Molecular genetic studies of muscle lactate dehydrogenase deficiency in white patients.
We identified two new mutations in 2 white patients with muscle lactate dehydrogenase deficiency. Both patients had exercise intolerance, cramps, and recurrent myoglobinuria. One patient was homozygous for a 2-bp deletion in exon 5, resulting in a frameshift with premature termination of translation. The second patient was homozygous for a G-->A substitution at the 3' end of exon 2, leading to exon skipping and splicing of exon 1 to exon 3; the aberrantly spliced messenger RNA contains a frameshift, resulting in premature termination of translation. The present report provides evidence of molecular genetic heterogeneity in white patients with muscle lactate dehydrogenase deficiency.


Incidence and diagnosis of thrombosis in children with short-term central venous lines of the upper venous system.
Deep venous thrombosis in children is frequently related to central venous lines. Study objectives were to determine objectively the incidence of deep venous thrombosis in children with short-term central venous lines and to assess the diagnostic value of venography, venous ultrasonography, and echocardiography, in a prospective cohort study. Consecutive children with congenital heart disease requiring short-term central venous lines in the upper venous system were screened systematically for deep venous thrombosis by using venography, venous ultrasonography, and echocardiography, according to standardized protocols. The study population consisted of 90 children (median age: 2.7 years; range: birth to 18 years). Most central venous lines (97%) were located in the jugular veins. The overall incidence of deep venous thrombosis was 25 cases (28%) among 90 children. Venography identified deep venous thrombosis located in the subclavian and central veins but missed most deep venous thrombosis in the jugular veins. Venous ultrasonography had good sensitivity in the jugular veins but did not detect deep venous thrombosis in central veins. Echocardiography detected only 1 case of central deep venous thrombosis. The incidence of central venous line-related deep venous thrombosis in children with short-term central venous lines is high and comparable to reports for children with long-term central venous lines. Sensitivities of venography, venous ultrasonography, and echocardiography in children vary depending on the affected venous segment. A combination of diagnostic tests is required for sensitive detection of central venous line-related deep venous thrombosis in the upper venous system.


Perioperative fluid management in kidney transplantation: a black box.
The incidence of delayed graft function in patients undergoing kidney transplantation remains significant. Optimal fluid therapy has been shown to decrease delayed graft function after renal transplantation. Traditionally, the perioperative volume infusion regimen in this patient population has been guided by central venous pressure as an estimation of the patient's volume status and mean arterial pressure, but this is based on sparse evidence from mostly retrospective observational studies. Excessive volume infusion to the point of no further fluid responsiveness can damage the endothelial glycocalyx and is no longer considered to be the best approach. However, achievement of adequate flow to maintain sufficient tissue perfusion without maximization of cardiac filling remains a challenge. Novel minimally invasive technologies seem to reliably assess volume responsiveness, heart function and perfusion adequacy. Prospective comparative clinical studies are required to better understand the use of dynamic analyses of flow parameters for adequate fluid management in kidney transplant recipients. We review perioperative fluid assessment techniques and discuss conventional and novel monitoring strategies in the kidney transplant recipient.


Deep-ultraviolet Raman spectroscopy study of the effect of aging on human cortical bone.
The age-related deterioration in bone quality and consequent increase in fracture incidence is an obvious health concern that is becoming increasingly significant as the population ages. Raman spectroscopy with deep-ultraviolet excitation (244 nm) is used to measure vibrational spectra from human cortical bone obtained from donors over a wide age range (34-99 years). The UV Raman technique avoids the fluorescence background usually found with visible and near-infrared excitation and, due to resonance Raman effects, is particularly sensitive to the organic component of bone. Spectral changes in the amide I band at 1640 cm(-1) are found to correlate with both donor age and with previously reported fracture toughness data obtained from the same specimens. These results are discussed in the context of possible changes in collagen cross-linking chemistry as a function of age, and are deemed important to further our understanding of the changes in the organic component of the bone matrix with aging.


Comparison of effects of khat extract and amphetamine on motor behaviors in mice.
The aim of this study was to determine if the psychostimulants, khat and amphetamine, exert similar effects in two tests of motor behaviors. Dose-response relationships were obtained for khat extract and D- and L-amphetamine given to mice by the intragastric route. Head twitch responses were significantly increased by khat and amphetamines. The latter were more potent than khat; dose-response curves for amphetamines had inverted U shapes. Khat extract decreased spontaneous motor activity, as measured by a photoactometer. Effects of amphetamines in this test were more variable and subject to dose dependent reversal. Other behaviors produced by higher doses of amphetamines interfered with specific motor responses under evaluation. Pretreatment with methysergide, a serotonin antagonist, significantly blocked head twitch responses but not spontaneous activity. Conversely, pretreatment with haloperidol decanoate, a dopamine receptor antagonist, prevented inhibition of spontaneous motor activity ordinarily evoked by khat and low dose D-amphetamine. We conclude that motor effects of khat and amphetamine resemble one another, but only at certain doses. Unlike khat, amphetamine causes additional behaviors that obscure motor responses of the types examined here. Results with transmitter receptor blockers suggest that motor effects of khat, like those of amphetamine, may be modulated by serotonin and dopamine.


Exogenous Cushing syndrome: a lesson of diaper rash cream.
A prolonged use of topical corticosteroids can result in Cushing syndrome, though this is less common than with oral or parenteral steroids. Most pediatric cases were due to application of topical steroids for diaper dermatitis. Adverse cardiovascular effects can occur in Cushing syndrome with significant long-term morbidity and mortality, though so far there have been no reports of cardiovascular complications due to excessive usage of topical steroids. We report a 2.5-month-old boy who rapidly developed severe Cushing syndrome induced by the misuse of topical clobetasol, a very potent steroid, without a doctor's prescription as a diaper rash cream, and developed moderate left ventricular hypertrophy and pericardial effusion.


Immunofluorescent localization of vimentin, prekeratin and actin during odontoblast and ameloblast differentiation.
The localization of constitutive proteins of different types of cytoskeletal components (prekeratin, vimentin, and actin) was examined in embryonic mouse molars using specific antibodies and immunofluorescence microscopy on frozen sections. Prekeratin and actin were found in the enamel organ. Preameloblasts demonstrated uniform staining, whereas ameloblasts demonstrated an apical accumulation of both prekeratin and actin. Vimentin and actin were observed in the dental papilla. A redistribution of vimentin accompanied the polarization of odontoblasts. A possible transmembranous control of cytoskeletal activities by the extracellular matrix is discussed.


Changes of adrenergic and muscarinic cholinergic receptors in nasal mucosa in nasal allergy.
Receptor-binding assays were performed to evaluate the changes of beta- and alpha 1-adrenergic and muscarinic receptors in the nasal mucosa of subjects with nasal allergy and in guinea pigs sensitized with ovalbumin using radioligands 3H-DHA, 3H-prazosin and 3H-QNB, respectively. In subjects with nasal allergy, a decrease in density of beta- and alpha 1-adrenergic receptors and an increase in density of muscarinic cholinergic receptors were observed. An increase in density of muscarinic cholinergic receptors could be reproduced in the nasal mucosa of guinea pigs which were sensitized with ovalbumin and had typical hyperreactive nasal symptoms. These results indicate that the increase in the density of muscarinic receptors observed in the nasal mucosa of subjects with nasal allergy has been induced secondarily by an allergic reaction in the nasal mucosa with hyperreactive nasal symptoms, which in turn acts as an aggravating factor in the vicious circle promoting hyperreactivity of the nasal mucosa.


Clinical aspects of congenital syphilis with Hutchinson's triad.
Congenital syphilis is an infectious disease caused by Treponema pallidum transmitted by infected mother to her baby during pregnancy. Late congenital syphilis is recognised with 2 or more years after birth. One of the main aspects is observed with the triad of Hutchinson, characterised by the presence of interstitial keratitis, eighth nerve deafness and Hutchinson's teeth. This manuscript reports a case of late congenital syphilis presenting with Hutchinson's triad at an age of 7 years. These clinical features are related to syphilis present during pregnancy and at birth, however they commonly become apparent after 5-years of age.


Reduction in central line-associated bloodstream infections among patients in intensive care units--Pennsylvania, April 2001-March 2005.
Each year, an estimated 250,000 cases of central line-associated (i.e., central venous catheter-associated) bloodstream infections (BSIs) occur in hospitals in the United States, with an estimated attributable mortality of 12%-25% for each infection. The marginal cost to the health-care system is approximately 25,000 dollars per episode. In 2001, CDC was invited by the Pittsburgh Regional Healthcare Initiative (PRHI) to provide technical assistance for a hospital-based intervention to prevent central line-associated BSIs among intensive care unit (ICU) patients in southwestern Pennsylvania. During a 4-year period, BSI rates among ICU patients declined 68%, from 4.31 to 1.36 per 1,000 central line days. The results suggest that a coordinated, multi-institutional infection-control initiative might be an effective approach to reducing health-care-associated infections.


Life-History Variation in a Colonial Ascidian: Broad-Sence Heritabilities and Tradeoffs in Allocation to Asexual Growth and Male and Female Reproduction.
Intraspecific variation in life-history strategy provides a valuable opportunity for examining how natural selection acts on life-history variants to mold reproductive strategies. Evaluating the consequences of selection requires knowledge of the range of phenotypic variation in life histories, the extent to which variation is genetically based, and possible correlations among different traits that might constrain or promote the effect of selection on individual traits. We explored life-history variation in the colonial ascidian Botryllus schlosseri (a cyclical hermaphrodite) by growing clonal replicates of 18 genotypes in a common-garden experiment. Colonies of this species have previously been shown to vary in egg production and growth rate. We demonstrate that genotypes also vary in sperm production, which is manifested as variation in testis size. We then calculate broad-sense heritabilities for a suite of life-history traits and demonstrate correlations among traits that suggest a three-way tradeoff in resource allocation to asexual growth and sexual reproduction via male and female function. This correlation structure suggests that selection cannot act independently on individual life-history traits.


