Associations between sleep disturbances and diabetes mellitus among blacks with metabolic syndrome: Results from the Metabolic Syndrome Outcome Study (MetSO).
The association between sleep disturbances and cardiometabolic diseases has been understudied in blacks with metabolic syndrome. This study is a cross-sectional analysis of the Metabolic Syndrome Outcome Study (MetSO) trial. We assessed insomnia symptoms, sleep duration, and risk for sleep apnea. Multivariate logistic regression models evaluated the association between sleep disturbances with diabetes mellitus (DM) and the combined outcomes of DM and hypertension as well as DM and dyslipidemia. The sample consisted of 1,013 participants, mean age of 62 ± 14 years and 61% female. DM was diagnosed in 60% of the sample. Sleep apnea risk was observed in 48% of the sample, while 10% had insomnia symptoms and 65% reported short sleep duration (< 6 hours). Sleep apnea risk, but not insomnia or sleep duration, was associated with DM (OR 1.66; 95% CI 1.21-2.28), adjusting for age, sex, income, obesity (BMI ≥ 30 kg/m(2)), tobacco use, alcohol use, hypertension, dyslipidemia, and depression. In fully adjusted models, sleep apnea risk was associated with the combined outcome of DM-hypertension (OR 1.95; 95% CI 1.42-2.69), but not with diabetes-dyslipidemia. We observed a strong association between sleep apnea risk and diabetes mellitus among blacks with metabolic syndrome.


A parameterization scheme for the x-ray linear attenuation coefficient and energy absorption coefficient.
A novel parameterization of x-ray interaction cross-sections is developed, and employed to describe the x-ray linear attenuation coefficient and mass energy absorption coefficient for both elements and mixtures. The new parameterization scheme addresses the Z-dependence of elemental cross-sections (per electron) using a simple function of atomic number, Z. This obviates the need for a complicated mathematical formalism. Energy dependent coefficients describe the Z-direction curvature of the cross-sections. The composition dependent quantities are the electron density and statistical moments describing the elemental distribution. We show that it is possible to describe elemental cross-sections for the entire periodic table and at energies above the K-edge (from 6 keV to 125 MeV), with an accuracy of better than 2% using a parameterization containing not more than five coefficients. For the biologically important elements 1 < or = Z < or = 20, and the energy range 30-150 keV, the parameterization utilizes four coefficients. At higher energies, the parameterization uses fewer coefficients with only two coefficients needed at megavoltage energies.


Influence of players' physique on rugby football injuries.
To determine whether there is an association between a player's physique and injuries incurred while playing rugby football. A cohort study was carried out involving all senior rugby clubs in the Scottish Borders during the 1993-1994 rugby season. Somatotype estimates were determined for 1152 (95%) of the 1216 eligible players. Body mass index (BMI), chest to waist ratio, and the ponderal index (PI) were used to classify players' physique as endomorphic (obese), mesomorphic (muscular), and ectomorphic (linear). A strong association was found between physique and age (chi 2 test: chi 2 = 317.2, df = 10, P < 0.0001). More younger players were ectomorphs. Older players were more often endomorphic. The physiques of forwards and backs were significantly different (chi 2 test: chi 2 = 58.6, df = 2, P < 0.0001), with forwards being of a heavier build than three-quarters, even after adjustment for age. Endomorphic players were more likely than ectomorphs to be injured in a match after adjustment for age (age-adjusted mean BMI for players who were injured in a match was 25.4 compared with 24.6 for players who were not injured in a match, P < 0.0001; adjusted chest to waist ratio means were 1.136 and 1.125 respectively, P = 0.0307; adjusted PI means were 0.414 and 0.417 respectively, P = 0.0056). Increased risk of injury may occur when players play out of position, since one fifth of all injuries occurred in this circumstance. Further research needs to be conducted using a more objective method of measuring somatotype on a further cohort of players so that the risk of injury for different body types can be examined more closely and related to other potential confounding factors. The level of increased risk for individuals playing out of their usual playing position needs to be established with a greater degree of certainty.


Utilization of very low density lipoprotein by rat heart: the effect of endotoxin.
The effect of endotoxin on myocardial utilization of very low density lipoprotein (VLDL) triacylglycerol (TAG) was studied. VLDL was prepared by rat liver perfusion and tested as substrate in the isolated working rat heart. Both liver and heart donor rats were pretreated in vivo with endotoxin or vehicle (control). VLDL-TAG synthesized by endotoxin-pretreated livers was assimilated and oxidized at an increased rate by hearts compared with control VLDL-TAG, regardless of the cardiac endotoxic status, with increased cardiac mechanical performance (cardiac output, hydraulic work). There was no change in incorporation of labeled VLDL lipids into myocardial tissue lipids. Lipoprotein lipase (LPL) activity was increased in endotoxin-pretreated hearts, and after perfusion with "endotoxic" VLDL, there was a tendency for translocation of LPL from tissue-residual to heparin-releasable compartments, but these changes were modest. Analysis of the VLDL composition showed that endotoxin-pretreated livers produced apolipoprotein (apo)-B48 VLDL with decreased particle size (and hence TAG content), but apo-B100 VLDL was unchanged. Oleate content of VLDL was increased, but there was no difference in apo-C or apo-E content. These results suggest that VLDL-TAG produced during sepsis/endotoxinemia may be destined for utilization by the heart as energy substrate. However, the mechanism for its increased efficacy is uncertain.


Potential oral manifestations of cardiovascular drugs.
The aim of this work was to determine the frequency and nature of oral manifestations secondary to use of cardiovascular drugs. Five hundred and thirty one patients attending an adult cardiology clinic in Saudi Arabia were questioned about the occurrence of oral dryness, dysgeusia, or burning sensation and were clinically evaluated for the presence of oral mucosal or gingival disease. Data were statistically analyzed with chi-squared tests, odds ratios and Student's t-test. Oral symptoms and/or signs were recorded in 75 (14.1%) patients with xerostomia being the most common (7.5%), followed by lichenoid (lichen planus-like) lesions (3.6%) and dysgeusia (1.9%). Xerostomia was significantly more frequent in patients with a history of diabetes mellitus and in female patients (P < 0.05). There were no statistically significant differences (P > 0.05) between patients with or without oral manifestations when age, gender, cardiovascular risk factor, cardiac disease, type of cardiac drug used or the number of medications were assessed. There was a trend for xerostomia to be less frequent in patients receiving therapy with angiotensin converting enzyme inhibitors and a slight trend of xerostomia to be more likely with increased number of non-cardiac and total number of agents per subject. The number of non-cardiac and total medications taken by patients with potential oral manifestations tended to be greater than that of patients without oral manifestations. The frequency of potential oral manifestations in patients receiving cardiovascular agents was 14.1%. The occurrence and character of the oral manifestations had no significant relation with individual cardiac drugs, although there was a trend for oral manifestations to be likely with increasing number of drugs.


No reason for optimism: the expected impact of commitments in the European Commission's Alcohol and Health Forum.
Europe is the heaviest-drinking region in the world, more than 2.5 times the rest of the world's average. THE COMMISSION'S CONCLUSION: The cornerstone for the European Commission's action to decrease the alcohol-related harm of this consumption and the main emphasis for its work is the Alcohol and Health Forum, with its Task Forces on Marketing Communication and Youth-Specific Aspects of Alcohol. The Forum, which was launched in June 2007, aims to provide a common platform for all interested stakeholders. Forum members are invited to make commitments to reduce alcohol-related harm, in the form of a monitored and evaluated action plan. By 29 February 2008, 79 commitments have been provided by the members of the Forum. Taking into account the limited information available, the proposed commitments indicate few evidence-based approaches. A large majority of the summaries do not, or only slightly, address the relevance of their commitment and give no evidence of why their proposed action is important in reducing alcohol-related harm. Even fewer commitments mention indicators of effectiveness of the proposed actions or propose to evaluate the effectiveness of the proposed actions. While most economic operators in the Forum have resources to undertake actions which could be highly effective, they commit principally to educational programmes which have been found to be mainly ineffective. This, and the neglect of existing legislation, do not give reason for optimism on the impact of the proposed commitments.


The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis.
Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS. Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry. Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1. Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and increased migratory potential of activated FLSs in RA.


Expression of Vacuolar H+-ATPases and the intracellular pH values in three adenocarcinoma cell lines of digestive system.
Vacuolar H+-ATPases function in bone resorption, pH homeostasis and tumor metastasis, play an important role in regulating the extra- and intracellular pH (pHe and pHi) in various eukaryotic cells. Acidity is one of the main features of the tumors. The Vacuolar H+-ATPases are the primary responsible for the control of tumor microenvironment by proton extrusion to the extracellular medium, which play a crucial role in tumor invasion, metastasis and chemoresistance. Therefore our study aimed to uncover the relationship between Vacuolar H+-ATPases and the pHi value. Three adenocarcinoma cell lines of digestive system including SGC7901, HT29 and PATU8988 were cultured in RPMI-1640 supplemented with 10% fetal bovine serum and antibiotics. BCECF-AM pH-sensitive fluorescent probe was used to measure the pHi value of cells. Western blot and immunofluorescent staining were respectively applied to determine the protein expression and intracellular distribution of Vacuolar H+-ATPases. The pHi value of HT29 was the highest, whereas the pHi value of PATU8988 was the lowest and of SGC7901 was in the midst according to fluorescent intensity of BCECF. Similar results were obtained in the protein expression and the IOD (integral optical density) of Vacuolar H+-ATPases in them. The pHi value indirectly represented by fluorescent intensity of BCECF was positively correlated with protein expression of Vacuolar H+-ATPases in an exponential manner.


