Toward guidance of epicardial cardiac radiofrequency ablation therapy using optical coherence tomography.
Radiofrequency ablation (RFA) is the standard of care to cure many cardiac arrhythmias. Epicardial ablation for the treatment of ventricular tachycardia has limited success rates due in part to the presence of epicardial fat, which prevents proper rf energy delivery, inadequate contact of ablation catheter with tissue, and increased likelihood of complications with energy delivery in close proximity to coronary vessels. A method to directly visualize the epicardial surface during RFA could potentially provide feedback to reduce complications and titrate rf energy dose by detecting critical structures, assessing probe contact, and confirming energy delivery by visualizing lesion formation. Currently, there is no technology available for direct visualization of the heart surface during epicardial RFA therapy. We demonstrate that optical coherence tomography (OCT) imaging has the potential to fill this unmet need. Spectral domain OCT at 1310 nm is employed to image the epicardial surface of freshly excised swine hearts using a microscope integrated bench-top scanner and a forward imaging catheter probe. OCT image features are observed that clearly distinguish untreated myocardium, ablation lesions, epicardial fat, and coronary vessels, and assess tissue contact with catheter-based imaging. These results support the potential for real-time guidance of epicardial RFA therapy using OCT imaging.


Characterization and conservation of the inner E2 core domain structure of branched-chain alpha-keto acid dehydrogenase complex from bovine liver. Construction of a cDNA encoding the entire transacylase (E2b) precursor.
A cDNA clone encoding the entire transacylase (E2b) precursor of the bovine branched-chain alpha-keto acid dehydrogenase complex has been constructed from two overlapping incomplete cDNA clones which were isolated from a lambda ZAP library prepared from bovine liver poly(A)+ RNA. Nucleotide sequencing indicates that this bovine E2b cDNA insert (bE2-11) is 2701 base pairs in length with an open reading frame of 1446 base pairs. The bE2-11 cDNA insert encodes a leader peptide of 61 residues and a mature E2b polypeptide of 421 amino acid residues with a calculated monomeric molecular mass of 46,518 daltons. The molecular mass of the native E2b component isolated from bovine liver is 1,110,000 daltons as determined by sedimentation equilibrium. This value establishes the 24-subunit octahedral model for the quaternary structure of bovine E2b. The amino-terminal sequences of two tryptic fragments (A and B) of the E2b protein have been determined. Fragment A comprises residues 175 to 421 of the E2b protein and is the inner E2 core domain which contains the transacylase active site. Fragment B, produced by further tryptic cleavage of fragment, comprises residues 205 to 421, but does not have transacylase activity. Both fragments A and B confer the highly assembled 24-mer structure. The primary structure of the inner E2 core domain of bovine E2b (fragment A) is very similar to those of three other E2 proteins (human E2p, Escherichia coli E2p, and E. coli E2k). These similarities suggest that these E2 proteins are structurally and evolutionarily related.


Importance of beta-lactamase inactivation in treatment of experimental endocarditis caused by Staphylococcus aureus.
To test the hypothesis that cephalosporins resistant to beta-lactamase are preferred in the treatment of serious staphyloccal infections, the ability of four cephalosporins to eradicate bacteria from the cardiac vegetations of rabbits with experimental endocarditis was examined. Two strains of Staphylococcus aureus were chosen as pathogens: one that rapidly and completely inactivated 50 micrograms of cefazolin in vitro (beta-lactamase-positive) and another that did not inactivate any cephalosporin (beta-lactamase-negative). Rabbits with a polyethylene catheter in the left ventricle were reliably infected witih 10(5) bacteria. Similar numbers of S. aureus were recovered from the cardiac vegetations of rabbits inoculated with the beta-lactamase-positive strain after 24 hr of treatment with each of four cephalosporins. However, when the animals were treated at intervals of 6 hr for four days, significantly fewer rabbits survived after treatment with cefazolin than with cephalothin. No difference in survival was observed in the treatment of rabbits with endocarditis due to the beta-lactamase-negative strain. The failure of cefazolin in the treatment of staphylococcal endocarditis in rabbits may be due to inactivation of the drug by beta-lactamase in vivo.


A novel inulin-type fructan from Asparagus cochinchinensis and its beneficial impact on human intestinal microbiota.
A purified inulin-type fructan named ACNP (Asparagus cochinchinensis neutral polysaccharide) with apparent molecular weight of 2690 Da was obtained from Asparagus cochinchinensis (Lour.) Merr. by ion-exchange and gel-filtration column chromatography. Structural analyses reveal that ACNP has a linear backbone composed of 2,1-β-D-Fruf residues, ending with a (1→2) bonded α-D-Glcp. The impacts of ACNP on gut microbiota were then investigated by in vitro fermentation with human fecal cultures. The results showed that ACNP was digested by gut microbiota, while the pH value in the fecal culture of ACNP was greatly decreased, and total short-chain fatty acids, acetic, propionic, i-valeric and n-valeric acids were significantly increased. Moreover, ACNP regulated the fecal microbiota composition by stimulating the growth of Prevotella, Megamonas, and Bifidobacterium while depleting Haemophilus. Collectively, these results indicated that ACNP beneficially regulates gut microbiota, which thus suggested that ACNP has the potential to be used as a dietary supplement or drug to improve health.


Devices for rapid induction of hypothermia.
In industrial countries it is estimated that the incidence of out-of-hospital sudden cardiac arrest lies between 36 and 128 per 100,000 inhabitants per year. Almost 80% of patients who initially survive a cardiac arrest present with coma lasting more than 1 h. Current therapy during cardiac arrest concentrates on the external support of circulation and respiration with additional drug and electrical therapy. Therapeutic hypothermia provides a new and very effective therapy for neuroprotection in patients after cardiac arrest. It is critical that mild hypothermia has to be applied very early after the ischaemic insult to be effective, otherwise the beneficial effects would be diminished or even abrogated. There are numerous methods available for cooling patients after ischaemic states. Surface cooling devices are non-invasive and range from simple ice packs to sophisticated machines with automatic feedback control. Other non-invasive methods include drugs and cold liquid ventilation. The newer devices have cooling rates comparable to invasive catheter techniques. Invasive cooling methods include the administration of ice-cold fluids intravenously, the use of intravascular cooling catheters, body cavity lavage, extra-corporeal circuits and selective brain cooling. Most of these methods are quite invasive and are still in an experimental stage. The optimal timing and technique for the induction of hypothermia after cardiac arrest have not yet been defined, and it is currently a major topic of ongoing research. The induction of hypothermia after cardiac arrest needs to be an integral component of the initial evaluation and stabilization of the patient.


Application of Bruchin B to pea pods results in the up-regulation of CYP93C18, a putative isoflavone synthase gene, and an increase in the level of pisatin, an isoflavone phytoalexin.
Bruchins, mono and bis (3-hydroxypropanoate) esters of long chain alpha,omega-diols, are a recently discovered class of insect elicitors that stimulate cell division and neoplasm formation when applied to pods of peas and certain other legumes. Differential display analysis resulted in the identification of an mRNA whose level was increased by the application of Bruchin B to pea pods. The corresponding amplification product was cloned and sequenced and a full length cDNA sequence was obtained. This cDNA and the gene from which it was derived were assigned the name CYP93C18 based upon sequence similarities to the cytochrome P450 mono-oxygenase CYP93C subfamily, which contains isoflavone synthase genes from legumes. RNA gel blots and quantitative RT-PCR demonstrated that expression of CYP93C18 increased within 8 h of bruchin treatment to a maximum of 100-200-fold of the level in untreated pods, and then declined. The up-regulation of CYP93C18 was followed by an increase in the level of the isoflavone phytoalexin, pisatin. Pisatin was detectable in the bruchin-treated pods after 16 h and reached a maximum between 32 h and 64 h. This, the first report of induction of phytoalexin biosynthesis by an insect elicitor, suggests that Bruchin B not only stimulates neoplasm formation, but also activates other plant defence responses.


One-Day Construction of Multiplex Arrays to Harness Natural CRISPR-Cas Systems.
CRISPR-Cas systems are prokaryotic immune systems that have proliferated widely not only in bacteria and archaea, but also much more recently, in human biological research and applications. Much work to date has utilized synthetic sgRNAs along with the CRISPR nuclease Cas9, but the discovery of array-processing nucleases now allows the use of more compact, natural CRISPR arrays in heterologous hosts, in addition to organisms with endogenous systems. Unfortunately, the construction of multiplex natural CRISPR arrays remains technically challenging, expensive, and/or time-consuming. This limitation hampers research involving natural CRISPR arrays in both native and heterologous hosts. To address this problem, we present a method to assemble CRISPR arrays that is simple, rapid, affordable, and highly scalable-we assembled 9-spacer arrays with 1 day's worth of work. We used this method to harness the endogenous CRISPR-Cas system of the highly competent bacterium Acinetobacter baylyi, showing that while single spacers are not always completely effective at blocking DNA acquisition through natural competence, multiplex natural CRISPR arrays enable both nearly complete DNA exclusion and genome editing, including with multiple targets for both. In addition to demonstrating a CRISPR array assembly method that will benefit a variety of applications, we also find a potential bet-hedging strategy for balancing CRISPR defense versus DNA acquisition in naturally competent A. baylyi.