The Influence of Coherent Oxide Interfaces on the Behaviors of Helium (He) Ion Irradiated ODS W.
Tungsten (W), as a promising plasma-facing material for fusion nuclear reactors, exhibits ductility reduction. Introducing high-density coherent nano-dispersoids into the W matrix is a highly efficient strategy to break the tradeoff of the strength-ductility performance. In this work, we performed helium (He) ion irradiation on coherent oxide-dispersoids strengthened (ODS) W to investigate the effect of coherent nanoparticle interfaces on the behavior of He bubbles. The results show that the diameter and density of He bubbles in ODS W are close to that in W at low dose of He ion irradiation. The radiation-induced hardening increment of ODS W, being 25% lower than that of pure W, suggests the involvement of the coherent interface in weakening He ion irradiation-induced hardening and emphasizes the potential of coherent nano-dispersoids in enhancing the radiation resistance of W-based materials.


External-cavity laser diode using acousto-optic deflector as tunable grating.
In this study, a novel, to the best of our knowledge, external-cavity laser diode (ECLD) without a diffraction grating is proposed and demonstrated. In the proposed configuration, an acousto-optic deflector (AOD) acts not only as a deflector but also as a diffraction grating. Thus, the AOD functions as a wavelength-selective device, which helps improve the overall performance of the ECLD. In fact, the proposed configuration realizes a wide range of wavelength scanning with a simple configuration, highly efficient optical feedback, and a steady optical resonator with a constant cavity length. We confirm that the wavelengths scanned with the proposed ECLD agree well with theoretical calculations. The scanning range and maximum frequency response reached approximately 60 nm and 50 kHz, respectively. Moreover, reproducible measurements of the three-dimensional thickness distribution of a thin glass plate indicates that the proposed ECLD can be used for optical coherence tomography imaging systems.


Genetic adaptations of sea anemone to hydrothermal environment.
Hydrothermal vent habitats are characterized by high hydrostatic pressure, darkness, and the continuous release of toxic metal ions into the surrounding environment where sea anemones and other invertebrates thrive. Nevertheless, the understanding of metazoan metal ion tolerances and environmental adaptations remains limited. We assembled a chromosome-level genome for the vent sea anemone, Alvinactis idsseensis sp. nov. Comparative genomic analyses revealed gene family expansions and gene innovations in A. idsseensis sp. nov. as a response to high concentrations of metal ions. Impressively, the metal tolerance proteins MTPs is a unique evolutionary response to the high concentrations of Fe2+ and Mn2+ present in the environments of these anemones. We also found genes associated with high concentrations of polyunsaturated fatty acids that may respond to high hydrostatic pressure and found sensory and circadian rhythm-regulated genes that were essential for adaptations to darkness. Overall, our results provide insights into metazoan adaptation to metal ions, high pressure, and darkness in hydrothermal vents.


Evaluation of multiple imputation approaches for handling missing covariate information in a case-cohort study with a binary outcome.
In case-cohort studies a random subcohort is selected from the inception cohort and acts as the sample of controls for several outcome investigations. Analysis is conducted using only the cases and the subcohort, with inverse probability weighting (IPW) used to account for the unequal sampling probabilities resulting from the study design. Like all epidemiological studies, case-cohort studies are susceptible to missing data. Multiple imputation (MI) has become increasingly popular for addressing missing data in epidemiological studies. It is currently unclear how best to incorporate the weights from a case-cohort analysis in MI procedures used to address missing covariate data. A simulation study was conducted with missingness in two covariates, motivated by a case study within the Barwon Infant Study. MI methods considered were: using the outcome, a proxy for weights in the simple case-cohort design considered, as a predictor in the imputation model, with and without exposure and covariate interactions; imputing separately within each weight category; and using a weighted imputation model. These methods were compared to a complete case analysis (CCA) within the context of a standard IPW analysis model estimating either the risk or odds ratio. The strength of associations, missing data mechanism, proportion of observations with incomplete covariate data, and subcohort selection probability varied across the simulation scenarios. Methods were also applied to the case study. There was similar performance in terms of relative bias and precision with all MI methods across the scenarios considered, with expected improvements compared with the CCA. Slight underestimation of the standard error was seen throughout but the nominal level of coverage (95%) was generally achieved. All MI methods showed a similar increase in precision as the subcohort selection probability increased, irrespective of the scenario. A similar pattern of results was seen in the case study. How weights were incorporated into the imputation model had minimal effect on the performance of MI; this may be due to case-cohort studies only having two weight categories. In this context, inclusion of the outcome in the imputation model was sufficient to account for the unequal sampling probabilities in the analysis model.


Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine.
Dihydropteroate synthase (H2Pte synthase) is the target of the sulfur-based antimalarial drugs, which are frequently used in synergistic combination with inhibitors of dihydrofolate reductase (H2folate reductase) to combat chloroquine-resistant malaria. We have isolated the H2Pte synthase coding sequence of the most pathogenic human parasite Plasmodium falciparum. It forms part of a longer coding sequence, located on chromosome 8, that also specifies 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (CH2OH-H2pterinPP kinase) at its 5' proximal end. This domain is unusually large, with two long insertions relative to other CH2OH-H2pterinPP kinase molecules. To investigate a possible genetic basis for clinical resistance to sulfa drugs, we sequenced the complete H2Pte synthase domains from eleven isolates of P. falciparum with diverse geographical origins and levels of sulfadoxine resistance. Overall, point mutations in five positions were observed, affecting four codons. Parasite lines exhibiting high-level resistance were found to carry either a double mutation, altering both Ser436 and Ala613, or a single mutation affecting Ala581. The mutations at positions 436 and 581 have the same location relative to each of two degenerate repeated amino acid motifs that are conserved across all other known H2Pte synthase molecules. The amino acid alteration at residue 613 is identically positioned relative to a different conserved motif. The fourth amino acid residue (437) affected by mutation, though adjacent to the apparently crucial residue 436, shows no obvious correlation with resistance. Although these mutations have no exact counterparts in any other organism, that at position 581 falls within a region of three amino acids where H2Pte synthase is modified in various ways in a number of sulfonamide-resistant pathogenic bacteria. Copy-number analysis indicated that there was no amplification of the H2Pte synthase domain in resistant parasite lines of P. falciparum, compared to sensitive lines.


Automatic classification of cancer cells in multispectral microscopic images of lymph node samples.
Histopathological analysis is crucial for the diagnosis of a large number of cancer types. A lot of progress has been made in the development of molecular based assays, but many of the cases still require the careful analysis of the stained tissue under a bright-field microscope and its analysis. This procedure is costly and time-consuming. We present a novel method for classification of cancer cells in lymph node images. It is based on the measurement of the spectral image of hematoxylin and eosin stained sample under the microscope and the analysis of the acquired data using state of the art machine learning techniques. The method is based on the analysis of the spectral information of the cells as well as their morphological properties. A large number of descriptors is extracted for each cell location, which are used to train a supervised classifier which discriminates between normal and cancer cells. We show that a reliable analysis can be made with detection rate (recall) of 81%-100% for the cancer class.


Perfluorinated compounds in the Cape Fear Drainage Basin in North Carolina.
Concern over perfluorinated organic compounds (PFCs), e.g., perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), is due to a number of recent studies which show that the PFCs are persistent, bioaccumulative, and toxic in animals. Despite sustained interest in this topic, little information is available concerning the environmental distributions of the compounds. In this study, a new method was developed for the analysis of 10 target PFCs and its performance was examined in a systematic evaluation of surface water in the Cape Fear River Basin in North Carolina. One hundred samples from 80 different locations were collected during the spring of 2006. Detectable levels of the target PFCs were found in all samples, and were comparable to values reported previously, with maximum PFOS at 132 ng/L, PFOA at 287 ng/L, perfluorononanoic acid (C9) at 194 ng/L, and perfluoroheptanoic acid (C7) at 329 ng/L. In general, the lowest concentrations of the PFCs were found in the smallest tributaries while the highest levels were found in middle reaches of the Drainage Basin. Variability of PFC concentrations suggests a series of source inputs throughout the Basin. Seventeen sample sites (22%) had PFOS concentrations greater than 43 ng/L, a conservative safe water concentration estimated to be protective of avian life. In addition, a total of 26 sites (32%) had PFOA concentrations above 40 ng/L.


Guidance for the discontinuation or switching of antidepressant therapies in adults.
Antidepressants (ADs) are commonly used for the treatment of various psychological and other medical disorders. Patient response and regimen duration with individual agents varies, necessitating discontinuation (DC) and/or switching between ADs. However, withdrawal symptoms may occur upon DC of the AD, and clinical symptom control may be compromised if the change to a new AD agent is not initiated appropriately. The purpose of this evaluation was to review the available literature and resources to compile documented methods for discontinuing or changing AD regimens in the clinical setting into a single guidance document. The results of this evaluation have yielded both detailed and general recommendations for practitioners to use and consider in discontinuing an AD and making changes between AD agents. The information provided herein is intended to provide useful guidance for clinicians and other health care professionals in their management of patients discontinuing or switching between selected AD agents.


Dynamic and randomized perturbed posturography in the follow-up of patients with polyneuropathy.
The purpose of the study was to investigate and follow the equilibrium performance of patients with chronic polyneuropathy using Dynamic Posturography (DP) and Randomized Perturbed Posturography (RPP). Fourteen patients with chronic polyneuropathy, aged 53-83 years, were evaluated by clinical investigation, vibrametry, DP and RPP in a six-year follow-up. The patient group was compared to 14 healthy volunteers, aged 63-80 years. The DP comprises a sensory organization (SO) part in which the platform and visual surround are stable or referenced to the patient sway, with eyes open or closed. In a movement coordination (MC) part, the platform makes active movements. In RPP, the platform moves randomly in the anteroposterior direction. Comparison between the first and second study of the patient group showed decreased equilibrium scores under stable conditions and when vision was excluded. Compared with controls, the patients showed significantly lower scores in most of the SO test conditions except when the platform was sway referenced with stable surround; in the MC part, the patients showed prolonged muscular response latencies, and in the RPP, the patients showed increased sway areas. The results are further evidence that proprioception is probably the single most important sensory input for postural control in humans. Posturography proved to be an objective method to study and follow the equilibrium performance in patients with PN.


