of leaves fractions applied uncovers the enhanced glucocorticoid-associated biological activities of the medium-polar fractions, which may be associated with their enrichment in the triterpenoids that showed structural similarity with the glucocorticoids. A reduction in GR protein levels is observed by the fraction which is shown to be associated with the medium polar-induced proteolytic degradation of the receptor. In addition, the enhanced cytotoxic, anti-inflammatory, and potential anti-glycemic activities of the fractions from the Southern P. lentiscus L. that exclusively produce the mastiha resin, is revealed, indicating that leaves fractions from mastiha tree, similarly to mastiha tree resin, may have the potential to be further analyzed for their potent applications in the pharmaceutical cosmetic and nutraceutical fields.


Stress and radiation-induced activation of multiple intracellular signaling pathways.
Exposure of cells to a variety of stresses induces compensatory activations of multiple intracellular signaling pathways. These activations can play critical roles in controlling cell survival and repopulation effects in a stress-specific and cell type-dependent manner. Some stress-induced signaling pathways are those normally activated by mitogens such as the EGFR/RAS/PI3K-MAPK pathway. Other pathways activated by stresses such as ionizing radiation include those downstream of death receptors, including pro-caspases and the transcription factor NFKB. This review will attempt to describe some of the complex network of signals induced by ionizing radiation and other cellular stresses in animal cells, with particular attention to signaling by growth factor and death receptors. This includes radiation-induced signaling via the EGFR and IGFI-R to the PI3K, MAPK, JNK, and p38 pathways as well as FAS-R and TNF-R signaling to pro-caspases and NFKB. The roles of autocrine ligands in the responses of cells and bystander cells to radiation and cellular stresses will also be discussed. Based on the data currently available, it appears that radiation can simultaneously activate multiple signaling pathways in cells. Reactive oxygen and nitrogen species may play an important role in this process by inhibiting protein tyrosine phosphatase activity. The ability of radiation to activate signaling pathways may depend on the expression of growth factor receptors, autocrine factors, RAS mutation, and PTEN expression. In other words, just because pathway X is activated by radiation in one cell type does not mean that pathway X will be activated in a different cell type. Radiation-induced signaling through growth factor receptors such as the EGFR may provide radioprotective signals through multiple downstream pathways. In some cell types, enhanced basal signaling by proto-oncogenes such as RAS may provide a radioprotective signal. In many cell types, this may be through PI3K, in others potentially by NFKB or MAPK. Receptor signaling is often dependent on autocrine factors, and synthesis of autocrine factors will have an impact on the amount of radiation-induced pathway activity. For example, cells expressing TGFalpha and HB-EGF will generate protection primarily through EGFR. Heregulin and neuregulins will generate protective signals through ERBB4/ERBB3. The impact on radiation-induced signaling of other autocrine and paracrine ligands such as TGFbeta and interleukin 6 is likely to be as complicated as described above for the ERBB receptors.


On diamond surface properties and interactions with neurons.
In this paper we report about the role the diamond surface morphology and atomic termination plays in the survival and viability of neuronal cells, which represent an appropriate experimental model for the development of cell-based biosensors. The samples we have investigated were both CVD homoepitaxial diamond films and nanocrystalline diamond layers deposited on quartz substrates. Different surface terminations were induced through exposure to atomic hydrogen and to intense UV irradiation. GT1-7 cells, a neuronal line of hypothalamic origin, were plated directly onto the diamond surfaces without exogenous adhesion molecules, in order to correlate the surface topography and chemistry to cell growth and viability. The cell density on nanocrystalline diamonds after 48 h from plating was approximately 55% of the control on plastic dishes, whatever is the atomic termination of the surface, whereas the performances of homoepitaxial samples in terms of cell growth depend on surface termination and were significantly lower, 30%.


Multifunctional dendrimer/combretastatin A4 inclusion complexes enable in vitro targeted cancer therapy.
We report here a unique approach to using multifunctional dendrimer/combretastatin A4 (CA4) inclusion complexes for targeted cancer therapeutics. Amine-terminated generation 5 polyamidoamine dendrimers were first partially acetylated to neutralize a significant portion of the terminal amines, and then the remaining dendrimer terminal amines were sequentially modified with fluorescein isothiocyanate as an imaging agent and folic acid as a targeting ligand. The multifunctional dendrimers formed (G5.NHAc-FI-FA) were utilized to encapsulate the anticancer drug, CA4, for targeted delivery into cancer cells overexpressing folic acid receptors. The inclusion complexes of G5.NHAc-FI-FA/CA4 formed were stable and are able to significantly improve the water solubility of CA4 from 11.8 to 240 μg/mL. In vitro release studies showed that the multifunctional dendrimers complexed with CA4 could be released in a sustained manner. Both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay and morphological cell observation showed that the inhibitory effect of the G5.NHAc-FI-FA/CA4 complexes was similar to that of free CA4 at the same selected drug concentration. More importantly, the complexes were able to target selectively and display specific therapeutic efficacy to cancer cells overexpressing high-affinity folic acid receptors. Multifunctional dendrimers may serve as a valuable carrier to form stable inclusion complexes with various hydrophobic anticancer drugs with improved water solubility, for targeting chemotherapy to different types of cancer.


