Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification.
Many radioligands have been developed for the visualization of atherosclerosis by targeting inflammation. However, interpretation of in vivo signals is often limited to plaque identification. We evaluated binding of some promising radioligands in an in vitro approach in atherosclerotic plaques with different phenotypes. Tissue sections of carotid endarterectomy tissue were characterized as early plaque, fibro-calcific plaque, or phenotypically vulnerable plaque. In vitro binding assays for the radioligands [111In]In-DOTATATE; [111In]In-DOTA-JR11; [67Ga]Ga-Pentixafor; [111In]In-DANBIRT; and [111In]In-EC0800 were conducted, the expression of the radioligand targets was assessed via immunohistochemistry. Radioligand binding and expression of radioligand targets was investigated and compared. In sections characterized as vulnerable plaque, binding was highest for [111In]In-EC0800; followed by [111In]In-DANBIRT; [67Ga]Ga-Pentixafor; [111In]In-DOTA-JR11; and [111In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm2, respectively). Binding of [111In]In-DANBIRT and [111In]In-EC0800 was highest across plaque phenotypes, binding of [111In]In-DOTA-JR11 and [67Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [111In]In-DOTATATE was the lowest across plaque phenotypes. The areas positive for cells expressing the radioligand's target differed between plaque phenotypes for all targets, with lowest percentage area of expression in early plaque sections and highest in phenotypically vulnerable plaque sections. Radioligands targeting inflammatory cell markers showed different levels of binding in atherosclerotic plaques and among plaque phenotypes. Different radioligands might be used for plaque detection and discerning early from vulnerable plaque. [111In]In-EC0800 and [111In]In-DANBIRT appear most suitable for plaque detection, while [67Ga]Ga-Pentixafor and [111In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.


Incidence of lower limb amputation in people with and without diabetes: a nationwide 5-year cohort study in Japan.
This study was conducted to investigate the incidence and time trend of lower limb amputation (LLA) among people with and without diabetes. This retrospective population-based cohort study was based on the national claims data in Japan, comprising a total population of 150 million. Data of all individuals who had LLA from April 2013 to March 2018 were obtained. We analysed the sex-adjusted and age-adjusted annual LLA rate (every fiscal year) in people with and without diabetes for major and minor amputation. To test for time trend, Poisson regression models were fitted. In the 5-year period, 30 187 major and 29 299 minor LLAs were performed in Japan. The sex-adjusted and age-adjusted incidence of major and minor LLAs was 9.5 (people with diabetes, 21.8 vs people without diabetes, 2.3, per 100 000 person-years) and 14.9 (people with diabetes, 28.4 vs people without diabetes, 1.9, per 100 000 person-years) times higher, respectively, in people with diabetes compared with those without. A significant decline in the annual major amputation rate was observed (p<0.05) and the annual minor amputation rate remained stable (p=0.63) when sex, age and people with and without diabetes were included as dependent variables. This is the first report of the national statistics of LLAs in Japan. The incidence of major and minor LLAs was 10 and 15 times higher, respectively, in people with diabetes compared with those without. A significant decline in the major amputation rate was observed, and the annual minor amputation rate remained stable during the observation period. This information can help to create an effective national healthcare strategy for preventing limb amputations, which affect the quality of life of patients with diabetes and add to the national healthcare expenditure.


A natural product from Cannabis sativa subsp. sativa inhibits homeodomain-interacting protein kinase 2 (HIPK2), attenuating MPP+-induced apoptosis in human neuroblastoma SH-SY5Y cells.
Homeodomain-interacting protein kinase 2 (HIPK2) is a conserved serine/threonine kinase, which regulate transcription, cell differentiation, proliferation and apoptosis. Previous evidences indicated that HIPK2 could be involved in the pathogenesis of neurodegenerative diseases, suggesting as a novel target for Parkinson's disease (PD) therapeutic development. Herein, gene microarray analysis was performed to verify the key regulatory function of HIPK2 in PD. (Z)-methylp-hydroxycinnamate (ZMHC, 7) with other eighteen compounds were isolated from Cannabis sativa subsp. sativa, growing in Bama Yao Autonomous County, one of the five largest longevity regions of the world. Intriguingly, ZMHC was identified to bind HIPK2 with high affinity through molecular modeling and molecular dynamics (MD) simulations. Moreover, cell morphology, flow cytometry and western blot assay suggested that ZMHC inhibited HIPK2, which attenuated MPP+-induced apoptosis in SH-SY5Y cells. In conclusion, these findings discovered a natural product that inhibited HIPK2, and highlighted that ZMHC could be a potential precursor agent for future PD therapy.


Challenges for the German Health Care System.
The German Health Care System (GHCS) faces many challenges among which an aging population and economic problems are just a few. The GHCS traditionally emphasised equity, universal coverage, ready access, free choice, high numbers of providers and technological equipment; however, real competition among health-care providers and insurance companies is lacking. Mainly in response to demographic changes and economic challenges, health-care reforms have focused on cost containment and to a lesser degree also quality issues. In contrast, generational accounting, priorisation and rationing issues have thus far been completely neglected. The paper discusses three important areas of health care in Germany, namely the funding process, hospital management and ambulatory care, with a focus on cost control mechanisms and quality improving measures as the variables of interest. Health Information Technology (HIT) has been identified as an important quality improvement tool. Health Indicators have been introduced as possible instruments for the priorisation debate.


Long-term follow-up of antiviral combination therapy in chronic hepatitis B.
For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in more than 40 percent of patients treated with combination therapy, 30 percent with interferon therapy, 18 percent with acyclovir, and 0 percent with no treatment. HBe reactivation occurred in two patients with cirrhosis. Hepatitis B surface seroconversion followed HBe seroconversion in 11 to 30 percent of treated patients. HBe seroconversion was significantly related to initial low levels of viral replication and to transient aminotransferase elevation during the second half of the interferon treatment of 16 weeks. Clinical improvement and persistent normalization of aspartate aminotransferase was observed in all patients with HBe seroconversion. Conversion to a state of virus latency (HBe negative) mostly occurred after therapy, suggesting that the specific immunologic host response had been brought about by the suppression of virus replication through antiviral agents. Recommendations for selection of patients for antiviral combination therapy are made on the basis of these long-term results.


Nonlocal constitutive relation for steady granular flow.
Extending recent modeling efforts for emulsions, we propose a nonlocal fluidity relation for flowing granular materials, capturing several known finite-size effects observed in steady flow. We express the local Bagnold-type granular flow law in terms of a fluidity ratio and then extend it with a particular Laplacian term that is scaled by the grain size. The resulting model is calibrated against a sequence of existing discrete element method data sets for two-dimensional annular shear, where it is shown that the model correctly describes the divergence from a local rheology due to the grain size as well as the rate-independence phenomenon commonly observed in slowly flowing zones. The same law is then applied in two additional inhomogeneous flow geometries, and the predicted velocity profiles are compared against corresponding discrete element method simulations utilizing the same grain composition as before, yielding favorable agreement in each case.


Celosiadines A and B, unusual guanidine alkaloids from Iresine diffusa.
Two unusual di-isopentenyl guanidine alkaloids, named celosiadines A (1) and B (2), were isolated from Iresine diffusa aerial parts. The structures of the compounds were elucidated from extensive spectroscopic analyses including HRMS, NMR and ECD. Celosiadines A and B showed favorable binding affinity to the androgen receptor (AR) in silico and were cytotoxic towards AR-sensitive (LNCaP) but not AR-insensitive (PC3) human prostate cancer cells in vitro.


"A state bordering on insanity"?: identifying drug addiction in nineteenth-century Canadian asylums.
This article examines the growing awareness of drug addiction as form of mental illness in several Canadian lunatic asylums in the last half of the nineteenth century and the beginning of the twentieth. Whereas in the 1870s and 1880s, medical and reform associations formed to cure and treat addiction and inebriety, asylum evidence suggests that it was not until the turn of the century that drug habituation was considered a condition which merited admission to asylum. Prior to the turn of the century, drug use appeared in the psychological profile of asylum entrants only as an attendant condition of a more traditional form of mental illness, such as mania or melancholia. Asylum physicians, seeking traditional categories, and utilizing subjective classification methods, generally would not consider addiction to be a distinct mental illness. At the end of the century, shifts in diagnostic convention and the official endorsement of those shifts signalled a change that was taking place in the asylum. The impact of drug addiction on the psychological profile of a patient was attracting more attention in the asylum. Subsequently drug addiction joined other earlier causes of mental illness, such as masturbation, and also began to be recognized as a mental condition worthy of treatment at the public asylum. Its status as mental disease proper, however, remained a point of debate.


Anomalous Origin of Pulmonary Artery From Aorta: Neonatal Autologous Aortopulmonary Reconstruction.
Anomalous origin of a branch pulmonary artery (PA) from the ascending aorta is rather rare within the spectrum of congenital cardiovascular anomalies. In the scarce subset of patients with anomalous origin of right PA (RPA) from the ascending aorta originating from the lateral aspect of the distal ascending aorta, early neonatal repair by employing native aortic tissue for RPA reconstruction combined with translocation of the aorta posteriorly to the RPA can be an alternative option in the surgical armamentarium.


Exciting extreme events in the damped and AC-driven NLS equation through plane-wave initial conditions.
We investigate, by direct numerical simulations and for certain parametric regimes, the dynamics of the damped and forced nonlinear Schrödinger (NLS) equation in the presence of a time-periodic forcing. It is thus revealed that the wave number of a plane-wave initial condition dictates the number of emerged Peregrine-type rogue waves at the early stages of modulation instability. The formation of these events gives rise to the same number of transient "triangular" spatiotemporal patterns, each of which is reminiscent of the one emerging in the dynamics of the integrable NLS in its semiclassical limit, when supplemented with vanishing initial conditions. We find that the L2-norm of the spatial derivative and the L4-norm detect the appearance of rogue waves as local extrema in their evolution. The impact of the various parameters and noisy perturbations of the initial condition in affecting the above behavior is also discussed. The long-time behavior, in the parametric regimes where the extreme wave events are observable, is explained in terms of the global attractor possessed by the system and the asymptotic orbital stability of spatially uniform continuous wave solutions.