The inhibitory effect of micafungin on biofilm formation by Pseudomonas aeruginosa.
This study assesses the potential effect of micafungin, an antifungal agent known to inhibit 1,3-β-D-glucan synthesis in Candida albicans, on biofilm formation of selected Pseudomonas aeruginosa isolates by decreasing the synthesis of extracellular matrix β-D-glucan forming units. The effect of an optimal therapeutic dose of 10 mg ml(-1) micafungin on the production of biofilm was monitored in vitro using a microtiter plate assay. Phenotypic reduction in the formation of biofilm was significant (based on average optical density; p < 0.05) in most of the isolates. Moreover, the relative gene expression of biofilm encoding genes for alginate and pellicles (algC and pelC, respectively), and the cell wall 1,3-β-D-glucan encoding gene (ndvB) was evaluated using quantitative reverse transcription PCR. For all the genes tested, the levels of mRNA transcription were also decreased significantly (p < 0.05) in micafungin-treated samples cf. their untreated counterparts. In conclusion, this study presents micafungin as a potential agent for disrupting the structure of a biofilm of P. aeruginosa allowing the possible exposure and treatment of core-planktonic cells.


Chronological and spatial analysis of the 1996 Ebola Reston virus outbreak in a monkey breeding facility in the Philippines.
To describe the transmission pattern of natural infection with Ebola Reston (EBO-R) virus in a breeding colony, the chronological and spatial analysis of mortality during the 1996 EBO-R virus outbreak was done in this study. The EBO-R virus infection among monkeys in the facility was widespread. Over a period of 3 months, 14 out of 21 occupied units were contaminated with antigen positive animals. A large number of wild-caught monkeys were involved in this outbreak suggesting that wild-caught monkeys have a high susceptibility to EBO-R virus infection. In this outbreak, morbidity patterns for individual animal units were very different regardless of the type and size of cages, individual or gang cages. The results suggest that not only the cage size but also poor animal husbandry practices may be risk factors for the spread of EBO-R infection.


Escape from fatal fusion.
In 1971, a seminal paper from the laboratory of Philip D'Arcy Hart reported that the intracellular pathogen Mycobacterium tuberculosis avoids destruction in the cell's lysosomes by avoiding these organelles altogether-a trick now known to be used by many other intracellular pathogens.


Effect on production of replacing dietary starch with sucrose in lactating dairy cows.
Replacing dietary starch with sugar has been reported to improve production in dairy cows. Two sets of 24 Holstein cows averaging 41 kg/d of milk were fed a covariate diet, blocked by days in milk, and randomly assigned in 2 phases to 4 groups of 6 cows each. Cows were fed experimental diets containing [dry matter (DM) basis]: 39% alfalfa silage, 21% corn silage, 21% rolled high-moisture shelled corn, 9% soybean meal, 2% fat, 1% vitamin-mineral supplement, 7.5% supplemental nonstructural carbohydrate, 16.7% crude protein, and 30% neutral detergent fiber. Nonstructural carbohydrates added to the 4 diets were 1) 7.5% corn starch, 0% sucrose; 2) 5.0% starch, 2.5% sucrose; 3) 2.5% starch, 5.0% sucrose; or 4) 0% starch, 7.5% sucrose. Cows were fed the experimental diets for 8 wk. There were linear increases in DM intake and milk fat content and yield, and linear decreases in ruminal concentrations of ammonia and branched-chain volatile fatty acids, and urinary excretion of urea-N and total N, and urinary urea-N as a proportion of total N, as sucrose replaced corn starch in the diet. Despite these changes, there was no effect of diet on microbial protein formation, estimated from total purine flow at the omasum or purine derivative excretion in the urine, and there were linear decreases in both milk/DM intake and milk N/N-intake when sucrose replaced dietary starch. However, expressing efficiency as fat-corrected milk/DM intake or solids-corrected milk/DM intake indicated that there was no effect of sucrose addition on nutrient utilization. Replacing dietary starch with sucrose increased fat secretion, apparently via increased energy supply because of greater intake. Positive responses normally correlated with improved ruminal N efficiency that were altered by sucrose feeding were not associated with increased protein secretion in this trial.


Thermal conductivity as influenced by the temperature and apparent viscosity of dairy products.
This study aimed to evaluate the rheological behavior and thermal conductivity of dairy products, composed of the same chemical components but with different formulations, as a function of temperature. Subsequently, thermal conductivity was related to the apparent viscosity of yogurt, fermented dairy beverage, and fermented milk. Thermal conductivity measures and rheological tests were performed at 5, 10, 15, 20, and 25°C using linear probe heating and an oscillatory rheometer with concentric cylinder geometry, respectively. The results were compared with those calculated using the parallel, series, and Maxwell-Eucken models as a function of temperature, and the discrepancies in the results are discussed. Linear equations were fitted to evaluate the influence of temperature on the thermal conductivity of the dairy products. The rheological behavior, specifically apparent viscosity versus shear rate, was influenced by temperature. Herschel-Bulkley, power law, and Newton's law models were used to fit the experimental data. The Herschel-Bulkley model best described the adjustments for yogurt, the power law model did so for fermented dairy beverages, and Newton's law model did so for fermented milk and was then used to determine the rheological parameters. Fermented milk showed a Newtonian trend, whereas yogurt and fermented dairy beverage were shear thinning. Apparent viscosity was correlated with temperature by the Arrhenius equation. The formulation influenced the effective thermal conductivity. The relationship between the 2 properties was established by fixing the temperature and expressing conductivity as a function of apparent viscosity. Thermal conductivity increased with viscosity and decreased with increasing temperature.


A time- and angle-resolved photoemission spectroscopy with probe photon energy up to 6.7 eV.
We present the development of a time- and angle-resolved photoemission spectroscopy based on a Yb-based femtosecond laser and a hemispherical electron analyzer. The energy of the pump photon is tunable between 1.4 and 1.9 eV, and the pulse duration is around 30 fs. We use a KBe2BO3F2 nonlinear optical crystal to generate probe pulses, of which the photon energy is up to 6.7 eV, and obtain an overall time resolution of 1 ps and energy resolution of 18 meV. In addition, β-BaB2O4 crystals are used to generate alternative probe pulses at 6.05 eV, giving an overall time resolution of 130 fs and energy resolution of 19 meV. We illustrate the performance of the system with representative data on several samples (Bi2Se3, YbCd2Sb2, and FeSe).


Construction of an instrument for measuring medical student satisfaction with virtual campus.
In France, the virtual campus became a pedagogical tool used in the medical education in year 2000. Therefore, it is appropriate to measure the student satisfaction, user of virtual campus. The objective of this research was to develop a student satisfaction instrument adapted to the medical field. Based on the literature, we obtained 36-item questionnaire, using 5-point Likert-type scale. 80 students in the Faculty of Medicine at the Nantes University participated to this survey. In this study, two analyses were conducted, the first included all the items and the second excluded items for which a high rate of non response were found. The results show that the instrument contains three dimensions: 'self evaluation - tutorial', 'appropriateness of content' and 'user-friendliness'. Nevertheless, this exploratory study need to be validated with a greater sample of students.


[Significance of pulmonary vein flow for the determination of left ventricular filling pressure].
The aim of the submitted study was to evaluate the blood flow in the pulmonary veins by transoesophageal Doppler echocardiography which is the ideal method for recording the blood flow in the pulmonary veins as the ultrasound probe is closely behind the left atrium. In 35 patients with ischaemic heart disease the authors evaluated the blood flow in the pulmonary veins to assess whether the rate of the blood flow in these vessels can serve a non-invasive estimate of the end-diastolic pressure in the left ventricle (LVEDP). It was revealed that venous blood flow has in the majority of cases two anterior peaks during ventricular systole, one anterior peak during diastole and one negative peak during atrial contraction. In patients with normal LVEDP the peak rate and integral time-velocity of the flow curve is greater during systole, while in patients with a higher LVEDP these parameters are higher during diastole. Dopplerian assessment of the flow in the pulmonary veins is safe, relatively non-invasive and simple. This method makes possible rapid visual estimates of the end-diastolic pressure in the left ventricle.


Serum folate and depressive symptoms among Japanese men and women: a cross-sectional and prospective study.
Although several studies have reported an association between blood folate concentrations and depressive symptoms, few studies have prospectively examined the association. This study aimed to investigate the cross-sectional and prospective associations between serum folate concentrations and depressive symptoms among Japanese. We analysed data among 545 subjects who participated in a health survey at the time of periodic check-up in 2009 for a cross-sectional association and among 272 subjects without depressive symptoms at baseline (in 2006) who responded to both baseline (2006) and follow-up (2009) surveys for prospective association. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. In a cross-sectional analysis, serum folate concentrations were significantly associated with a decreased prevalence of depressive symptoms (CES-D scale of ≥16). Moreover, serum folate concentrations at baseline were significantly inversely associated with depressive symptoms after 3 years; the multivariate-adjusted odds ratios (95% confidence intervals) of depressive symptoms for the lowest through highest tertile categories of serum folate concentrations were 1.00 (reference), 0.66 (0.29-1.52) and 0.40 (0.16-0.99) (P for trend=0.047). Our findings suggest that a higher serum folate may be associated with decreased risk of depressive symptoms in Japanese.