Causal language and strength of inference in academic and media articles shared in social media (CLAIMS): A systematic review.
The pathway from evidence generation to consumption contains many steps which can lead to overstatement or misinformation. The proliferation of internet-based health news may encourage selection of media and academic research articles that overstate strength of causal inference. We investigated the state of causal inference in health research as it appears at the end of the pathway, at the point of social media consumption. We screened the NewsWhip Insights database for the most shared media articles on Facebook and Twitter reporting about peer-reviewed academic studies associating an exposure with a health outcome in 2015, extracting the 50 most-shared academic articles and media articles covering them. We designed and utilized a review tool to systematically assess and summarize studies' strength of causal inference, including generalizability, potential confounders, and methods used. These were then compared with the strength of causal language used to describe results in both academic and media articles. Two randomly assigned independent reviewers and one arbitrating reviewer from a pool of 21 reviewers assessed each article. We accepted the most shared 64 media articles pertaining to 50 academic articles for review, representing 68% of Facebook and 45% of Twitter shares in 2015. Thirty-four percent of academic studies and 48% of media articles used language that reviewers considered too strong for their strength of causal inference. Seventy percent of academic studies were considered low or very low strength of inference, with only 6% considered high or very high strength of causal inference. The most severe issues with academic studies' causal inference were reported to be omitted confounding variables and generalizability. Fifty-eight percent of media articles were found to have inaccurately reported the question, results, intervention, or population of the academic study. We find a large disparity between the strength of language as presented to the research consumer and the underlying strength of causal inference among the studies most widely shared on social media. However, because this sample was designed to be representative of the articles selected and shared on social media, it is unlikely to be representative of all academic and media work. More research is needed to determine how academic institutions, media organizations, and social network sharing patterns impact causal inference and language as received by the research consumer.


Lung cancer and air pollution: a 27 year follow up of 16 209 Norwegian men.
The well documented urban/rural difference in lung cancer incidence and the detection of known carcinogens in the atmosphere have produced the hypothesis that long term air pollution may have an effect on lung cancer. The association between incidence of lung cancer and long term air pollution exposure was investigated in a cohort of Oslo men followed from 1972/73 to 1998. Data from a follow up study on cardiovascular risk factors among 16 209 40 to 49 year old Oslo men in 1972/73 were linked to data from the Norwegian cancer register, the Norwegian death register, and estimates of average yearly air pollution levels at the participants' home address in 1974 to 1998. Survival analyses, including Cox proportional hazards regression, were used to estimate associations between exposure and the incidence of lung cancer. During the follow up period, 418 men developed lung cancer. Controlling for age, smoking habits, and length of education, the adjusted risk ratio for developing lung cancer was 1.08 (95% confidence interval, 1.02 to 1.15) for a 10 micro g/m(3) increase in average home address nitrogen oxide (NO(x)) exposure between 1974 and 1978. Corresponding figures for a 10 micro g/m(3) increase in sulphur dioxide (SO(2)) were 1.01 (0.94 to 1.08). Urban air pollution may increase the risk of developing lung cancer.


Preventing food waste in subsidy-based university dining systems: An artificial neural network-aided model under uncertainty.
Food waste planning at universities is often a complex matter due to the large volume of food and variety of services. A major portion of university food waste arises from dining systems including meal booking and distribution. Although dining systems have a significant role in generating food wastes, few studies have designed prediction models that could control such wastes based on reservation data and behavior of students at meal delivery times. To fill this gap, analyzing meal booking systems at universities, the present study proposed a new model based on machine learning to reduce the food waste generated at major universities that provide food subsidies. Students' reservation and their presence or absence at the dining hall (show/no-show rate) at mealtime were incorporated in data analysis. Given the complexity of the relationship between the attributes and the uncertainty observed in user behavior, a model was designed to analyze definite and random components of demand. An artificial neural network-based model designed for demand prediction provided a two-step prediction approach to dealing with uncertainty in actual demand. In order to estimate the lowest total cost based on the cost of waste and the shortage penalty cost, an uncertainty-based analysis was conducted at the final step of the research. This study formed a framework that could reduce the food waste volume by up to 79% and control the penalty and waste cost in the case study. The model was investigated with cost analysis and the results proved its efficiency in reducing total cost.


Prediction of coronary artery stenosis at rest in patients with normal left ventricular wall motion. Segmental analyses using strain imaging diastolic index.
Noninvasive detection of coronary artery stenosis usually requires a stress test in patients without left ventricular (LV) regional wall motion abnormalities (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may persist beyond recovery from transient ischemia. The aim of the present study was to determine whether segmental analysis of abnormal regional LV relaxation using the strain imaging diastolic index (SI-DI) at rest could predict coronary artery stenosis in the three major vessels in patients without LV dysfunction or RWMA. We performed 2D speckle tracking echocardiography and coronary angiography in 85 patients without RWMA with suspected coronary artery disease. Patients with LV dysfunction or acute coronary syndrome were excluded. Echocardiographic images of the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6 segments. In each segment, SI-DI derived from transverse strain imaging was determined. Forty-eight patients had significant coronary artery stenosis (≥ 70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal segment for detecting left anterior descending artery stenosis (sensitivity, 83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity, 90.3%), and 61.5% in the basal inferior segment for detecting right coronary artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of SI-DI at rest predicted coronary artery stenosis in the three major vessels in patients without RWMA. This noninvasive method may be useful for detecting coronary artery stenosis without a stress test.


Regulation of growth hormone secretion by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in infantile, prepubertal, and adult male rats.
Excitatory amino acids, such as glutamate, constitute a major transmitter system in the control of hypothalamic-pituitary function. Different subtypes of glutamate receptors, such as N-methyl-D-aspartic acid and kainate receptors, have been involved in the control of GH secretion. Other excitatory amino acid receptor subtypes, as alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), amino-4-phosphobutyric acid, and metabotropic receptors, have been identified, yet their role in the control of neuroendocrine function remains to be completely characterized. The purpose of this study was to assess the potential involvement of AMPA receptors in the control of GH secretion. In a first set of experiments, neonatal (5 and 10 days) and prepubertal (23 days) male rats were injected with AMPA (1, 2.5, or 5 mg/kg) or the antagonist of AMPA receptors, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide (NBQX; 0.25 or 0.50 mg/kg). Serum GH concentrations significantly increased 15 min after i.p. administration of AMPA in both neonatal and prepubertal male rats. In addition, serum GH concentrations decreased after NBQX treatment. The stimulatory effect of AMPA was abolished by pretreatment with the blocker of nitric oxide synthase, nitro(w)-arginine-methyl ester (40 mg/kg), and was partially counteracted by the simultaneous administration of GH-releasing hormone (500 microg/kg). Moreover, AMPA was unable to elicit in vitro GH secretion by hemipituitaries from prepubertal males, pointing out that the hypothalamus is probably the site of action for the reported stimulatory action of AMPA on GH release. In a second set of experiments, the effects of AMPA and NBQX were tested in adult male rats. As in prepubertal animals, AMPA significantly increased GH secretion in adult males, whereas NBQX (20 or 40 nmol), administered through intracerebroventricular injection, induced a significant decrease in the amplitude of GH pulses. In conclusion, our data indicate that AMPA receptors have a physiological stimulatory role in the control of GH secretion in male rats throughout the life span. This effect depends on appropriate nitric oxide synthesis during the prepubertal age. In addition, AMPA receptors appear to modulate pulsatile GH secretion in adulthood.


Lessons I have learned (so far).
This article is a personal reflection on a long career in cardiovascular nursing. The author focuses on some of the lessons learned and on individuals pivotal to her learning. Major lessons relate to managing stress by maintaining a sense of perspective in the face of minor frustrations, creating significance from seemingly insignificant interactions and situations, and making career decisions that are based on personal as well as monetary rewards. She also discusses the satisfaction of developing expertise in a health care specialty and the importance of finding clinical mentors. Finally, she reflects on the challenges and rewards of teaching.


Results of percutaneous coronary intervention for chronic total occlusions of coronary arteries: a single center report.
Percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) is associated with lower rates of procedural success and higher complication rates compared with PCIs in non-CTO lesions. The purpose of this study was to analyze the relationship between lesion characteristics and procedural success rates and in-hospital outcomes after PCI for CTO with novel equipment. We evaluated the prospectively entered data of 63 consecutive patients undergoing PCI for CTO at our institute between August 2009 and June 2012. A total of 63 patients (mean age: 64±11, 71% male) with one CTO lesion each underwent PCI. There were 46 patients (mean age: 63±10, 70% male) in the CTO success group and 17 patients (mean age: 65±13, 76.5% male) in the CTO failure group. Successful revascularization was achieved in 73% of patients. We used antegrade approach in 61 cases and retrograde approach in 2 cases. Our predominant strategy was single-wire technique, which was used in 54 cases (85.7%), followed by parallel-wire technique in 7 cases (11.1%). Moderate-to-severe tortuosity (odds ratio [OR]: 9.732, 95% confidence interval [CI]: 1.783-53.115, p=0.009) and occlusion duration (OR: 1.536, 95% CI: 1.178-2.001, p=0.002) were independent predictors of procedural failure in the multivariate analysis. No in-hospital major cardiac events occurred. We have reported a study with a relatively high success rate of PCI with very low procedural and in-hospital complications. Moderate-to-severe tortuosity was observed as the most challenging problem despite the utilisation of novel equipment and techniques for CTO recanalization.


Social Support and Caregiver Strain.
Informal social supports have been consistently associated with the physical and mental well-being of the elderly. In this study the associations between sense of strain and three types of social support are described for a sample of 131 spouse caregivers. Adverse social contacts were associated with increased strain, while positive contacts were insignificant. When sources of social support were examined daughters figured prominently, as important sources of both positive and adverse social contacts. Findings also emphasize the importance of interventions which include friends, neighbors, and others.


Bee pollen increases hippocampal brain-derived neurotrophic factor and suppresses neuroinflammation in adult rats with chronic immobilization stress.
Chronic stress is a potential problem associated with anxiety, depression, and cognitive dysfunction. Bee pollen, a powerful antioxidant, has many therapeutic effects. In this study, we aimed to examine the effects of one of the Anatolian bee pollens on depression/anxiety. 24 male Sprague Dawley rats were divided into 3 groups as control, stress, and bee pollen + stress. Bee pollen (200 mg/kg/day) was given to rats exposed to physical stress for 10 days. Open field test (OFT) and forced swimming test (FST) were applied to monitor the behavioral changes of the rats. After behavioral tests, the rats were euthanized. Brain-derived neurotrophic factor (BDNF), interleukin 1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were measured by ELISA to evaluate neurological and biochemical changes in rat hippocampal tissue. In addition, malondialdehyde (MDA) and glutathione (GSH) levels in the brain were evaluated. According to the behavioral test results, bee pollen reduced anxiety-like behavior but did not affect depression-like behavior. We also found that bee pollen suppressed neuroinflammation while reducing oxidative stress and lipid peroxidation in hippocampal tissues. Moreover, bee pollen significantly increased the level of BDNF in the hippocampus. In conclusion, bee pollen reduced oxidative damage and neuroinflammation caused by immobilization stress in rat brain tissue. Therefore, we suggest that bee pollen may be an effective natural compound in alleviating the negative effects caused by immobilization stress.


