The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles.
Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.


Role of vitamin B12 in treating recurrent aphthous stomatitis: A review.
Vitamin B12, a water-soluble vitamin, plays a vital role in the formation of hematopoietic stem cells and has been associated with oral mucosal diseases, mainly recurrent aphthous stomatitis (RAS). The latter is a debilitating condition, and B12 was proposed as a potential treatment given its role in regenerating oral mucosal tissue. There is conflicting evidence that B12 deficiency causes RAS. Five of the seven randomized controlled trials reviewed used the inactive form of B12 (cyanocobalamin) as intervention, while the other two used the active form (methylcobalamin). Of the latter two, buccal discs (500 μg B12) showed significant improvement and reduced perceived pain in 77% of the subjects, and submucosal injections showed a significant difference in pain, starting from the second day. Moreover, three studies administered vitamin B12 sublingually with different dosages, which revealed that the higher dose (1000 μg) achieved a significant reduction in outbreaks, number, and duration of ulcers, especially after six months. Multivitamins showed no difference in new RAS episodes and duration. Injectable B12 was compared with the oral form, and nearly 50% of the injection group reported a desired response by the eighth week. An ointment form (500 μg) showed a significant reduction in pain levels after two days of treatment. Based on the available literature, we suggest that a daily dose of 1000 μg of vitamin B12 sublingually for six months can be used to treat RAS. Nevertheless, this conclusion should be considered tentative due to the lack of high quality, large scale studies.


Characterization of polyphenolic metabolites in the seeds of Vitis germplasm.
The composition and content of polyphenols in the seeds of 91 grape accessions from 17 Vitis species were characterized. Eleven compounds, including 2 gallic derivatives, 3 monomeric flavan-3-ols, 3 flavonols, resveratrol, and procyanidin B1 and B2, were identified via HPLC-MS and quantified by HPLC-DAD. In addition, seventeen dimeric and trimeric flavan-3-ols were also quantified. Tremendous variation was observed both among and within species for these compounds. Monomeric flavan-3-ols were the most abundant polyphenols in seeds, followed by dimeric and trimeric flavan-3-ols, which collectively accounted for more than 96% of the total polyphenols. V. palmata, V. vinifera, and V. vulpina had significantly higher content of total polyphenols than other species. A number of Vitis accessions with high content of various types of seed polyphenols were identified, and they can serve as potential germplasm for improving the composition and content of seed polyphenols in cultivated grapes.


Properties of the chaperonin complex from the halophilic archaeon Haloferax volcanii.
The halophilic archaeon Haloferax volcanii has three genes encoding type II chaperonins, named cct1, cct2 and cct3. We show here that the three CCT proteins are all expressed but not to the same level. All three proteins are further induced on heat shock. The CCT proteins were purified by ammonium sulphate precipitation, sucrose gradient centrifugation and hydrophobic interaction chromatography. This procedure yields a high molecular mass complex (or complexes). The complex has ATPase activity, which is magnesium dependent, low salt-sensitive and stable to at least 75 degrees C. Activity requires high levels of potassium ions and was reduced in the presence of an increasing concentration of sodium ions.


Collaborative liver and psychiatry care in the Royal Bolton Hospital for people with alcohol-related disease.
Since 1990, the Royal Bolton Hospital has been evolving a patient-centred, collaborative, seamless, holistic, gastroenterology, psychiatry, community model of alcohol care, team working, governance, research, training, education and health promotion. The aim is to deliver an accessible, responsive, cost-effective, rolled-out service. Consultant gastroenterologists, a specialist liaison psychiatrist, psychiatric alcohol liaison nurse, gastroenterology-based liver nurse practitioner and ward nurses provide joint inpatient and outpatient care for people with alcohol misuse, especially alcohol-related liver disease. A ward based, consultant-led, multidisciplinary team, with a dedicated social worker, meets daily to discuss all inpatients, unify treatment and facilitate discharges. On Monday-Friday, the two alcohol specialist nurses assess, triage and give brief advice to all alcohol-related medical admissions, liaise with consultants about admission or arrange outpatient appointments with the community alcohol team. This has reduced the average length of stay from 8.0 days to 5.7 days, saving the Trust more than 1000 bed days annually. This highlights the need for a 7 day alcohol specialist nurse service, one of 11 key recommendations in a recent position paper by the British Society of Gastroenterology, Alcohol Health Alliance UK and British Association for Study of the Liver on future alcohol care required in British district general hospitals. Other key recommendations include a hospital 'alcohol care team', with a lead clinician, coordinated policies in accident and emergency, with an outreach service, psychiatry input, adequate consultant numbers and integrated alcohol treatment pathways between primary and secondary care.


Evaluation of the diagnostic validity of noninvasive tests for predicting liver fibrosis stage in chronic hepatitis B patients.
The aim of this study was to evaluate the effectiveness of noninvasive tests in predicting liver fibrosis levels in chronic hepatitis B (CHB) patients. A total of 539 treatment naive patients aged 18 years and older with CHB who underwent liver biopsy were included. Patients with coinfections and comorbidities were excluded. Data were obtained retrospectively from patient' follow- up files. Liver biopsy was evaluated according to the Ishak scoring system. SPSS 22.0 program was used for statistical analysis. Diagnostic sensitivity of APRI, FIB-4, NLR, GPR, AAR, RPR, API, King's score, Fibro Q and MPV was determined for predicting ≥F2, ≥F3, ≥F4, ≥F5 groups. The median age of the CHB patients was 41 ±11.57 / year and 49.2% of the patients were female. The distribution of fibrosis stages was : F0, 16.5% ; F1, 26.4% ; F2, 39.7% ; F3, 10.4% ; F4, 4.1% ; F5, 2.4% ; F6 0.4%. Age, AST, ALT, GGT, ALP, RDW, HBV DNA levels were significantly higher, platelet and albumin levels were significantly lower in the ≥F3 group. All noninvasive tests except NLR and AAR predicted ≥F3 adequately (AUROC >0.5). King's score for predicting ≥F2, ≥F5, and GPR for predicting ≥F3 had the highest diagnostic power. The tests predicted the fibrosis stage better, as the fibrosis stage progressed. As a result, most of the noninvasive tests we evaluated could predict significant fibrosis and cirrhosis with significant accuracy. The rate of unnecessary biopsies can be reduced with the help of these noninvasive tests.


The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study.
Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.


Inducing a 6-hour phase advance in the elderly: effects on sleep and temperature rhythms.
The aim of this experiment was to study the effects on sleep and temperature rhythms of a 6-hour (h) phase advance of the sleep/wake cycle in healthy elderly subjects. Twenty-five subjects (77-91 y.o.) lived in a time-isolation apartment on an experimenter-controlled routine for 15 days. The experiment started with five baseline days. The wake time on the 6th night was phase advanced by 6-h and the routine for the remaining nine days was held constant to the new phase position. After the phase shift, temperature circadian rhythms showed rapid phase adjustment leading to a small (1.1 h) phase angle disturbance. Sleep efficiency decreased and showed little evidence of recovery back to baseline following the phase shift. The amount of wakefulness in the first two hours of sleep increased after the phase shift while no effect was found for the amount of wakefulness in the last two hours of sleep. The 6-h phase shift did not change the percentages of REM and SWS. Early night sleep propensity appeared to be very sensitive to a small phase angle disturbance of the circadian oscillator in this healthy elderly sample. The phase angle disturbance induced in this study did not seem to be large enough to have a systematic effect on sleep propensity at the end of the night or on REM sleep parameters, suggesting that these variables are less sensitive to an altered phase relationship with the circadian oscillator than early night sleep propensity. These results indicate that there might be a variable phase tolerance for different sleep parameters in older subjects.


Nuclear Magnetic Resonance Spectroscopy for the Study of B-Cell Epitopes
High-resolution nuclear magnetic resonance (NMR) spectroscopy is a structural technique that is finding increasing use in the study of antibody-antigen interactions. In this review we describe how the dynamic structural parameters obtained from NMR spectroscopy can further our understanding of B-cell epitopes and their function. Specific applications of NMR spectroscopy to examine the residues on peptides and proteins that contact the antibody combining site are also described. These include "footprinting" techniques using H-D exchange-COSY NMR spectroscopy, which are particularly useful for epitope mapping of protein antigens. For smaller systems, such as Fab-or Fv-peptide complexes, nuclear magnetization transfer difference NMR spectroscopy, transferred nuclear Overhauser effect spectroscopy, double-quantum-filtered NOE spectroscopy, and isotope editing techniques have been applied. The interpretation and limitations of the data obtained from these procedures and anticipated improvements in these applications in the future are discussed.


National Adoption Council Act 1987 (No. 21 of 1987), 18 December 1987.
This Act creates a National Adoption Council in Mauritius with the following objectives: "1) to inquire into all demands for the adoption of citizens by noncitizens before any application is made to the Judge in Chambers; 2) to advise the Minister on all matters relating to demands specified in paragraph 1); 3) to coordinate with overseas official agencies engaged in the adoption and welfare of children." Further provisions of the Act deal with the composition of the Board of the Council, staff, the General Fund of the Council, execution of documents, service of process, and offenses, among other things. The Act also requires all foreign citizens to obtain the approval of the Council before proceeding with the adoption of Mauritian citizens.


[A case of aggressive primary squamous cell carcinoma of the breast refractory to preoperative neoadjuvant chemotherapy].
A 42-year-old woman came to our hospital complaining of an enlarging tumor in her right breast. A core needle biopsy of the involved area demonstrated primary squamous cell carcinoma (SCC) of the breast. Preoperative neoadjuvant chemotherapies included 5-fluorouracil: 5-FU+epirubicin: EPI+cyclophosphamide: CPA (FEC), paclitaxel (PTX), vinorelbine (VNR) and 5-FU+nedaplatin (254-S) given in the order listed, but the mass continued to enlarge. Therefore, surgical resection was performed. Local recurrence and lung metastasis occurred after surgery. Although postoperative adjuvant chemotherapy consisting of carboplatin (CBDCA) +etoposide (VP-16) was administered, the patient died three months after surgery. SCC of the breast is generally treated according to clinical stage using protocol for common types of breast cancer. However, effective regimens have not been established for SCC, because it tends to be treatment-refractory. Therefore, in patients with SCC, it is important to consider surgery at an earlier stage than would be considered for a common breast cancer requiring preoperative neoadjuvant chemotherapy.


The impact of menstrual cycle phase on cardiac autonomic regulation.
This study investigated menstrual cycle phase differences in heart rate (HR) and RR interval variability (RRV) in 49 healthy, premenopausal, eumenorrheic women (age 30.2+/-6.2 years). HR and RRV were computed from ambulatory 24-h electrocardiogram, collected for up to 6 days, with at least 1 day each during early to midfollicular and midluteal menstrual phases. Phase effects on HR and RRV were assessed using linear mixed effects models with a random intercept to account for the correlation of observations within each subject as well as intrasubject variation. During follicular phase monitoring, women had significantly lower average HR (-2.33 bpm), and higher standard deviation, the root mean squared successive difference, and high frequency (0.04-0.15 Hz) and low frequency (0.15-0.40 Hz) RRV than during the luteal phase. These results provide strong support for the influence of menstrual phase on cardiac autonomic regulation in premenopausal women.


Expression cloning of a cDNA encoding a sulfotransferase involved in the biosynthesis of the HNK-1 carbohydrate epitope.
The HNK-1 carbohydrate epitope is expressed on several neural adhesion glycoproteins and as a glycolipid, and is involved in cell interactions. The structural element of the epitope common to glycoproteins and glycolipids has been determined to be sulfate-3-GlcAbeta1--> 3Galbeta1-->4GlcNAc. The glucuronyltransferase and sulfotransferase are considered to be the key enzymes in the biosynthesis of this epitope because the rest of the structure occurs often in glycoconjugates. Here we describe the isolation of the rat sulfotransferase cDNA via an expression cloning strategy. The clone finally isolated predicts a protein of 356 amino acids, with characteristics of a type II transmembrane protein and with no sequence similarity to other known sulfotransferases. Both the enzyme expressed as a soluble fusion protein and homogenates of cells transfected with the full-length cDNA could transfer sulfate from a sulfate donor to acceptor substrates containing terminal glucuronic acid.


Multiple drug resistance mechanisms in cancer.
Multiple drug resistance (multidrug resistance; MDR), a phenomenon whereby human tumours that acquire resistance to one type of therapy are found to be resistant to several other drugs that are often quite different in both structure and mode of action, has been recognised clinically for several decades. An important advance in our understanding of MDR came with the identification of P-glycoprotein and other related transporters that were expressed in some cancer cells and could recognise and catalyse the efflux of diverse anticancer drugs from cells. A second advance came from an understanding of the mechanism of programmed cell death or apoptosis, leading to MDR mediated by increased to resistance to anticancer drug-induced apoptosis. A third advance came with the finding that the proliferation of human tumours was driven by a small population of self-renewing tumour cells, focussing attention on the MDR properties of these so-called tumour stem cells rather than on the cells that comprised the majority of the tumour population. A fourth advance was the delineation of features of the tumour microenvironment, including immunosuppression, which essentially provided tumour stem cells with an MDR phenotype. Most published work on the overcoming of MDR has concentrated on inhibition of drug transporters but the complexity of mechanisms contributing demands a broad strategy for the development of methods to overcome MDR in a clinical setting.


Postoperative expressive aphasia associated with intravenous midazolam administration: a 5-year retrospective case-control study.
This study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA). The incidence rate, risk ratio, and contributing factors to intravenous midazolam-induced postoperative EA were analyzed retrospectively in 6756 orthopedic patients. A telephone interview was conducted with patients with EA after surgery. Patients were allocated to either the midazolam group (n = 6178) or no-midazolam group (n = 578). Twelve patients developed EA in the midazolam group, with an incidence of 0.19%, and no patient developed EA in the no-midazolam group. The mean age of EA patients was 70 years, and 92% were women. Among them, 75% received general anesthesia, and the mean dose of midazolam was 1.8 mg. EA was reversed in nine of 12 (75%) patients within 4 minutes of flumazenil administration, and >60 minutes were required to reverse EA in the other three patients (25%). Intravenous midazolam administration for preoperative sedation caused transient EA in 0.19% of patients, especially elderly women who received general anesthesia, and EA could be reversed by flumazenil.


Structure, function and floristic relationships of plant communities in stressful habitats marginal to the Brazilian Atlantic rainforest.
The Brazilian Atlantic rainforest consists of a typical tropical rainforest on mountain slopes, and stands out as a biodiversity hotspot for its high species richness and high level of species endemism. This forest is bordered by plant communities with lower species diversity, due mostly to more extreme environmental conditions than those found in the mesic rainforest. Between the mountain slopes and the sea, the coastal plains have swamp forests, dry semi-deciduous forests and open thicket vegetation on marine sand deposits. At the other extreme, on top of the mountains (>2000 m a.s.l.), the rainforest is substituted by high altitude fields and open thicket vegetation on rocky outcrops. Thus, the plant communities that are marginal to the rainforest are subjected either to flooding, drought, oceanicity or cold winter temperatures. It was found that positive interactions among plants play an important role in the structuring and functioning of a swamp forest, a coastal sandy vegetation and a cold, high altitude vegetation in the state of Rio de Janeiro. Moreover, only a few species seem to adopt this positive role and, therefore, the functioning of these entire systems may rely on them. Curiously, these nurse plants are often epiphytes in the rainforest, and at the study sites are typically terrestrial. Many exhibit crassulacean acid metabolism. Conservation initiatives must treat the Atlantic coastal vegetation as a complex rather than a rainforest alone.


Interspecific competition alters natural selection on shade avoidance phenotypes in Impatiens capensis.
Shade avoidance syndrome is a known adaptive response for Impatiens capensis growing in dense intraspecific competition. However, I. capensis also grow with dominant interspecific competitors in marshes. Here, we compare the I. capensis shade-avoidance phenotypes produced in the absence and presence of heterospecific competitors, as well as selection on those traits. Two treatments were established in a marsh; in one treatment all heterospecifics were removed, while in the other, all competitors remained. We compared morphological traits, light parameters, seed output and, using phenotypic selection analysis, examined directional and nonlinear selection operating in the different competitive treatments. Average phenotypes, light parameters and seed production all varied depending on competitive treatment. Phenotypic selection analyses revealed different directional, disruptive, stabilizing and correlational selection. The disparities seen in both phenotypes and selection between the treatments related to the important differences in elongation timing depending on the presence of heterospecifics, although environmental covariances between traits and fitness could also contribute. Phenotypes produced by I. capensis depend on their competitive environment, and differing selection on shade-avoidance traits between competitive environments could indirectly select for increased plasticity given gene flow between populations in different competitive contexts.


Supracrestal soft tissue preservation with enamel matrix proteins in treatment of deep intrabony defects.
The purpose of the present study was to investigate the effectiveness of a regenerative procedure based on supracrestal soft tissue preservation in association with enamel matrix proteins (EMP) in the treatment of deep intrabony defects. The subjects included 35 consecutively treated patients, 23 females and 12 males, aged 28-61 years, 11 of whom were smokers. Patients presented with at least one intrabony defect with probing pocket depth > or = 6 mm and a radiographic depth of the defect > or = 4 mm at the initial visit. Immediately before surgery and 9-12 months after surgery, Local Plaque Score (LPS), Local Bleeding Score (LBS), probing pocket depth (PPD), clinical attachment level (CAL), gingival recession (REC), and radiographic depth of the defect (DEPTH) were recorded. Thirty-one (88.6%) defects were LPS-negative presurgery, while 29 (82.9%) defects presented with no plaque postsurgery. The prevalence of LBS-positive defects shifted from 94.3% presurgery to 8.4% postsurgery (p < 0.0000). PPD was 8.9 mm before surgery, and decreased to 3.5 mm postsurgery (p < 0.0000). CAL varied from 10.1 mm presurgery to 5.4 mm postsurgery (p < 0.0000), with an average improvement (gain) of 4.7 +/- 1.7 mm. Twenty-six (74.3%) defects presented a gain of least 4 mm. Regression analysis showed a positive correlation between CAL gain as a dependent variable, and presurgery PPD and amount of supracrestal soft tissues as predictors. DEPTH improvement (gain) was 3.9 +/- 1.8 mm, which represented 65% of defect fill. Twenty (57.1%) defects presented a DEPTH gain of at least 4 mm. DEPTH gain was significantly correlated to presurgery PPD (p < 0.000). No significant differences were found between smokers and non-smokers in terms of CAL and DEPTH gain. Results from the present study indicated that the regenerative procedure based on supracrestal soft tissue preservation and EMP application leads to clinically and statistically significant improvement of hard and soft tissue conditions of deep intrabony defects.


Failure to increase glucose consumption through the pentose-phosphate pathway results in the death of glucose-6-phosphate dehydrogenase gene-deleted mouse embryonic stem cells subjected to oxidative stress.
Mouse embryonic stem (ES) glucose-6-phosphate (G6P) dehydrogenase-deleted cells ( G6pd delta), obtained by transient Cre recombinase expression in a G6pd -loxed cell line, are unable to produce G6P dehydrogenase (G6PD) protein (EC 126.96.36.199). These G6pd delta cells proliferate in vitro without special requirements but are extremely sensitive to oxidative stress. Under normal growth conditions, ES G6pd delta cells show a high ratio of NADPH to NADP(+) and a normal intracellular level of GSH. In the presence of the thiol scavenger oxidant, azodicarboxylic acid bis[dimethylamide], at concentrations lethal for G6pd delta but not for wild-type ES cells, NADPH and GSH in G6pd delta cells dramatically shift to their oxidized forms. In contrast, wild-type ES cells are able to increase rapidly and intensely the activity of the pentose-phosphate pathway in response to the oxidant. This process, mediated by the [NADPH]/[NADP(+)] ratio, does not occur in G6pd delta cells. G6PD has been generally considered essential for providing NADPH-reducing power. We now find that other reactions provide the cell with a large fraction of NADPH under non-stress conditions, whereas G6PD is the only NADPH-producing enzyme activated in response to oxidative stress, which can act as a guardian of the cell redox potential. Moreover, bacterial G6PD can substitute for the human enzyme, strongly suggesting that a relatively simple mechanism of enzyme kinetics underlies this phenomenon.


Transition from Amorphous Cyclosporin A Nanoparticles to Size-Reduced Stable Nanocrystals in a Poloxamer 407 Solution.
Amorphous drug nanoparticles usually exhibit low storage stability. A comprehensive understanding of the molecular states and physicochemical properties of the product is indispensable for designing stable formulations. In the present study, an amorphous cyclosporin A (CyA) nanosuspension with a mean particle size of approximately 370 nm was prepared by wet bead milling with poloxamer 407 (P407). Interestingly, the prepared amorphous CyA nanoparticles were transformed into uniform CyA nanocrystals with a reduced mean particle size of approximately 200 nm during storage at 25 °C. The CyA nanocrystals were stably maintained for at least 1 month. The particle morphologies and molecular structures of the CyA nanosuspensions before and after storage were thoroughly characterized by cryogenic transmission electron microscopy and magic-angle spinning nuclear magnetic resonance spectroscopy, respectively. They revealed that the freshly prepared amorphous CyA nanoparticles (∼370 nm) were secondary particles composed of aggregated primary particles with an estimated size of 50 nm. A portion of P407 was found to be entrapped at the gaps between the primary particles due to aggregation, while most of P407 was dissolved in the solution either adsorbing at the solid/liquid interface or forming polymeric micelles. The entrapped P407 is considered to play an important role in the destabilization of the amorphous CyA nanoparticles. The resultant CyA nanocrystals (∼200 nm) were uniform single crystals of Form 2 hydrate and showed corner-truncated bipyramidal features. Owing to the narrow particle size distribution of the CyA nanocrystals, the rate of Ostwald ripening was slow, giving long-term stability to the CyA nanocrystals. This study provides new insights into the destabilization mechanism of amorphous drug nanoparticles.


[Course of recovery from motor aphasia in four patients with localized lesions in the vicinity of Broca's area].
The neuropsychological signs and prognosis of patients with localized lesions in the vicinity of Broca's area of the left inferior frontal gyrus have been controversial. We studied periodic changes in the neuropsychological signs of four patients who had relatively localized lesions in the vicinity of Broca's area and manifested aphasia of the non-fluent type. The ages of the four patients at the onset were 62, 66, 30 and 37 years. The localized lesions in their brains were the result of brain infarctions revealed by CT scans, and included so-called Broca's center in the left inferior frontal gyrus along with adjacent brain tissue. The neuropsychological signs of the four patients were periodically assessed by means of the standard language test of aphasia (SLTA). In the early stage of aphasia, they had moderate difficulties in speaking to explain test materials or recall words and mild difficulties in reading aloud, repeating and writing words. One year later, most of their neuropsychological signs disappeared except for mild difficulties in speaking fluently and recalling words. It should be noted, however, that all four patients were able to return to their previous occupations one or two years later, because they had recovered from aphasia. Based on the results of this study, we conclude that the neuropsychological signs of Broca's aphasia caused by relatively localized lesions in the left inferior frontal gyrus are mild and largely disappear within one or two years.


Analgesics Self-Medication and its Association with Sleep Quality among Medical Undergraduates.
Self medication especially with analgesics is a common practice among undergraduate medical students. Variation in analgesic self medication prevalence and pattern is often seen due to geographical and target population differences. The mutual influence of pain and sleep quality might persuade students self medication behaviour. To assess analgesic self medication and its association with sleep quality among the medical undergraduates. A cross-sectional questionnaire based study was conducted from December 2015 to February 2016 among 320 medical undergraduates. The information about socio-demographic profile, symptoms, types of analgesics, source of information and reason for analgesic self medication was collected. The sleep quality of students was assessed by Pittsburgh Sleep Quality Index (PSQI). The qualitative variables were expressed as percentages. Odds Ratio (OR) with 95% Confidence Interval (CI) was also calculated. Chi-square test was used. Analgesic self medication prevalence was 49.7%, more prevalence seen among males, seniors, urban residents and students of working parents. Headache (48.4%) was the most common cause and paracetamol (79.7%) was most frequent drug used, based on knowledge obtained through textbook and internet (47.1%). Mildness of symptoms (49.1%) was the most important motivation behind self medication. Analgesic use was more (57.4%) among "poor sleepers" compared to "normal sleepers" (45.2%). Despite having easy accessibility to expert consultations, high prevalence of analgesic self medication among medical students and its association with poor sleep quality is a distressing issue. This indicates an urgent need of awareness programmes about harmful effects of self medication and healthy sleep practices.


Cloning, heterologous expression and developmental regulation of a Drosophila receptor for tachykinin-like peptides.
We identified clones encoding a Drosophila receptor for tachykinin-like peptides by low stringency screening of an embryonic cDNA library with probes from the bovine substance K receptor. The cDNAs encode a seven transmembrane domain protein (DTKR) of 519 amino acids with 40-48% amino acid identity to mammalian tachykinin receptors within transmembrane regions. Xenopus oocytes injected with DTKR cRNAs showed selective responses to vertebrate substance P, its agonists and not to other vertebrate tachykinin peptides. These responses were eliminated by treatment of oocytes with pertussis toxin. In the adult fly, Northern and PCR analysis demonstrated preferential expression of DTKR in the head; in situ hybridization indicated that DTKR is accumulated in the cell bodies of neurons in the adult CNS. The levels of DTKR transcript are regulated during development. Northern and PCR amplification analysis showed that while DTKR transcripts are present at all stages, high levels of expression occur in later stages of embryogenesis (starting at 10-14 h), coinciding with the beginning of major periods of neural development. Whole mount embryo in situ hybridization demonstrated that DTKR is expressed at these later stages of embryogenesis (11-15 h) in the brain and in a specific subset of neurons in each neuromere of the developing ventral ganglion. The gene encoding DTKR was mapped by in situ hybridization to a single location at 99D on the right arm of chromosome 3. These observations demonstrate that the tachykinin family of peptide transmitters and their receptors represent an evolutionarily ancient form of cellular communication within the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)


The italian determiner system in normal acquisition, specific language impairment, and childhood aphasia.
The paper presents a comparison of the development of the Italian determiner system in three different populations: normally developing children, a child recovering from childhood aphasia from the age of 3 years, 9 months, and 11 specific language impairment (SLI) children. Data from Italian normal children provide evidence for the hypothesis (1) that no prefunctional stage exists as far as the determiner system is concerned and (2) that the syntactic properties of determiners play an essential triggering role early on. The analysis of the determiner system in the aphasic child has a double interest. On the one hand, it may help to shed light on some of the intriguing questions concerning this type of disorder; on the other, it may be relevant for the discussion of the notion of agrammatism. Results of the morphosyntactic analysis reveal that, apart from timing differences, recovery from childhood aphasia shares important features with normal development. Differently from mean length of utterance (MLU)-matched normal controls and the aphasic child, SLI children omit determiners significantly more often than almost any other functional category or free morpheme. We will argue that the reasons for the SLI children's atypical behavior have to be sought in the nonaccessibility to or in the misappreciation of one fundamental syntactic property of determiners: their role as elements that assign argumenthood to nominal expressions (Szabolcsi, 1987; Longobardi, 1994).


Persistent electrocardiographic ST segment elevation from previous myocarditis.
Various conditions may present with an electrocardiographic pattern of ST segment elevation simulating myocardial infarction. We present an asymptomatic 16-year-old male patient, whose ECG showed persistent anterolateral ST segment elevation and magnetic resonance imaging showed wall motion abnormalities from previous myocarditis but no evidence of inflammation.


Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles.
With the wide recognition of oncostatic effect of melatonin, the current study proposes a potential breast cancer target multimodality treatment based on melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). Melatonin-MNPs were fabricated by the single emulsion solvent extraction/evaporation method. Based on the facilitated transport of melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can be more favorably uptaken by MCF-7 cells compared with the melatonin-free nanocomposite particles, which indicates the cancer targeting ability of melatonin molecule. Inductive heating can be generated by exposure to the Melatonin-MNPs internalized within cancer cells under alternative magnetic field, so as to achieve the "inside-out" magnetic nano-thermotherapy. In addition to demonstrating the superior cytotoxic effect of such nano-thermotherapy over the conventional exogenous heating by metal bath, more importantly, the sustainable release of melatonin from the Melatonin-MNPs can be greatly promoted upon responsive to the magnetic heating. The multimodality treatment based on Melatonin-MNPs can lead to more significant decrease in cell viability than any single treatment, suggesting the potentiated effect of melatonin on the cytotoxic response to nano-thermotherapy. This study is the first to fabricate the precisely engineered melatonin-loaded multifunctional nanocomposite particles and demonstrate the potential in breast cancer target multimodality treatment.


Detection of trace concentrations of S-nitrosothiols by means of a capacitive sensor.
Small molecule S-nitrosothiols are a class of endogenous chemicals in the body, which have been implicated in a variety of biological functions. However, the labile nature of NO and the limits of current detection assays have made studying these molecules difficult. Here we present a method for detecting trace concentrations of S-nitrosothiols in biological fluids. Capacitive sensors when coupled to a semiconducting material represent a method for detecting trace quantities of a chemical in complex solutions. We have taken advantage of the semiconducting and chemical properties of polydopamine to construct a capacitive sensor and associated method of use, which specifically senses S-nitrosothiols in complex biological solutions.


Recent trends in CE of inorganic ions: from individual to multiple elemental species analysis.
The major methodological developments in CE related to inorganic analysis are overviewed. This is an update to a previous review article by the author (Timerbaev, A. R., Electrophoresis 2004, 25, 4008-4031) and it covers the review work and innovative research papers published between January 2004 and the first part of 2006. As was underlined in that review, a growing interest of analytical community in providing elemental speciation information found a sound response of the CE method developers. Presently, almost every second research paper in the field of interest deals with element species analysis, the use of inductively coupled plasma MS detection and biochemical applications being the topics of utmost research efforts. On the other hand, advances in general methodology traditionally centered on a CE system modernization for improvements in sensitivity and separation selectivity have attracted less attention over the review period. While there is no indication that inorganic ion applications would surpass by the developmental rate the more matured analysis of organic analytes, CE can now be seen as an analytical technique to be before long customary in a number of inorganic analysis arenas.


Vascular endothelial growth factor receptor 1 contributes to Escherichia coli K1 invasion of human brain microvascular endothelial cells through the phosphatidylinositol 3-kinase/Akt signaling pathway.
Escherichia coli is the most common Gram-negative organism causing neonatal meningitis. Previous studies demonstrated that E. coli K1 invasion of brain microvascular endothelial cells (BMEC) is required for penetration into the central nervous system, but the microbe-host interactions that are involved in this process remain incompletely understood. Here we report the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) expressed on human brain microvascular endothelial cells (HBMEC) in E. coli K1 invasion of HBMEC. Our results showed that treatment of confluent HBMEC with pan-VEGFR inhibitors significantly inhibited E. coli K1 invasion of HBMEC. Immunofluorescence results indicated the colocalization of VEGFR1 with E. coli K1 during bacterial invasion of HBMEC. The E. coli-induced actin cytoskeleton rearrangements in HBMEC were blocked by VEGFR inhibitors but not by VEGFR2-specific inhibitors. The small interfering RNA (siRNA) knockdown of VEGFR1 in HBMEC significantly attenuated E. coli invasion and the concomitant actin filament rearrangement. Furthermore, we found an increased association of VEGFR1 with the p85 subunit of phosphatidylinositol 3-kinase (PI3K) in HBMEC infected with E. coli K1 and that E. coli K1-triggered Akt activation in HBMEC was blocked by VEGFR1 siRNA and VEGFR inhibitors. Taken together, our results demonstrate that VEGFR1 contributes to E. coli K1 invasion of HBMEC via recruitment of the PI3K/Akt signaling pathway.


Assay of naproxen by high-performance liquid chromatography and identification of its photoproducts by LC-ESI MS.
A rapid, accurate and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of naproxen and its photodegradation products in methanol was developed and validated. An Inertsil 5-ODS-3V column (5 microm, C18, 250 x 4.6 mm i.d.) was used with a mobile phase of acetonitrile-methanol-1% HOAc in H2O (40:20:40, v/v/v). UV detection was set at 230 nm. The developed method satisfies system suitability criteria, peak integrity and resolution for the parent drug and its photoproducts. The intraday and interday standard deviations of five replicate determinations for five consecutive days at the working concentrations of 5.0, 10, 25, 50, and 100 microm were 0.23-0.98 with coefficients of variance (CVs) of between 0.96 and 4.56% for the former, and 0.14-1.15 with CVs of between 1.13 and 3.82% for the latter. The percentage recoveries were determined to be 98.34, 99.19, 100.18, 102.97 and 99.81%, respectively, at the five concentrations between 5.0 and 100 microm. The limit of quantitation of naproxen was determined to be 0.29 microg/mL, while the detection limit was 64 ng/mL. Four major photoproducts were observed from the HPLC chromatogram using a Panchum PR-2000 reactor which equipped with 8 W x 16 low-pressure quartz mercury lamps as the light source for irradiation of a naproxen sample in methanol. The structures of the photoproducts were confirmed by LC-ESI MS.


A linear systems analysis of the yaw dynamics of a dynamically scaled insect model.
Recent studies suggest that fruit flies use subtle changes to their wing motion to actively generate forces during aerial maneuvers. In addition, it has been estimated that the passive rotational damping caused by the flapping wings of an insect is around two orders of magnitude greater than that for the body alone. At present, however, the relationships between the active regulation of wing kinematics, passive damping produced by the flapping wings and the overall trajectory of the animal are still poorly understood. In this study, we use a dynamically scaled robotic model equipped with a torque feedback mechanism to study the dynamics of yaw turns in the fruit fly Drosophila melanogaster. Four plausible mechanisms for the active generation of yaw torque are examined. The mechanisms deform the wing kinematics of hovering in order to introduce asymmetry that results in the active production of yaw torque by the flapping wings. The results demonstrate that the stroke-averaged yaw torque is well approximated by a model that is linear with respect to both the yaw velocity and the magnitude of the kinematic deformations. Dynamic measurements, in which the yaw torque produced by the flapping wings was used in real-time to determine the rotation of the robot, suggest that a first-order linear model with stroke-average coefficients accurately captures the yaw dynamics of the system. Finally, an analysis of the stroke-average dynamics suggests that both damping and inertia will be important factors during rapid body saccades of a fruit fly.


Correlation between Scratch Behavior and Tensile Properties in Injection Molded and Extruded Polymers.
This study investigates the validity and applicability of the correlation between scratch and tensile properties for extruded polymer strands. The mechanical properties could be predicted for extruded samples, which allows skipping the step of injection molding and therefore enables a faster material development. Extruded polymer strands and tensile test specimens out of PMMA, PS, POM, PP and PE have been investigated. A correlation of the Young's modulus and the elastic deformation as well as a correlation of the yield stress and the plastic deformation during scratching is given for both flat molded and cylindrical extruded specimens. SEM images of the scratch grooves are used to analyze the scratch deformation mechanism. The deformation mechanism correlates well to the variation coefficient of the indentation depth. Polarized light microscopy of thin cross sections of both types of specimens provides information about skin layer thickness and morphology. However, the optical analysis could not provide an explanation for the different levels of the indentation depth in the two specimen types. Further investigations should include a study of differences in process induced morphology and the effect of two layers with different mechanical properties, i.e., skin and center, on the stress and strain fields underneath the scratch.


[Endodontic diagnosis].
In this article endodontic diagnosis is discussed following the clinical diagnostic process. A description is given about pain from endodontic origin and a comprehensive overview of the clinical diagnostic tests is discussed. In the chapter clinical classification of pulpal and periapical disorders all the possible endodontic diagnoses are extensively discussed.


Expertise and responsibility effects on pilots' reactions to flight deck alerts in a simulator.
Flight deck alerts provide system malfunction information designed to lead corresponding pilot reactions aimed at guaranteeing flight safety. This study examined the roles of expertise and flight responsibility and their relationship to pilots' reactions to flight deck alerts. There were 17 pilots composing 12 flight crews that were assigned into pairs according to flight hours and responsibilities. The experiment included 9 flight scenarios and was carried out in a CRJ-200 flight simulator. Pilot performance was recorded by a wide angle video camera, and four kinds of reactions to alerts were defined for analysis. Pilots tended to have immediate reactions to uninterrupted cautions, with a turning off rate as high as 75%. However, this rate decreased sharply when pilots encountered interrupted cautions and warnings; they also exhibited many wrong reactions to warnings. Pilots with more expertise had more reactions to uninterrupted cautions than those with less expertise, both as pilot flying and pilot monitoring. Meanwhile, the pilot monitoring, regardless of level of expertise, exhibited more reactions than the pilot flying. In addition, more experienced pilots were more likely to have wrong reactions to warnings while acting as the monitoring pilot. These results suggest that both expertise and flight responsibility influence pilots' reactions to alerts. Considering crew pairing strategy, when a pilot flying is a less experienced pilot, a more experience pilot is suggested to be the monitoring pilot. The results of this study have implications for understanding pilots' behaviors to flight deck alerts, calling for specialized training and design of approach alarms on the flight deck.


Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for advanced gastric carcinoma.
To evaluate the activity and safety of a combination chemotherapy with epirubicin, cisplatin, and a protracted venous infusion of 5-fluorouracil (ECF) in unresectable or metastatic gastric cancer, a phase II study was performed. Thirty-five chemotherapy-naive patients were given ECF. Epirubicin (50 mg/m(2) intravenous, i.v.) and cisplatin (60 mg/m(2) i.v.) were administered every three weeks during a continuous intravenous infusion of 5-fluorouracil (250 mg/m(2) /day) using infusion pump. One complete response and 19 partial responses (response rate=62%) were achieved. Eight patients remained stable, whereas in four patients the disease progressed. The median duration of response was 22 weeks (95% confidence interval, 18-27 weeks). The median survival for all patients was 10 months (95% confidence interval, 6-14 months), with a 1-yr survival rate of 40%. A total of 184 cycles of chemotherapy were administered. Grade 3 or 4 emesis occurred in 3%, mucositis in 2%, anemia in 10%, and leukopenia in 3% of the cycles. