Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals.
Older age is one of the most important shared risk factors for multiple chronic diseases, increasing the medical burden to contemporary societies. Current research focuses on identifying aging biomarkers to predict aging trajectories and developing interventions aimed at preventing and delaying the progression of multimorbidity with aging. Here, a transcriptomic changes analysis of whole blood genes with age was conducted. The age-related whole blood gene-expression profiling datasets were downloaded from the Gene Expression Omnibus (GEO) database. We screened the differentially expressed genes (DEGs) between healthy young and old individuals and performed functional enrichment analysis. Cytoscape with Cytohubba and MCODE was used to perform an interaction network of DEGs and identify hub genes. In addition, ROC curves and correlation analysis were used to evaluate the accuracy of hub genes. In total, we identified 29 DEGs between young and old samples that were enriched mainly in immunoglobulin binding and complex, humoral immune response, and immune response-activating signaling pathways. In combination with the PPI network and topological analysis, 4 hub genes (IGLL5, Jchain, POU2AF1, and Bach2) were identified. Pearson analysis showed that the expression changes of these hub genes were highly correlated with age. Among them, 3 hub genes (IGLL5, POU2AF1, and Bach2) were identified with good accuracy (AUC score > 0.7), indicating that these genes were the best indicators of age. Together, our results provided potential biomarkers IGLL5, POU2AF1, and Bach2 to identify individuals at high early risk of age-related disease to be targeted for early interventions and contribute to understanding the molecular mechanisms in the progression of aging.


Effect of occupation on lipid peroxidation and antioxidant status in coal-fired thermal plant workers.
Air pollution from coal-fired power units is large and varied, and contributes to a significant number of negative environmental and health effects. Reactive oxygen species (ROS) have been implicated in the pathogenesis of coal dust-induced toxicity in coal-fired power plants. The aim of the study was to measure free radical damage and the antioxidant activity in workers exposed to varying levels of coal dust. The study population consisted of workers in coal handling unit, turbine unit, and boiler unit (n = 50 each), working in thermal power plant; and electricians (n = 50) from same department were taken as controls. Lipid peroxidation was measured by malondialdehyde (MDA) levels and antioxidant activity was determined by superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. Statistical analysis was carried out by Student's unpaired t-test. MDA levels showed significant increase (P > 0.001) in the thermal power plant workers than the electricians working in the city. The levels of SOD and GPx were significantly higher (P > 0.001) in electricians as compared to subjects working in thermal plant. Among the thermal plant workers, the coal handling unit workers showed significant increase (P > 0.001) in MDA and significant decrease in SOD and GPx than the workers of boiler and turbine unit workers. Oxidative stress due to increase in lipid peroxidation and decrease in antioxidant activity results from exposure to coal dust and coal combustion products during thermal plant activities.


Transcription factors in Escherichia coli prefer the holo conformation.
The transcriptional regulatory network of Escherichia coli K-12 is among the best studied gene networks of any living cell. Transcription factors bind to DNA either with their effector bound (holo conformation), or as a free protein (apo conformation) regulating transcription initiation. By using RegulonDB, the functional conformations (holo or apo) of transcription factors, and their mode of regulation (activator, repressor, or dual) were exhaustively analyzed. We report a striking discovery in the architecture of the regulatory network, finding a strong under-representation of the apo conformation (without allosteric metabolite) of transcription factors when binding to their DNA sites to activate transcription. This observation is supported at the level of individual regulatory interactions on promoters, even if we exclude the promoters regulated by global transcription factors, where three-quarters of the known promoters are regulated by a transcription factor in holo conformation. This genome-scale analysis enables us to ask what are the implications of these observations for the physiology and for our understanding of the ecology of E. coli. We discuss these ideas within the framework of the demand theory of gene regulation.


Comparison of Wrist and Forearm EMG for Multi-day Biometric Authentication.
Recently, electromyography (EMG) has been established as a promising new biometric trait that provides a unique dual mode security: biometrics and knowledge. For authentication that is used daily and long-term by general consumers, the wrist is a suitable location, which could be easily integrated into the existing form of smartwatches and fitness trackers. However, current EMG-based biometrics still follow the historical path of powered prosthetics research, where EMG signals were usually recorded from forearm positions. Moreover, the robustness of EMG processing algorithms across multiple days is still an open problem that needs to be addressed before for long-term reliable use. This study intends to investigate the difference in authentication performance between wrist and forearm EMG signals, in a within-day and two cross-day analyses. Our open dataset (GRABMyo dataset) was used to examine this difference, which contains forearm and wrist EMG data collected from 43 participants over three different days with long separation (Days 1, 8, and 29). The results showed wrist EMG signals led to at least comparable with forearm EMG signals in within-day Equal-error rate (EER). In cross-day analysis, the EER of the wrist EMG signals was higher than that of forearm signals. In general, the low median EER (<0.1) of wrist EMG in cumulative cross-day analysis demonstrates the promise of using wrist EMG signals for authentication in long-term applications.


Genetic and metabolic determinants of nutritional phenotype in an insect-bacterial symbiosis.
The pervasive influence of resident microorganisms on the phenotype of their hosts is exemplified by the intracellular bacterium Buchnera aphidicola, which provides its aphid partner with essential amino acids (EAAs). We investigated variation in the dietary requirement for EAAs among four pea aphid (Acyrthosiphon pisum) clones. Buchnera-derived nitrogen contributed to the synthesis of all EAAs for which aphid clones required a dietary supply, and to none of the EAAs for which all four clones had no dietary requirement, suggesting that low total dietary nitrogen may select for reduced synthesis of certain EAAs in some aphid clones. The sequenced Buchnera genomes showed that the EAA nutritional phenotype (i.e. the profile of dietary EAAs required by the aphid) cannot be attributed to sequence variation of Buchnera genes coding EAA biosynthetic enzymes. Metabolic modelling by flux balance analysis demonstrated that EAA output from Buchnera can be determined precisely by the flux of host metabolic precursors to Buchnera. Specifically, the four EAA nutritional phenotypes could be reproduced by metabolic models with unique profiles of host inputs, dominated by variation in supply of aspartate, homocysteine and glutamate. This suggests that the nutritional phenotype of the symbiosis is determined principally by host metabolism and transporter genes that regulate nutrient supply to Buchnera. Intraspecific variation in the nutritional phenotype of symbioses is expected to mediate partitioning of plant resources among aphid genotypes, potentially promoting the genetic subdivision of aphid populations. In this way, microbial symbioses may play an important role in the evolutionary diversification of phytophagous insects.


Bronchial wall thickness in toll collectors.
There is an increasing concern about the possible adverse effects of diesel exhaust particulates on human health. In a diesel exposed occupational group composed of 120 toll collectors, a cross-sectional study was performed to evaluate the chest radiographs and 40 toll collectors were selected for computed tomography examination according to hyperinflation and linear markings. The wall thicknesses and luminal diameters of trachea, main bronchi, and segmental bronchi of right apical and posterior basal segments were measured with manual tracing method. The walls of right upper bronchus in exsmoker toll collectors were significantly thicker than those of nonsmokers (p=0.011). A positive correlation was observed between age and the right upper bronchus wall thickness (r=0.577, p=0.000). An inverse correlation was found between the working duration and the diameter of right main bronchus (r=-0.366, p=0.020). A positive correlation was seen between smoking and the right upper bronchus wall thickness (r=0.457, p=0.005). Diesel exposure might have a role in increase of thickness of large airways wall and a decrease in the diameters of large airways. Studies in this area are needed to protect the population under the diesel exposure risk.


Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor imaging.
Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location.


Structure-Activity Relationships for DNA Damage by Alkenylbenzenes in Turkey Egg Fetal Liver.
Certain alkenylbenzenes (AB), flavoring chemicals naturally occurring in spices and herbs, are established to be cytotoxic and hepatocarcinogenic in rodents. The purpose of the present study was to determine the DNA damaging potential of key representatives of this class using the Turkey Egg Genotoxicity Assay. Medium white turkey eggs with 22- to 24-day-old fetuses received three injections of nine AB with different carcinogenic potentials: safrole (1, 2 mg/egg), methyl eugenol (2, 4 mg/egg), estragole (20, 40 mg/egg), myristicin (25, 50 mg/egg), elemicin (20, 50 mg/egg), anethole (5, 10 mg/egg), methyl isoeugenol (40, 80 mg/egg), eugenol (1, 2.5 mg/egg), and isoeugenol (1, 4 mg/egg). Three hours after the last injection, fetal livers were harvested for measurement of DNA strand breaks, using the comet assay and DNA adducts formation, using the nucleotide(3) (2)P-postlabeling assay. Estragole, myristicin, and elemicin induced DNA stand breaks. These compounds as well as safrole, methyl eugenol and anethole, at the highest doses tested, induced DNA adduct formation. Methyl isoeugenol, eugenol, and isoeugenol did not induce genotoxicity. The genotoxic AB all had the structural features of either a double bond in the alkenyl side chain at the terminal 2',3'-position, favorable to formation of proximate carcinogenic 1'-hydroxymetabolite or terminal epoxide, or the absence of a free phenolic hydroxyl group crucial for formation of a nontoxic glucuronide conjugate. In contrast, methyl isoeugenol, eugenol and isoeugenol, which were nongenotoxic, possessed chemical features, unfavorable to activation.