Magnetic resonance cholangiopancreatography in diagnosis of biliary disorders in children - Sharing our experience.
To evaluate the role of Magnetic Resonance Cholangio-pancreatography in the diagnosis of biliary disorders in children. The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data related to the period between August 2005 and December 2013. All children from age of 1 day to 17 years who had undergone Magnetic Rasonance Cholangio-pancreatography examination for suspected pancreaticobiliary disorders were included. Clinical presentation, Magnetic Rasonance Cholangio-pancreatography findings, operative findings and histopathological results were recorded. Sensitivity and specificity of Magnetic Rasonance Cholangio-pancreatography for different diseases was worked out. Of the 50 patients in the study, 12(24%) showed findings of choledochal cyst. Of these patients, 11(91.6%) underwent surgery and operative findings were consistent with choledochal cyst. Only 1(8.3%) who was assessed as biliary atresia was found to have choledochal cyst on surgery Magnetic Resonance Cholangio-pancreatography was found to be 91% sensitive and 100% specific for diagnosis of choledochal cyst with diagnostic accuracy of 98%. Magnetic Resonance Cholangio-pancreatography is a very accurate non-invasive investigation for the diagnosis of biliary disorders.


A machine learning approach in the non-invasive prediction of intracranial pressure using Modified Photoplethysmography.
The ideal Intracranial pressure (ICP) estimation method should be accurate, reliable, cost-effective, compact, and associated with minimal morbidity/mortality. To this end several described non-invasive methods in ICP estimation have yielded promising results, however the reliability of these techniques have yet to supersede invasive methods of ICP measurement. Over several publications, we described a novel imaging method of Modified Photoplethysmography in the evaluation of the retinal vascular pulse parameters decomposed in the Fourier domain, which enables computationally efficient information filtering of the retinal vascular pulse wave. We applied this method in a population of 21 subjects undergoing lumbar puncture manometry. A regression model was derived by applying an Extreme Gradient Boost (XGB) machine learning algorithm using retinal vascular pulse harmonic regression waveform amplitude (HRWa), first and second harmonic cosine and sine coefficients (an1,2, bn1,2) among other features. Gain and SHapley Additive exPlanation (SHAP) values ranked feature importance in the model. Agreement between the predicted ICP mean, median and peak density with measured ICP was assessed using Bland-Altman bias±standard error. Feature gain of intraocular pressure (IOPi) (arterial = 0.6092, venous = 0.5476), and of the Fourier coefficients, an1 (arterial = 0.1000, venous = 0.1024) ranked highest in the XGB model for both vascular systems. The arterial model SHAP values demonstrated the importance of the laterality of the tested eye (1.2477), which was less prominent in the venous model (0.8710). External validation was achieved using seven hold-out test cases, where the median venous predicted ICP showed better agreement with measured ICP. Although the Bland-Altman bias from the venous model (0.034±1.8013 cm water (p<0.99)) was lower compared to that of the arterial model (0.139±1.6545 cm water (p<0.94)), the arterial model provided a potential avenue for internal validation of the prediction. This approach can potentially be integrated into a neurological clinical decision algorithm to evaluate the indication for lumbar puncture.


Capuchin monkeys (Cebus [sapajus] apella) show planning in a manual maze task.
The capacity for planning in nonhuman species has long been an interest of many comparative and cognitive psychologists. There is now considerable evidence that at least great apes show both motor planning and planning for future needs in various contexts and modalities. Few studies, however, have investigated planning ability in a monkey species, and most of these exceptions have used computerized procedures. To gain a broader view, in the current study, we tested capuchin monkeys' capacity for motor planning using the "paddle-box" apparatus, a manual maze task originally designed for testing planning skills in apes (Tecwyn, Thorpe, & Chappell, 2013). This consisted of a box containing different levels of paddles that subjects rotated to drop food into a tube that delivered it to the subject. To evaluate subjects' degree of skill in the task, the initial locations of the food and the final goal (i.e., the "paths" the food could take) were chosen according to the probability of retrieving the reward, starting with those that gave the highest probability of success and moving sequentially to those with the lowest probability. Most subjects solved all levels of difficulty in the task, and capuchin monkeys succeeded as a group in a generalization test with novel paths. These findings demonstrate that some monkeys, like apes, show planning in different contexts and modalities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Image analysis by Krawtchouk moments.
In this paper, a new set of orthogonal moments based on the discrete classical Krawtchouk polynomials is introduced. The Krawtchouk polynomials are scaled to ensure numerical stability, thus creating a set of weighted Krawtchouk polynomials. The set of proposed Krawtchouk moments is then derived from the weighted Krawtchouk polynomials. The orthogonality of the proposed moments ensures minimal information redundancy. No numerical approximation is involved in deriving the moments, since the weighted Krawtchouk polynomials are discrete. These properties make the Krawtchouk moments well suited as pattern features in the analysis of two-dimensional images. It is shown that the Krawtchouk moments can be employed to extract local features of an image, unlike other orthogonal moments, which generally capture the global features. The computational aspects of the moments using the recursive and symmetry properties are discussed. The theoretical framework is validated by an experiment on image reconstruction using Krawtchouk moments and the results are compared to that of Zernike, pseudo-Zernike, Legendre, and Tchebyscheff moments. Krawtchouk moment invariants are constructed using a linear combination of geometric moment invariants; an object recognition experiment shows Krawtchouk moment invariants perform significantly better than Hu's moment invariants in both noise-free and noisy conditions.


Donkey milk consumption exerts anti-inflammatory properties by normalizing antimicrobial peptides levels in Paneth's cells in a model of ileitis in mice.
In this study, we showed the beneficial effects of donkey milk (DM) on inflammatory damages, endogenous antimicrobial peptides levels and fecal microbiota profile in a mice model of Crohn's disease. Nowadays, new strategies of microbiome manipulations are on the light involving specific diets to induce and/or to maintain clinical remission. Interest of DM is explained by its high levels of antimicrobial peptides which confer it anti-inflammatory properties. C57BL/6 mice were orally administered with or without indomethacin for 5 days and co-treated with vehicle, DM or heated DM during 7 days. Intestinal length and macroscopic damage scores (MDSs) were determined; ileal samples were taken off for microscopic damage (MD), lysozyme immunostaining and mRNA α-defensin assessments. Ileal luminal content and fecal pellets were collected for lysozyme enzymatic activity and lipocalin-2 (LCN-2) evaluations. Fecal microbiota profiles were compared using a real-time quantitative PCR-based analysis. Administration of indomethacin caused an ileitis in mice characterized by (1) a decrease in body weight and intestinal length, (2) a significant increase in MDS, MD and LCN-2, (3) a reduction in both α-defensin mRNA expression and lysozyme levels in Paneth's cells reflected by a decrease in lysozyme activity in feces, and (4) a global change in relative abundance of targeted microbial communities. DM treatment significantly reduced almost of all these ileitis damages, whereas heated DM has no impact on ileitis. DM consumption exerts anti-inflammatory properties in mice by restoring the endogenous levels of antimicrobial peptides which contribute in turn to reduce microbiota imbalance.


Biology, Predatory Potential, Life Table, and Field Evaluation of Propylea dissecta (Coleoptera: Coccinellidae), Against Lipaphis erysimi (Hemiptera: Aphididae) on Broccoli.
Propylea dissecta (Mulsant) (Coleoptera: Coccinellidae) is one of the most promising ladybird beetle against many sucking pests. Predation rates, developmental biology, life table, and field assessment of this ladybird were examined against mustard aphid, Lipaphis erysimi (Kalt.) (Hemiptera: Aphididae), on broccoli. Data on the life history were collected at 23 ± 1°C and 70 ± 1% RH and were evaluated using the two-sex, age-stage life table. Results showed that the two-sex, age-stage life table-based net reproductive rate (R0) was 11.264 ± 6.197 offspring. The adult females lived longer (33.8 ± 2.356 d) than the adult males (32.2 ± 0.841 d). The fourth instar consumed most of L. erysimi (113.97 ± 5.76) compared to the other larval stages of the predator. Male (1,821) and female (2,673) consumed more aphids than larvae. The net consumption rate was 741.78 ± 89.91 aphids. Other aphidophagous predators such as Coccinella septempunctata L., Micraspis discolor (F.), Coccinella transversalis (F.), and syrphid (Diptera: Syrphidae) were also noted in broccoli. Our research showed that inoculative release of 150 or 200 adults per 1,000 m2 for two times on broccoli achieved a significant decrease in aphids L. erysimi and Brevicoryne brassicae L. (Hemiptera: Aphididae) (>95%). The release rate of 150 adults per 1,000 m2 for two times may, therefore, be recommended to manage the aphid population on broccoli.


Cultural and Social Predictors of Substance Abuse Recovery among American Indian and Non-American Indian Pregnant and Parenting Women.
Substance abuse is especially undesirable among pregnant or parenting women (PPW). As such, there is a need to examine the factors impacting positive treatment outcomes, particularly among American Indian/Alaska Native (AI/AN) PPW, as they are seeking substance abuse treatment at rates considerably higher than the national average. This study aimed to identify the social and cultural mechanisms that support their recovery. Qualitative analyses were used to identify mechanisms used by AI and non-AI PPW in their recovery. Several differences between AI and non-AI PPW emerged. AI participants mentioned their families more often as the reason why they wanted to become or stay sober. In addition to familial support, AI participants relied on a variety of other sources for assistance in their recovery. Many of the women had difficulty defining specific aspects of their culture, especially in relation to their recovery. However, for AI PPW, many aspects of AI culture were identified as they described their recovery, suggesting the often subtle ways culture can impact everyday life. Our findings indicated that women utilized cultural supports in different ways; therefore, it is necessary to help them define their culture in ways that are meaningful in their recovery.