Specialized respiratory management for acute cervical spinal cord injury:: a retrospective analysis.
In individuals with cervical spinal cord injury (SCI), respiratory complications arise within hours to days of injury. Paralysis of the respiratory muscles predisposes the patient toward respiratory failure. Respiratory complications after cervical SCI include hypoventilation, hypercapnea, reduction in surfactant production, mucus plugging, atelectasis, and pneumonia. Ultimately, the patient must use increased work to breathe, which results in respiratory fatigue and may eventually require intubation for mechanical ventilation. Without specialized respiratory management for individuals with tetraplegia, recurrent pneumonias, bronchoscopies, and difficulty in maintaining a stable respiratory status will persist. This retrospective analysis examined the effectiveness of specialized respiratory management utilized in a regional SCI center. Individuals with C1-C4 SCI (N = 24) were the focus of this study as these neurological levels present with the most complicated respiratory status. All of the study patients' respiratory status improved with the specialized respiratory management administered in the SCI specialty unit. For a majority of these patients, respiratory improvements were noted within 1 week of admission to our SCI unit. Utilization of high tidal volume ventilation, high frequency percussive ventilation, and mechanical insufflation- exsufflation have demonstrated efficacy in stabilizing the respiratory status of these individuals. Optimizing respiratory status enables the patients to participate in rehabilitation therapies, allows for the opportunity to vocalize, and results in fewer days on mechanical ventilation for patients who are weanable.


[Fever and Headache after a Vacation in Thailand].
History 50 year-old man with fever and headache starting one week after returning from his vacation in Thailand. His general practitioner prescribed amoxicillin/clavulanic acid, without further analyses to pinpoint the infection. Examinations The examination of cerebro-spinal fluid was crucial for the final diagnosis. Lumbar puncture demonstrated a predominantly mononuclear pleocytosis of 80 cells/µl (< 5) with an elevated protein of 782 mg/l (< 450); glucose and lactate were within normal limits. Treatment and course Initially we tried to treat a broad range of organisms potentially causing meningitis or encephalitis. Typical bacteria and viruses endemic to Switzerland were not found, thus anti-infective treatment was stopped. Also the search for malaria, HIV, Chikungunya and Dengue infections yielded negative results. After 10 days we received a positive serologic test for Japanese encephalitis virus (JEV). Conclusions The Japanese encephalitis virus is transmitted by mosquitoes and is epidemiologically one of the most important transmissible neurologic diseases in Asia. Although only a minority of infected patients are gravely ill, their sequelae and death toll are considerable. Since 2009 a well-tolerated vaccine is available.


Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men.
To study the impact of obesity, age and varicocele on sexual hormones of adult and elderly men. 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men.


Common inflammatory mechanisms in Lewy body disease and Alzheimer disease.
Cortical Lewy body disease as a cause of dementia has been recognized for more than 40 years. Only in the past 15 to 20 years, however, has the true frequency of this entity come to be appreciated, primarily because of the advent of sensitive and specific immunohistochemical diagnostic techniques. We now know that there is frequent and extensive overlap, both clinically and pathologically, between Lewy body and Alzheimer diseases. Although some of this overlap may be attributable to common genetic and environmental risk factors, it is also now apparent that the 2 diseases share common neuroinflammatory mechanisms involving activation of microglia, overexpression of interleukin-1 and other inflammatory mediators, and inflammatory toxicity to neurons. Activated microglia are found in association with alpha-synuclein-containing neurons and glia in Parkinson disease, in dementia with Lewy bodies, and in multiple system atrophy, and these associations are reminiscent of microglial associations with neurofibrillary tangle-containing neurons in Alzheimer disease. In vitro and in vivo experimental work has shown reciprocal induction between alpha-synuclein and injured neurons on one hand and activated microglia and cytokine overexpression on the other. These neuroinflammatory processes may be a common link driving progression in both diseases and explaining the frequent overlap between the 2 diseases.


Atlantic overturning: new observations and challenges.
This paper provides an introduction to the special issue of the Philosophical Transactions of the Royal Society of London of papers from the 2022 Royal Society meeting on 'Atlantic overturning: new observations and challenges'. It provides the background and rationale for the meeting, briefly summarizes prior progress on observing the Atlantic overturning circulation and draws out the new challenges that papers presented at the meeting raise, so pointing the way forward for future research. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.


Combination of computed tomography-guided iodine-125 brachytherapy and bronchial arterial chemoembolization for locally advanced stage III non-small cell lung cancer after failure of concurrent chemoradiotherapy.
To evaluate the efficacy and safety of the combination of computed tomography (CT)-guided iodine-125 brachytherapy and bronchial arterial chemoembolization (BACE) for locally advanced stage III non-small cell lung cancer (NSCLC) after failure of concurrent chemoradiotherapy. We retrospectively evaluated 28 patients with locally advanced stage III NSCLC in whom concurrent chemoradiotherapy had failed and were consequently, treated with radioactive iodine-125 seed implantation followed by BACE. The prescribed radiation dose was 140 Gy, with a median radioactivity of 0.60 mCi. The tumor-feeding arteries were detected on angiography, and chemotherapeutic agents (gemcitabine 1000 mg/m2 + lobaplatin 30 mg/m2) were then administered via arterial infusion. The tumor-feeding arteries were embolized using 300-500 μm embosphere microspheres. The endpoints were treatment response rate, progression-free survival (PFS), and toxicity. The median number of implanted iodine-125 seeds was 58 pellets (range, 44-114 pellets). The median post-operative dose covering 90 % of the target volume (D90) was 143.4 Gy (range, 123.6-159.9 Gy). A total of 73 cycles of BACE were conducted (2.61 cycles per case). The bronchial arteries were the main tumor-feeding arteries. In total, 11 patients had hemoptysis, and it was significantly alleviated within 24 h after BACE. There was no serious procedure-related complication. The 6-month objective response and disease control rates were 71.42 % and 92.86 %, respectively. No severe complications occurred during the follow-up. Local control duration ranged from 5-12 months, and the median PFS was 8 months (95 % confidence interval: 7.3-8.8 months). The combination of CT-guided iodine-125 brachytherapy and BACE is an effective and safe approach for the treatment of NSCLC after failure of concurrent chemoradiotherapy and is worthy of clinical application.


Death Due to Myocardial Bridging.
Myocardial bridging is a congenital coronary pathology described as a segment of coronary artery which courses through the myocardial wall beneath the muscle bridge. Although the myocardial bridging prognosis is benign, have been also reported sudden death in medical literature. ¬A 30-year-old married woman was found dead at her home. After local prosecutors' investigation the death was declared as suspicious and forensic autopsy was obliged. The left anterior descending coronary artery was detected embedded deeply in the myocardium 2 cm from its coronary ostial origin. There were no other pathology to explain death. We analyzed sudden death case occurred because of myocardial bridging and the pathophysiological mechanisms in the light of medico-legal literature.


Pedicle screw placement accuracy impact and comparison between grading systems.
Pedicle screw instrumentation is widely used for spinal stabilization. However, the accuracy for free-hand screw placement ranges from 69% to 94%. This study assesses the value of the existing classification systems, and investigates their impact on the ability to assess the accuracy of free-hand screw placement. Data were collected retrospectively from the medical records of 34 patients who received 224 pedicle screws placed utilizing a free-hand technique. Screw placement was evaluated employing the 2-mm increment and Zdichavsky et al. classification systems. Kappa coefficient and Landis and Koch interpretations were employed for statistical analysis. The 2-mm increment classification system resulted in a total of 18 (8.03%) misplaced screws. Lateral screw misplacement was observed in 13 (5.8%) instances, with medial pedicle wall penetration being noted in 5 (2.23%). Of the 18 misplaced screws, 4 (22.22%) were classified as minor (≤2 mm), 12 (66.67%) as moderate (2-4 mm), and 2 (11.11%) as severe (>4 mm) (K = 0.882). The Zdichavsky et al. grading system categorized 208 (92.84%) pedicle screws as Ia, 10 (4.46%) as Ib, 1 (0.45%) as IIa, 2 (0.90%) as IIb, 2 (0.90%) as IIIa, and 1 (0.45%) as IIIb grade; this resulted in a total of 16 (7.14%) misplaced screws (K = 0.980). One patient exhibited a new postoperative radiculopathy attributed to poor screw placement. There were no additional early or late postsurgical complications attributed to screw misplacement. The free-hand pedicle screw placement technique is both safe and effective. Postoperative computed tomography studies; however, are useful to confirm the accuracy of screw placement. Although, the available grading systems proved reliable, easy to use, and clearly reflected the individual surgeon's skills, they do not clearly document whether screws are safely placed.


Plasma risperidone concentrations during combined treatment with sertraline.
The effect of sertraline on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was studied in 11 patients with schizophrenia or schizoaffective disorder. To treat concomitant depressive symptoms, additional sertraline, at the dose of 50 mg/d, was administered for 4 weeks to patients stabilized on risperidone (4-6 mg/d). Mean plasma concentrations of risperidone, 9-OH-risperidone, and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) did not change significantly during combined treatment with sertraline. At the end of week 4, sertraline dosage was adjusted in some patients on the basis of the individual response and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the 4 patients who were still receiving the initial sertraline dose, but concentrations were slightly but not significantly increased (by a mean 15% over pretreatment) in the subgroup of 5 subjects treated with a final dose of 100 mg/d. In the 2 patients receiving the highest dose of sertraline, 150 mg/d, at week 8 total plasma risperidone concentrations were increased by 36% and 52%, respectively, as compared with baseline values. Sertraline coadministration with risperidone was well tolerated, and no patient developed extrapyramidal symptoms. These findings indicate that sertraline at dosages up to 100 mg/d is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of sertraline may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of sertraline on CYP2D6-mediated 9-hydroxylation of risperidone.