A life history model of the ecological and evolutionary dynamics of polyaneuploid cancer cells.
Therapeutic resistance is one of the main reasons for treatment failure in cancer patients. The polyaneuploid cancer cell (PACC) state has been shown to promote resistance by providing a refuge for cancer cells from the effects of therapy and by helping them adapt to a variety of environmental stressors. This state is the result of aneuploid cancer cells undergoing whole genome doubling and skipping mitosis, cytokinesis, or both. In this paper, we create a novel mathematical framework for modeling the eco-evolutionary dynamics of state-structured populations and use this framework to construct a model of cancer populations with an aneuploid and a PACC state. Using in silico simulations, we explore how the PACC state allows cancer cells to (1) survive extreme environmental conditions by exiting the cell cycle after S phase and protecting genomic material and (2) aid in adaptation to environmental stressors by increasing the cancer cell's ability to generate heritable variation (evolvability) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to allow cancer cells to persist under therapy and evolve therapeutic resistance. By eliminating cells in the PACC state through appropriately-timed PACC-targeted therapies, we show how we can prevent the emergence of resistance and promote cancer eradication.


Color perception in children with autism.
This study examined whether color perception is atypical in children with autism. In experiment 1, accuracy of color memory and search was compared for children with autism and typically developing children matched on age and non-verbal cognitive ability. Children with autism were significantly less accurate at color memory and search than controls. In experiment 2, chromatic discrimination and categorical perception of color were assessed using a target detection task. Children with autism were less accurate than controls at detecting chromatic targets when presented on chromatic backgrounds, although were equally as fast when target detection was accurate. The strength of categorical perception of color did not differ for the two groups. Implications for theories on perceptual development in autism are discussed.


Pharmacokinetics and competitive pharmacodynamics of ADP-induced platelet activation after oral administration of clopidogrel to horses.
To determine pharmacokinetics and pharmacodynamics after oral administration of a single dose of clopidogrel to horses. 6 healthy adult horses. Blood samples were collected before and at various times up to 24 hours after oral administration of clopidogrel (2 mg/kg). Reactivity of platelets from each blood sample was determined by optical aggregometry and phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Concentrations of clopidogrel and the clopidogrel active metabolite derivative (CAMD) were measured in each blood sample by use of liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined with a noncompartmental model. Compared with results for preadministration samples, platelet aggregation in response to 12.5μM ADP decreased significantly within 4 hours after clopidogrel administration for 5 of 6 horses. After 24 hours, platelet aggregation was identical to that measured before administration. Platelet aggregation in response to 25μM ADP was identical between samples obtained before and after administration. Phosphorylation of VASP in response to ADP (20μM) and prostaglandin E1 (3.3μM) was also unchanged by administration of clopidogrel. Time to maximum concentration of clopidogrel and CAMD was 0.54 and 0.71 hours, respectively, and calculated terminal-phase half-life of clopidogrel and CAMD was 1.81 and 0.97 hours, respectively. Clopidogrel or CAMD caused competitive inhibition of ADP-induced platelet aggregation during the first 24 hours after clopidogrel administration. Because CAMD was rapidly eliminated from horses, clopidogrel administration may be needed more frequently than in other species in which clopidogrel causes irreversible platelet inhibition. (Am J Vet Res 2019;80:505-512).


[The molecular spectra and existence state of sulfonated phthalimidomethyl phthalocyanine hydroxyl aluminum as amphiphilic photosensitizer in aqueous alcoholic solutions and water].
The sulfonated phthalimidomethyl phthalocyanine hydroxyl aluminum (Al(OH)PcSP) is an amphiphilic photosensitizer which was proved to have the photodynamic activities against cancer. The electronic absorption spectra and aggregation state of the Al(OH)PcSP in aqueous alcoholic solutions and water were investigated. The results showed that the Al(OH)PcSP existed in the form of monomer in aqueous alcoholic solutions. The increase in the carbon chain and hydroxy of alcohol in solutions had no significant effects on the absorption spectra behaviors of Al(OH)PcSP. But in water, the Al(OH)PcSP existed in the equilibrium between monomer and dimer. The dimerization constant was 5.7307 x 10(4) mol-1.L. The characteristic absorption peak of the Q band of the Al(OH)PcSP dimer was red shifted to 740.5 nm from that of the monomer (676.5 nm), which contrast with those of other metal phthalocyanines dimer. The study on the fluorescence spectra of Al(OH)PcSP in aqueous alcoholic solutions suggested that the fluorescence of the dimer was weak.


Immediate occlusal versus non-occlusal loading of single zirconia implants. A multicentre pragmatic randomised clinical trial.
To evaluate whether immediate non-occlusal loading of single zirconia implants could reduce early failures when compared to immediate occlusal loading. Forty partially edentulous patients who received one single zirconia implant (Z-Systems) at least 10 mm long and 3.25 mm wide inserted with a torque of at least 35 Ncm were randomised to immediate occlusal or non-occlusal loading groups. All patients received provisional acrylic crowns the same day of implant placement. Provisional crowns were replaced after 4 to 5 months by definitive full ceramic crowns. Outcome measures were implant success, any complications and peri-implant marginal bone levels. One year after loading, no patients had dropped out. Five implants (12.5%) failed early: three occlusally loaded and two non-occlusally loaded. Three complications occurred, all after delivery of the definitive crowns: one crown fractured (occlusal loading), one had to be remade after debridement because of hyperplastic tissues (occlusal loading), and one crown decemented (nonocclusal loading). These differences were not statistically significant. Both groups gradually lost periimplant bone in a highly statistically significant way. One year after loading, patients subjected to non-occlusal loading lost an average of 0.7 mm of peri-implant bone versus 0.9 mm in the occlusal group. This difference in bone loss between groups was not statistically significant. There was an association between immediate post-extractive implants and implant failures (P=0.01). Four of the 10 immediate post-extractive implants (40%) failed versus one out of 30 delayed implants (3%). The results of this study do not provide a conclusive answer to whether immediate non-occlusal loading may decrease implant failures. Immediately loaded zirconia implants placed in post-extractive sites had high failure rates.


Rank selection for non-negative matrix factorization.
Non-Negative Matrix Factorization (NMF) is a widely used dimension reduction method that factorizes a non-negative data matrix into two lower dimensional non-negative matrices: one is the basis or feature matrix which consists of the variables and the other is the coefficients matrix which is the projections of data points to the new basis. The features can be interpreted as sub-structures of the data. The number of sub-structures in the feature matrix is also called the rank. This parameter controls the model complexity and is the only tuning parameter for the NMF model. An appropriate rank will extract the key latent features while minimizing the noise from the original data. However due to the large amount of optimization error always present in the NMF computation, the rank selection has been a difficult problem. We develop a novel rank selection method based on hypothesis testing, using a deconvolved bootstrap distribution to assess the significance level accurately. Through simulations, we compare our method with a rank selection method based on hypothesis testing using bootstrap distribution without deconvolution and a method based on cross-validation; we demonstrate that our method is not only accurate at estimating the true ranks for NMF, especially when the features are hard to distinguish, but also efficient at computation. When applied to real microbiome data (eg, OTU data and functional metagenomic data), our method also shows the ability to extract interpretable subcommunities in the data.


Redox-Sensitive Regulation of Myocardin-Related Transcription Factor (MRTF-A) Phosphorylation via Palladin in Vascular Smooth Muscle Cell Differentiation Marker Gene Expression.
Vascular smooth muscle cells (VSMCs) undergo a phenotypic switch from a differentiated to synthetic phenotype in cardiovascular diseases such as atherosclerosis and restenosis. Our previous studies indicate that transforming growth factor-β (TGF-β) helps to maintain the differentiated phenotype by regulating expression of pro-differentiation genes such as smooth muscle α-actin (SMA) and Calponin (CNN) through reactive oxygen species (ROS) derived from NADPH oxidase 4 (Nox4) in VSMCs. In this study, we investigated the relationship between Nox4 and myocardin-related transcription factor-A (MRTF-A), a transcription factor known to be important in expression of smooth muscle marker genes. Previous work has shown that MRTF-A interacts with the actin-binding protein, palladin, although how this interaction affects MRTF-A function is unclear, as is the role of phosphorylation in MRTF-A activity. We found that Rho kinase (ROCK)-mediated phosphorylation of MRTF-A is a key event in the regulation of SMA and CNN in VSMCs and that this phosphorylation depends upon Nox4-mediated palladin expression. Knockdown of Nox4 using siRNA decreases TGF-β -induced palladin expression and MRTF-A phosphorylation, suggesting redox-sensitive regulation of this signaling pathway. Knockdown of palladin also decreases MRTF-A phosphorylation. These data suggest that Nox4-dependent palladin expression and ROCK regulate phosphorylation of MRTF-A, a critical factor in the regulation of SRF responsive gene expression.


[Competence of senior medical students in diagnosing tuberculosis based on chest X-rays].
To evaluate the competence of senior medical students in diagnosing tuberculosis (TB) based on their reading of chest X-rays, as well as to identify the factors associated with high scores for the overall interpretation of chest X-rays. In October 2008, a convenience sample of senior medical students who had undergone formal training in radiology at the Federal University of Rio de Janeiro School of Medicine, in the city of Rio de Janeiro, Brazil, were invited to participate in the study. Six chest X-rays (three of TB patients and three of patients without TB) were selected. Participants were asked to choose one of the three probable radiological interpretations, and one of the four subsequent suitable clinical approaches. They also completed a questionnaire designed to collect data related to demographics, career of interest, time spent in emergency rooms and year of study. The sensitivity and specificity related to competence in the radiological diagnosis of TB, as well as a score for the overall interpretation of chest X-rays, were calculated. The sensitivity of the probable radiological diagnosis of pulmonary TB, based on the three chest X-rays of patients with TB (minimal, moderate and extensive) was 86.5%, 90.4% and 94.2%, respectively, and the specificity was 90%, 82% and 42%. The only factor associated with a high score for the overall radiological interpretation was the year of study. In this sample of medical students, who had received formal training in radiology early in their medical school course, the competence in interpreting the chest X-rays of TB patients was good. The year of study seems to influence overall chest X-ray reading skill.