Reporting quality of abstracts of veterinary randomized controlled trials.
To evaluate the adherence of veterinary randomized controlled trial (RCT) abstracts to the recommendations on minimum abstract information included in the Consolidated Standards of Reporting Trials (CONSORT) checklist for RCT abstracts and to identify characteristics associated with the number of CONSORT items reported. 212 abstracts representing all RCTs published in 5 general veterinary journals in 2013 and 2018. 2 investigators independently assessed whether each of the 15 CONSORT checklist items for abstracts applicable to veterinary medicine was reported. Generalized linear mixed models were built to explore associations of selected variables with the total number of checklist items reported. Abstracts included a median of 5 checklist items (range, 2 to 10 items). None met the recommendations for reporting participant recruitment and funding source. Less than 25% of abstracts met the recommendations for the title, participant eligibility criteria, primary outcome, randomization technique, blinding, numbers analyzed, primary outcome results, and harms to participants. The number of items reported was higher in abstracts of RCTs that included clinical patients (vs other participants; OR, 1.13; 95% CI, 1.05 to 1.22). The number of items reported did not significantly change over time. Results suggested that the reporting quality of abstracts of RCTs in general veterinary journals was suboptimal per CONSORT recommendations. Because abstracts may be the only reference material available in certain settings, improvements are warranted to ensure readers have the information they need to properly interpret reported findings.


Roles and competencies of nurses and physicians in shared decision-making in cardiac surgery: A scoping review.
Identification and synthesis of research data related to the roles and competencies of physicians and nurses that are prerequisites for careful shared decision-making with patients potentially undergoing cardiac surgery. A scoping review was conducted in accordance with the Joanna Briggs Institute's methodology for scoping reviews and the PRISMA Extension for Scoping Reviews. PubMed, EMBASE and CINAHL were searched from inception dates up to March 2022, to identify primary studies published in a peer-reviewed journal. Study selection, assessment of the methodological quality and data extracting of the included studies were done by at least two independent researchers. To describe the findings of the studies, an emergent synthesis approach was used to visualize a descriptive representation of professional roles and competencies in shared decision-making, in an overview. The systematic search revealed 10,055 potential papers, 8873 articles were screened on title and abstract and 76 full texts were retrieved. Eight articles were included for final evaluation. For nurses and physicians, 26 different skills were identified in the literature to practice shared decision-making in cardiac surgery. The skills that emerged were divided into five professional roles: moderator; health educator; data collector; psychological supporter and translator. This review specifies the professional roles and required competencies related to shared decision-making in cardiac surgery. Further research is needed to compare our findings with other clinical areas and from there to arrive at a professional division of roles between the different clinical disciplines involved. The visualization of generic shared decision-making competencies and roles should establish the professional division of positions between various clinical physician and nurse disciplines in order to create a treatment plan based on evidence, values, preferences and the patient's personal situation. No patient or public contribution.


Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria.
Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower microvascular function, respectively (P = .03); and 29% and 25% higher VO2, respectively. RHIs correlated with microvascular function in all children with malaria (P < .001) and all with severe malaria (P < .001). Children with malaria have decreased endothelial and microvascular function and increased oxygen consumption, likely contributing to the pathogenesis of the disease.


Effect of urogastrone on gastric secretion and serum gastrin concentration in patients with duodenal ulceration.
A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.


Evidence for the genetic unrelatedness of nosocomial vancomycin-resistant Enterococcus faecium strains in a pediatric hospital.
Vancomycin-resistant enterococci are now found with increasing frequency. Up to now, epidemiological studies of enterococci have been limited by the lack of convenient and accessible methods for comparing strains. In this study, we report an epidemiological investigation on 16 nosocomial vancomycin-resistant Enterococcus faecium strains isolated from 15 patients in four different wards of a children's hospital over a period of 17 months. Analysis of restriction fragment length polymorphism (RFLP) of total DNA and of ribosomal DNA regions (ribotyping) was used as a typing approach. Each strain produced a different total DNA RFLP pattern after HindIII and PvuII digestion, except for two strains that were isolated from a single patient and that gave indistinguishable patterns. In our system, ribotyping was less discriminative than RFLP of total DNA. This approach, therefore, shows the genetic unrelatedness of the nosocomial strains studied and excludes patient-to-patient strain transmission either in the same ward or between wards.


Heitmania gen. nov., a new yeast genus in Microbotryomycetes, and description of three novel species: Heitmania litseae sp. nov., Heitmania castanopsis sp. nov. and Heitmania elacocarpi sp. nov.
Nine anamorphic yeast strains isolated from various plant leaves collected in southern China were phylogenetically characterized based on sequences of the internal transcribed spacer (ITS) region, the D1/D2 domains of the large subunit (LSU) rRNA gene, the small subunit (SSU) rRNA gene, the two subunits of the RNA polymerase II gene (RPB1 and RPB2) and the translation elongation factor 1-α (TEF1). Phylogenetic analysis of the combined sequences of the six genes showed that the new strains formed a distinct clade in the class Microbotryomycetes but could not be assigned to any of the existing genera, families or orders of the class. Three separate groups were consistently resolved from the nine new strains based on the combined sequences of the six genes and single gene sequences of ITS, RPB1, RPB2 and TEF1. The results suggest that the nine yeast strains compared represent three novel species in a novel genus. The names Heitmania gen. nov. (MycoBank registration number MB819987), Heitmania litseae sp. nov. (MB820112, type strain CGMCC 2.5697T=CBS 14756T), Heitmania castanopsis sp. nov. (MB819988, CGMCC 2.5698T=CBS 14750T) and Heitmania elacocarpi sp. nov. (MB820113, CGMCC 2.5695T=CBS 14752T) are proposed for the new taxa.


Prevention of sexually transmitted diseases (STDs) in female sex workers: prospective evaluation of condom promotion and strengthened STD services.
In Perú, a previous study of government-sponsored periodic examinations of female sex workers (FSWs) found no significant impact on rates of sexually transmitted diseases (STDs). This study assessed the impact of technically improved periodic STD services on STD prevalence and on consistent condom use (CCU). The study involved monthly follow-up of 917 FSWs at two STD clinics, with evaluations before and during implementation of strengthened STD services, which included periodic screening and treatment for gonorrhea, chlamydial infection, trichomoniasis, bacterial vaginosis (BV), and syphilis; counseling; and supply of condoms. Outcome analyses were adjusted for participation bias. During 7908 person-months of observation, the prevalences of gonorrhea, chlamydial infection, trichomoniasis, and BV declined significantly and CCU increased significantly, with similar trends in both clinics. During follow-up, gonorrhea, chlamydial infection, trichomoniasis, and BV were negatively associated with follow-up after screening. BV also was positively associated with use of an intrauterine device and negatively with douching. CCU during follow-up was associated with significantly decreased risk of gonorrhea, chlamydial infection, and trichomoniasis. Strengthened periodic screening for and treatment of confirmed STD, in addition to condom promotion and provision, represent feasible, effective interventions in commercial sex, and time series analyses can provide a useful approach to evaluating new interventions.


Production and partial purification of membrane proteins using a liposome-supplemented wheat cell-free translation system.
Recently, some groups have reported on cell-free synthesis of functional membrane proteins (MPs) in the presence of exogenous liposomes (liposomes). Previously, we reported synthesis of a functional AtPPT1 plant phosphate transporter that was associated with liposomes during translation. However, it is unclear whether or not lipid/MP complex formation is common to all types of MPs in the wheat cell-free system. AtPPT1 was synthesized using a wheat cell-free system with or without liposomes. AtPPT1 synthesized with liposomes showed high transport activity, but the activity of AtPPT1 synthesized without liposomes was less than 10% activity of that with liposomes. To test whether co-translational association with liposomes is observed in the synthesis of other MPs, we used 40 mammalian MPs having one to 14 transmembrane domains (TMDs) and five soluble proteins as a control. The association rate of all 40 MPs into liposomes was more than 40% (mean value: 59%), while that of the five soluble proteins was less than 20% (mean value: 12%). There were no significant differences in association rate among MPs regardless of the number of TMDs and synthesis yield. These results indicate that the wheat cell-free system is a highly productive method for lipid/MP complex formation and is suitable for large-scale preparation. The liposome association of green fluorescent protein (GFP)-fusion MPs were also tested and recovered as lipid/MP complex after floatation by Accudenz density gradient ultracentrifugation (DGU). Employment of GFP-MPs revealed optimal condition for Accudenz floatation. Using the optimized Accudenz DGU condition, P2RX4/lipid complexes were partially purified and detected as a major band by Coomassie Brilliant Blue (CBB)-staining after SDS-PAGE. Formation of lipid/AtPPT1 complex during the cell-free synthesis reaction is critical for synthesis of a functional MP. The lipid/MP complex during the translation was observed in all 40 MPs tested. At least 29 MPs, as judged by their higher productivity compared to GFP, might be suitable for a large-scale preparation. MPs synthesized by this method form lipid/MP complexes, which could be readily partially purified by Accudenz DGU. Wheat cell-free protein synthesis in the presence of liposomes will be a useful method for preparation of variety type of MPs.


Predictive factors of disease-free survival after complete pathological response to neoadjuvant radiotherapy for rectal adenocarcinoma: retrospective case series.
Many data suggest that patients with low rectal adenocarcinoma who achieved ypT0N0 status have improved survival and disease-free survival (DFS) compared to all other stages however only few data are available regarding the specific prognosis factors of this subgroup. This study aimed to evaluate predictive factors for disease free survival after complete pathological response (CPR) in cases of low rectal adenocarcinoma. From January 2005 to December 2013, all patients with low rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision and achieved CPR were included at 7 Moroccan and 1 Algerian centres. Predictive factors for disease-free survival were analysed by uni and multivariate analysis. Eigthy-four (12.1%) patients achieved a CPR (ypT0N0). Multivariate analysis revealed that both poorly differentiated tumors (OR, 9.23; 95 CI 1.35-62.82; P = 0.023) and the occurrence of perineal sepsis (OR, 13.51; 95 CI 1.96-93.12; P = 0.008) were independently associated with impaired DFS. Patients with low rectal cancer who exhibited a CPR after neoadjuvant therapy have good prognoses; however, the occurrence of perineal sepsis and/or poor initial differentiation may be associated with impaired DFS in these patients. The study was retrospectively registered the 28th July 2018 in ClinicalTrials.gov register with the reference NCT03601689.


