Redox proteomics identification of oxidatively modified proteins in Alzheimer's disease brain and in vivo and in vitro models of AD centered around Abeta(1-42).
Alzheimer's disease is a progressive neurodegenerative disease associated with loss of memory and cognition. One hallmark of AD is the accumulation of amyloid beta-peptide (Abeta), which invokes a cascade of oxidative damage to neurons that can eventually result in neuronal death. Several markers of oxidative stress have been identified in AD brain, thus providing greater understanding into potential mechanisms involved in the disease pathogenesis and progression. In the present article, we review the application of redox proteomics to the identification of oxidized proteins in AD brain and also our recent findings on amyloid beta-peptide (Abeta)-associated in vivo and in vitro models of AD. Our redox proteomics approach has made possible the identification of specifically oxidized proteins in Alzheimer's disease (AD) brain, providing for the first time evidence on how oxidative stress plays a crucial role in AD-related neurodegeneration. The information obtained has great potential to aid in determining the molecular pathogenesis in and detecting disease markers of AD, as well as identifying potential targets for drug therapy in AD. Application of redox proteomics to study cellular events, especially related to disease dysfunction, may provide an efficient tool to understand the main mechanisms involved in the pathogenesis and progression of oxidative stress-related neurodegenerative disorders.


Genetics of microstructure of the corpus callosum in older adults.
The current study sought to examine the relative influence of genetic and environmental factors on corpus callosum (CC) microstructure in a community sample of older adult twins. Analyses were undertaken in 284 healthy older twins (66% female; 79 MZ and 63 DZ pairs) from the Older Australian Twins Study. The average age of the sample was 69.82 (SD = 4.76) years. Brain imaging scans were collected and DTI measures were estimated for the whole CC as well as its five subregions. Parcellation of the CC was performed using Analyze. In addition, white matter lesion (WMLs) burden was estimated. Heritability and genetic correlation analyses were undertaken using the SOLAR software package. Age, sex, scanner, handedness and blood pressure were considered as covariates. Heritability (h(2)) analysis for the DTI metrics of whole CC, indicated significant h(2) for fractional anisotropy (FA) (h(2) = 0.56; p = 2.89×10(-10)), mean diffusivity (MD) (h(2) = 0.52; p = 0.30×10(-6)), radial diffusivity (RD) (h(2) = 0.49; p = 0.2×10(-6)) and axial diffusivity (AD) (h(2) = 0.37; p = 8.15×10(-5)). We also performed bivariate genetic correlation analyses between (i) whole CC DTI measures and (ii) whole CC DTI measures with total brain WML burden. Across the DTI measures for the whole CC, MD and RD shared 84% of the common genetic variance, followed by MD-AD (77%), FA-RD (52%), RD-AD (37%) and FA-MD (11%). For total WMLs, significant genetic correlations indicated that there was 19% shared common genetic variance with whole CC MD, followed by CC RD (17%), CC AD (16%) and CC FA (5%). Our findings suggest that the CC microstructure is under moderate genetic control. There was also evidence of shared genetic factors between the CC DTI measures. In contrast, there was less shared genetic variance between WMLs and the CC DTI metrics, suggesting fewer common genetic variants.


[Chilaiditi syndrome - a case report].
The abnormality being the result of a certain transposition of the large intestine winding in between diaphragm and the liver, owes it's name to a so called Chilaiditi symptom. This symptom is rarely recognized for at most 0,025-0,28% of the whole population statistics - wise. The Chilaiditi symptom can be examined without any serious (abdominal) pain indication, when conducting the gastrointestinal examination with the implication of the different disorders. When carrying out the diagnostic examination, it is strongly recommended to take notice of patients suffering from the pain in abdominal area, especially in case of the patients with the developed air - structure under the right side copula of the diaphragm. The transposition of the large instestine winding between the diaphragm and the liver, may lead to the blood structure disorders along the part of patient's spot - pressed intestine and be the cause of the other afflictions. The circumstance as such is thus called by the name of Chilaiditi syndrome. The respective recognition of this syndrome may prevent the patient from any unnecessary assignment for a diagnostic and (or) any other therapeutic procedures in place.It may as well minimize the overall diagnostic treatment time lapse - usually concentrated on the pain relief treatment in the aftermath. The patients without examined affliction, (ex.) due to the liver disorders and the awareness of the existence of this syndrome in general, can be an indicator for taking up a decision for when it comes to the liver biopsy. This due to the risk of any perforation of the digestive tract. The report describes case of the 56-year-old male patient, directed onto the surgery department by cause of a quite significant epigastric pain in the right side of the abdomen, however without any of the peritoneal symptoms indicated. The x-ray examination of the chest has indicated presence of the air - structure under the diaphragm copula. Having stated that and without any other signals of the serious abdominal inflammation, this symptom gave trigger for the assumption of the gastrointestinal perforation. As a result, the tomography scan has revealed high curve placement of the diaphragm going along the patient's front lobe of the liver. In the result the Chilaiditi syndrome has been recognized by the patient, where the symptom based treatment has prescribed leading the same to the absolute healing results as an outcome. After leaving the surgery by the patient, it has been made use of the re-directory to the leading gastroenterology practice for any further control checks. In the aftermath of the several year long observation, none of the abdominal pains have been reported back. Presence of the air - structure under the diaphragm copula without any typical affliction in relation to digestive tract perforation might be the result of transposition of the large intestine winding between diaphragm and the liver - called the Chilaiditi syndrome.


Ectopic pregnancy is associated with high anandamide levels and aberrant expression of FAAH and CB1 in fallopian tubes.
Ectopic pregnancy is associated with significant morbidity and mortality, but the molecular mechanisms underlying this condition remain unclear. Although the endocannabinoids, N-arachidonoylethanolamine (anandamide), N-oleoylethanolamine, and N-palmitoylethanolamine, are thought to play a negative role in ectopic pregnancy, their precise role(s) within the fallopian tube remains unclear. Anandamide activates cannabinoid receptors (CB1 and CB2) and, together with its degrading [e.g. fatty acid amide hydrolase (FAAH)] and synthesizing enzymes (e.g. N-acyl-phosphatidylethanolamine-specific phospholipase D), forms the endocannabinoid system. High anandamide levels are associated with tubal arrest of embryos in mice and may have a similar role in women. The aims were to quantify the levels of the endocannabinoids and evaluate the expression of the modulating enzymes and the cannabinoid receptors in fallopian tubes of women with ectopic pregnancy compared to those of nonpregnant women. We conducted a prospective study at the University Hospitals of the Leicester National Health Service Trust. Fallopian tubes collected from women with ectopic pregnancy and nonpregnant women with regular menstrual cycles were used for quantification of endocannabinoids by ultra-HPLC tandem mass spectrometry, were fixed in formalin for immunohistochemistry, and had RNA extracted for RT-quantitative PCR or protein extracted for immunoblotting. Anandamide, but not N-oleoylethanolamine and N-palmitoylethanolamine, levels were significantly higher in ectopic fallopian tubes. Endocannabinoid levels from isthmus to ampulla were not significantly different. Cannabinoid receptors and endocannabinoid modulating enzymes were localized in fallopian tube epithelium by immunohistochemistry and showed reduced CB1 and FAAH expression in ectopic pregnancy. High anandamide levels and reduced expression of CB1 and FAAH may play a role in ectopic implantation.


Temporal and spatial patterns of small vertebrate roadkill in a supercity of eastern China.
An assessment of animal roadkill can help develop road mitigation measures. This article is the first to report data on animal-vehicle collisions (AVCs) in Nanjing, a supercity in eastern China. The research was conducted on a 224.27 km stretch of nine roads in Nanjing. In the period, between November 2020 and October 2021, 26 fortnightly monitoring missions were conducted to gather roadkill carcasses so that we could analyze their temporal and spatial distribution patterns. A total of 259 carcasses were collected, comprising 22 different species, of which 46.42% were mammals and 48.81% were birds. Cats and dogs are the most roadkill mammals, and blackbirds and sparrows are the most roadkill birds. The temporal analysis demonstrated that the peak of vertebrate roadkill occurred from May to July. Spatial analysis showed that the distribution patterns of vertebrate roadkill on different roads varied with a generally non-random distribution and aggregation. By mapping accidents using kernel density analysis, we were able to pinpoint locations that were at high risk for roadkill. Due to the fortnightly survey, our results would underestimate the casualties, even if, our study suggests that the problem of car accidents due to animals should be a cause for concern, and the results of the analysis of temporal and spatial patterns contribute to the establishment of mitigation measures.


[Burnout syndrome among physiotherapists].
Burnout is a syndrome of emotional exhaustion, depersonalization, and a reduced sense of personal accomplishment. Symptoms of burnout include mental and physical exhaustion, accompanied by psychosomatic disorders and emotional problems. Burnout occurs most often in people employed in occupations requiring working with people (human services) as a result of coping with stress and experience numerous failures at work. The aim of the research is the analysis of burnout among physiotherapists and demographic factors and conditions that may contribute to the burnout. 212 (137 woman and 75 man) physiotherapists completed an anonymous questionnaire to assess burnout created by Owczarek and Olczyk. The age of respondents ranged between 20 to 56 years, with work experience from several months to more than 30 years. Total score of burnout was 115,66 (SD 21,78). On the scale of attitude to work 36,82 was achieved, workload - 34,76, contact with the patient - 27,54, and an attitude towards stress - 16,54, which means that the result obtained fit in the lower zone including average results concerning the level of burnout. Women had a higher level of professional burnout than men. Respondents who reported that their working conditions are not conducive to achieving therapeutic success (quality of equipment, size of treatment rooms, treatment technologies), exhibited a higher level of burnout. The average result of the level of burnout among physiotherapists is lower than all the results obtained in other occupational groups of health care workers, lead with the same diagnostic tool. Burnout syndrome among practicing physiotherapists require further study, taking into account the type and quality of jobs, but also the level of referral among professional physiotherapists.