Glucocorticoid-induced osteoporosis: 2013 update.
Glucocorticoids are the most common cause of secondary osteoporosis leading to the so-called glucocorticoid-induced osteoporosis (GIO). A treatment with 10 mg/d of prednisone or equivalent for more than 3 months leads to a 7-fold increase in hip fractures and a 17-fold increase in vertebral fractures. The difference between bone quantity and quality in GIO makes bone mineral density measurements inadequate to detect patients at risk of fracture. The adverse effects of glucocorticoids on the skeleton derive from a direct impact on bone cells with a severe impairment of mechanical competence. Crucial to prevention of GIO is early timing of intervention. The World Health Organization has adopted a fracture prevention algorithm (FRAX) intended to estimate fracture risk in GIO. The American College of Rhematology modified its prevention and treatment guidelines taking into account the individual risk of fracture calculated in GIO on the basis of the FRAX algorithm. Recently, also a joint Guideline Working Group of the International Osteoporosis Foundation (IOF) and the European Calcified Tissue Society (ECTS) published a framework for the development of national guidelines for the management of GIO. Bisphosphonates are the first-line drugs to treat GIO; teriparatide counteracts several fundamental pathophysiologic aspects of GIO; denosumab is useful in patients with renal failure and in potentially pregnant young women. Vertebroplasty and kyphoplasty may be less beneficial in GIO than in primary involutional osteoporosis.


A method for the comparison of multi-platform spectral histopathology (SHP) data sets.
Results of a study comparing infrared imaging data sets collected on different instruments or instrument platforms are reported, along with detailed methods developed to permit such comparisons. It was found that different instrument platforms, although employing different detector technologies and pixel sizes, produce highly similar and reproducible spectral results. However, differences in the absolute intensity values of the reflectance data sets were observed that were caused by heterogeneity of the sample substrate in terms of reflectivity and planarity.


The 21st annual Bioinformatics Open Source Conference (BOSC 2020, part of BCC2020).
Launched in 2000 and held every year since, the Bioinformatics Open Source Conference (BOSC) is a volunteer-run meeting coordinated by the Open Bioinformatics Foundation (OBF) that covers open source software development and open science in bioinformatics. Most years, BOSC has been part of the Intelligent Systems for Molecular Biology (ISMB) conference, but in 2018, and again in 2020, BOSC partnered with the Galaxy Community Conference (GCC). This year's combined BOSC + GCC conference was called the Bioinformatics Community Conference (BCC2020, bcc2020.github.io). Originally slated to take place in Toronto, Canada, BCC2020 was moved online due to COVID-19. The meeting started with a wide array of training sessions; continued with a main program of keynote presentations, talks, posters, Birds of a Feather, and more; and ended with four days of collaboration (CoFest). Efforts to make the meeting accessible and inclusive included very low registration fees, talks presented twice a day, and closed captioning for all videos. More than 800 people from 61 countries registered for at least one part of the meeting, which was held mostly in the Remo.co video-conferencing platform.


Clinical notes as prognostic markers of mortality associated with diabetes mellitus following critical care: A retrospective cohort analysis using machine learning and unstructured big data.
Clinical notes are ubiquitous resources offering potential value in optimizing critical care via data mining technologies. To determine the predictive value of clinical notes as prognostic markers of 1-year all-cause mortality among people with diabetes following critical care. Mortality of diabetes patients were predicted using three cohorts of clinical text in a critical care database, written by physicians (n = 45253), nurses (159027), and both (n = 204280). Natural language processing was used to pre-process text documents and LASSO-regularized logistic regression models were trained and tested. Confusion matrix metrics of each model were calculated and AUROC estimates between models were compared. All predictive words and corresponding coefficients were extracted. Outcome probability associated with each text document was estimated. Models built on clinical text of physicians, nurses, and the combined cohort predicted mortality with AUROC of 0.996, 0.893, and 0.922, respectively. Predictive performance of the models significantly differed from one another whereas inter-rater reliability ranged from substantial to almost perfect across them. Number of predictive words with non-zero coefficients were 3994, 8159, and 10579, respectively, in the models of physicians, nurses, and the combined cohort. Physicians' and nursing notes, both individually and when combined, strongly predicted 1-year all-cause mortality among people with diabetes following critical care. Clinical notes of physicians and nurses are strong and novel prognostic markers of diabetes-associated mortality in critical care, offering potentially generalizable and scalable applications. Clinical text-derived personalized risk estimates of prognostic outcomes such as mortality could be used to optimize patient care.


The kinetics of inhibition of thrombin by antithrombin in the presence of components of the hemostatic system.
The inhibition of human thrombin by antithrombin has been measured in pure systems in the presence of other components of the hemostatic system that might affect the kinetics of the reaction. These included fibrinogen, calcium ions, phospholipid, prothrombin, platelets (both adenosine diphosphate [ADP]-stimulated and -unstimulated), and platelet extracts. Inhibition rates were measured in each case by a discontinuous amidolytic assay over a range of antithrombin concentrations, from 0 to 4.5 mumol/L. Under all conditions, rates of inhibition were proportional to antithrombin concentration. Calcium ions at 5 mmol/L caused a small (20%) reduction in rate, but phospholipid and prothrombin had no additional effect. In contrast, both fibrinogen and platelets significantly changed the rate of inhibition. In the presence of calcium, fibrinogen at concentrations from 0 to 12 mumol/L reduced the rate of inhibition in a competitive manner, giving an apparent Kd for fibrinogen of 6.0 mumol/L. As the plasma fibrinogen level is about 8 mumol/L, one may therefore predict that variations in fibrinogen level will have a significant effect on the rate of thrombin inhibition in plasma. More unexpected was the observation that platelets increase the rate of inhibition: unstimulated platelets increased the rate constant by 40%, and ADP-stimulated platelets increased it by 55%. However, this acceleratory effect could not be mimicked with either a KCI extract or a Triton extract of platelets, and its cause remains unknown. In sum, it has been shown that the rate of inhibition of thrombin can be modulated in at least three ways-antithrombin concentration, fibrinogen concentration, and platelets; each of which can vary independently in vivo. It is well known that defects of the first lead to an increased risk of thrombosis, and it is proposed that this may be substantially caused by changes in the kinetics of inhibition such as those described. Additionally, it is suggested that changes in inhibition rate caused by other components may also be significant, for the same reason, in modulating the clotting system in vivo.


Hemispheric differences in the number of parvalbumin-positive neurons in subdivisions of the rat basolateral amygdala complex.
The amygdala is a bilateral temporal lobe brain region which plays an important role in emotional processing. Past studies on the amygdala have shown hemispheric differences in amygdalar processes and responses associated with specific pain and fear behaviors. Despite the functional differences in the amygdala, few studies have been performed to characterize whether anatomical differences exist between the left and right amygdala. Parvalbumin (PV) is a phenotypic marker for an inhibitory interneuronal population in cortical brain structures such as the basolateral amygdala complex (BLC). This study examined the number of PV-positive neurons in the left and right BLC of adult, male Long-Evans rats using unbiased stereology. Coronal sections through the rostral-caudal extent of the BLC were immunohistochemically-stained for PV and the optical fractionator method was used to obtain an unbiased estimate of the number of PV-positive neurons in subdivisions through the BLC. The lateral and basolateral amygdala divisions of the BLC were analyzed, were subdivided into the dorsolateral, ventrolateral and ventromedial and the posterior, anterior and ventral subdivisions, respectively. The results indicate that there are significantly more PV-positive neurons in the left basolateral amygdala compared to the right, with a significant difference specifically in the posterior subdivision. This difference in PV neuronal number could help explain the distinct hemispheric roles of the BLC in the behavioral processing following exposure to painful and fearful stimuli.


Comparison between a conventional treatment energy and 50 MV photons for the treatment of lung tumours.
Radiation therapy in the thoracic region is difficult due to the presence of many dose-limiting structures and the large density differences that affect the dose distribution. Conventional irradiation techniques use low-energy photon beams to avoid build-up effects superficially in the tumour and increased lateral scattering of the beams. For deep-seated tumours higher beam energies could have lung-sparing properties that would enable dose escalation. A comparison was made for a conventional low photon energy (6 MV) and 50 MV photons for the treatment of a lung tumour. A representative patient geometry was selected, consisting of a small tumour semi-enclosed in lung tissue. Treatment plans were designed using a commercial 3D-pencil beam treatment planning system. The treatment beams designed in the TPS were simulated with the Monte Carlo code EGS4/BEAM and the dose distribution in the phantom created from the patients CT-data was calculated using MCDOSE with identical beam geometry for both energies. The intrinsic difference between the two photon energies implies a sparing effect of lung that can be utilized for dose escalation. For a treatment with two beams the mean total dose to the tumour could be increased by 5.3% for 50 MV, corresponding to 3.2 Gy for a prescription dose of 60 Gy, with the same complication probability for the treated lung as for 6 MV. In conclusion, high-energy beams have qualities that can be taken advantage of for irradiation of lung tumours. Optimum solutions would probably require the use of both high- and low-energy beams.


Effect of pentoxifylline on fracture healing: an experimental study.
This study aims to investigate the effect of pentoxifylline on fracture healing in an experimental animal model. Sixty-one male, Wistar-Albino rats were divided randomly into two groups as the pentoxifylline and control groups. Standard, closed femoral shaft fractures were established in all rats using a three-point bending device under general anesthesia. The rats were administered either pentoxifylline or isotonic NaCl injections everyday, beginning after production of fracture until they were sacrificed. Ten rats (11 rats in the pentoxifylline group on the 14(th) day) in each group were sacrificed on the 7(th), 14(th) and the 21(st) days and clinical, radiological, and histological examinations were performed to evaluate bony union. Radiological evaluation of callus did not reveal any significant difference between the control and the pentoxifylline groups in the first, second and the third weeks. However histological callus formation was significantly superior in pentoxifylline group compared to the control group at the end of the first week and callus formation was better in the control group in the third week. Pentoxifylline can be used to accelerate fracture union in early phases. Because of its hematological effects pentoxifylline accelerates the hematoma stage of fracture healing. But it inhibits fracture union in the later stages, presumably due to its anti-inflammatory effect. This should be taken into consideration during the clinical use of this drug.


State dependent excitability changes of spinal flexor reflex in patients with restless legs syndrome secondary to chronic renal failure.
Periodic limb movement in sleep (PLMS) is a common dysfunction of motor control during sleep, occurring either in isolation or associated with a variety of neurological disorders including restless legs syndrome (RLS). Although the PLMS generators have not been established, their occurrence in patients with spinal cord injury and their clinical resemblance to the spinal cord flexor withdrawal reflex (FR) suggest that PLMS may originate in the circuitry that mediates the FR. The significantly increased spinal cord excitability noted in primary RLS/PLMS patients may play an important role in the pathophysiology of primary RLS. The aim of this study is to establish whether the enhanced spinal cord excitability, which is represented by a lower threshold and/or greater spatial spread of the FR, is also true for the RLS/PLMS patients whose RLS is secondary to chronic renal failure (CRF). Twenty patients with RLS/PLMS secondary to CRF have been compared with matched controls according to the state dependent changes in FR excitability. All patients met the diagnostic criteria for RLS and PLMS. They had CRF for 5.2+/-3.5 years, and were under the hemodialysis treatment. Twenty healthy, age and sex matched subjects were tested as controls. The electrophysiological testing of the FR was performed during wakefulness (9:30-10:30 p.m.) and sleep (beginning of stage II, the first sleep cycle). A significant increase in FR excitability was found in RLS/PLMS patients with CRF. This abnormality was prominent during sleep, which was also true for the primary RLS. Our results suggest that similar neuronal pathways are involved in primary and secondary RLS/PLMS patients. Our results also support that RLS/PLMS and FR share a common spinal mechanism.


Computed tomography for the diagnosis and treatment monitoring of bacterial pneumonia in Indian pythons (Python molurus).
Eight Indian pythons (Python molurus) with clinical and microbiological evidence of pneumonia were examined by computed tomography (ct) before and after treatment. The results were assessed subjectively and measurements were taken following a standard protocol. Changes in the lung tissue of all the pythons were diagnosed, and the extent of the disease could be assessed. ct examinations after treatment showed an improvement in the six pythons whose clinical condition had improved, but in the other two pythons they demonstrated the severity of the disease. The subjective assessments were superior to the evaluation of measurements of attenuation in regions of interest. However, the average and the maximum attenuation provided additional information on the extent of the disease. Except for one python with only mild clinical signs, the attenuation after successful treatment was still higher than in healthy pythons.


The performance of the Congruence Among Distance Matrices (CADM) test in phylogenetic analysis.
CADM is a statistical test used to estimate the level of Congruence Among Distance Matrices. It has been shown in previous studies to have a correct rate of type I error and good power when applied to dissimilarity matrices and to ultrametric distance matrices. Contrary to most other tests of incongruence used in phylogenetic analysis, the null hypothesis of the CADM test assumes complete incongruence of the phylogenetic trees instead of congruence. In this study, we performed computer simulations to assess the type I error rate and power of the test. It was applied to additive distance matrices representing phylogenies and to genetic distance matrices obtained from nucleotide sequences of different lengths that were simulated on randomly generated trees of varying sizes, and under different evolutionary conditions. Our results showed that the test has an accurate type I error rate and good power. As expected, power increased with the number of objects (i.e., taxa), the number of partially or completely congruent matrices and the level of congruence among distance matrices. Based on our results, we suggest that CADM is an excellent candidate to test for congruence and, when present, to estimate its level in phylogenomic studies where numerous genes are analysed simultaneously.


Anisotropic Angstrom-Wide Conductive Channels in Black Phosphorus by Top-down Cu Intercalation.
Intercalation in black phosphorus (BP) can induce and modulate a variety of the properties including superconductivity like other two-dimensional (2D) materials. In this perspective, spatially controlled intercalation has the possibility to incorporate different properties into a single crystal of BP. We demonstrate anisotropic angstrom-wide (∼4.3 Å) Cu intercalation in BP, where Cu atoms are intercalated along a zigzag direction of BP because of its inherent anisotropy. With atomic structure, its microstructural effects, arising from the angstrom-wide Cu intercalation, were investigated and extended to relation with macrostructure. As the intercalation mechanism, it was revealed by in situ transmission electron microscopy and theoretical calculation that Cu atoms are intercalated through top-down direction of BP. The Cu intercalation anisotropically induces transition of angstrom-wide electronic channels from semiconductor to semimetal in BP. Our findings throw light on the fundamental relationship between microstructure changes and properties in intercalated BP, and tailoring anisotropic 2D materials at angstrom scale.


A review of the use of time-varying covariates in the Fine-Gray subdistribution hazard competing risk regression model.
In survival analysis, time-varying covariates are covariates whose value can change during follow-up. Outcomes in medical research are frequently subject to competing risks (events precluding the occurrence of the primary outcome). We review the types of time-varying covariates and highlight the effect of their inclusion in the subdistribution hazard model. External time-dependent covariates are external to the subject, can effect the failure process, but are not otherwise involved in the failure mechanism. Internal time-varying covariates are measured on the subject, can effect the failure process directly, and may also be impacted by the failure mechanism. In the absence of competing risks, a consequence of including internal time-dependent covariates in the Cox model is that one cannot estimate the survival function or the effect of covariates on the survival function. In the presence of competing risks, the inclusion of internal time-varying covariates in a subdistribution hazard model results in the loss of the ability to estimate the cumulative incidence function (CIF) or the effect of covariates on the CIF. Furthermore, the definition of the risk set for the subdistribution hazard function can make defining internal time-varying covariates difficult or impossible. We conducted a review of the use of time-varying covariates in subdistribution hazard models in articles published in the medical literature in 2015 and in the first 5 months of 2019. Seven percent of articles published included a time-varying covariate. Several inappropriately described a time-varying covariate as having an association with the risk of the outcome.


Conservative management vs early surgery for high grade pediatric renal trauma--do nephrectomy rates differ?
Guidelines for management of pediatric high grade renal injuries are currently based on limited pediatric data and algorithms from adults, for whom initial nonoperative management is associated with decreased nephrectomy risk. Using a national database, we compared nephrectomy rates between children with high grade renal injury managed conservatively and those undergoing early surgical intervention. All children with high grade renal injuries were identified in the National Trauma Data Bank®. High grade renal injuries were defined as American Association for the Surgery of Trauma grade IV or V renal injuries. After excluding fatalities within 24 hours of hospitalization, 419 pediatric patients comprised our study cohort. A total of 81 patients underwent early (within 24 hours of hospitalization) surgical intervention, while 338 were initially treated conservatively. Using stratified analysis with adjustment for relevant covariates, we compared nephrectomy rates between these groups. Nephrectomy was performed less often in patients treated conservatively (RR 0.24, 95% CI 0.16 to 0.36, adjusted for age, renal injury grade and injury mechanism). The decreased risk of nephrectomy was more marked among children with grade IV vs grade V renal injuries (adjusted RR 0.16, 95% CI 0.08 to 0.23). Multiple procedures were more common in patients initially observed. Of pediatric patients with grade IV and V renal injuries 11% still underwent nephrectomy. Conservative management of high grade renal injuries is common in children. Although mechanism of injury and renal injury grade impact initial clinical management decisions, the risk of nephrectomy was consistently decreased in children with high grade renal trauma managed conservatively regardless of injury characteristics.


Aldosterone and 18-Oxocortisol Coaccumulation in Aldosterone-Producing Lesions.
Primary aldosteronism is a secondary hypertensive disease caused by autonomous aldosterone production that often caused by an aldosterone-producing adenoma (APA). Immunohistochemistry of aldosterone synthase (CYP11B2) shows the presence of aldosterone-producing cell clusters (APCCs) even in non-primary aldosteronism adult adrenal cortex. An APCC-like structure also exists as possible APCC-to-APA transitional lesions (a speculative designation) in primary aldosteronism adrenals. However, whether APCCs produce aldosterone or 18-oxocortisol, a potential serum marker of APA, remains unknown because of lack of technology to visualize adrenocorticosteroids on tissue sections. To address this obstacle, in this study, we used highly sensitive Fourier transform ion cyclotron resonance mass spectrometry to image various adrenocorticosteroids, including 18-oxocortisol, in adrenal tissue sections from 8 primary aldosteronism patients with APCC (cases 1-4), possible APCC-to-APA transitional lesions (case 5), and APA (cases 6-8). Further analyses by tandem mass spectrometry imaging allowed us to differentially visualize aldosterone from cortisone, which share identical mass-to-charge ratio value ( m/z). In conclusion, these advanced imaging techniques revealed that aldosterone and 18-oxocortisol coaccumulated within CYP11B2-expressing lesions. These imaging outcomes along with a growing body of aldosterone research led us to build a progressive development hypothesis of an aldosterone-producing pathology in the adrenal glands.


Long-range effect of mutation of calcium binding aspartates [correction of asparates] on the catalytic activity of alkaline protease from Pseudomonas aeruginosa.
Apart from a catalytic domain, the alkaline protease of Pseudomonas aeruginosa has a novel parallel beta-helix domain stabilized through Ca2+ binding. In order to clarify the importance of the beta-helix structure in maturation of the enzyme, aspartic residue D-356 or D-365 in the Ca2+ binding sequence motif was replaced with L-alanine, and the catalytic activity of each mutant was assayed. These mutants did not show any proteolytic activity, although the composition of their polypeptide chains was the same as that of the wild type except for the mutated alanine residue. These results suggest that D-356 and D-365 are important in control of the beta-helix folding induced by Ca2+ binding and that incomplete beta-helix folding due to the lack of their side-chains affects the maturation of the enzyme in the long-range order.


The influence of dietary fat source on liver and skeletal muscle mitochondrial modifications and lifespan changes in calorie-restricted mice.
The Membrane Theory of Aging proposes that lifespan is inversely related to the level of unsaturation in membrane phospholipids. Calorie restriction (CR) without malnutrition extends lifespan in many model organisms, which may be related to alterations in membrane phospholipids fatty acids. During the last few years our research focused on studying how altering the predominant fat source affects the outcome of CR in mice. We have established four dietary groups: one control group fed 95 % of a pre-determined ad libitum intake (in order to prevent obesity), and three CR groups fed 40 % less than ad libitum intake. Lipid source for the control and one of the CR groups was soybean oil (high in n-6 PUFA) whereas the two remaining CR groups were fed diets containing fish oil (high in n-3 PUFA), or lard (high in saturated and monounsaturated fatty acids). Dietary intervention periods ranged from 1 to 18 months. We performed a longitudinal lifespan study and a cross-sectional study set up to evaluate several mitochondrial parameters which included fatty acid composition, H(+) leak, activities of electron transport chain enzymes, ROS generation, lipid peroxidation, mitochondrial ultrastructure, and mitochondrial apoptotic signaling in liver and skeletal muscle. These approaches applied to different cohorts of mice have independently indicated that lard as a fat source often maximizes the effects of 40 % CR on mice. These effects could be due to significant increases of monounsaturated fatty acids levels, in accordance with the Membrane Theory of Aging.


The regulation of mobile medical applications.
The rapidly expanding number of mobile medical applications have the potential to transform the patient-healthcare provider relationship by improving the turnaround time and reducing costs. In September 2013, the U.S. Food and Drug Administration (FDA) issued guidance to regulate these applications and protect consumers by minimising the risks associated with their unintended use. This guidance distinguishes between the subset of mobile medical apps which may be subject to regulation and those that are not. The marketing claims of the application determine the intent. Areas of concern include compliance with regular updates of the operating systems and of the mobile medical apps themselves. In this article, we explain the essence of this FDA guidance by providing examples and evaluating the impact on academia, industry and other key stakeholders, such as patients and clinicians. Our assessment indicates that awareness and incorporation of the guidelines into product development can hasten the commercialisation and market entry process. Furthermore, potential obstacles have been discussed and directions for future development suggested.


Computationally efficient finite-difference modal method for the solution of Maxwell's equations.
In this work, a new implementation of the finite-difference (FD) modal method (FDMM) based on an iterative approach to calculate the eigenvalues and corresponding eigenfunctions of the Helmholtz equation is presented. Two relevant enhancements that significantly increase the speed and accuracy of the method are introduced. First of all, the solution of the complete eigenvalue problem is avoided in favor of finding only the meaningful part of eigenmodes by using iterative methods. Second, a multigrid algorithm and Richardson extrapolation are implemented. Simultaneous use of these techniques leads to an enhancement in terms of accuracy, which allows a simple method such as the FDMM with a typical three-point difference scheme to be significantly competitive with an analytical modal method.


Individual differences in the spontaneous recruitment of brain regions supporting mental state understanding when viewing natural social scenes.
People are able to rapidly infer complex personality traits and mental states even from the most minimal person information. Research has shown that when observers view a natural scene containing people, they spend a disproportionate amount of their time looking at the social features (e.g., faces, bodies). Does this preference for social features merely reflect the biological salience of these features or are observers spontaneously attempting to make sense of complex social dynamics? Using functional neuroimaging, we investigated neural responses to social and nonsocial visual scenes in a large sample of participants (n = 48) who varied on an individual difference measure assessing empathy and mentalizing (i.e., empathizing). Compared with other scene categories, viewing natural social scenes activated regions associated with social cognition (e.g., dorsomedial prefrontal cortex and temporal poles). Moreover, activity in these regions during social scene viewing was strongly correlated with individual differences in empathizing. These findings offer neural evidence that observers spontaneously engage in social cognition when viewing complex social material but that the degree to which people do so is mediated by individual differences in trait empathizing.


Pathology of the peritoneum: a review of selected topics.
Mesothelial lesions of the peritoneum may pose significant diagnostic problems. Accurate identification of these lesions is important because of their distinctive behavior and treatment requirements. This review discusses the clinical, pathological, and differential diagnosis of a variety of mesothelial lesions of the peritoneum, which includes mesothelial hyperplasia, multilocular peritoneal inclusion cysts (benign cystic mesothelioma), well-differentiated papillary mesotheliomas, and diffuse malignant mesothelioma, and the role of immunohistochemistry in the distinction from the more common primary peritoneal serous carcinomas. In addition, borderline serous tumors, psammocarcinomas, and solitary fibrous tumors of the peritoneum are briefly mentioned.


Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study.
The hypothesis of the Dilated Cardiomyopathy Precision Medicine Study is that most dilated cardiomyopathy has a genetic basis. The study returns results to probands and, when indicated, to relatives. While both the American College of Medical Genetics and Genomics/Association for Molecular Pathology and ClinGen's MYH7-cardiomyopathy specifications provide relevant guidance for variant interpretation, further gene- and disease-specific considerations were required for dilated cardiomyopathy. To this end, we tailored the ClinGen MYH7-cardiomyopathy variant interpretation framework; the specifications implemented for the study are presented here. Modifications were created and approved by an external Variant Adjudication Oversight Committee. After a pilot using 81 probands, further adjustments were made, resulting in 27 criteria (9 modifications of the ClinGen MYH7 framework and reintroduction of 2 American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria that were deemed not applicable by the ClinGen MYH7 working group). These criteria were applied to 2059 variants in a test set of 97 probands. Variants were classified as benign (n=1702), likely benign (n=33), uncertain significance (n=71), likely pathogenic (likely pathogenic; n=12), and pathogenic (P; n=3). Only 2/15 likely pathogenic/P variants were identified in Non-Hispanic African ancestry probands. We tailored the ClinGen MYH7 criteria for our study. Our preliminary data show that 15/97 (15.5%) probands have likely pathogenic/P variants, most of which were identified in probands of Non-Hispanic European ancestry. We anticipate continued evolution of our approach, one that will be informed by new insights on variant interpretation and a greater understanding of the genetic architecture of dilated cardiomyopathy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.


The genomic characteristics and pathogenicity of a mammalian orthoreovirus within a new lineage from wild pika in plateau.
Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years. Herein, we isolated a new mammalian orthoreovirus (MRV), Pika/MRV/GCCDC7/2019 (PMRV-GCCDC7), in the Qinghai-Tibet Plateau wild pika (Ochotona curzoniae). Though the PMRV-GCCDC7 shows features of typical reovirus with ten gene segments arranged in 3:3:4 in length, the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis. The results of cellular susceptibility, species tropism, and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines (A549, Huh7, HCT, and LoVo) and six non-human cells lines, including Vero-E6, LLC-MK2, BHK-21, N2a, MDCK, and RfKT cell, derived from diverse mammals, i.e. monkey, mice, canine and bat, which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts. Infection of BALB/c mice with PMRV-GCCDC7 via intranasal inoculation led to relative weight loss, lung tissue damage and inflammation with the increase of virus titer, but no serious respiratory symptoms and death occurred. The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.


Evaluation of early and late effects into the acute spinal cord injury of an injectable functionalized self-assembling scaffold.
The complex physiopathological events occurring after spinal cord injury (SCI) make this devastating trauma still incurable. Self-assembling peptides (SAPs) are nanomaterials displaying some appealing properties for application in regenerative medicine because they mimic the structure of the extra-cellular matrix (ECM), are reabsorbable, allow biofunctionalizations and can be injected directly into the lesion. In this study we evaluated the putative neurorigenerative properties of RADA16-4G-BMHP1 SAP, proved to enhance in vitro neural stem cells survival and differentiation. This SAP (RADA16-I) has been functionalized with a bone marrow homing motif (BMHP1) and optimized via the insertion of a 4-glycine-spacer that ameliorates scaffold stability and exposure of the biomotifs. We injected the scaffold immediately after contusion in the rat spinal cord, then we evaluated the early effects by semi-quantitative RT-PCR and the late effects by histological analysis. Locomotor recovery over 8 weeks was assessed using Basso, Beattie, Bresnahan (BBB) test. Gene expression analysis showed that at 7 days after lesion the functionalized SAP induced a general upregulation of GAP-43, trophic factors and ECM remodelling proteins, whereas 3 days after SCI no remarkable changes were observed. Hystological analysis revealed that 8 weeks after SCI our scaffold increased cellular infiltration, basement membrane deposition and axon regeneration/sprouting within the cyst. Moreover the functionalized SAP showed to be compatible with the surrounding nervous tissue and to at least partially fill the cavities. Finally SAP injection resulted in a statistically significant improvement of both hindlimbs' motor performance and forelimbs-hindlimbs coordination. Altogether, these results indicate that RADA16-4G-BMHP1 induced favourable reparative processes, such as matrix remodelling, and provided a physical and trophic support to nervous tissue ingrowth. Thus this biomaterial, eventually combined with cells and growth factors, may constitute a promising biomimetic scaffold for regenerative applications in the injured central nervous system.


Consuming almonds with chocolate or lettuce influences oral processing behaviour, bolus properties and consequently predicted lipid release from almonds.
Lipids in almonds are naturally encapsulated by cell walls which may reduce the actual metabolizable energy content of almonds. Oral processing increases the accessibility of lipids to digestive enzymes by grinding the almond matrix. This study aimed to investigate the effect of adding accompanying foods (chocolate and iceberg lettuce) to almonds on oral processing behaviour, bolus properties and predicted lipid release. Natural chewing times of four almond model foods including one almond (1.3 g), four almonds (4.6 g), one almond with chocolate (4.3 g) and one almond with iceberg lettuce (4.3 g) were collected from n = 59 participants in duplicate. Expectorated boli at the moment of swallowing were characterized for number and mean area of almond bolus particles. Predicted lipid bioaccessibility was estimated using a previously validated model. At similar bite size (4.3-4.6 g), the addition of chocolate and iceberg lettuce to almonds significantly decreased (p < 0.05) chewing time and significantly increased (p < 0.05) eating rate compared to consumption of almonds alone. Almond bolus particle sizes were similar for almonds consumed alone (one and four almonds) and with chocolate, while consuming almonds with lettuce generated significantly fewer and larger almond bolus particles (p < 0.05). Predicted lipid bioaccessibility of almonds consumed with iceberg lettuce was significantly lower (p < 0.05) than for almonds consumed alone (one and four almonds) and almonds consumed with chocolate. Eating rate correlated significantly and positively with the mean area of bolus particles and significantly and negatively with predicted lipid release. In conclusion, combining almonds with other foods such as chocolate and lettuce influences oral processing behaviour and bolus properties and consequently predicted lipid bioaccessibility of almonds, highlighting the impact of food matrix and consumption context on these aspects.


Seasonal and perennial changes in the distribution of water in the sapwood of conifers in a sub-frigid zone.
An analysis was made of progressive changes in patterns of cavitation in the sapwood of three species of conifer (Larix kaempferi, Abies sachalinensis, and Picea jezoensis) that were growing in a sub-frigid zone. In all three conifers, all tracheids of the newly forming outermost annual ring were filled with water or cytoplasm during the period from May to August. However, many tracheids in the transition zone from earlywood to latewood lost water in September, presumably through drought-induced cavitation. Cavitated tracheids tended to be continuously distributed in a tangential direction. Subsequently, some earlywood tracheids of the outermost annual ring lost water during the period from January to March. This was associated with freeze-thaw cycles. In the second and third annual rings from the cambium of all three conifers, the lumina of most tracheids in the transition zone from earlywood to latewood contained no water. In contrast, some latewood tracheids near the annual ring boundary and many earlywood tracheids retained water in their lumina. The third annual ring had more cavitated tracheids than the second annual ring. Our observations indicated that cavitation progressed gradually in the tracheids of the conifers and that they were never refilled once cavitation had occurred. The region involved in water transport in conifers did not include the entire sapwood and differed among annual rings.


Integration of Behavioral Cough Suppression Therapy Into Lung Cancer Care: Nonpharmacologic Interventions for Chronic Cough.
Chronic cough is a demanding symptom of lung cancer. Clinical research tends to underestimate the impact of lung cancer-related cough on patient quality of life. Current guidelines do not describe how oncology nurses, as a vital part of the interprofessional team, can use nonpharmacologic interventions described by behavioral cough suppression therapy (BCST) techniques for patients with lung cancer. This article aims to provide oncology nurses with insight into BCST and investigates how to integrate BCST into lung cancer care. A literature search for primary articles related to BCST was conducted using the electronic databases PubMed® and CINAHL®. The 2017 American College of Chest Physicians' guideline and expert panel report served as a major resource. Oncology nurses can investigate the use of BCST techniques for patients with lung cancer with chronic cough as a nonpharmacologic intervention. Assessment of patients with chronic cough should be carried out before initiating referral for BCST, including identifying cough triggers, causes of cough, and cough types.


A Simple Tool to Predict Development of Delirium After Elective Surgery.
To identify a quick clinical tool to assess the risk of delirium after elective surgery. Prospective observational study. Preoperative assessment clinic at the Veterans Affairs Portland Health Care System. Community-living veterans aged 65 and older scheduled for elective surgery requiring general or major anesthesia. Confusion Assessment Method (CAM) or Family Confusion Assessment Method (FAM-CAM). Data on education, medications, substance use, Patient Health Questionnaire (PHQ-9), Study of Osteoporotic Fractures Frailty, Mini-Cog, and Charlson-Deyo score were collected preoperatively. Of 114 veterans who agreed to participate, 76 completed the final delirium assessment. Ten of the 76 (13%) developed delirium in the 72 hours after surgery as assessed using the CAM or FAM-CAM. In bivariate analysis, factors that increased the odds of delirium at least three times were low education; poor PHQ-9, clock draw, word recall, Mini-Cog, and poor preoperative orientation scores; alcohol use; and higher comorbidities as measured using Charlson-Deyo index. Scoring the Mini-Cog from 0 to 5 had a higher predictive power (area under the receiving operating characteristic curve = 0.77) than other approaches to scoring the Mini-Cog. Other models did not significantly improve prediction of postoperative delirium risk and would be complicated to use in a clinical setting. In this sample of veterans who had elective surgery with major anesthesia, Mini-Cog score predicted likelihood of postoperative delirium.


Effect on lipid metabolism of beet fibre in desert nomads with low habitual fibre intake.
The present study was conducted to test the efficacy of fibre supplementation for hypercholesterolaemia in subjects from the desert Nomads. Ten males (53 +/- 8 years of age) participated in this study which consisted of three phases: baseline-1 period (2 weeks) in which subjects were on their normal, habitual dietary intake, followed by a period of fibre supplementation (5 weeks) in which subjects were supplemented with 26 g fibre/d, and baseline-2 period (4 weeks) in which fibre supplement was withdrawn. Fibre supplementation resulted in a significant decrease in levels of total serum cholesterol (10 per cent decrease, P less than 0.005 during the second week; and 13.4 per cent decrease, P less than 0.0005 during the fifth week) and LDL-cholesterol (14.3 per cent decrease, P less than 0.01 during the second week; and 16.8 per cent decrease, P less than 0.005 during the fifth week. The LDL/HDL ratio dropped 5.2 per cent (P less than 0.005) during the second week and 10.4 per cent (P less than 0.0001) during the fifth week of the fibre supplementation period. Concentrations of serum triglycerides decreased 4.8 per cent (not significant) during the second week and 9.5 per cent (P less than 0.01) during the fifth week. Daily intake of nutrients, body weight, and HDL-cholesterol levels did not change significantly. We conclude that, in populations such as the desert Nomads, where dietary manipulation and/or therapeutic options are quite limited, fibre supplementation may provide an alternative and effective therapy for the control of hypercholesterolaemia.


Role of RyRs and IP3 receptors after traumatic injury to spinal cord white matter.
Calcium influx and elevation of intracellular free calcium (Ca2+i), with subsequent activation of degenerative enzymes is hypothesized to cause cell injury and death after trauma. We examined the effects of traumatic compressive injury on (Ca2+)i dynamics in spinal cord white matter. We conducted electrophysiological studies with ryanodine and inositol (1,4,5)-triphosphate (IP3) receptor agonists and antagonists in an in vitro model of spinal cord injury (SCI). A 25-30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber (37 degrees C) and injured with a modified clip (2-g closing force) for 15 sec. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential (CAP) with glass microelectrodes. The CAP decreased to 55.2+/-6.8% of control (p < 0.05) after spinal cord injury (SCI). Chelation of Ca2+i with BAPTA-AM (a high-affinity calcium chelator) promoted significantly greater recovery of CAP amplitude (83.2+/-4.2% of control; p < 0.05) after injury. Infusion of caffeine (1 and 10 mM) exacerbated CAP amplitude decline (45.1+/-5.9% of control; p < 0.05; 44.6+/-3.1% of control; p < 0.05) postinjury. Blockade of Ca2+i release through ryanodine-sensitive receptors (RyRs) with dantrolene (10 microM) and ryanodine (50 microM), conferred significant (p < 0.05) improvement in CAP amplitude after injury. On the other hand, blockade of Ca2+i with inositol (1,4,5)-triphosphate receptor (IP3Rs) blocker 2APB (10 microM) also conferred significant improvement in CAP amplitude after injury (82.9+/-7.9%; p < 0.05). In conclusion, the injurious effects of Ca2+i in traumatic central nervous system (CNS) white matter injury appear to be mediated both by RyRs and through IP3Rs calcium-induced calcium release receptors (CICRs).


Tumor necrosis factor clearances during veno-venous hemodiafiltration in the critically ill.
Tumor necrosis factor alpha (TNF) is a mediator of injury in the critically ill. Its small molecular size (17 kd) should allow its clearance during continuous hemodiafiltration (CHD). The authors studied TNF extraction in 12 critically ill patients (APACHE II score 26.3 mean; range, 19-34) receiving CHD. Tumor necrosis factor levels were measured in prefiltered and filtered blood and ultradiafiltrate at 0.4 and 24 hours of therapy. Before CHD, mean plasma TNF levels were 261 pg/ml (95% confidence interval [CI]: 184-578) and 291 pg/ml (95% CI: 0-589) after 24 hours. There were no statistically significant differences between prefilter and postfilter TNF levels. Most ultradiafiltrate samples (74%) contained demonstrable TNF (mean, 314 pg/ml; 95% CI: 67-561). Daily TNF excretion was a mean of 15.9 micrograms (+5.6 standard error [SE]), with a mean daily clearance of 27.5 L (95% CI: 2.5-52.5). The authors conclude that significant amounts of TNF are excreted in the ultradiafiltrate during CHD. This observation may provide a rationale for use of similar therapies in critically ill patients in the absence of conventional indications for dialytic support.


Assessing gene expression in lung subcompartments utilizing in situ RNA preservation.
The mechanisms of toxicant-mediated lung injury and repair are influenced by the considerable spatial heterogeneity that exists within the conducting airways of the lungs. As a result of this heterogeneity, significant differences and similarities in gene expression are observed throughout lung subcompartments. RNA-based technologies such as real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and cDNA microarray analysis of gene expression provide valuable clues to understanding the mechanisms of toxicant-induced injury. Isolating RNA from lung subcompartments has previously involved considerable time and labor-intensive processes that limit the number of animals that could be processed in a day. The aim of this study was to determine if intact, high-quality RNA could be preserved in situ over a period of time to delay the need to immediately perform site-specific lung subcompartment microdissections and RNA isolations. Two hours after 1-nitronaphthalene treatment, rat lungs were inflated with and stored in RNA preservation solution and stored at 4 degrees C for 7 days. RNA was isolated from the lung subcompartments isolated by microdissection. After 7 days of storage, the RNA was intact, of high quality, and could be used for real-time RT-PCR to examine heterogeneous gene expression in the lung subcompartments. In summary, this simplified technique of in situ RNA preservation and site-specific lung subcompartment microdissection allows the isolation of intact, high-quality RNA that may be used with molecular RNA-based technologies that will significantly accelerate our understanding of pulmonary injury and repair mechanisms.


Compliance with clinical guidelines for whiplash improved with a targeted implementation strategy: a prospective cohort study.
Implementation strategies for clinical guidelines have shown modest effects in changing health professional's knowledge and practice, however, targeted implementations are suggested to achieve greater improvements. This study aimed to examine the effect of a targeted implementation strategy of the Australian whiplash guidelines on health professionals' knowledge, beliefs and practice and to identify predictors of improved knowledge. 94 health professionals (Physiotherapists, Chiropractors and Osteopaths) who manage whiplash participated in this study. Prior to their inclusion in the study, health professionals were classified as compliant with clinical guidelines for whiplash (n = 52) or non-compliant (n = 42), according to a record of clinical practice. All participants completed a 2- day interactive workshop with outcomes measured at baseline and 3 months following the workshop. The workshop was delivered by opinion leaders, with the educational content focused on the pre-identified knowledge and practice gaps in relation to clinical guidelines for whiplash. Knowledge and health professional beliefs were assessed by a questionnaire and professional practice by record of clinical practice. Participants significantly increased knowledge (p < 0.0001) and were more likely to be compliant with the guidelines at follow-up (compliant at baseline 58%, follow-up 79%, p = 0.002). Health professional belief systems significantly changed to be more behavioural (p = 0.02) and less biomedical (p = 0.000). Predictors of improved knowledge were baseline knowledge (parameter estimate = -0.6, p = 0.000) and profession (parameter estimate = -3.8, p = 0.003) (adj R2 = 35%). A targeted implementation strategy improved health professional's knowledge and clinical practice so that they became more compliant with clinical guidelines for whiplash. In addition health professionals' belief systems significantly changed to be more behavioural in orientation. Baseline knowledge and profession predicted 35% of the variance in improved knowledge.


Assessing outcomes for cost-utility analysis in depression: comparison of five multi-attribute utility instruments with two depression-specific outcome measures.
Many mental health surveys and clinical studies do not include a multi-attribute utility instrument (MAUI) that produces quality-adjusted life-years (QALYs). There is also some question about the sensitivity of the existing utility instruments to mental health. To compare the sensitivity of five commonly used MAUIs (Assessment of Quality of Life - Eight Dimension Scale (AQoL-8D), EuroQoL-five dimension (EQ-5D-5L), Short Form 6D (SF-6D), Health Utilities Index Mark 3 (HUI3), 15D) with that of disease-specific depression outcome measures (Depression Anxiety Stress Scales (DASS-21) and the Kessler Psychological Distress Scale (K10)) and develop 'crosswalk' transformation algorithms between the measures. Individual data from 917 people with self-report depression collected as part of the International Multi-Instrument Comparison Survey. All the MAUIs discriminated between the levels of severity measured by the K10 and the DASS-21. The AQoL-8D had the highest correlation with the disease-specific measures and the best goodness-of-fit transformation properties. The algorithms developed in this study can be used to determine cost-effectiveness of services or interventions where utility measures are not collected.


Age-related differences in brain activity during true and false memory retrieval.
Compared to young adults, older adults show not only a reduction in true memories but also an increase in false memories. We investigated the neural bases of these age effects using functional magnetic resonance imaging and a false memory task that resembles the Deese-Roediger-McDermott (DRM) paradigm. Young and older participants were scanned during a word recognition task that included studied words and new words that were strongly associated with studied words (critical lures). During correct recognition of studied words (true memory), older adults showed weaker activity than young adults in the hippocampus but stronger activity than young adults in the retrosplenial cortex. The hippocampal reduction is consistent with age-related deficits in recollection, whereas the retrosplenial increase suggests compensatory recruitment of alternative recollection-related regions. During incorrect recognition of critical lures (false memory), older adults displayed stronger activity than young adults in the left lateral temporal cortex, a region involved in semantic processing and semantic gist. Taken together, the results suggest that older adults' deficits in true memories reflect a decline in recollection processes mediated by the hippocampus, whereas their increased tendency to have false memories reflects their reliance on semantic gist mediated by the lateral temporal cortex.


Antibiotic prophylaxis following low-velocity gunshot fractures: an updated review.
Low-velocity gunshot fractures (LVGFs) are a common type of gunshot-induced trauma with the potential for complications such as infection and osteomyelitis. The effectiveness of antibiotic therapy in LVGFs remains uncertain, leading to ongoing debate about the appropriate treatment. In this review, we evaluate recent updates on the current understanding of antibiotic therapy in LVGFs, how previous studies have investigated the use of antibiotics in LVGFs, and the current state of institutional policies and protocols for treating LVGFs with antibiotics. We conducted a review of PubMed, Embase, and Web of Science databases to identify studies that investigated the use of antibiotics in LVGFs after the last review in 2013. Due to the lack of quantitative clinical trial studies, we employed a narrative synthesis approach to analyze and present the findings from the included primary studies. We categorized the outcomes based on the anatomical location of the LVGFs. After evaluating 67 publications with the necessary qualifications out of 578 abstracts, 17 articles were included. The sample size of the studies ranged from 22 to 252 patients. The antibiotics used in the studies varied, and the follow-up period ranged from three months to ten years. The included studies investigated the use of antibiotics in treating LVGFs at various anatomic locations, including the humerus, forearm, hand and wrist, hip, femur, tibia, and foot and ankle. Our study provides updated evidence for the use of antibiotics in LVGFs and highlights the need for further research to establish evidence-based guidelines. We also highlight the lack of institutional policies for treating LVGFs and the heterogeneity in treatments among institutions with established protocols. A single-dose antibiotic approach could be cost-effective for patients with non-operatively treated LVGFs. We suggest that a national or international registry for gunshot injuries, antibiotics, and infections could serve as a valuable resource for collecting and analyzing data related to these important healthcare issues.


Breast feeding in infancy and social mobility: 60-year follow-up of the Boyd Orr cohort.
To assess the association of having been breast fed with social class mobility between childhood and adulthood. Historical cohort study with a 60-year follow-up from childhood into adulthood. 16 urban and rural centres in England and Scotland. 3182 original participants in the Boyd Orr Survey of Diet and Health in Pre-War Britain (1937-39) were sent follow-up questionnaires between 1997 and 1998. Analyses are based on 1414 (44%) responders with data on breast feeding measured in childhood and occupational social class in both childhood and adulthood. Odds of moving from a lower to a higher social class between childhood and adulthood in those who were ever breast fed versus those who were bottle fed. The prevalence of breast feeding varied by survey district (range 45-86%) but not with household income (p = 0.7), expenditure on food (p = 0.3), number of siblings (p = 0.7), birth order (p = 0.5) or social class (p = 0.4) in childhood. Participants who had been breast fed were 41% (95% CI 10% to 82%) more likely to move up a social class in adulthood (p = 0.007) than bottle-fed infants. Longer breastfeeding duration was associated with greater odds of upward social mobility in fully adjusted models (p for trend = 0.003). Additionally controlling for survey district, household income and food expenditure in childhood, childhood height, birth order or number of siblings did not attenuate these associations. In an analysis comparing social mobility among children within families with discordant breastfeeding histories, the association was somewhat attenuated (OR 1.16; 95% CI 0.74 to 1.8). Breast feeding was associated with upward social mobility. Confounding by other measured childhood predictors of social class in adulthood did not explain this effect, but we cannot exclude the possibility of residual or unmeasured confounding.


Structure and biosynthesis of rabbit lens capsule collagen.
The present study was designed to compare collagen synthesized by rabbit lens epithelial cells in culture with rabbit lens capsule collagen. Confluent monolayers of rabbit lens epithelial cells were established. Incorporation of [3H]-proline into glycoproteins secreted into the medium and cell surface components were analyzed in the presence of protease inhibitors. Gel filtration chromatography on sodium dodecyl sulfate--agarose (Bio-gel A-5m) of [3H]-labeled newly synthesized proteins by lens epithelial cells in culture resolved into a single precursor of approximate molecular weight of 160,000 daltons. Neither the medium nor the cell layer showed any evidence of low-molecular weight hydroxyproline-containing material. Limited pepsin digestion of this material cleaved the higher molecular weight chains into smaller components ranging from 25,000 to 110,000 daltons. Pepsin digestion and direct extraction of the collagenous components of the rabbit lens capsule revealed materials of high--molecular weight proteins similar to that synthesized in culture. Low--molecular weight (55,000 daltons) protein was only detected in lens capsules after prolonged pepsin digestion. S-Carboxylation of the lens capsules collagens did not affect their mobilities, but repepsinization gave rise to 110,000 dalton protein, although no significant changes in the amino acid composition were noticed. The absence of synthesis of low--molecular weight protein by cell culture and the presence of low--molecular weight components only after prolonged pepsin digestion of lens capsule could be the result of unusual susceptibility of the basement membrane collagens to pepsin attack.


Squamous cell carcinomas of the esophagus arise from a telomere-shortened epithelial field.
Critically shortened telomeres make chromosomes susceptible to the instability and widespread cytogenetic alterations that characterize most human cancers. We hypothesized that the very rapid cell proliferation observed in esophageal squamous cell carcinomas might accelerate telomere shortening and chromosomal instability associated with carcinogenesis. We used a number of telomere measurement techniques including quantitative fluorescence in situ hybridization (Q-FISH) to compare chromosomal aberrations and telomere lengths of individual chromosomes in esophageal squamous cell carcinomas (ESCCs) and nearby non-neoplastic esophageal epithelium (NNEE) cells. Our results showed that the mean telomere length in ESCC cells was significantly less than that in adjacent NNEE cells, and that telomeres in all NNEE cells were significantly shorter than those in normal esophageal epithelium (reported previously). In addition, there was no evidence linking telomere shortening of a particular chromosome to field cancerization in ESCC. However, a mechanistic link between telomere shortening and chromosomal instability was supported by a higher frequency of anaphase/telophase bridges and an increase in the frequency of aneuploidy. This study furthers our understanding of the mechanism by which telomere shortening and chromosomal instability lead to carcinogenesis and field cancerization in the esophagus.


Seasonal and diel patterns in cetacean use and foraging at a potential marine renewable energy site.
Marine renewable energy (MRE) developments often coincide with sites frequented by small cetaceans. To understand habitat use and assess potential impact from development, echolocation clicks were recorded with acoustic click loggers (C-PODs) in Swansea Bay, Wales (UK). General Additive Models (GAMs) were applied to assess the effects of covariates including month, hour, tidal range and temperature. Analysis of inter-click intervals allowed the identification of potential foraging events as well as patterns of presence and absence. Data revealed year-round presence of porpoise, with distinct seasonal and diel patterns. Occasional acoustic encounters of dolphins were also recorded. This study provides further evidence of the need for assessing temporal trends in cetacean presence and habitat use in areas considered for development. These findings could assist MRE companies to monitor and mitigate against disturbance from construction, operation and decommissioning activities by avoiding times when porpoise presence and foraging activity is highest in the area.


Production and function of activin A in human dendritic cells.
Activin A, a member of the transforming growth factor-beta superfamily, has a role in tissue repair and inflammation. In our previous studies, we identified by immunohistochemistry DC-SIGN(+) dendritic cells as a source of activin A in vivo. The present study was aimed at investigating activin A production by dendritic cells (DC) in vitro and its function. Here we demonstrate that monocyte-derived DC (Mo-DC) released abundant levels of activin A during the maturation process induced by TLR agonists, bacteria (B. henselae, S. thyphimurium), TNF and CD40L. Activin A was also induced in monocyte-derived Langerhans cells (LC) and in blood myeloid DC by LPS and/or CD40L stimulation, but not in blood plasmacytoid DC following stimulation with influenza virus. Activin A production by DC was selectively down-regulated by anti-inflammatory molecules such as dexamethasone or IL-10. Neutralization of endogenous activin A using its inhibitor follistatin, or the addition of exogenous activin A during LPS maturation did not affect Mo-DC maturation marker expression, cytokine release or allostimulatory function. However, Mo-DC matured with LPS in the presence of exogenous activin A displayed a higher FITC-dextran uptake, similar to that of immature DC. Moreover, activin A promoted monocyte differentiation to DC and reversed the inhibitory effects of IL-6 on DC differentiation of monocytes. These findings demonstrate that different subsets of DC release activin A, a cytokine that promotes DC generation, and affects the ability of mature DC to take up antigens (Ags).


Implementing the second generation social health maintenance organization.
In 1996 the Health Care Financing Administration implemented a second generation of the Social HMO demonstration. This model retained the chronic care benefits of the original Social HMOs while attempting to develop a geriatric service model integrated into primary care and a screening and assessment process focused directly on healthcare risk factors. Other refinements included risk-adjusted capitation payment, broadened eligibility for expanded care benefits, low co-payments for these benefits, and no caps on the expanded care benefits expenditures. The geriatric approach is designed to facilitate integration among providers and levels of care. This includes timely application of primary care monitoring and treatment to reduce illness and disability as well as a geriatric education and consultation program to provide specialty support for complex cases. Care management is designed for those requiring home-based care, those discharged from hospitals or nursing homes, and those having difficulty with treatment regimens. A case study of the Social HMO implementation through the Fall of 1999. Health Plan of Nevada (HPN), with locations in Las Vegas, Reno, and surrounding areas. More than 25,000 Medicare beneficiaries participated during the study period. Administrative reports, charts, and interviews with administrators and clinicians. Within 12 months of operation under this authority, HPN succeeded in putting in place most of the components of the planned geriatric approach: a screening program to identify patients "at risk" for high service costs and disability and timely application of primary care treatment to reduce illness and disability. Geriatric education and a consultation program for complex cases were available, but full implementation was delayed until the plan was able to hire a full time geriatrician. Health Plan of Nevada's Social HMO program reflects current perspectives on how to integrate chronic care into an HMO. The accomplishments affirm that the provision of risk-adjusted reimbursement, along with the 5 % supplement to the normal Medicare capitation payment, are sufficient incentives for a health plan to restructure itself so that it places a priority on retaining and serving populations at risk for high expenditures.


Pallister-Killian syndrome in a girl with mild developmental delay and mosaicism for hexasomy 12p.
We report on a 5-year-old girl with Pallister-Killian syndrome (OMIM #601803) due to mosaicism of two supernumerary isochromosomes (hexasomy 12p). Hexasomy 12p was found in 20% of the cells by chromosome analysis of cultured skin fibroblasts and confirmed by FISH- and arrayCGH analysis. The girl has woolly and sparse hair, absence of lateral eyebrows, dry skin, brittle nails, hypopigmented patches, frontal bossing, hearing loss, hypertrophic dilated cardiomyopathy, polydactyly, and mild developmental delay. This is the second live case of mosaicism for hexasomy 12p to be reported. A gene-dosage hypothesis has previously suggested that cases with hexasomy 12p would have a worse phenotype than cases with tetrasomy 12p. The relatively mild symptoms found in the current girl with hexasomy 12p may to contradict this hypothesis.


Bisphenol A induces hypothalamic down-regulation of the the cannabinoid receptor 1 and anorexigenic effects in male mice.
Bisphenol A is an environment-polluting industrial chemical able to interfere with the endocrine system. An obesogenic effect in perinatally exposed rodents has been described as estrogenic activity. We exposed male mice to Bisphenol A during fetal-perinatal period (from 10 days post coitum to 31 days post partum) and investigated the effects of this early-life exposure at 78 days of age. Body weight, food intake, fat mass, and hypothalamic signals related to anorexigenic control of food intake were analyzed. Results show that Bisphenol A exposure reduced body weight and food intake. In addition, the exposure decreased epididymal fat mass and adiposity, acting negatively on adipocyte volume. At hypothalamic level, Bisphenol A exposure reduced the expression of the cannabinoid receptor 1 and induced gene expression of cocaine and amphetamine-regulated transcript-1. This observation suggests that Bisphenol A induces activation of anorexigenic signals via down-regulation of the hypothalamic cannabinoid receptor 1 with negative impact on food intake.


Clinical research education study teams: a research curriculum for obstetric and gynecology residents.
Research education is a requirement for obstetrics and gynecology residents. Most obstetrics and gynecology residencies struggle with barriers to efficient, effective research education and productivity for their residents. These barriers include constraints on faculty time, lack of intrinsic desire within individual residents, and lack of relevant outcome measures. We developed an efficient, novel research education curriculum that overcomes many of these barriers and provides obstetrics and gynecology residents with a structured format that maximizes the likelihood of a successful, positive research experience. Since the start of the Clinical Research Education Study Team program, the graduating resident cohorts reliably complete and present prospective research projects, including three registered randomized trials. Residency-wide support for other team research has grown dramatically. The residents' work was acknowledged with several research awards, which further reinforces the positive perception of the program. The certainty of completion of their research requirement relieved our residents of the anxiety commonly reported by residents nearing graduation. The Clinical Research Education Study Team program's team design makes efficient use of faculty time. In addition, Clinical Research Education Study Team mentors also have incorporated junior faculty members who wish to improve their own research education skills. We offer our experience with this program in hopes that it may be of value to other programs that wish to improve their resident research education curriculum. It remains important for residents to acquire research skills before continuing into practice or fellowship. The Clinical Research Education Study Team program facilitates this education in an efficient, organized manner.


Organization and phylogenetic interrelationships of genes encoding components of the botulinum toxin complex in proteolytic Clostridium botulinum types A, B, and F: evidence of chimeric sequences in the gene encoding the nontoxic nonhemagglutinin component.
The cluster of genes encoding components of the botulinum neurotoxin (BoNT) complex was mapped in proteolytic (group I) Clostridium botulinum strains encoding BoNT types A, B, and F. Two different arrangements of genes were found: type A strain 62A and type B strain NCTC 7273 have similar organizations of genes encoding BoNT, the nontoxic nonhemagglutinin component (NTNH), hemagglutinin components, and P-21; type F strain Langeland has genes encoding BoNT, NTNH, and P-21, and a previously unidentified open reading frame encoding a protein of 416 amino acids. A group of type A strains typified by infant strain Kyoto-F, which is unlike type A strain 62A, lacks genes for hemagglutinin components and exhibits an organization similar to that of type F. Sequencing and pairwise analysis revealed the presence of possible chimeric sequences in some NTNH genes of proteolytic C. botulinum. Discordance in genealogical trees derived from different regions of the NTNH genes was observed which could be symptomatic of recombination and which may indicate that the NTNH gene represents a hot spot for such events within the cluster of genes encoding the BoNT complex. It is also evident that the phylogenetics of the NTNH gene, which is linked to the gene encoding BoNT, does not mirror the evolutionary history of the BoNT, upon which the C. botulinum species complex is defined and subdivided.