Thriving under pressure: The effects of stress-related wise interventions on affect, sleep, and exam performance for college students from disadvantaged backgrounds.
Nearly all students experience stress as they pursue important academic goals. Because stress can be magnified for students from disadvantaged backgrounds, it becomes important to identify interventions that can help mitigate this stress, particularly for these populations as they enter academic environments. We examine the effects of stress mindset and stress management interventions administered to students from disadvantaged backgrounds (N = 140) before freshman year. We compare effects on affect, sleep, and performance during end-of-year exams seen in a subset of these students who could be tracked via experience sampling (N = 57) to those of a comparison group at the same elite university (N = 74) receiving no such stress interventions. As predicted, we find significant differences in exam-week positive affect between the stress mindset and comparison groups. However, there was no difference in positive affect between the stress mindset and management groups or the stress management and comparison groups. For negative affect, stress, sleep, and exam performance, we find no significant differences between any of the three groups. However, both stress interventions decoupled the significant negative association between exam-week stress and exam performance exhibited by the comparison group, rendering the relationship nonsignificant. The reduction in this association was somewhat more pronounced for the mindset relative to the management group. These findings suggest that mindset and management approaches both confer benefits in certain circumstances and highlight the potential value of targeting mindsets about stress using a "wise intervention" approach for students from disadvantaged backgrounds during stressful times. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Vasoactive Drugs and Hemodynamic Monitoring in Pediatric Cardiac Intensive Care: An Italian Survey.
Little is known about practitioner preference, the availability of technology, and variability in practice with respect to hemodynamic monitoring and vasoactive drug use after congenital heart surgery. The aim of this study was to characterize current hospital practices related to the management of low cardiac output syndrome (LCOS) across Italy. We issued a 22-item questionnaire to 14 Italian hospitals performing pediatric cardiac surgery. Electrocardiogram, invasive blood pressure, central venous pressure, pulse oximetry, diuresis, body temperature, arterial lactate, and blood gas analysis were identified as routine in hemodynamic monitoring. With regard to advanced hemodynamic monitoring, pulmonary arterial catheter and transpulmonary thermodilution were available in 43% of the centers, uncalibrated pulse contour methods in 29% of the centers, and transesophageal/transthoracic echocardiograms in all of the centers. Dopamine added to milrinone was the most frequent drug regimen for LCOS prevention after cardiopulmonary bypass. Overall, 86% of centers used milrinone alone as the initial treatment for LCOS with elevated systemic vascular resistances and levosimendan, the second preferred choice. In cases of LCOS with low vascular resistance, epinephrine was the first choice (10 centers), dopamine was the second choice (4 centers), followed by vasopressin and norepinephrine (3 centers). For treatment of LCOS with elevated pulmonary resistances, milrinone was the first choice (eight centers), followed by inhaled nitric oxide (five centers). The survey shows that advanced hemodynamic monitoring is rarely performed. The most commonly used vasoactive drugs are milrinone, levosimendan, dopamine, epinephrine, vasopressin, and norepinephrine. Guidelines on the topic are warranted.


Stabilizing and Enhancing Link Prediction through Deepened Graph Auto-Encoders.
Graph neural networks have been widely used for a variety of learning tasks. Link prediction is a relatively under-studied graph learning task, with current state-of-the-art models based on one- or two-layer shallow graph auto-encoder (GAE) architectures. In this paper, we overcome the limitation of current methods for link prediction of non-Euclidean network data, which can only use shallow GAEs and variational GAEs. Our proposed methods innovatively incorporate standard auto-encoders (AEs) into the architectures of GAEs to capitalize on the intimate coupling of node and edge information in complex network data. Empirically, extensive experiments on various datasets demonstrate the competitive performance of our proposed approach. Theoretically, we prove that our deep extensions can inclusively express multiple polynomial filters with different orders. The codes of this paper are available at https://github.com/xinxingwu-uk/DGAE.


[Spatial and temporal characteristics of flue-cured tobacco water requirement and irrigation requirement index in Yunnan Province, China].
Based on the daily meteorological data of 124 agricultural meteorological sites during 1977-2010 in Yunnan Province, using recommended Penman-Monteith formula by FAO, water requirement and irrigation requirement index in the growth period of flue-cured tobacco were calculated to analyze their spatial and temporal characteristics and change patterns. The results showed that water requirements of flue-cured tobacco in root extending, vigorous, mature periods and field growth period during 1977-2010 were 76.73-174.73, 247.50-386.64, 180.28-258.14 and 528.18-764.08 mm, respectively, and the water requirement of vigorous period was the highest. The average irrigation demand index of each period was -0.02, 0.38, 0.17 and 0.26, respectively. Effective precipitation could meet the demand of flue-cured tobacco in root extending period. Water requirement of flue-cured tobacco in Yunnan Province decreased annually, and the rates of water requirement under the climate change trend in the four periods abovementioned were -12. 42, -21.46, -7.17 and -47.15 mm . (10 a)-1, respectively. The smallest irrigation demand index was observed in Dehong, and the largest in Diqing. The irrigation demand indexes of Dehong, Xishuangbanna and Puer regions were negative in flue-cured tobacco field growth period. The reference crop evapotranspiration, water requirement and effective precipitation decreased, but the irrigation requirement and irrigation requirement index increased with the increase of latitude. The effective precipitation decreased, but the irrigation requirement and irrigation requirement index increased with the increase of altitude.


MRGBP as a potential biomarker for the malignancy of pancreatic ductal adenocarcinoma.
MORF4-related gene-binding protein (MRGBP), which is also known as chromosome 20 open reading frame 20 (C20orf20), is commonly highly expressed in several types of malignant tumors and tumor progression. However, the expression pattern and underlying mechanism of MRGBP in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In the study, we found that MRGBP was frequently upregulated in PDAC tissues and cell lines. In addition, the upregulation of MRGBP was positively associated with TNM stage, T classification, and poor prognosis. Knockdown of MRGBP in the PDAC cell lines ASPC-1 and Mia PaCa-2 by transiently transfected with small interfering RNA (siRNA) drastically attenuated the proliferation, migration, and invasion of those cells, whereas ectopic MRGBP overexpression in BxPC-3 cells produced exactly the opposite effect. Furthermore, we also found that overexpression of MRGBP remarkably led to cell morphological changes and induced an increased expression of mesenchymal marker Vimentin, whereas a decreased expression of epithelial marker E-cadherin. Taken together, this study indicates that MRGBP acts as a tumor oncogene in PDAC and is a promising target of carcinogenesis.


[Synchronous manifestation of bladder inverted papilloma and transitional carcinoma of the renal pelvis].
To review briefly the histological and biological aspects of inverted papilloma and to determine whether it is a benign tumor or low-grade malignant lesion. We report a patient with synchronous presentation of bladder inverted papilloma and renal pelvis transitional cell carcinoma. After endoscopic resection of the bladder tumor and left ureteral meatus, a radical nephroureterectomy was carried out with success. The clinical features, diagnostic and therapeutic aspects are briefly reviewed. Inverted papilloma accounts for 2.2% of all urothelial tumors; the bladder is most commonly involved. It is frequently a single lesion with endophytic growth pattern. The clinical significance remains a controversy. Most investigators consider them as benign neoplastic tumors, although in one third of the patients it may be associated with synchronous urothelial carcinomas, implying a malignant condition. Therapeutic management and follow-up are emphasized.


Long-term orthodontic and surgical treatment and stability of a patient with Beckwith-Wiedemann syndrome.
Beckwith-Wiedemann syndrome (BWS) is a congenital growth disorder. Children born with BWS develop enlarged organs, including the tongue, a large body, and other signs. A woman with BWS was treated and followed for 30 years. Treatment consisted of tongue reduction, orthopedic and orthodontic treatment, orthognathic surgery, and retention. The patient was first treated when she was 5 years old. Her original orthodontic problems included macroglossia, anterior open bite, anterior crossbite, and a skeletal Class III jaw relationship caused by significant mandibular protrusion. The jaw-base relationships did not improve in the early preadolescent period after phase 1 of orthodontic treatment with a vertical chincap. With the growth spurt accompanying puberty, she developed a severe skeletal Class III jaw relationship and a constricted maxillary arch. Surgically assisted rapid maxillary expansion was performed at 23 years of age to correct the severe discrepancy between the maxillary and mandibular dental arch widths. Then, at 26 years, a LeFort I osteotomy, a horseshoe osteotomy, a bilateral sagittal split ramus osteotomy, and genioplasty were performed after presurgical orthodontic treatment with extraction of the mandibular first molars. Both the facial profile and the occlusion were stable after 6 years of retention. This case report discusses the result of long-term observation of a patient with BWS who underwent tongue reduction, early orthodontic treatment, and surgical-orthodontic treatment.


Brain-IL-1 beta triggers astrogliosis through induction of IL-6: inhibition by propranolol and IL-10.
Gliosis is a characteristic pathology in many central nervous system (CNS) diseases. Cytokines are considered to be effectors of gliosis. It has been shown that pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 boost glia scar formation. On the other hand, anti-inflammatory cytokines, such as IL-10 and IL-1 receptor antagonist (ra), can act neuroprotectively. Furthermore, various immune mediators and neurotransmitters can modulate the onset of gliosis. We used 100 male Sprague-Dawley rats to investigate the mechanisms of brain-cytokine-induced astrogliosis using an in vivo model of convection-enhanced delivery of cytokines (IL-beta, IL-6, tumor necrosis factor (TNF)-alpha) into the cerebro-ventricular system. The protective effects of the anti-inflammatory cytokine IL-10 and the neurotransmitter propranolol were also investigated. With this paradigm, we could clearly demonstrate that IL-6 is a key cytokine mediating astrogliosis, noticeable in the increased expression of glial fibrillary acidic protein (GFAP). Thus intra-cerebroventricular infusion of IL-6 increased GFAP expression in a dose-dependent manner. Furthermore, GFAP expression was also increased by IL-beta, which correspondingly triggered an IL-6 release into the CSF. Accordingly, TNF-alpha, which did not induce IL-6 release, also did not induce gliosis. On the other hand, substances which decrease IL-beta-induced IL-6 production, such as propranolol and IL-10, also dramatically decreased IL-beta triggered gliosis. IL-6 infusion, as well as IL-beta-induced IL-6 release into the CSF, increase GFAP expression in the cerebral cortex and hippocampus. Accordingly, blockade of the IL-beta-induced IL-6 release by IL-10 and propranolol decreases GFAP expression.


Long-term objective assessments of skin rejuvenation using solar protection and solar repair shown through digital facial surface analysis and three-dimensional volumetric assessment.
Despite the knowledge that the vast majority of skin aging is caused by the sun, and the widespread prevalence of sunscreen usage, solar skin damage continues to occur due to the combined biological impact of ultraviolet, visible light and near-infrared radiation. Sunscreens have only proven effective at filtering ultraviolet light. They do not attenuate visible light or near-infrared. To evaluate the effectiveness of a novel, solar-specific skincare approach embracing both comprehensive daily solar protection from ultraviolet through to near-infrared radiation and nightly solar repair. Eighteen Japanese patients were enrolled in this study. Topical skincare products (The Essential Six, RATIONALE, Victoria, Australia), comprising solar protection preparations to be used in the morning and topical solar repair at night, were applied to the patients' skin for 12 months. Patients refrained from using any other skincare formulations and did not undergo any form of medical esthetic treatment during the study. Digital facial skin and three-dimensional volumetric assessment were performed pre- and post-treatment, and patient assessments were recorded after 6 and 12 months post-treatment. Improvements in skin texture and luminosity as recorded via digital photography, significant amelioration of skin redness and pigmentation in facial surface analysis, and volumetric reduction in three-dimensional volumetric assessment were observed compared to the pre-treatment for all patients. Eighty-nine percent, and 94% of patients self-reported their approval of treatment outcomes after 6 and 12 months post-treatment, respectively. Minor complications, characterized by slight pain and itching were observed in 3 patients. These minor complications resolved spontaneously. The results of this study indicate that the solar-specific skincare formulations focused on the daily comprehensive prevention of negative solar effects and nightly repair of photodamage provide a safe and highly effective pathway to skin preservation and rejuvenation.


Both duration and degree of hypercalcemia influence the reduced parathyroid hormone response to hypocalcemia after hypercalcemia.
The stimulation of parathyroid hormone (PTH) secretion by hypocalcemia is reduced when hypocalcemia is preceded by hypercalcemia. The present study investigates whether the duration and degree of hypercalcemia influence the reduced PTH response to hypocalcemia after hypercalcemia. In addition, the implication of the arachidonic acid (AA) signaling pathway in this effect is evaluated. The PTH response to hypocalcemia has been studied in a control group and in four groups of rabbits subjected to hypercalcemia for different periods of time (between 30 and 120 min) and at two levels of hypercalcemia (1 x 9 and 2 x 1 mM). AA levels have been measured in parathyroid glands from rabbits subjected to hyper- and hypocalcemia. When compared with controls, rabbits that had been hypercalcemic (2 x 1 mM) for 2 h showed a markedly attenuated PTH response to hypocalcemia (50% of normal PTHmax), rabbits that had been in hypercalcemia (2 x 1 mM) for 75 min had an intermediate PTH response to hypocalcemia (70% of normal PTHmax) and rabbits that had been subjected to either 30 min hypercalcemia of 2 x 1 mM or 120 min hypercalcemia of 1 x 9 mM had a normal PTH response to hypocalcemia. AA levels increased in hypercalcemia and decreased in hypocalcemia; however, no differences were observed at either calcium level in short-time (30 min) versus long-time (120 min) hypercalcemia. In conclusion, the attenuated PTH response to hypocalcemia after hypercalcemia is dependent on both the period of time that the parathyroid glands have been exposed to hypercalcemia and the degree of hypercalcemia. In addition, this reduced PTH response does not seem to be related to changes in the AA signaling pathway.


A cluster randomized controlled trial of the Promoting Alternative Thinking Strategies (PATHS) curriculum.
This randomized controlled trial (RCT) evaluated the efficacy of the Promoting Alternative Thinking Strategies curriculum (PATHS; Kusche & Greenberg, 1994) as a means to improve children's social-emotional competence (assessed via the Social Skills Improvement System (SSIS); Gresham & Elliot, 2008) and mental health outcomes (assessed via the Strengths and Difficulties Questionnaire (SDQ); Goodman, 1997). Forty-five schools in Greater Manchester, England, were randomly assigned to treatment and control groups. Allocation was balanced by proportions of children eligible for free school meals and speaking English as an additional language via minimization. Children (N=4516) aged 7-9years at baseline in the participating schools were the target cohort. During the two-year trial period, teachers of this cohort in schools allocated to the intervention group delivered the PATHS curriculum, while their counterparts in the control group continued their usual provision. Teachers in PATHS schools received initial training and on-going support and assistance from trained coaches. Hierarchical linear modeling of outcome data was undertaken to identify both primary (e.g., for all children) and secondary (e.g., for children classified as "at-risk") intervention effects. A primary effect of the PATHS curriculum was found, demonstrating increases in teacher ratings of changes in children's social-emotional competence. Additionally, secondary effects of PATHS were identified, showing reductions in teacher ratings of emotional symptoms and increases in pro-social behavior and child ratings of engagement among children identified as at-risk at baseline. However, our analyses also identified primary effects favoring the usual provision group, showing reductions in teacher ratings of peer problems and emotional symptoms, and secondary effects demonstrating reductions in teacher ratings of conduct problems and child ratings of co-operation among at-risk children. Effect sizes were small in all cases. These mixed findings suggest that social and emotional learning interventions such as PATHS may not be as efficacious when implemented outside their country of origin and evaluated in independent trials.


Benzene and total hydrocarbon exposures in the upstream petroleum oil and gas industry.
Occupational exposures to benzene and total hydrocarbons (THC) in the Canadian upstream petroleum industry are described in this article. A total of 1547 air samples taken by 5 oil companies in various sectors (i.e., conventional oil/gas, conventional gas, heavy oil processing, drilling and pipelines) were evaluated and summarized. The data includes personal long- and short-term samples and area long-term samples. The percentage of samples over the occupational exposure limit (OEL) of 3.2 mg/m3 or one part per million for benzene, for personal long-term samples ranges from 0 to 0.7% in the different sectors, and area long-term samples range from 0 to 13%. For short-term personal samples, the exceedance for benzene is at 5% with respect to the OEL of 16 mg/m3 or five parts per million in the conventional gas sector and none in the remaining sectors. THC levels were not available for all sectors and had limited data points in others. The percentage exceedance of the OEL of 280 mg/m3 or 100 parts per million for THC as gasoline ranged from 0 to 2.6% for personal long-term samples. It is recommended that certain operations such as glycol dehydrators be carefully monitored and that a task-based monitoring program be included along with the traditional long- and short-term personal exposure sampling.


Facial wrinkles as a predictor of decreased renal function.
Oxidative stress generated either by exogenous or endogenous sources can lead to progressive organ damage and skin ageing over a long period of time. Moreover, some dermatological signs are independent of chronological ageing, and may reflect the long-term redox state of internal organs. Therefore, we hypothesized that there might be an association between facial wrinkles and decreased renal function, an oxidative stress-related disease. A cross-sectional study was carried out in a Korean population of 264 adults aged 30 years and older. Facial wrinkle scores in the crow's-foot area were estimated using a standardized form of visual assessment. As an index of renal function, we determined estimated glomerular filtration rate (eGFR). Lipid hydroperoxide (LPO) assay was performed to measure the levels of oxidative stress. After adjusting for possible confounders, lower eGFRs and higher LPO levels were found in those with severe facial wrinkles. We conclude that severe facial wrinkles might be used as a predictive marker of decreased renal function, independently of age, gender and other established risk factors.


Distributed and accumulated reinforcement arrangements: evaluations of efficacy and preference.
We assessed the efficacy of, and preference for, accumulated access to reinforcers, which allows uninterrupted engagement with the reinforcers but imposes an inherent delay required to first complete the task. Experiment 1 compared rates of task completion in 4 individuals who had been diagnosed with intellectual disabilities when reinforcement was distributed (i.e., 30-s access to the reinforcer delivered immediately after each response) and accumulated (i.e., 5-min access to the reinforcer after completion of multiple consecutive responses). Accumulated reinforcement produced response rates that equaled or exceeded rates during distributed reinforcement for 3 participants. Experiment 2 used a concurrent-chains schedule to examine preferences for each arrangement. All participants preferred delayed, accumulated access when the reinforcer was an activity. Three participants also preferred accumulated access to edible reinforcers. The collective results suggest that, despite the inherent delay, accumulated reinforcement is just as effective and is often preferred by learners over distributed reinforcement.


Acute otitis media--a brief explanation to parents and antibiotic use.
Acute otitis media (AOM) is a common self-limiting disease in children. Antibiotic use is controversial. Physicians in the USA and in Israel prescribe antibiotics almost universally, while physicians in other countries report good outcome without any treatment. Parents' expectation is an important factor influencing a physician's decision to prescribe antibiotics. Our aim was to assess whether a brief explanation to parents regarding the self-limited nature of AOM and the controversy regarding antibiotic prescription for the disease will influence the parents' decision regarding antibiotics use. Parents of the children participating in the study in two primary care clinics belonging to HMO-Clalit Health Services (CHS) in the southern district of Israel were randomly assigned to an intervention (44) and control (37) group. The intervention group received the brief explanation. The two groups received prescription for antibiotics. The subjects comprised 81 children aged 3 months to 4 years visiting the family practice clinics and diagnosed with AOM. The rate of antibiotics purchase, using the prescription given and the factors influencing the decision were evaluated. Fewer parents administered antibiotics to their children in the intervention group compared with the control group (37% versus 63%, respectively, P < 0.0001). Mother's education level was the only factor found to be significantly lower in the group that eventually purchased antibiotics (P < 0.05). In children with AOM, a brief explanation by the family physician to the child's parents about the disease and the expected spontaneous recovery could decrease antibiotic use by approximately 50%.