Safety in more than just numbers.
The National Institute for Health and Care Excellence (NICE) is developing a series of evidence-based guidelines on safe staffing with a focus on nursing and midwifery care. This article discusses how these recommendations could be put into practice to ensure that staffing across the NHS is safe enough to provide good quality care for patients.


Craniosynostosis, telecanthus, scalp hair abnormalities, and sensorineural deafness in two sibs.
A sister and a brother with anomalous skull configuration, facial abnormalities, abnormal scalp hair growth, sensorineural hearing loss and, in the boy, proven craniosynostosis, severe mental retardation, and autism were reported in 1986 in an abstract by Hersh et al. We reexamined this family and here review the literature focusing on the major clinical findings, and suggest that their clinical manifestations may represent a previously unreported syndrome.


Roles of CRAC channel in cancer: implications for therapeutic development.
The Ca2+release-activated Ca2+ (CRAC) channel, composed of Orai and STIM proteins, represents one of the main routes of Ca2+ entry in most non-excitable cells. There is accumulating evidence to suggest that CRAC channel can influence various processes associated with tumorigenesis. Overexpression of CRAC channel proteins has been observed in several types of cancer tissues and cells, indicating that blocking CRAC channel activated Ca2+ influx can have therapeutic benefits for cancer patients. In this review, we have primarily focused on the molecular composition and activation mechanism of CRAC channel as well as the myriad roles this Ca2+ channel play in various cancers. We further describe relevant information about several efforts aimed at developing CRAC channel blockers and their likely implications for cancer therapy. We have extensively utilized the available literature on PubMed to this end. The possibility of targeting CRAC channel mediated Ca2+ entry in cancer cells has generated considerable interest in recent years. Use of CRAC channel blockers in cancer preclinical studies and clinical trials has been relatively limited as compared to other diseases. The future lies in developing and testing more potent and selective drugs that target cancer cell specific CRAC channel proteins, hence opening better avenues for cancer therapeutic development.


Emergency medical services and the pediatric patient: are the needs being met?
Emergency medical systems are being developed throughout the United States primarily to deal with myocardial infarction and trauma. These programs often fail to recognize the special needs of the critically ill child. Data collected in Los Angeles County from the LA County Trauma Surveys, Mobile Intensive Care Unit Rescue Reports, and Base Station Hospitals demonstrate that children represent approximately 10% of the paramedic calls. The calls are for medical problems as well as trauma. These data suggest that children have a higher death rate in the field than adults, and deaths occur more commonly in areas where there are no pediatric centers. Children are often secondarily transferred from emergency departments to other centers for definitive care. This study suggests that the needs of children in the prehospital setting are not being met.


Tumor microenvironment changes leading to resistance of immune checkpoint inhibitors in metastatic melanoma and strategies to overcome resistance.
Immunotherapy with checkpoint inhibitors targeting CTLA-4 and/or PD-1 receptors independent of the BRAF mutational status and targeted therapy with BRAF and MEK inhibitors in BRAF V600 mutated patients have taken the forefront of advanced melanoma treatment. The main advantage of immunotherapy is its ability to provide durable responses in a subset of patients. However, significant proportions of patients either do not respond or have progression after initial response to immunotherapies. Multiple changes in the tumor microenvironment, such as down regulation of immune checkpoint ligands by tumor, alteration in interferon signaling, and activation of alternate immune suppressive pathways, have been identified as possible reasons for failure of immune checkpoint therapy. Here, we review the resistance mechanisms adopted by cancer cells to checkpoint inhibitor therapy and targeted therapy. In addition, we focus on the available and emerging evidence on tumor microenvironment modulation by BRAF/MEK inhibitor therapy and its role in improving responses to checkpoint inhibitor therapy.


Membrane-bound beta-lactamase forms in Escherichia coli.
Frameshift pseudo-revertants of Escherichia coli RTEM beta-lactamase were obtained by a selection procedure, starting from frameshift mutants at the signal-processing site. These pseudo-revertant proteins, which have a totally altered COOH-terminal part of the signal sequence, are attached to the outer face of the inner membrane. The mutant proteins are enzymatically active in vitro and in vivo, and the membrane localization has no deleterious effect on cell growth. We conclude that initiation of transport across the membrane does not require the COOH-terminal part of the signal, but this part of the sequence determines whether the protein is released to the periplasm either with or without cleavage of the signal, or whether the protein remains anchored to the membrane. Mutants with two signals in series were used to show that a truncated signal is not refractory to transport per se. If neither signal contains a functional cleavage site, the protein is at least partially found on the outer face of the inner membrane. If both signals contain functional cleavage sites, both are removed and the protein is released to the periplasm. If only the first signal contains a cleavage site, a longer fusion protein is transported and released. The results presented here show that a pre-beta-lactamase-like protein can fold properly even as a membrane-bound species.


Characterization of a human B cell-specific antigen (B2) distinct from B1.
A human B lymphocyte-specific antigen (B2) was identified and characterized by the use of a monoclonal antibody. By indirect immunofluorescence and quantitative absorption, B2 was shown to be expressed exclusively on Ig+ B cells isolated from peripheral blood and lymphoid tissues. In contrast, B2 was not found on monocytes, resting and activated T cells, Null cells, or granulocytes, nor was it found on cell lines or tumor cells of T cell or myeloid origin. Functional studies demonstrated that only B2 antigen-positive splenocytes could be induced to differentiate into plasma cells under the stimulus of pokeweed mitogen, further confirming the B cell specificity of B2. It was then demonstrated that the B2 antigen was distinct from the previously described B cell-surface determinants including surface immunoglobulin, Ia-like antigens, and Fc and C3 receptors. More importantly, the B2 antigen has been clearly shown to be distinct from the previously described B cell-specific antigen, B1, by its m.w. and expression on normal and malignant B lymphocytes. The distinct distribution of B2 on normal and malignant lymphocytes supports the notion of B cell heterogeneity and provides further evidence for existence of subpopulations of human B lymphocytes.


Solid plan, 'gut instinct' are disaster response keys.
Even with the most intricate disaster response plan, not all contingencies will be accounted for. In the case of the Minnesota bridge collapse, one ED manager had to rely on his experience and judgment to determine exactly when to implement the plan. Don't wait until you are sure your ED will be overwhelmed with new patients to begin preparing for that eventuality. Assess your resources, and have additional help lined up. If you do not have insufficient data to definitively state there is a disaster, err on the side of caution and initiate disaster response. Make sure your plan has a well thought-out strategy for making additional beds available.


Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes.
Wax apple (Syzygium samarangense) has received growing research interest for its high nutritional and medicinal value due to its constituents such as polysaccharide, organic acids, flavonoids, minerals, and other substances. In this study, wax apple polysaccharide (WAP) was isolated from this plant and its protective effect against ethyl carbamate (EC)-induced oxidative damage was evaluated in human hepatocytes (L02 cells). Firstly, a series of analyses such as high-performance liquid chromatography (HPLC), high-performance gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass spectrometry (GC/MS), and 1H and 13C nuclear magnetic resonance (NMR) were conducted to identify the structure of WAP. Thereafter, in vitro cell experiments were performed to verify the protective effects of WAP against EC-induced cytotoxicity, genotoxicity, and oxidative damage in L02 cells. Our results revealed that WAP is composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose in a molar ratio of 2.20:3.94:4.45:8.56:8.86:30.82:39.78:1.48. Using a combination of methylation and NMR spectroscopic analysis, the primary structure of WAP was identified as Araf-(1→, Glcp-(1→, →2)-Araf-(1→, →3)-Galp-(1→, →3)-Araf-(1→, and →6)-Galp-(1→. Cell experiments indicated that WAP exhibited significant protective effects on EC-treated L02 cells via suppressing cytotoxicity and genotoxicity, reducing reactive oxygen species (ROS) and O2•- formation, as well as improving mitochondrial membrane potential (MMP) and glutathione (GSH). In a nutshell, WAP has the potential as an important therapeutic agent or supplement for hepatic oxidative damage. Meanwhile, further studies are needed to prove the above effects in vivo at the biological and clinical levels.


Genetically modified foods, science, consumers and the media.
In contrast to the situation in the USA, where a wide range of genetically modified (GM) foods is available, in Europe very few GM products have been approved for marketing as foods, and there is widespread public concern about their safety and environmental impact. The marketing of a GM crop for food use in Europe falls under the EC novel foods regulations, and applications require the submission of an extensive dossier of information. The safety evaluation of GM foods presents considerable problems both in the conduct and interpretation of experimental studies, because conventional toxicity tests used in the evaluation of simple chemicals may not be appropriate for whole foods. To rationalise the safety evaluation process and to circumvent the difficulties in toxicological assessment of food materials, the concept of substantial equivalence has been developed. The concept is that if it can be demonstrated that the novel food is essentially similar to its conventional counterpart in terms of critical nutritional or anutritional components, then it is likely to be no more or less toxic than the latter. The possible introduction of unintended effects by the genetic modification process is particularly problematic for the safety evaluation process. The new genomic and post-genomic techniques are potentially valuable in the safety evaluation of GM foods, although they are as yet in their infancy.


Human T-cell Lymphotropic Virus Type-1-associated Bronchioloalveolar Disorder with Non-necrotizing Granulomas: A Case Report and Literature Review.
Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the peribronchiolar space and interstitium in HTLV-1 carriers and in adult T-cell leukemia/lymphoma (ATLL). We herein report an 85-year-old woman carrying HTLV-1 with HABA who presented with a miliary pattern of micronodules in both lungs on high-resolution computed tomography and a lymphocytic infiltrate with non-necrotizing granulomas on pathology. This rare case of HABA should be differentiated from sarcoidosis, hypersensitivity pneumonitis, or miliary tuberculosis.


Determinants of shooting performance in elite air rifle shooters.
The purpose of this study was to identify the determinants of shooting performance in elite 10 m air rifle shooters. Twelve international-level 10 m air rifle shooters belonging to China's national team completed 60 shots using their normal shooting procedures. A SCATT MX-02 optoelectronic shooting test system was used to collect shooting score and shooting technical variables, while a footscan1.0 force platform was used to collect postural balance parameters. The principal component analysis identified five principal factors from 14 postural balance and shooting technical variables in elite 10 m air rifle shooters: holding and aiming, stability of triggering, time, A-P balance and M-L balance. Principal component regression analysis indicated that these five components explained the 83.1% variance of shooting performance. From these, the holding and aiming ability was the most important component, which could explain the 36.3% variance of shooting performance. The stability of triggering was the second important component, which could explain the 24.5% variance of shooting performance. The results of this study can be used to assess the strengths and weaknesses of performance-determining factors and to obtain more comprehensive information about the shooting action process during training.


Dissimilarities between benzodiazepine-binding sites and adenosine uptake sites in astrocytes and neurons in primary cultures.
The question whether the benzodiazepine receptor site in astrocytes or in neurons might be identical to the adenosine uptake site was studied by determining pharmacological profiles, inhibition types, and the effects of benzodiazepine antagonists in primary cultures of either astrocytes or neurons. Fourteen different benzodiazepines and five different adenosine uptake inhibitors displaced [3H] diazepam and inhibited adenosine uptake in both astrocytes and neurons. However, the rank orders (determined as IC50 values) with which these two parameters were affected were profoundly different, indicating dissimilarities between these two sites. For several of the compounds a difference in inhibition type (competitive vs. noncompetitive) was observed between the benzodiazepine-binding site and the adenosine uptake site in astrocytes and/or neurons, which further corroborated the conclusion of a difference between the benzodiazepine-binding site and the adenosine uptake site. Finally, the neuronal benzodiazepine antagonists RO 15-1788 and CGS-8216 and the astrocytic benzodiazepine antagonist PK 11195, which reverse the action of benzodiazepines, were not able to reverse inhibition of adenosine uptake by diazepam but exerted an inhibitory effect of their own.


A double-blind, placebo-controlled trial of TRH in amyotrophic lateral sclerosis.
A double-blind, placebo-controlled trial of single doses of thyrotropin releasing hormone (TRH) was performed on 12 patients with amyotrophic lateral sclerosis. Each patient was given subcutaneous injections of TRH 150 mg or placebo, and IV infusions of TRH 500 mg or placebo at 72- to 96-hour intervals. Eight motor and functional ratings were scored at regular intervals after each injection. Side effects were seen in all patients and were obvious to patients and examiners, making true blinding impossible. Nevertheless, statistically significant improvement was seen only in dynametric strength 1 hour after subcutaneous injection (p less than 0.05). Significant improvement occurred, in one patient only, on subjective speech testing during IV infusion of TRH. In none of six other ratings was there a significant difference between TRH and placebo. Subjective improvement was noted by 11 of 12 patients.


[Effects of some drugs on plasma uric acid in rats--actions of catecholamines and beta-blocking agents].
Effects of catecholamines on plasma uric acid and allantoin levels were studied in oxonate-treated rats and non-treated rats. 1) In non-treated rats, epinephrine, isoproterenol and phenylephrine, which were injected intravenously, clearly increased plasma uric acid and allantoin, and norepinephrine had only a slight effect. The orders of potency to increase plasma uric acid and allantoin were epinephrine greater than isoproterenol greater than phenylephrine greater than norepinephrine. Beta-adrenoceptor agonists also increased plasma uric acid and allantoin in non-treated rats. The order of potency to increase plasma uric acid was isoproterenol salbutamol trimetoquinol greater than terbutaline, and that of potency to increase plasma allantoin was isoproterenol salbutamol greater than or equal to trimetoquinol greater than terbutaline. 2) In oxonate-treated rats, the four beta-adrenoceptor agonists (50 micrograms/kg, i.v.) markedly potentiated the hyperuricemic effect of oxonate. These effects of beta-adrenoceptor agonists were inhibited by propranolol (2.0 mg/kg. i.v.). In addition, the effect of isoproterenol was inhibited by butoxamine (1.0 mg/kg, i.v.), but not by atenolol (1.0 mg/kg, i.v.). These results suggest that hyperuricemia induced by catecholamines is closely related to beta 2-adrenoceptor action.


[Idiopathic chylothorax: usefulness of aetiologic survey and the follow-up].
Chylothorax is an uncommon condition. It's characterized by the presence of chyle in the pleura. The most common causes are malignancy and trauma. When an underlying cause is excluded, the chylothorax is called idiopathic. We report a case of a 68 aged woman, admitted for abundant chylothorax. Thoraco-abdominal computed tomography, magnetic resonance imaging of the chest and thoracotomy showed no lesion of the lymphatic duct. Fibrothorax has developed after pleurodesis. Stable clinical and radiological condition was noticed during 3 years. We discuss the difficulty in the exclusion of a malignancy and the necessity of the follow up for these patients.


Training and distribution of neurologists worldwide.
Information about the global distribution, number, and training of neurologists and other neuro-specialists is vital for the planning of prevention, care, and treatment of disorders of the nervous system, which are a major cause of death and disability worldwide. Delegates of the World Federation of Neurology (WFN) were surveyed about the number, training, and location of neurologists in their countries. Sixty-three out of 84 responded (75%). Most neurologists receive full-time training in neurology, but pass an examination or board in neurology in only 41/63 (65%) of countries. Comprehensive training in neurology is available in only 35/59 (59%) of countries responding, with some training abroad for the rest. Very few neurologists are located in developing countries. Populations per neurologist range from 6240 to over 4 million. Continuing medical education is required for neurologists in only 34/63 (54%) of countries. In 45/64 (71%) of countries, only a small proportion (0-25%) of neurologists work full time in academic centers. A substantial majority (75-100%) of neurologists work in private practice in many countries (17/63 or 27%). In 31/63 (49%) of countries, most neurologists practice in large cities.


Lipids and immunology.
Dietary fat plays an important regulatory role in the pathogenesis of a range of immune reactions. In food allergies, especially in type I allergic reactions, dietary fat can modulate the development of clinical symptoms through influencing the production of immunoglobulins (Ig), cytokines and chemical mediators. In general, polyunsaturated fatty acids (PUFA) of the n-3 family in relation to those of the n-6 family reduce the production of eicosanoids and hence, mitigate hypersensitivity. In this context, it is interesting that conjugated derivatives of linoleic acid (CLA) reduce the production of eicosanoids and regulate the production of Ig in a manner favourable to the prevention of allergic reactions. Trans monoene fatty acid (that is, elaidic acid), in relation to cis monoenoic fatty acid (that is, oleic acid), also behaves as an anti-allergic agent through interfering with the desaturation of linoleic acid. The information available indicates that different dietary fats influence differently the immune indices related to food allergic reaction. The effects appeared to be readily modified by the combination of food components, including dietary fats. Thus, an appropriate combination of a specific fat or fatty acid may be one approach to the regulation of allergic reaction.


Biologic role of interferon beta in multiple sclerosis.
The mode of action of interferon-beta (IFNbeta) as a therapeutic agent for multiple sclerosis is still insufficiently elucidated. Of the known immunomodulatory effects of IFNbeta, those that seem important are its [1] effects on the production of cytokines by T helper lymphocytes, [2] antagonistic effect against some of the proinflammatory and immunoregulatory effects of IFNgamma, [3] inhibitory effect on resistance of T lymphocytes to apoptotic signals, [4] inhibitory effect on the production of matrix metalloproteases, and [5] modulatory effect on the expression of adhesion molecules and chemokines. The relative importance of each of these actions is presently unknown, and still other actions of IFNbeta may be at play. The possibility that therapeutic IFNbeta compensates for a lack of endogenous IFNbeta production is discussed.


Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer.
Alterations in protein glycosylation have been related to malignant transformation and tumour progression. We recently showed that low mRNA levels of Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer patients. We analysed the role of MAN1A1 on a protein level using western blot analysis (n=105) and studied the impact of MAN1A1-related glycosylation on the prognostic relevance of adhesion molecules involved in breast cancer using microarray data (n=194). Functional consequences of mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were investigated in breast cancer cells in vitro. Patients with low/moderate MAN1A1 expression in tumours showed significantly shorter disease-free intervals than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression correlated significantly with nodal status, grading and brain metastasis. At an mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or mannosidase inhibition led to a significantly increased adhesion of breast cancer cells to endothelial cells. Our study demonstrates the prognostic role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour cells and the strong influence of this glycosylation enzyme on the prognostic impact of some adhesion proteins.


Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast.
There is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.


Confirmation of the borderline personality within a psychodynamic framework.
Using a psychodynamic framework and an underlying structural configuration, the borderline patient is described. Statistical methods are then used to differentiate this group from both a schizophrenic and a character disorder group of patients. The borderline group emerges as a clear-cut entity characterized by (1) the lack of an integrated self concept, and (2) a particular ego structure consisting of a specific pattern of superficial ego strengths and underlying ego weaknesses.


A dual role of p53 in the control of autophagy.
Genotoxic stress can induce autophagy in a p53-dependent fashion and p53 can transactivate autophagy-inducing genes. We have observed recently that inactivation of p53 by deletion, depletion or inhibition can trigger autophagy. Thus, human and mouse cells subjected to knockout, knockdown or pharmacological inhibition of p53 manifest signs of autophagy such as depletion of p62/SQSTM1, LC3 lipidation, redistribution of GFP-LC3 in cytoplasmic puncta, and accumulation of autophagosomes and autolysosomes, both in vitro and in vivo. Inhibition of p53 causes autophagy in enucleated cells, indicating that the cytoplasmic, non-nuclear pool of p53 can regulate autophagy. Accordingly, retransfection of p53(-/-) cells with wild-type p53 as well as a p53 mutant that is excluded from the nucleus (due to the deletion of the nuclear localization sequence) can inhibit autophagy, whereas retransfection with a nucleus-restricted p53 mutant (in which the nuclear localization sequence has been deleted) does not inhibit autophagy. Several distinct autophagy inducers (e.g., starvation, rapamycin, lithium, tunicamycin and thapsigargin) stimulate the rapid degradation of p53. In these conditions, inhibition of the p53-specific E3 ubiquitin ligase HDM2 can avoid p53 depletion and simultaneously prevent the activation of autophagy. Moreover, a p53 mutant that lacks the HDM2 ubiquitinylation site and hence is more stable than wild-type p53 is particularly efficient in suppressing autophagy. In conclusion, p53 plays a dual role in the control of autophagy. On the one hand, nuclear p53 can induce autophagy through transcriptional effects. On the other hand, cytoplasmic p53 may act as a master repressor of autophagy.