Leucocyte adhesion molecules and alcoholic liver disease.
The causative agent of alcoholic liver disease is self-evident although the pathogenesis of the liver damage is not well understood. There is increasing evidence from both animal experiments and human studies that inflammation triggered in response to alcohol or its metabolites is important in the tissue damage and fibrosis of alcoholic liver disease. Both alcoholic hepatitis and alcoholic cirrhosis are characterized by inflammation of the liver, although the nature of the inflammatory infiltrate differs between the two diseases. The activation of leucocytes, their migration into tissue and subsequent interaction with target cells are all dependent on regulated adhesion. Therefore, leucocyte adhesion molecules and their counter-receptors will play a crucial role in determining the nature and activity of leucocytes infiltrating the liver in alcoholic liver disease. Evidence is now emerging that suggests roles for particular adhesion pathways in two aspects of the inflammatory response in alcoholic liver disease, (1) leucocyte recruitment to the liver, and (2) cell-mediated hepatocyte damage. It is important that these pathways are defined since therapy aimed at blocking leucocyte adhesion molecules might provide an effective future therapy for selected patients with alcoholic liver disease.


Applying contemporary neuroscience in exercise interventions for chronic spinal pain: treatment protocol.
Nonspecific chronic spinal pain is a common problem within the chronic pain population and is characterized by high social, economic and personal impact. To date, therapists are still struggling in adequately treating these types of patients, as seen in the small and short-term benefits of frequently applied primary care treatments. It is remarkable that despite the well-documented presence of abnormalities in central nociceptive processing in nonspecific chronic spinal pain patients, the implementation of this knowledge in clinical practice is still nearly non-existent. This paper provides the treatment protocol used in a large randomized controlled trial that aimed to assess the effectiveness of a modern neuroscience approach compared to usual care evidence-based physiotherapy. This comprehensive pain neuroscience treatment program combines pain neuroscience education and cognition-targeted exercise therapy. Based on previous small-scaled studies, this treatment protocol is expected to normalize central alterations by addressing central nervous system dysfunctions, psychological factors, as well as peripheral dysfunctions in a broader biopsychosocially-driven framework.


Green synthesis, characterization and bioactivity of biogenic zinc oxide nanoparticles.
In this study, we tried to enlighten the structure of zinc oxide nanoparticles (ZnO NPs) obtained from Thymbra Spicata L. plant by using green synthesis method in various ways. Some properties of zinc oxide nanoparticles were determined by using the characterization methods that scanning electron microscopy (SEM), Energy Dispersive X-ray analysis (EDX), fouirer transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet visible spectroscopy (UV-Vis) spectroscopy methods. The detected Zn nanoparticle sizes were determined to be between 6.5 nm and 7.5 nm. In addition to these studies, we investigated the antimicrobial effects of zinc oxide nanoparticles obtained by green synthesis against some pathogens. According to the results, it was seen that zinc oxide nanoparticles formed zones with a diameter of 16.3 mm, 10.25 mm, 13 mm and 10.2 mm, respectively, against Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25952, Pseudomonas aeruginosa ATCC 27853 bacteria and Candida albicans ATTC 90028 fungus, respectively. However, the radical quenching activity (DPPH) of the nanoparticles (Ts-ZnONP (79.67%)) was determined to be quite good compared to the positive control BHA. In addition, it is seen that the protective effect of ZnO NPs against DNA damage increases depending on the concentration. At a concentration of 100 mg/L, the DNA damage inhibitory effect was found to be maximum. In line with the comprehensive results, it was determined that the zinc oxide nanoparticles obtained with the green synthesis method have the potential of use in a wide variety of fields.


Structural characterization of lipid A obtained from Pantoea agglomerans lipopolysaccharide.
Lipopolysaccharide isolated from Pantoea agglomerans showed higher priming and triggering activities for macrophages in terms of tumor necrosis factor production than other lipopolysaccharides. To identify the difference in biological activities of lipopolysaccharide of Pantoea agglomerans from other lipopolysaccharides on the basis of structure, we determined the structure of the lipid A part, which is the biological center of lipopolysaccharides, by quantitative analysis, nuclear magnetic resonance spectroscopy and mass spectrometry. Lipopolysaccharide of Pantoea agglomerans is constructed with at least two kinds of lipid A of different levels of acylation. One is of the same type as that of Escherichia coli with hexa-acyl lipid A and the other is the Salmonella minnesota type with hepta-acyl lipid A.


Post-Validation Survey in Two Districts of Morocco after the Elimination of Trachoma as a Public Health Problem.
Trachoma is the leading infectious cause of blindness. In 2016, Morocco was validated by WHO as having eliminated trachoma as a public health problem. We evaluated two previously endemic districts in Morocco for trachomatous inflammation-follicular (TF), trachomatous trichiasis (TT), and antibodies against Chlamydia trachomatis, the causative agent of trachoma. Community-based cross-sectional surveys in the districts of Boumalene Dades and Agdez included 4,445 participants for whom both questionnaire and serology data were available; 58% were aged 1-9 years. Participants had eyes examined for TF and blood collected for analysis of antibodies to the C. trachomatis antigen Pgp3 by both a multiplex bead assay (MBA) and lateral flow assay (LFA). Seroconversion rates (SCR) per 100 people per year were used to estimate changes in the force of infection using Bayesian serocatalytic models. In Agdez, TF prevalence in 1-9-year-olds was 0.3%, seroprevalence ranged from 9.4% to 11.4%, and SCR estimates ranged from 2.4 to 3.0. In Boumalene Dades, TF prevalence in 1-9-year-olds was 0.07%, and modeling data from the different assays indicated a decrease in transmission between 20 and 24 years ago. The TF data support an absence of active trachoma in the two districts examined. However, seroprevalence and SCR in younger people were higher in Agdez than Boumalene Dades, showing that there can be differences in serology metrics in areas with similar TF prevalence. Data will be included in multicountry analyses to better understand potential thresholds for serological surveillance in trachoma.


Validation of quantitative bound- and pore-water imaging in cortical bone.
To implement and validate a previously proposed ultra-short echo time method for measuring collagen-bound- and pore-water concentrations in bone based on their T2 differences. Clinically compatible ultra-short echo time image sequences for quantitative T2 -based bound and pore-water imaging in bone were implemented and validated on a 3T human scanner and a 4.7T small bore system. Bound- and pore-water images were generating using T2 -selective adiabatic pulses. In both cases, the magnetization preparation was integrated into a three-dimensional ultra-short echo time acquisition, with 16 radial spokes acquired per preparation. Images were acquired from human cadaveric femoral mid-shafts from which isolated bone samples were subsequently extracted for nonimaging analysis using T2 spectroscopic measurements. A strong correlation was found between imaging-derived concentrations of bound and pore water and those determined from the isolated bone samples. These studies demonstrate the translation of the previously developed approaches for distinguishing bound and pore water from human cortical bone using practical human MRI constraints of gradient performance and radiofrequency power deposition.


Orally induced tolerance. Definition at the cellular level.
Several elements of the phenomenon of oral tolerance were examined. It was shown that whereas intragastric (i.g.) exposure of mice to the T-dependent antigens ovalbumin (OVA), bovine serum albumin, and human gamma globulin severely compromised the ability to respond to a subsequent challenge with the homologous antigen, i.g. treatment with T-independent antigens such as dinitrophenylated Ficoll, polyvinylpyrrolidone and bacterial lipopolysaccharide (LPS) did not induce anergy. Furthermore, mice parenterally primed to OVA were not only refractory to the induction of oral tolerance with OVA, but displayed an anamnestic response following i.g. treatment with the antigen. In a final line of investigation, it was shown that whereas mice administered OVA orally lost specific T cell functions such as the ability to (a) provide helper activity; (b) proliferate in response to antigen, and (c) mediate delayed-type hypersensitivity, such animals possessed OVA-specific functional B cells as evidenced by the ability to respond to OVA when the antigen was administered either linked to a recognizable carrier or in conjunction with LPS.


Successful endoscopic removal of a lighter swallowed 17 months before.
The majority of ingested foreign bodies will pass safely through the gastrointestinal tract, but long and rigid foreign bodies are associated with an increased risk of gastrointestinal impaction, perforation and bleeding. However, large foreign bodies which have been swallowed can remain trapped in the stomach over a longer period of time without any significant symptoms. This case report describes the case of a 36-year-old man addicted to heroin who purposefully swallowed a lighter (double wrapped in cellophane) and presented with hematemesis and melena 17 months after the ingestion of the foreign body. The lighter was successfully removed via flexible endoscopy using a polypectomy snare. Swallowed long and rigid foreign bodies trapped in the stomach over a long period of time always represent a special clinical and endoscopic challenge. In cases where endoscopic removal fails, a laparoscopic surgical approach may be an alternative.


[Comparative characteristics of carotid atherosclerosis in patients with hypertension concurrent with chronic coronary heart disease among the indigenous and non-indigenous population of the Yamal-Nenets Autonomic District].
To evaluate the degree of carotid artery (CA) atherosclerotic lesion and lipid metabolic disturbances in patients with hypertension and in those with hypertension concurrent with coronary heart disease (CHD) in the indigenous and non-indigenous population living in the Yamal-Nenets Autonomic District. Two hundred men and women aged 21 to 55 years (mean age 48.2 ± 0.7 years), who resided in the Far North, were examined. The patients were divided into 4 gender-and age-matched groups of 50 persons in each: 1) natives; 2) newcomers with hypertension only; 3) natives with CHD and hypertension; 4) non-natives with the above conditions. To study CA involvement, all the patients underwent duplex scanning of the brachiocephalic arteries at the extracranial level and blood lipid analysis in an outpatient setting (Salekhard). In all the patients, common CA intima-media thickness was significantly greater than the upper limit of the normal range defined in the Guidelines, this indicator proved to be highest in the groups of indigenous people (p<0.001). The latter with CHD and hypertension more commonly tended to have atherosclerotic lesion in the left CA (p=0.06) than the non-indigenous people whereas the number of stenosis in other CAs was similar. In the natives versus the newcomers with CHD and hypertension, the atherogenic blood lipid composition was due to the higher levels of total cholesterol and low-density lipoproteins. In the non- indigenous patients with CHD and hypertension, the atherogenicity of the blood lipid composition was characterized by the higher levels of triglycerides (p=0.04) and very low-density lipoproteins (p=0.02) with the lower concentrations of high-density lipoproteins as compared to those in the natives with CHD and hypertension.