Healing Childhood Psychological Trauma and Improving Body Image Through Cosmetic Surgery.
Cosmetic surgery is an interdisciplinary field involving cosmetics and medicine that stems from the early modern obsession with disfigurement. The "correcting" of facial features and body parts was very likely because beauty was at the heart of most reconstructive desires. Cosmetic surgery patients typically experience improvements in body image, and some are very satisfied with the impact of cosmetic surgery in changing their behaviors and improving self-esteem. The doctrine of mind-body connection supports the concept of healing the heart through the body. However, some people feel disgraced after revealing their experiences of cosmetic surgery. It is known that people who experience childhood psychological trauma, such as abuse and school bullying, may opt for cosmetic surgery later in life. The present study aimed to explore the relationship between childhood psychological trauma, cosmetic surgery, and body image. Three female adults who had undergone different types of cosmetic surgery completed the Acceptance of Cosmetic Surgery Scale (ACSS), the Fear of Negative Appearance Evaluation Scale (FNAES), and the Multidimensional Body-Self Relations Questionnaire (MBSRQ), followed by semistructured face-to-face interviews. According to the results, 1) undergoing cosmetic surgery can enhance self-confidence, reduce body dissatisfaction, resolve inner conflicts, and somewhat relieve psychological distress; 2) self-esteem and body image obtained from cosmetic surgery can resolve the distressing aftereffects of childhood trauma that occur later in life; and 3) the perceived sense of beauty achieved from cosmetic surgery contributes to a certain degree of self-confidence in the short term and promotes appearance-enhancing behaviors while increasing the distress of others discovering their cosmetic surgery experiences. The implications of this study are that undergoing cosmetic surgery can have healing effects on childhood trauma; however, there are certain drawbacks that can occur, such as distress and an insatiable desire for or an "addiction" to surgery.


Asthma and gastroesophageal reflux: acid suppressive therapy improves asthma outcome.
To determine (1) the appropriate omeprazole (Prilosec) dose required for adequate acid suppression in asthmatics with gastroesophageal reflux, (2) whether aggressive acid suppressive therapy of gastroesophageal reflux improves asthma outcome in asthmatics with gastroesophageal reflux, (3) the time course of asthma improvement, and (4) demographic, esophageal, or pulmonary predictors of a positive asthma response to antireflux therapy. Thirty nonsmoking adult asthmatics with gastroesophageal reflux (asthma defined by American Thoracic Society criteria and reflux defined by symptoms and abnormal 24-hour esophageal pH testing) were recruited from the outpatient clinics of a 900-bed university hospital. Patients underwent baseline studies including a demographic questionnaire, esophageal manometry, dual-probe 24-hour esophageal pH test, barium esophogram, and pulmonary spirometry. During the 4-week pretherapy phase, patients recorded reflux and asthma symptom scores and peak expiratory flow rates (PEFs) upon awakening, 1 hour after dinner, and at bedtime. Patients began 20 mg/d omeprazole, and the dose was titrated until acid suppression was documented by 24-hour pH test. Patients remained on this acid suppressive dose for 3 months. Responders were identified by a priori definitions: asthma symptom reduction by >20% and/or PEF increase by >20%. Asthma symptom scores, PEF's baseline and posttherapy pulmonary spirometry were analyzed. Twenty-two (73%) patients were asthma symptom and /or PEF responders: 20 (67%) were asthma symptom responders, and 6 (20%) were PEF responders. Responders reduced their asthma symptoms by 57% (P<0.001), improved their morning and night PEFs by 8% and 9% (both P <0.005), and had improvement in forced expiratory volume at 1 second (P <0.02), mean forced expiratory flow during the middle half (25% to 75%) of the forced vital capacity (P <0.04), and peak expiratory flow (P <0.01) with acid suppressive therapy. Mean acid suppressive dose of omeprazole was 27 mg/d (+/-2.2) with 27% (8) patients requiring more than 20 mg/d. The presence of regurgitation or excessive proximal esophageal reflux predicted asthma response with 100% sensitivity, 100% negative predictive value, specificity of 44% and a positive predictive value of 79%. Acid suppressive therapy with omeprazole improves asthma symptoms and/or PEFs by >20% and improves pulmonary function in 73% of asthmatics with gastroesophageal reflux after 3 months of acid suppressive therapy. Many asthmatics (27%) required >20 mg/d of omeprazole to suppress acid. The presence of regurgitation and/or excessive proximal esophageal reflux predicts a positive asthma outcome.


WNT2 promoter methylation in human placenta is associated with low birthweight percentile in the neonate.
Neonates with birthweights below the tenth percentile for gestational age are considered small for gestational age (SGA). Such infants have an increased risk for perinatal mortality and morbidity as well as an increased lifetime risk for adult onset disorders. Low birth weight percentile is etiologically heterogeneous and may result from maternal, fetal, placental and environmental factors. However, the molecular determinants of human SGA are not well elucidated. We proposed that fetal growth potential could be negatively impacted by the epigenetic dysregulation of specific genes in the placenta. Using methyl DNA immunoprecipitation coupled with Agilent CpG island microarrays, we analyzed the differences in DNA methylation between placentas of eight SGA neonates and eight controls with birthweight percentiles above the tenth percentile. We identified several candidate genomic regions with differential DNA methylation between the two groups. The DNA methylation differences identified in the promoter of the WNT2 gene were prioritized for further study in an extended cohort of 170 samples given the important function of this gene in mouse placental development and its high expression in human placenta. High WNT2 promoter methylation (WNT2PrMe) was found only in placental tissue and not in the cord blood of the fetus. It was significantly associated with reduced WNT2 expression in placenta and with low birthweight percentile in the neonate. Our results show that WNT2 expression can be epigenetically downregulated in the placenta by DNA methylation of its promoter and that high WNT2PrMe is an epigenetic variant that is associated with reduced fetal growth potential. Note: All of the array data in the manuscript can be accessed from the Gene Expression Omnibus (GEO) NCBI database under GEO accession number GSE22326.


Non-covalent complexes of the peptide fragment Gly-Asn-Asn-Gln-Gln-Asn-Tyr in the gas-phase. Photodissociative cross-linking, Born-Oppenheimer molecular dynamics, and ab initio computational binding study.
Non-covalent complexes of the short amyloid peptide motif Gly-Asn-Asn-Gln-Gln-Asn-Tyr (GNNQQNY) with peptide counterparts that were tagged with a diazirine ring at the N-termini (*GNNQQNY) were generated as singly charged ions in the gas phase. Specific laser photodissociation (UVPD) of the diazirine tag in the gas-phase complexes at 355 nm generated transient carbene intermediates that underwent covalent cross-linking with the target GNNQQNY peptide. The crosslinking yields ranged between 0.8 and 4.5%, depending on the combinations of peptide C-terminal amides and carboxylates. The covalent complexes were analyzed by collision-induced dissociation tandem mass spectrometry (CID-MS3), providing distributions of cross-links at the target peptide amino acid residues. A general preference for cross-linking at the target peptide Gln-4-Gln-5-Asn-6-Tyr-7 segment was observed. Born-Oppenheimer molecular dynamics calculations were used to obtain 100 ps trajectories for nine lowest free-energy conformers identified by ωB97X-D/6-31+G(d,p) gradient geometry optimizations. The trajectories were analyzed for close contacts between the incipient carbene atom and the X-H bonds in the target peptide. The close-contact analysis pointed to the Gln-5 and Tyr-7 residues as the most likely sites of cross-linking, consistent with the experimental CID-MS3 results. Non-covalent binding in the amide complexes was evaluated by DFT calculations of structures and energies. Although antiparallel arrangements of the GNNQQNY and *GNNQQNY peptides were favored in low-energy gas-phase and solvated complexes, the conformations and peptide-peptide interface surfaces were found to differ from the secondary structure of the dry interface in GNNQQNY motifs of amyloid aggregates.


USP24 stabilizes bromodomain containing proteins to promote lung cancer malignancy.
Bromodomain (BRD)-containing proteins are important for chromatin remodeling to regulate gene expression. In this study, we found that the deubiquitinase USP24 interacted with BRD through its C-terminus increased the levels of most BRD-containing proteins through increasing their protein stability by the removal of ubiquitin from Lys391/Lys400 of the BRD. In addition, we found that USP24 and BRG1 could regulate each other through regulating the protein stability and the transcriptional activity, respectively, of the other, suggesting that the levels of USP24 and BRG1 are regulated to form a positive feedback loop in cancer progression. Loss of the interaction motif of USP24 eliminated the ability of USP24 to stabilize BRD-containing proteins and abolished the effect of USP24 on cancer progression, including its inhibition of cancer cell proliferation and promotion of cancer cell migration, suggesting that the interaction between USP24 and the BRD is important for USP24-mediated effects on cancer progression. The targeting of BRD-containing proteins has been developed as a strategy for cancer therapy. Based on our study, targeting USP24 to inhibit the levels of BRD-containing proteins may inhibit cancer progression.


Demographic adjustments to driver death rates by vehicle type and size.
Driver death rates per million registered vehicles are often used to compare the real-world crash experiences of vehicles of different types and sizes. However, these rates are affected by the risky behavior of drivers (e.g., speeding, impaired driving, lack of restraint use) that differs by age and gender. This paper presents a method for adjusting driver death rates to account for differences in driver age and gender. Driver death rates per million registered vehicles per year were calculated for passenger vehicles of model year 2020. To account for potential differences in driver exposure by age and gender, which can affect motor vehicle crash and injury experience, an algebraic method was used to standardize these rates to a common distribution of female drivers ages 25-64. The standardization depends upon an independent estimate of the relative fatality risk for female drivers ages 25-64. The smallest vehicles tended to have higher driver death rates compared with larger vehicles. However, for sports cars, this trend was reversed; larger sports cars had higher driver death rates. Vehicle types popular with male drivers, such as sports cars and pickups, had standardized death rates that were much lower than the raw rates. The adjustment for driver age and gender greatly reduced the variability of driver death rates among vehicle types. The procedure used here to adjust driver death rates for driver age and gender can be extended to any situation where it is desired to compare the crash rates of two or more subgroups of a population.