Atrial pacing as an adjunct to the management of post-surgical His bundle tachycardia.
To examine the benefits of restoring atrioventricular synchrony to children with His bundle tachycardia after operation for congenital heart disease. Review of clinical outcome of adopting the technique of R wave synchronised atrial pacing as an adjunct to the management of His bundle tachycardia from September of 1987 till June of 1990. Eleven consecutive children (aged between 3 days and 13 years) with haemodynamically significant His bundle tachycardia after cardiopulmonary bypass surgery. Atrial pacing synchronised either manually or automatically to the R wave of the His bundle tachycardia was implemented so that atrial depolarisation preceded the following R wave by an appropriate PR interval. An immediate and sustained increase in mean systemic blood pressure (average 15 mm Hg, range 6-30 mm Hg) was seen with the onset of atrial pacing in 10 of the 11 children. One child, who had undergone a Fontan procedure, developed atrial flutter shortly after the onset of atrial pacing and required direct current cardioversion. Four children died. Of the seven survivors, six have sustained sinus rhythm which returned between two and 10 days after the onset of tachycardia. One of the survivors has severe neurological impairment attributed to a period of low cardiac output during tachycardia; the others are alive and well. In those children who did badly the mean time between arrhythmia occurrence and the start of atrial pacing or cooling or both was nine hours; in those who did well it was one hour. Atrial pacing synchronous with the His bundle is a useful adjunct in the management of children with His bundle tachycardia after surgery for congenital cardiac disease.


Three-dimensional in silico breast phantoms for multimodal image simulations.
Anatomic simulators have provided researchers with the realistic objects needed to develop and evaluate medical imaging approaches. Today we have new insights into the cellular biology of breast tissues that is driving many new targeted diagnostic and therapeutic approaches, including molecular imaging. We report on our initial efforts to build a scalable framework for the construction of realistic 3-D in silico breast phantoms (ISBP) capable of leveraging existing knowledge and yet adaptable to fully integrate future discoveries. The ISBP frames are developed with scalable anatomical shapes and morphologic features as adapted from a rich literature on this topic. Frames are populated with tissue subtypes essential for imaging and object contrast functions are assigned. These data can be resampled to match the intrinsics scales of various imaging modalities; we explore mammography, sonography and computed tomography. Initial comparisons between simulated and clinical images demonstrate reasonable agreement and provides guidance for future development of a more realistic ISBP. An end-to-end simulation of breast images is described to demonstrate techniques for including stochastic variability and deterministic physical principles on which image formation is based.


Lactobacillus pentosus var. plantarum C29 increases the protective effect of soybean against scopolamine-induced memory impairment in mice.
Biological activities of soybean saponins are dependent on their metabolism by gut microbiota, which generate absorbable bioactive metabolites. Therefore, to enhance the pharmacological effect of soybean, we fermented defatted soybean powder (SP) with Lactobacillus pentosus var. plantarum C29 and measured its protective effect against scopolamine-induced memory impairment in mice using the passive avoidance, Y-maze and Morris water maze tasks. Fermentation increased soyasapogenol B, genistein and daidzein content of soybean and enhanced the protective effect of soybean against scopolamine-induced memory impairment. Additionally, compared with the exthanol extract of soybean, fermented SP (FSP) increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampi of scopolamine-treated mice. Furthermore, FSP inhibited acetylcholinesterase (AChE) activity in vitro and ex vivo. These findings suggest that C29 fermentation might increase the ameliorating effect of soybean against memory impairments by inhibiting AChE activity and increasing BDNF expression.


Methodology in longitudinal studies on psychological effects of predictive DNA testing: a review.
In the last two decades predictive testing programs have become available for various hereditary diseases, often accompanied by follow-up studies on the psychological effects of test outcomes. The aim of this systematic literature review is to describe and evaluate the statistical methods that were used in these follow-up studies. A literature search revealed 40 longitudinal quantitative studies that met the selection criteria for the review. Fifteen studies (38%) applied adequate statistical methods. The majority, 25 studies, applied less suitable statistical techniques. Nine studies (23%) did not report on dropout rate, and 18 studies provided no characteristics of the dropouts. Thirteen out of 22 studies that should have provided data on missing values, actually reported on the missing values. It is concluded that many studies could have yielded more and better results if more appropriate methodology had been used.


Species-specific double-strand break repair and genome evolution in plants.
Even closely related eukaryotic species may differ drastically in genome size. While insertion of retroelements represents a major source of genome enlargement, the mechanism mediating species- specific deletions is fairly obscure. We analyzed the formation of deletions during double-strand break (DSB) repair in Arabidopsis thaliana and tobacco, two dicotyledonous plant species differing >20-fold in genome size. DSBs were induced by the rare cutting restriction endonuclease I-SCE:I and deletions were identified by loss of function of a negative selectable marker gene containing an I-SCE:I site. Whereas the partial use of micro-homologies in junction formation was similar in both species, in tobacco 40% of the deletions were accompanied by insertions. No insertions could be detected in Arabidopsis , where larger deletions were more frequent, indicating a putative inverse correlation between genome size and the average length of deletions. Such a correlation has been postulated before by a theoretical study on the evolution of related insect genomes and our study now identifies a possible molecular cause for the phenomenon, indicating that species-specific differences in DSB repair might indeed influence genome evolution.


Bilateral peroneal artery aneurysms.
True aneurysm of the tibial arteries is a rare clinical condition. We report the case of a 67-year-old man who presented with a gradual onset of right calf swelling and pain. Imaging revealed large aneurysms arising from the proximal peroneal arteries bilaterally, measuring 7.4cm and 4cm on the right and left respectively. A detailed medical history, clinical examination and laboratory investigations did not identify evidence of an underlying cause. A surgical reconstruction with an interposition vein graft was successfully performed. To our knowledge, this is the first reported case of primary aneurysm of the peroneal artery in the English literature. We undertook a systematic literature review to identify all reported cases of primary aneurysms of the tibial arteries. The clinical presentation, modes of investigation and interventional treatments are discussed.


A 10-year review of primary major salivary gland cancers.
Primary salivary gland cancers comprise a heterogeneous group of histological entities and represent less than 5% of head and neck malignancies. Surgical resection is the main treatment, and adjuvant radiotherapy is performed in selected cases. Chemotherapy is an option in metastatic or recurrent disease, with poor evidence. We aimed to review a 10-year experience of a cancer centre on major salivary gland cancers, focusing on clinical, pathological, treatment and patients' outcomes data. A total of 93 patients were identified, median age at diagnosis was 64 years (IQR, 23), and 51.6% were male. The parotid gland was the site of origin in 76.3% of cases. The most frequent histological type was salivary duct carcinoma (21.5%). All patients were submitted to surgery and adjuvant radiotherapy was performed in 74.2%. From 26 patients diagnosed with metastatic disease, 9 were treated with systemic therapy. At 8 years, disease-free survival was 54.6% and overall survival was 48.4%. Male sex, salivary duct carcinoma, stage pT3-4, stage pN2-3, high histologic grade, lymphovascular invasion and perineural invasion were negative prognostic indicators for disease-free survival and overall survival. Extracapsular spread was a negative prognostic indicator for overall survival. In the multivariable analysis, histological type-salivary duct carcinoma-kept significant negative impact in disease-free survival and high histologic grade in overall survival. The most frequent histological type was salivary duct carcinoma, which is estimated to represent only 9% of salivary tumours. Patients with salivary duct carcinoma relapsed more than other histological types. High histologic grade was a negative prognostic indicator for overall survival.


[Reliability and validity of the auditory hallucination-like experience scale].
Auditory hallucinations are important symptoms when making a diagnosis of schizophrenia. Since normal people may also experience auditory hallucinations, there may be a spectrum of auditory hallucinations ranging from those experienced in schizophrenia to those experienced by normal people. To assess the propensity to auditory hallucinations in a non-clinical population, we selected forty items from the questionnaire in Tanno, Ishigaki, & Morimoto (1998) and developed the Auditory Hallucination-like Experience Scale (AHES). Test-retest reliability showed that the AHES was internally consistent. There were high correlations between the AHES and the STA subscale and the overall O-LIFE (especially'unusual experiences'), both of which are thought to be strongly related to schizophrenia. Furthermore, the rate of false positives was higher in people more prone to auditory hallucinations than in the group less prone to auditory hallucinations. Factor analysis revealed that the AHES consists of four factors. The results suggest that the AHES has high reliability and validity as a measure of susceptibility to hallucinations.


Microarray analyses of Xylella fastidiosa provide evidence of coordinated transcription control of laterally transferred elements.
Genetically distinct strains of the plant bacterium Xylella fastidiosa (Xf) are responsible for a variety of plant diseases, accounting for severe economic damage throughout the world. Using as a reference the genome of Xf 9a5c strain, associated with citrus variegated chlorosis (CVC), we developed a microarray-based comparison involving 12 Xf isolates, providing a thorough assessment of the variation in genomic composition across the group. Our results demonstrate that Xf displays one of the largest flexible gene pools characterized to date, with several horizontally acquired elements, such as prophages, plasmids, and genomic islands (GIs), which contribute up to 18% of the final genome. Transcriptome analysis of bacteria grown under different conditions shows that most of these elements are transcriptionally active, and their expression can be influenced in a coordinated manner by environmental stimuli. Finally, evaluation of the genetic composition of these laterally transferred elements identified differences that may help to explain the adaptability of Xf strains to infect such a wide range of plant species.