A new method for sperm characterization for infertility treatment: hypothesis testing by using combination of watershed segmentation and graph theory.
Shape and movement features of sperms are important parameters for infertility study and treatment. In this article, a new method is introduced for characterization sperms in microscopic videos. In this method, first a hypothesis framework is defined to distinguish sperms from other particles in captured video. Then decision about each hypothesis is done in following steps: Selecting some primary regions as candidates for sperms by watershed-based segmentation, pruning of some false candidates during successive frames using graph theory concept and finally confirming correct sperms by using their movement trajectories. Performance of the proposed method is evaluated on real captured images belongs to semen with high density of sperms. The obtained results show the proposed method may detect 97% of sperms in presence of 5% false detections and track 91% of moving sperms. Furthermore, it can be shown that better characterization of sperms in proposed algorithm doesn't lead to extracting more false sperms compared to some present approaches.


Low-dose botulinum toxin-a treatment of cervical dystonia - a double-blind, randomized pilot study.
The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study. Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport treatments received either a mean total target dose of 547 +/- 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 +/- 32 MU (group B, 125 MU Dysport/ml). Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS). Additionally, a self-response scale evaluated the patients' subjective condition for 12 weeks after injection. TWST rating before and after injection revealed comparable clinical improvement in both groups. The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation. Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection. Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time. Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen. Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders.


Urinary transforming growth factor-beta excretion in patients with hypertension, type 2 diabetes, and elevated albumin excretion rate: effects of angiotensin receptor blockade and sodium restriction.
Transforming growth factor-beta (TGF-beta) is a prosclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. In addition to high glucose, other factors implicated in renal fibrosis and increased TGF-beta synthesis include angiotensin II and high dietary sodium intake. The aim of this study was to examine the effect of angiotensin receptor blockade (ARB) and dietary sodium restriction on the plasma concentration and urinary excretion of TGF-beta in hypertensive patients with type 2 diabetes and elevated albumin excretion rate (AER). Twenty-one subjects with hypertension and AER between 10 and 200 microg/min were randomized to receive either 50 mg losartan daily (n = 11) or placebo (n = 10). Drug therapy was given in two 4-week phases, separated by a 4-week washout period. In the last 2 weeks of each phase, patients were assigned to regular- or low-sodium diets in random order. Parameters measured at week 0 and 4 of each phase included plasma TGF-beta concentration, TGF-beta urinary excretion, AER, clinic mean arterial blood pressure, and urinary sodium excretion. Plasma TGF-beta was unaffected by losartan treatment or sodium intake. In the losartan group, urinary TGF-beta excretion decreased by 23.2% (-39.2 and 13.6) [median (interquartile range)] and 38.5% (-46.8 and -6.1) in the regular- and low-sodium phases, respectively (P < 0.05 for drug effect). In the placebo group, median changes of 0.0% (-12.1 and 44.4) and 0.0% (-29.2 and 110.7) occurred in the regular- and low-sodium phases, respectively. Sodium restriction did not affect urinary TGF-beta excretion in either losartan- or placebo-treated patients (P = 0.54 for overall dietary effect), and there was no evidence of interaction between drug and diet (P = 0.29). In hypertensive type 2 diabetic patients with elevated AER, the ARB losartan, but not sodium restriction, reduced urinary TGF-beta excretion. These data suggest that the renoprotective effects of losartan in patients with type 2 diabetes and nephropathy may include a reduction in renal TGF-beta production.


Acoustic Correlates of English Lexical Stress Produced by Chinese Dialect Speakers Compared to Native English Speakers.
English second language learners often experience difficulties in producing native-like English lexical stress. It is unknown which acoustic correlates, such as fundamental frequency (F0), duration, and intensity, are the most problematic for Chinese dialect speakers. The present study investigated the prosodic transfer effects of first language (L1) regional dialects on the production of English stress contrasts. Native English speakers (N = 20) and Chinese learners (N = 60) with different dialect backgrounds (Beijing, Changsha, and Guangzhou dialects) produced the same stimulus including both trochaic and iambic patterns. Results showed that (a) all participants produced the stressed syllable with greater values of F0, duration, and intensity; (b) Native speakers of English employed an exquisite combination of F0, duration, and intensity, while the dialect groups transfer their native prosody into their production of English lexical stress, resulting in the deviation or abnormality of acoustic cues. Results suggest that L1 native dialect background is considered as a potentially influential factor which may transfer in L2 speech encoding and decoding process.


Thymic-dependence and immune memory in mice vaccinated with meningococcal polysaccharide group B complexed to outer membrane protein.
Athymic mice were capable of producing IgM antibodies to B polysaccharide of N. meningitidis when immunized with the polysaccharide complexed to outer membrane proteins, whereas no immunogenicity could be demonstrated with the purified polysaccharide. Transfer of T cells to athymic cells demonstrated that the primary anti-B response was truly thymus-independent but the bulk of the secondary response was thymus-dependent. Transfer of T and B cells purified from spleens of immune mice into irradiated recipients showed the presence of memory T cells, but no memory B cells could be found.


Timing of evidence-based non-surgical interventions as part of multimodal treatment guidelines for the management of cervical radiculopathy: a Delphi study protocol.
Cervical radiculopathy (CR) is a clinical condition whereby motor, reflex and/or sensory changes such as radicular pain, paraesthaesia or numbness can exist. Conservative management is a preferred first treatment option as the risk-benefit ratio for surgery is less favourable. Systematic reviews and treatment guidelines gather evidence on the effectiveness of non-surgical management of patients with CR from randomised controlled trials, which do not consider the natural course of recovery to modify the management strategy accordingly. The aim of this study is to establish consensus on effective non-surgical treatment modalities for patients in different stages (acute, subacute and chronic) of CR, using the Delphi method approach. Through an iterative multistage process, experts within the field will rate their agreement with a list of proposed treatment modalities and suggest any missing treatment modalities during each round. Agreement will be measured using a five-point Likert scale. Descriptive statistics will be used to measure agreement (median, IQR and percentage of agreement). Consensus criteria will be defined a priori for each round. Data analysis at the end of round three will produce a consensus list of effective treatment modalities for the management of patients with CR in different stages of recovery. Ethical approval has been granted from the University of Birmingham ethics committee under ERN_20-1121. The study findings will be submitted to a peer-reviewed journal and to relevant conferences for dissemination of the study results.


Kinetic logic: a tool for describing the dynamics of infectious disease behavior.
Most of the infectious diseases imply biological regulations controlled by several feedback loops or circuits. Kinetic logic, which is a method easily accessible to biologists or physicians, and which takes time and thresholds of activity into account, seems a convenient method for building simplified models related to this field. This implies usually qualitative predictions concerning the dynamics of such biological systems, leading to a movement back and forth between experimentation or observation and logical description. Here, we illustrate this simple modelling method in building elementary models concerning prion infection to demonstrate how to proceed. We also discuss and summarize how this method has been used for studying several viral diseases. As an example, we show how predictions related to the rhabdovirus cycle, were experimentally verified.


Injury risk for children in rear impacts: role of the front seat occupant.
As more children move to the rear rows, there is a need to understand the rear impact environment for children to guide future regulatory and due care activities in this impact direction. A probability sample of 1,035 restrained child occupants, aged 0-12 years, seated in a second row outboard position in rear impact tow-away crashes, weighted to represent 10,079 children, was collected from an on-going child specific crash surveillance system between 3/1/00 and 12/31/06. These data were analyzed to quantify the overall injury risk and the influence of both front seat occupant presence and reported front seat back deformation on injury risk. Overall risk of AIS 2+ injury for restrained child occupants seated in the rear row outboard position in rear impact crashes was 2.3%. Occupants were seated in front of these children in 71% of cases and deformation of the front seat back into the child's space was reported in 8% of cases. For those children with seatback deformation occurring directly in front of them, there was a doubling of the injury risk (4.8% vs. 2.1%, adjusted OR=2.4, 95% CI=1.2-4.8). This paper provides the first population-based estimates of the injury risk of rear row-seated children in rear impact crash events and points to the importance of understanding the role of front seat back design on rear impact injury risk for both the front seat and rear seat occupants.


Electronic signatures of large amplitude motions: dipole moments of vibrationally excited local-bend and local-stretch states of S0 acetylene.
A one-dimensional local bend model is used to describe the variation of electronic properties of acetylene in vibrational levels that embody large amplitude local motions on the S0 potential energy surface. Calculations performed at the CCSD(T) and MR-AQCC levels of theory predict an approximately linear dependence of the dipole moment on the number of quanta in either the local bending or local stretching excitation. In the local mode limit, one quantum of stretching excitation in one CH bond leads to an increase of 0.025 D in the dipole moment, and one quantum of bending vibration in the CCH angle leads to an increase of 0.068 D. The use of a one-dimensional model for the local bend is justified by comparison to the well-established polyad model which reveals a decoupling of the large amplitude bending from other degrees of freedom in the range of Nbend = 14-22. We find that the same one-dimensional large amplitude bending motion emerges from two profoundly different representations, a one-dimensional cut through an ab initio, seven-dimensional Hamiltonian and the three-dimensional (l = 0) pure-bending experimentally parametrized spectroscopic Hamiltonian.


