Characteristics of U.S. veterans who begin and complete prolonged exposure and cognitive processing therapy for PTSD.
This retrospective chart-review study examined patient-level correlates of initiation and completion of evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) among treatment-seeking U.S. veterans. We identified all patients (N = 796) in a large Veterans Affairs PTSD and anxiety clinic who attended at least 1 individual psychotherapy appointment with 1 of 8 providers trained in EBP. Within this group, 91 patients (11.4%) began EBP (either Cognitive Processing Therapy or Prolonged Exposure) and 59 patients (7.9%) completed EBP. The medical records of all EBP patients (n = 91) and a provider-matched sample of patients who received another form of individual psychotherapy (n = 66) were reviewed by 4 independent raters. Logistic regression analyses revealed that Iraq and Afghanistan veterans were less likely to begin EBP than veterans from other service eras, OR = 0.48, 95% CI = [0.24, 0.94], and veterans who were service connected for PTSD were more likely than veterans without service connection to begin EBP, OR = 2.33, 95% CI = [1.09, 5.03]. Among those who began EBP, Iraq and Afghanistan veteran status, OR = 0.09, 95% CI = [0.03, 0.30], and a history of psychiatric inpatient hospitalization, OR = 0.13, 95% CI = [0.03, 0.54], were associated with decreased likelihood of EBP completion.


Comparative Evaluation of Bulk-Fill Composite Resins: Knoop Microhardness, Diametral Tensile Strength and Degree of Conversion.
Bulk-fill composite resins were developed to reduce time and facilitate the restorative procedure. However, considering their recent introduction on the market and the new formulations, their performance still requires evaluation. This study aimed to evaluate Knoop microhardness (KHN), diametral tensile strength (DTS) and degree of conversion (DC) of three Bulk-Fill composite resins and a conventional one. Sixty samples (n = 15; 8 mm ø x 4 mm height) were confectioned using a mold. Filtek Bulk-Fill (FBF), Tetric N-Ceram Bulk-Fill (TNC) and SonicFill 2 (SF2) were placed in 4 mm increments, and Filtek Z350 (FZ350) was placed in 2 mm increments. The KHN of top and bottom surfaces were tested using Knoop Hardness tester at 10 gf/10s. The DTS was tested under compressive load at 1.0 mm/min. The DC was measured by Fourier Transform Infrared (FTIR) spectroscopy. Differences in DTS and DC were analyzed by ANOVA and Tukey post hoc test. For KHN, Kruskal-Wallis and Wilcoxon tests were performed at α = 0.05. Top surfaces of all composite resins had higher KHN than bottom surfaces. At top and bottom surfaces, FZ350 showed higher KHN than TNC and SF2. The highest DTS was obtained by FBF, followed by FZ350 and SF2. The highest DC was obtained by SF2, the lowest one was obtained by FBF. From Bulk-Fill composite resins, FBF presented the best KHN and DTS results. The SF2 showed the best DC. Further studies are required to ensure whether these differences can negatively influence the behavior of in vivo restorations.


Specific elimination of cytotoxic effector cells. I. Adsorptive behavior of effectors and their precursors and spleen cell monolayers.
Monolayers formed of normal mouse spleen cells attached to polystyrene coated with poly-L-lysine were tested for their ability to bind specifically antigen-reactive cells in normal or primed mouse spleen. 88 to greater than 98% of the activity of cytotoxic populations was removed by a single adsorption. However, normal spleen cells or spleen cells previously primed in vitro could not be depleted of their capacity to be sensitized, even when adsorption effectively removed all residual cytotoxic activity from the same previously primed population. In fact, exposure to an immunoadsorbent augmented the ultimate cytotoxicity generated in a nonspecific fashion. This augmentation was especially dramatic in the case of a previously primed population and may have reflected the removal of a nonspecific suppressor. If antigen-reactive precursors cannot be removed efficiently by adsorption, other approaches to the generation of tolerant lymphoid populations, such as specific suppression of precursor differentiation must be sought.


Epidemiology of hepatitis C virus among hemodialysis patients in the Middle East and North Africa: systematic syntheses, meta-analyses, and meta-regressions.
We aimed to investigate hepatitis C virus (HCV) epidemiology among hemodialysis (HD) patients in the Middle East and North Africa (MENA). Our data source was an HCV biological measures database populated through systematic literature searches. Descriptive epidemiologic syntheses, effects meta-analyses and meta-regressions, and genotype analyses were conducted. We analyzed 289 studies, including 106 463 HD patients. HCV incidence ranged between 0 and 100% as seroconversion risk, and between 0 and 14·7 per 1000 person-years as incidence rate. The regional pooled mean estimate was 29·2% (95% CI: 25·6-32·8%) for HCV antibody positive prevalence and 63·0% (95% CI: 55·4-70·3%) for the viremic rate. Region within MENA, country income group, and year of data collection were associated with HCV prevalence; year of data collection adjusted odds ratio was 0·92 (95% CI: 0·90-0·95). Genotype diversity varied across countries with four genotypes documented regionally: genotype 1 (39·3%), genotype 2 (5·7%), genotype 3 (29·6%), and genotype 4 (25·4%). Our findings showed that one-third of HD patients are HCV antibody positive and one-fifth are chronic carriers and can transmit the infection. However, HCV prevalence is declining. In context of growing HD patient population and increasing HCV treatment availability, it is critical to improve standards of infection control in dialysis and expand treatment coverage.


Child care in the United States today.
This article describes the consumers and providers of child care in the United States. It uses data from nationally representative surveys and research studies conducted from the late 1960s through 1995 to examine the child care arrangements parents select for their young children, comparing today's arrangements with those made by parents decades ago. It then discusses the availability of child care, examining both the number of child care spaces available and whether quality programs are available to suit the needs and resources of parents. The article concludes with speculation about how proposed new policies and continuing trends may lead to future changes in child care.


USING COUPLES' DISCORDANT REPORTS TO ESTIMATE FEMALE COVERT USE OF MODERN CONTRACEPTION IN SUB-SAHARAN AFRICA.
Substantial numbers of married women use contraceptives without their partner's knowledge in sub-Saharan Africa, but studies of female covert use across time are rare. This study investigates the levels, trends and correlates of covert use in nine countries and determines which contraceptive methods are more frequently used covertly by women. Data from monogamous couples in Demographic and Health Surveys were used from nine sub-Saharan African countries that had experienced an increase of 10 percentage points in current modern contraceptive use between an earlier (1991-2004) and later (2007-2011) survey. Covert use was indirectly estimated as the percentage of women who reported a female modern method whose husband did not report a modern method. The percentage of women using covertly increased in eight of the countries studied (significantly in three of them), yet when comparing across countries cross-sectionally, covert use was lower where contraceptive prevalence was higher. In general, women with more years of schooling and those with larger spousal schooling gaps had lower odds of covert use. There was no significant difference between covert and open injectable use, though more than half of both groups used this method in the later surveys. Encouraging couple communication about contraception, where the woman feels it is safe to do so, could be an important strategy to minimize covert use. Further research is needed to better identify the contraceptive prevalence and social context in which covert use declines within a country.


Boceprevir.
Boceprevir is a hepatitis C virus (HCV) serine protease NS3 inhibitor that has recently been approved by the U.S. Food and Drug Administration, the European Medicines Agency and Health Canada for the treatment of chronic genotype 1 HCV infection. It has potent in vitro antiviral activity against HCV genotypes 1a and 1b and is primarily metabolized via the aldoketoreductase pathway with minor cytochrome P450 3A4 metabolism. Boceprevir is well tolerated with few drug-drug interactions which are easy to manage; no dose adjustment is required in patients with hepatic or renal impairment. Phase I trials of boceprevir demonstrated favorable pharmacokinetic, metabolic and safety profiles. Phase II and III trials of boceprevir confirmed the antiviral activity of the drug and its use at a dose of 800 mg three times daily. Clinical trials in treatment-naive and previously treated HCV-infected patients demonstrated a 26% and 45% (respectively) improvement in sustained viral response when boceprevir was added to standard pegylated interferon and ribavirin anti-HCV therapy. Boceprevir is the first-in-class of an exciting new phase of HCV treatment.


A case of pneumonia presenting with the acute respiratory distress syndrome.
Adult respiratory distress syndrome (ARDS) or high permeability pulmonary oedema (HPPE) is an uncommon presentation of a viral pneumonia and usually occurs in the setting of a fulminant or severe viral pneumonia. High permeability pulmonary oedema (HPPE) can be loosely defined as those forms of pulmonary oedema with normal cardiac function associated with the accumulation of protein-rich fluid in the interstitial or intraalveolar spaces. Through the years, a number of phrases have been used to describe this entity: white lung, shock lung, wet lung, adult hyaline membrane disease, ARDS and others. The aetiology is varied but the clinical, radiologic and pathologic pictures are similar. In fact the pathologic picture is so consistent from patient to patient regardless of aetiology that it has been suggested that the term HPPE be used in place of the other commonly used ones. A case of HPPE of possible viral aetiology who responded to prompt intervention with a successful outcome, is described here.


Different staphylococcal strains elicit different levels of production of T-helper 1-inducing cytokines.
Cytokine production has been implicated in the pathogenic mechanisms of infections caused by the staphylococci, since these bacteria may act as strong cytokine inducers. To gain deeper insight into the Th1 immune response activated by these bacteria, we have analyzed the interferon (IFN), interleukin-12 (IL-12) and IL-18-inducing activities of different Staphylococcus aureus (S. aureus), S. epidermidis and S. saprophyticus strains in human monocytes and murine bone marrow macrophages. A large majority of the S. aureus strains elicited the simultaneous production of IL-12 p70 and IFN-alpha in the human monocytes, while the S. epidermidis and S. saprophyticus strains induced only a low level of production, if any, of these cytokines. Furthermore, a majority of the S. aureus strains induced significantly higher IL-12 p70 and IL-18 titers in the murine bone marrow macrophages than did the S. epidermidis and S. saprophyticus strains. As IL-12, IL-18 and IFN-alpha stimulate Th1 differentiation synergistically, we suggest that S. aureus strains bias the immune response toward a Th1 phenotype, whereas S. epidermidis and S. saprophyticus strains provide a weaker stimulus for the production of Th1-inducing cytokines, and accordingly possibly elicit a less extensive Th1-associated adaptive immunity.


Adrenaline and noradrenaline: relation to performance in a visual vigilance task.
Concentrations of adrenaline and noradrenaline in the circulating blood were measured in blood samples taken from subjects as they performed a visual vigilance task or viewed movies, both under identical conditions. For those subjects whose vigilance performance deteriorated it was concluded that the concentration of circulating adrenaline decreases as a function of time in a vigilance task but not under "relaxed" conditions, such as watching motion pictures. crementers under "relaxed"conditions.


The carcinogenic effect of localized fission fragment irradiation of rat lung.
In a preliminary investigation of 'hot particle' carcinogenesis uranium oxide particles were introduced into the lungs of rats either by intubation of a liquid suspension of the particles or by inhalation of an aerosol. Subsequently the animals were briefly exposed to slow neutrons in a nuclear reactor, resulting in localized irradiation of the lung by fission fragments emitted from 235U atoms in the oxide particles. The uranium used in the intubation experiments was either enriched or depleted in 235U. Squamous cell carcinomas developed at the site of deposition of the enriched uranium oxide in many cases but no lung tumours occurred in the rats with the depleted uranium oxide, in which the lung tissue was exposed to very few fission fragments. Only enriched uranium oxide was used in the inhalation experiments. Pulmonary squamous cell carcinomas occurred after the fission fragment irradiation but were fewer than in the intubation experiments. Adenocarcinomas of the lung were seen in rats exposed to uranium oxide without subsequent irradiation by neutrons in the reactor and in rats irradiated with neutrons but not previously exposed to uranium oxide. It is concluded that (i) fission fragments were possibly implicated in the genesis of the squamous cell carcinomas, which only developed in those animals exposed to enriched uranium oxide and neutrons and (ii) the adenocarcinomas in the rats inhaling enriched uranium oxide only were likely to have been caused by protracted irradiation of the lung with alpha-rays emitted from the enriched uranium.


Cross-population evaluation of cervical cancer risk prediction algorithms.
Cervical cancer is a preventable disease, despite being one of the most common types of female cancers worldwide. Integrating existing programs for cervical cancer screening with personalized risk prediction algorithms can improve population-level cancer prevention by enabling more targeted screening and contrive preventive healthcare innovations. While algorithms developed for cervical cancer risk prediction have shown promising performance in internal validation on more homogeneous populations, their ability to generalize to external populations remains to be assessed. To address this gap, we perform a cross-population comparative study of personalized prediction algorithms for more personalized cervical cancer screening. Using data from the Norwegian and Estonian populations, the algorithms are validated on internal and external datasets to study their potential biases and limitations when applied to different populations. We evaluate the algorithms in predicting progression from low-grade precancerous cervical lesions, simulating a clinically relevant application of more personalized risk stratification. As expected, our numerical experiments show that algorithm performance varies depending on the population. However, some algorithms show strong generalization capacity across different data sources. Using Kaplan-Meier estimates, we demonstrate the strengths and limitations of the algorithms in detecting cancer progression over time by comparing to the trends observed from data. We assess their overall discrimination performance in personalized risk predictions by analyzing the accuracy and confidence in individual risk estimates. This study examines the effectiveness of personalized prediction algorithms across different populations. Our results demonstrate the potential for generalizing risk prediction algorithms to external populations. These findings highlight the importance of considering population diversity when developing risk prediction algorithms.


The military aviator with renal stone disease.
Regulations currently in force governing the flight status of military aviators with urinary calculus disease are more restrictive than necessary and result in a substantial loss of aviation manpower. Those regulations and policies currently in force are reviewed, and more liberal guidelines, designed to provide for the safe return to useful flight status of aviation personnel with renal stone episodes, are proposed.


Advanced coagulation using in-situ generated liquid ferrate, Fe (VI), for enhanced pretreatment in seawater RO desalination during algal blooms.
Harmful algal blooms (HABs) are considered a major threat for seawater reverse osmosis (SWRO) plants. The presence of HABs in the raw feed water can cause increase of chemical consumption within the desalination plant, increase membrane fouling rate and might lead to plant shutdown. The removal of Algal Organic Matters (AOMs) during the pretreatment will help in increasing the membrane lifetime, reduce operation cost and increase the plant reliability. In this study, the efficiency of liquid ferrate and ferric chloride during coagulation on the removal of AOMs was investigated. The liquid ferrate was generated in-situ by wet oxidation of ferric iron using hypochlorite in a caustic medium. Two seawater models were employed, the first one contains 10 mg c/L of sodium alginate and the second one contains also 10 mg c/L of Chaetoceros affinis algae (CA). During the advanced coagulation, liquid ferrate proved to be more effective in removing AOM than ferric chloride, with an overall DOC removal of 90%, enabling 100% algal removal and the inactivation of 99.99% of the microorganisms. The results presented in this study highlights the efficiency of liquid ferrate as seawater pretreatment during the HABs events.


A multi-institutional review of outcomes in biopsy-proven chronic invasive fungal sinusitis.
Chronic invasive fungal sinusitis (CIFS) is a rare, life-threatening infection of the nose and sinuses. This study aims to identify factors that impact survival in 1 of the largest cohorts to date. Pathology records were reviewed for biopsy-proven CIFS from 3 tertiary academic institutions from 1995 to 2016. Variables were analyzed using log-rank survival analysis. Univariate Cox regression was performed at 1 and 12 months. Thirty-eight patients were included. Hematologic malignancy and diabetes were the most common underlying diseases (32% each). Aspergillus was the most common fungus (63%). Greater than 75% of the patients had an absolute neutrophil count (ANC) >1000 at the time of diagnosis. Overall survival at 1, 6, and 12 months was 89%, 68%, and 48%, respectively. In univariate analysis, factors associated with worse survival included: ANC <500 at 12 months (hazard ratio [HR] 4.8; p = 0.01), ANC <1000 at 12 months (HR 5.8; p = 0.001), and recent chemotherapy (HR 4; p = 0.01). The following factor was associated with improved survival in univariate analysis: ANC as a linear variable in the entire cohort (HR 0.7; p = 0.005). We present a multi-institutional case-series of CIFS and long-term follow-up. ANC <1000 at time of diagnosis and recent chemotherapy (within 1 month of diagnosis) are associated with poorer survival, whereas a rising ANC >1000 is associated with improved survival at 12 months. Further prospective studies are needed to further define factors that affect outcomes.


[Health-related quality of life in the oncology departments of the hospital of Navarra. The EORTC Quality of Life Group].
Quality of life assessment is one of the key elements of the care that is offered to cancer patients. The aim of this work is to present the research line on quality of life that has been carried out since 1992 in the Oncology Departments of the Hospital de Navarra. These departments actively collaborate with the European Organisation of Research and Treatment of Cancer - EORTC - Quality of Life Group in creating questionnaires and also in other projects of this group. Our institution has coordinated the development process of the EORTC information module. Different EORTC questionnaires have been validated for use in our country. Quality of life studies have been carried out in the main tumour sites and in other areas, such as patients' satisfaction with care. This research line has a direct benefit on the attention that patients receive.


Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics.
Although cystic fibrosis (CF) is attributed to dysfunction of a single gene, the relationships between the abnormal gene product and the development of inflammation and progression of lung disease are not fully understood, which limits our ability to predict an individual patient's clinical course and treatment response. To better understand CF progression, we characterized the molecular signatures of CF disease status with plasma-based functional genomics. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with plasma samples from CF patients ( n = 103) and unrelated, healthy controls ( n = 31). Gene expression levels were measured with an Affymetrix microarray (GeneChip Human Genome U133 Plus 2.0). Peripheral blood samples from a subset of the CF patients ( n = 40) were immunophenotyped by flow cytometry, and the data were compared with historical data for age-matched healthy controls ( n = 351). Plasma samples from another subset of CF patients ( n = 56) and healthy controls ( n = 16) were analyzed by multiplex enzyme-linked immunosorbent assay (ELISA) for numerous cytokines and chemokines. Principal component analysis and hierarchical clustering of induced transcriptional data revealed disease-specific plasma-induced PBMC profiles. Among 1,094 differentially expressed probe sets, 51 genes were associated with pancreatic sufficient status, and 224 genes were associated with infection with Pseudomonas aeruginosa. The flow cytometry and ELISA data confirmed that various immune modulators are relevant contributors to the CF molecular signature. This study provides strong evidence for distinct molecular signatures among CF patients. An understanding of these molecular signatures may lead to unique molecular markers that will enable more personalized prognoses, individualized treatment plans, and rapid monitoring of treatment response.


Size heterogeneity of rat pituitary prolactin.
The occurrence of multiple forms of rat prolactin with different molecular weights (size heterogeneity) was studied with anterior pituitary extracts, purified rat prolactin and 125I-labelled rat prolactin. In each case, three main forms of the hormone were detected by gel filtration on Sephadex G-100: a major one (80--90%) corresponding to monomeric prolactin (mol.wt. 22000--25000), a peak (8--20%) that could be a dimer (mol.wt. 45000--50000) and a small quantity (1--5%) of a component of much greater molecular weight. On freezing and thawing of 125I-labelled rat prolactin, there was little interconversion of monomer and 'dimer' peaks, but both were converted substantially to very high-molecular-weight material. All three peaks of 125I-labelled rat prolactin could be precipitated by anti-(rat prolactin) serum and all three gave similar patterns of radioactive peptides after digestion with chymotrypsin followed by high-voltage paper electrophoresis. On sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the monomer peak of 125I-labelled prolactin migrated as a single component of mol.wt. 22000, the very high-molecular-weight peak largely dissociated to a component running in the same position as the monomer, and the 'dimer' peak migrated partly as a component of mol.wt. 45000 and partly as a component migrating with monomeric prolactin. No treatment was found that could dissociate the 'dimer' peak completely to monomeric prolactin.