Pharmacological action of Hedysarum polysaccharides: a review.
Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.


Acrolein acts as a neurotoxin in the nigrostriatal dopaminergic system of rat: involvement of α-synuclein aggregation and programmed cell death.
Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain.


Altered xanthine oxidase and N-acetyltransferase activity in obese children.
It is well established that oxidative and conjugative enzyme activity differs between obese and healthy-weight adults. However, the effect of obesity on drug metabolism in children has not been studied extensively. This study examined whether obese and healthy-weight children vary with respect to oxidative enzyme activity of CYP1A2, xanthine oxidase (XO) and conjugative enzyme activity of N-acetyltransferase 2 (NAT2). In vivo CYP1A2, XO and NAT2 activity was assessed in obese (n= 9) and lean (n= 16) children between the ages of 6-10 years using caffeine (118.3 ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8 h. Caffeine and metabolites were measured using LC/MS, and urinary metabolic ratios were determined based on reported methods. Sixteen healthy-weight and nine obese children were evaluated. XO activity was elevated in paediatric obese volunteers compared with non-obese paediatric volunteers (XO metabolic ratio of 0.7 ± 0.06 vs. 0.6 ± 0.06, respectively, 95% CI 0.046, 0.154, P < 0.001). NAT2 activity was fivefold higher in the obese (1 ± 0.4) as compared with non-obese children (0.2 ± 0.1), 95% CI 0.26, 1.34, P < 0.05. However, no difference was observed in CYP1A2 activity between the groups (95% CI -2.72, 0.12, P > 0.05). This study provides evidence that obese children have elevated XO and NAT2 enzyme activity when compared with healthy-weight controls. Further studies are needed to determine how this may impact the efficacy of therapeutic agents that may undergo metabolism by these enzymes.


Development of tolerance to kava in mice.
1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice. 2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance. 3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2-week period. 4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated. 5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mice.


Development of Nano-SiO2 and Bentonite-Based Mortars for Corrosion Protection of Reinforcing Steel.
In this study, the use of nano-silica (nano-SiO2) and bentonite as mortar additives for combating reinforcement corrosion is reported. More specifically, these materials were used as additives in ordinary Portland cement (OPC)/fly ash blended mortars in different amounts. The effects of nano-silica and bentonite addition on compressive strength of mortars at different ages was tested. Accelerated corrosion testing was used to assess the corrosion resistance of reinforced mortar specimens containing different amounts of nano-silica and bentonite. It was found that the specimens containing nano-SiO2 not only had higher compressive strength, but also showed lower steel mass loss due to corrosion compared to reference specimens. However, this was accompanied by a small reduction in workability (for a constant water to binder ratio). Mortar mixtures with 4% of nano-silica were found to have optimal performance in terms of compressive strength and corrosion resistance. Control specimens (OPC/fly ash mortars without any additives) showed low early age strength and low corrosion resistance compared to specimens containing nano-SiO2 and bentonite. In addition, samples from selected mixtures were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Finally, the influence of Ca/Si ratio of the calcium silicate hydrate (C-S-H) in different specimens on the compressive strength is discussed. In general, the study showed that the addition of nano-silica (and to a lesser extent bentonite) can result in higher strength and corrosion resistance compared to control specimens. Furthermore, the addition of nano-SiO2 can be used to offset the negative effect of fly ash on early age strength development.


"To teach is to learn twice" Added value of peer learning among medical students during COVID-19 Pandemic.
This article was migrated. The article was marked as recommended. In medical education, peer learning has a significant impact on deeper learning and considered an effective method of collaborative and deeper learning. This article highlights the adjustment of the final year medical students to the peer learning style during the COVID-19 pandemic. It explores the additional benefits of peer learning style and recommend key points that can help medical students to combat the current stressful situation. Adaptation to peer learning strategy may help to overcome this stressful situation and motivate each other to focus on studies. This approach can assist medical students to stay in touch with each other, collaborate, communicate, and boost each other morally. The peer learning style provides an opportunity for students to share thoughts and emotional reactions freely and friendly. This way can help to reduce stress and develop resilience. Students get rapid adaptation to technology-enhanced learning smoothly and effectively by helping each other to learn new skills. The feeling of staying connected with peers during the online sessions significantly augmented the ability to combat the crisis and augment social interactions.


Nontypeable Haemophilus influenzae strain 2019 produces a biofilm containing N-acetylneuraminic acid that may mimic sialylated O-linked glycans.
Previous studies suggested that nontypeable Haemophilus influenzae (NTHI) can form biofilms during human and chinchilla middle ear infections. Microscopic analysis of a 5-day biofilm of NTHI strain 2019 grown in a continuous-flow chamber revealed that the biofilm had a diffuse matrix interlaced with multiple water channels. Our studies showed that biofilm production was significantly decreased when a chemically defined medium lacking N-acetylneuraminic acid (sialic acid) was used. Based on these observations, we examined mutations in seven NTHI strain 2019 genes involved in carbohydrate and lipooligosaccharide biosynthesis. NTHI strain 2019 with mutations in the genes encoding CMP-N-acetylneuraminic acid synthetase (siaB), one of the three NTHI sialyltransferases (siaA), and the undecaprenyl-phosphate alpha-N-acetylglucosaminyltransferase homolog (wecA) produced significantly smaller amounts of biofilm. NTHI strain 2019 with mutations in genes encoding phosphoglucomutase (pgm), UDP-galactose-4-epimerase, and two other NTHI sialyltransferases (lic3A and lsgB) produced biofilms that were equivalent to or larger than the biofilms produced by the parent strain. The biofilm formed by the NTHI strain 2019pgm mutant was studied with Maackia amurensis fluorescein isothiocyanate (FITC)-conjugated and Sambucus nigra tetramethyl rhodamine isocyanate (TRITC)-conjugated lectins. S. nigra TRITC-conjugated lectin bound to this biofilm, while M. amurensis FITC-conjugated lectin did not. S. nigra TRITC-conjugated lectin binding was inhibited by incubation with alpha2,6-neuraminyllactose and by pretreatment of the biofilm with Vibrio cholerae neuraminidase. Matrix-assisted laser desorption ionization-time of flight mass spectometry analysis of lipooligosaccharides isolated from a biofilm, the planktonic phase, and plate-grown organisms showed that the levels of most sialylated glycoforms were two- to fourfold greater when the lipooligosaccharide was derived from planktonic or biofilm organisms. Our data indicate that NTHI strain 2019 produces a biofilm containing alpha2,6-linked sialic acid and that the sialic acid content of the lipooligosaccharides increases concomitant with the transition of organisms to a biofilm form.


Effects of Colloidal Oatmeal Topical Atopic Dermatitis Cream on Skin Microbiome and Skin Barrier Properties.
Atopic dermatitis is characterized by dry, itchy, inflamed skin with a dysbiotic microbiome. In this clinical study (NCT03673059), we compared the effects of an eczema cream containing 1% colloidal oat and a standard moisturizer on the skin microbiome and skin barrier function of patients with mild to moderate eczema. Patients were randomly assigned to treatment with 1% colloidal oat eczema cream or a standard, non-fragranced daily moisturizer. Treatment lasted 14 days, followed by a 7-day regression period. Of 61 patients who completed the study, 30 received the 1% colloidal oat eczema cream and 31 received the standard moisturizer. At 14 days, the 1% colloidal oat eczema cream reduced mean Eczema Area Severity Index and Atopic Dermatitis Severity Index scores by 51% and 54%, respectively. Unlike treatment with the standard moisturizer, treatment with the 1% colloidal oat eczema cream was associated with trends towards lower prevalence of Staphylococcus species and higher microbiome diversity at lesion sites. The 1% colloidal oat eczema cream significantly improved skin pH, skin barrier function, and skin hydration from baseline to day 14, whereas the standard moisturizer improved hydration. Overall, the results demonstrate that topical products can have differing effects on the skin barrier properties and the microbiome. Importantly, we show that the use of a 1% colloidal oat eczema cream improves microbiome composition and significantly repairs skin barrier defects. J Drugs Dermatol. 2020;19(5):   doi:10.36849/JDD.2020.4924.


Blunted beta-adrenoceptor-mediated fat oxidation in overweight subjects: a role for the hormone-sensitive lipase gene.
Obesity is associated with blunted beta-adrenoceptor-mediated lipolysis and fat oxidation, which persist after weight reduction. We investigated whether dinucleotide (CA)(n) repeat polymorphisms in intron 6 (i6) or 7 (i7) and a C-60G promoter substitution of the hormone-sensitive lipase (HSL) gene are associated with a blunted in vivo beta-adrenoceptor-mediated increase in circulating fatty acids and glycerol (estimation of lipolytic response) and fat oxidation in overweight-obese subjects. A total of 103 overweight (25 kg/m(2) < or = body mass index < 30 kg/m(2)) and obese (body mass index > or =30 kg/m(2)) subjects (62 men, 41 women) were included. Energy expenditure, respiratory quotient (RQ), and circulating fatty acid and glycerol were determined after stepwise infusion of increasing doses of the nonselective beta-agonist isoprenaline. The i6, i7 (CA)(n) repeat polymorphisms were determined by size-resolved capillary electrophoresis; and a C-60G promoter substitution was determined by restriction enzyme digestion assay. Female noncarriers of allele 184 i7 (n = 18) and female carriers of allele 240 i6 (n = 12) showed an overall reduced fat oxidation (as indicated by changes in RQ) after beta-adrenoceptor-mediated stimulation, explaining, respectively, 6.9% and 20.8% of the variance in RQ. These effects were not seen in male subjects. In conclusion, our results suggest that variation in i7 and i6 of the HSL gene might be associated with a physiological effect on in vivo beta-adrenoceptor-mediated fat oxidation, at least in overweight-obese female subjects.