Measurement of single electrons and implications for charm production in Au+Au collisions at square root[s(NN)] = 130 GeV.
Transverse momentum spectra of electrons from Au+Au collisions at square root[s(NN)] = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025+/-0.004(stat)+/-0.010(syst) in central collisions, and the corresponding charm cross section is 380+/-60(stat)+/-200(syst) microb per binary nucleon-nucleon collision.


Elution of interferon beta from blue sepharose by poly(vinylpyrrolidone).
Interferon beta produced by a cell line (MRC-5) of human embryonic lung fibroblasts adsorbs to Blue Sepharose CL-6B and may be dissociated at neutral pH using a buffer containing poly(vinylpyrrolidone) and sodium chloride. Poly(vinylpyrrolidone) of Mr 2500 or of Mr 25 000 is equally efficient on a w/w basis. The effect of substituting volatile ammonium salts for the sodium chloride has been investigated. The benefits of the use of poly(vinylpyrrolidone) compared with the use of the commonly-used dissociating agent, 1,2-ethanediol, are discussed. It is concluded that interferon preparations eluted by poly(vinylpyrrolidone) from Blue Sepharose may be suitable for clinical use with minimal additional processing or formulation.


Small-scale field trials of Bacillus sphaericus (strain 2362) formulations against Mansonia mosquitoes in Malaysia.
Five formulations of Bacillus sphaericus (strain 2362) including aqueous suspension BSP 1, BSP 2, technical powder ABG 6184, corncob granules ABG 6185 (potencies 2 x 10(10), 2 x 10(7), 9.5 x 10(10), 5 x 10(10), 5 x 10(10) spore/g, respectively) and wettable powder ABG 6232 (1,000 BS ITU/mg) were tested against laboratory-cultured late third/early fourth instar larvae of Mansonia uniformis in floating screened cages in small plots at swampy ditches on Penang Island, Malaysia. Mean dosage/response values at 90% mortality levels were 6.93, 95.32, 1.45, 11.92 and 2.86 liters or kg per ha, respectively, for the formulations tested. There were practically no residual effects for the formulations tested with larvae introduced at 48, 96, and 168 h post-treatment. In trials of BSP 1, ABG 6184 and ABG 6185 (1 liter or 1 kg per ha) against immature Mansonia spp. in impounded paddy field ditches, improved efficacy and residual effects were obtained with mean reductions of 93.1, 91.9 and 80.4% at days 3, 7 and 14 posttreatment, respectively.


Cannabinoid receptor 2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing.
Kidney is one of the most important organs in maintaining the normal life activities. With the high abundance of mitochondria, renal tubular cell plays the vital role in functioning in the reabsorption and secretion of kidney. Reports have shown that mitochondrial dysfunction is of great importance to renal tubular cell senescence and subsequent kidney ageing. However, the underlying mechanisms are not elucidated. Cannabinoid receptor 2 is one of the two receptors responsible for the activation of endocannabinoid system. CB2 is primarily upregulated in renal tubular cells in chronic kidney diseases and mediates fibrogenesis. However, the role of CB2 in tubular mitochondrial dysfunction and kidney ageing has not been clarified. In this study, we found that CB2 was upregulated in kidneys in 24-month-old mice and d-galactose (d-gal)-induced accelerated ageing mice, accompanied by the decrease in mitochondrial mass. Furthermore, gene deletion of CB2 in d-gal-treated mice could greatly inhibit the activation of β-catenin signalling and restore the mitochondrial integrity and Adenosine triphosphate (ATP) production. In CB2 knockout mice, renal tubular cell senescence and kidney fibrosis were also significantly inhibited. CB2 overexpression or activation by the agonist AM1241 could sufficiently induce the decrease in PGC-1α and a variety of mitochondria-related proteins and trigger cellular senescence in cultured human renal proximal tubular cells. CB2-activated mitochondrial dysfunction and cellular senescence could be blocked by ICG-001, a blocker for β-catenin signalling. These results show CB2 plays a central role in renal tubular mitochondrial dysfunction and kidney ageing. The intrinsic mechanism may be related to its activation in β-catenin signalling.


Computer-aided B-mode ultrasound diagnosis of hepatic steatosis: a feasibility study.
Fatty liver (steatosis) occurs in obese patients, among others, and is related to the development of diabetes type-2. Timely diagnosis of steatosis is therefore of great importance. Steatosis is also the most common liver disease of high-yielding dairy cattle during early lactation. This makes it a suitable animal model for studying liver steatosis. Furthermore, reference of derived ultrasound parameters against a "gold standard" is possible in cattle by taking a liver biopsy for the assessment of fat concentration. The authors undertook this pilot study to investigate the hypothesis that quantitative, computer-aided B-mode ultrasound enables the noninvasive detection of hepatic steatosis. Echographic images were obtained postpartum from dairy cows (n = 12) in transcutaneous and direct (intraoperative) applications using a convex array transducer at 4.2 MHz. During surgery, a biopsy was taken from the caudate lobe to assess the liver fat content (fat score). A custom-designed software package for computer-aided ultrasound diagnosis (CAUS) was developed. After linearizing the post-processing look-up-table (LUT), the image gray levels were transferred into echo levels in decibels relative to the mean echo level in a tissue-mimicking phantom. The quantitative comparison of transcutaneous and intraoperative images enabled the correction for the attenuation effect of skin and subcutaneous fat layer on the mean echo level in the liver, as well as for the effects of the beam formation and attenuation of liver tissue on the echo level vs. depth. The residual attenuation coefficient (dB/cm) in fatty liver vs. normal liver was estimated and compensated for. Finally, echo level was estimated relative to the phantom used for calibration, and echo texture was characterized by the mean axial and lateral speckle size within the regions of interest. In the no fat/low fat group (n = 5) skin plus fat layer attenuation was 3.4 dB/cm. A correlation of skin layer thickness vs. fat score of r = 0.48 was found. The mean transcutaneous liver tissue echo level correlated well with fat score: r = 0.80. A residual liver attenuation coefficient of 0.76 dB/cm and 1.19 dB/cm was found in medium and high fat liver, respectively. In transcutaneous images, correlation of residual attenuation coefficient with fat score was r = 0.69. Axial and lateral speckle sizes were on the order of 0.2 and 1.0 cm, respectively, and no correlation was found with liver fat content. Results for transcutaneous and intraoperative images were similar. The authors conclude that this pilot study shows the feasibility of calibrated, computer-aided ultrasound for noninvasively diagnosing, possibly even screening, steatosis of the liver.


Urinary 8-hydroxydeoxyguanosine and sister chromatid exchanges in patients with total hip replacements.
Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices. In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements. A broad range of individual levels of metals has been observed in these patients: chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24 h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24 h. By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found. However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old. Smoking significantly increased the frequency of SCE. Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements.


Knowledge of Critical Issues in the Intrapartum Period: a Cross-sectional Study Among Undergraduate Final Year Midwifery Students.
Dealing with critical issues in the intrapartum period requires comprehensive knowledge and a full understanding of the basic principles and skills involved, as complications during labor and birth occur unexpectedly.. The aim of this study was to evaluate the knowledge of critical issues in the intrapartum period among undergraduate final year midwifery students. This is a descriptive observational cross-sectional study conducted between February-July 2017. Final year undergraduate midwifery students were recruited from one institution and four public hospitals. The research instrument was a questionnaire designed by the research team. Statistical significance was set at p<0.05 and analyses were performed using the IBM SPSS Statistics version 22. The final study sample consisted of 100 participants. The 36.0% of the students had started their final year internship, with a mean duration of 4.3 months. Only 2% of the participants had obtained a bachelor degree from another department, 76% had attended general high school, 17% had pre-graduate work experience and 48.0% had attended a seminar on critical issues in the intrapartum period. Participants' final scores ranged from 5% to 90%, with mean value being 49.7% (SD=16.5%). The knowledge score was found to be significantly higher in midwifery students who had started the internship. However, it was not significantly correlated with other educational characteristics. Finally, no significant correlation was observed between knowledge score and age (r= -0.15, p=0.138) or knowledge score and months of internship (r=0.27, p=0.114). In the core midwifery curriculum, the design and integration of didactic and clinical courses focusing on emergency management in midwifery practice is considered of paramount importance. However, teachers should provide midwifery students with guidance on independent learning ability and implement effective strategies to enhance students' self-study skills.


A Catholic perspective on human gene therapy.
The questions of changes in the human genetic program have been debated by world legislatures, churches, and scientific communities. Papal teachings emphasize a global respect for each patient and the sacred dignity of all human beings. We outline six moral principles proposed as Catholic Christian perspective applicable to a bioethical evaluation of advances in human gene transfer.


Clinical outcome in patients treated with endoscopic submucosal dissection for superficial Barrett's neoplasia.
The role of endoscopic submucosal dissection (ESD) in Barrett's neoplasia is ill-defined, although it might provide a higher curative resection rate and better histologic assessment than endoscopic mucosal resection (EMR). We aimed to assess efficacy, safety, and long-term results of ESD. A retrospective analysis was done of 75 consecutive patients with Barrett's esophagus who underwent ESD between January 2007 and February 2014. ESD was performed for visible lesions that were multiple, larger than 15 mm, or poorly lifting, or suspected of submucosal infiltration. The primary end point was the rate of curative resection of carcinoma. Median patient age was 68 years (interquartile range [IQR] 61 - 76), median follow-up was 20 months (IQR 8.5 - 37.5), and median maximum specimen diameter was 52.5 mm (IQR 43 - 71). En bloc resection rate was 90 % (66 /73), and rates of curative resection of carcinoma and high grade dysplasia/carcinoma were 85 % (47 /55) and 64 % (42 /66), respectively. G3 differentiation and invasion to greater than pT1m2 were observed in 25 % (14 /55) and 67 % (37 /55) of patients with adenocarcinoma, respectively. There were 5 early ( < 48 hours) adverse events (2 delayed hemorrhages and 3 perforations), all treated endoscopically. No ESD-specific death occurred. Esophageal strictures developed in 60 % of patients, all treated endoscopically. Additional treatment (median sessions 2 [IQR 2 - 3]) for residual Barrett's esophagus were recommended to 62 % (42 /68). At latest follow-up, complete remission of neoplasia and intestinal metaplasia was found in 92 % (54 /59) and 73 % (43 /59) of patients, respectively. ESD appears to be safe and effective, with a high rate of curative resection of carcinoma. ESD should be considered for patients with Barrett's neoplasia at risk of incomplete resection or poor pathologic assessment with conventional EMR.