Buffer layer of PEDOT:PSS/graphene composite for polymer solar cells.
High-efficiency polymer solar cells were made with a hydrophilic graphene oxide (GO) doped in poly(ethylene dioxythiophene) (PEDOT)-polystyrene sulfonic acid (PSS) composites using a structure of indium tin oxide/PEDOT:PSS:GO (40 nm)/poly(3-hexylthiophene-1,3-diyl) (P3HT)-[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) (1:0.6, 100 nm)/LiF (1 nm)/Al (70 nm). The energy conversion efficiency eta was enhanced from 2.1 to 3.8% by doping GO into the PEDOT:PSS buffer layer under AM1.5G 100 mW cm(-2) illumination in air. The pre-annealing of GO makes energy conversion efficiency 1.8 times that of the device based on a pristine PEDOT:PSS buffer layer. Because of the low price and ease of preparation, soluble graphene will be a promising buffer layer used in photovoltaic applications. Furthermore, it can be used in other electronic applications.


Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast-like Synoviocytes.
Since previous studies indicate that metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), we undertook this study to determine if changes in the genome-wide chromatin and DNA states in genes associated with nutrient transporters could help to identify activated metabolic pathways in RA FLS. Data from a previous comprehensive epigenomic study in FLS were analyzed to identify differences in genome-wide states and gene transcription between RA and osteoarthritis. We utilized the single nearest genes to regions of interest for pathway analyses. Homer promoter analysis was used to identify enriched motifs for transcription factors. The role of solute carrier transporters and glutamine metabolism dependence in RA FLS was determined by small interfacing RNA knockdown, functional assays, and incubation with CB-839, a glutaminase inhibitor. We performed 1 H nuclear magnetic resonance to quantify metabolites. The unbiased pathway analysis demonstrated that solute carrier-mediated transmembrane transport was one pathway associated with differences in at least 4 genome-wide states or gene transcription. Thirty-four transporters of amino acids and other nutrients were associated with a change in at least 4 epigenetic marks. Functional assays revealed that solute carrier family 4 member 4 (SLC4A4) was critical for invasion, and glutamine was sufficient as an alternate source of energy to glucose. Experiments with CB-839 demonstrated decreased RA FLS invasion and proliferation. Finally, we found enrichment of motifs for c-Myc in several nutrient transporters. Our findings demonstrate that changes in the epigenetic landscape of genes are related to nutrient transporters, and metabolic pathways can be used to identify RA-specific targets, including critical solute carrier transporters, enzymes, and transcription factors, to develop novel therapeutic agents.


Design of Calcium-Binding Proteins to Sense Calcium.
Calcium controls numerous biological processes by interacting with different classes of calcium binding proteins (CaBP's), with different affinities, metal selectivities, kinetics, and calcium dependent conformational changes. Due to the diverse coordination chemistry of calcium, and complexity associated with protein folding and binding cooperativity, the rational design of CaBP's was anticipated to present multiple challenges. In this paper we will first discuss applications of statistical analysis of calcium binding sites in proteins and subsequent development of algorithms to predict and identify calcium binding proteins. Next, we report efforts to identify key determinants for calcium binding affinity, cooperativity and calcium dependent conformational changes using grafting and protein design. Finally, we report recent advances in designing protein calcium sensors to capture calcium dynamics in various cellular environments.


A Simple Fluorometry of Hydroperoxides in Oils and Foods.
A fluorometry of hydroperoxides in oil and food samples was developed using diphenyl-1-pyrenylphosphine (DPPP) with a sample size of less than 20 mg by a batch method. The sensitivity was more than 10,000 times that of the conventional iodometry. A good accordance was obtained between peroxide values (POV) measured this way and by iodometry (r = 0.9995, n = 41, POV = 0.04-240).


The Effects of the Use of Patient-Accessible Electronic Health Record Portals on Cancer Survivors' Health Outcomes: Cross-sectional Survey Study.
In the past decade, patient-accessible electronic health record (PAEHR) systems have emerged as an important tool for health management both at the hospital level and individual level. However, little is known about the effects of PAEHR portals on the survivorship of patients with chronic health conditions (eg, cancer). This study aims to investigate the effects of the use of PAEHR portals on cancer survivors' health outcomes and to examine the mediation pathways through patient-centered communication (PCC) and health self-efficacy. Data for this study were derived from the Health Information National Trends Survey (HINTS 5, Cycle 4) collected from February 2020 to June 2020. This study only involved respondents who reported having been diagnosed with cancer (N=626). Descriptive analyses were performed, and the mediation models were tested using Model 6 from the SPSS macro PROCESS. Statistically significant relationships among PAEHR portal use, PCC, health self-efficacy, and physical and psychological health were examined using bootstrapping procedures. In this study, we referred to the regression coefficients generated by min-max normalization as percentage coefficients (bp). The 95% bootstrapped CIs were used with 10,000 resamplings. No positive direct associations between PAEHR portal use and cancer survivors' health outcomes were found. The results supported the indirect relationship between PAEHR portal use and cancer survivors' psychological health via (1) PCC (bp=0.029; β=.023, 95% CI .009-.054), and (2) PCC and health self-efficacy in sequence (bp=0.006; β=.005, 95% CI .002-.014). Besides, the indirect association between PAEHR portal use and cancer survivors' physical health (bp=0.006; β=.004, 95% CI .002-.018) via sequential mediators of PCC and health self-efficacy was also statistically acknowledged. This study offers empirical evidence about the significant role of PAEHR portals in delivering PCC, improving health self-efficacy, and ultimately contributing to cancer survivors' physical and psychological health.


The effect of photoperiod on adrenocortical stress response in mountain chickadees (Poecile gambeli).
Birds respond to environmental changes by modulating their levels of plasma corticosterone, a stress hormone produced by the adrenal glands. Baseline levels of corticosterone and the magnitude of adrenocortical response to acute stress are known to vary seasonally. Photoperiod is one of several potential factors which could affect the seasonal modulation of corticosterone secretion. In this study, we examined the effects of photoperiod on baseline and acute-stress-induced levels of corticosterone in adult mountain chickadees (Poecile gambeli). We exposed 20 mountain chickadees to short days (8L:16D h) for 60 days, after which half of the chickadees were switched to long days (14L:10D h). We collected blood samples from both groups 33 days after the switching. Our results showed that photoperiod had no significant effect either on baseline levels of corticosterone or on the maximum levels reached during the adrenocortical response to acute stress. However, photoperiod had a significant effect on the way that chickadees responded to acute stress: birds maintained on long days reached significantly higher levels of corticosterone between 5 and 20 min after capture than birds maintained on short days, which reached their maximum levels of corticosterone between 20 and 50 min. Females reached significantly higher levels of corticosterone than males in response to acute stress. Our results suggest that factors other than photoperiod are responsible for the observed seasonal changes in baseline levels of corticosterone, whereas photoperiod is directly involved in regulation of adrenocortical stress response.


Physiological and Metabolic Requirements, and User-Perceived Exertion of Immersive Virtual Reality Exergaming Incorporating an Adaptive Cable Resistance System: An Exploratory Study.
Objective: To measure metabolic and physiological demand, subjective fatigue, and enjoyment during a signature 30-minute immersive virtual reality (IVR) adaptive cable resistance exergaming session. Methods: Fourteen healthy college-aged individuals (seven females) were initially acquainted with the IVR equipment and gameplay dynamics. Participants then underwent a 30-minute IVR exergaming session performing six different cable resistance exercises. A portable metabolic gas exchange analyzer concurrently assessed energy expenditure (EE) through indirect calorimetry while a chest-worn monitor captured heart rate (HR). Participants subsequently completed questionnaires, including the Borg scale for rating of perceived exertion (RPE), Physical Activity Enjoyment Scale (PACES), and Simulator Sickness Questionnaire (SSQ). Results: The mean EE, mean metabolic equivalent, and average total calories expended during the 30-minute session were 14.7 (standard deviation [SD] 2.8) kcal/minute, 12.9 (SD 0.5), and 440 (SD 84) kcals respectively. The mean HR was 176 (SD 3.1) beats per minute (bpm) with a mean max HR of 188 SD (SD 2.9) bpm. The combined training volume among all participants was 16,102 kg (SD 4137). Participants classified the IVR training session to be "somewhat hard-to-hard" with a RPE score of 14 (SD 1) while indicating the session to be "enjoyable" with a PACES score of 4.31 (SD 0.36). The participants did not report any cybersickness symptoms, demonstrating an average total SSQ score of 24.04 (SD 24.13). Conclusions: IVR exergaming incorporating cable resistance training elicits high EE and physiological demand with high enjoyment scores while attenuating perceived fatigue. The potential for IVR to elicit these acute training effects over long-term training periods warrants further investigation into its contribution to fitness and health.


Cellular target of streptomycin in the internal ear.
The cellular target of streptomycin (STP) was investigated by analyzing the activity of glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT) enzymes of synthesis of GABA and acetylcholine (Ach), respectively, [supposedly located in hair cells (GAD) or efferent terminals (ChAT)] in control and in 50 day-STP-treated colored guinea pig vestibular homogenates. Vestibular and auditory function were assessed by measuring postrotatory nystagmus response (PNR) and auditory brainstem evoked potentials (ABP). Morphological changes were followed by light and electron microscopy. STP-treated animals exhibited a GAD decrease of 83.6% with respect to controls whereas ChAT did not suffer any change. Assessment of PNR and ABP showed that STP affected only the former since animals lost it between the 20th and the 30th day of treatment, whereas ABP was not modified. Morphological experiments detected vestibular hair cell deterioration as the only cell type affected by STP. These results confirm the predilection of STP to affect vestibular function by damage to hair cells and show that this effect can be followed by measurement of GAD and ChAT in the vestibule as markers for hair cells and efferent terminals, respectively.