[Diclof 0.1% eyedrops in pediatric ophthalmology].
The authors analyze their two years experience with 208 patients hospitalized at the Clinic of Pediatric Ophthalmology treated by the locally administered antiprostaglandin diclophenac, 0.1% eye drops. The spectrum of the disease was wide and comprised different conditions after intraocular surgery, in particular of cataract, glaucoma and perforation injuries, Yag laser capsulotomy, and conservatively treated conditions, in particular inflammatory processes, uveitis and keratoconjunctivitis. Diclophenac was not combined with other non-steroid antiphlogistics but frequently it was adjuvant treatment of corticosteroids, antibiotics and mydriatics. The authors did not observe any side-effects of the preparation, even after long-term administration or after short-term administration to neonates. As to the intensity of effect, diclophenac was comparable with other prostaglandin inhibitors and in pediatric ophthalmology it is an effective and safe antiphlogistic agent.


Dynamic Modeling and Attitude Decoupling Control for a 3-DOF Flexible Piezoelectric Nano-Positioning Stage Based on ADRC.
The paper proposes a three-degrees-of-freedom flexible nano-positioning stage constructed from compliant flexures and piezoelectric thin-sheet actuators, featuring a compact size and fast dynamic responses, which can be extensively applied to the typical micro/nano-positioning applications. Meanwhile, the dynamic model of the flexible PZT nano-positioning with distributed parameter characteristics is established to distinctly reflect the piezoelectric-mechanical coupling relationship between the four flexible PZT actuators and the three outputs of such a system. Furthermore, the attitude decoupling control for the 3-DOF flexible piezoelectric nano-positioning stage is achieved by the Active Disturbance Rejection Control (ADRC) method to compensate for the positioning errors in the actual positioning process. After this, a real-time experimental apparatus with two Position-Sensitive Detectors (PSDs) is also proposed and fabricated to test the three outputs of the flexible piezoelectric thin-sheet (PZT-5A) nano-positioning stage and validate the effectiveness of the dynamic modeling method and attitude decoupling control in the piezoelectric nano-positioning stage ranges.


Relationships between clinical assessments and patients' perceptions of the effects of heart failure on their quality of life.
Hypothetically, most of the effects of heart failure on quality of life might be attributed to symptoms produced by the pathology. Relationships between measures of these concepts need to be quantified to test this conceptual model. Measurements of heart failure pathology and symptoms and quality of life as measured by the Minnesota Living with Heart Failure (MLHF) questionnaire at the 4-month visit in the Valsartan Heart Failure Trial were analyzed. Correlation and regression analyses corrected for estimated reliability of measurements were used to quantify relationships. The percentage of variance in dependent variables that was related to explanatory variables was summarized by the coefficient of determination (100 xR(2)) from regression models. Dyspnea at rest, dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, fatigue, and New York Heart Association class were significantly related to MLHF scores. Combined, these symptoms explained 41% of the variation in MLHF scores. Controlling for symptoms, age explained an additional 4.5% of the variation in MLHF scores, whereas race, gender, and available comorbidities each explained <1%. Pathologic measures including ejection fraction, B-type natriuretic peptide, jugular venous distension, rales, peripheral edema, systolic blood pressure, creatinine, and hemoglobin were not strongly related to symptom assessments (combined R(2) = 17%) or MLHF scores (combined R(2) = 7%). Symptoms of heart failure explain a substantial proportion of the variation in the effects of heart failure on patients' quality of life as measured by the MLHF score. The effects of heart failure on quality of life can vary with age independently of symptoms. Pathologic measures of heart failure including some well-known correlates of the risk of hospitalization and death are not strongly related to symptoms or quality of life. Further studies are needed to understand the relationships between heart failure pathology and symptoms and to identify determinants of the effects of heart failure on patients' quality of life that were not related to symptoms.


Phase behavior of lipid mixtures based on human ceramides: coexistence of crystalline and liquid phases.
The lipid regions in the outermost layer of the skin (stratum corneum) form the main barrier for diffusion of substances through the skin. In this layer the main lipid classes are ceramides, cholesterol (CHOL), and FFA. Previous studies revealed a coexistence of two crystalline lamellar phases with periodicities of approximately 13 nm (referred to as long periodicity phase) and 6 nm (short periodicity phase). Additional studies showed that lipid mixtures prepared with isolated pig ceramides (pigCER) mimic lipid phase behavior in stratum corneum closely. Because the molecular structure of pigCER differs in some important aspects from that of human ceramides (HCER), in the present study the phase behavior of mixtures prepared with HCER has been examined. Phase behavior studies of mixtures based on HCER revealed that in CHOL:HCER mixtures the long periodicity phase dominates. In the absence of HCER1 the short periodicity phase is dominant. Addition of FFA promotes the formation of the short periodicity phase and induces a transition from a hexagonal sublattice to an orthorhombic sublattice. Furthermore, the presence of FFA promotes the formation of a liquid phase. Finally, cholesterol sulfate, a minor but important lipid in the stratum corneum, reduces the amount of cholesterol that phase separates in crystalline domains. From these observations it can be concluded that the phase behavior of mixtures prepared from HCER differs in some important aspects from that prepared from pigCER. The most prevalent differences are the following: i) the addition of FFA promotes the formation of the short periodicity phase; and ii) liquid lateral packing is obviously present in CHOL:HCER:FFA mixtures. These changes in phase behavior might be due to a larger amount of linoleic acid moiety in HCER mixtures compared with that in pigCER mixtures.


Inhibition of tumor growth and metastasis by EMMPRIN multiple antigenic peptide (MAP) vaccination is mediated by immune modulation.
Previously, we have identified a new epitope in EMMPRIN, a multifunctional protein that mediates tumor cell-macrophage interactions and induces both MMP-9 and VEGF. Here, we synthesized this epitope as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, and sometimes regressed, tumor growth in a dose-dependent manner, reaching 94%, 71% and 72% inhibition, respectively, at a 50 μg dose (p < 0.01). Mice with regressed tumors demonstrated immune memory, preventing tumor recurrence upon re-implantation (p < 0.001). When tumor cells were administered through the tail vein to generate lung metastases, vaccination reduced the number of metastatic foci (by 15- and 23-folds, p < 0.001), and increased the median survival time by 25% and 53% in RENCA and CT26 metastases, respectively (p < 0.01) relative to scrambled-MAP controls. No significant adverse responses were observed in all experiments. We show that the tumor microenvironment was immune modulated, as vaccination induced production of EMMPRIN-specific antibodies, increased CD8+ T cells infiltration and cytotoxicity, alleviated immune suppression by decreasing TGFβ concentrations, reduced angiogenesis and cell proliferation, and enhanced apoptosis. Thus, our successful active peptide vaccination strategy differs from previous, unsuccessful attempts, both in the selected target (the EMMPRIN epitope) and in the use of a modified, MAP configuration, and demonstrates that this may be an efficient approach for the treatment and prevention of some types of cancer.


Exogenous subclinical hyperthyroidism: effect on the cardiovascular system.
To evaluate the effects of exogenous subclinical hyperthyroidism on left ventricular structure and function. Twenty-three patients of both sexes, aged 27 to 70 years, with a diagnosis of exogenous subclinical hyperthyroidism (serum thyroid-stimulating hormone [TSH] ≤ 0.4mU/ml and normal free thyroxine [FT4]) were evaluated. The patients had been taking levothyroxine in suppressive doses for an average of 6.7 years (1 to 35 years). Twenty euthyroid individuals matched for age, sex and body mass index were selected as controls. A medical history was obtained and symptoms of thyrotoxicosis were quantified in all subjects. To evaluate left ventricular structure and function, as well as atrial conduction time, a two-dimensional echocardiogram and pulsed echo and tissue echo Doppler with electrocardiography monitoring were performed. The index of hemodynamic compensation of the left ventricular mass was calculated. Hyperthyroid symptom scores were significantly higher in patients than in controls (p=0.0001). A positive correlation was found between hyperthyroidism scores and FT4 (p=0.005) and ejection fraction (p=0.04) and a negative correlation was found with TSH levels (p=0.03). End-diastolic volume, stroke volume, cardiac output and stroke work were significantly higher in patients with SH (p=0.04, p=0.02, p=0.05 and p=0.01, respectively). A positive correlation was found between fractional shortening and FT4 level (p=0.022) and levothyroxine dose (p=0.016) and between stroke work and FT4 level (p=0.034). Left ventricular mass, diastolic function and atrial conduction time were similar in patients and controls. Our study suggests that patients with exogenous subclinical hyperthyroidism have hemodynamic changes resulting from adaptation to the biological effects of levothyroxine on the cardiovascular system. However, structural changes are not produced.