How do dentists use CBCT in dental clinics? A Norwegian nationwide survey.
Cone beam computed tomography (CBCT) was introduced to Norwegian dental clinics in 2007. The aim of the study was to investigate how dental clinics use this imaging modality, including factors related to workflow and image quality, and to evaluate dentists' opinions on and experiences of using it. A web-based 59-item questionnaire regarding the clinical use of CBCT was sent to all 39 CBCT clinics in Norway. Twenty-nine clinics (74%) responded. Most respondents (93%) were from clinics with more than one dentist and 83% had at least one specialist. All clinics had digital intraoral x-ray receptors and all but one had panoramic imaging. The most common indications for CBCT were implant treatment planning (34% of all clinics) and localization of impacted teeth (43% of specialist clinics). Seventy-two per cent of clinics reported an average of four or fewer CBCT examinations each week and 83% of respondents were subjectively satisfied with the image quality. The most commonly used enhancement functions were contrast (97%), brightness (90%) and zoom (86%). The Norwegian CBCT clinics surveyed were fully digitized and had multiple dentists. Periodontists and oral and maxillofacial surgeons were the most frequent specialties represented in the clinics. Clinics with only dental specialists performed more CBCT examinations/week than clinics with general practitioners or both general practitioners and specialists. The most common indications for CBCT examinations were related to treatment planning. This study found some challenges related to image quality and communication within the radiological team.


Matrix metalloproteinase 9 and epileptogenesis - the crucial role of the enzyme and strategies to prevent the disease development.
Epileptogenesis is the process responsible for converting normal brain into an epileptic. It may be triggered by an event such as brain injury or status epilepticus (SE). The main mechanisms responsible include neuroinflammation and blood-brain barrier (BBB) disruption, pathologic neuronal networks' reorganisation and aberrant synaptic plasticity. Accumulating amount of evidence from animal models and epileptic patients strongly suggest that matrix metalloproteinase 9 (MMP-9) is potentially one of the key executors of the processes of epileptogenesis. MMP-9 by affecting synaptic plasticity is suggested to enable epileptic remodelling of the brain circuitry. MMP-9's dependent cleavage of BBB followed by inflammatory cell infiltration into the brain contributes to the neuroinflamation component of epileptogenesis. The goal of this review was to analyse all possible ways MMP-9 may be involved in epileptogenesis and consider MMP-9 inhibition as potential therapeutic strategy.


[Assessment of eating disorders-related risk in a cohort of adolescents living in Northern Italy. Results from a multicenter study].
Clinical evidence and epidemiological research show an increasing number of subjects trying to become lean and reaching consequently harmful weight conditions. Aim of this paper is to assess the risk for eating disorders during adolescence. In a multicentric study high school students of 5 different districts of Northern Italy have been asked to fill up anonymously the Italian version of the American YRBSS (Youth Risk Behaviour Surveillance System) questionnaire. For each school a section has been selected and between January and March 1999, students of every level have been involved. The data enrollected have been analysed using EpiInfo6. The study involved 4135 adolescents (57% girls and 43% boys) coming from 260 classes and 47 different schools. The proportion of boys perceiving themselves as overweight and underweight was the same (22%), while the proportion of girls considering themselves overweight raised up to 42%. The majority of the girls (53%) is trying to slim making use of physical activity (48%), diets (32%), vomiting (8%) and drugs (5%). Our data suggest that specific projects focusing on primary and secondary prevention of eating disorders should be considered for high schools. In addition, further studies are suggested to understand characteristics and behaviours related to eating disorders.


Pharmacological characterization of the inhibitory effects of neurotensin on the rabbit ileum myenteric plexus preparation.
Neurotensin in picomolar concentrations caused a concentration-related inhibition of the spontaneous contractile activity of the longitudinal muscle from the rabbit isolated ileum. Neurotensin was approximately 100 times more potent than adrenaline and about 10000 times as active as adenosine triphosphate (ATP) in producing similar relaxations. The neurotensin-induced inhibitory effect did not follow activation of adrenoceptors or P1-purinoceptors since the effect of the neuropeptide was not antagonized by a combination of phentolamine plus (-)-propranolol, nor by pretreatment with theophylline. Tetrodotoxin did not reduce the potency of neurotensin in relaxing the rabbit ileum, suggesting that the neurotensin-induced inhibition is not neuronally mediated. The inhibitory responses of neurotensin were blocked non-competitively by apamin. The inhibitory effect of neurotensin was short-lived with the subsequent development of tachyphylaxis, which was not crossed to the inhibitory action of adrenaline or ATP. Similarly, when tachyphylaxis to adrenaline or to ATP was established, the inhibitory action of neurotensin was unaffected. Desensitization was characterized by a gradual shift of the neuropeptide concentration-response curve to the right and downwards. Preincubation of rabbit ileum strips with 10 nM dynorphin (1-13) significantly increased the inhibitory action of neurotensin.


The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner.
Tolerance to replication-blocking DNA lesions is achieved by means of ubiquitylation of PCNA, the processivity clamp for replicative DNA polymerases, by components of the RAD6 pathway. In the yeast Saccharomyces cerevisiae the ubiquitin ligase (E3) responsible for polyubiquitylation of the clamp is the RING finger protein Rad5p. Interestingly, the RING finger, responsible for the protein's E3 activity, is embedded in a conserved DNA-dependent ATPase domain common to helicases and chromatin remodeling factors of the SWI/SNF family. Here, we demonstrate that the Rad5p ATPase domain provides the basis for a function of the protein in DNA double-strand break repair via a RAD52- and Ku-independent pathway mediated by the Mre11/Rad50/Xrs2 protein complex. This activity is distinct and separable from the contribution of the RING domain to ubiquitin conjugation to PCNA. Moreover, we show that the Rad5 protein physically associates with the single-stranded DNA regions at a processed double-strand break in vivo. Our observations suggest that Rad5p is a multifunctional protein that--by means of independent enzymatic activities inherent in its RING and ATPase domains--plays a modulating role in the coordination of repair events and replication fork progression in response to various different types of DNA lesions.


Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage.
Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (>0.9) in a large animal model, with superior performance to vital sign metrics.


Evolution of the diabetic diet: Fats and fallacies.
The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study (UKPDS) trials have provided evidence for the pivotal importance of optimizing glycaemic control to prevent complications in type 1 and 2 diabetes mellitus. Both patients and diabetes professionals consider lifestyle change and appropriate medication as cornerstones for achieving good glycaemic control. The frequent reversals in the recommended diabetic diet in the past century warn that in the nutritional area the hypotheses are many, but the proofs are few. In type 1 diabetes, the patient is still advised to spread out carbohyrate foods during the day with three short-acting insulin injections at meal times to minimize postprandial hyperglycaemia. In type 2 diabetes, weight loss is the major target, because 80% of patients are overweight or obese. However, it is salutory to note that in the UKPDS trial, no modality of treatment delayed the relentless deterioration of glycaemic control in type 2 diabetes, the extent of which was predicted by the insulin secretion. Controversy still exists regarding whether lowering the dietary fat enhances weight loss of itself and whether dietary carbohydrate, fat and fibre influence insulin sensitivity and glycaemia. The American Diabetes Association's evidence-based recommendations currently offer a choice between a high carbohyrate and modified fat diet, with monounsaturated fat replacing the saturated fat instead of carbohydrate. The role of omega-3 fatty acids in man is not resolved. The reason for the surprising lack of definitive evidence lies in the limitations of nutritional research. Under-reporting of diet is common and dietary assessment tools are often inaccurate. Sustained weight loss is unattainable by the majority of patients, perhaps because of the strongly genetic nature of obesity and the sedentary lifestyle. Compliance may be improved by suggesting small, sustained dietary changes, setting small weight loss targets and encouraging a permanent increase in total activity.


Risk of recurrence after a first seizure and implications for driving: further analysis of the Multicentre study of early Epilepsy and Single Seizures.
To determine for how long after a first unprovoked seizure a driver must be seizure-free before the risk of recurrence in the next 12 months falls below 20%, enabling them to regain their driving licence. Randomised controlled trial: Multicentre study of early Epilepsy and Single Seizures (MESS). UK hospital outpatient clinics from 1 January 1993 to 31 December 2000. People entered MESS if they had had one or more unprovoked seizures and both the participant and the clinician were uncertain about the need to start antiepileptic drug treatment. The subset of people used for this analysis comprised participants aged at least 16 years with a single unprovoked seizure. Risk of seizure recurrence in the 12 months after a seizure-free period of 6, 12, 18, or 24 months from the date of the first (index) seizure. Regression modelling was used to investigate how antiepileptic treatment and several clinical factors influence the risk of seizure recurrence. At six months after the index seizure the risk of recurrence in the next 12 months for those who start antiepileptic drugs was significantly below 20% (unadjusted risk 14%, 95% confidence interval 10% to 18%). For patients who did not start treatment the risk estimate was less than 20% but the upper limit of the confidence interval was greater than 20% (18%, 13% to 23%). Multivariable analyses identified subgroups with a significantly greater than 20% risk of seizure recurrence in the 12 months after a six month seizure-free period, such as those with a remote symptomatic seizure with abnormal electroencephalogram results. After a single unprovoked seizure this reanalysis of MESS provides estimates of seizure recurrence risks that will inform policy and guidance about regaining an ordinary driving licence. Further guidance is needed as to how such data should be utilised; in particular, whether a population approach should be taken with a focus on the unadjusted results or whether attempts should be made to individualise risk. Guidance is also required as to whether the focus should be on risk estimates only or on the confidence interval as well. If the focus is on the estimate only our unadjusted estimates suggest that treated and untreated patients are eligible to drive after being seizure-free for six months. If the focus is also on confidence intervals, direction is needed as to whether a conservative or liberal approach should be taken. Current Controlled Trials ISRCTN98767960.