Controlling the C1/C2+ product selectivity of electrochemical CO2 reduction upon tuning bimetallic CuIn electrocatalyst composition and operating conditions.
Electrochemical carbon dioxide (CO2) reduction (eCO2R) over Cu-based bimetallic catalysts is a promising technique for converting CO2 into value-added multi-carbon products, such as fuels, chemicals, and materials. For improving the process efficiency, electrocatalyst development for the eCO2R must be integrated with tuning of operating conditions. For example, CuIn-based materials typically lead to preferential C1 product selectivity, which delivers the desired C2+ products upon varying the In/Cu ratio and operating conditions (i.e., in 0.1 M KHCO3 electrolytes using an H-type cell with a cation exchange membrane vs. in 1 M KOH electrolytes using a flow cell with an anion exchange membrane). At lower Cu-loading (i.e., InCu5Ox material), the maximum faradaic efficiency of HCOOH (FEHCOOH) of 70% was achieved at -1 V versus the reversible hydrogen electrode (vs. RHE) in an H-type cell. However, upon increasing the Cu loading, the preferential product selectivity could be altered: the InCu73Ox material led to a high CO selectivity (maximum FE of 51%) in the H-type cell at -0.8 V vs. RHE and delivered a current density of 100 mA cm-2 with a FEC2+ of up to 37% at -0.8 V vs. RHE in the flow cell configuration. Various characterization tools were also employed to probe the catalytic materials to rationalize the electrocatalytic performance.


X-ray crystallographic structure of BshC, a unique enzyme involved in bacillithiol biosynthesis.
Bacillithiol is produced by many Gram-positive bacteria via a pathway utilizing the enzymes BshA, BshB, and BshC. Here we report the 1.77 Å resolution crystal structure of BshC, the putative cysteine ligase in bacillithiol production. The structure reveals that BshC contains a core Rossmann fold with connecting peptide motifs (CP1 and CP2) and a unique α-helical coiled-coil domain that facilitates dimerization. The model contains citrate and glycerol in the canonical active site and ADP in a second binding pocket. The overall structure and bound ligands give insight into the function of this unique enzyme.


Third trimester abortion for fetal abnormality.
Developments in medical technology have increased the possibility of diagnosing severe structural abnormalties in the fetus. If these occur, a woman may request termination of her pregnancy. This raises serious ethical and legal questions, in particular if the anomalies are discovered in the third trimester when the fetus is considered viable. Should doctors be allowed to act upon a request for abortion in such a situation, and, if so, which safeguards should be in place? These questions are discussed with special reference to the Netherlands where a commission established by the government recently published a report on this matter.


Activating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents.
Multiple areas within the reticular activating system (RAS) can hasten awakening from sleep or light planes of anesthesia. However, stimulation in individual sites has shown limited recovery from deep global suppression of brain activity, such as coma. Here we identify a subset of RAS neurons within the anterior portion of nucleus gigantocellularis (aNGC) capable of producing a high degree of awakening represented by a broad high frequency cortical reactivation associated with organized movements and behavioral reactivity to the environment from two different models of deep pharmacologically-induced coma (PIC): isoflurane (1.25%-1.5%) and induced hypoglycemic coma. Activating aNGC neurons triggered awakening by recruiting cholinergic, noradrenergic, and glutamatergic arousal pathways. In summary, we identify an evolutionarily conserved population of RAS neurons, which broadly restore cerebral cortical activation and motor behavior in rodents through the coordinated activation of multiple arousal-promoting circuits.


Contemporary human diets and their relation to health and growth: overview and conclusions.
Contemporary human diets are probably as diverse now as they have ever been in the history of mankind. The abundance of food in the western world is in stark contrast to the lack of food and near starvation in parts of Africa, the continent where Homo sapiens evolved. The development of agriculture has enabled the population of the world to expand and to colonize almost the whole of its land surface, but the dependence on one staple food has introduced problems. If the staple crop fails, for example because of drought, there may be no alternative, and undernutrition and starvation are the result. Further, if the rest of the diet does not provide the nutrients that the staple food lacks, diseases due to specific nutrient deficiencies become widespread. Vitamin deficiencies among adults are less common now than they were 50 years ago, but even today millions of children in the poor rice-eating areas of the world are blind because their diets were deficient in vitamin A. For physiological reasons infants and young children will suffer most wherever there is a scarcity of food, of water, or of specific nutrients.


[Cognitive impairments in psychoactive drug addicts].
This short literature review addresses common features of the pathogenesis and treatment of cognitive impairment in people with drug addiction (cocaine, opioids, hashish, amphetamine, benzodiazepines). A role of cholinergic deficit in the development of cognitive impairment and possibilities of its treatment with acetylcholineesterase inhibitions are analyzed.


The 11 A resolution projection map of Na+/K+-ATPase calculated by application of single particle analysis to two-dimensional crystal images.
Two-dimensional (2D) crystals of Na+/K+-ATPase were vitrified and observed with an electron cryo-microscope that allowed specimen observation at liquid helium temperature. Images showing 19 A spots on the optical diffraction patterns were digitized and processed by a crystallographic method. After optimization of parameters for the image processing, the locally averaged images revealed that each 2D crystal contained heterogeneous molecules. Single particle analysis was therefore applied to the 2D crystal images to select homogeneous molecule images, and averaging the selected images significantly improved map quality. Five major peak densities were clearly resolved in the new projection map, while two were found previously.


Limitations of risk score models in patients with acute chest pain.
Cardiac multidetector computed tomography (CMCT) has potential to be used as a screening test for patients with acute chest pain, but several tools are already used to risk-stratify this population. Risk models exist that stratify need for intensive care (Goldman), short-term prognosis (Thrombolysis in Myocardial Infarction, TIMI), and 1-year events (Sanchis). We applied these cardiovascular risk models to candidates for CMCT and assessed sensitivity for prediction of in-hospital acute coronary syndrome (ACS). We hypothesized that none of the models would achieve a sensitivity of 90% or greater, thereby justifying use of CMCT in patients with acute chest pain. We analyzed TIMI, Goldman, and Sanchis in 148 consecutive patients with chest pain, nondiagnostic electrocardiogram, and negative initial cardiac biomarkers who previously met inclusion and exclusion criteria for the Rule-Out Myocardial Infarction Using Coronary Artery Tomography Study. ACS was adjudicated, and risk scores were categorized based on established criteria. Risk score agreement was assessed with weighted kappa statistics. Overall, 17 (11%) of 148 patients had ACS. For all risk models, sensitivity was poor (range, 35%-53%), and 95% confidence intervals did not cross above 77%. Agreement to risk-classify patients was poor to moderate (weighted kappa range, 0.18-0.43). Patients categorized as "low risk" had nonzero rates of ACS using all 3 scoring models (range, 8%-9%). Available risk scores had poor sensitivity to detect ACS in patients with acute chest pain. Because of the small number of patients in this data set, these findings require confirmation in larger studies.


Empyema thoracis: Surgical management in children.
Empyema thoracis can produce significant morbidity in children if inadequately treated. Correct evaluation of the stage of the disease, the clinical condition of the child and proper assessment of the response to conservative treatment is crucial in deciding the mode of further surgical intervention. This ranges from intercostal chest tube drainage and video-assisted thoracoscopic surgery to open decortication. Surgical decortication becomes mandatory in neglected cases; it gives very gratifying results ameliorating the disease rapidly and is well tolerated by young patients. This article reviews the current literature and discusses the important considerations while managing these patients. Indications for surgery are highlighted, based on our large experience at a tertiary care center.


Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: correlation of Leu-2, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression.
Three-color immunofluorescence has been used to determine the co-expression of cell surface antigens on human peripheral blood lymphocytes. Monoclonal antibodies or avidin were coupled to either FITC (green), phycoerythrin (orange), or Texas Red (red) fluorochromes. These three fluorochromes could be independently measured by using a dual laser FACS IV system equipped with an argon ion laser (488 nm) and a dye laser (600 nm). Human peripheral blood lymphocytes were stained with the following combinations of reagents: (1) FITC anti-Leu-11a + PE anti-Leu-2a + TR avidin/biotin anti-Leu-7; (2) FITC anti-Leu-11a + PE anti-Leu-3a + TR avidin/biotin anti-Leu-7; (3) FITC anti-Leu-8 + PE anti-Leu-2a + TR avidin/biotin anti-Leu-7; and (4) FITC anti-Leu-11a + PE anti-Leu-2 + TR avidin/biotin anti-Leu-8. The light scatter, green fluorescence, orange fluorescence, and red fluorescence signals for each sample were stored by a Consort 40 PDP/11 computer in list mode files. Sequential reanalysis of the data directly demonstrated the existence of several unrecognized subpopulations of lymphocytes. Previously, we reported that the anti-Leu-7 and anti-Leu-11 antibodies can be used to identify discrete subsets of human NK cells with distinct functional capacities. In this report, we show that these subsets can be further subdivided on the basis of Leu-8 and Leu-2 expression. Thus, these studies illustrate how multicolor and multiparameter flow cytometry can further our understanding of cellular heterogeneity within this group of lymphocytes.


The role of histamine in allergic diseases.
Histamine, which is stored mainly in mast cells and basophils, is a prominent contributor to allergic disease. Elevations in plasma or tissue histamine levels have been noted during anaphylaxis and experimental allergic responses of the skin, nose, and airways. Of the four cardinal signs of asthma (bronchospasm, edema, inflammation, and mucus secretion), histamine is capable of mediating the first two through its H1 receptor and mucus secretion through its H2 receptor. Of the five cardinal signs of allergic rhinitis (pruritus, mucosal edema, sneezing, mucus secretion, and late-phase inflammatory reactions), histamine is capable of mediating the first three through its H1 receptor. In the nose, mucus secretion can be reflexively mediated by H1 and possibly also by H2 receptors. In the skin the cardinal features of urticaria (vasodilation, vascular permeability, and pruritus) can be mediated by stimulation of the H1 receptor. In anaphylaxis histamine H1-receptor stimulation can mediate vascular permeability, smooth muscle contraction, and tachycardia, whereas H2-receptor stimulation can mediate mucus secretion. Stimulation of both receptors can mediate vasodilation and reduce peripheral vascular resistance. Thus although histamine is only one of many mediators of allergic disease, it plays a primary role in allergic rhinitis, urticaria, anaphylaxis, and to a lesser degree, asthma.