Decreased cardiac responses to auditory stimulation during prone sleep.
To evaluate the relationship between body position during sleep and the infants' cardiac responses to auditory stimulation. Thirty healthy infants with a median age of 11 weeks were studied polygraphically for one night, while sleeping successively prone and supine, or vice versa. Their behavioral and cardiac responses were recorded during rapid eye movement (REM) sleep, both before and after exposure to 90 dB (A) of white-noise. Ten infants were excluded from the study, because they woke up during the challenge. For the 20 infants included in the analysis, no significant difference was seen between the prone and the supine position for total sleep time, sleep efficiency, percent of REM and nonrapid eye movement sleep, number of gross body movements, transcutaneous oxygen saturation levels, mean cardiac rate, heart rate variability, number of heart rate drops; mean respiratory rate, and number or duration of central or obstructive apneas. Auditory challenges induced significantly less overall changes in heart rate, less heart rate drops, less heart rate variability, as well as fewer and shorter central apneas in the prone than in the supine position. Autoregressive power spectral analysis of the heart rate was consistent with a possible increase in orthosympathetic tone in the prone position. Prone sleeping was associated with a decrease in cardiac responses to auditory stimulation and a possible increase in orthosympathetic activity. Prone positioning could favor a reduced reactivity to danger-signaling stimuli during REM sleep.


Polymeric cyclosporine-A nanoparticles for ocular application.
In the present study, cyclosporine A (CsA) was incorporated successfully into cationic Eudragit RS 100 nanoparticles (EPNs) aiming ocular application. Physicochemical characterization of the EPNs prepared was performed during the storage period of 6 months. Following in vitro release tests, sheep were used in in vivo studies where 100 microL of formulation was applied to both eyes (n = 6) under veterinarian supervision. Aqueous and vitreous humour samples were collected at predetermined time intervals and analyzed by enzyme immune assay (EIA). In vitro relase studies showed the extended release of the incorporated drug from the nanoparticles. However in vivo results demonstrated the prolonged residence time of CsA in the deeper layers (vitreous humour) of the eye with positively charged EPNs.


[The morphological changes in the internal organs in hemochromatosis].
Visceral changes were studied by histological and electron-microscopic methods in cadavers of 18 subjects dead from hemochromatosis. Pronounced visceral changes in all cases represented a characteristic tetrad of signs: bronze-colored skin, pigmentary cirrhosis of the liver, involvement of the pancreas, and cardiomyopathy. In forensic medical practice hemochromatosis can be found in subjects who were probably genetically predisposed to it and, as a rule, had a history of alcohol abuse. Among the numerous complications of the disease, the most incident are cardiac pathology (dilatation cardiomyopathy) and diabetes mellitus with concomitant intoxications caused by various inflammations.


Validity and Reliability of a 10 Hz GPS for Assessing Variable and Mean Running Speed.
Our purpose was to assess the 10 Hz Viper GPS devices' validity and reliability (STATSport) in both instantaneous and mean speed measuring in accelerations and decelerations in straight-line running conditions. Eight amateur team sport players participated in the study, performing firstly 21 x 40 m sprints at submaximal incremental speed, and secondly 21 x 40 m sprints, with the first stage consisting of submaximal incremental speed, and the second stage of subsequent submaximal decreasing speed. Criteria systems used to evaluate the GPS validity were a radar gun for instantaneous speed, and timing-gates for mean speed. Reliability was measured with two GPS devices carried by the same athlete, running 10 x (20 m + 20 m) sprints with a 180º change of direction and a 10 s inter-set rest interval. Results showed an agreement between GPS devices and the criteria systems measuring instantaneous speed (r = 0.98; standardized mean bias (SMB) = -0.07; standard typical error (STE) = 0.22) and mean speed (r = 0.99; SMB = 0.38; STE = 0.17). The reliability study presented a nearly perfect correlation between devices, a trivial SMB and a small STE (r = 0.97; SMB = 0.04; STE = 0.23). 10 Hz GPS devices are an adequate solution to monitor straight-line running speed in acceleration and deceleration conditions, but we would like to draw attention to the small errors and bias detected, such as the speed overestimation compared with timing gates.


A multicenter, open-label, sequential study comparing preferences for carbidopa-levodopa orally disintegrating tablets and conventional tablets in subjects with Parkinson's disease.
Patients with Parkinson's disease (PD) may have difficulty taking their medications for various reasons. In these patients, orally disintegrating tablets (ODTs) can be given without water and may provide greater convenience and ease of use than conventional tablets. This study compared preferences for ODTs with those of the conventional tablet formulation of the antiparkinsonism combination drug carbidopa-levodopa (C.-L.) in subjects with PD. Subjects aged > or =18 years with PD controlled using a stable dosage of C-L were enrolled in this multicenter, open-label, sequential study. Subjects received their stable dose of conventional C-L for 7 +/- 3 days. They were then switched to the same dose of C-L in the ODT formulation for 14.+/- 3 days. During the last 3 days of each treatment period, subjects were to record in a diary their "on" and "off" times (asymptomatic and symptomatic parkinsonism, respectively) and medication use. On the final day of each treatment period, the Unified Parkinson's Disease Rating Scale (UPDRS) was administered to subjects before the first morning dose and then after dosing when they mentioned they were experiencing the "on" state. A Global Preference Questionnaire (GPQ) was completed by subjects at the end of the study. The primary variable was response to all GPQ items. Secondary variables were changes in UPDRS score and mean amount of "off" time per 24 hours. Adverse effects (AEs) also were monitored. Sixty-one subjects (31 men, 30 women; mean[SD] age, 71.8 [8.3] years; mean body weight, 76.2 kg) participated in the study and were included in the AE assessment; 60 completed the study and were included in the efficacy assessment. Twenty-seven subjects (45%) preferred ODTs compared with 12 (20%) who preferred the conventional tablets (P < 0.017). The remaining 21 subjects (35%) had no preference. The attributes of the ODTs that influenced subjects' preference for that formulation included accessibility to medication to treat "off" times (30 [50%]); ease of activities of daily living (28 [47%]); reduced concern about swallowing the medication (27 [45%]); and use for nighttime dosing, ease of compliance with dosing schedule, and feeling less self-conscious about others noticing medication use (each, 25 [42%]) (all, P < 0.001). No statistically significant differences in UPDRS scores in the "on" and "off" states were found between the 2 formulations. The incidence of AEs was statistically similar between the 2 formulations. In this small study of ODT C-L versus conventional C-L tablets in these adult subjects with PD, the results suggest that the ODTs may be of value in certain patients with PD, depending on their personal preferences, disease status, and willingness to alter an aspect of their medication use. For selected patients with PD, the ODT C-L formulation may provide increased convenience, ease of use, and rapid access to medication.


Experimental studies on spinal cord injuries in the last fifteen years.
Experimental studies on spinal cord (SC) injuries published from 1975 to 1989 in some of the most widely circulating neurosurgical journals were reviewed. The relatively large number of animal species utilized as well as the intensely variable dynamic or static methods employed to induce SC injury represent elements of confusion more than objective necessities in this field of research. In fact, the objective of SC injury research should be to solve the problem of severe SC injuries by either preventing and/or repairing SC damage, rather than looking for modalities to provoke a large spectrum of SC injuries with the result of establishing a correlation between for example, the clinical picture and trauma magnitude. It should be time to study all variables and treatments mainly in only one experimental model. The rat with a permanent paraplegia should represent such a model; the abdominal aorta occlusion for 45 minutes, distal to the renal arteries in rabbits should be the experimental model of choice for ischaemia. If a significant result, such as reversing permanent paraplegia, were obtained in rats, it would be logical to repeat the study in higher mammals and if successful, in humans. For the last decade of this century it is necessary to further study all the mechanisms implied in secondary SC damage as well as to attempt to repair definitive SC damage by using grafts and enhancing the potential regenerative ability of the SC with known and new growth factors. Presently, methylprednisolone, dexametasone, thiopental, naloxone, and hypothermia seem to have some clinical potentials that require studies in humans.


James R. Learmonth: the first peripheral nerve surgeon.
The life and education of James R. Learmonth are reviewed. His experimental and clinical activities place him historically as the first surgeon to devote himself to peripheral nerve surgery.


Integrative aspects of zinc transporters.
Cells maintain zinc concentrations with relatively narrow limits. Nevertheless, physiologically relevant changes in free Zn(II) pools or changes in Zn bound to specific ligands or within vesicles may occur without a major change in total cellular zinc concentrations. The task of maintaining such levels rests in part with zinc transporter proteins. The genes for some putative zinc transporters have recently been cloned. As of this time, most have not been directly shown to transport zinc in functional studies, albeit evidence is strong that they have such a function. Zinc transporter (ZnT)-1 was identified as a rescue agent for cells maintained in very high extracellular zinc conditions; therefore, ZnT-1 has been suggested to function as an exporter. ZnT-1 is expressed in a variety of tissues, including intestine, kidney and liver. Intestinal expression is regional, being much greater in duodenum and jejunum and in villus versus crypt cells. Immunolocalization places ZnT-1 at the basolateral membrane of intestinal enterocytes and epithelial cells of the distal renal tubules. Regulation of ZnT-1 mRNA and ZnT-1 protein does not change markedly with changes in dietary zinc level except when a large single oral zinc supplement is provided. ZnT-1 is induced by transient ischemia of the forebrain. ZnT-2 and ZnT-3 may function in tissue-specific vesicular zinc transport. ZnT-4 is believed to be abundant in mammary gland and may be associated with zinc secretion into milk. A mutation of the ZnT-4 gene may account for the lethal milk (lm) syndrome. The putative zinc transporters identified thus far appear to have characteristics commensurate with functions in integrative zinc acquisition and homeostasis.