Con un pie en dos islas: cultural bridges that inform sexual and reproductive health in the Dominican Republic and New York.
Immigrants from the Dominican Republic have grown in number and currently make up a substantial portion of New York City's population. In order to better understand the cultural context of Dominican women's sexual and reproductive health attitudes and practices, focus groups were conducted with Dominican women living in New York City as well as with women living in the Dominican Republic. Analysis found that women in the USA had more economic independence and a greater sense of freedom in regards to sexuality than women in the Dominican Republic. However, those in New York City also hoped to maintain their cultural identity in many ways. Women associated the prevalence of gender-based violence with male unemployment and alcohol abuse. Women in both locales reported limited condom use and saw contraception as a woman's responsibility. Many barriers to using the healthcare system were identified and, in many cases, there exists a preference for herbal treatments and folk remedies. This study provided many important insights that have the potential to increase the quality of sexual and reproductive health care for Dominican women.


Experimental evaluation of the velvet pad rinse technique as a microbiological sampling method.
The use of velvet pads glued to aluminium foil has been evaluated as a microbiological sampling method in quantitative bacterial recovery experiments, and the efficiency and precision have been determined. The velvet pads uptake of Staphylococcus epidermidis was 0.93 (or 93 per cent) after sampling from a test surface on blood agar, while the release by subsequent imprinting on blood agar was 0.02, the median effective transfer being 0.02. A mechanical rinse and shake procedure of the velvet pad in 0.9 per cent saline followed by centrifugation and surface plating significantly increased the median release to 0.66, the median effective transfer being 0.61. There was no difference in uptake, release and effective transfer between a pure culture of S. epidermidis and a mixed culture of S. epiderimidis and Escherichia coli. Storage of the velvet pad in 0.9 per cent saline for 2 h at room temperature did not influence bacterial recovery significantly, in contrast to a significant decrease after storage in saline for 24 h or storage in a dry Petri dish for 2 h. The high and fairly constant efficiency of bacterial recovery of the velvet pad rinse technique suggests that it could be employed clinically.


Predictors of return to work after stroke: a prospective, observational cohort study with 6 months follow-up.
To determine, in Brazil, the proportion of individuals who return to a paid work after stroke, and the factors which predict this. A prospective observational cohort study was carried out for six months. Participants were recruited early after stroke from four public hospitals. The outcome of interest was return to work, and the following predictors were investigated: age, sex, education, marital status, contribution to household income, type of work, independence, and depression. Logistic regression was used to identify multivariate predictors of return to work. Of the 117 included participants, 52 (44%) had returned to work by 6 months. Contribution to household income (OR 2.4; 95% CI 1.0 to 5.9), being a white-collar worker (OR 4.0; 95% CI 1.8 to 8.6) and being independent in daily activities at 3 months (OR 10.6; 95% CI 2.9 to 38.3), in combination, positively predicted return to work. Less than 50% of stroke survivors returned to work six months after stroke. Among predictors, only the level of dependence in daily activities is a modifiable factor. Interventions aimed at reducing disability after stroke might increase rates of return to work.Implications for rehabilitationIn Brazil, less than 50% of stroke survivors returned to work six months after stroke.Clinicians may collect information regarding household income, type of work and dependence in daily activities to estimate chances of returning to work, in developing countries.Being independent at 3 months was the strongest predictor of return to work; therefore, interventions aimed at reducing disability after stroke may increase rates of return to work.


Protease-activated receptors are potential regulators in the development of arterial endofibrosis in high-performance athletes.
High-performance athletes can develop symptomatic arterial flow restriction during exercise caused by endofibrosis. The pathogenesis is poorly understood; however, coagulation enzymes, such as tissue factor (TF) and coagulation factor Xa, might contribute to the fibrotic process, which is mainly regulated through activation of protease-activated receptors (PARs). Therefore, the aim of this explorative study was to evaluate the presence of coagulation factors and PARs in endofibrotic tissue, which might be indicative of their potential role in the natural development of endofibrosis. External iliac arterial specimens with endofibrosis (n = 19) were collected during surgical interventions. As control, arterial segments of the external iliac artery (n = 20) were collected post mortem from individuals with no medical history of cardiovascular disease who donated their body to medical science. Arteries were paraffinized and cut in tissue sections for immunohistochemical analysis. Positive staining within lesions was determined with ImageJ software (National Institutes of Health, Bethesda, Md). Endofibrotic segments contained a neointima, causing intraluminal stenosis, which was highly positive for collagen (+150%; P < .01) and elastin (+148%; P < .01) in comparison with controls. Intriguingly, endofibrosis was not limited to the intima because collagen (+213%) and elastin (+215%) were also significantly elevated in the media layer of endofibrotic segments. These findings were accompanied by significantly increased α-smooth muscle actin-positive cells, morphologically compatible with the presence of myofibroblasts. In addition, PAR1 and PAR4 and the membrane receptor TF were increased as well as coagulation factor X. We showed that myofibroblasts and the accompanying collagen and elastin synthesis might be key factors in the development of endofibrosis. The special association with increased presence of PARs, factor X, and TF suggests that protease-mediated cell signaling could be a contributing component in the mechanisms leading to endofibrosis.


Influence of diaphragmatic contraction on ventilation distribution in horizontal man.
The washout of a bolus of helium (inhaled from residual volume) during relaxed expiration (RE) through a resistance was compared with that during expiration with voluntary diaphragmatic contraction (VDCE) achieved by tensing the abdominal muscles while maintaining constant expiratory flow (less than 0.4 l/s). In six subjects in the lateral decubitus position, phase IV during RE started at 58 +/- 1.6% vital capacity (VC) (mean +/- 1 SE). During VDCE, when the transdiaphragmatic pressure (Pdi) exceeded 30 cmH2O, phase IV commenced at 8.2 +/- 0.8% VC. The expired He concentration (FEHe) at lung volumes greater than 70% VC was 1.3 +/- 0.05 times that during RE. In supine subjects VDCE flattened the slope of the alveolar plateau and decreased closing volume by 3.7 +/- 0.4% VC. Our results suggest that when the diaphragm is relaxed in the horizontal subject, the hydrostatic gradient of pressure within the abdomen enhances early emptying of dependent lung zones. Diaphragmatic contraction results in more homogeneous emptying. We conclude that diaphragmatic tone influences the vertical gradient of regional volume, and hence of pleural pressure. The latter is not constant, being less during inspiration than during expiration. Therefore, differences in the changes of applied pressure between dependent and nondependent lung regions influence ventilation distribution in subjects in the horizontal posture.


Stop codon mutagenesis for homogenous expression of human papillomavirus L1 protein in Escherichia coli.
Human papillomavirus (HPV) is widely accepted to be the major causative pathogen of cervical cancer, warts, and other epithelial tumors. Virus infection and subsequent disease development can be prevented by vaccination with HPV vaccines derived from eukaryotic expression systems. Here, we report the soluble expression of the major capsid protein L1 of HPV31, a dominant carcinogenic HPV genotype, in Escherichia coli. HPV31 L1 protein and its elongated form (L1+) were observed in SDS-PAGE and CE-SDS analysis, generated by the native HPV31 L1 gene with a TAA stop codon. Replacing the TAA with TAG but not TGA could completely terminate protein translation. Mass spectrometry sequencing showed that L1+ comprised L1 with a C-terminal extension of 38 amino acids (aa). RNA folding analysis revealed that the unfaithful L1+ expression may result from translational read-through, as TAG is more stable and accessible than the other stop codons. The 38-aa elongated fragment perturbs self-assembly of HPV31 L1+, as shown in size and morphology analyses. By 3D cryo-electron microscopy structure determination, we show self-assembly of purified HPV31 L1 (TAG) VLPs into T = 7 icosahedral symmetry particles, resembling the native HPV virion. Finally, through additional characterization and antigenicity/immunogenicity assays, we verified that the E.coli-derived HPV31 VLPs are an ideal immunogen for HPV vaccine development. Our findings outline a codon optimization stratagem for protein expression and provide a method for the in-depth investigation of prokaryotic translation regulation.


Digital Health Care and the Fourth Industrial Revolution.
We live in a world where big medical data are being compiled. Many people make use of biometric information gathered by a variety of health care devices linked to smartphones, such as Fitbit devices. In addition, the development of medical information management schemes and the introduction of health information systems have greatly increased the possibility of using medical records stored in medical institutions. With the development of sensor technology and analytical capabilities, we have gained new knowledge through big data, stemming from the collection of data that was not important in the current medical area. Digital health care is moving toward creating value while creating utility as well based on data collected beyond the level of those collected by sensors. Only organizations that have quickly entered the market and accumulated data and have already developed advanced algorithms based on the data can be competitive. However, digital health care companies that survive in the market will lead the change and will reorganize the health care sector. In addition, a big data-based health care platform can help increase the number of e-patients through patient participation.


Left Habenular Activity Attenuates Fear Responses in Larval Zebrafish.
Fear responses are defensive states that ensure survival of an organism in the presence of a threat. Perception of an aversive cue causes changes in behavior and physiology, such as freezing and elevated cortisol, followed by a return to the baseline state when the threat is evaded [1]. Neural systems that elicit fear behaviors include the amygdala, hippocampus, and medial prefrontal cortex. However, aside from a few examples, little is known about brain regions that promote recovery from an aversive event [2]. Previous studies had implicated the dorsal habenular nuclei in regulating fear responses and boldness in zebrafish [3-7]. We now show, through perturbation of its inherent left-right (L-R) asymmetry at larval stages, that the dorsal habenulo-interpeduncular (dHb-IPN) pathway expedites the return of locomotor activity following an unexpected negative stimulus, electric shock. Severing habenular efferents to the IPN, or only those from the left dHb, prolongs the freezing behavior that follows shock. Individuals with a symmetric, right-isomerized dHb also exhibit increased freezing. In contrast, larvae that have a symmetric, left-isomerized dHb, or in which just the left dHb-IPN projection is optogenetically activated, rapidly resume swimming post shock. In vivo calcium imaging reveals a neuronal subset, predominantly in the left dHb, whose activation is correlated with resumption of swimming. The results demonstrate functional specialization of the left dHb-IPN pathway in attenuating the response to fear.


Endoscopic pubic symphysectomy for reclacitrant osteitis pubis associated with bilateral femoroacetabular impingement.
This is the first reported case of the completely endoscopic management of osteitis pubis with pubic symphysectomy. A 31-year-old woman suffered from recalcitrant osteitis pubis that had progressed to an end-stage auto-fused condition. Ossified pubic symphyseal fibrocartilage and adjacent heterotopic bone were endoscopically removed as part of a comprehensive surgery that also involved bilateral arthroscopic surgery for symptomatic femoroacetabular impingement. An innovative dual-portal (anterior and supra-pubic) endoscopic technique is presented along with the rationale for the preservation of the inferior (arcuate) pubic ligament and the posterior pubic ligament. Twelve months following this single-stage surgery, the patient reported high satisfaction with decreased pain, improved function, and resolution of a classic waddling gait. The association of intra-articular hip pathology with osteitis pubis is noted. We believe that this minimally invasive bone-conserving surgery may be useful in the management of recalcitrant osteitis pubis and perhaps find broader application in the outpatient endoscopic treatment of athletes afflicted with this condition.


Predatory and competitive interaction in Anopheles gambiae sensu lato larval breeding habitats in selected villages of central Uganda.
Malaria is often persistent in communities surrounded by mosquito breeding habitats. Anopheles gambiae sensu lato exploit a variety of aquatic habitats, but the biotic determinants of its preferences are poorly understood. This study aimed to identify and quantify macroinvertebrates in different habitat types with determined water physico-chemical parameters to establish those preferred by An. gambiae s.l. larvae as well as their predators and competitors. A field survey was conducted in Kibuye and Kayonjo villages located in the vicinity of the River Sezibwa, north-eastern Uganda to identify Anopheline larval habitats shared by aquatic insects. Habitats were geo-recorded and as streams, ponds, temporary pools and roadside ditches. From October to December 2017, random microhabitats/quadrats were selected from each habitat type, their water physico-chemical parameters (electrical conductivity, total dissolved solids, temperature and pH) were measured, and they were sampled for macroinvertebrates using standard dippers. All collected arthropod macroinvertebrates were then morphologically identified to family level and enumerated. Principal component analysis showed that the four larval habitat types were characterized by distinct physico-chemical parameter profiles. Ponds and streams had the highest number and diversity of macroinvertebrate insect taxa and sustained few An. gambiae s.l. larvae. Anopheles gambiae s.l. were more common in roadside ditches and particularly abundant in temporary pools which it commonly shared with Dytiscidae (predaceous diving beetles) and Culex spp. Cluster correlation analysis conducted on the abundance of these taxa within quadrats suggested that An. gambiae s.l. and Dytiscidae have the most similar patterns of microhabitat use, followed by Cybaeidae (water spiders). Whilst Culex spp. co-occurred with An. gambiae s.l. in some habitats, there was only partial niche overlap and no clear evidence of competition between the two mosquito taxa. Ponds and streams are habitats that host the largest diversity and abundance of aquatic insect taxa. Anopheles gambiae s.l. larvae distinctively preferred temporary pools and roadside ditches, where they were exposed to few predators and no apparent competition by Culex spp. Further studies should aim to test the impact of Dytiscidae and Cybaeidae on An. gambiae s.l. dynamics experimentally.


[Imaging studies of excretory urography and computed tomography scan for patients suffering from renal colic].
Renal colic mainly due to urolithiasis is one of the most common morbid conditions in urology and commonly seen in the urology emergency clinic. Imaging studies were performed to evaluate the upper urinary tract of 29 patients suffering from renal colic in the 2 years between November, 1994 and October, 1996. After intramuscular injection of the analgesic (pentazocine, 15 mg), all 29 patients were examined by excretory urography (IVP) at the time of the first visit. In some patients abdominal plain computed tomography (CT) scan was performed consecutively even when extravasation of the contrast medium was not seen. Spontaneous peripelvic extravasation was seen in 14 patients (11 males and 3 females) with urolithiasis; 7 of them were diagnosed by IVP, 5 by IVP plus CT scan and 2 with CT scan only. IVP imaging study followed by plain abdominal CT scan is useful even when the contrast medium is not extravasated on IVP in patients suffering from renal colic.


DANoC: An Efficient Algorithm and Hardware Codesign of Deep Neural Networks on Chip.
Deep neural networks (NNs) are the state-of-the-art models for understanding the content of images and videos. However, implementing deep NNs in embedded systems is a challenging task, e.g., a typical deep belief network could exhaust gigabytes of memory and result in bandwidth and computational bottlenecks. To address this challenge, this paper presents an algorithm and hardware codesign for efficient deep neural computation. A hardware-oriented deep learning algorithm, named the deep adaptive network, is proposed to explore the sparsity of neural connections. By adaptively removing the majority of neural connections and robustly representing the reserved connections using binary integers, the proposed algorithm could save up to 99.9% memory utility and computational resources without undermining classification accuracy. An efficient sparse-mapping-memory-based hardware architecture is proposed to fully take advantage of the algorithmic optimization. Different from traditional Von Neumann architecture, the deep-adaptive network on chip (DANoC) brings communication and computation in close proximity to avoid power-hungry parameter transfers between on-board memory and on-chip computational units. Experiments over different image classification benchmarks show that the DANoC system achieves competitively high accuracy and efficiency comparing with the state-of-the-art approaches.


Transesophageal cardioversion of atrial flutter and atrial fibrillation using an electric balloon electrode system.
To determine the feasibility and efficiency of terminating atrial flutter (AFL) and atrial fibrillation (AF) using synchronous low-energy shocks delivered through a novel transesophageal electric balloon electrode system. By using a novel electric balloon electrode system, we attempted 91 transesophageal cardioversions in 52 patients, to treat 53 episodes of AFL and 38 episodes of AF. Of the 40 patients of AFL that failed to respond to drug therapy, 37 (92.5%) were successfully countershocked to sinus rhythm by transesophageal cardioversion, with a mean energy of (22.70 +/- 4.50) J (20 - 30 J). Of the 19 patients in AF, transesophageal cardioversion was successful in 16 (84.2%) cases, requiring a mean delivered energy of (17.38 +/- 8.58) J (3 - 30 J). There were no complications such as heart block or ventricular fibrillation, and no evidence of esophageal injury. Transesophageal cardioversion using an electric balloon electrode system is an effective and feasible method for the treatment of AFL and AF. It requires low energy and no anesthesia, leads to less trauma, and shows a high cardioversion success rate that may prove valuable in the management of tachyarrhythmias.


A new coumarin and a new norlignan from Ficus tsiangii.
Chemical investigation of the stem bark of Ficus tsiangii led to the isolation of a new coumarin ficuscoumarin (1) and a new norlignan ficuslignan (2) by chromatographic methods. Their structures were elucidated on the basis of spectroscopic analyses.


Parameter tuning in machine learning based on radiomics biomarkers of lung cancer.
Lung cancer is one of the most common cancers, and early diagnosis and intervention can improve cancer cure rate. To improve predictive performance of radiomics features for lung cancer by tuning the machine learning model parameters. Using a dataset involving 263 cases (125 benign and 138 malignant) acquired from our hospital, each classifier model is trained and tested using 237 and 26 cases, respectively. We initially extract 867 radiomics features of CT images for model development and then test 10 feature selections and 7 models to determine the best method. We further tune the parameter of the final model to reach the best performance. The adjusted final model is then validated using 224 cases acquired from Lung Image Database Consortium (LIDC) dataset (64 benign and 160 malignant) with the same set of selected radiomics features. During model development, the feature selection via concave minimization method show the best performance of area under ROC curve (AUC = 0.765), followed by l0-norm regularization (AUC = 0.741) and Fisher discrimination criterion (AUC = 0.734). Support vector machine (SVM) and random forest (RF) are the top two machine learning algorithms showing the best performance (AUC = 0.765 and 0.734, respectively), using by the default parameter. After parameter tuning, SVM with linear kernel achieves the best performance (AUC = 0.837), whereas the best tuned RF with the number of trees is 510 and yields a slightly lower performance (AUC = 0.775) in 26 test samples data. During model validation, the SVM and RF models yield AUC = 0.78 and 0.77, respectively. Appropriate quantitative radiomics features and accurate parameters can improve the model's performance to predict lung cancer.


Lack of awareness of neurogastroenterology and motility within medical education: Time to fill the gap.
Disorders of gut-brain interaction (DGBI), previously referred to as functional gastrointestinal disorders, affect 40.3% of adults in the general population and are diagnosed in 34.9% of new adult referrals to secondary care gastroenterology services. Despite their high prevalence, studies published in this issue of Neurogastroenterology and Motility by investigators based in Germany, the UK, and the USA demonstrate a mismatch between the clinical burden of DGBI and their representation in medical school and postgraduate curricula. This review outlines the salient findings of these studies and explores why and how negative perceptions toward DGBI exist, including factors related to misinformation and internalized stigma. The authors propose a selection of strategies to ameliorate physicians' attitudes toward and knowledge of neurogastroenterology and motility including linking trainees with dedicated clinician mentors with an interest in motility, exposing trainees to expert patients who can enhance empathy, extending Balint groups into gastroenterology training, and offering motility apprenticeships in specialist units. Urgent improvements to medical school and postgraduate curricula are required to ensure the longevity of this subspecialty field in gastroenterology, and to ensure the needs of a sizeable proportion of gastroenterology patients are appropriately met.