Pediatric high-grade glioma: biologically and clinically in need of new thinking.
High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.


Isolation by phenology synergizes isolation by distance across a continuous landscape.
Pollen is generally dispersed over short distances, which promotes population genetic structure across continuous two-dimensional space. Quantitative genetic variance in flowering time structures mating pools in the temporal dimension, at least with respect to the phenology loci. We asked if these two phenomena, isolation by distance (IBD) and isolation by phenology (IBP), synergistically promote genetic structure. We constructed an individual-based model that tracked genotype frequencies at flowering time and neutral loci across a uniform landscape, over multiple generations, under four mating schemes: panmixia, IBD only, IBP only, and IBP × IBD. IBD × IBP divided the population into spatial clusters of early-, mid-, and late-flowering genotypes and strongly increased its quantitative genetic variance. Flowering time did not cluster under IBP, but its genetic variance increased moderately. IBD induced mild spatial structure in a nonassortative reference trait but did not change its variance. Importantly, the spatial correlation of genotypes at neutral loci was twice as strong under IBD × IBP compared with IBD alone. IBD × IBP also drew neutral loci into gametic disequilibrium with flowering time loci, structuring them temporally. Temporal and spatial mating pool structure promotes local differentiation. This trend would facilitate adaptation on small spatial scales.


Anatomy and histology of the frontalis muscle.
To determine the gross and histologic configurations of the medial and lateral frontalis muscle. After making a midcoronal incision and bluntly dissecting to the orbital rim, the frontalis muscle was marked and measured. A protractor was used to measure the frontalis-orbicularis angle (FOA) and, when present, the angle of central bifurcation (AOB). Three strips of full-thickness forehead soft tissue measuring 0.5 cm × 8 cm were excised 3, 4.5, and 6 cm above the supraorbital notch and analyzed histologically for the presence of skeletal muscle fibers. Data were analyzed using 2-sample t tests, paired t tests, Pearson correlations, and mixed effect models. A p value of ≤ 0.05 was considered statistically significant. Sixty-four hemifaces of 32 cadavers (16 males) were dissected. All specimens were Caucasian. The average age was 78.2 years (range, 56-102 years). The average FOA was 88.7° (13.0°), and the average AOB was 90.0° (26.4°). A visible midline bifurcation occurred in 28 of 32 subjects (88%) at an average height of 4.7 cm (range, 2.4-7.2 cm) superior to the supraorbital notch. Continuous skeletal muscle fibers were present within the midline bifurcation histologically in 89%, 75%, and 11% of specimens 3.5, 5.0, and 6.5 cm above the supraorbital notch, respectively. In 46% of individuals, skeletal muscle fibers were continuously present microscopically within the gross bifurcation. While a medial frontalis muscle bifurcation occurs grossly in most senescent Caucasians, muscle fibers exist microscopically within this zone in nearly half of individuals.


PRMT5 Interacting Partners and Substrates in Oligodendrocyte Lineage Cells.
The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells and immunoprecipitated with PRMT5 antibodies, we identified 1196 proteins as PRMT5 interacting partners. These proteins were related to molecular functions such as RNA binding, ribosomal structure, cadherin and actin binding, nucleotide and protein binding, and GTP and GTPase activity. We then investigated PRMT5 substrates using iTRAQ-based proteomics on cytosolic and nuclear protein extracts from CRISPR-PRMT5 knockdown immortalized oligodendrocyte progenitors compared to CRISPR-EGFP controls. This analysis identified a similar number of peptides in the two subcellular fractions and a total number of 57 proteins with statistically decreased symmetric methylation of arginine residues in the CRISPR-PRMT5 knockdown compared to control. Several PRMT5 substrates were in common with cancer cell lines and related to RNA processing, splicing and transcription. In addition, we detected ten oligodendrocyte lineage specific substrates, corresponding to proteins with high expression levels in neural tissue. They included: PRC2C, a proline-rich protein involved in methyl-RNA binding, HNRPD an RNA binding protein involved in regulation of RNA stability, nuclear proteins involved in transcription and other proteins related to migration and actin cytoskeleton. Together, these results highlight a cell-specific role of PRMT5 in OPC in regulating several other cellular processes, besides RNA splicing and metabolism.


Study on Numerical Simulation for Component Transportation and Oil Displacement of a Microbial System.
Component transportation is one of the main mechanisms for numerical simulation in microbial oil recovery. However, the research on the component transportation considering the inhibition of metabolites is very limited. A mathematical model of oil displacement in a microorganism system including microbial growth and metabolism equation, component transport equation, and porous media physical property variation equation was established in this paper. The equation was discretized and solved by implicit pressure and explicit saturation. The MATLAB simulation results showed that the chromatographic separation between microorganisms and nutrients happened because of the adsorption of porous media and the activity of microorganisms during the transportation, and the separation degree of the chromatography became higher as the permeability became lower and the injection speed became slower. The multislug alternative injection mode could reduce the degree of chromatographic separation, and the recovery rate can be increased to 50.82%. The results of this study could provide theoretical guidance for the popularization and application of microbial enhanced oil recovery (MEOR).


[Effect of destruction of individual nuclei of the amygdaloid complex on elaboration of avoidance reaction in rats].
Formation of one-trial passive avoidance reactions (PAR) after bilateral symmetrical ablations of some nuclei of the amygdala complex (AC) was studied in Wistar male rats. Some nuclei belonging to the corticomedial or basolateral group of AC nuclei were subjected to electrolythical ablation. It has been found that ablations of individual AC nuclei statistically significantly prevent PAR elaboration. The data obtained are interpreted from the standpoint of disturbance of the morpho-functional organization of the AC efferent systems.


The impact of thyroid dysfunction in subclinical ranges on metabolic syndrome (MetS) is not well known. The aim of the present study is to evaluate the association of thyroid dysfunction with MetS and its components. In the cross-sectional population-based Tehran Thyroid Study, out of 5 786 randomly selected participants, aged≥20 years, subjects with thyroid nodules and cancer or any severe systemic disease, those who were pregnant and those using thyroid medication were excluded, leaving 5 422 subjects to be investigated. Body weight, waist circumference, and blood pressure were measured. Fasting blood glucose and concentrations of lipids and lipoproteins, free T4, and TSH were assayed. Mean age of the participants was 40.3±14.4 of whom 101 (2%) had overt hypothyroidism, 294 (5%) subclinical hypothyroidism, 82 (2%) overt hyperthyroidism, and 178 (3%) had subclinical hyperthyroidism; 1 704 (32%) had MetS. Clinically hypothyroid subjects had the highest prevalence of MetS (41.6%), abdominal obesity (45%), and hypertriglyceridemia (58%) compared to other groups (p<0.05). Significant odds ratio for prevalent MetS was observed only in clinically hypothyroid men [OR: 2.9, 95% CI: 1.04, 8.4, p=0.04]. In women, the association between overt hypothyroidism and MetS was marginally significant only in the crude model [OR: 0.068, 95% CI (0.97-2.42), p=0.06]. There was higher risk of Mets in subclinically hypothyroid subjects, aged>50. Overt and subclinical hyperthyroidism had significantly higher odds of hyperglycemia in men and women after full adjustment for age, smoking, and BMI. Overt hypothyroidism and subclinical hypothyroidism especially in the elderly could be associated with MetS. Hyperthyroidism may induce hyperglycemia.


Sexual life of women in the climacterium: A community-based study.
Our purpose of conducting this community-based study was to determine sexual functions of women in climacterium and effects of menopausal symptoms on sexual functions. It was descriptive, cross-sectional, and community-based. The study sample consisted of 282 climacteric women. Menopause Rating Scale (MRS), Female Sexual Function Index (FSFI), and Sexual Satisfaction Scale for Women (SSS-W) were used for data collection. The total score was 13.42 ± 8.82 for MRS, 18.73 ± 9.79 for FSFI, and 82.56 ± 18.07 for SSS-W. Seventy-nine-point four percent of the women had sexual dysfunction. While complaints typical of the climacteric period increased, sexual functions and satisfaction decreased.


Acute subdural hematoma: new model delineation and effects of coagulation inhibitors.
To develop a highly reproducible rat model and behavioral tests for acute subdural hematoma (ASDH) and to investigate the role of intravascular coagulation and thrombin in the pathogenesis of brain injury in this model. A new method was implemented to inject 200 microl of autologous blood subdurally in rats. Immunohistochemistry was used to investigate intravascular fibrin deposition and thrombin levels in the cortex underlying the ASDH. Effectiveness of systemic heparin, argatroban, or ginkgolide B treatment was determined by histological lesion volume, number of occluded microvessels, and neurological deficits. Neurological deficits were monitored for 7 days after ASDH by use of forelimb placing, forelimb use asymmetry, and corner turn tests. Consistent brain damage and sensorimotor deficits were observed in all animals with ASDH. Histological analysis demonstrated occluded microvessels and enlarged perivascular spaces in the underlying cortex starting 1 hour after hematoma induction. Fibrin and thrombin immunoreactivity were increased in the lesioned cortical parenchyma at 4 and 24 hours. However, no intravascular fibrin deposition was detected. Heparin induced hemorrhagic transformation in the cortical lesion and did not attenuate microvessel occlusion. Argatroban and ginkgolide B did not induce hemorrhage but failed to improve microvessel occlusion, lesion volume, and neurological deficits. Intravascular coagulation and thrombin are not the major mediators of brain damage after ASDH. The model and behavioral tests presented in this study can be used to investigate other putative mechanisms of injury and to test future therapeutic interventions in ASDH.


Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis.
Matrix metalloproteinases (MMPs) are believed to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described as a useful biomarker for IPF. However, little is known regarding the significance of MMP-10 as a biomarker for IPF. This observational cohort study included 57 patients with IPF. Serum MMPs were comprehensively measured in all patients, and the relationships between these markers and both disease severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7 and -10 levels were measured in 19 patients to investigate the correlation between these markers and their corresponding serum values. Immunohistochemical staining for MMP-10 was also performed in IPF lung tissue. Serum MMP-7 and -10 levels correlated significantly with both the percentage of predicted forced vital capacity (ρ = -0.31, p = 0.02 and ρ = -0.34, p < 0.01, respectively) and the percentage of predicted diffusing capacity of the lung for carbon monoxide (ρ = -0.32, p = 0.02 and ρ = -0.43, p < 0.01, respectively). BALF MMP-7 and -10 levels correlated with their corresponding serum concentrations. Only serum MMP-10 predicted clinical deterioration within 6 months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced and localized to the alveolar epithelial cells, macrophages, and peripheral bronchiolar epithelial cells. MMP-10 may be a novel biomarker reflecting both disease severity and prognosis in patients with IPF.


Growth assessment in children with extra-hepatic portal vein obstruction and portal hypertension.
Several studies carried out to examine the growth of children with extra-hepatic portal vein obstruction and portal hypertension have reported a variety of findings. To assess anthropometric indices in children with portal hypertension due to extra-hepatic portal vein obstruction and who were treated by endoscopic variceal sclerotherapy. Anthropometric data were obtained retrospectively from the medical records of 24 patients who had been followed for 3.8 +/- 2.5 years at the Pediatric Gastroenterology Outpatient Clinic of the University Hospital, Campinas, SP, Brazil. The mean Z scores of weight for age, height for age and body mass index at diagnosis and at the last consultation were compared to reference data of the National Center for Health Statistics. The two recordings were compared to assess the long-term effect of the condition. The mean Z scores at diagnosis and at the last follow-up visit were all within normal ranges when compared to the reference population, with the following respective values: weight for age, 0.042 +/- 1.09 and 0.132 +/- 1.29; height for age, 0.200 +/- 1.04 and 0.466 +/- 1.24, and body mass index, -0.223 +/- 0.98 and -0.198 +/- 0.98. In addition, there were no significant differences between the Z score values obtained in the two recordings. Portal hypertension due to extra-hepatic portal vein obstruction was not associated with growth impairment in the group of children studied.


Release and mobility of hexavalent chromium in contaminated soil with chemical factory waste: Experiments, Cr isotope analysis and reactive transport modeling.
Our study focused on the leaching processes in soil contaminated with hexavalent chromium (Cr(VI)), traced to industrial waste from a disused site and resulting in groundwater contamination. Mineral and geochemical characterization of the soil by means of XRD, SEM-EDS, total digestion and sequential extractions revealed that the main Cr content was from solid waste located in the upper meter of the soil profile. Flow-through and column experiments were carried out to investigate the processes responsible for Cr(VI) release. Cr(VI) mobility along the soil profile was also assessed. Moreover, Cr isotope signatures were used to evaluate a potential Cr(VI) reduction process, which preferably could immobilize toxic Cr(VI) complexes. One-dimensional (1D) numerical simulations reproduced the Cr(VI) release from the flow-through experiment containing the Cr(VI) rich-solid waste and also the Cr(VI) mobility along the column experiment. These results enabled us to interpret quantitatively the processes resulting in Cr(VI) contamination and mobility along the soil profile. Cr(VI) was released from dissolving Cr(VI)-rich phases (e.g., sodium chromate, Cr(VI)-hydrocalumite and Cr(VI)-ettringite) of the solid waste layer. Cr(VI) reduction and Cr(VI) adsorption did not take place along the column. Such accurate characterization of these processes is necessary for the mitigation of Cr(VI) mobility in contaminated soils.


[Knotted intravascular catheters--what should be done?].
Fixed intravasal catheters are mainly caused by knots. Removal can be achieved by intervention or surgical exploration, but this is associated with additional morbidity and mortality. 2 patients were operated for knotted catheters in our institution during the last 2 years, and their records are demonstrated. Treatment options, possible complications, catheter types and locations of knotting are analyzed by a medline search. the search revealed the data from 115 patients. 53 (46.1%) of all "lost" catheters were Swan-Ganz catheters. In 60.9% the catheters could be removed by radiological interventions. Open revision was necessary in 33% of all cases. The catheters were left in place when the clinical condition of the patient did not allow removal (n = 7). However, these patients suffered from a high mortality (5 of 7 patients). Over all mortality reached 8.7%. In the own two cases one removal by sternotomy and one by exploration of the right internal jugular vein were necessary, both operations succeeded without complications. Most of all "lost" intravasal catheters are removed by radiological intervention; only one third needs open surgical therapy. These procedures are harmful for the patient and bear considerable risks for complications.


Evaluation of biosafe alternative to eosin in hematoxylin and eosin staining procedure: A comparative study.
Hematoxylin and eosin staining is the globally accepted staining technique for histology and histopathology sections. Hematoxylin is a natural dye as compared to eosin which is a synthetic dye manufactured from chemicals. Eosin acts as a counterstain to hematoxylin giving a sharp contrast to its blue color. Eosin being a chemical, can cause health hazards and environmental pollution. Using eco-friendly materials and going organic is the demand of this era. Curcuma longa rhizomes are proven to contain curcuminoids that exhibit various medicinal properties and curcumin the bright yellow component of the plant, that is, being used as a colorant. This natural dye from C. longa provides a significant alternative to eosin as they are safer to use without health hazards and are biodegradable and have easy disposability. To evaluate and compare the staining qualities of C. longa (turmeric) with hematoxylin and eosin (H&E). A total of 100 paraffin-embedded tissue block specimens of various pathological tissues were stained with H and E and hematoxylin and curcumin (H&C). Evaluation and comparison of the staining efficacy were done for all the pathological tissues. The obtained data were subjected to statistical analysis. H&C staining gave comparable results with H and E staining with a statistically insignificant P value (p > 0.05). Curcumin has shown equivalent staining to that of eosin. Thus, it can be used as a better alternative.


Maintenance of above-branch balance during primate arboreal quadrupedalism: coordinated use of forearm rotators and tail motion.
Animals that live and travel in trees display a variety of morphological and behavioral adaptations to help them maintain balance on narrow flexible supports. Among these adaptations are long tails that can be used as counterweights, and freely mobile limbs in order to reach discontinuous supports. Here we describe two additional ways in which these features can contribute to balance during arboreal locomotion. Electromyographic (EMG) recordings of the forearm rotators pronator quadratus and supinator during over-ground and above-branch quadrupedal locomotion in five species of Old World monkeys revealed their contribution to shifting the weight of the body to help change the direction of travel and maintain balance on a branch. In addition, we observed a coordinated mechanism consisting of a sweeping tail rotation toward the direction of imbalance, to impart an angular momentum to the body that assists in the restoration of balance. While all five primate species utilized forearm rotators to shift their bodies toward one side or the other during quadrupedal walking along a branch, the tail-whip mechanism was most frequently used by the largest and most terrestrial species. We suggest that their large size and/or terrestrial habits have made them less adept at arboreal locomotion, and therefore most likely to utilize auxiliary balancing mechanisms. The usefulness of a long tail as a balancing aid during arboreal locomotion highlights the puzzling nature of the evolutionary loss of a tail in the ape and human lineage.


Neoplastic transformation and lineage switching of rat liver epithelial cells by retrovirus-associated oncogenes.
Tumors produced by a chemically transformed rat liver epithelial (RLE) cell line and its single cell-derived clonal subpopulations demonstrate wide-ranging morphological presentations including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors [Am J Pathol 127:168-181, 1987]. To address the question of heterogeneity of tumors derived from transformed RLE cells, we have used recombinant retroviruses containing the following transforming oncogenes: v-raf (3611-MSV), v-raflv-myc (J2), v-myc (J5), and v-Ha-ras (pRNR16). All of the oncogenes, with the exception of v-myc (J5), were efficient transforming agents in the RLE cells. Tumors derived from the v-raf- and, to a lesser extent, those from v-Ha-ras-transformed RLE cells showed mixed epithelial-mesenchymal morphology, whereas the combination of v-raflv-myc (J2) consistently produced differentiated trabecular carcinomas. These data suggest that the lineage commitment of the RLE cells can be perturbed by a single transforming oncogene and that different tumor types derived from these cells may reflect the expression of a selective oncogene or a combination of oncogenes.


"You have no good blood in your body". Oral communication in sixteenth-century physicians' medical practice.
In his personal notebooks, the little known Bohemian physician Georg Handsch (1529-c. 1578) recorded, among other things, hundreds of vernacular phrases and expressions he and other physicians used in their oral interaction with patients and families. Based primarily on this extraordinary source, this paper traces the terms, concepts and images to which sixteenth-century physicians resorted when they explained the nature of a patient's disease and justified their treatment. At the bedside and in the consultation room, Handsch and his fellow physicians attributed most diseases to a local accumulation of impure, putrid or otherwise pathological humours. The latter were commonly said to result, in turn, from an insufficient concoction and assimilation of food and drink in the stomach and the liver or from an obstruction of the humoral flow inside the body and across its borders. By contrast, other notions and explanatory models, which had a prominent place in contemporary learned medical writing, hardly played a role at all in the physicians' oral communication. Specific disease terms were rarely used, a mere imbalance of the four natural humours in the body was almost never inculpated, and the patient's personal life-style and other non-naturals did not attract much attention either. These striking differences between the ways in which physicians explained the patients' diseases in their daily practice and the explanatory models we find in contemporary textbooks, are attributed, above all, to the physicians' precarious situation in the early modern medical marketplace. Since dissatisfied patients were quick to turn to another healer, physicians had to explain the disease and justify their treatment in a manner that was comprehensible to ordinary lay people and in line with their expectations and beliefs, which, at the time, revolved almost entirely around notions of impurity and evacuation.