Application of Automated Text Analysis to Examine Emotions Expressed in Online Support Groups for Quitting Smoking.
Online support groups offer social support and an outlet for expressing emotions when dealing with health-related challenges. This study examines whether automated text analysis of emotional expressions using Linguistic Inquiry and Word Count (LIWC) can identify emotions related to abstinence expressed in online support groups for quitting smoking, suggesting promise for offering targeted mood management to members. The emotional expressions in 1 month of posts by members of 36 online support groups were related to abstinence at month end. Using the available LIWC dictionary, posts were scored for overall positive emotions, overall negative emotions, anxiety, anger, sadness, and an upbeat emotional tone. Greater expressions of negative emotions, and specifically anxiety, related to nonabstinence, while a more upbeat emotional tone related to abstinence. The results indicate that automated text analysis can identify emotions expressed in online support groups for quitting smoking and enable targeted delivery of mood management to group members.


Genetic alterations in Japanese extrahepatic biliary tract cancer.
Biliary tract cancer (BTC) is one of the most devastating types of malignant neoplasms worldwide. However, the mechanisms underlying the development and progression of BTC remain unresolved. BTC includes extrahepatic bile duct carcinoma (EBDC), gallbladder carcinoma (GBC) and ampulla of Vater carcinoma (AVC), named according to the location of the tumor. Although genetic alterations of intrahepatic cholangiocarcinoma have been investigated, those of EBDC, GBC and AVC have not yet been fully understood. The present study analyzed somatic mutations of 50 cancer-associated genes in 27 Japanese BTC cells, including: 11 EBDC, 14 GBC and 2 AVC. Next-generation sequencing using an Ion AmpliSeq Cancer Panel identified a total of 44 somatic mutations across 14 cancer-associated genes. Among the 44 mutations, 42 were judged as pathological mutations. Frequent mutations were identified in tumor protein 53 (TP53) (14/27), SMAD family member 4 (SMAD4) (6/27), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA) (6/27), and Kirsten rat sarcoma (KRAS) (6/27); no significant differences were identified between EBDC and GBC tissues. Notably, the frequency of the PIK3CA mutation was higher when compared with previous reports. This result may suggest that the activation of the PIK3CA-protein kinase B signaling pathway, in addition to the abrogation of p53, SMAD4 and RAS mitogen-activated protein kinase may have a crucial role in the carcinogenesis of Japanese BTC. These findings may be useful for the development of personalized therapies for BTC.


[Depression is a XXI century challenge].
Depression is one of the most relevant and discussed problems at the present stage of psychiatry's development, both in numerous scientific studies and in the media. Described for the first time several millennia ago, depressive states have been embodied in numerous cultural monuments dating back to antiquity and ancient Egypt. As early as the fifth century, Byzantine literature described "gratuitous sorrow" (John Cassian the Roman), corresponding to the modern understanding of endogenous depression.


Leishmanicidal activity of polysaccharides and their oxovanadium(IV/V) complexes.
The parasites of the genus Leishmania cause a range of leishmaniasis diseases, whose treatment is impaired due to intramacrophage parasites living in the mammalian host. Immunostimulation has been considered an important strategy to leishmaniasis treatment. The immunomodulatory effects of the polysaccharides arabinogalactan (ARAGAL), galactomannan (GMPOLY), and xyloglucan (XGJ), as well as their oxovanadium (IV/V) complexes (ARAGAL:VO, GMPOLY:VO, and XGJ:VO) were evaluated on peritoneal macrophages. At 25 μg/mL of GMPOLY:VO and of XGJ:VO, and 10 μg/mL of ARAGAL:VO, nitric oxide (NO) production by the macrophages was not altered compared with the control group. All polymers increased the production of interleukins 1 beta and 6 (IL-1β and IL-6), but the oxovanadium complexes were more potent activators of these mediators. ARAGAL:VO 10 μg/mL, GMPOLY:VO and XGJ:VO 25 μg/mL led to an increase of 562%, 1054%, and 523% for IL-1β, respectively. For IL-6 at the same concentration, the levels increased by 539% and 794% for ARAGAL:VO and GMPOLY:VO, respectively. Polysaccharides and their oxovanadium complexes exhibited important leishmanicidal effects on amastigotes of Leishmania (L.) amazonensis. The native and complexed polymers reduced the growth of promastigote-form Leishmania by ∼60%. This effect was reached at concentrations 12 times lower than that observed for Glucantime (300 μg/mL promoted an inhibition of ∼60%). The 50% inhibitory concentration (IC50) values for the complexes were determined. XGJ:VO showed the lowest IC50 value (6.2 μg/mL; 0.07 μg/mL of vanadium), which for ARAGAL:VO was 6.5 μg/mL (0.21 μg/mL of vanadium) and 7.3 μg/mL (0.06 μg/mL of vanadium) for GMPOLY:VO. The upregulation of IL-1β and IL-6 release and downregulation of NO production by macrophages and the important leishmanicidal effect are essential to stablish their potential use against this pathology.


The decrease in VO(2) slow component induced by prior exercise does not affect the time to exhaustion.
In previous studies decreases in the VO(2) slow component were observed after prior heavy exercise. The observed effects after prior low-intensity exercise were rather controversial. The purpose of the present study was to more thoroughly examine the effects of prior low-intensity exercise on the VO(2) slow component. Furthermore, it has been suggested that the VO(2) slow component may be a determinant of exercise tolerance. Therefore we tested the hypothesis whether an attenuated VO(2) slow component induced by prior exercise could affect the time to exhaustion. Ten subjects performed four exercise protocols consisting of heavy cycling exercise (95 % VO(2)peak) until exhaustion. This constant-load exercise was performed without prior exercise (protocol NPE), or was preceded by 6 min heavy cycling exercise (protocol 6HPE), 12 min low-intensity cycling exercise (protocol 12LPE) or 6 min low-intensity cycling exercise (protocol 6LPE). The VO(2) slow component quantified as Delta VO(2 (end-2)) (669 +/- 90 ml x min (-1) in NPE) was significantly reduced after heavy as well as low-intensity exercise (respectively 47 %, 29 % and 17 % in 6HPE, 12LPE and 6LPE). This reduction lead to a significantly lower end VO(2) in 6HPE and 12LPE. The time to exhaustion (594 +/- 139 s in NPE), however, was unaffected by prior exercise rejecting our hypothesis that the attenuated VO(2) slow component could improve the capability to sustain exercise performance.


[Pharmacogenetics and antiplatelet drugs].
The observation of inherited drug response variability gave rise to the field of pharmacogenetics. Pharmacogenetic research on drug targets, particularly platelet enzymes and receptors, is more recent and is becoming an emerging field. In the Framingham study, the heritability of platelet aggregation response ranges from 44 to 62%, depending on the agonists used. The gene coding for GPIIIa, a sub-unit of the fibrinogen receptor GPIIbIIIa, is one of the most extensively studied gene in relation with aggregation tests and antiplatelet drugs. The GPIIIa PLA1/PLA2 polymorphism has been associated with clopidogrel and orbofiban platelet response. However, data are more controversial concerning the association with aspirin response. Recently, Cox-1 and GPIa (part of the GPIaIIa collagen receptor) genetic variations have also been pointed out as possible candidates to explain part of the variability of the response to antiplatelet agents. Finally, the H1/H2 polymorphism of the platelet ADP receptor P2Y12 gene has been associated with ADP-induced platelet aggregation response and peripheral arterial disease. This polymorphism may modulate the effect of P2Y12 antagonists like clopidogrel and its clinical implication is currently under study. Gene-expression profiling and proteomics may allow the identification of new candidate genes whose variations may be associated with the heritability of platelet aggregation response. In the next future, phenotypic or genotypic studies could be available to tailor the prescription of antiplatelet drugs.


[Two cases of phytobezoars treated by adminsitration of Coca-Cola by oral route].
Bezoars are concretions of foreign bodies found in the gastrointestinal tract. In the past, most common method for the treatment of bezoar was surgical management. However, the current treatment methods include chemical dissolution and endoscopic mechanical lithotripsy. There were few reports on the treatment of phytobezoars by nasogastric Cola lavage. However, there was no report succeeded by oral route alone. In our two cases, phytobezoars were treated by oral administration of Coca-Cola. Our patients drank 700-800 mL of Coca-Cola daily, and after two months, complete dissolutions of bezoars were achieved. We report two cases of phytobezoars completely treated by drinking Coca-Cola.


Prenatal diagnosis of in utero fetal gastrointestinal bleeding.
A case of prenatal gastrointestinal bleeding is presented. Abnormal echogenic amniotic fluid was detected by routine ultrasound during the third trimester of a normal pregnancy. The diagnosis and postnatal implications of antenatal hemorrhage are discussed, with a review of the literature. To our knowledge, this is the first case to be diagnosed in utero and resulting in preterm delivery.


Prognosis in autoimmune and infectious disease: new insights from genetics.
A well-recognised feature of autoimmune and infectious diseases is that their clinical course and eventual outcome can vary substantially between affected individuals. This variability in disease prognosis critically determines patient well-being, and yet is relatively poorly understood and largely understudied-with many investigators opting instead to study what causes disease development in the first place. Better understanding of what determines prognosis could provide unique insights into disease biology, potentially revealing new therapeutic targets, and will also be essential if prognosis-based 'personalised medicine' is ever to become a reality. Here, we highlight the previously under-appreciated role that genetics has in determining prognosis in autoimmune and infectious disease, and the common role that FOXO3 has been shown to have as a modulator of inflammatory responses, and thereby of outcome, across several distinct diseases.


