Effect of climate and farm environment on Campylobacter spp. colonisation in Norwegian broiler flocks.
Campylobacteriosis is the most frequently reported zoonosis in the EU. A recent report states that between 50% and 80% of the human campylobacteriosis cases could be attributed to broiler as a reservoir. The current study was conducted to investigate associations between the presence of Campylobacter spp. in Norwegian broiler flocks and factors related to the climate and the farm environment. Data from 18,488 broiler flocks from 623 different farms during 2002-2007 were included in the study. A logistic regression analysis was conducted where Campylobacter spp. status of a broiler flock at the time of slaughter was defined as the dependent variable and farm was modelled as a random effect. The following factors were found to increase the probability for a broiler flock to test positive for Campylobacter spp.: daily mean temperature above 6°C during the rearing period, private water supply, presence of other livestock farms within a distance of 2 km, presence of other broiler farms within a distance of 4 km with flocks positive for Campylobacter spp. within 30 days prior to slaughter, heavy rainfall 11-30 days prior to slaughter, region and year. Daily mean temperature below 0°C reduced the probability. The study emphasises the importance of the farm environment and the climate for the occurrence of Campylobacter spp. in broiler flocks. The farm environment is probably a part of the Campylobacter spp. pathway into and between broiler flocks where farmyard run-off and humans or flies entering the houses might constitute vehicles transporting the organism. Fly activity is temperature-driven and flies might be a part of the explanation of the increased risk for Campylobacter spp. related to increased temperature demonstrated in the study.


Absence of platelet membrane glycoproteins IIb/IIIa from monocytes.
Two-dimensional gel electrophoresis, immunoprecipitation, and crossed immunoelectrophoresis were used in the investigation of glycoproteins IIb/IIIa in platelets, monocytes, and monocyte-derived macrophages from human blood. All techniques detected the glycoproteins in platelets but not in the mononuclear phagocytes. Similar results were obtained by immunochemistry using a monoclonal antibody against the platelet glycoproteins IIb/IIIa (revealed by a gold-labeled second antibody) which bound heavily to the platelet but not to the monocyte surface. The biochemical techniques used for the analysis of mononuclear phagocytes would have reliably detected the level of glycoproteins IIb/IIIa contributed by a 5% contamination with platelets, calculated on a per cell basis. We conclude that human monocytes and monocyte-derived macrophages lack glycoproteins IIb/IIIa. Our results further indicate that centrifugal elutriation yields monocyte preparations with minimal contamination by platelets. It seems likely that the positive results obtained by other authors were due to the presence of platelets or fragments on the monocytes.


'What's in the NIDDK CDR?'--public query tools for the NIDDK central data repository.
The National Institute of Diabetes and Digestive Disease (NIDDK) Central Data Repository (CDR) is a web-enabled resource available to researchers and the general public. The CDR warehouses clinical data and study documentation from NIDDK funded research, including such landmark studies as The Diabetes Control and Complications Trial (DCCT, 1983-93) and the Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) follow-up study which has been ongoing for more than 20 years. The CDR also houses data from over 7 million biospecimens representing 2 million subjects. To help users explore the vast amount of data stored in the NIDDK CDR, we developed a suite of search mechanisms called the public query tools (PQTs). Five individual tools are available to search data from multiple perspectives: study search, basic search, ontology search, variable summary and sample by condition. PQT enables users to search for information across studies. Users can search for data such as number of subjects, types of biospecimens and disease outcome variables without prior knowledge of the individual studies. This suite of tools will increase the use and maximize the value of the NIDDK data and biospecimen repositories as important resources for the research community. Database URL: https://www.niddkrepository.org/niddk/home.do.


Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain.
Cross-sectional studies suggest that the microbes in the human gut have a role in obesity by influencing the human body's ability to extract and store calories. The aim of this study was to assess if there is a correlation between change in body weight over time and gut microbiome composition. We analysed 16S ribosomal RNA gene sequence data derived from the faecal samples of 1632 healthy females from TwinsUK to investigate the association between gut microbiome measured cross-sectionally and longitudinal weight gain (adjusted for caloric intake and baseline body mass index). Dietary fibre intake was investigated as a possible modifier. Less than half of the variation in long-term weight change was found to be heritable (h2=0.41 (0.31, 0.47)). Gut microbiota diversity was negatively associated with long-term weight gain, whereas it was positively correlated with fibre intake. Nine bacterial operational taxonomic units (OTUs) were significantly associated with weight gain after adjusting for covariates, family relatedness and multiple testing (false discovery rate <0.05). OTUs associated with lower long-term weight gain included those assigned to Ruminococcaceae (associated in mice with improved energy metabolism) and Lachnospiraceae. A Bacterioides species OTU was associated with increased risk of weight gain but this appears to be driven by its correlation with lower levels of diversity. High gut microbiome diversity, high-fibre intake and OTUs implicated in animal models of improved energy metabolism are all correlated with lower term weight gain in humans independently of calorie intake and other confounders.


Real-Time Data Collection to Examine Relations Between Physical Activity and Affect in Adults With Mental Illness.
Adults with serious mental illness engage in limited physical activity, which contributes to significant health disparities. This study explored the use of both ecological momentary assessments (EMAs) and activity trackers in adults with serious mental illness to examine the bidirectional relationship between activity and affect with multilevel modeling. Affective states were assessed up to seven times per day using EMA across 4 days. The participants (n = 20) were equipped with a waist-worn accelerometer to measure moderate to vigorous physical activity. The participants had a mean EMA compliance rate of 88.3%, and over 90% of completed EMAs were matched with 30-min windows of accelerometer wear. The participants who reported more positive affect than others had a higher probability of engaging in moderate to vigorous physical activity. Engaging in more moderate to vigorous physical activity than one's usual was associated with more negative affect. This study begins to address the effect of momentary mood on physical activity in a population of adults that is typically difficult to reach.


Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated pregnancies: a prospective cohort study.
to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia. a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing ≥ 4000 g (study group) or < 4000 g (control group). Women were recruited in a 1:1 ratio from antenatal clinics in Northern Ireland. Women wore a SenseWear(®) Body Media Pro3 physical activity armband and completed a food diary for four consecutive days in the third trimester. Physical activity was measured in Metabolic Equivalent of Tasks (METs) where 1 MET = 1 kcal per kilogram of body weight per hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model to adjust for potential confounders. of the 112 women recruited, 100 complete datasets were available for analysis. There was no significant difference in energy balance between the two groups. Intensity of free living physical activity (average METs) of women predicted to deliver macrosomic infants (n = 50) was significantly lower than that of women in the control group (n = 50) (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in means -0.1 METs (95% confidence interval: -0.19, -0.01); p = 0.021). Women predicted to deliver macrosomic infants also spent significantly more time in sedentary behaviour (≤ 1 MET) than the control group (16.1 (2.8) hours versus 13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p = 0.020). although there was no association between predicted fetal macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks.


Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.
Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.


Combining magnetic nanoparticle capture and poly-enzyme nanobead amplification for ultrasensitive detection and discrimination of DNA single nucleotide polymorphisms.
The development of ultrasensitive methods for detecting specific genes and discriminating single nucleotide polymorphisms (SNPs) is important for biomedical research and clinical disease diagnosis. Herein, we report an ultrasensitive approach for label-free detection and discrimination of a full-match target-DNA from its cancer related SNPs by combining magnetic nanoparticle (MNP) capture and poly-enzyme nanobead signal amplification. It uses a MNP linked capture-DNA and a biotinylated signal-DNA to sandwich the target followed by ligation to offer high SNP discrimination: only the perfect-match target-DNA yields a covalently linked biotinylated signal-DNA on the MNP surface for subsequent binding to a neutravidin-horseradish peroxidase conjugate (NAV-HRP) for signal amplification. The use of polymer nanobeads each tagged with thousands of copies of HRPs greatly improves the signal amplification power, allowing for direct, amplification-free quantification of low aM target-DNA over 6 orders of magnitude (0.001-1000 fM). Moreover, this sensor also offers excellent discrimination between the perfect-match gene and its cancer-related SNPs and can positively detect 1 fM perfect-match target-DNA in the presence of 100 fold excess of co-existing single-base mismatch targets. Furthermore, it works robustly in clinically relevant media (e.g. 10% human serum) and gives even higher SNP discrimination than that in clean buffers. This ultrasensitive DNA sensor appears to have excellent potential for rapid detection and diagnosis of genetic diseases.


Co-composting of spent coffee ground with olive mill wastewater sludge and poultry manure and effect of Trametes versicolor inoculation on the compost maturity.
The co-composting of spent coffee grounds, olive mill wastewater sludge and poultry manure was investigated on a semi-industrial scale. In order to reduce the toxicity of the phenolic fraction and to improve the degree of composting humification, composts were inoculated with the white-rot fungus Trametes versicolor in the early stages of the maturation phase. During composting, a range of physico-chemical parameters (temperature and both organic matter and C/N reduction), total organic carbon, total nitrogen, elemental composition, lignin degradation and spectroscopic characteristics of the humic acids (HAs) were determined; impacts of the composting process on germination index of Hordeum vulgare and Lactuca sativa were assessed. The coffee waste proved to be a highly compostable feedstock, resulting in mature final compost with a germination index of 120% in less than 5 months composting. In addition, inoculation with T. versicolor led to a greater degree of aromatization of HA than in the control pile. Moreover, in the inoculated mixture, lignin degradation was three times greater and HA increased by 30% (P<0.05), compared to the control pile. In the T. versicolor inoculated mixture, the averages of C and N were significantly enhanced in the HA molecules (P<0.05), by 26% and 22%, respectively. This improvement in the degree of humification was confirmed by the ratio of optical densities of HA solutions at 465 and 665 nm which was lower for HA from the treated mixture (4.5) than that from the control pile (5.4).