Nitric oxide modulates ATP-evoked currents in mouse Leydig cells.
Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice. For this purpose, we recorded ATP-evoked currents in isolated Leydig cells using the whole cell patch clamp technique after treatment with L-NAME (300 μM and 1 mM), L-arginine (10, 100, 300, and 500 μM), ODQ (300 μM), and 8-Br-cGMP (100 μM). Our results show that NO produced by Leydig cells in basal conditions is insufficient to change the ATP-evoked currents and that extra NO provided by adding 300 μM L-arginine positively modulates the current through a mechanism involving the NO/cGMP signaling pathway. Thus, we report an interaction between the nitrergic and purinergic systems in Leydig cells and suggest that Ca2+ entry via the purinergic receptors can be regulated by NO.


A twin study of human red blood cell catechol-o-methyl transferase.
Significant sibling-sibling and within-family correlations of human red blood cell catechol-o-methyl transferase activity have suggested a high degree of genetic control over levels of activity of this catecholamine-related enzyme. However, family studies do not disentangle genetic from environmental similarities as causative of within-family correlations. We therefore undertook a human twin study using the monozygotic-dizygotic comparison method. Twelve pairs of monozygotic twins had an intraclass correlation of 90 in red blood cell catechol-o-methyl transferase activity, and seven pairs of dizygotic twins had an intraclass correlations of 37. Heritability of the enzyme activity was estimated by different methods as between 68-100 per cent.


Probing native protein structures by chemical cross-linking, mass spectrometry, and bioinformatics.
Chemical cross-linking of reactive groups in native proteins and protein complexes in combination with the identification of cross-linked sites by mass spectrometry has been in use for more than a decade. Recent advances in instrumentation, cross-linking protocols, and analysis software have led to a renewed interest in this technique, which promises to provide important information about native protein structure and the topology of protein complexes. In this article, we discuss the critical steps of chemical cross-linking and its implications for (structural) biology: reagent design and cross-linking protocols, separation and mass spectrometric analysis of cross-linked samples, dedicated software for data analysis, and the use of cross-linking data for computational modeling. Finally, the impact of protein cross-linking on various biological disciplines is highlighted.


A model for Plasmodium falciparum sporozoite challenge and very early therapy of parasitaemia for efficacy studies of sporozoite vaccines.
Plasmodium falciparum parasitaemias were induced in four non-immune volunteers by the bites of mosquitoes infected from cultured gametocytes. Radical cure was accomplished before three of the four volunteers developed clinical malaria. Despite very low peak levels of parasitaemia, the plasmodium was recultured from the blood of all volunteers. This volunteer model of early detection of parasitaemia and prompt treatment will contribute to the safe and practical efficacy testing of sporozoite vaccines, thus facilitating the selection of candidate vaccines for large scale definitive field trials.


Early endoscopic intervention versus early conservative management in patients with acute gallstone pancreatitis and biliopancreatic obstruction: a randomized clinical trial.
To test the hypothesis that early endoscopic intervention, performed on patients with acute gallstone pancreatitis and biliopancreatic obstruction, reduces systemic and local inflammation. The role of early endoscopic intervention, in the treatment of acute gallstone pancreatitis, remains controversial. Previous randomized trials have not focused on the subgroup of patients with clinical evidence of biliopancreatic obstruction. This single-center randomized clinical trial was performed between May 2000 and September 2005. Of 238 patients, admitted within 48 hours after the onset of acute gallstone pancreatitis, 103 with a distal bile duct measuring > or =8 mm combined with a total serum bilirubin > or =1.20 mg/dL, were randomized to receive either endoscopic retrograde cholangiopancreatography followed by endoscopic papillotomy for bile duct stones (EEI, n = 51) or early conservative management (ECM, n = 52). Patients with clinical evidence of coexisting acute cholangitis were excluded. Outcome measures included changes in organ failure score and computed tomography (CT) severity index during the first week after admission, incidence of local complications, and overall morbidity and mortality. The incidence of bile duct stones at EEI was 72% and 40% of patients in the ECM group had persisting bile duct stones at elective biliary surgery. No significant differences were found between the EEI and ECM groups regarding changes in mean organ failure score (P = 0.87), mean CT severity index (P = 0.88), incidence of local complications (6% vs. 6%, P = 0.99), overall morbidity (21% vs. 18%, P = 0.80), and mortality (6% vs. 2%, P = 1). The present study failed to provide evidence that early endoscopic intervention reduces systemic and local inflammation in patients with acute gallstone pancreatitis and biliopancreatic obstruction. If acute cholangitis can be safely excluded, early endoscopic intervention is not mandatory and should not be considered a standard indication.


A cross-sectional ecological analysis of blood pressure and its determinants in eleven Pacific populations.
A cross-sectional interpopulation analysis of blood pressure and its determinants was conducted with the data collected during epidemiologic surveys in 11 Pacific island populations from 1975 to 1981. In each of these populations, the mean arterial blood pressure increased with age; the overall blood pressure levels differed among the populations. The multivariate analyses suggest that dietary factors that result in differences in body mass, plasma cholesterol, and glucose intolerance contribute considerably to interpopulation differences in blood pressure. The impact of these differences in effects of dietary factors on interpopulation blood pressure seemed to be uniform, even though the overall levels of each of these three variables differed significantly among the populations. This study of blood pressure data, accrued from 6224 men and 7029 women aged 20-79 years, supports the hypothesis that dietary factors strongly contribute to high blood pressure as well as to interpopulation differences in the prevalence of hypertension. We propose using these data in planning programs for prevention and control of hypertension in the Pacific countries.


Two-Component Systems in Francisella Species.
Bacteria alter gene expression in response to changes in their environment through various mechanisms that include signal transduction systems. These signal transduction systems use membrane histidine kinase with sensing domains to mediate phosphotransfer to DNA-binding proteins that alter the level of gene expression. Such regulators are called two-component systems (TCSs). TCSs integrate external signals and information from stress pathways, central metabolism and other global regulators, thus playing an important role as part of the overall regulatory network. This review will focus on the knowledge of TCSs in the Gram-negative bacterium, Francisella tularensis, a biothreat agent with a wide range of potential hosts and a significant ability to cause disease. While TCSs have been well-studied in several bacterial pathogens, they have not been well-studied in non-model organisms, such as F. tularensis and its subspecies, whose canonical TCS content surprisingly ranges from few to none. Additionally, of those TCS genes present, many are orphan components, including KdpDE, QseC, QseB/PmrA, and an unnamed two-component system (FTN_1452/FTN_1453). We discuss recent advances in this field related to the role of TCSs in Francisella physiology and pathogenesis and compare the TCS genes present in human virulent versus. environmental species and subspecies of Francisella.


Influence of plant beneficial Stenotrophomonas rhizophila strain CASB3 on the degradation of diuron-contaminated saline soil and improvement of Lactuca sativa growth.
Diuron is one of the major hazardous pollutants which posses severe risk to the environment and human healthiness. On the other hand, salinity is the most severe environmental stressor that limits crop productivity. Therefore, it is required to address this co-existing abiotic stresses in agricultural soil. Plant growth-promoting rhizobacteria have gained an engaging role in the degradation of pesticides in agricultural soil. However, their role against the restoration of diuron-contaminated saline soil is still not known. Thus, in this study, diuron-degrading, salinity-tolerant Stenotrophomonas rhizophila strain CASB3 was isolated and characterized. Strain CASB3 showed important PGP traits under normal and diuron or salt stresses. Complete degradation of 10-50 mg L-1 diuron in the aqueous medium under normal and salinity stress conditions was achieved within 48-120 h and 48-192 h, respectively. A unique pathway for diuron biodegradation was proposed based on GC-MS analysis. In a greenhouse study, CASB3 inoculated into diuron-contaminated saline soil efficiently degraded diuron (50 mg kg-1) by 94% in 42 days and simultaneously resulted in an enhancement of root-shoot length (47.22-63.41%), fresh-dry biomass (136.36-156.66%), and photosynthetic pigments (36.93-92.28%) in Lactuca sativa plants. These results suggest the strain CASB3 could be used as a bioresource for the reclamation of diuron-contaminated saline soils.


Novel technique for avoidance of pressure competition between a negative pressure wound therapy device and chest drains in the management of deep sternal wound infections.
In recent years, the use of negative pressure wound therapy (NPWT) devices has changed the way sternal wound infections are being managed. It is not uncommon for deep sternal wound infections to occur together with mediastinal or even pleural collections requiring underwater seal drainage. In these patients in whom there is a communication between the pleural and mediastinal cavities, the concomitant use of an NPWT device negates the pressure gradient within the pleural and mediastinal drains, allowing suppurative fluid to stagnate. We present a novel technique to address this limitation of NPWT devices in patients with sternal wound infections that communicate with a pleural collection.


A scoring system to effectively evaluate central nervous system tuberculosis in patients with military tuberculosis.
There is currently no convenient way to effectively evaluate whether a miliary tuberculosis patient is complicated with central nervous system (CNS) tuberculosis. We aimed to find such a way by analyzing the clinical data of these patients. Fifty patients with confirmed miliary tuberculosis and 31 patients with confirmed miliary tuberculosis complicated with CNS tuberculosis from 2010 to 2014 were selected. Their general conditions, clinical features and laboratory tests were analyzed. Factors that were significantly different between them were chosen to performed multivariate and univariate logistic regression analyses, and factors with significant P values were used to establish a scoring system. Eight factors, i.e., age, cough, nausea, headache, hemoglobin (HGB), serum albumin (ALB), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were significantly different (P < 0.05). Multivariate logistic regression analysis showed that ALB was the independent risk predictor (HR = 1.29, 95% CI 1.09-1.52, P < 0.01), whereas the others were non-independent predictors except age (P < 0.05). The scoring system was based on a summation of the scores of the assigned values of the seven predictors and had an area under the curve (AUC) of 0.86 to confirm CNS tuberculosis, with a sensitivity of 81.5% and a specificity of 81.4% at a score of 0.75 and with a specificity of 95.3% at a score of 2.75. In contrast, a score below -0.75 excluded CNS tuberculosis, with a sensitivity of 88.9% and a specificity of 62.7%. The scoring system should be useful to evaluate whether a miliary tuberculosis patient is complicated with CNS tuberculosis and could help doctors avoid excessive investigation.