[Prevention of transmissible spongiform encephalopathy and methods for prion inactivation].
Transmissible Spongiform Encephalopathies (TSEs) are infectious, progressive, lethal neurodegenerative diseases which affect both human and other mammalian species. The knowledge on the agent responsible for the infection and its pathogenetic mechanism is still limited. Specific diagnostic tests are currently not available; diagnosis is based on clinical symptoms and confirmed by a post-mortem examination which can reveal the typical brain lesions. There is some evidence on the relationship between the agent responsible for Bovine Spongiform Encephalopathy (BSE) and the new human variant of the Creutzfeldt-Jakob disease (nvCJD). The TSEs agents have some peculiarities: they overcome the interspecies barriers and are resistant to the normal disinfections and sterilization procedures. On the basis of current scientific evidence, the aim of this article was: to make an excursus on the efficacy of inactivation methods and to give an overview of what has been issued by International and Italian Regulatory Agencies for the prevention of such diseases in hospital and occupational environments. We examined current scientific literature on inactivation of TSEs by physical or chemical methods or combinations thereof. We also reviewed the most relevant guidelines on exposure risk, containment and occupational exposure to TSEs agents. Due to the peculiarity of the prion protein and its transmission, it is very important to have effective methods to inactivate the TSE agents and to prevent them spreading. At present, no certain data are available on TSE development in occupational environments, while sources of exposure risk are known for several occupational categories, such as health-care personnel, pathologists, technicians in diagnostic and research laboratories, farmers, veterinary surgeons, slaughter house operators. For these workplaces, after an accurate risk assessment, it is necessary to implement certain precautionary measures, based on containment procedures and on the adoption of specific inactivation protocols.


Chitinase secreted by Leishmania functions in the sandfly vector.
Leishmania major parasites ingested with host blood by the sandfly Phlebotomus papatasi multiply confined within the peritrophic membrane. This membrane consists of a chitin framework and a protein carbohydrate matrix and it is secreted around the food by the insect midgut. Histological sections of infected flies show lysis of the chitin layer in the anterior region of the peritrophic membrane that permits the essential forward migration of a concentrated mass of parasites. Both the location and the nature of this disintegration are specific to infected flies. At a later stage the parasites concentrate in the cardiac valve region and subsequently this segment of the fore gut loses its cuticular lining. We have found that chitinase and N-acetylglucosaminidase are secreted by cultured L. major promastigotes, but not by sandfly guts. Hence lysis of the chitin layer of the peritrophic membrane could be catalysed by these enzymes of the parasites. Activity of both enzymes was also observed in other trypanosomatids, including L. donovani, L. infantum, L. braziliensis, Leptomonas seymouri, Crithidia fasciculata and Trypanosoma lewisi.


[Pars plana vitrectomy following accidental injection of depot steroids into the vitreous body].
The authors describe a case of accidental intraocular injection of depot steroids after treatment of a chalazion by an intralesional corticosteroid injection. The eye was treated by pars plana vitrectomy. Visual acuity improved postoperatively, ultimately attaining 1/16. As late complications, pathologic changes of the macula were observed, with macular pucker and optic nerve atrophy.


Callose synthase (CalS5) is required for exine formation during microgametogenesis and for pollen viability in Arabidopsis.
Callose (beta-1,3-glucan) is produced at different locations in response to biotic and abiotic cues. Arabidopsis contains 12 genes encoding callose synthase (CalS). We demonstrate that one of these genes, CalS5, encodes a callose synthase which is responsible for the synthesis of callose deposited at the primary cell wall of meiocytes, tetrads and microspores, and the expression of this gene is essential for exine formation in pollen wall. CalS5 encodes a transmembrane protein of 1923 amino acid residues with a molecular mass of 220 kDa. Knockout mutations of the CalS5 gene by T-DNA insertion resulted in a severe reduction in fertility. The reduced fertility in the cals5 mutants is attributed to the degeneration of microspores. However, megagametogenesis is not affected and the female gametes are completely fertile in cals5 mutants. The CalS5 gene is also expressed in other organs with the highest expression in meiocytes, tetrads, microspores and mature pollen. Callose deposition in the cals5 mutant was nearly completely lacking, suggesting that this gene is essential for the synthesis of callose in these tissues. As a result, the pollen exine wall was not formed properly, affecting the baculae and tectum structure and tryphine was deposited randomly as globular structures. These data suggest that callose synthesis has a vital function in building a properly sculpted exine, the integrity of which is essential for pollen viability.


Myosin isoenzyme expression in rat ventricle: effects of thyroid hormone analogs, catecholamines, glucocorticoids and high carbohydrate diet.
The effects on ventricular myosin isoenzyme expression of naturally occurring and synthetic thyroid analogs (3,5,3'-L-triiodothyronine, 3,5,3'-D-triiodothyronine, 3,3',5'-L- triiodothyronine , 3,5,3'-L-triiodothyroacetic acid and 3,5-L-diiodothyronine), catecholamines and high carbohydrate diets have been studied in thyroidectomized and hypophysectomized rats. Also, the effects on myosin isoenzyme expression of adrenalectomy and hydrocortisone replacement have been studied in euthyroid animals. Myocardial CO2 production and hepatic alpha-glycerolphosphate dehydrogenase activity were measured to monitor the effects of these interventions on tissue respiration. The results indicate that there was no significant separation between the actions of thyroid analogs on metabolic parameters and myosin isoenzyme patterns. However, high carbohydrate feeding in hypophysectomized rats increased the isoenzyme V1 from 12% to about 36% of total myosin; partial replacement with 3,5,3'-L-triiodothyronine and fructose feeding had synergistic actions. In thyroidectomized rats, feeding a high carbohydrate diet increased the V1 form from undetectable levels to about 28% of total myosin; partial 3,5,3'-L-triiodothyronine replacement had an additive effect. Beta adrenergic stimulation with isoproterenol and blockade with propranolol did not affect myosin isoenzyme expression. Adrenalectomy in euthyroid rats caused a 33% decrease in the V1 form and a corresponding increase in the V3 isoenzyme, which could be reversed by treatment with hydrocortisone. Thus, thyroid analogs do not selectively stimulate myosin isoenzyme expression as compared with their effects on energy production. Furthermore, the results suggest that the mechanism for regulation of cardiac myosin isoenzymes may involve a primary signal related to dietary carbohydrate, which is modulated by thyroid hormone, and possibly glucocorticoids.


Adaptive ultrasonic sensor using a fiber ring laser with tandem fiber Bragg gratings.
We propose and demonstrate an intensity-demodulated fiber-optic ultrasonic sensor system that can be self-adaptive to large quasi-static background strain perturbations. The sensor system is based on a fiber ring laser (FRL) whose laser cavity includes a pair of fiber Bragg gratings (FBGs). Self-adaptive ultrasonic detection is achieved by a tandem design where the two FBGs are engineered to have differential spectral responses to ultrasonic waves and are installed side-by-side at the same location on a structure. As a result, ultrasonic waves lead to relative spectral shifts of the FBGs and modulations to the cold-cavity loss of the FRL. Ultrasonic waves can then be detected directly from the laser intensity variations in response to the cold-cavity loss modulation. The sensor system is insensitive to quasi-static background strains because they lead to identical responses of the tandem FBGs. Based on the principle, a FRL sensor system was demonstrated and tested for adaptive ultrasonic detection when large static strains as well as dynamic sinusoidal vibrations were applied to the sensor.


Differential Susceptibility to the Environment and Borderline Personality Disorder.
Evolutionary models of psychopathology can shed light on gene-environment interactions. Differential susceptibility to the environment means that heritable traits can have positive or negative effects, depending on environmental context. Thus, traits that increase risk for mental disorders when the environment is negative can be adaptive when the environment is positive. This model can be applied to borderline personality disorder, with predictors such as emotional dysregulation and impulsivity seen as temperamental variations leading to negative effects in an unfavorable environment but to positive effects in a favorable environment. This model may also be useful in conceptualizing the mechanisms of effective therapy for borderline personality disorder.


Insulin stimulates postsynaptic density-95 protein translation via the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway.
Insulin receptors are highly enriched at neuronal synapses, but whose function remains unclear. Here we present evidence that brief incubations of rat hippocampal slices with insulin resulted in an increased protein expression of dendritic scaffolding protein postsynaptic density-95 (PSD-95) in area CA1. This insulin-induced increase in the PSD-95 protein expression was inhibited by the tyrosine kinase inhibitor, AG1024, phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin, translational inhibitors, anisomycin and rapamycin, but not by LY303511 (an inactive analogue of LY294002), and transcriptional inhibitor, actinomycin D, suggesting that insulin regulates the translation of PSD-95 by activating the receptor tyrosine kinase-PI3K-mammalian target of rapamycin (mTOR) signaling pathway. A similar insulin-induced increase in the PSD-95 protein expression was detected after stimulation of the synaptic fractions isolated from the hippocampal neurons. Furthermore, insulin treatment did not affect the PSD-95 mRNA levels. In agreement, insulin rapidly induced the phosphorylation of 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (Akt), and mTOR, effects that were prevented by the AG1024 and LY294002. We also show that insulin stimulated the phosphorylation of 4E-binding protein 1 (4E-BP1) and p70S6 kinase (p70S6K) in a mTOR-dependent manner. Finally, we demonstrate the constitutive expression of PSD-95 mRNA in the synaptic fractions isolated from hippocampal neurons. Taken together, these findings suggest that activation of the PI3K-Akt-mTOR signaling pathway is essential for the insulin-induced up-regulation of local PSD-95 protein synthesis in neuronal dendrites and indicate a new molecular mechanism that may contribute to the modulation of synaptic function by insulin in hippocampal area CA1.