Effects of intrathecal dexmedetomidine on shivering after spinal anesthesia for cesarean section: a double-blind randomized clinical trial.
Shivering is among the common troublesome complications of spinal anesthesia (SA), and causes discomfort and discontentment in parturients undergoing cesarean sections (CSs). The aim of this study was to investigate the effects of intrathecal dexmedetomidine in the prevention of shivering in those who underwent CS under SA. Fifty parturients planned for elective CSs under SA were enrolled in this prospective, double-blinded, controlled study and randomly divided into two equal groups. Spinal block was achieved with 12.5 mg 0.5% heavy bupivacaine plus 5 μg dexmedetomidine (BD group) or 0.5 mL 0.9% normal saline (BN group). The incidence and intensity of shivering, peripheral and core body temperature, hemodynamic parameters, and adverse events was recorded. The incidence of shivering was significantly higher in the BN group (52%) than the BD group (24%) (P=0.04). Likewise, the intensity of shivering was significantly higher in the BN group than the BD group (P=0.04). The incidence of adverse events, such as hypotension, nausea/vomiting, and bradycardia, was not significantly different between the two groups, although the grade of sedation was higher in the BD group than the BN group (P=0.004). We conclude that intrathecal dexmedetomidine is effective in lowering the incidence and intensity of shivering in parturients undergoing CSs under SA without major adverse effects.


A Silica-Aerogel-Reinforced Composite Polymer Electrolyte with High Ionic Conductivity and High Modulus.
High-energy all-solid-state lithium (Li) batteries have great potential as next-generation energy-storage devices. Among all choices of electrolytes, polymer-based systems have attracted widespread attention due to their low density, low cost, and excellent processability. However, they are generally mechanically too weak to effectively suppress Li dendrites and have lower ionic conductivity for reasonable kinetics at ambient temperature. Herein, an ultrastrong reinforced composite polymer electrolyte (CPE) is successfully designed and fabricated by introducing a stiff mesoporous SiO2 aerogel as the backbone for a polymer-based electrolyte. The interconnected SiO2 aerogel not only performs as a strong backbone strengthening the whole composite, but also offers large and continuous surfaces for strong anion adsorption, which produces a highly conductive pathway across the composite. As a consequence, a high modulus of ≈0.43 GPa and high ionic conductivity of ≈0.6 mS cm-1 at 30 °C are simultaneously achieved. Furthermore, LiFePO4 -Li full cells with good cyclability and rate capability at ambient temperature are obtained. Full cells with cathode capacity up to 2.1 mAh cm-2 are also demonstrated. The aerogel-reinforced CPE represents a new design principle for solid-state electrolytes and offers opportunities for future all-solid-state Li batteries.


Clinicopathological and prognostic characteristics of triple- negative breast cancer (TNBC) in Chinese patients: a retrospective study.
To determine the clinical, pathological and prognostic features associated with triple-negative breast cancer (TNBC). Clinical and histologic data of 21,749 breast cancer patients who were treated at Tianjin Medical University Cancer Institute and Hospital between July 2002 and December 2011 were collected. Patients were divided into two groups: those with TNBC and those with other types of breast cancer. Patients and tumor characteristics were compared between the two groups using the Chi-square test. The prognostic results of 9,823 patients in the study population were also analyzed to determine long-term survival rates in the two groups of breast cancer patients. Among the breast cancer patients treated in our hospital between 2003 and 2011, 10.4%-13.5% of them had triple-negative breast cancers. Data analyses revealed significant differences in disease onset age, family history of breast cancer, tumor size, tumor histologic grade, lymph note positivity and metastatic status between TNBC and non-TNBC patients. There were also significant differences in 5-year, 7-year and 9-year disease-free and 7-year and 9-year overall survival probability between the groups. TNBC are associated with younger disease onset age, larger tumor size, higher rate of axillary lymph node positivity, and higher tumor histologic grade. TNBC is also related to family history of breast cancer, increased metastatic risk and poor prognosis.


Therapeutic challenges of managing inflammatory bowel disease in the elderly patient.
The rapid advancements in the management of inflammatory bowel disease (IBD) have given clinicians many new therapeutic options. The prevalence of IBD in the elderly is increasing, and the role of these therapeutic agents in the elderly population with IBD is still uncertain. In this review, we will highlight the challenges facing clinicians managing IBD in the elderly, the considerations to take when starting new medications, when to consider for surgical referral, the potential pitfalls to avoid, and the non-pharmacological management measures that clinicians should be aware of. Expert Commentary: The safety of prescribing new IBD medications in elderly patients must be taken into consideration. Managing comorbidities, polypharmacy, functional status and drug interactions can also be challenging and requires an individualized approach.


Explained compared with unexplained fever in postoperative myomectomy and hysterectomy patients.
To confirm that fever with localized findings is less prevalent among febrile postoperative myomectomy patients than it is among hysterectomy patients. Hospital records of 341 hysterectomy patients and 250 myomectomy patients were reviewed. Rate of overall febrile morbidity, proportion of fever with localized findings, proportion of febrile patients worked-up, and other perioperative parameters were recorded. Fever was prospectively defined both inclusively (temperature at least 38.0 degrees C occurring at least 4 hours postoperatively) and in standard fashion (temperature at least 38.0 degrees C after 24 hours postoperatively). A localized fever required a positive laboratory, radiologic, or clinical finding. Chi-square, Student t test, and multivariable logistic regression were used. The proportion of patients who developed postoperative fever after at least 4 hours was identical between myomectomy and hysterectomy patients (39.2% compared with 39.3%, P=.98). However, the proportion of febrile myomectomy patients with localized findings was significantly lower than hysterectomy patients (14.3% compared with 31.3%, P=.003). Likewise, when comparing respective rates of overall and localized fever after at least 24 hours postoperatively, similar results were obtained. Multivariable analysis confirmed the lower likelihood of localized findings among febrile postoperative myomectomy patients compared with hysterectomy patients (odds ratio of localized fever 0.30, 95% confidence interval 0.12-0.75, P=.01). Additionally, obesity raised the likelihood of localized findings in each group by 6% per unit of body mass index (odds ratio 1.06, 95% confidence interval 1.01-1.10, P=.03). Overall postoperative fever rates are similar, but myomectomy is independently associated with fewer localized fevers than hysterectomy. Given the relatively low likelihood of localized fever, clinicians may consider simplifying the fever workup of postoperative myomectomy patients. II.


Enhanced prostanoid release from monocytes of patients with rheumatoid arthritis and active systemic lupus erythematosus.
In patients with rheumatoid arthritis high levels of prostaglandin E1 have been found in the joint fluid, and its increased production by adherent synovial cells and macrophages clearly supports the notion that this arachidonic acid metabolite is involved in the pathology of the disease. Besides its known inflammatory qualities and the suppressive effects on various lymphocyte functions prostaglandin E2 has proved to be an essential cofactor in the secretion of the lymphokine osteoclast activating factor. In this study we have discovered an enhanced release of prostaglandin E1 and thromboxane B2 from a subpopulation of blood monocytes from patients with rheumatoid arthritis and active systemic lupus erythematosus. No correlation between prostanoid release from monocytes and inflammatory activity of the disease was found. However, even monocytes from patients with early stage or mild inflammatory activity displayed a 'stimulated' arachidonic acid metabolism. In contrast only patients with active systemic lupus erythematosus showed in this respect comparable secretory activity or monocytes. Our findings may point to a possible pathogenic role of prostanoids in rheumatoid arthritis, which may also have some implication for the early diagnosis of this disease and for its differentiation from other chronic inflammatory rheumatic conditions.


Thermalization via heat radiation of an individual object thinner than the thermal wavelength.
Modeling and investigating the thermalization of microscopic objects with arbitrary shape from first principles is of fundamental interest and may lead to technical applications. Here, we study, over a large temperature range, the thermalization dynamics due to far-field heat radiation of an individual, deterministically produced silica fiber with a predetermined shape and a diameter smaller than the thermal wavelength. The temperature change of the subwavelength-diameter fiber is determined through a measurement of its optical path length in conjunction with an ab initio thermodynamic model of the fiber structure. Our results show excellent agreement with a theoretical model that considers heat radiation as a volumetric effect and takes the emitter shape and size relative to the emission wavelength into account.


[Protein quality control and psychiatric disorder--involvement of sigma-1 receptor].
The protein quality control mechanism in the endoplasmic reticulum is referred to as the unfolded protein response (UPR), and its failure may be involved in the onset of some psychiatric disorders. We showed that induction of the sigma-1 receptor plays a role in the UPR, and suggested the possibility that this mechanism is impaired in disorders such as schizophrenia. We also demonstrated that fluvoxamine induces expression of the sigma-1 receptor. Therefore, it has the potential to be developed as a drug which exerts an anti-ER-stress effect, i. e., protein quality control effect.