Worsening Racial Disparities in Utilization of Intensity Modulated Radiation Therapy.
The benefits of intensity modulated radiation therapy (IMRT) compared with standard 3-dimensional conformal radiation therapy have been demonstrated in many cancer sites and include decreased acute and late toxicity, improved quality of life, and opportunities for dose escalation. Limited literature suggests non-white patients may have lower utilization of IMRT. We hypothesized that as the use of IMRT has increased in recent years, racial inequities have persisted and disproportionately affect non-Hispanic Black (NHB) patients. We aim to evaluate temporal trends in IMRT utilization focusing on disparities among minoritized populations. The National Cancer Database was queried to identify the 10 disease sites with the highest total number of cancer patients treated with definitive intent IMRT in 2017, the most recent year for which data are available. Exclusions included stage IV, age <18 years, unknown insurance status, unknown race, and palliative intent radiation. Race and ethnicity variables were combined and classified as non-Hispanic White, Hispanic, NHB, Asian, Native American/Eskimo, and Hawaiian/Pacific Islander. Multivariable logistic regression for IMRT utilization was performed for each disease site for both early (2004-2010) and contemporary (2011-2017) cohorts, adjusting for clinical and demographic covariates. Among the 10 selected disease sites, 1,010,292 patients received radiation therapy as part of definitive treatment between 2004 and 2017. Overall IMRT utilization rates increased from 22.0% in 2004 to 57.8% in 2017. After adjustment and compared with non-Hispanic White patients, NHB patients were significantly less likely to receive IMRT in 1 of 10 disease sites in the 2004 to 2010 cohort, and 5 of 10 disease sites in the 2011 to 2017 cohort. Despite greater awareness of racial disparities in cancer care and outcomes, this study demonstrates worsening disparities in the use of IMRT, particularly for NHB patients. These differences may exacerbate racial disparities in cancer outcomes; therefore, identification of underlying drivers of differential IMRT utilization is warranted.


Inhibitory effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at early stage of steroid-induced femoral head necrosis.
Apoptosis and DNA oxidative damage serve significant roles in the pathogenesis of steroid‑induced femoral head necrosis. Vitamin E demonstrates anti‑apoptotic and anti‑oxidant properties. Therefore, the present study investigated the effects of vitamin E on osteocyte apoptosis and DNA oxidative damage in bone marrow hemopoietic cells at an early stage of steroid‑induced femoral head osteonecrosis. Japanese white rabbits were randomly divided into three groups (steroid, vitamin E‑treated, and control groups), each comprising 12 rabbits. Those in the steroid group (group S) were initially injected twice with an intravenous dose of 100 µg/kg Escherichia coli endotoxin, with a 24 h interval between the two injections, and then with an intramuscular dose of 20 mg/kg methylprednisolone, three times at intervals of 24 h in order to establish a rabbit model of osteonecrosis. The vitamin E treated group (group E) received the same treatment as group S, and were administered 0.6 g/kg/d vitamin E daily from the beginning of modeling. The control group (group C) was injected with normal saline at the equivalent dosage and times as the aforementioned two groups. Two time points, weeks 4 and 6 following the completion of modeling, were selected. Osteonecrosis was verified by histopathology with hematoxylin-eosin staining. The apoptosis rate of osteonecrosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The apoptosis expression levels of caspase‑3 and B‑cell lymphoma 2 (Bcl‑2), and DNA oxidative damage of bone marrow hematopoietic cells were analyzed by immunohistochemistry. At weeks 4 and 6 following the completion of modeling, the vacant bone lacunae rates of group E were 15.87±1.97 and 25.09±2.67%, respectively, lower than the results of 20.02±2.21 and 27.79±1.39% for group S; and the osteocyte apoptosis indexes of group E were 20.99±2.95 and 33.93±1.62%, respectively, lower than the results of 26.46±3.37 and 39.90±3.74% from group S. In addition, the Bcl-2 expression at week 4 in the femoral head tissues of group E was higher compared with group S; and the proportion of Bcl‑2‑positive cells of group E was 9.81±1.01%, higher compared with group S at 8.26±1.13%. The caspase‑3 staining data at week 4 in femoral head tissues demonstrated that in the 12 femoral heads of group S, four were negative (32%) and eight were positive (68%); in group E, five were negative (45%) and seven were positive (55%); and in group C, 11 were negative (95%) and one was positive (5%). In addition, the DNA oxidative damage rate at week 4 in the bone marrow hemopoietic cells of group E was (7.24±1.44%), lower compared with group S (11.80±1.26%), and higher compared with group C (5.75±1.47%). Vitamin E is effective in intervening in apoptosis through decreasing caspase‑3 expression and upregulating Bcl‑2 expression, and by alleviating DNA oxidative damage in bone marrow hemopoietic cells at the early stage of steroid‑induced femoral head necrosis in rabbit models.


How useful are housekeeping genes? Variable expression in melanoma metastases.
There is a certain difference in opinion regarding the optimal choice of housekeeping genes used as normalization factors in gene expression analysis. We have therefore examined the suitability of three housekeeping genes, hypoxanthine phosphoribosyl transferase, beta-glucuronidase and beta2-micro-globulin, for normalization of expression data from melanoma metastases. The expression of the three housekeeping genes was quantified by quantitative reverse transcription PCR in snap-frozen sections from 44 melanoma metastases, of which 19 were from patients treated with cisplatinum, dacarbazine and interferon-alpha2b. The expression of each housekeeping gene varied considerably between the different metastases. Histopathological examination of the tissue sections revealed variation in the amount of tumor cells in the tissue, necrosis, varying degrees of lymphocyte infiltration, and lymph node remnants. Based on this examination, 16 biopsies were omitted from further analysis because they had cracked, contained empty or necrotic areas, or were dominated by lymph node tissue. Even in sections with more than 90% tumor cells, a wide variation in the expression of the three housekeeping genes was found. The amount of lymphatic infiltrate in the tumors can have an effect on the expression of housekeeping genes in the metastases, whereas treatment did not seem to influence the expression. We conclude that the choice of housekeeping genes can have great impact on the normalization of specific genes in melanoma metastases. Furthermore, in the analysis of mRNA expression in tumor tissue, microscopic examination is of great importance to evaluate the integrity and cellular composition of the biopsy.


Tailored treatment of intestinal angiodysplasia in elderly.
Angiodysplasia of the gastrointestinal tract is an uncommon, but not rare, cause of bleeding and severe anemia in elderly. Different treatments exist for this kind of pathology. The aim of this work was to study 40 patients treated for intestinal angiodysplasia with two different kind of endoscopic treatments: argon plasma coagulation (APC) and bipolar electrocoagulation (BEC). Age of patients was similar in both groups (76,2 ± 10.8 years vs 74,8 ± 8,7 years, P = 0,005). Angiodysplasia treated were located in small bowel, right colon, left colon, transverse colon and cecum. We analysed number of treatment, recurrence, hospital discharge, needs of blood transfusions before and after endoscopic treatment. Number of treatment was the same in both groups (1,2 ± 0,2 vs 1,1 ± 0,1, P < 0,001). We had more recurrence in patients treated with BEC (4/20 vs 2/20, P < 0,001). Hospital discharge was comparable in both groups (5,3 ± 3,1 days vs 5,4 ± 2,8 years, P < 0.001). Treatment of angiodysplasia in elderly is not easy. Different kinds of treatment could be adopted. APC and BEC are both safe and effective. The choice of a treatment should consider several factors: age, comorbidity, source of bleeding. In conclusion we think that treatment of bleeding for angiodysplasia in elder population should be a tailored treatment.


Multimodal determinants of phase-locked dynamics across deep-superficial hippocampal sublayers during theta oscillations.
Theta oscillations play a major role in temporarily defining the hippocampal rate code by translating behavioral sequences into neuronal representations. However, mechanisms constraining phase timing and cell-type-specific phase preference are unknown. Here, we employ computational models tuned with evolutionary algorithms to evaluate phase preference of individual CA1 pyramidal cells recorded in mice and rats not engaged in any particular memory task. We applied unbiased and hypothesis-free approaches to identify effects of intrinsic and synaptic factors, as well as cell morphology, in determining phase preference. We found that perisomatic inhibition delivered by complementary populations of basket cells interacts with input pathways to shape phase-locked specificity of deep and superficial pyramidal cells. Somatodendritic integration of fluctuating glutamatergic inputs defined cycle-by-cycle by unsupervised methods demonstrated that firing selection is tuneable across sublayers. Our data identify different mechanisms of phase-locking selectivity that are instrumental for flexible dynamical representations of theta sequences.


Partial depletion of intracellular ATP mediates the stress-survival function of the PCPH oncoprotein.
Promotion of cellular resistance to stressful stimuli, including ionizing radiation and chemotherapeutic drugs, contributes to the transforming activity of the PCPH oncogene. The mechanism of this action, however, has remained unknown. Consistent with its intrinsic ATP diphosphohydrolase activity, expression of the PCPH oncoprotein in cultured cells has now been shown to result in partial depletion of intracellular ATP and consequent inhibition of the c-JUN NH2-terminal kinase-mediated stress signaling pathway. Supplementation of cells expressing the PCPH oncoprotein with exogenous ATP restored both stress-response signaling and sensitivity to cisplatin-induced apoptosis. In contrast, overexpression of the wild-type PCPH protein had a minimal effect on stress-induced signaling and on the cellular ATP content and did not protect cells from apoptosis. These results suggest that the PCPH oncoprotein confers resistance to stressors by reducing the cellular ATP concentration to levels below those required for optimal stress-induced signaling and apoptosis. Treatment with adenosine or nucleoside analogues may thus enhance the response to radiation or chemotherapy of tumors that express the PCPH oncogene.