Somitogenesis in the anole lizard and alligator reveals evolutionary convergence and divergence in the amniote segmentation clock.
The axial skeleton is a defining feature of vertebrates and is patterned during somitogenesis. Cyclically expressed members of the notch and other signaling pathways, described as the 'segmentation clock', regulate the formation of somite boundaries. Comparisons among vertebrate model systems have revealed fundamental shifts in the regulation of expression among critical genes in the notch pathway. However, insights into the evolution of these expression differences have been limited by the lack of information from non-avian reptiles. We analyzed the segmentation clock of the first Lepidosaurian reptile sequenced, the green anole lizard, Anolis carolinensis, for comparison with avian and mammalian models. Using genomic sequence, RNA-Seq transcriptomic data, and in situ hybridization analysis of somite-stage embryos, we carried out comparative analyses of key genes and found that the anole segmentation clock displays features common to both amniote and anamniote vertebrates. Shared features with anamniotes, represented by Xenopus laevis and Danio rerio, include an absence of lunatic fringe (lfng) expression within the presomitic mesoderm (PSM), a hes6a gradient in the PSM not observed in the chicken or mouse, and EGF repeat structure of the divergent notch ligand, dll3. The anole and mouse share cycling expression of dll1 ligand in the PSM. To gain insight from an Archosaurian reptile, we analysed LFNG and DLL1 expressions in the American alligator. LFNG expression was absent in the alligator PSM, like the anole but unlike the chicken. In contrast, DLL1 expression does not cycle in the PSM of the alligator, similar to the chicken but unlike the anole. Thus, our analysis yields novel insights into features of the segmentation clock that are evolutionarily basal to amniotes versus those that are specific to mammals, Lepidosaurian reptiles, or Archosaurian reptiles.


Effectiveness of Maternal mRNA COVID-19 Vaccination During Pregnancy Against COVID-19-Associated Hospitalizations in Infants Aged <6 Months During SARS-CoV-2 Omicron Predominance - 20 States, March 9, 2022-May 31, 2023.
Infants aged <6 months are not eligible for COVID-19 vaccination. Vaccination during pregnancy has been associated with protection against infant COVID-19-related hospitalization. The Overcoming COVID-19 Network conducted a case-control study during March 9, 2022-May 31, 2023, to evaluate the effectiveness of maternal receipt of a COVID-19 vaccine dose (vaccine effectiveness [VE]) during pregnancy against COVID-19-related hospitalization in infants aged <6 months and a subset of infants aged <3 months. VE was calculated as (1 - adjusted odds ratio) x 100% among all infants aged <6 months and <3 months. Case-patients (infants hospitalized for COVID-19 outside of birth hospitalization and who had a positive SARS-CoV-2 test result) and control patients (infants hospitalized for COVID-19-like illness with a negative SARS-CoV-2 test result) were compared. Odds ratios were determined using multivariable logistic regression, comparing the odds of receipt of a maternal COVID-19 vaccine dose (completion of a 2-dose vaccination series or a third or higher dose) during pregnancy with maternal nonvaccination between case- and control patients. VE of maternal vaccination during pregnancy against COVID-19-related hospitalization was 35% (95% CI = 15%-51%) among infants aged <6 months and 54% (95% CI = 32%-68%) among infants aged <3 months. Intensive care unit admissions occurred in 23% of all case-patients, and invasive mechanical ventilation was more common among infants of unvaccinated (9%) compared with vaccinated mothers (1%) (p = 0.02). Maternal vaccination during pregnancy provides some protection against COVID-19-related hospitalizations among infants, particularly those aged <3 months. Expectant mothers should remain current with COVID-19 vaccination to protect themselves and their infants from hospitalization and severe outcomes associated with COVID-19.


Microbial Trends in Infection-related Readmissions Following Radical Cystectomy for Bladder Cancer.
To report microbial pathogens detected at infection-related readmissions, including their susceptibility to antimicrobials. A retrospective review of 785 patients who underwent radical cystectomy for bladder cancer at a tertiary center in Denmark between 2009 and 2019. All patients received prophylactic cefuroxime preoperatively and pivmecillinam at stent- or catheter removal. Data were collected through the national medical records and microbiology database. The primary outcome was readmission rate and pathogens detected at infection-related readmissions. Univariable and multivariable regression analyses were carried out to identify risk factors of readmission. Within 90days of surgery, 225 (29%) patients experienced at least one infection-related readmission. The most common pathogen identified was Enterococcus spp (24% of all positive samples). In blood cultures, the most dominant species were Escherichia coli (29%) and Staphylococcus spp (26%). Due to the heterogeneity in microbial species identified, more than one-third of the bacteria where mecillinam was tested showed resistance. Most isolates were susceptible to piperacillin+tazobactam. Orthotopic neobladder and continent cutaneous reservoir were associated with the highest risk of infection-related readmission compared to ileal conduit (odds ratios 2.78 [95%CI 1.66;4.65] and 3.08 [95%CI 1.58;5.98], respectively). Patients with diabetes had an increased risk of infection-related readmission compared to patients without diabetes (odds ratio 1.67 [95%CI 1.02;2.73]). Nearly one-third of all patients experienced at least one postoperative infection-related readmission with a wide range of microbial etiologies. Generalizability of our results is uncertain, but the data can be used to plan interventional trials of antibiotic prophylaxis.


Antibacterial activity of essential oils from Eucalyptus and of selected components against multidrug-resistant bacterial pathogens.
Eucalyptus globulus Labill (Myrtaceae) is the principal source of eucalyptus oil in the world and has been used as an antiseptic and for relieving symptoms of cough, cold, sore throat, and other infections. The oil, well known as 'eucalyptus oil' commercially, has been produced from the leaves. Biological properties of the essential oil of fruits from E. globulus have not been investigated much. The present study was performed to examine the antimicrobial activity of the fruit oil of E. globulus (EGF) and the leaf oils of E. globulus (EGL), E. radiata Sieber ex DC (ERL) and E. citriodora Hook (ECL) against multidrug-resistant (MDR) bacteria. Furthermore, this study was attempted to characterize the oils as well as to establish a relationship between the chemical composition and the corresponding antimicrobial properties. The chemical composition of the oils was analyzed by GLC-MS. The oils and isolated major components of the oils were tested against MDR bacteria using the broth microdilution method. EGF exerted the most pronounced activity against methicillin-resistant Staphylococcus aureus (MIC ~ 250 µg/ml). EGF mainly consisted of aromadendrene (31.17%), whereas ECL had citronellal (90.07%) and citronellol (4.32%) as the major compounds. 1,8-cineole was most abundant in EGL (86.51%) and ERL (82.66%). The activity of the oils can be ranked as EGF > ECL > ERL ~ EGL. However, all the oils and the components were hardly active against MDR Gram-negative bacteria. Aromadendrene was found to be the most active, followed by citronellol, citronellal and 1,8-cineole.


Effect of Berberine on Pharmacokinetics and Pharmacodynamics of Atorvastatin in Hyperlipidemia Rats.
1 Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with berberine. Atorvastatin is the substrate of CYP3A4 and P-gp. However, berberine is the inhibitor. The combination might lead to DDIs. The aim of this study was to assess the effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in rats.2 Plasma concentrations of atorvastatin with or without berberine were determined by HPLC. Pharmacokinetics parameters were calculated and used to evaluate pharmacokinetics interactions. The effect of berberine on pharmacodynamics of atorvastatin was investigated by detecting blood lipid, SOD, MDA, GSH-Px, AST, ALT, and liver histopathology.3 Cmax, tmax, and AUC0-t of atorvastatin in combination group significantly increased both in normal and model rats (P < 0.01). The increase of t1/2, AUC0-t in model rats was more significant than that in normal rats (P < 0.05). Pharmacodynamics indexes in treatment groups were significantly improved, especially combination group (P < 0.05). Moreover, it could be found that significant recovery in liver histopathology.4 In conclusion, berberine could affect pharmacokinetics of atorvastatin, enhance lipid-lowering effect and improve liver injury in rats. More attention should be paid to plasma exposure in clinical to avoid adverse reactions.


[Supplementary feeding of infants in a developed city within the context of a developing country].
To establish the timing for introducing supplementary foods in the diet of infants from the city of Campinas, state of São Paulo, Brazil. This cross-sectional study included 2 857 children younger than 2 years of age randomly selected from the city department of health live birth database between 2004 and 2005. The mothers answered a questionnaire that included 87 closed questions designed to collect information concerning socioeconomic status, breastfeeding, and timing of introduction of supplementary foods. Assessment of the mothers revealed that 13.5% were adolescents, 73.1% had completed elementary or high school education, 45.9% had technical level jobs, 6,7% had jobs requiring a university degree, and 2.7% were health professionals. On average, participants belonged to socioeconomic class C (ranging from A, highest, to E, lowest), but all socioeconomic classes were represented. The median duration of exclusive breastfeeding was 90 days (95%CI: 87.6-92.4). Water (95%CI: 118.6-121.4) and tea (95 CI%: 113.2-126.8) were introduced at a median of 120 days. Semi-solid foods (95%CI: 178.6-181,4) and powdered milk (95%CI: 169.0-191.0) were introduced at a median of 180 days. Powdered milk and soft drinks had been ingested by 39.1% and 2.1%, respectively, at 4 months, and by 63.2 and 69.1%, respectively, at 1 year of age. Shorter breastfeeding duration was observed for women with technical level jobs, those who were unemployed, and those without a partner. The median duration of exclusive breastfeeding was far from that recommended due to the offer of supplementary fluids. Supplementary foods were introduced precociously, especially sweets.


Tribology considerations for hip joint articulations in relation to the "new orthopaedic patient".
The purpose of this review is to examine alternative bearings used in total hip arthroplasty (THA) and discuss the specific tribologic needs of the "New Orthopaedic Patient". As orthopaedic patients today are younger and more active, there is a clear need for hip joint implants and articulations minimising the amount of wear and guarantying better stability. Recent modern developments in tribology with highly cross-linked polyethylenes and hard-on-hard bearings allow the safe and effective use of larger diameter articulations in THA.


[The thoracic picture in acute traumatic aortic rupture].
We tried to find out the validity of 16 wellknown signs indicating an acute traumatic aortic rupture on plain chest radiographs of 22 patients. Angiographically 11 of all patients had a tear at the aortic isthmus. It turned out that 7 of the 16 signs (widened mediastinum, loss of the aortic knob contour, opacification in the aortopulmonary window, bulging of the vascular pedicle predominantly to the left, left apical cap, depression of the left main stem bronchus and displacement of the right paraspinous interface) are of great diagnostic value.