Ultra-processed foods and added sugars in the US diet: evidence from a nationally representative cross-sectional study.
To investigate the contribution of ultra-processed foods to the intake of added sugars in the USA. Ultra-processed foods were defined as industrial formulations which, besides salt, sugar, oils and fats, include substances not used in culinary preparations, in particular additives used to imitate sensorial qualities of minimally processed foods and their culinary preparations. Cross-sectional study. National Health and Nutrition Examination Survey 2009-2010. We evaluated 9317 participants aged 1+ years with at least one 24 h dietary recall. Average dietary content of added sugars and proportion of individuals consuming more than 10% of total energy from added sugars. Gaussian and Poisson regressions estimated the association between consumption of ultra-processed foods and intake of added sugars. All models incorporated survey sample weights and adjusted for age, sex, race/ethnicity, family income and educational attainment. Ultra-processed foods comprised 57.9% of energy intake, and contributed 89.7% of the energy intake from added sugars. The content of added sugars in ultra-processed foods (21.1% of calories) was eightfold higher than in processed foods (2.4%) and fivefold higher than in unprocessed or minimally processed foods and processed culinary ingredients grouped together (3.7%). Both in unadjusted and adjusted models, each increase of 5 percentage points in proportional energy intake from ultra-processed foods increased the proportional energy intake from added sugars by 1 percentage point. Consumption of added sugars increased linearly across quintiles of ultra-processed food consumption: from 7.5% of total energy in the lowest quintile to 19.5% in the highest. A total of 82.1% of Americans in the highest quintile exceeded the recommended limit of 10% energy from added sugars, compared with 26.4% in the lowest. Decreasing the consumption of ultra-processed foods could be an effective way of reducing the excessive intake of added sugars in the USA.


Fewer rainy days and more extreme rainfall by the end of the century in Southern Africa.
Future changes in the structure of daily rainfall, especially the number of rainy days and the intensity of extreme events, are likely to induce major impacts on rain-fed agriculture in the tropics. In Africa this issue is of primary importance, but the agreement between climate models to simulate such descriptors of rainfall is generally poor. Here, we show that the climate models used for the fifth assessment report of IPCC simulate a marked decrease in the number of rainy days, together with a strong increase in the rainfall amounts during the 1% wettest days, by the end of the 21st century over Southern Africa. These combined changes lead to an apparent stability of seasonal totals, but are likely to alter the quality of the rainy season. These evolutions are due to the superposition of slowly-changing moisture fluxes, mainly supported by increased hygrometric capacity associated with global warming, and unchanged short-term atmospheric configurations in which extreme events are embedded. This could cause enhanced floods or droughts, stronger soil erosion and nutriment loss, questioning the sustainability of food security for the 300 million people currently living in Africa south of the Equator.


Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor.
Malignant gliomas are the most aggressive forms of brain tumors; whose metastasis and recurrence contribute to high rates of morbidity and mortality. Glioma stem cell-like cells are a subpopulation of tumor-initiating cells responsible for glioma tumorigenesis, metastasis, recurrence and resistance to therapy. Epidermal growth factor receptor (EGFR) has been reported to be dysregulated in most cancers, including gliomas and its functions are closely linked to initiating tumor metastasis and a very poor prognosis. In search for compounds that may reduce the tumorigenic potential of gliomas/glioblastomas honokiol attracted our attention. Honokiol, purified from the bark of traditional Chinese herbal medicine Magnolia species, is beneficial in vitro and in animal models via a variety of pharmacological effects, including anti-inflammatory, anti-angiogenetic, anti-arrhythmic and antioxidant activities, as well as anti-proliferative and proapoptotic effects in a wide range of human cancer cells. However, its effects on glioma cells are unknown. Here, we used different concentrations of honokiol in treating U251 and U-87 MG human glioma/glioblastoma cells in cell culture. Results showed that honokiol inhibited glioma cell viability and colony formation and promoted apoptosis. It also inhibited glioma cell migration/proliferation and invasion. In addition, honokiol promoted apoptosis and reduced Bcl-2 expression, accompanied by increase in Bax expression. Honokiol reduced expression of EGFR, CD133 and Nestin. Moreover, honokiol inhibited the activation of both AKT and ERK signaling pathways, increased active caspase-3 level and reduced phosphorylation of STAT3. U-87 MG xenografts in nude mice and in immunotolerant zebrafish yolk sac showed that honokiol inhibits tumor growth and metastasis. Altogether, results indicate that honokiol reduces tumorigenic potentials, suggesting hopes for honokiol to be useful in the clinical management of glioma/glioblastoma.


Inhibitory effects of bisphosphonates on growth of amoebae of the cellular slime mold Dictyostelium discoideum.
Bisphosphonates are inhibitors of bone resorption and are used increasingly as therapeutic agents for treating clinical disorders of skeletal metabolism. Their mode of action is still not fully understood. The demonstration that methylenebisphosphonate, a simple methylene analog of pyrophosphate, inhibits the axenic growth of amoebae of the slime mold Dictyostelium discoideum and is incorporated into adenine nucleotides suggested that this organism might be useful in elucidating the cellular effects of bisphosphonates. We examined 24 bisphosphonates, including all those of clinical interest as inhibitors of osteoclast-mediated bone resorption in vivo, for their effects on D. discoideum. All the geminal bisphosphonates inhibited growth of Dictyostelium, although the effectiveness of individual compounds varied widely. When the bisphosphonates were ranked there was a remarkable similarity between the order of potency as inhibitors of growth of Dictyostelium and the order of potency as inhibitors of bone resorption. Thus, bisphosphonates with more complex side-chain structures, especially those containing a nitrogen group, were more potent than simple substituted bisphosphonates, some inhibiting Dictyostelium growth even at concentrations below 10 microM. It therefore appears that the mechanism by which bisphosphonates prevent Dictyostelium growth could be similar to the mechanism by which these compounds affect the activity of osteoclasts. Because the mechanisms of action of bisphosphonates on osteoclasts remains unclear, Dictyostelium may provide an additional model for studying the biochemical mode of action of bisphosphonates. Furthermore, these studies suggest that Dictyostelium may also be a convenient organism for rapid evaluation of potentially active bisphosphonates.


Electron microscopic and histochemical observations of muscle degeneration after tourniquet.
As an experimental model for the different forms of muscle degeneration, injury caused by 2 hours' ischemia has been studied from 20 minutes to 16 hours after release of the tourniquet. Discoid degeneration developed in stretched fibers by dissolution of the I bands (Z substances and actin). The discs represented the Q bands (A-H-A). In fibers which passively maintained contraction lengths during degeneration, the Z substances were dissolved, but the continuity of the fibrils was preserved, since the filaments are continuous over all sarcomeres under these conditions. Mitochondria and the tubules of the endoplasmic reticulum swelled, ruptured, and disintegrated. Granular degeneration developed in fibers where mitochondria were abundant. Unstretched degenerating fibers with few mitochondria gave a homogeneous or hyaline appearance. The different forms of degeneration therefore were dependent on the status of stretch and the fiber type. The extent of degeneration was not a function of time after ischemia, there being both nearly normal and severely damaged fibers at 20 minutes and 16 hours after the release of tourniquets. When degeneration occurred, however, the basic alterations were the same in all fibers; there was mitochondrial and reticular swelling, dissolution of the Z substances, and finally disintegration of the contractile material. Some damage developed in the sarcolemmas and capillaries. The mitochondrial disintegration was not linked with inactivation of the succinic dehydrogenase system.


Nutritional composition of mungbean and soybean sprouts compared to their adult growth stage.
This study determined the level of phytonutrients in mungbean and soybean sprouts compared to mature mungbean grain and vegetable soybean. The comparison included landraces and improved mungbean and soybean varieties to assess the effect of breeding on the phytonutrient content of both crops. Sprouting mungbean enhanced vitamin C content 2.7-fold compared to mature mungbean grain. Relatively old mungbean accessions were superior in protein, calcium (Ca), iron (Fe), zinc (Zn), carotenoid and vitamin C content compared to improved mungbean lines at the fully mature stage. With regard to nutritional value, the vegetable soybean stage was superior to soybean sprouts in terms of content of protein (14% increase), Zn (45%), Ca (72%), and Fe (151%). Isoflavones, reported to have beneficial effects on human health, are found at high concentrations in soybean sprouts and could easily provide the recommended anticarcinogenic dose range from 1.5 to 2.0mg/kg of body weight per day.