Isotope fractionation of iron(III) in chemical exchange reactions using solvent extraction with crown ether.
This work reports on the chemical isotope fractionation of Fe(III) by a solvent extraction method with a crown ether of dicyclohexano-18-crown-6. The (56)Fe/(54)Fe and (57)Fe/(54)Fe ratios were analyzed by multiple-collector inductively coupled plasma mass spectrometry. We determined the dependence of the isotope enrichment factors (epsilon) on the strength of HCl. The relative deviation of the (56)Fe/(54)Fe ratios relative to the unprocessed material (10(4) epsilon(56)) increases from -15.3 to -6.3 with [HCl] increasing from 1.6 to 3.5 mol/L. Likewise, 10(4) epsilon(57) increases from -22.8 to -9.6 under the same conditions. The correlation between epsilon(56) and epsilon(57) is mass dependent within the errors. The observed fractionation was broken down into the effects of competing extraction reactions and of a reaction between Fe(III) species (FeCl(2)(+) and FeCl(3)) in the aqueous phase. We found that the isotope fractionation between the Fe(III) species is mass dependent, which we confirmed by calculating the reduced partition function ratios.


Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.
Inflammasomes are caspase-1-activating multiprotein complexes. The mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome was identified as the sensor of Bacillus anthracis lethal toxin (LT) in mouse macrophages from sensitive strains such as BALB/c. Upon exposure to LT, the NLRP1b inflammasome activates caspase-1 to produce mature IL-1β and induce pyroptosis. Both processes are believed to depend on autoproteolysed caspase-1. In contrast to human NLRP1, mouse NLRP1b lacks an N-terminal pyrin domain (PYD), indicating that the assembly of the NLRP1b inflammasome does not require the adaptor apoptosis-associated speck-like protein containing a CARD (ASC). LT-induced NLRP1b inflammasome activation was shown to be impaired upon inhibition of potassium efflux, which is known to play a major role in NLRP3 inflammasome formation and ASC dimerization. We investigated whether NLRP3 and/or ASC were required for caspase-1 activation upon LT stimulation in the BALB/c background. The NLRP1b inflammasome activation was assessed in both macrophages and dendritic cells lacking either ASC or NLRP3. Upon LT treatment, the absence of NLRP3 did not alter the NLRP1b inflammasome activity. Surprisingly, the absence of ASC resulted in IL-1β cleavage and pyroptosis, despite the absence of caspase-1 autoprocessing activity. By reconstituting caspase-1/caspase-11(-/-) cells with a noncleavable or catalytically inactive mutant version of caspase-1, we directly demonstrated that noncleavable caspase-1 is fully active in response to the NLRP1b activator LT, whereas it is nonfunctional in response to the NLRP3 activator nigericin. Taken together, these results establish variable requirements for caspase-1 cleavage depending on the pathogen and the responding NLR.


Role of purinergic P2X receptors in the control of liver homeostasis.
It is now accepted that extracellular ATP and other nucleotides are potent signaling molecules, akin to neurotransmitters, hormones and lipid mediators. In the liver, several clues support a significant role for extracellular ATP-induced signaling pathways in the control of tissue homeostasis. First, ATP and other nucleotides are physiologically detected in extracellular fluids within the liver, including sinusoidal blood and intraductular bile, in various mammalian species including human and rodents. Moreover, finely tuned mechanisms of ATP release by different liver cell types have been described, under physiological cellular changes. In addition, most hepatic cells constitutively express, at the membrane level, several ATP-metabolizing ectoenzymes and ATP-sensitive receptors that modulate and transduce these mediator signals respectively. Finally, hepatic cells also express numerous membrane transporters that actively contribute to purinergic salvage pathways. Once released in the extracellular medium, unmetabolised ATP molecules can bind to purinergic P2X and P2Y receptors, and subsequently trigger various intracellular signal transduction pathways collectively referred to as purinergic signaling. In the liver, purinergic signaling has been shown to regulate key basic cellular functions, such as glucose/lipid metabolism, protein synthesis and ionic secretion, and homeostatic processes, such as cell cycle, inflammatory response and immunity. Whilst the functional relevance of P2Y receptors in liver physiology has been well documented, limited information is available regarding the potential role of hepatic P2X receptors in the modulation of liver homeostasis.


Associational susceptibility in broccoli: mediated by plant volatiles, impeded by ozone.
Plant-emitted volatile organic compounds (VOCs) mediate interactions within a plant community. Typically, receiving a signal from a damaged neighbour enhances the defensive attributes of a receiver plant. The mechanisms underlying plant-plant interactions may be divided into active and passive processes, both of which involve transit of VOCs between plants and are vulnerable to environmental perturbation. Numerous studies have documented between-plant interactions, but the specific effects on a receiver plant's interactions with herbivores have received little attention. Moreover, the relative contributions of active and passive processes to plant defence and the effects of environmental pollutants on the processes have been largely unexplored. We used a system comprising Brassica oleracea var. italica (broccoli) and the specialist herbivore Plutella xylostella to test whether plants previously exposed to herbivore-damaged neighbours differed from nonexposed plants in their susceptibility to oviposition. We then investigated the roles of active and passive mechanisms in our observations and whether differences in susceptibility remained under elevated ozone concentrations. Plants exposed to herbivore-damaged neighbours were more susceptible to oviposition than plants exposed to undamaged neighbours, which indicates associational susceptibility. Mechanistically, active and passive volatile-mediated processes occurred in tandem with the passive process - involving adsorption of sesquiterpenes to receiver plants - appearing to structure the oviposition response. Exposure to ozone rapidly degraded the sesquiterpenes and eliminated the associational susceptibility. Plant volatiles have typically been thought to play roles in between-plant interactions and to promote receiver plant defence. Here, we show that receiver plants may also become more susceptible to oviposition and thus more likely to be damaged. Extensive disruption of volatile-mediated interactions by an atmospheric pollutant highlights the need to consider the pervading environment and changes therein when assessing their ecological significance.


Interstitial pneumonitis following allogeneic bone marrow transplantation in the treatment of leukemia based on BMT survey in Japan.
Data from 208 patients with leukemia who were treated with allogeneic bone marrow transplantation between 1975 and 1985 were reported to the Japanese Bone Marrow Transplant Registry and were available for this analysis. These patients were classified into 82 of acute lymphocytic leukemia, 91 of acute non-lymphocytic leukemia, and 35 of chronic myelocytic leukemia. The incidence of interstitial pneumonitis (IP) was 39% (81/208) and fatality rate was 60% (49/81). Cytomegalovirus was the most frequent causative organism (54%). Using Cox's proportional hazard regression model, age of recipient (P = 0.0068), status of disease (P = 0.0191), and number of platelet transfusion (P = 0.0425) were found to be significant risk factors associated with IP. Probabilities of developing IP at three years were 65% and 42% in single dose and fractionated total body irradiation (TBI), respectively. In single dose TBI group, dose-rate affected the incidence of IP. On the contrary, in fractionated TBI group, number of fractions as well as dose-rate had no impact on the incidence of IP.


Does subitizing reflect numerical estimation?
Subitizing is the rapid and accurate enumeration of small sets (up to 3-4 items). Although subitizing has been studied extensively since its first description about 100 years ago, its underlying mechanisms remain debated. One hypothesis proposes that subitizing results from numerical estimation mechanisms that, according to Weber's law, operate with high precision for small numbers. Alternatively, subitizing might rely on a distinct process dedicated to small numerosities. In this study, we tested the hypothesis that there is a shared estimation system for small and large quantities in human adults, using a masked forced-choice paradigm in which participants named the numerosity of displays taken from sets matched for discrimination difficulty; one set ranged from 1 through 8 items, and the other ranged from 10 through 80 items. Results showed a clear violation of Weber's law (much higher precision over numerosities 1-4 than over numerosities 10-40), thus refuting the single-estimation-system hypothesis and supporting the notion of a dedicated mechanism for apprehending small numerosities.


Tick exposure and Lyme disease at a summer camp in Maryland.
After investigating an outbreak of Lyme Disease among counselors at a summer camp in Kent County, Maryland in 1994, we wanted to determine the incidence of Lyme Disease (LD) at the camp the following summer and identify risk factors for tick exposure. Any ticks that were detected on campers' skin or clothing were collected by the camp nurse and we studied them for infection with Borrelia burgdorferi. In addition, we sent detailed questionnaires home with the 1,623 campers. A total of 537 campers returned the questionnaire and 200 had found ticks on their skin or clothing while at camp. Risks were analyzed using logistic regression models. Participation in the ropes-course, night-trip and camp-out events significantly increased the risk of tick exposure (OR 1.6 to 2.3). Six cases of LD were identified among campers, which was an estimated incidence of 3.3 per 1,000 campers/10-14 day camp session, and two counselors had LD. Of the 238 ticks collected mainly in June-July 1995, 19% were identified as Ixodes scapularis larvae and nymphs; 11% of the latter were infected with B. burgdorferi. The risk for LD in campers and staff was much higher than that of the general population despite the use of tick-exposure precautions. Focused interventions need to be put in place in summer camps to prevent transmission of LD.


Growth factors of the future.
Hematopoietic growth factors stimulate proliferation and enhance functional activity of hematopoietic cells. Erythropoietin, recombinant human (rh) granulocyte colony stimulating factor (CSF), rh granulocyte macrophage CSF and rh interferon have been proven to be a clinically useful therapy. Several other cytokines with other unique effects are being developed for possible clinical usage. The purpose of this manuscript is to review novel uses of current approved cytokines and potential application of experimental growth factors.