[Roaming through methodology. XXXI. Estimating partially hidden populations: heroin addicts in Amsterdan].
To estimate the size of a partly hidden population the capture-recapture method can be used. The estimation is based on analysis of the overlap between several samples of the population of interest. The quality of this capture-recapture estimation highly depends on whether the assumptions of the method are or are not met: samples should be independent, the population should be closed, the overlap should be recognised, and samples should contain only individuals originating from the population of interest. Violation of these assumptions may lead to a serious underestimation or (more often) overestimation. The number of problematic heroin addicted people in Amsterdam was estimated on the basis of registered numbers in the easily accessible methadone programme of the municipal health organisation, in the police station methadone treatment programme, and in the hospital registration in the first quarter of 1997: 4130 (95% confidence interval: 3750-4570).


Nutritional Issues in Head and Neck Cancer Patients.
The purpose of this paper is to update the oncologist on the correct approach to the nutritional care of the head and neck cancer patient. Recent scientific contributions on this issue, with a special emphasis on international guidelines and randomised clinical trials (RCTs), are reviewed. The following points are noteworthy: 1. Despite the advances in early diagnosis and modern treatment of head and neck cancer, this tumour still ranks first regarding frequency and severity of weight loss, both at the clinical presentation and during the therapy. 2. This is due to the combination of poor alimentation because of the tumour mass localization, as well as of the presence of an inflammatory response which furtherly drives catabolism. 3. Several studies have shown a very limited role for a dietary counselling unless it includes oral nutritional supplements which are protein or omega-3 fatty acid enriched. 4. A parental nutritional supplementation could represent an acceptable short-term alternative. 5. Long-term nutritional support relies on the use of percutaneous endoscopic gastrostomy (PEG), whereas the role of a prophylactic or "a la demande" PEG is still unsettled and requires further investigations. In conclusion, the nutritional approach using specific formulas and the appropriate route of administration should be part of the therapeutic armamentarium of the modern oncologist.


Evaluation of continuous renal replacement therapy and risk factors in the pediatric intensive care unit.
Acute kidney injury (AKI) is one of the most common causes of increased mortality and morbidity in the pediatric intensive care unit (PICU). Continuous renal replacement therapy (CRRT) is the mainstay treatment for AKI in children as it allows continuous and programmed removal of fluids, which is tolerated better hemodynamically. Defining the risk factors of CRRT related to mortality and morbidity will help improve the outcomes of patients in the PICU. In this study, we aimed to determine the prognostic factors and outcomes of patients who received CRRT. This was a single-center, retrospective study on PICU patients requiring CRRT. Patients with a history of chronic renal failure and PICU stay duration of <24 h and those who died on the 1st day of admission were excluded from the study. A total of 447 patients admitted between October 2016 and March 2018 were included in the study. Children who received CRRT for the management of AKI and/or other nonrenal indications, such as metabolic acidosis, poisoning, electrolyte imbalance, and congenital metabolic diseases, were also included in the study. Fifty patients underwent CRRT. There was a statistically significant relationship between CRRT support and prognostic factors, including age (P = 0.012), inotropic drug usage (P = 0.000), concomitant infection (P = 0.010), blood component transfusion (P = 0.005), pediatric risk of mortality score (P = 0.027), and mortality (P = 0.003). The odds ratio for mortality was 5.396 (95% confidence interval: 1.732-16.809). In conclusion, CRRT is associated with increased morbidity and mortality in the PICU.


Screening of crude extracts of six medicinal plants used in South-West Nigerian unorthodox medicine for anti-methicillin resistant Staphylococcus aureus activity.
Six Nigerian medicinal plants Terminalia avicennioides, Phylantus discoideus, Bridella ferruginea, Ageratum conyzoides, Ocimum gratissimum and Acalypha wilkesiana used by traditional medical practitioners for the treatment of several ailments of microbial and non-microbial origins were investigated for in vitro anti-methicillin Resistant Staphylococcus aureus (MRSA) activity. Fresh plant materials were collected from the users. Water and ethanol extracts of the shredded plants were obtained by standard methods. The Bacterial cultures used were strains of MRSA isolated from patients. MRSA was determined by the reference broth microdilution methods using the established National Committee for Clinical Laboratory Standards break points. Staphylococcus aureus NCIB 8588 was used as a standard strain. Susceptibility testing and phytochemical screening of the plant extracts were performed by standard procedures. Controls were maintained for each test batch. Both water and ethanol extracts of T. avicennioides, P. discoideus, O. gratissimum, and A. wilkesiana were effective on MRSA. The Minimum Inhibition Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the ethanol extracts of these plants range from 18.2 to 24.0 mcg/ml and 30.4 to 37.0 mcg/ml respectively. In contrast, MIC range of 30.6 to 43.0 mcg/ml and 55.4 to 71.0 mcg/ml were recorded for ethanol and water extracts of B. ferruginea, and A. conyzoides respectively. Higher MBC values were obtained for the two plants. These concentrations were too high to be considered active in this study. All the four active plants contained at least trace amount of anthraquinones. Our results offer a scientific basis for the traditional use of water and ethanol extracts of A. wilkesiana, O. gratissimum, T. avicennioides and P. discoideus against MRSA-associated diseases. However, B. ferruginea and A. conyzoides were ineffective in vitro in this study; we therefore suggest the immediate stoppage of their traditional use against MRSA-associated diseases in Lagos, Nigeria.


Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles.
The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as "long COVID". Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.


Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis: 1-year follow-up data of a randomized-controlled trial.
Essentials Acute iliofemoral deep vein thrombosis can be treated with catheter-directed thrombolysis (CDT). We performed a randomized trial comparing conventional CDT versus ultrasound-assisted CDT (USAT). Clinical and duplex sonographic outcomes at 12 months were similar in the CDT and USAT groups. In both groups, incidence of postthrombotic syndrome was very low with good quality of life. Background In patients with acute iliofemoral deep vein thrombosis (IFDVT), catheter-directed thrombolysis (CDT) aims to prevent the postthrombotic syndrome (PTS). Adding intravascular high-frequency, low-power ultrasound energy to CDT does not seem to improve the immediate thrombolysis results but its impact on clinical outcomes at 12 months is not known. Patients/Methods In this randomized-controlled trial, 48 patients (mean age 50 ± 21 years; 52% women) with acute IFDVT were randomized to conventional CDT (n = 24) or ultrasound-assisted CDT (USAT; n = 24). In both groups, a fixed-dose thrombolysis regimen (20 mg r-tPA over 15 h) was used, followed by routine stenting of residual venous obstruction. At 12 months, PTS and venous disease severity (Villalta score and revised Venous Clinical Severity Score [rVCSS]), disease-specific quality of live (QOL; CIVIQ-20) and duplex-sonographic outcomes were assessed. Results Among the 45 surviving patients, 40 (89%; 95% confidence interval [CI] 76-96%) patients were free from PTS (defined as Villalta score < 5 points; 83%, 95% CI 61-95% in the USAT and 96%, 95% CI 77-100% in the CDT group), with a similar mean total Villalta score of 2.3 ± 2.9 vs. 1.7 ± 1.6, and a mean total rVCSS of 3.0 ± 3.5 vs. 2.7 ± 2.9 in the USAT and the CDT groups, respectively. Both groups had good disease-specific QOL with a CIVIQ-20 score of 29.4 ± 11.8 vs. 26.1 ± 7.8, respectively. Primary (100% vs. 92%) and secondary (100% vs. 96%) iliofemoral patency rates and presence of femoro-popliteal venous reflux (39% vs. 33%) were similar in both groups. Conclusion The addition of intravascular ultrasound energy to conventional CDT for the treatment of acute IFDVT did not have any impact on relevant clinical or duplex sonographic outcomes, which were favorable in both study groups. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier:NCT01482273.


Clarifying the relationship of veterinary medical education and moral development.
To clarify the relationship between veterinary medical education and moral development in response to 2 previous studies that presented conflicting evidence that the experience of veterinary medical education may inhibit moral development. The Defining Issues Test (DIT) was used to survey the moral reasoning of veterinary medical students at the beginning and end of their education. First and fourth-year veterinary medical students. The moral reasoning of 98 veterinary medical students was assessed at the beginning of their first semester of veterinary medical education and again, 4 years later, at the end of their last semester to determine whether their moral reasoning scores would reflect the expected maturity-related increases usually found at this age range and education level. The DIT scores ranged from 8.3 to 70.0 for first-year students and from 16.7 to 76.7 for fourth-year students. The first-year mean was 44.0 and the fourth-year mean was 45.4. The mean change of +1.45 points was not significant. Statistical analysis did not reveal any significant correlation between the moral reasoning scores and age; however, there was a significant correlation between the moral reasoning scores and gender, with females scoring higher on the first and second test. The difference in the rate of change between tests by gender was not significant. This study appears to confirm the findings of an earlier study suggesting veterinary medical education inhibits an increase of moral reasoning in veterinary medical students.