Oral steroids for the resolution of otitis media with effusion (OME) in children (OSTRICH): study protocol for a randomised controlled trial.
Otitis media with effusion (OME) is an accumulation of fluid in the middle ear affecting about 80 % of children by the age of 4 years. While OME usually resolves spontaneously, it can affect speech, behaviour and development. Children with persistent hearing loss associated with OME are usually offered hearing aids or insertion of ventilation tubes through the tympanic membrane. Oral steroids may be a safe and effective treatment for OME, which could be delivered in primary care. Treatment with oral steroids has the potential to benefit large numbers of children and reduce the burden of care on them and on health services. However, previous trials have either been too small with too short a follow-up period, or of too poor quality to give a definite answer. The aim of the Oral Steroids for the Resolution of Otitis Media with Effusion in Children (OSTRICH) trial is to determine if a short course of oral steroids improves the hearing of children with OME in the short and longer term. A total of 380 participants (children of 2 to 8 years of age) are recruited from Hospital Ear, Nose and Throat departments in Wales and England. A trained clinician seeks informed consent from parents of children with symptoms for at least 3 months that are attributable to OME and with confirmed bilateral hearing loss at study entry. Participants are randomised to a course of oral steroid or a matched placebo for 1 week. Outcomes include audiometry, tympanometry and otoscopy assessments; symptoms; adverse effects; functional health status; quality of life; resource use; and cost effectiveness. Participants are followed up at 5 weeks, and at 6 and 12 months after the day of randomisation. The primary outcome is audiometry-confirmed satisfactory hearing at 5 weeks. An important evidence gap exists regarding the clinical and cost effectiveness of short courses of oral steroid treatment for OME. Identifying an effective, safe, nonsurgical intervention for OME in children for use in primary care would be of great benefit to children, their families and the NHS. ISRCTN49798431 (Registered 7 December 2012).


Suicide and fatal drug overdose in child sexual abuse victims: a historical cohort study.
To determine the rate and risk of suicide and accidental fatal drug overdose (ie, overdose deemed not to have been suicide) in individuals who had been medically ascertained as having been sexually abused during childhood. A historical cohort linkage study of suicide and accidental drug-induced death among victims of child sexual abuse (CSA). Forensic medical records of 2759 victims of CSA who were assessed between 1964 and 1995 were obtained from the Victorian Institute of Forensic Medicine and linked with coronial data representing a follow-up period of up to 44 years. Rates of suicide and accidental fatal drug overdose recorded in coronial databases between 1991 and 2008, and rates of psychiatric disorders and substance use recorded in public mental health databases. Twenty-one cases of fatal self-harm were recorded. Relative risks for suicide and accidental fatal overdose among CSA victims, compared with age-limited national data for the general population, were 18.09 (95% CI, 10.96-29.85; population-attributable risk, 0.37%), and 49.22 (95% CI, 36.11-67.09; population-attributable risk, 0.01%) respectively. Relative risks were higher for female victims. Similar to the general population, CSA victims who died as a result of self-harm were predominantly aged in their 30s at time of death. Most had contact with the public mental health system and half were recorded as being diagnosed with an anxiety disorder. Our data highlight that CSA victims are at increased risk of suicide and accidental fatal drug overdose. CSA is a risk factor that mediates suicide and fatal overdose.


Three perspectives on addiction.
Three perspectives on addiction promulgated during the 1990s are reviewed, along with many earlier contributions to the understanding of addictive illness. It is suggested that these distinct yet overlapping formulations of the dynamics of addiction form a hierarchy for each patient suffering from an addiction. Assessment of a patient's ego strength, and of the relative importance of addictive behaviors in overall character structure, allows referral to various types of treatment, including psychoanalytic therapy. Case examples are presented, including material from the psychoanalysis of a woman addicted to heroin, methadone, cocaine, amphetamines, nicotine, alcohol, and shopping.


Variation of the carrier-envelope phase of few-cycle laser pulses owing to the Gouy phase: a solid-state-based measurement.
The carrier-envelope phase of a laser pulse has recently become an important quantity in extreme nonlinear optics. Because of the topological Gouy phase, it changes while the pulse propagates through the focus of a lens. This variation is measured by a simple solid-state-based approach. The experimental results are analyzed by comparison with simple analytical model calculations.


Magnetic resonance imaging to evaluate patency of aortocoronary bypass grafts.
To assess the efficacy of magnetic resonance (MR) imaging in evaluating graft patency after coronary bypass surgery, 20 patients who had prior surgery (average 5.5 years, range 1.5 to 14) and recent cardiac catheterization because of chest pain were studied. No patient had surgical intervention or change in symptoms in the time interval between catheterization and MR imaging. These 20 patients had a total of 47 grafts, defined as proximal anastomoses: 20 to the left anterior descending or diagonal artery (LAD), 13 to the left circumflex artery marginal branches (LCX), and 14 to the right coronary artery or posterior descending artery (RCA). The patients underwent cardiac and respiratory gated MR scans in a 0.5 tesla magnet with an echo time of 22 msec and two repetitions in a 128 X 256 matrix. In-plane resolution was 2.7 mm. Every patient had a scan in the transaxial plane and some underwent scanning in the sagittal and coronal planes as well. A graft was considered patent by MR when a signal-free lumen was visualized in an anatomic position consistent with that of a bypass graft, had a lumen larger than the native vessels, was seen on more than one slice, and was seen at a level higher than that of the native vessels. If a known graft was not seen it was considered occluded. The scans were interpreted by consensus of two physicians aware of the operative but not the cardiac catheterization data.(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of the antidepressant-like effects of sustained administration of carisbamate and lamotrigine on monoaminergic systems: electrophysiological studies in the rat brain.
Carisbamate and lamotrigine are anticonvulsants that act on neuronal voltage-gated sodium channels. Carisbamate has shown antidepressant-like effects in animal models of depression, and lamotrigine is a mood stabilizer with a therapeutic effect in depressive episodes of patients with bipolar disorder. This study examined the effects of carisbamate and lamotrigine on monoaminergic transmission in rodents, which could contribute to their antidepressant action. In vivo electrophysiological recordings were carried out in rats after 2 and 14 days administration of vehicle, carisbamate (60 mg/kg daily), or lamotrigine (25 mg/kg daily). Overall firing activity of the dorsal raphe nucleus (DRN) serotonin (5-HT), locus coeruleus norepinephrine, and ventral tegmental area dopamine (DA) neurons was decreased with carisbamate. Lamotrigine also decreased 5-HT neuronal firing, and this effect was abolished by lesion of the prefrontal cortex. Despite these decreases in firing activity after their prolonged administration, both anticonvulsants exhibited a significant increase in tonic activation of hippocampus 5-HT1A receptors, as shown by a disinhibition of the firing activity of pyramidal neurons in response to the selective antagonist WAY-100635 (N-{2-[4(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). This finding reveals an increase in the 5-HT level that may be attributed to a desensitization of the terminal 5-HT1B autoreceptors. This study demonstrates that sustained carisbamate and lamotrigine administration decreases 5-HT firing in the DRN but nevertheless enhances 5-HT transmission in the forebrain. This serotonergic effect may be associated with an antiglutamatergic action and may contribute to the antidepressant-like effect of carisbamate in the forced swim test and the antidepressant properties of lamotrigine.


The Need for Psychosocial Interventions to Facilitate the Transition to Extended-Release Naltrexone (XR-NTX) Treatment for Opioid Dependence: A Concise Review of the Literature.
Given the increase of opioid dependence and opioid-related morbidity and mortality, improving treatment options for individuals with opioid dependence warrants increased attention. This article provides a concise review of work in this area. Remission from opioid dependence can be very difficult to sustain, particularly in the absence of opioid replacement or opioid antagonist therapy. For those who wish to transition from opioid use or opioid replacement therapy to opioid antagonist therapy, a significant challenge can be the period of withdrawal symptoms that must be endured prior to the initiation of opioid antagonist therapy. Studies that have incorporated psychosocial interventions into detoxification protocols have found that they can result in improved treatment outcomes. Interventions based on Acceptance and Commitment Therapy have shown promise in the treatment of clinical disorders that present with symptoms similar to those of opioid withdrawal and have been found to positively impact outcomes among those tapering from methadone. However, the use of an Acceptance and Commitment Therapy-based intervention has yet to be studied among opioid-dependent patients transitioning to XR-NTX, and its value to those transitioning to XR-NTX is currently unknown.


Micellar confinement disrupts collective structure and accelerates collective dynamics of encapsulated water.
This computational study deals with the collective structure and dynamics as well as their interaction seen from a dielectric viewpoint in zwitterionic reverse micelles for which a force field was designed de novo. For this end, a dualistic strategy is followed: the raw data are generated by extensive microscopic molecular dynamics (MD) simulations while the subsequent analysis has a focus on mesoscopic dielectric properties. The unusually low dielectric signals as well as the remarkable acceleration of collective dynamics is elucidated in great detail. This structural and dynamic behaviour is caused essentially by non-specific micellar boundary conditions. We found that in these ion lacking reverse micelles the water core and the water sheath compensate each other dielectrically which can be understood as a LeChatelier phenomenon facilitating the transition from highly polar encapsulated water to the non-polar low dielectric medium octane. In addition, specific chemical effects are brought about by the perturbing influence of the surfactants. This comprehensive analysis aids both in understanding and designing the dipolar properties of liquid polar spherical colloids dispersed in a hydrophobic medium.