Validation of scores from self-learning scales for primary students using true-score and Rasch measurement methods.
The validation of scores from the Self-learning Scales for primary pupils is presented in this study. The sample for the study comprised 1253 pupils from 20 Year-3 and 20 Year-5 classes from ten primary schools in Hong Kong. The 10-item Usefulness Scale is designed to measure primary pupils' attitudes toward the usefulness of self-learning strategies situated in ten learning contexts. The 10-item Deployment Scale is designed to measure pupils' frequency in using the self-learning strategies. Both scales use 3-point Likert response scale. Construct validity of scores from the scales for use with primary pupils is supported by confirmatory factor analysis and Rasch measurement. Gender and year level differences were identified on the Rasch person measures. Generalizability of the scores from the two scales across gender and year level needs to be undertaken with caution.


Comparison of intramedullary nailing and plate fixation in the surgical treatment of isolated fractures of the distal two-thirds of ulna diaphysis.
This study aims to compare the clinical and radiological results of intramedullary nailing and plating, which are both techniques utilized frequently in the surgical treatment of isolated fractures of the distal third of the ulna diaphysis. Between January 2010 and December 2016, a total of 54 patients (34 males, 20 females; mean age: 37.8±7.4 years; range, 22 to 56 years) with isolated fractures of the distal third of the ulna diaphysis were retrospectively analyzed. The patients were divided into those treated with locking plates (Plating group, n=25) and those treated with intramedullary nailing (IMN group, n=29). The operating time and clinical and radiological results were compared between the groups. The median follow-up time was 93 (range, 84.5 to 99.5) months in the Pg and 86 (range, 80 to 97) months in the IMNg (p=0.179). No significant difference was observed between the groups in respect of age, sex, trauma mechanism, fracture classification, smoking status, and time from trauma to surgery. The median operating time was 46 min in the Pg and 33 min in the IMNg (p<0.001). No significant difference was found in the postoperative length of stay in hospital, reduction quality, infection rates, clinical results, radiological results, and the Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score between the groups. Implant removal was only needed in the locking plate group (p=0.007). In the surgical treatment of isolated fractures of the distal third of the ulna diaphysis, locked IMN seems to be a good alternative to the plate method with a shorter operating time and less need for implant removal.


Bilateral Absence of the Arcuate Artery on the Dorsum of the Foot: With anomalous origin of dorsal metatarsal arteries.
Bilateral absence of the arcuate artery was observed during routine dissection of the lower limbs of a 60-year-old male cadaver. Running distally on the dorsal aspect of both feet and opposite the tarso-metatarsal joint, the dorsalis pedis artery diverged 2cm lateral to the tendon of the extensor hallucis longus. The 2nd dorsal metatarsal artery was found originating from the dorsalis pedis artery opposite the intermediate cuneiform bone. The 3rd and 4th dorsal metatarsal arteries originated from the lateral tarsal artery. Although absence of the arcuate artery has been previously described, the arterial variant described here is thought to be distinct from those previously reported. The variant 2(nd) dorsal metatarsal artery was found to originate from the dorsalis pedis artery. Knowledge of anatomical variations of arteries supplying the feet and toes has important clinical significance in reconstructive surgery and in determining associated pathology.


Elucidating the Role of Ion Suppression in Secondary Electrospray Ionization.
Ion suppression is a known matrix effect in electrospray ionization (ESI), ambient pressure chemical ionization (APCI), and desorption electrospray ionization (DESI), but its characterization in secondary electrospray ionization (SESI) is lacking. A thorough understanding of this effect is crucial for quantitative applications of SESI, such as breath analysis. In this study, gas standards were generated by using an evaporation-based system to assess the susceptibility and suppression potential of acetone, deuterated acetone, deuterated acetic acid, and pyridine. Gas-phase effects were found to dominate ion suppression, with pyridine exhibiting the most significant suppressive effect, which is potentially linked to its gas-phase basicity. The impact of increased acetone levels on the volatiles from exhaled breath condensate was also examined. In humid conditions, a noticeable decrease in intensity of approximately 30% was observed for several features at an acetone concentration of 1 ppm. Considering that this concentration is expected for breath analysis, it becomes crucial to account for this effect when SESI is utilized to quantitatively determine specific compounds.


Benefits from adding the 5-lipoxygenase inhibitor zileuton to conventional therapy in aspirin-intolerant asthmatics.
From bronchoprovocation studies and investigations of the acute effects of drugs that inhibit leukotrienes (LT), the hypothesis has emerged that leukotrienes are important mediators of airway obstruction and other symptoms in aspirin-intolerant asthma (AIA). However, it has yet not been shown if subjects with AIA respond favorably to clinical treatment with leukotriene inhibitors. Therefore, in a double-blind placebo-controlled crossover study, we examined the effects of 6 wk of treatment with the leukotriene-pathway inhibitor zileuton (600 mg, four times daily) in 40 patients with well-characterized AIA. The treatment was added to existing therapy, which included medium to high doses of inhaled (average daily dose 1,030 microg of beclomethasone or budesonide) or oral glucocorticosteroids (4 to 25 mg/d) for all but one of the patients. On top of this treated baseline, there were no significant effects of adding placebo, indicating that their asthma was kept relatively stable. However, there was an acute and chronic improvement in pulmonary function after treatment with zileuton, expressed both as increased FEV1 from baseline compared with placebo, and higher morning and evening peak expiratory flow rate (PEFR) values on zileuton treatment compared with placebo. The improvements occurred despite lower use of rescue bronchodilator with zileuton. Zileuton also diminished nasal dysfunction, which is one of the cardinal signs of AIA. There was a remarkable return of smell, less rhinorrhea, and a trend for less stuffiness and higher nasal inspiratory flow during treatment with zileuton. Zileuton caused a small but distinct reduction of bronchial hyperresponsiveness to histamine and inhibited aspirin-induced bronchoconstriction. Zileuton inhibited urinary excretion of LTE4 but did not change airway reactivity to inhaled LTD4, supporting that zileuton specifically inhibited leukotriene biosynthesis. The findings indicate that leukotrienes are important mediators of persistent airway obstruction and chronic nasal dysfunction in AIA. The study also suggests that addition of a leukotriene pathway inhibitor such as zileuton may bring about greater control of asthma than what is achieved by treatment with medium to high doses of glucocorticosteroids alone.


Topographic and morphometric anatomy of the proximal part of the dorsal scapular nerve.
The dorsal scapular nerve (DSN) entrapment neuropathy has recently been recognized as a common cause of circumscapular pain and cases of winged scapula. Course of the nerve is important because the middle scalene muscle is frequently accessed for surgical treatments. Studies in the literature have not focused on the morphometric relationship of the DSN with the scalene muscles and its relationship with the long thoracic nerve (LTN). The neck regions of 13 adult cadavers were dissected bilaterally. The relationship of DSN with scalene muscles and LTN was evaluated. Cervical spinal nerves involved in the formation of the DSN were identified. Three types of DSN were observed based on the cervical spinal nerves from which it originates, five types of DSN from its relationship with the scalene muscles, and two types of DSN from its relationship with the LTN. The distance from where the nerve pierces the scalene muscle to the mastoid process was found to be greater in DSNs originating from C4 and C5 (93.85 ± 4.11 mm, p = 0.033). In DSNs not connected with LTN, the distance from where the nerve pierces the scalene muscle to the superior trunk/C5 (12.74 ± 7.73 mm, p = 0.008) and the length of the nerve within the scalene muscle (14.94 ± 5.5 mm, p = 0.029) were found to be statistically significantly greater. The topographic and morphometric anatomy of the proximal part of the DSN is important, especially for scalene muscles-focused surgical treatments and interscalene nerve blocks. We believe our results may guide clinical approaches and surgery.


Topological polymer chemistry by dynamic selection from electrostatic polymer self-assembly.
A collection of recent developments in topological polymer chemistry is presented. First, topological isomerism occurring on randomly coiled, flexible polymer molecules having cyclic and linear structures is discussed. Second, an electrostatic self-assembly and covalent fixation strategy has been developed for the synthesis of polymeric topological isomers. These isomers have double cyclic, manacle-, and theta-shaped constructions, and are prepared by using either linear or star telechelic polymer precursors having moderately strained cyclic ammonium salt groups, which carry multifunctional carboxylate counteranions. A technique of reversed-phase chromatography (RPC) is demonstrated as an effective means to separate polymers with different topologies, especially polymeric topological isomers. A further extension of topological polymer chemistry has been observed by dynamic selection from electrostatic polymer self-assembly to enable the effective formation of tadpole-shaped, cyclic-linear hybrid topologies.


FOXJ2 Inhibits the Proliferation, Migration and Epithelial-Mesenchymal Transition of Prostate Carcinoma Cells.
Forkhead box J2 (FOXJ2) which belongs to FOX transcription factors family has been regarded as diagnostic, prognostic biomarker and therapeutic target of various cancers. The aim of this study is to investigate the role of FOXJ2 in prostate carcinoma. Western blot and qRT-PCR were applied to detect expression of FOXJ2 in prostate carcinoma cells. MTT and colony formation assays were used to detect cell proliferation. Cell migration and invasion were assessed by wound healing and transwell assays. FOXJ2 was down-regulated in primary prostate carcinoma tissues compared to the normal tissues based on the TCGA database. Prostate carcinoma cells also showed lower expression of FOXJ2 than normal prostate cell line (RWPE-1). pcDNA-mediated ectopical expression of FOXJ2 increased cell viability of prostate carcinoma cells, and promoted the proliferation, migration and invasion. Over-expression of FOXJ2 enhanced protein expression of E-cadherin, reduced N-cadherin, vimentin and fibronectin in the prostate carcinoma cells. Protein expression of Notch 1, Jagged-1, and Hes 1 were up-regulated in prostate carcinoma cells by over-expression of FOXJ2. FOXJ2 inhibited the proliferation, migration and epithelial-mesenchymal transition (EMT) of prostate carcinoma cells through inactivation of Jagged-1/Notch-1/Hes-1 pathway.