[Reactive anxiety crisis and chronic adjustment disorder: a unique case of work injury and suspected occupational disease].
The present study aims to describe a case of work injury and occupational disease which is unique for the type of disease diagnosed, conditions of onset and mode of management by INAIL (Italian National Institute of Insurance for Injuries at Work and Occupational Diseases). A worker, after a verbal animated dispute with some collegues and superiors, had an acute psychiatric agitation attack and went to the nearest emergency room, where he was subjected to clinical exams. No neuropsychiatric alteration was found, but the physicians diagnosed an anxiety crisis reactive to the work environment. Consequently, the medical certificate for work injury was edited and sent to INAIL. The worker has been off work for 110 days because of a anxious and depressive syndrome, due to the verbal conflict. In a later assessment, INAIL recognized only the first 30 days of the employee's time off as injury at work, while judging the following period off work as related to affectivity disturbance due to common disease, not related to work environment. The following year, "anxious-depressive syndrome" is worsened and attributed by the same worker to the recurrence of acts of persecution and discrimination against him at work. For this reason he applied for recognition of occupational disease diagnosed as "Chronic Adjustment Disorder with prolonged depressive reaction and somatic anxiety, which developed into a protracted conflict marked the employment situation". INAIL rejected that request, but in the same year the employee has submitted the complaint for "mobbing". Even this request was rejected. Literature shows many examples of traumatic events during working activities which cause psychiatric disturbances. These events include industrial disasters, explosions, transport and mining accidents, accidents in psychiatric units with high risks of assaults, armed conflicts, war, assault and sexual assault, natural disasters. Victims show symptoms of acute stress disorder (ASD) or post-traumatic stress disorder (PTSD). Cases of acute stress disorder resulting only from verbal conflict recognised as work injury aren't currently described. This case opens new perspective for the occupational physician in the assessment of ASD as work injury and of PTSD as professional disease, suggesting to put more attention to psychiatric health of workers.


Echocardiographic Indices in Pediatric Chronic Kidney Disease.
Cardiovascular disease (CVD) may accompany chronic kidney disease (CKD), resulting in additional complications and increased death rate. This study was performed to evaluate cardiac structure and function and several risk factors in hospitalized CKD children. Seventy-four children with CKD were enrolled in this cross-sectional descriptive study. Two-dimensional and M-mode ultrasonography, Doppler flow velocity and Tissue Doppler Imaging (TDI) were used to evaluate cardiac chamber size, left ventricular mass (LVM) and echocardiographic indices of ventricular function. Advanced stages of CKD showed statistically insignificant increased LVM and LVM indexed to height2.7 (LVMI), and mildly reduced diastolic function. Hypertensive patients had an insignificant increase in the incidence of left ventricular hypertrophy (LVH) defined as LVMI greater than 95th percentile for age and sex and LVH2 as LVMI2 more than 95 gr/m2 for girls and more than 115gr/ m2 for boys older than 8 years. Patients with LVH had lower left ventricular ejection fraction (LVEF) and abnormal right ventricular (RV) function based on the tricuspid valve systolic velocity (TV S') survey. LVH2 cases, however, revealed decreased LV systolic function according to ejection fraction (EF) and abnormal mitral valve systolic velocity (MV S'). LVH related to hypertension and mild systolic and diastolic dysfunction were more prevalent in advanced CKD cases, however TDI showed no statistically significant difference in the prevalence of MV S' and TV S'. We recommend strict blood pressure control and prevention of renal function deterioration as effective tools for cardiac protection in CKD children. DOI: 10.52547/ijkd.6643.


Contemporary scientific principles and family medicine.
Twentieth century developments in the sciences of physics, chemistry, and biology have led to new principles and paradigms with which the social, philosophical, and clinical tenets of family medicine are fully consistent. Familiarity with these new scientific models can give not only validation for the concepts inherent in family medicine but also a rigorous framework to guide family medicine research in a direction of the richest intellectual integrity.


[Implication of laparoscopy in diagnostics of genital tb among women through cytohistological testing of bioptic specimen].
Diagnostics of genital TB among women is a serious challenge because of the absence of specific clinical manifestation and difficulty to obtain material for bacteriological verification of the pathogen. All the cases with ascites and masses in pelvic cavity must undergo thorough testing to exclude tuberculosis. The present article describes 14 suspect cases of genital TB, where along with the mandatory clinical diagnostic studies (including PCR of ascites and bacteriological testing for TB, also on carcinoma of CA-125 ovary) they have conducted laparoscopy, with further cytological and bacteriological testing of bioptic sample. This method allowed us to diagnose genital and abdominal tuberculosis among women in 85,7% of cases through cytologic and histologic testing and to exclude ovarian carcinoma. Effectiveness of laparoscopy has been confirmed in diagnostics of genital and abdominal TB.


Economics of the Iceberg: Informal Care Provided to French Elderly with Dementia.
Dementia has a substantial effect on patients and their relatives, who have to cope with medical, social, and economic changes. In France, most elderly people with dementia live in the community and receive informal care, which has not been well characterized. Using a sample of 4680 people aged 75 years and older collected in 2008 through a national comprehensive survey on health and disability, we compared the economic value of the care received by 513 elderly people with dementia to that received by a propensity score- matched set of older people without dementia. More than 85% of elderly people with dementia receive informal care; the estimation of its economic value ranges from €4.9 billion (proxy good method) to €6.7 billion (opportunity cost method) per year. The informal care provided to people with dementia has substantial annual costs; further work should be done to examine the social and economic roles foregone as a result of this care.


Coercion and compulsion in community mental health care.
There is ongoing debate in the UK as to the place of coercion and compulsion in community mental health care. Recent changes in service provision and amendments to the Mental Health Act in England and Wales have increased the scope for compulsion in the community. This has intensified the debate revealing fault lines in the psychiatric and legal professions. Despite powerful arguments from all sides there is little empirical evidence to inform this debate at a clinical or a theoretical level. This review utilizes evidence from articles in peer reviewed journals. Papers were identified from electronic databases, the authors' databases of relevant literature and personal correspondence with experts in the field. The evidence base is relatively small but is expanding. It has been demonstrated that informal coercion is common in USA mental health services and can be experienced negatively by patients. There is evidence that powers of compulsion in community mental health care are used frequently when available and their availability is generally seen as positive by clinicians when practice becomes embedded. The evidence for the effectiveness of compulsion in community mental health care is patchy and conflicting, with randomized or other trials failing to show significant benefits overall even if secondary analyses may suggest positive outcomes in some subgroups. There are widespread regional and international differences in the use of community compulsion. Research examining treatment pressures (or 'leverage') and the subjective patient experience of them appears to be expanding and is increasing our awareness and understanding of these complex issues. There is an urgent need for evidence regarding the usefulness and acceptability of compulsion in the community now that powers have been made available. Trials of the effectiveness of compulsion are needed as is qualitative work examining the experiences of those involved in the use of such orders. These are needed to help clinicians utilize the powers available to them in an informed and judicious fashion and to ensure adequate training.


Cytochrome P450-catalysed reactive oxygen species production mediates the (-)schisandrin B-induced glutathione and heat shock responses in AML12 hepatocytes.
Sch B (schisandrin B), the most abundant dibenzocyclooctadiene lignan in Fructus schisandrae, can induce glutathione antioxidant and heat shock responses, as well as protect against oxidant-induced injury in various tissues, including the liver in rodents and AML12 (alpha mouse liver 12) hepatocytes. (-)Sch B is the most potent stereoisomer of Sch B in its cytoprotective action on AML12 hepatocytes. To define the role of ROS (reactive oxygen species) arising from CYP (cytochrome P450)-catalysed metabolism of (-)Sch B in triggering glutathione antioxidant and heat shock responses, the effects of a CYP inhibitor [ABT (aminobenzotriazole)] and antioxidants [DMTU (dimethylthiouracil) and TRX (trolox)] on (-)Sch B-induced ROS production and associated increases in cellular GSH level, as well as Hsp25/70 (heat-shock protein 25/70) production, were investigated in AML12 hepatocytes. The results indicated that (-)Sch B causes a dose dependent and sustained increase in ROS production over 6 h in AML12 hepatocytes, which was completely suppressed by pre-/co-treatment with ABT or DTMU/TRX. Incubation with (-)Sch B for 6 h caused optimal and dose-dependent increases in cellular GSH level and Hsp25/70 production at 16 h post-drug exposure in AML12 hepatocytes. These cellular responses were associated with protection against menadione-induced apoptosis. Pre-/co-treatment with ABT or antioxidants completely abrogated the (-)Sch B-induced glutathione antioxidant and heat shock responses, as well as protection against menadione-induced apoptosis. Experimental evidence obtained thus far supports the causal role of ROS arising from the CYP-catalysed metabolism of (-)Sch B in eliciting glutathione antioxidant and heat shock responses in AML12 hepatocytes.


The interaction of zinc and vitamin A in human schistosomiasis.
Levels of vitamin A and components of its transport protein complex, retinol binding protein and prealbumin, as well as zinc and its major binding proteins albumin and alpha 2-macroglobulin were measured in plasma of ninety-one male Egyptian patients with active schistosomal infection and thirty-two healthy adult males. Patients were divided into four groups: Group I had active schistosomiasis without associated complications; Group II had schistosomiasis complicated by colonic polyposis; Group III had advanced schistosomiasis, hepatosplenomegaly and/or ascites; and Group IV had chronic salmonella septicaemia in addition to schistosomiasis. Results showed that all patient groups had subnormal levels of plasma vitamin A, retinol binding protein, prealbumin, zinc and albumin (P less than 0.005 for all parameters) but elevated alpha 2-macroglobulin (P less than 0.001) when compared to the control group. Alterations in the vitamin A transport proteins increased with schistosomal complications and were closely correlated to changes in vitamin A (P less than 0.005), but alterations of albumin and alpha 2-macroglobulin were less consistent and did not correlate with changes in zinc levels. There was a highly significant correlation, however, between plasma zinc concentrations and those of vitamin A, retinol binding protein and prealbumin (P less than 0.001 for all correlations) in all groups of patients as well as the control group. These findings indicate that the binding and transport proteins of both zinc and vitamin A were adversely affected by schistosomiasis and its various complications. Deficiencies of both zinc and vitamin A seem to be interrelated in this disease and the vitamin A transport system may be largely dependent on zinc status.