Antiretroviral drugs to prevent mother-to-child transmission of HIV during breastfeeding.
In low and middle-income countries (LMIC), transmission of HIV during breastfeeding represents a major public health challenge. Several viral, maternal clinical, immunological and genetic factors, as well as maternal-infant host factors and type of infant feeding may influence the risk of breastfeeding transmission of HIV. The mechanisms of breast milk HIV transmission are poorly understood. For mothers who are healthy and do not need combination antiretroviral therapy for their own health, randomized controlled trials have proven that administration of extended maternal triple-drug antiretroviral (ARV) prophylaxis or extended infant ARV prophylaxis can significantly reduce the risk of HIV transmission during breastfeeding. Based on this evidence, the World Health Organization (WHO) published new guidance in 2010 on the use of ARVs for treating pregnant women, and preventing mother-to-child HIV transmission (PMTCT). Although, remarkable advances have occurred in prevention of postnatal transmission during breastfeeding using antiretroviral strategies, a number of challenges remain. Future research must focus on field studies to evaluate programmatic implementation of new WHO PMTCT regimens, monitor long-term safety of ART exposure during pregnancy and lactation, and study emergence of ARV resistance (in mothers and infected infants despite prophylaxis).


Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.
Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval estimated a mean maximum QTc interval of 456 ms (50% effective concentration of 209 ng/ml). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98 to 2.46% risk of having QTc prolongation of >60 ms in all treatment settings. Although piperaquine administration resulted in QTc prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern. (This study has been registered at ClinicalTrials.gov under identifier NCT02199951.).


Panton-Valentine leukocidin in community and hospital-acquired Staphylococcus aureus strains.
Staphylococcus aureus causes serious hospital-acquired (HA) and community-acquired (CA) infections. Skin and soft-tissue infections especially are sometimes caused by strains harbouring Panton-Valentine leukocidin (PVL). PVL belongs to a family of bi-component leukocidal toxins produced by staphylococci. It is a pore-forming toxin encoded by lukF-PV and lukS-PV. A total of 70 S. aureus strains: 38 (54%) methicillin-resistant (MRSA) and 32 (46%) methicillin-susceptible (MSSA), were isolated from patients admitted to Dicle University Hospital (Turkey). Identification of S. aureus and antibiotics-susceptibility testing were performed with PHOENIX 100. PVL genes and mecA genes were detected by polymerase chain reaction. Of the 70 studied strains, 36 ones (51%) were community acquired and 34 ones (49%) were hospital acquired . A total of 38 (54%) strains were positive for mecA (mecA+), of which 32 ones (84%) were HA. Of the mecA- strains, 30 (94%) were CA. Of the 70 studied strains, 12 (17%) strains were PVL+: 8 (22%) of the 36 CA strains and 4 (12%) of the 34 HA strains. Of the 12 PVL+ strains, 4 strains were mecA+. The PVL positivity rate was 25% in MSSA, whereas 10.5% in MRSA. Of the overall PVL+ strains, seven strains were obtained from wounds; four ones from skin abscess; and one from blood culture. Taken together, the obtained results showed a substantial level of PVL genes in the studied region. Although PVL is known as a common virulence factor of CA MRSA, HA MRSA isolates in our study showed a considerable rate of PVL positivity.


Super-resolution imaging through a planar silver layer.
It has been proposed that a planar silver layer could be used to project a super-resolution image in the near field when illuminated near its plasma frequency [J. B. Pendry, Phys. Rev. Lett. 86, 3966 (2000)]. This has been investigated experimentally using a modified form of conformal-mask photolithography, where dielectric spacers and silver layers are coated onto a tungsten-on-glass mask. We report here on the experimental confirmation that super-resolution imaging can be achieved using a 50-nm thick planar silver layer as a near-field lens at wavelengths around 365 nm. Gratings with periods down to 145 nm have been resolved, which agrees well with our finite-difference time domain (FDTD) simulations.


Diffuse gliomas with FGFR3-TACC3 fusion have characteristic histopathological and molecular features.
Adult glioblastomas, IDH-wildtype represent a heterogeneous group of diseases. They are resistant to conventional treatment by concomitant radiochemotherapy and carry a dismal prognosis. The discovery of oncogenic gene fusions in these tumors has led to prospective targeted treatments, but identification of these rare alterations in practice is challenging. Here, we report a series of 30 adult diffuse gliomas with an in frame FGFR3-TACC3 oncogenic fusion (n = 27 WHO grade IV and n = 3 WHO grade II) as well as their histological and molecular features. We observed recurrent morphological features (monomorphous ovoid nuclei, nuclear palisading and thin parallel cytoplasmic processes, endocrinoid network of thin capillaries) associated with frequent microcalcifications and desmoplasia. We report a constant immunoreactivity for FGFR3, which is a valuable method for screening for the FGFR3-TACC3 fusion with 100% sensitivity and 92% specificity. We confirmed the associated molecular features (typical genetic alterations of glioblastoma, except the absence of EGFR amplification, and an increased frequency of CDK4 and MDM2 amplifications). FGFR3 immunopositivity is a valuable tool to identify gliomas that are likely to harbor the FGFR3-TACC3 fusion for inclusion in targeted therapeutic trials.


Clinical study of critical patients with hemorrhagic fever with renal syndrome complicated by acute respiratory distress syndrome.
The aim of this study was to investigate the clinical characteristics and outcomes of critical patients with hemorrhagic fever with renal syndrome (HFRS) complicated by acute respiratory distress syndrome (ARDS). To observe the demographic, epidemiological and clinical characteristics, and to explore the predictive effects for prognosis in laboratory findings, we conducted a detailed retrospective analysis of clinical records for critical patients with HFRS complicated by ARDS, treated at the center for infectious diseases, Tangdu Hospital, between January 2008 and December 2012. A total of 48 critical patients with laboratory confirmed HFRS accompanied by ARDS were enrolled in the study, including 27 survivors and 21 non-survivors, with a fatality rate of 43.75%. Thirty-one individuals (64.6%) contracted HFRS between the months of September and December. The non-survivors tended to have lower incidence of overlapping phase (P = 0.025). There were no obvious differences in the needs for mechanical ventilation (MV) and renal replacement therapy (RRT), except for the need for vasoactive drugs between the survivors and non-survivors (P = 0.001). The non-survivors were found to have higher frequencies of encephalopathy, refractory shock and multiple organ dysfunction syndrome (MODS), lower incidences of acute renal failure (ARF) and secondary hypertension (P<0.05). The non-survivors tended to have lower levels of serum creatinine (Scr) (P<0.001) and fibrinogen (Fib) (P = 0.003), higher incidences of prolonged prothrombin time (PT) (P = 0.006) and activated partial thromboplastin time (APTT) (P = 0.020) and higher levels of aspartate aminotransferase (AST) (P = 0.015), and the laboratory parameters mentioned above reached statistical significance for predicting prognosis (P<0.05). The high mortality rate of critical patients with HFRS complicated by ARDS emphasizes the importance of clinicians' alertness and timely initiation of systemic supportive therapy.


Angiotensin II induces water absorption behavior in two species of desert anurans.
The octapeptide, angiotensin II (A-II), induces drinking behavior in several vertebrate species; however, relatively little is understood about A-II-induced thirst in amphibians. Scaphiopus couchii and Bufo cognatus were dehydrated to 90% of their ad libitum weight. This level of dehydration was sufficient to induce water absorption response (WR) behavior in both species. Fully hydrated toads injected intraperitoneally with A-II exhibited a significant amount of WR behavior. The minimum effective dose for inducing WR behavior was 10 micrograms/100 g-animal for S. couchii and 100 micrograms/100 g-animal for B. cognatus. When dehydrated toads were treated with the A-II receptor antagonist, Thr8-saralasin, S. couchii, exhibited a significant increase in WR behavior, while B. cognatus did not respond behaviorally. Finally, treatment of dehydrated toads with captopril, a compound that inhibits conversion of angiotensin I to A-II, did not significantly affect WR behavior in either species. These results support other findings that A-II may be involved in WR behavior in amphibians. However, the failure of Thr2-saralasin or captopril to inhibit WR behavior in dehydrated toads suggests that the receptor mechanisms involved in thirst regulation in toads may be different from those in mammals, and the renin-angiotensin system may not be the only potential mediator of WR behavior in these species.


Gadolinium inhibits group III but not group IV muscle afferent responses to dynamic exercise.
Dynamic exercise has been shown to stimulate rapidly both group III and IV muscle afferents. The often rapid (i.e. 2 s) onset latencies of the group IV afferents is particularly surprising because these unmyelinated afferents are thought to respond to the gradual accumulation of metabolites signalling a mismatch between blood/oxygen demand and supply in exercising muscles. One explanation for the rapid onset to exercise by group IV afferents is that they are mechanosensitive, a concept that has been supported by the finding that these afferents were stimulated by vasodilatation induced by injection of vasoactive drugs. We therefore examined in decerebrated cats the effect of gadolinium, a blocker of mechanogated channels, on the responses of group III and IV muscle afferents to dynamic exercise induced by electrical stimulation of the mesencephalic locomotor region. We found that gadolinium (10 mm; 1 ml) injected into the abdominal aorta had no significant effect (P > 0.05) on the responses of 11 group IV afferents to dynamic exercise. In contrast, gadolinium markedly attenuated the responses of 11 group III afferents to exercise (P < 0.05). Our findings suggest that group IV afferents are not responding to a mechanical stimulus during exercise. Instead their rapid response to dynamic exercise might be caused by a chemical substance whose concentration is directly proportional to blood flow, which increases in the skeletal muscles when they are dynamically exercising.


Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi.
The contribution of autoimmunity in the genesis of chronic Chagas' heart pathology is not clear. In the present study, we show that: (a) BALB/c mice chronically infected with Trypanosoma cruzi reject syngeneic newborn hearts; (b) in vivo treatment with anti-CD4 but not anti-CD8 monoclonal antibodies (mAbs) abrogates rejection; (c) CD4+ T cells from chronically infected mice proliferate in vitro to syngeneic myocardium antigens and induce heart graft destruction when injected in situ; (d) anti-CD4 treatment of chronically infected mice establishes long-term tolerance to syngeneic heart grafts; and (e) the state of tolerance is related to in vitro and in vivo unresponsiveness of the CD4+ T cells. These findings allow us to suggest that autoimmunity is the major mechanism implicated in the rejection of syngeneic heart tissues grafted into the pinna of the ear of mice chronically infected with T. cruzi. The similarity of the lesions to those found in humans suggests that autoimmunity is involved in the pathogenesis of chagasic cardiomyopathy in humans. Moreover, this could imply therapeutic strategies by reestablishing long-term tissue-specific tolerance with anti-CD4 mAb treatment, mediating anergy, or deleting the responder CD4+ T cells to heart tissue antigens.


High-fat diet, muscular lipotoxicity and insulin resistance.
A high dietary fat intake and low physical activity characterize the current Western lifestyle. Dietary fatty acids do not stimulate their own oxidation and a surplus of fat is stored in white adipose tissue, liver, heart and muscle. In these organs intracellular lipids serve as a rapidly-available energy source during, for example, physical activity. However, under conditions of elevated plasma fatty acid levels and high dietary fat intake, conditions implicated in the development of modern diseases such as obesity and type 2 diabetes mellitus, fat accumulation in liver and muscle (intramyocellular lipids; IMCL) is associated with the development of insulin resistance. Recent data suggest that IMCL are specifically harmful when combined with reduced mitochondrial function, both conditions that characterize type 2 diabetes. In the (pre)diabetic state reduced expression of the transcription factor PPARgamma co-activator-1alpha (PGC-1alpha), which is involved in mitochondrial biogenesis, has been suggested to underlie the reduced mitochondrial function. Importantly, the reduction in PGC-1alpha may be a result of low physical activity, consumption of high-fat diets and high plasma fatty acid levels. Mitochondrial function can also be impaired as a result of enhanced mitochondrial damage by reactive oxygen species. Fatty acids in the vicinity of mitochondria are particularly prone to lipid peroxidation. In turn, lipid peroxides can induce oxidative damage to mitochondrial RNA, DNA and proteins. The mitochondrial protein uncoupling protein 3, which is induced under high-fat conditions, may serve to protect mitochondria against lipid-induced oxidative damage, but is reduced in the prediabetic state. Thus, muscular lipotoxicity may impair mitochondrial function and may be central to insulin resistance and type 2 diabetes mellitus.


Indicators of publicly funded prescription opioid use among persons with traumatic spinal cord injury in Ontario, Canada.
To describe the proportion and identify predictors of community-dwelling individuals with traumatic spinal cord injury (TSCI) who were dispensed ≥1 publicly funded opioid in the year after injury using a retrospective cohort study. Ontario, Canada. We used administrative data to identify predictors of receiving publicly funded prescription opioids during the year after injury for individuals who were injured between April 2004 and March 2015. Our outcome was modeled using robust Poisson multivariable regression and we reported adjusted relative risks (aRR) with 95% confidence intervals. In our retrospective cohort of 934 individuals with TSCI who were eligible for the provincial drug program, 510 (55%) received ≥1 prescription opioid in the year after their injury. Most individuals were male (71%) and the median age was 63 years (interquartile range: 42-72). Being male (aRR 1.15, 95% confidence interval [CI] 1.01-1.31), having chronic obstructive pulmonary disease (aRR 1.25, 95% CI 1.05-1.50), and using prescription opioids before injury (aRR 1.46, 95% CI 1.29-1.66) were significantly associated with receiving opioids in the year after TSCI. Short durations of hospital stay after injury were also identified as being a significant risk factor of outpatient opioid use (aRR = 1.28, 95% CI = 1.08-1.51) when compared to longer hospital stays. This study presented evidence showing that most individuals eligible for Ontario's public drug program who experienced a TSCI used opioids in the year following their injury. Due to the paucity of research on this population and their potential for elevated risks of adverse events, it is important for additional studies to be conducted on opioid use in this population to understand short-term and long-term risks and benefits.


Human cerebral circulation: positron emission tomography studies.
We reviewed the literature on human cerebral circulation and oxygen metabolism, as measured by positron emission tomography (PET), with respect to normal values and of regulation of cerebral circulation. A multicenter study in Japan showed that between-center variations in cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) values were not considerably larger than the corresponding within-center variations. Overall mean +/- SD values in cerebral cortical regions of normal human subjects were as follows: CBF = 44.4 +/- 6.5 ml/100 ml/min; CBV = 3.8 +/- 0.7 ml/100 ml; OEF = 0.44 +/- 0.06; CMRO2 = 3.3 +/- 0.5 ml/100 ml/min (11 PET centers, 70 subjects). Intrinsic regulation of cerebral circulation involves several factors. Autoregulation maintains CBF in response to changes in cerebral perfusion pressure; chemical factors such as PaCO2 affect cerebral vascular tone and alter CBF; changes in neural activity cause changes in cerebral energy metabolism and CBF; neurogenic control of CBF occurs by sympathetic innervation. Regional differences in vascular response to changes in PaCO2 have been reported, indicating regional differences in cerebral vascular tone. Relations between CBF and CBV during changes in PaCO2 and during changes in neural activity were in good agreement with Poiseuille's law. The mechanisms of vascular response to neural activation and deactivation were independent on those of responses to PaCO2 changes. CBV in a brain region is the sum of three components: arterial, capillary and venous blood volumes. It has been reported that the arterial blood volume fraction is approximately 30% in humans and that changes in human CBV during changes in PaCO2 are caused by changes in arterial blood volume without changes in venous blood volume. These findings should be considered in future studies of the pathophysiology of cerebrovascular diseases.


Supporting Medical Home Transformation Through Evaluation of Patient Experience in a Large Culturally Diverse Primary Care Safety Net.
The prevalence of chronic disease in the United States is rapidly increasing, with a disproportionate number of underserved, vulnerable patients sharing the burden. The Patient-Centered Medical Home (PCMH) is a care delivery model that has shown promise to improve primary care and address the burden of chronic illness. The purpose of this study was to (1) understand patient characteristics that might influence perceived patient experience in a large primary care safety net undergoing PCMH transformation; (2) identify community-level quality improvement opportunities to support ongoing transformation activities; and (3) establish a baseline of patient experience across the primary care safety net that could be used in repeated evaluations over the course of transformation. A cross-sectional study design was used to conduct this research. A total of 351 racially and ethnically diverse patients of 4 primary care safety net organizations in Broward County, Florida, were surveyed regarding their experience with access to care and coordination of care. Reported access to care and coordination of care. Patients with chronic disease who reported having visited the clinic 3 or more times in the past 12 months reported a better coordination of care experience than patients who had fewer than 3 visits in the past 12 months (odds ratio = 3.57; 95% confidence interval, 1.76-7.24). Patients without chronic disease who had been receiving care at the clinic for 2 or more years of care reported worse experience with access to care than patients with less than 2 years of care (odds ratio = 0.26; 95% confidence interval, 0.11-0.60.) Race, ethnicity, language, and education were not significant predictors of patient experience. Findings support ongoing efforts to improve patient engagement among all patients and to enhance resources to manage chronic disease, including community-based self-management programs, in primary care safety nets undergoing PCMH transformation.


Focused antibody response to influenza linked to antigenic drift.
The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses.


Real-Time Shape Illustration Using Laplacian Lines.
This paper presents a novel object-space line drawing algorithm that can depict shapes with view-dependent feature lines in real time. Strongly inspired by the Laplacian-of-Gaussian (LoG) edge detector in image processing, we define Laplacian lines as the zero-crossing points of the Laplacian of the surface illumination. Compared to other view-dependent feature lines, Laplacian lines are computationally efficient because most expensive computations can be preprocessed. We further extend Laplacian lines to volumetric data and develop the algorithm to compute volumetric Laplacian lines without isosurface extraction. We apply the proposed Laplacian lines to a wide range of real-world models and demonstrate that Laplacian lines are more efficient than the existing computer generated feature lines, and can be used in interactive graphics applications.