Religious anti-gay prejudice as a predictor of mental health, abuse, and substance use.
Anti-gay, or homonegative, prejudice is generally considered harmful to the wellbeing of sexual minority individuals. However, the origins or nature of such prejudice may vary. Despite a sizable body of literature suggesting homonegative prejudice is frequently religious-based, the psychological impact of exposure to religious anti-gay prejudice remains largely undetermined. Addressing this research gap, the authors examined whether opposition to same-sex sexuality on religious grounds predicted detrimental outcomes among same- and both-sex attracted individuals, as well as their heterosexual counterparts. A nationwide U.S. sample of 1600 individuals-recruited using contemporary online crowd-sourcing techniques designed to limit selection bias-completed a novel inventory assessing interpersonal exposure to religious (as well as nonreligious) homonegative disapproval. Outcome variables assessed included a number of clinically relevant measures spanning general mental health, social support, suicidality, abuse, and substance use. Analyses revealed that greater exposure to religious anti-gay prejudice predicted higher levels of anxiety, stress, and shame; more instances of physical and verbal abuse; and more problematic alcohol use. Furthermore, while sexual minority individuals tended to fare more poorly than their heterosexual counterparts on almost every outcome measure assessed, homonegative prejudice predicted poorer outcomes among all respondents regardless of their sexual orientation or religious identification. Hence, results are among the first to demonstrate that anti-gay religious exposure is associated with substantial threats to wellbeing, and that such effects may be observed beyond religious sexual minorities. Overall, findings imply that homonegative religious social conditions may be of broader health and mental health concern than is conventionally recognized. (PsycINFO Database Record


Identification of cortical lamination in awake monkeys by high resolution magnetic resonance imaging.
Brodmann divided the neocortex into 47 different cortical areas based on histological differences in laminar myeloarchitectonic and cytoarchitectonic defined structure. The ability to do so in vivo with anatomical magnetic resonance (MR) methods in awake subjects would be extremely advantageous for many functional studies. However, due to the limitations of spatial resolution and contrast, this has been difficult to achieve in awake subjects. Here, we report that by using a combination of MR microscopy and novel contrast effects, cortical layers can be delineated in the visual cortex of awake subjects (nonhuman primates) at 4.7 T. We obtained data from 30-min acquisitions at voxel size of 62.5 × 62.5 × 1000 μm(3) (4 nl). Both the phase and magnitude components of the T(2)*-weighted image were used to generate laminar profiles which are believed to reflect variations in myelin and local cell density content across cortical depth. Based on this, we were able to identify six layers characteristic of the striate cortex (V1). These were the stripe of Kaes-Bechterew (in layer II/III), the stripe of Gennari (in layer IV), the inner band of Baillarger (in layer V), as well as three sub-layers within layer IV (IVa, IVb, and IVc). Furthermore, we found that the laminar structure of two extrastriate visual cortex (V2, V4) can also be detected. Following the tradition of Brodmann, this significant improvement in cortical laminar visualization should make it possible to discriminate cortical regions in awake subjects corresponding to differences in myeloarchitecture and cytoarchitecture.


[Squamous carcinoma of the esophagus with extensive pagetoid dissemination].
A case of squamous carcinoma of the esophagus with pagetoid spreading in a 59-year-old male in presented. Signs of glandular differentiation (PAS-diastase, Alcian blue) and CEA were negative in the Paget-like cells. Pagetoid spreading of squamous carcinoma and true Paget's disease are very similar histologically and very rare in the esophagus (only 6 cases reported) and they must be differentiated from each other. Paget's disease demonstrates glandular differentiation and the cells are CEA positive. The absence of glandular differentiation in the Paget-like cells of pagetoid spreading versus Paget's disease may be a good criteria to differentiate these diseases.


Adipocytes regulate fibroblast function, and their loss contributes to fibroblast dysfunction in inflammatory diseases.
Fibroblasts play critical roles in tissue homeostasis, but in pathologic states can drive fibrosis, inflammation, and tissue destruction. In the joint synovium, fibroblasts provide homeostatic maintenance and lubrication. Little is known about what regulates the homeostatic functions of fibroblasts in healthy conditions. We performed RNA sequencing of healthy human synovial tissue and identified a fibroblast gene expression program characterized by enhanced fatty acid metabolism and lipid transport. We found that fat-conditioned media reproduces key aspects of the lipid-related gene signature in cultured fibroblasts. Fractionation and mass spectrometry identified cortisol in driving the healthy fibroblast phenotype, confirmed using glucocorticoid receptor gene ( NR3C1 ) deleted cells. Depletion of synovial adipocytes in mice resulted in loss of the healthy fibroblast phenotype and revealed adipocytes as a major contributor to active cortisol generation via Hsd11 β 1 expression. Cortisol signaling in fibroblasts mitigated matrix remodeling induced by TNFα- and TGFβ, while stimulation with these cytokines repressed cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease.


Genome-wide association mapping for wood characteristics in Populus identifies an array of candidate single nucleotide polymorphisms.
Establishing links between phenotypes and molecular variants is of central importance to accelerate genetic improvement of economically important plant species. Our work represents the first genome-wide association study to the inherently complex and currently poorly understood genetic architecture of industrially relevant wood traits. Here, we employed an Illumina Infinium 34K single nucleotide polymorphism (SNP) genotyping array that generated 29,233 high-quality SNPs in c. 3500 broad-based candidate genes within a population of 334 unrelated Populus trichocarpa individuals to establish genome-wide associations. The analysis revealed 141 significant SNPs (α ≤ 0.05) associated with 16 wood chemistry/ultrastructure traits, individually explaining 3-7% of the phenotypic variance. A large set of associations (41% of all hits) occurred in candidate genes preselected for their suggested a priori involvement with secondary growth. For example, an allelic variant in the FRA8 ortholog explained 21% of the total genetic variance in fiber length, when the trait's heritability estimate was considered. The remaining associations identified SNPs in genes not previously implicated in wood or secondary wall formation. Our findings provide unique insights into wood trait architecture and support efforts for population improvement based on desirable allelic variants.


Quantitative trait locus mapping of the transpiration ratio related to preflowering drought tolerance in sorghum (Sorghum bicolor).
To meet future food needs, grain production must increase despite reduced water availability, so waterproductivity must rise. One way to do this is to raise the ratio of biomass produced to water transpired, which is controlled by the ratio of CO2 assimilation (A) to transpiration (E) (i.e. the transpiration ratio, A : E divided by vapour pressure deficit) or anything affecting stomatal movement.. We describe the genetic variation and basis of A, E and A : E among 70 recombinant inbred lines (RILs) of sorghum (Sorghum bicolor (L.) Moench), using greenhouse experiments. Experiment 1 used 40% and 80% of field capacity (FC) as water regimes; Experiment 2 used 80% FC. Genotype had a significant effect on A, E and A : E. In Experiment 1, mean values for A : E were 1.2-4.4 mmol CO2 mol-1 H2O kPa-1 and 1.6-3.1 mmol CO2 mol-1 H2O kPa-1 under 40% and 80% FC, respectively. In Experiment 2, values were 5.6-9.8 mmol CO2 mol-1 H2O kPa-1. Pooled data for A : E and A : E VPD-1 from Experiment 1 indicate that A : E fell quickly at temperatures >32.3°C. A : E distributions were skewed. Mean heritabilities for A : E were 0.9 (40% FC) and 0.8 (80% FC). Three significant quantitative trait loci (QTLs) associated with A:E, two on SBI-09 and one on SBI-10, accounted for 17-21% of the phenotypic variation. Subsequent experiments identified 38 QTLs controlling variation in height, flowering, biomass, leaf area, greenness and stomatal density. Colocalisation of A : E QTLs with agronomic traits indicated that these QTLs can be used for improving sorghum performance through marker assisted selection (MAS) under preflowering drought stress.


Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis.
To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI). For 69 nodules [12 Edmondson (Ed)-I, 48 Ed-II, 9 Ed-III] in 54 HCC patients, signal intensity patterns and enhancement patterns of gadopentate dimeglumine (Gd-DTPA) dynamic studies were correlated with histological differentiation and serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) level, which is an indicator of poor prognosis. Hypointensity on T1-weighted imaging was seen in 17, 72, and 89% of Ed-I, Ed-II, and Ed-III HCCs, respectively (P < 0.001). Meanwhile, hyperintensity on T2-weighted imaging was seen in 42, 88, and 89% (P < 0.005). Tumor stain during the arterial phase of Gd dynamic MRI was seen in 75, 86, and 89%. Tumor stain washout during the portal phase was seen in 43% of Ed-II and 100% of Ed-III HCCs (P < 0.005). In the Ed-II and Ed-III HCCs, hypointensity on T1-weighted imaging was seen in 65% of AFP-L3-negative HCCs and 90% of AFP-L3-positive HCCs (P = 0.071). Washout of tumor stain during the portal phase was seen in 39% of AFP-L3-negative HCCs and 75% of AFP-L3-positive HCCs (P < 0.05). Although hyperintensity of tumor on T2-weighted imaging and arterial hypervascularity of tumor are considered to be useful for differential diagnosis between well differentiated HCCs and moderately/poorly differentiated HCCs, hypointensity of tumor on T1-weighted imaging and tumor stain washout during the portal phase of Gd-DTPA dynamic MRI reflected poorer histological differentiation of HCCs and correlated with AFP-L3 levels.


Changes in survival of colorectal cancer patients in Świętokrzyskie Province (Southern Poland) from the second half of the 1990s to the early 21st century - a population-based study.
For years, the increase in cancer incidence and deaths has constituted a significant health and social problem. Variation in the burden in cancers in different regions of the world requires constant monitoring of the epidemiological situation in this regard. Assessing survival in cancer patients is a valuable source of information for patients and physicians alike, as well as for politicians who have a direct impact on the shaping of health policy and health systems. The aim of the present study was to assess the changes in the 5-year relative survival of colorectal cancer patients during 1995-2014. The data of 8,970 patients with colorectal cancer in the years 1995-2014, 5,033 males and 3,937 females aged 67.5 ± 11.7 from Świętokrzyskie Cancer Registry were used. Cases were classified according to the topographical codes ICD-O-3: C18.0-C18.9, C19.9, C20.9, C21.0-C21.2, C21.8. The end of follow-up was fixed at 31 December 2014. Four five-year calendar periods were defined. In each calendar period, relative survival rates using the Ederer II method were estimated separately for males and females. In 2010-2014 (against 1995-1999), the absolute increase in the 5-year relative survival in males and females with colon cancer was the highest and reached 9.8 percentage point (p.p.) and 9.6 p.p., respectively. Patterns of survival for both colon and rectal cancer patients according to gender and age were very similar. In 1995-2014, an increase in the value of relative survival rates of males and females with colorectal cancer was observed. Systematic increase in funding in health care was a chance for reducing the burden of colorectal cancer by more widespread and equal access of effective early detection and cancer treatment.


Mutagenesis by reversible promoter insertion to study the activation of NF-kappaB.
Genetic dissection of signaling pathways in mammalian cells involves screening or selecting phenotypic mutants obtained by a variety of techniques. Limitations in current methods include inadequate genome coverage and difficulty in validating the link between mutation and phenotype. We describe an improved method for insertional mutagenesis with retroviral vectors and show that the ability to induce mutations increases greatly if a randomly inserted promoter directs transcription into the host DNA. The mutant phenotype is due to the expression of a hybrid transcript derived from the vector and the insertion site. Because other alleles of the affected gene remain intact, the phenotype is dominant, but is reversible by inactivating the promoter, for example, by site-specific recombination. Importantly, in mutant clones with multiple inserts, limited excision yields progeny with different patterns of inserts remaining. Characterizing these progeny allows the mutant phenotype to be associated with a specific target gene. Relative simplicity and robust target validation make the method suitable for a broad range of applications. We have used this technique to search for proteins that regulate NF-kappaB-dependent signaling in human cells. Two validated targets are the relA gene, which codes for the NF-kappaB p65 subunit, and the NF-kappaB regulator act1. Overexpression of the corresponding proteins, caused by insertion of a promoter into the first intron of each gene, leads to NF-kappaB-dependent secretion of factors that activate NF-kappaB through cell-surface receptors, establishing an autocrine loop.


Ureteral stent failure in pediatric patients under 10 years: occurrence and risk factors.
To examine the occurrence of ureteral stent failure in pediatric patients aged <10 years and to determine risk factors for failure. We performed a retrospective cohort analysis of 100 patients who underwent ureteral stent insertion between January 2006 and December 2013. All patients were aged <10 years and were followed up until ureteral stent removal. Information regarding patient demographics, reason for stent insertion, duration of stent maintenance, stent diameter and length, and postoperative results was collected. Risk factors for stent failure were analyzed. Ureteral stenting was performed in 114 ureter units. The median age at stenting was 34.1 months (interquartile range [IQR], 8.1-71.2 months), and the median duration of stent maintenance was 35.0 days (IQR, 21.0-44.3 days). A 3-Fr stent was used in 39.5% of patients. Stent failure was observed in 11 ureter units (9.6%) at a median of 11.5 days (IQR, 7.8-24.5 days) after insertion, and the stent was subsequently removed. Use of a 3-Fr ureteral stent was the only risk factor for the development of stent failure; the failure rate was 20.0% with this stent diameter. Ureteral stenting was a useful procedure with a high success rate, even in patients aged <10 years. A 3-Fr ureteral stent was the only risk factor for stent failure; its substantial failure rate should be considered when deciding whether to insert a stent. Also, short-term re-evaluation after ureteral stent insertion is mandatory, especially with 3-Fr ureteral stents.


Optimization of cell seeding efficiencies on a three-dimensional gelatin scaffold for bone tissue engineering.
Bone tissue engineering techniques hold great potential for the treatment of clinical defects. However, there is much optimization needed before bone tissue engineering can be used therapeutically. This study evaluated various cell seeding methods onto a porous three-dimensional (3D) scaffold for bone tissue engineering optimization. MG63 human osteoblast-like cells were seeded onto a resorbable, porous gelatin sponge in different suspension volumes (50 microl and 5 ml), and culture conditions, (static, shaken, rolled, or rotatory bioreactor). The DNA of the cells in the scaffold, the media and the containers were quantitated separately to determine the cell number and location after 3 days of culture. The samples were stained with calcein and viewed using confocal microscopy to determine cell viability and location. Placing a small cell suspension (50 microl) directly onto the scaffold produced a significantly higher proportion of cells adhered to the scaffold than a larger cell suspension (5 ml). In all conditions except the rotatory bioreactor, the percentage of cells remaining on the scaffold after 3 days in a small seeding volume (63 +/- 22%) was significantly higher than the larger seeding volume (36 +/- 25%). In the case of the rotatory bioreactor, the opposite appeared to be true (39 +/- 9% small volume and 72 +/- 14% larger volume). It was important to keep the seeding dynamics of the cultivated tissue engineered construct consistent throughout the experiments to ensure reproducibility. For this scaffold type, cells applied in a small volume and cultured on a plate shaker at 120 rpm (giving 81 +/- 14% of cells adhered to the scaffold) for 3 days is recommended.


Cross-sectional and longitudinal associations between receptive arts engagement and loneliness among older adults.
Loneliness in older adulthood is a societal and public health challenge warranting identification of sustainable and community-based protective factors. This study investigated whether frequency of receptive arts engagement is associated with lower odds of loneliness in older adults. We used data of respondents from waves 2 (2004-2005) and 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) and examined cross-sectional (n = 6222) and longitudinal (n = 3127) associations between frequency of receptive arts engagement (including visits to the cinema, museums/galleries/exhibitions, theatre/concerts/opera) and odds of loneliness (cut-off ≥ 6 on three-item short form of the Revised UCLA Loneliness Scale). We fitted logistic regression models adjusted for a range of sociodemographic, economic, health and social, community and civic engagement factors. Cross-sectionally, we found dose-response negative associations between engagement with all receptive arts activities and odds of loneliness. Prospectively, in the fully-adjusted models we found most robust evidence for the negative association between engagement with museums/galleries/exhibitions and odds of loneliness (OR = 0.68, 95% CI 0.48-0.95) for those who engaged every few months or more often compared with those who never engaged. We found weaker evidence for lower odds of loneliness for more frequent engagement with theatre/concerts/opera. Frequent engagement with certain receptive arts activities and venues, particularly museums, galleries and exhibitions, may be a protective factor against loneliness in older adults. Future research is needed to identify the mechanisms through which this process may occur, leading to better understanding of how arts activities and venues can reduce loneliness among older adults.


Minimizing transfusion in sagittal craniosynostosis surgery: the Children's Hospital of Minnesota Protocol.
To assess the success of a protocol using preoperative erythropoietin (EPO) and iron with perioperative tranexamic acid (TXA) in reducing blood transfusion in sagittal craniosynostosis surgery. A retrospective chart review of all sagittal craniosynostosis patients undergoing open repair at our institution since 2010 was conducted. A novel protocol of preoperative EPO with iron and perioperative TXA, along with a shift away from automatic transfusion, was initiated in 2014. Perioperative hemoglobin levels, length of stay, and transfusion rates were compared between the historical control and the study group receiving the protocol. A total of 36 patients met inclusion criteria. Twenty-eight patients were male and 8 were female. Twenty-two patients were in the control group receiving neither TXA nor EPO and automatically received a transfusion, while 14 were in the study group and received the full protocol. There were no significant demographic differences between groups. Within the control group, 100% of patients were transfused compared with 14.3% of the study group (p < 0.0001). The study group also had a shorter postoperative length of stay in the hospital (mean, 3.4 days; range, 3-6) than the control (mean, 4 days; range, 2-5.5, p = 0.038). The study group had a higher preoperative hemoglobin than the control (13.6 vs. 11.8 g/dL, p = 0.0001). Our protocol of preoperative EPO and iron with perioperative TXA increased the preoperative hemoglobin and was associated with a low transfusion rate without negatively impacting postoperative course.


Sentrin-specific protease 1 maintains mitochondrial homeostasis through targeting the deSUMOylation of sirtuin-3 to alleviate oxidative damage induced by hepatic ischemia/reperfusion.
Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis. Further mechanistic exploration indicated that the protective mitochondrial protein sirtuin-3 (Sirt3) was inactivated by SUMOylation during HIRI, which was reversed by SENP1. Overexpression of SENP1 could restore mitochondrial function, mitigate oxidative stress and attenuated apoptosis through recovering the expression of Sirt3 during HIRI. Nevertheless, 3-TYP, an inhibitor of Sirt3, could eliminate the therapeutic effects brought by overexpression of SENP1. In conclusion, our findings demonstrated that SENP1 mediated the deSUMOylation of Sirt3 and maintained mitochondrial homeostasis, thus alleviating HIRI induced oxidative damage. SENP1 might be a promising therapeutic target for HIRI.


Stripping in hot mix asphalt produced by aggregates from construction and demolition waste.
This paper analyses the effect of water on the durability of hot asphalt mixtures made with recycled aggregates from construction and demolition debris. Indirect tensile stress tests were carried out to evaluate stripping behaviour. The mixtures tested were fabricated with 0, 20, 40 and 60% recycled aggregates. Two types of natural aggregates were used: schist and calcite dolomite. An increase in the percentage of recycled aggregates was found to produce a decrease in the tensile stress ratio of the hot asphalt mixtures. To study this phenomenon, two and three factor analyses of variance (ANOVA) were performed with indirect tensile stress being used as the dependent variable. The factors studied were the percentage of recycled aggregates (0, 20, 40 and 60%), the moisture state (dry, wet) and the type of natural aggregate (schist, calcite). On the basis of the ANOVA results, it was found that the most important factor affecting resistance was the moisture state (dry, wet) of the specimens. The percentage of recycled aggregate also affected indirect tensile stress, especially in the dry state. The type of natural aggregate did not have a significant effect on indirect tensile stress. The hot asphalt mixture specimens made with different percentages of recycled aggregates from construction and demolition debris and of natural quarry aggregates showed poor stripping behaviour. This stripping behaviour can be related to both the poor adhesion of the recycled aggregates and the high absorption of the mortar of cement adhered to them.


MnCO3-mineralized polydopamine nanoparticles as an activatable theranostic agent for dual-modality imaging-guided photothermal therapy of cancers.
Background: Single imaging modality is still insufficient to evaluate the biological and anatomical structures of tumors with high accuracy and reliability. Generation of non-specific contrast, leading to a low target-to-background signal ratio, results in low imaging resolution and accuracy. Tumor environment-specific activatable multifunctional contrast agents need to maximize the contrast signals, representing a dual imaging-guided photothermal therapy (PTT) at target tumor sites. Methods: Cellular uptake, cytotoxicity assay, and in vitro photothermal conversion efficiency of MnCO3-mineralized fluorescent polydopamine nanoparticles (MnCO3-FPNPs) were evaluated using 4T1 breast cancer cells. In vivo dual-modality imaging was performed using IVIS imaging and a 4.7 T animal MRI systems after injection into 4T1 tumor-bearing nude mice. The effects of photothermal therapeutic through PTT were measured after irradiation with an 808 nm laser (1.5 W/cm2) for 10 min, measuring the size of the tumors every 2 days. Results: At physiological pH (7.4), MnCO3-FPNP is efficiently quenched. Conversely, at acidic pH (5.4), the strong fluorescence (FL) is recovered due to the dissociation of Mn2+ from the FPNPs. At pH 7.4, MnCO3-FPNP activity is silenced to enhance water proton relaxation due to unionized MnCO3 maintenance; conversely, at acidic pH (5.4), MnCO3-FPNPs efficiently release Mn2+ ions, thereby resulting in T 1-weighted magnetic resonance (MR) contrast enhancement. MnCO3-FPNPs display a promising diagnostic ability for 4T1 breast cancer xenograft models, as well as exhibit a high photothermal conversion efficiency. A successful tumor treatment via their photothermal activity is accomplished within 14 days. Conclusions: Our studies exhibited unique "OFF-ON" activation abilities in FL/MR dual imaging and PTT functions. This approach suggests that the MnCO3-FPNPs may serve as a useful platform for various mineralization-based multimodal imaging-guided PTT models for many cancer theranostic applications.


[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer].
As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis. Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis. It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter. The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.


Microglia-derived TNFα induces apoptosis in neural precursor cells via transcriptional activation of the Bcl-2 family member Puma.
Neuroinflammation is a common feature of acute neurological conditions such as stroke and spinal cord injury, as well as neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Previous studies have demonstrated that acute neuroinflammation can adversely affect the survival of neural precursor cells (NPCs) and thereby limit the capacity for regeneration and repair. However, the mechanisms by which neuroinflammatory processes induce NPC death remain unclear. Microglia are key mediators of neuroinflammation and when activated to induce a pro-inflammatory state produce a number of factors that could affect NPC survival. Importantly, in the present study we demonstrate that tumor necrosis factor α (TNFα) produced by lipopolysaccharide-activated microglia is necessary and sufficient to trigger apoptosis in mouse NPCs in vitro. Furthermore, we demonstrate that microglia-derived TNFα induces NPC apoptosis via a mitochondrial pathway regulated by the Bcl-2 family protein Bax. BH3-only proteins are known to play a key role in regulating Bax activation and we demonstrate that microglia-derived TNFα induces the expression of the BH3-only family member Puma in NPCs via an NF-κB-dependent mechanism. Specifically, we show that NF-κB is activated in NPCs treated with conditioned media from activated microglia and that Puma induction and NPC apoptosis is blocked by the NF-κB inhibitor BAY-117082. Importantly, we have determined that NPC apoptosis induced by activated microglia-derived TNFα is attenuated in Puma-deficient NPCs, indicating that Puma induction is required for NPC death. Consistent with this, we demonstrate that Puma-deficient NPCs exhibit an ∼13-fold increase in survival as compared with wild-type NPCs following transplantation into the inflammatory environment of the injured spinal cord in vivo. In summary, we have identified a key signaling pathway that regulates neuroinflammation induced apoptosis in NPCs in vitro and in vivo that could be targeted to promote regeneration and repair in diverse neurological conditions.


Comparison of intravenous versus intramuscular administration of corticotropin-releasing hormone in healthy cats.
Because of the lack of a current validated assay for feline endogenous adrenocorticotropic hormone (ACTH) in response to administration of currently available ovine corticotropin-releasing hormone (oCRH) preparations, a complete evaluation of the hypothalamic-pituitary-adrenal axis in cats has not been possible. This study was undertaken to (1) determine the pituitary (ACTH) and adrenal (cortisol) response to both IV and IM administration of a currently available oCRH product in healthy cats, and (2) validate an endogenous ACTH assay for use in cats. Seventeen healthy cats receiving oCRH (n = 11) or placebo (n = 6). Prospective, randomized, placebo-controlled study. oCRH at 1 μg/kg or placebo was given either IM or IV. Endogenous cortisol and ACTH concentrations were evaluated after the injection. A comparison of IM versus IV and placebo versus treatment was made. The DiaSorin immunoradiometric assay (IRMA) assay for ACTH performed well, showing both parallelism and acceptable intra- and interassay coefficients of variation. There was a significant difference between groups (P = .025) and a significant difference between times (P = .025) when endogenous ACTH concentrations were compared after oCRH IV or IM. No significant differences were observed in cortisol concentrations comparing IV to IM oCRH. IM administration of oCRH results in significantly greater ACTH concentrations but not cortisol concentrations when compared with IV administration. Samples should be drawn before and at 60 minutes after the injection. The Diasorin IRMA is valid for feline endogenous ACTH measurements.


An Exploration on Attribute Non-attendance Using Discrete Choice Experiment Data from the Irish EQ-5D-5L National Valuation Study.
Generic measures of health-related quality of life (HRQoL) permit comparisons of competing demands for healthcare resources using outcomes that reflect the preferences of tax payers. EQ-5D instruments are the most commonly used generic, preference-based measures of HRQoL. The EQ-5D-5L enables respondents to describe their health state using five dimensions of health, each with five response levels. The standardised protocol for the valuation of EQ-5D-5L health states comprises use of the composite time trade-off valuation technique, supplemented by a discrete choice experiment (DCE). This paper presents the first exploration on attribute non-attendance (ANA) to the dimensions of the EQ-5D-5L using DCE data collected following the standardised protocol. This paper uses the equality constrained latent class model and the endogenous attribute attendance model to examine ANA to the dimensions of the EQ-5D-5L. The results suggest that respondents are less likely to consider the physical dimensions of the EQ-5D-5L (such as self-care and usual activities) when evaluating the health states. The effects of ANA on utility scores depends on the interpretation of the underlying reasons for ANA. We recommend that future value sets based in whole or in part on DCE data examine the impact of and reasons for non-attendance in national valuation studies.


Career choice influences in Australian anaesthetists.
All female members and a randomly selected group of male members of the Australian Society of Anaesthetists (n = 488) were surveyed by questionnaire as part of a broader study of gender issues in anaesthesia. This paper reports on reasons for career choice and the importance of role models. Responses were received from 199 women and 98 men (60.9% of those surveyed), representing all States and one Territory. Most males (95.9%) and a majority of females (55.7%) worked full-time. Reasons for career choice varied with gender, with a significantly greater proportion of women (39.7%) than men (8.7%) choosing anaesthesia because of controllable hours, particularly the ability to work part-time. Experiences in anaesthesia during internship and residency were important for 19.1% of women and 14.1% of men, although very few mentioned undergraduate exposure. Other important factors in career choice were the application of physiology and pharmacology in patient care, practical and procedural aspects of practice, and chance. A majority of women (56%) and men (55%) named specific role models who were influential and encouraging in their choice. These results are similar to those of other studies.


Studies on the subunit structure of 4-deoxy-5-oxoglucarate hydro-lyase (decarboxylating) from Pseudomonas acidovorans.
1. Homogeneous preparations of D-4-deoxy-5-oxoglutarate hydro lyase (decarboxylating)(EC22.214.171.124) were analysed in the ultracentrifuge by the high-speed sedimentation-equilibrium method of Yphantis (1964). The molecular weight in 0.1 M-potassium phosphate buffer, pH 7.2, in 6M-guanidine hydrochloride and in 0.1 M-beta-mercaptoethanol in 6M-guanidine hydrochloride was 113,000, 56,000 and 30,400 respectively. Polyacrylamidegel electrophoresis in the presence of sodium dodecyl sulphate indicated a minimum molecular weight of 30,500. 2. Measurement of the thiol content of the enzyme, before and after reduction with NaBH4 or dithiothreitol under denaturing conditions, indicated the presence of eight thiol residues and two interchain disulphide bridges/enzyme molecule. 3. Amino acid analysis showed that the intact enzyme contains a total of approximately 100 arginine and lysine residues, but digestion of the enzyme with trypsin yielded about 49 peptides staining with ninhydrin in a peptide "map". 4. With the knowledge that the enzyme contains only two substrate-binding sites, it is suggested that the enzyme probably consists of four polypeptide chains arranged in an alpha2beta2 confirmation.


Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice.
Susceptibility to atherosclerosis is determined by a combination of genetic and environmental factors, including diet. Consumption of diets rich in soy protein has been claimed to protect against the development of atherosclerosis. Potential mechanisms include cholesterol lowering, inhibition of lipoprotein oxidation and inhibition of cell proliferation by soy proteins or isoflavones, such as genistein, that are present in soy. This study was designed to determine whether soy isoflavones confer protection against atherosclerosis in mice and whether they reduce serum cholesterol levels and lipoprotein oxidation. C57BL/6 and LDL receptor-deficient (LDLr-null) mice were fed soy protein-based, high fat diets with isoflavones present (IF+, 20.85 g/100 g protein, 0.027 g/100 g genistein, 0.009 g/100 g daidzein) or diets from which isoflavones, and possibly other components, had been extracted (IF-, 20.0 g/100 g protein, 0.002 g/100 g genistein, 0.001 g/100 g daidzein). Because LDLr-null mice develop extensive atherosclerosis and hypercholesterolemia after minimal time on a high fat diet, they were fed the diets for 6 wk, whereas C57BL/6 mice were fed the diets for 10 wk. Plasma cholesterol levels did not differ between LDLr-null mice fed IF- and those fed IF+, but were 30% lower in C57BL/6 mice fed the IF+ diet than in those fed the IF- diet. Susceptibility of LDL to oxidative modification, measured as the lag phase of conjugated diene formation in LDLr-null mice, was not altered by isoflavone consumption. All LDLr-null mice developed atherosclerosis, and the presence or deficiency of dietary isoflavones did not influence atherosclerotic lesion area. In contrast, atherosclerotic lesion area was significantly reduced in C57BL/6 mice fed IF+ compared with those fed IF-. Thus, this study demonstrates that although the isoflavone-containing diet resulted in a reduction in cholesterol levels in C57BL/6 mice, it had no effect on cholesterol levels or on susceptibility of LDL to oxidative modification in LDLr-null mice. Further, dietary isoflavones did not protect against the development of atherosclerosis in LDLr-null mice but did decrease atherosclerosis in C57BL/6 mice. These findings suggest that soy isoflavones might lower cholesterol levels by increasing LDL receptor activity, and the reduction in cholesterol may offer some protection against atherosclerosis.