Association between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population.
Recent genome-wide analysis identified a genetic variant on 5p14.1 (rs4307059), which is associated with risk for autism spectrum disorder. This study investigated whether rs4307059 also operates as a quantitative trait locus underlying a broader autism phenotype in the general population, focusing specifically on the social communication aspect of the spectrum. Study participants were 7,313 children from the Avon Longitudinal Study of Parents and Children. Single-trait and joint-trait genotype associations were investigated for 29 measures related to language and communication, verbal intelligence, social interaction, and behavioral adjustment, assessed between ages 3 and 12 years. Analyses were performed in one-sided or directed mode and adjusted for multiple testing, trait interrelatedness, and random genotype dropout. Single phenotype analyses showed that an increased load of rs4307059 risk allele is associated with stereotyped conversation and lower pragmatic communication skills, as measured by the Children's Communication Checklist (at a mean age of 9.7 years). In addition a trend toward a higher frequency of identification of special educational needs (at a mean age of 11.8 years) was observed. Variation at rs4307059 was also associated with the phenotypic profile of studied traits. This joint signal was fully explained neither by single-trait associations nor by overall behavioral adjustment problems but suggested a combined effect, which manifested through multiple sub-threshold social, communicative, and cognitive impairments. Our results suggest that common variation at 5p14.1 is associated with social communication spectrum phenotypes in the general population and support the role of rs4307059 as a quantitative trait locus for autism spectrum disorder.


Review of evoked and event-related delta responses in the human brain.
In the last decade, the brain's oscillatory responses have invaded the literature. The studies on delta (0.5-3.5Hz) oscillatory responses in humans upon application of cognitive paradigms showed that delta oscillations are related to cognitive processes, mainly in decision making and attentional processes. The present manuscript comprehensively reviews the studies on delta oscillatory responses upon cognitive stimulation in healthy subjects and in different pathologies, namely Alzheimer's disease, Mild Cognitive Impairment (MCI), bipolar disorder, schizophrenia and alcoholism. Further delta oscillatory response upon presentation of faces, facial expressions, and affective pictures are reviewed. The relationship between pre-stimulus delta activity and post-stimulus evoked and event-related responses and/or oscillations is discussed. Cross-frequency couplings of delta oscillations with higher frequency windows are also included in the review. The conclusion of this review includes several important remarks, including that delta oscillatory responses are involved in cognitive and emotional processes. A decrease of delta oscillatory responses could be a general electrophysiological marker for cognitive dysfunction (Alzheimer's disease, MCI, bipolar disorder, schizophrenia and alcoholism). The pre-stimulus activity (phase or amplitude changes in delta activity) has an effect on post-stimulus EEG responses.


Silane-Acrylate Chemistry for Regulating Network Formation in Radical Photopolymerization.
Photoinitiated silane-ene chemistry has the potential to pave the way toward spatially resolved organosilicon compounds, which might find application in biomedicine, microelectronics, and other advanced fields. Moreover, this approach could serve as a viable alternative to the popular photoinitiated thiol-ene chemistry, which gives access to defined and functional photopolymer networks. A difunctional bis(trimethylsilyl)silane with abstractable hydrogens (DSiH) was successfully synthesized in a simple one-pot procedure. The radical reactivity of DSiH with various homopolymerizable monomers (i.e., (meth)acrylate, vinyl ester, acrylamide) was assessed via 1H NMR spectroscopic studies. DSiH shows good reactivity with acrylates and vinyl esters. The most promising silane-acrylate system was further investigated in cross-linking formulations toward its reactivity (e.g., heat of polymerization, curing time, occurrence of gelation, double-bond conversion) and compared to state-of-the-art thiol-acrylate resins. The storage stability of prepared resin formulations is greatly improved for silane-acrylate systems vs thiol-ene resins. Double-bond conversion at the gel point (DBCgel) and overall DBC were increased, and polymerization-induced shrinkage stress has been significantly reduced with the introduction of silane-acrylate chemistry. Resulting photopolymer networks exhibit a homogeneous network architecture (indicated by a narrow glass transition) that can be tuned by varying silane concentration, and this confirms the postulated regulation of radical network formation. Similar to thiol-acrylate networks, this leads to more flexible photopolymer networks with increased elongation at break and improved impact resistance. Additionally, swelling tests indicate a high gel fraction for silane-acrylate photopolymers.


Cu(0), O2 and mechanical forces: a saving combination for efficient production of Cu-NHC complexes.
Mechanical forces induced by ball-milling agitation enabled the highly efficient and widely applicable synthesis of Cu-carbene complexes from N,N-diaryl-imidazolium salts and metallic copper. The required amount of gaseous dioxygen and insoluble copper could be reduced down to stoichiometric quantities, while reaction rates clearly outperformed those obtained in solution. Utilisation of Cu(0) as the copper source enabled the application of this approach to a wide array of N,N-diaryl-imidazolium salts (Cl-, BF4- and PF6-) that transferred their counter anion directly to the organometallic complexes. Cu-NHC complexes could be produced in excellent yields, including utilisation of highly challenging substrates. In addition, five unprecedented organometallic complexes are reported.


Using video podcasting to enhance the learning of clinical skills: A qualitative study of physiotherapy students' experiences.
Video podcasts, or vodcasts are increasingly used by a range of healthcare professions in the mastery of new skills. Little is known about the experiences of using vodcasts in physiotherapy education. Traditional pedagogic strategies have been employed in order to master those skills required for physiotherapy practice. There have been advances in the use of technology in medical education in the nursing, dentistry and medical fields. Vodcasts offer great versatility and potential when used as a pedagogical tool, embedded within a physiotherapy curriculum. To explore students' experiences of using technology enhanced learning, namely vodcasts, in the Physiotherapy curriculum to develop the learning of clinical skills. A series of focus groups were carried out with undergraduate and pre-registration physiotherapy students (n=31). Students valued the versatility and audio-visual nature of vodcasts; helpful in revising for practical examinations and practising their skills prior to, during and after taught skills classes. Watching and practising simultaneously allowed students to practice repeatedly and formulate a process for each skill. When learning a new skill, a combination of teaching and learning approaches was favoured, marrying traditional approaches with those that utilise technology. This study's findings add to the existing body of evidence in skills based teaching and support a multi-media, blended approach in those disciplines involved in the learning and teaching of clinical skills.


[C-methionine PET in assessment of brain lesions in patients with glial tumors after combined treatment].
Positron emission tomography (PET) with amino acid-based radiopharmaceuticals is considered as an effective method to diagnose continued growth of cerebral gliomas, but the variability of 11C-methionine uptake by brain lesions of different genesis after combined treatment still remains poorly understood. The aim of this study was to explore the information value of 11C-methionine PET in delimitating progression of cerebral gliomas and stable disease and to assess the risk of tumor recurrence at different values of the 11C-methionine uptake index. MATERIAL AND METHODS: We performed a retrospective analysis of the results of 11C-methionine PET or PET/CT in 324 patients suspected for continued growth of cerebral tumor based on magnetic resonance imaging (MRI) findings. A quantitative analysis of the results included calculation of the 11C-methionine uptake index (UI). RESULTS: A ROC analysis revealed that the specificity of PET in the diagnosis of continued tumor growth (CTG) was 98%, and the sensitivity was 71% for a UI of more than 1.9. We found that 98% of lesions with a negative level of RP uptake were related to radiation brain lesions (RBLs) or residual tumors combined with radiation pathomorphims. The UI in a range of 1.2-1.6 in 75% of lesions characterized a stable disease, but 25.5% of the lesions represented continued glioma growth. The proportion of recurrences increased to 40% in a UI range of 1.6-1.9, and 95.5% of brain lesions with a UI of more than 1.9 were tumor recurrences. Therefore, high 11C-methionine uptake with the UI above 1.9 in brain lesions characterized by radiological signs of disease progression is a highly specific indicator of CTG; however, the UI may significantly vary during tumor growth, and a substantial fraction of recurrent gliomas may have lower radiopharmaceutical uptake. In the case of borderline UI values, early dynamic control or complementary additional MRI or CT techniques should be used.


Unexpected sites of wear in the femoral head.
In a study of 637 femoral heads removed surgically because of osteoarthritis, the wear was predominantly on the posterior half in 13.2% and was more than two-thirds posterior in 7.5%. Wear was more than two-thirds anterior in 37.8%. In 36 heads from patients with rheumatoid arthritis, the wear was predominant posterior in 27.8%. No anatomical reason was found for these marked asymmetries, which, from their position, could not possibly be the result of simple weight bearing. The finding underlines the importance of muscular action in the causation of wear.


6-Thioguanine therapy in Crohn's disease--observational data in Swedish patients.
Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohn's disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n=18) or resistance (n=5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.


Comparing geographical genetic differentiation between candidate and noncandidate loci for adaptation strengthens support for parallel ecological divergence in the marine snail Littorina saxatilis.
The Galician sympatric ecotypes of Littorina saxatilis have been proposed as a model system for studying parallel ecological speciation. Such a model system makes a clear prediction: candidate loci (for divergent adaptation) should present a higher level of geographical differentiation than noncandidate (neutral) loci. We used 2356 amplified fragment length polymorphisms (AFLPs) and four microsatellite loci to identify candidate loci for ecological adaptation using the F(ST) outlier method. Three per cent of the studied AFLP loci were identified as candidate loci associated with adaptation, after multitest adjustments, thus contributing to ecotype differentiation (candidate loci were not detected within ecotypes). Candidate and noncandidate loci were analysed separately at four different F(ST) partitions: differences between ecotypes (overall and local), differences between localities and micro-geographical differences within ecotypes. The magnitude of F(ST) differed between candidate and noncandidate loci for all partitions except in the case of micro-geographical differentiation within ecotypes, and the microsatellites (putatively neutral) showed an identical pattern to noncandidate loci. Thus, variation in candidate loci is determined partially independent by divergent natural selection (in addition to stochastic forces) at each locality, while noncandidate loci are exclusively driven by stochastic forces. These results support the evolutionary history described for these particular populations, considered to be a clear example of incomplete sympatric ecological speciation.


Lipoprotein-based nanoparticles rescue the memory loss of mice with Alzheimer's disease by accelerating the clearance of amyloid-beta.
Amyloid-beta (Aβ) accumulation in the brain is believed to play a central role in Alzheimer's disease (AD) pathogenesis, and the common late-onset form of AD is characterized by an overall impairment in Aβ clearance. Therefore, development of nanomedicine that can facilitate Aβ clearance represents a promising strategy for AD intervention. However, previous work of this kind was concentrated at the molecular level, and the disease-modifying effectiveness of such nanomedicine has not been investigated in clinically relevant biological systems. Here, we hypothesized that a biologically inspired nanostructure, apolipoprotein E3-reconstituted high density lipoprotein (ApoE3-rHDL), which presents high binding affinity to Aβ, might serve as a novel nanomedicine for disease modification in AD by accelerating Aβ clearance. Surface plasmon resonance, transmission electron microscopy, and co-immunoprecipitation analysis showed that ApoE3-rHDL demonstrated high binding affinity to both Aβ monomer and oligomer. It also accelerated the microglial, astroglial, and liver cell degradation of Aβ by facilitating the lysosomal transport. One hour after intravenous administration, about 0.4% ID/g of ApoE3-rHDL gained access to the brain. Four-week daily treatment with ApoE3-rHDL decreased Aβ deposition, attenuated microgliosis, ameliorated neurologic changes, and rescued memory deficits in an AD animal model. The findings here provided the direct evidence of a biomimetic nanostructure crossing the blood-brain barrier, capturing Aβ and facilitating its degradation by glial cells, indicating that ApoE3-rHDL might serve as a novel nanomedicine for disease modification in AD by accelerating Aβ clearance, which also justified the concept that nanostructures with Aβ-binding affinity might provide a novel nanoplatform for AD therapy.


Communication in deafblind adults with Usher syndrome: retrospective observational study.
To characterize the communication and the main mechanisms that facilitate interpersonal relationships of deafblind, especially in relation to communication and locomotion and the impact of these aspects on deafblindness. Report of a series of cases conducted from semi-structured interviews with questions relating to the functionality of communication, with Usher syndrome patients attended in a specialized clinic in a university service, in the year 2007. The sample consisted of 11 deafblind subjects, with Usher syndrome, aged between 20 and 57 years (mean age 43 years and SD=12.27), of which 7 (63.6%) were female. The responses were analyzed by qualitative-quantitative technique of the Discurso do Sujeito Coletivo (DSC). All participants reported that visual and auditory symptoms began in childhood. Of the 11 interviewed, 6 reported that the disease has negatively affected their daily activities, 6 experienced difficulty at work, and 2 at leisure. Four reported that there was a change in family relationships, and 5 reported no change in the interaction with family and friends. In discourse analysis, almost 30% of respondents reported to use alternative forms of communication, 40% said move alone if the way is known before. Only 1 of 11 participants said they did not ask for help when needed. Individuals diagnosed with Usher syndrome face challenging situations in daily activities, personal relationships, at work and at play. Alternative forms of communication are often used when verbal communication is not possible. The majority of respondents have independence of locomotion, or seeking ways to achieve it.


[Surgical treatment of hand deformities in hereditary dystrophic bullous epidermolysis].
In the period 1996-2001 in the Clinic for Plastic Surgery and Burns of the Military Medical Academy, 18 patients. 12 male and 6 female, with hereditary dystrophic epidermolysis bullosa (HDEB) and hand deformities were surgically treated, to achieve the complete separation of fingers, correction of the thumb adduction contracture and flexion or extension contracture of finger joints. The period of wound healing on flat surfaces after surgery, and the period between two operations was estimated. The most common deformity was the flexion contractures of metacarpophalangeal (MP) joints (45%) and one or both interphalangeal (IP) joints (types A1, A2). In 20% of the hands MP joint was stretched with the flexion contracture in distal interphalangeal (DIP) or both IP joints (types B1, B2). In 35% of hands MP joint was in hyperextension with folded proximal interphalangeal (PIP) or both IP joints (C1 i C2). The adduction deformity of the thumb type 1, without the possibility of abduction, was present in 15%, type 2, when the thumb was placed above the palm in 60% and type 3, when the thumb was fused in the palm in 25%. Pseudosyndactyly of the first degree (till PIP joint) was found in 30% of hands, the second degree (till DIP joint) in 25%, and the third degree (the whole finger length) in 45% of hands. Fingers were completely separated and stretched surgically. The period of spontaneous healing was 15 days on the average. EBDC represents great medical and social problem that requires multidisciplinary approach of physicians of various specialties (surgeons, dermatologists, pediatrists, geneticists, nutritionists, physiatrists, ophthalmologists, dentists, ENT, as well as specially trained persons and families). The efficient specific systemic therapy aiming to increase the skin resistance to mechanical trauma does not exist yet, and should be developed in the field of gene therapy. The surgical correction of hand deformities, acrylate glove use in the longer post operative period combined with physiotherapy, the active use of hands, the protection of injuries and skin care are the measures which prolong the period between the recurrence of contractures.


Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia.
Chronic myeloid leukemia (CML) is characterized by an increased proliferative activity of the leukemic progenitors that produce an elevated number of mature granulocytes. Nevertheless, cell cycle-active agents, even in very high doses, are alone unable to eradicate the leukemic clone, suggesting the presence of a rare subset of quiescent leukemic stem cells. To isolate such cells, we first used Hoechst 33342 and Pyronin Y staining to obtain viable G(0) and G(1)/S/G(2)/M fractions of CD34(+) cells by fluorescence-activated cell sorting (FACS) from 6 chronic-phase CML patients' samples and confirmed the quiescent and cycling status of the 2 fractions by demonstration of expected patterns of Ki-67 and D cyclin expression. Leukemic (Ph(+)/BCR-ABL(+)) cells with in vitro progenitor activity and capable of engrafting immunodeficient mice were identified in the directly isolated G(0) cells. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that many leukemic CD34(+) G(0) cells also expressed BCR-ABL mRNA. CD34(+) from 8 CML patients were also labeled with carboxyfluorescein diacetate succinimidyl diester (CFSE) before being cultured (with and without added growth factors) to allow viable cells that had remained quiescent (ie, CFSE(+)) after 4 days to be retrieved by FACS. Leukemic progenitors were again detected in all quiescent populations isolated by this second strategy, including those exposed to a combination of flt3-ligand, Steel factor, interleukin-3, interleukin-6, and granulocyte colony-stimulating factor. These findings provide the first direct and definitive evidence of a deeply but reversibly quiescent subpopulation of leukemic cells in patients with CML with both in vitro and in vivo stem cell properties.


Mutational analysis of state-dependent contacts in the pore module of eukaryotic sodium channels.
Voltage-gated sodium channels have residues that change or may change contacts upon gating. Contributions of individual contacts in stability of different states are incompletely understood. Pore-lining inner helices contain exceptionally conserved asparagines in positions i20. Here we explored how mutations in positions i20 and i29 affect electrophysiological properties of insect sodium channels. In repeat interfaces I/IV, III/II and IV/III, alanine substitutions caused positive activation shifts in positions i20 and i29, negative shifts of slow inactivation in positions i20 and positive shifts of slow inactivation in positions i29. The results support the hypothesis on open state inter-repeat H-bonding of residues i20 and i29. The shift magnitudes vary between interfaces, reflecting structural asymmetry of the channels. Mutations in positions i20 of repeats III and IV caused much longer recovery delay from the slow and fast inactivation than other mutations. In repeat IV, alanine substitution of tyrosine i30 rescued positive activation shift of mutation in position i29. Our data suggest that polar residues in positions i29 are involved in stabilization of both the open and slow-inactivated states. Transition between the states may involve switching of H-bonding partners of residues i29 from the conserved asparagines to currently unknown residues.


Effects of Chemotherapy Regimen and Radiation Modality on Hematologic Toxicities in Patients Receiving Definitive Platinum-based Doublet Chemoradiation for Non-Small Cell Lung Cancer.
Predictors of acute hematologic toxicities during definitive chemoradiation for non-small cell lung cancer (NSCLC) are incompletely defined. We retrospectively analyzed 604 patients treated with definitive platinum-based doublet chemoradiation therapy for stage III NSCLC. The outcome of interest was grade ≥3 acute hematologic toxicities, specifically white blood cell, hemoglobin, platelet, neutrophil, and lymphocyte decrease during chemoradiation therapy. We assessed the association between any grade ≥3 acute hematologic toxicity with patient demographic, disease, radiation factors (specifically modality and dose), and chemotherapy agents via stepwise multivariate logistic regression. Survival was compared via log-rank and univariate Cox regression analyses. There was no significant association between radiation modality and any hematologic toxicity on multivariate analysis. However, use of etoposide was found to be significantly associated with white blood cell, platelet, and neutrophil decrease compared with paclitaxel and docetaxel (all P<0.05). No differences were found between platinum agents. Overall survival (OS) and event-free survival (EFS) were significantly worse in patients who experienced grade ≥3 hemoglobin (OS: hazard ratio [HR]=1.5; 95% confidence interval [CI], 1.05-2.26; P=0.03, EFS: HR=1.7; 95% CI, 1.2-2.4; P=0.0032) and lymphocyte (OS: HR=1.5; 95% CI, 1.1-2.1; P=0.01, EFS: HR=1.4; 95% CI, 1.1-1.9; P=0.02) decreases. Chemotherapy identity, specifically the nonplatinum agent, was significantly associated with grade ≥3 hematologic toxicities, whereas radiation modality was not.


Data of NODDI diffusion metrics in the brain and computer simulation of hybrid diffusion imaging (HYDI) acquisition scheme.
This article provides NODDI diffusion metrics in the brains of 52 healthy participants and computer simulation data to support compatibility of hybrid diffusion imaging (HYDI), "Hybrid diffusion imaging"[1] acquisition scheme in fitting neurite orientation dispersion and density imaging (NODDI) model, "NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain"[2]. HYDI is an extremely versatile diffusion magnetic resonance imaging (dMRI) technique that enables various analyzes methods using a single diffusion dataset. One of the diffusion data analysis methods is the NODDI computation, which models the brain tissue with three compartments: fast isotropic diffusion (e.g., cerebrospinal fluid), anisotropic hindered diffusion (e.g., extracellular space), and anisotropic restricted diffusion (e.g., intracellular space). The NODDI model produces microstructural metrics in the developing brain, aging brain or human brain with neurologic disorders. The first dataset provided here are the means and standard deviations of NODDI metrics in 48 white matter region-of-interest (ROI) averaging across 52 healthy participants. The second dataset provided here is the computer simulation with initial conditions guided by the first dataset as inputs and gold standard for model fitting. The computer simulation data provide a direct comparison of NODDI indices computed from the HYDI acquisition [1] to the NODDI indices computed from the originally proposed acquisition [2]. These data are related to the accompanying research article "Age Effects and Sex Differences in Human Brain White Matter of Young to Middle-Aged Adults: A DTI, NODDI, and q-Space Study" [3].


Evidence-Based Role of Nutrients and Antioxidants for Chronic Pain Management in Musculoskeletal Frailty and Sarcopenia in Aging.
Musculoskeletal disorders in aging and pain are closely connected because of multiple mechanisms leading to loss of mobility and autonomy. Pain is predictive of diability and worsening frailty and the strength of this relationship increases with the severity of pain. This study presents a systematic review of randomized controlled trials, cross sectional studies, and observational studies based on treatment of pain in adults with musculoskeletal disorders using nutritional non-pharmacological (nutrients and antioxidants) interventions. The review found the efficiency of the following topics: (a) accession of the patient to a dietary counselling (e.g., daily recommended amount of protein-equivalent to at least of 1 g of protein per kilogram of body weight); (b) intake of glutamic acid-rich such as soy, egg, and cod and tryptophan-rich foods such as milk and peanuts-or taking quick-acting, free-form supplements; (c) supplementation of vitamin D and magnesium, if lacking; (d) weekly consumption of fish or supplements of omega-3 fatty acids; and (e) availability of botanicals, in particular curcumin and gingerol. These non-pharmacological interventions can help the pain therapist to create a personalized medicine (precision medicine), acting with the maximum efficacy and safety, and also reducing the dosage of analgesic drugs needed.


Relationship Between Alcohol Consumption and Prostatic Hyperplasia According to Facial Flushing After Drinking in Korean Men.
The purpose of this study was to examine whether facial flushing after drinking influences the relationship between alcohol consumption and prostatic hyperplasia among Korean men. The subjects were 957 Korean men (180 non-drinkers, 389 with drinking-related facial flushing, 388 without facial flushing) in the 40-69 age group, who underwent prostate ultrasound at the health promotion center of Chungnam National University Hospital between 2008 and 2014. Alcohol consumption and alcohol-related facial flushing were assessed through a questionnaire. In terms of the amount consumed, 14 g of alcohol was considered a standard drink. With the non-drinker group as reference, logistic regression was used to analyze the relationship between weekly alcohol intake and prostatic hyperplasia in the flushing and non-flushing groups, with adjustment for confounding factors such as age, body mass index, smoking, and exercise patterns. Individuals aged 50-59 years who experienced drinking-related facial flushing had a significantly lower risk of prostatic hyperplasia than the non-drinker group, depending on alcohol consumption: ≤4 standard drinks (adjusted odds ratio [OR], 0.38; 95% confidence interval [CI], 0.16 to 0.86); >4 ≤8 standard drinks (OR, 0.35; 95% CI, 0.13 to 0.95); >8 standard drinks (OR, 0.33; 95% CI, 0.13 to 0.84). However, no significant relationship was observed between the number of drinks consumed and the risk of prostate hyperplasia in the non-flushing group. The risk of prostatic hyperplasia appears to be reduced by alcohol consumption among Korean men aged 50-59 years who exhibit drinking-related facial flushing.


Photon beams for radiosurgery produced by laser Compton backscattering from relativistic electrons.
The frontal collisions of a laser beam with relativistic electrons result in Compton-backscattered photons. The energy of these photons is dependent on the laser and electron energy in the range from kilo-electron-volts to tens of mega-electron-volts. In a sufficiently narrow backscattering angle the photons are nearly monochromatic. Over the past 30 years there have been several attempts to produce photon beams by laser backscattering from relativistic electrons stored in magnetic ring structures. One aim is to produce photons in the high mega-electron-volt energy range with fluxes useful for nuclear physics research; another is to produce photons in the high kilo-electron-volt energy range, which would be useful for medical applications, such as coronary angiography or treatment of tumour. Our present interest is to investigate the possibility of using 34 keV to 10 MeV photon beams for applications in stereotactic functional radiosurgery. We foresee the possibility of neurosurgical operations through the intact skull with precise and effective destruction of deeply lying millimetre-sized targets with minimal effects on intervening structures, high reproducibility and good prediction of the results. Our paper presents: a Monte Carlo study of radiosurgery based on cross firing with 34 keV to 100 MeV photon beams and 200 and 580 MeV proton beams, a theoretical description of the kinematics of Compton backscattering and estimates of the backscattered photon flux from several combinations of laser cavities at Nd:YAG (1.17 eV) and CO2 (0.117 eV) laser energies and electron storage rings energies in the range 0.1-1.3 GeV. As examples, existing magnetic structures, such as the DA phi NE Accumulator in the lower energy range and the Trieste Synchrotron Light Source ELETTRA in the higher energy range have been utilized in the calculations. The Monte Carlo study has shown that radiosurgery with photon beams of energies in mega-electron-volt energy range enables precise destruction of deeply lying millimetre-sized targets with minimal effects on intervening structures. Its precision is comparable to that of radiosurgery with 200-580 MeV proton beam, but our hope is that radiosurgery with lower energy photon beams could be more precise and less expensive. An average dose of 200 Gy can be delivered to a target of diameter 2 mm at the centre of an 18 cm diameter phantom in 1 h using photon beams of fluences 7.3 x 10(10), 1.8 x 10(10), 6.5 x 10(8), 2.2 x 10(8), 8.6 x 10(7) and 7.8 x 10(6) photons per second at 34 keV, 100 keV, 1 MeV, 3 MeV, 10 MeV and 100 MeV per cross section of beam of 2 mm diameter, respectively. 34-100 keV photon beams were studied in the hope of finding a strong enhancement of their efficiency if a stable high-Z element were to be introduced into the target's DNA. It is shown that, with a low-energy ring running at about 0.4 GeV and a Nd:YAG laser, it would be possible to obtain the required 3 MeV photon beam flux to deliver the average dose within 1 h, assuming an average distance between the source and the target of about 5 m. With a similar machine used at about 1.3 GeV and a CO2 laser, a 3 MeV photon beam is obtained and the exposure time can be reduced to less than 1 min, assuming a roughly 10 m distance between source and target (here a beam angle of 0.1 mrad only had to be considered due to the larger angular energy and yield spread). With a lower electron energy of 138 MeV and a CO2 laser, a 34 keV photon beam can be produced. More than 45 h would be needed to deliver the same dose. We hope that this time could be shortened considerably if stable iodine were introduced into the target with the help of a DNA-seeking molecular carrier. In this case the geometrical precision would be further improved.