Na(+)-Ca2+ exchange, myoplasmic Ca2+ concentration, and contraction of arterial smooth muscle.
Na(+)-Ca2+ exchange is proposed to be an important regulator of myoplasmic intracellular Ca2+ concentration ([Ca2+]i) and contraction in vascular smooth muscle. We investigated the role of Na(+)-Ca2+ exchange in regulating [Ca2+]i in swine carotid arterial tissues that were loaded with aequorin to allow simultaneous measurement of [Ca2+]i and force. Reversal of Na(+)-Ca2+ exchange, by reduction of extracellular Na+ concentration ([Na+]o) to 1.2 mM, induced a large increase in aequorin-estimated [Ca2+]i and a low [Ca2+]i sensitivity. The contraction induced by 1.2 mM [Na+]o was partially caused by depolarization and opening of L-type Ca2+ channels because 10 microM diltiazem partially attenuated the 1.2 mM [Na+]o-induced increases in [Ca2+]i. High dose ouabain (10 microM), a putative endogenous Na+,K(+)-ATPase inhibitor, increased both [Ca2+]i and force. However, the increases in [Ca2+]i and force were mostly blocked by 10 microM phentolamine, suggesting the predominant effect of ouabain was to increase norepinephrine release from nerve terminals. In the presence of 10 microM phentolamine, 10 microM ouabain slightly accentuated 1 microM histamine-induced increases in [Ca2+]i and force. The ouabain dose necessary to induce contraction in the absence of phentolamine was significantly less than the ouabain dose necessary to accentuate histamine-induced contractions in the presence of phentolamine. These results suggest that Na(+)-Ca2+ exchange exists in swine arterial smooth muscle. These data also suggest that ouabain (which should increase [Na+]i and inhibit Na(+)-Ca2+ exchange) primarily enhances contractile function in the swine carotid artery by releasing catecholamines from nerve terminals; direct action of Na+,K(+)-ATPase inhibitors on smooth muscle appears to occur only with very high doses.


Sodium iron EDTA [NaFe(III)EDTA] as a food fortificant does not influence absorption and urinary excretion of manganese in healthy adults.
NaFe(III)EDTA is a promising iron (Fe) compound for food fortification programs because of its high Fe bioavailability from meals containing dietary inhibitors of Fe absorption such as phytic acid. However, this Fe compound is not currently used in any large-scale fortification program because of concern over its possible negative influence on the metabolism of other essential minerals or its possible influence on the absorption of potentially toxic elements, such as manganese (Mn). In this study, Mn absorption and urinary excretion were studied in adults after intake of an Fe-fortified weaning cereal labeled with 54Mn. In a crossover design, the fortification of the weaning cereal with Fe as NaFeEDTA was compared with ferrous sulfate. Manganese absorption was measured by extrapolation from whole-body retention data 10-30 d after intake, and urinary excretion of 54Mn was measured over 7 d. No significant differences in 54Mn absorption or urinary excretion were found; 1.1 +/- 0.15 and 0.91 +/- 0.35% of the ingested dose was absorbed from the cereal fortified with NaFe(III)EDTA and FeSO4, respectively. Urinary excretion of 54Mn was very low; the total radioactivity in urine represented 1.1 +/- 0.55% of the absorbed dose with NaFe(III)EDTA and 0.72 +/- 0.53% of the absorbed dose with FeSO4. Until now, Fe-fortification programs have met with only limited success. The introduction of NaFeEDTA as a food fortificant could be a useful tool to provide bioavailable Fe to vulnerable groups in the population and thus aid in combating Fe deficiency.


Designing and fabricating diffractive optical elements with a complex profile by interference.
We demonstrate a novel (to our knowledge) method for the design and the fabrication of diffractive optical elements (DOEs) with an arbitrary complex phase profile based on interference. The DOEs are designed to modulate the complex light wave by the analytical formulas, and an asymmetric holographic DOE with cubic phase modulation is fabricated by a two-step exposure technique. The desired Airy beams are produced experimentally, which demonstrates the validity of this method. It is a simple approach with a low cost for the design and the fabrication of DOEs with a large area and arbitrary phase distribution.


Emergency department characteristics of male sexual assault.
To characterize the nature, frequency, and treatment of male sexual assault encountered by physicians in an ED. A minor objective compared the lengths of time the victim knew the assailant between males and females to determine whether there were differences between male and female victims. Retrospective review over four years of all male patients with a diagnosis of sexual assault presenting to an urban academic ED in New York City. Demographics, types of injury, assailant/victim information, and treatment of the assault were obtained. Twenty-seven male sexual assaults (approximately 12% of all sexual assaults) were documented during this time period. Forcible rectal, oral, or both rectal and oral intercourse occurred 14, 4, and 9 times, respectively. Documented physical trauma occurred in nine of 27 visits, with two admissions for head trauma. Five additional patients complained of rectal pain with no independent objective evidence of trauma. Prophylactic treatment with antibiotics for the prevention of Neisseria gonorrhoeae and Chlamydia trachomatis was offered in 26 of 27 episodes and prophylactic HIV protection was given to only two of 21 eligible patients. Documentation of HIV status and HIV counseling occurred only in ten and five visits, respectively. The male-to-female odds ratios for whether the assailant was unknown, known less than 24 hours, or known more than 24 hours were 0.43 (95% CI = 0.15 to 1.26), 2.48 (95% CI = 0.94 to 6.53), and 0.92 (95% CI = 0.31 to 2.71), respectively. The percentage of total sexual assaults occurring in males who present to an ED is now more than 10% of all sexual assaults seen in this urban ED. These assaults are associated with a high proportion of patients with documented trauma. Although the treatment of traditional sexually transmitted diseases appears to be covered well, the need for HIV documentation, counseling, and possible HIV prophylaxis should be addressed more aggressively. In comparing the lengths of the relationships between the victim and the assailant, it appears twice as likely that the female victim will not know her assailant compared with the male, and twice as likely that the male victim will know his assailant less than 24 hours compared with the female.


MicroRNA expression, survival, and response to interferon in liver cancer.
Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease. We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase-polymerase-chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy. In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor kappaB and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA. The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa.


Effects of COVID-19 Lockdown on Movement Disorders Patients With Deep Brain Stimulation: A Multicenter Survey.
Background: The containment measures taken by Italian government authorities during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused the interruption of neurological activities of outpatient clinics. Vulnerable patients, as Parkinson's disease (PD) and dystonic patients with deep brain stimulation (DBS), may have an increased risk of chronic stress related to social restriction measures and may show a potential worsening of motor and psychiatric symptoms. Methods: This cross-sectional multicenter study was carried out during the SARS-CoV-2 pandemic and was based on a structured survey administered during a telephone call. The questionnaire was designed to gather motor and/or psychiatric effects of the lockdown and coronavirus disease 2019 (COVID-19) epidemiologic information in PD and dystonic patients with a functioning DBS implant. Results: One hundred four patients were included in the study, 90 affected by PD and 14 by dystonia. Forty-nine patients reported a subjective perception of worsening of global neurological symptoms (motor and/or psychiatric) related to the containment measures. In the multivariate analysis, having problems with the DBS device was the only independent predictor of motor worsening [odds ratio (OR) = 3.10 (1.22-7.91), p = 0.018]. Independent predictors of psychiatric worsening were instrumental activities of daily living (IADL) score [OR = 0.78 (0.64-0.95), p = 0.012] and problems with DBS [OR = 5.69 (1.95-16.62), p = 0.001]. Only one patient underwent nasopharyngeal swabs, both negative, and no patient received a diagnosis of COVID-19. Conclusions: Lockdown restriction measures were associated with subjective worsening of motor and psychiatric symptoms in PD and dystonic patients treated with DBS, and they may have exacerbated the burden of neurological disease and increased the chronic stress related to the DBS management.


Glycosylation of Pseudomonas aeruginosa strain Pa5196 type IV pilins with mycobacterium-like alpha-1,5-linked d-Araf oligosaccharides.
Pseudomonas aeruginosa is a gram-negative bacterium that uses polar type IV pili for adherence to various materials and for rapid colonization of surfaces via twitching motility. Within the P. aeruginosa species, five distinct alleles encoding variants of the structural subunit PilA varying in amino acid sequence, length, and presence of posttranslational modifications have been identified. In this work, a combination of mass spectrometry and nuclear magnetic resonance spectroscopy was used to identify a novel glycan modification on the pilins of the group IV strain Pa5196. Group IV pilins continued to be modified in a lipopolysaccharide (wbpM) mutant of Pa5196, showing that, unlike group I strains, the pilins of group IV are not modified with the O-antigen unit of the background strain. Instead, the pilin glycan was determined to be an unusual homo-oligomer of alpha-1,5-linked d-arabinofuranose (d-Araf). This sugar is uncommon in prokaryotes, occurring mainly in the cell wall arabinogalactan and lipoarabinomannan (LAM) polymers of mycobacteria, including Mycobacterium tuberculosis and Mycobacterium leprae. Antibodies raised against M. tuberculosis LAM specifically identified the glycosylated pilins from Pa5196, confirming that the glycan is antigenically, as well as chemically, identical to those of Mycobacterium. P. aeruginosa Pa5196, a rapidly growing strain of low virulence that expresses large amounts of glycosylated type IV pilins on its surface, represents a genetically tractable model system for elucidation of alternate pathways for biosynthesis of d-Araf and its polymerization into mycobacterium-like alpha-1,5-linked oligosaccharides.


Thrombophilia testing in children: What and when should be tested?
Venous thrombosis (VTE) in children is gaining increased awareness and apart from underlying medical conditions, recently reported systematic reviews on pediatric VTE (70% provoked) have shown significant associations between thrombosis and presence of inherited thrombophilic risk factors (IT), such as protein C-, protein S- and antithrombin deficiency, mutations of factor 5 (F5: rs6025) and factor 2 (F2: rs1799963), even more pronounced when combined IT were involved. Although we have learned more about the pathophysiology of VTE with the increased discovery of IT evidence is still lacking as to whether IT influence the clinical outcome in pediatric VTE. It still remains controversial as to whether children with VTE or offspring from thrombosis-prone families benefit from IT screening. Thus, IT testing in children should be individualized. If the decision "pro screening" is discussed as an appropriate option in adolescents with unprovoked VTE and in children with a positive family history for VTE screening should be performed in a specialized coagulation unit for acquired or inherited and prothrombotic defects based on the individual population background. Apart from the laboratory assessment for the presence/absence of lupus anticoagulants and antiphospholipid antibodies screening should be performed beyond the acute VTE onset and after withdrawal of anticoagulant medication possibly influencing laboratory results.


Accelerated evolution of snake venom phospholipase A2 isozymes for acquisition of diverse physiological functions.
The nucleotide sequences of two cDNAs and four genes encoding Trimeresurus gramineus venom gland phospholipase A2 (PLA2) isozymes were determined and compared internally and externally with those encoding Trimeresurus flavoviridis venom gland PLA2 isozymes. It was revealed that the protein-coding regions are much more diversified than the 5' and 3' untranslated regions (UTRs) and the introns except for the signal peptide domain. The numbers of nucleotide substitutions per site (KN) for the UTRs and the introns were approximately one-quarter of the numbers of nucleotide substitutions per synonymous site (KS) for the protein-coding regions and were at the same level as the KN value of T. gramineus and T. flavoviridis TATA box-binding protein (TBP) genes, indicating that the protein-coding regions of PLA2 isozyme genes are unusually variable and that the UTRs including the introns of venom gland PLA2 isozyme genes have evolved at similar rate to those of non-venomous genes. The numbers of nucleotide substitutions per non-synonymous site (KA) values were close to or larger than the KS values for the protein-coding regions in venom gland PLA2 isozyme genes, indicating that the protein-coding regions of snake venom gland PLA2 isozyme genes have evolved via accelerated evolution. Furthermore, the evolutionary trees derived from the combined sequences of the 5' and 3' UTRs and the signal peptide domain of cDNAs were in accord with the consequences from taxonomy. In contrast, the evolutionary trees from the mature protein-coding region sequences of cDNAs and from the amino acid sequences showed random patterns. Estimations of nucleotide divergence of genes and the phylogenetic analysis reveal that snake venom group IJ PLA2 isozyme genes have been evolving under adaptive pressure to acquire new physiological activities.


Growth of Candida albicans hyphae.
The fungus Candida albicans is often a benign member of the mucosal flora; however, it commonly causes mucosal disease with substantial morbidity and in vulnerable patients it causes life-threatening bloodstream infections. A striking feature of its biology is its ability to grow in yeast, pseudohyphal and hyphal forms. The hyphal form has an important role in causing disease by invading epithelial cells and causing tissue damage. This Review describes our current understanding of the network of signal transduction pathways that monitors environmental cues to activate a programme of hypha-specific gene transcription, and the molecular processes that drive the highly polarized growth of hyphae.


Phylogeny, biogeography, and processes of molecular differentiation in Quercus subgenus Quercus (Fagaceae).
Quercus is one of the most abundant and economically important genera of woody plants in the Northern Hemisphere. To infer phylogenetic relationships within Quercus subgenus Quercus, chloroplast DNA (cpDNA) restriction sites and nucleotide sequences of the internal transcribed spacers (ITS) and the 5.8S coding region of the nuclear ribosomal DNA repeat were obtained for 44 individuals, including 25 species, intraspecific samples, and three outgroups. Separate parsimony analyses of each data set showed that individual gene trees were congruent and often complementary in supporting clades that generally corresponded to previously recognized taxonomic groups. Only one instance of strongly supported gene tree incongruence was detected and this anomalous pattern was explained best by ancient introgression of cpDNA across sectional boundaries. Simultaneous parsimony analysis of the pruned data sets supported the recognition of the strictly Eurasian section Cerris and resolved a novel hypothesis for the major infrageneric groups (Cerris- (Lobatae- (Protobalanus + Quercus sensu stricto))). The biogeographic hypothesis that all major oak lineages evolved locally at middle latitudes within the general distribution of their fossil ancestors was fully supported. This set of relationships also suggested a New World origin for the widespread white oaks of the Northern Hemisphere (section Quercus s. s.). For both data sets, inter- and intraspecific sampling within section Protobalanus showed little correspondence to morphological species. Greater cladistic structure among the samples was obtained by cpDNA restriction sites and two well-delimited plastomes types comprising a total of 15 distinct haplotypes were resolved. Haplotypes of 2 of the peripheral species in this species complex occupy terminal portions of one of the plastome clades, suggesting a more recent origin relative to those of more widespread species. The phylogeography of the two divergent plastome types suggested a north-south pattern, consistent with a Late Tertiary disjunction in the ancestral distribution of section Protobalanus.


Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man.
The left ventricular diastolic pressure-volume relationship shifts upward during angina, but why this happens is not known. To assess regional myocardial stiffness, we studied 12 patients who had coronary artery disease using simultaneous left ventricular micromanometer pressure recording and M-mode echocardiography before and during angina induced by pacing tachycardia. All patients had two- or three-vessel coronary artery disease that involved the posterior left ventricular wall circulation and had positive pacing stress tests, i.e., development of angina and a postpacing rise in left ventricular end-diastolic pressure (15 +/- 3 to 31 +/- 6 mm Hg, p less than 0.001). A marked upward shift in the relationship between the diastolic left ventricular pressure and the posterior wall thickness (h) occurred after pacing tachycardia, but the change in left ventricular posterior wall end-diastolic thickness was minimal (8.9 +/- 2.1 to 9.2 +/- 2.1 mm, NS). After pacing, the peak rate of left ventricular posterior wall thinning decreased (82 +/- 37 to 48 +/- 27 mm/sec, p less than 0.005) and the time constant of relaxation derived from the best exponential fit to the isovolumic left ventricular pressure decay increased (49 +/- 5 to 58 +/- 7 msec, p less than 0.001). Diastolic active left ventricular pressure decay, extrapolated from the exponential fit, was subtracted from the measured left ventricular pressure (which is equal in magnitude but opposite in sign to the radial stress at the endocardium) to calculate residual left ventricular pressure (PR) and hence residual stress (sigma R = -PR). A radial stiffness modulus (ER) was determined by the slope of the PR vs log h plots before and after pacing. Over the same range of residual radial stress (sigma R), ER was always higher during pacing-induced angina, indicating increased residual myocardial stiffness. Increased myocardial stiffness in addition to a decreased rate of wall thinning and slow active pressure decay contribute to the upward shift in left ventricular pressure-wall thickness and pressure-volume relationships during pacing-induced angina.


Stress fracture healing: fatigue loading of the rat ulna induces upregulation in expression of osteogenic and angiogenic genes that mimic the intramembranous portion of fracture repair.
Woven bone is formed in response to fatigue-induced stress fractures and is associated with increased local angiogenesis. The molecular mechanisms that regulate this woven bone formation are unknown. Our objective was to measure the temporal and spatial expression of osteo- and angiogenic genes in woven bone formation in response to increasing levels of fatigue-induced damage. We used the rat forelimb compression model to produce four discrete levels of fatigue damage in the right ulna of 115 male Fischer rats. Rats were killed at 0 (1 h), 1, 3 and 7 days after loading. Using qRT-PCR, we quantified gene expression associated with osteogenesis (BMP2, Msx2, Runx2, Osx, BSP, Osc), cell proliferation (Hist4), and angiogenesis (VEGF, PECAM-1) from the central half of the ulna. The spatial distribution of BMP2, BSP and PCNA was assessed by immunohistochemistry or in situ hybridization in transverse histological sections 1, 4, and 7 mm distal to the ulnar mid-diaphysis. One hour after loading, BMP2 was significantly upregulated in neurovascular structures in the medial ulnar periosteum. Expression of angiogenic markers (VEGF, PECAM-1) increased significantly between Day 0 and 1 and, as with BMP2 expression, remained upregulated through Day 7. While Osx and BSP were upregulated on Day 1, the other osteogenic genes (Msx2, Runx2, Osx, BSP and Osc) were induced on Day 3 in association with the initiation of periosteal woven bone formation and continued through Day 7. The magnitude of osteogenic gene expression, particularly matrix genes (BSP, Osc) was significantly proportional the level of fatigue damage. The woven bone response to fatigue injury is remarkably similar to the "intramembranous" portion of fracture repair - rapid formation of periosteal woven bone characterized by early BMP2 expression, cell proliferation, and upregulation of osteogenic genes. We speculate that woven bone repair of fatigue damage may be an abbreviated fracture response without the requirement for endochondral repair. We conclude that bone fatigue repair is a process similar to intramembranous fracture repair characterized by increases in the expression of genes associated with angiogenesis, cell proliferation and osteoblastogenesis, and that the response from the local vasculature precedes the osteogenic response to fatigue loading.


Developing a descriptive system for a new preference-based measure of health-related quality of life for children.
The use of preference-based measures (PBMs) of health-related quality of life (HRQoL) is increasing in health care resource allocation decisions. Whilst there are measures widely used for this purpose in adults, research in the paediatric field is more limited. This paper reports on how the descriptive system for a new paediatric generic PBM of HRQoL was developed from dimensions identified in previous research. Existing scales from the paediatric literature were reviewed for suitability, and scales were also developed empirically, based on qualitative interview data from children, by taking adverbial phrases and confirming the ordinality by a ranking exercise with children. The resulting scales were applied to the dimensions from the previous research. No suitable scales were found in the paediatric literature, so the empirically derived scales were used resulting in seven different types. Children were successfully able to rank these to determine the ordinality, and these types were applied to the dimensions. This work has empirically developed a descriptive system for the dimensions of HRQoL identified in previous research. Further research is needed to test the descriptive system on a paediatric population and reduce the number of dimensions to be amenable to health state valuation.


The experience of being disabled and obese.
This qualitative study was designed to explore the experiences of disabled and severely obese people living in the community. The challenges that their size and disabilities posed within their homes and in accessing community facilities were explored, with particular reference to the provision and use of assistive technologies. The study comprised in-depth interviews with a sample of six severely obese, disabled people using a grounded theory approach. Three key themes emerged: the experience of daily life; accessing services; and responses to challenges. The study participants found that their home and community environments were seldom adequate for their size. Difficulties were identified in relation to accessing and using NHS services and negative attitudes and treatment from staff. Assessments and quality of assistive devices and housing adaptations received were criticised by some. Participants identified a range of responses to these challenges. The challenges that obesity bring are compounded by disability, including the need for higher levels of care and the higher costs of assistive devices for this client group. The study suggests there may be a need for training for professionals who work with obese, disabled people to ensure their needs are met in appropriate and cost-effective ways.


Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder.
Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, guilt) relative to those associated with blaming others (eg, indignation). Recent functional magnetic resonance imaging (fMRI) studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown. To use fMRI to test the hypothesis that, in comparison with control individuals, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration. Case-control study from May 1, 2008, to June 1, 2010. Clinical research facility. Twenty-five patients with remitted MDD (no medication in 16 patients) with no current comorbid Axis I disorders and 22 controls with no personal or family history of MDD. Between-group difference of ATL coupling with a priori SCSR region of interest for guilt vs indignation. We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs controls (familywise error-corrected P=.001 over the region of interest) and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire). Vulnerability to MDD is associated with temporofrontolimbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism ofMDD vulnerability that accounts for self-blaming biases.


A review on Insulin plant (Costus igneus Nak).
Costus igneus Nak and Costus pictus D. Don, commonly known as Spiral flag, is a member of Costaceae and a newly introduced plant in India from South and Central America. It is a perennial, upright, spreading plant reaching about two feet tall, with spirally arranged leaves and attractive flowers. In southern India, it usually grows as an ornamental plant and its leaves are used as a dietary supplement in the treatment of diabetes mellitus. Recently, a number of researches have been carried out to evaluate the anti-diabetic potential of this plant. Besides, it has been proven to possess various pharmacological activities like hypolipidemic, diuretic, antioxidant, anti-microbial, anti-cancerous. Further, various phytochemical investigations reveal the presence of carbohydrates, triterpenoids, proteins, alkaloids, tannins, saponins, flavonoids, steroid, and appreciable amounts of trace elements. This work is an attempt to compile and explore the different pharmacological and phytochemical studies reported till date.


Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells.
As a powerful antioxidant, vitamin C protects cells from oxidative damage by inhibiting production of free radicals. However, high levels of vitamin C shows cytotoxicity especially on cancerous cells through generating excessive ROS and blocking the energy homeostasis. Although the double-sided character of vitamin C has been extensively studied in many cell types, there is little research on the consequence of vitamin C treatment in stem cells. Here, we identified that high-dose vitamin C shows cellular toxicity on proliferating NSPCs. We also demonstrated that undifferentiated NSPCs are more sensitive to vitamin C-driven DNA damage than differentiated cells, due to higher expression of Glut genes. Finally, we showed that high-dose vitamin C selectively induces DNA damage on cancer stem cells rather than differentiated tumor cells, raising a possibility that vitamin C may be used to target cancer stem cells.


Analysis of the relations between the shape of the reconstructed tongue and postoperative functions after subtotal or total glossectomy.
For reconstruction after subtotal or total glossectomy, both preserving the larynx and maintaining postoperative swallowing and speech functions can greatly improve quality of life; however, postoperative functional results are often unstable. Our experiences suggest that insufficient flap volume in the oral area and postoperative prolapse of the preserved larynx affect postoperative function. The objective was to investigate the relations of the shape of the reconstructed tongue to postoperative swallowing and speech functions. The shape of the reconstructed tongue was classified on the basis of magnetic resonance and intraoral inspection as protuberant, semi-protuberant, flat, or depressed. Speech intelligibility was evaluated, and body weight, which might affect the shape of the transferred flap, was measured before and after surgery. Thirty patients who had undergone subtotal or total glossectomy and subsequent reconstruction were reviewed. We found that speech intelligibility (P <.001), food (P <.01), and deglutition (P <.003) scores were significantly lower in patients with flat or depressed tongues than in patients with semi-protuberant or protuberant tongues. Weight loss after surgery was significantly greater in patients with depressed tongues than in other patients (P <.013). Our results indicate that postoperative function is related to the shape of the reconstructed tongue. We suggest that 1) wider and thicker flaps, such as rectus abdominis musculocutaneous flaps, be used; 2) flaps be designed to be approximately 30% wider than the defect; 3) laryngeal suspension be used to prevent prolapse of the transferred flap; and 4) careful general management and sufficient nutrition are important in the early postoperative period.


Failure of a Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of H. pylori Eradication in H. pylori-Infected Patients with Functional Dyspepsia.
The role of Helicobacter pylori eradication in patients with functional dyspepsia (FD) is still uncertain. We originally planned a randomized clinical study to observe dyspeptic symptoms after H. pylori eradication therapy. However, we failed to complete the study; therefore, we analyzed the factors that affected the failure of the study. Interviews and questionnaire surveys were conducted to analyze the factors that induced early termination from the study. Many patients were screened by gastroenterologists at 11 tertiary referral hospitals between July 2009 and August 2010; however, only 4 patients met the enrollment criteria. Most patients who visited our clinics had been experiencing FD symptoms for less than 6 months or were already taking medication. They also demanded to continue taking medications and using other drugs. Only 3 of the 4 patients signed informed consent. The application of the current Rome III criteria to FD is difficult to evaluate in Korean patients with dyspeptic symptoms because of the early medical evaluation. Most Korean patients who were diagnosed with FD by the Rome III criteria did not overcome their fear of being unable to use rescue medications during the study period.


A SitABCD homologue from an avian pathogenic Escherichia coli strain mediates transport of iron and manganese and resistance to hydrogen peroxide.
An operon encoding a member of the family of ATP-binding cassette (ABC) divalent metal ion transporters, homologous to Salmonella enterica SitABCD, has been identified in the avian pathogenic Escherichia coli (APEC) strain chi7122. The sitABCD genes were located on the virulence plasmid pAPEC-1, and were highly similar at the nucleotide level to the chromosomally encoded sitABCD genes present in Shigella spp. A cloned copy of sitABCD conferred increased growth upon a siderophore-deficient E. coli strain grown in nutrient broth supplemented with the chelator 2,2'-dipyridyl. Ion rescue demonstrated that Sit-mediated growth promotion of this strain was due to the transport of iron. SitABCD mediated increased transport of both iron and manganese as demonstrated by uptake of 55Fe, 59Fe or 54Mn in E. coli K-12 strains deficient for the transport of iron (aroB feoB) and manganese (mntH) respectively. Isotope uptake and transport inhibition studies showed that in the iron transport deficient strain, SitABCD demonstrated a greater affinity for iron than for manganese, and SitABCD-mediated transport was higher for ferrous iron, whereas in the manganese transport deficient strain, SitABCD demonstrated greater affinity for manganese than for iron. Introduction of the APEC sitABCD genes into an E. coli K-12 mntH mutant also conferred increased resistance to the bactericidal effects of hydrogen peroxide. APEC strain chi7122 derivatives lacking either a functional SitABCD or a functional MntH transport system were as resistant to hydrogen peroxide as the wild-type strain, whereas a Deltasit DeltamntH double mutant was more sensitive to hydrogen peroxide. Overall, the results demonstrate that in E. coli SitABCD represents a manganese and iron transporter that, in combination with other ion transport systems, may contribute to acquisition of iron and manganese, and resistance to oxidative stress.


Causality and Kramers-Kronig relations for waveguides.
Starting from the condition that optical signals propagate causally, we derive Kramers-Kronig relations for waveguides. For hollow waveguides with perfectly conductive walls, the modes propagate causally and Kramers-Kronig relations between the real and imaginary part of the mode indices exist. For dielectric waveguides, there exists a Kramers-Kronig type relation between the real mode index of a guided mode and the imaginary mode indices associated with the evanescent modes. For weakly guiding waveguides, the Kramers-Kronig relations are particularly simple, as the modal dispersion is determined solely from the profile of the corresponding mode field.


CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.
We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we have analyzed in detail the relative antigenicity and in vitro immunogenicity of natural and modified NY-ESO-1 peptide sequences. The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients. In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently. In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level. Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic. The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions. The findings reported here have significant implications for the formulation of NY-ESO-1-based vaccines as well as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL responses in cancer patients.