Aquablation versus TURP: 5-year outcomes of the WATER randomized clinical trial for prostate volumes 50-80 mL.
To report the 5-year efficacy and safety of Aquablation compared with transurethral resection of the prostate for the management of lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with prostate volumes 50-80 mL. In a large double-blinded, multicenter, and prospective randomized controlled trial, 96 randomized men with 50-80 mL prostates who underwent Aquablation or transurethral prostate resection were prospectively identified for subgroup analysis. Follow up was performed for up to 5 years. The primary efficacy endpoint was the reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo (CD) postoperative complications grade 1 persistent and grade 2 or higher at 3 months. Both groups had comparable baseline characteristics. Reduction in IPSS score was significantly higher in the Aquablation group across 5 years of follow up (-14.1 vs. -10.8, p = 0.02). The Aquablation group achieved a significantly lower rate of CD1P and CD2 or higher events at 3 months follow up (risk difference of -23.1%). Among recorded adverse events, de novo postoperative ejaculatory dysfunction was notably lower in Aquablation (risk difference of -21.9%), while the risk of bleeding remained similar after 6 months. The surgical and medical retreatment rate at 6 months was also lower in Aquablation (risk difference of -14.4%). In the 50-80 mL prostate volume subgroup, Aquablation yields superior long-term symptom relief and lower complication rates than standard transurethral resection, with notably lower rates of ejaculatory dysfunction. This further supports the adoption of Aquablation for men with medium-sized prostates.


Biological pacing by gene and cell therapy.
At present, cardiac rhythm disorders such as sick sinus syndrome (SSS) or AV nodal block (AVB) are usually treated by electronic pacemakers. These devices have significant shortcomings, including lack of autonomic modulation, and the need for repetitive procedures for battery replacement or lead repositioning. Biological pacemakers as replacement or complement to electronic pacemakers have been the subject of increasing research interest. This research has resulted in many encouraging preclinical studies. Various approaches in the field of gene and cell therapy have been developed by different groups and this combined effort makes it increasingly realistic that this therapy will eventually find its way to clinical applicability. (Neth Heart J 2007;15:318-22.).


Cladosporium cladosporioides-complex infection in a mixed-breed dog.
A 3-year-old female mixed-breed dog was referred with a 2-day history of serious dyspnea, coughing, lethargy, anorexia, and a low-grade right anterior lameness. At presentation, the dog had an increased respiratory rate, dull heart and lung sounds, and cyanotic mucous membranes. It was hyperthermic and slightly dehydrated. Laboratory findings showed mild neutrophilia with a left shift, while serum biochemistry variables were in the normal range. However, urinalysis revealed mild proteinuria and rare erythrocytes and leukocytes on sediment examination. Thoracic radiographs showed a diffuse mixed interstitial and alveolar pattern with an air bronchogram, while appendicular radiographs showed a right humeral interrupted brush-like periosteal reaction. Thoracic ultrasonography revealed mediastinal lymph node enlargement. Cytology from a fine-needle aspirate of mediastinal lymph nodes revealed a pyogranulomatous lymphadenitis with numerous fungal hyphae. Culture on Sabouraud dextrose agar isolated dark fungal colonies with microscopic features consistent with Cladosporium spp. Sequencing of the internal transcribed spacer region identified the fungus as a species of the Cladosporium cladosporioides-complex.


Antifibrotic effects of a polysaccharide extracted from Ganoderma lucidum, glycyrrhizin, and pentoxifylline in rats with cirrhosis induced by biliary obstruction.
For the past few years, we have been investigating polysaccharides from Ganoderma lucidum as antifibrotic agents. In a previous study, we discovered that polysaccharides extracted from G. Iucidum lowered the collagen content in liver but had no effect on serum biochemical parameters in rats subjected to bile duct ligation and scission-induced fibrosis. In this study, we changed the extraction method and obtained polysaccharides extracted from G. Iucidum. The polysaccharide from G. Iucidum reduced the serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin and also reduced the collagen content in liver and improved the morphology. Pentoxifylline, which is reported to exhibit an antifibrotic effect in pigs with fibrosis induced by yellow phosphorus, did not have any antifibrotic effects in fibrosis induced by biliary obstruction. Glycyrrhizin, which is used in the treatment of hepatitis, reduced serum ALT and AST values but there was no significance. It had no effect on liver hydroxyproline content which implies that glycyrrhizin has no antifibrotic effect in the rats with fibrosis induced by bile duct ligation and scission. These data suggest that the polysaccharide from Ganoderma lucidum could be a promising antifibrotic agent. However, further study is needed to understand the inhibition mechanism of collagen deposition of polysaccharides from Ganoderma Iucidum and its clinical applicability remains to be established.


Blood glucose monitoring and management in acute stroke care.
Diabetes mellitus is a major risk factor for stroke. Concerns have been raised that adults with acute stroke, irrespective of whether or not they have a history of diabetes mellitus, are at increased risk of experiencing hyperglycaemia and hypoglycaemia. Hyperglycaemia is associated with severe stroke and poor clinical outcomes, therefore blood glucose monitoring and management are essential skills for healthcare professionals caring for patients who have had a stroke.


Targeting myostatin for therapies against muscle-wasting disorders.
In addition to gene correction therapy and cell transplantation techniques, multidisciplinary approaches to drug discovery and development offer promising therapeutic strategies for intractable genetic muscular disorders including muscular dystrophy. Inhibition of the production and activity of myostatin, a potent growth factor that determines skeletal muscle size, is a novel strategy for the treatment of muscle-wasting disorders such as muscular dystrophy, cachexia and sarcopenia. Myostatin blockers include myostatin-blocking antibodies, myostatin propeptide, follistatin and follistatin-related proteins, soluble myostatin receptors, small interfering RNA and small chemical inhibitors. This review describes the discovery and development of myostatin inhibitors.


Isolation and Identification of Proteins Secreted by Cells Cultured within Synthetic Hydrogel-Based Matrices.
Cells interact with and remodel their microenvironment, degrading large extracellular matrix (ECM) proteins (e.g., fibronectin, collagens) and secreting new ECM proteins and small soluble factors (e.g., growth factors, cytokines). Synthetic mimics of the ECM have been developed as controlled cell culture platforms for use in both fundamental and applied studies. However, how cells broadly remodel these initially well-defined matrices remains poorly understood and difficult to probe. In this work, we have established methods for widely examining both large and small proteins that are secreted by cells within synthetic matrices. Specifically, human mesenchymal stem cells (hMSCs), a model primary cell type, were cultured within well-defined poly(ethylene glycol) (PEG)-peptide hydrogels, and these cell-matrix constructs were decellularized and degraded for subsequent isolation and analysis of deposited proteins. Shotgun proteomics using liquid chromatography and mass spectrometry identified a variety of proteins, including the large ECM proteins fibronectin and collagen VI. Immunostaining and confocal imaging confirmed these results and provided visualization of protein organization within the synthetic matrices. Additionally, culture medium was collected from the encapsulated hMSCs, and a Luminex assay was performed to identify secreted soluble factors, including vascular endothelial growth factor (VEGF), endothelial growth factor (EGF), basic fibroblast growth factor (FGF-2), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α). Together, these methods provide a unique approach for studying dynamic reciprocity between cells and synthetic microenvironments and have the potential to provide new biological insights into cell responses during three-dimensional (3D) controlled cell culture.


Overlapping Functional Representations of Self- and Other-Related Thought are Separable Through Multivoxel Pattern Classification.
Self-reflection and thinking about the thoughts and behaviors of others are important skills for humans to function in the social world. These two processes overlap in terms of the component processes involved, and share overlapping functional organizations within the human brain, in particular within the medial prefrontal cortex (MPFC). Several functional models have been proposed to explain these two processes, but none has directly explored the extent to which they are distinctly represented within different parts of the brain. This study used multivoxel pattern classification to quantify the separability of self- and other-related thought in the MPFC and expanded this question to the entire brain. Using a large-scale mega-analytic dataset, spanning three separate studies (n = 142), we find that self- and other-related thought can be reliably distinguished above chance within the MPFC, posterior cingulate cortex and temporal lobes. We highlight subcomponents of the ventral MPFC that are particularly important in representing self-related thought, and subcomponents of the orbitofrontal cortex robustly involved in representing other-related thought. Our findings indicate that representations of self- and other-related thought in the human brain are described best by a distributed pattern rather than stark localization or a purely ventral to dorsal linear gradient in the MPFC.


The transcription factor Pitx3 is expressed selectively in midbrain dopaminergic neurons susceptible to neurodegenerative stress.
The homeodomain transcription factor Pitx3 is critical for the survival of midbrain dopaminergic (mDA) neurons. Pitx3-deficient mice exhibit severe but selective developmental loss of mDA neurons, with accompanying locomotor deficits resembling those seen in Parkinson's disease (PD) models. Here, we identify specific mDA cell subpopulations that are consistently spared in adult Pitx3-hypomorphic (aphakia) mice, demonstrating that Pitx3 is not indiscriminately required by all mDA neurons for their survival. In aphakia mice, virtually all surviving mDA neurons in the substantia nigra (SN) and the majority of neurons in the adjacent ventral tegmental area (VTA) also express calbindin-D28k, a calcium-binding protein previously associated with resistance to injury in PD and in animal models. Cell-mapping studies in wild-type mice revealed that Pitx3 is primarily expressed in the ventral SN, a region particularly susceptible to MPTP and other dopaminergic neurotoxins. Furthermore, Pitx3-expressing SN cells are preferentially lost following MPTP treatment. Finally, SN mDA neurons in Pitx3 hemizygous mice show increased sensitivity when exposed to MPTP. Thus, SN mDA neurons are represented by at least two distinct subpopulations including MPTP-resistant Pitx3-autonomous, calbindin-positive neurons, and calbindin-negative Pitx-3-dependent cells that display elevated vulnerability to toxic injury, and probably correspond to the subpopulation that degenerates in PD. Impairment of Pitx3-dependent pathways therefore increases vulnerability of mDA neurons to toxic injury. Together, these data suggest a novel link between Pitx3 function and the selective pattern of mDA cell loss observed in PD.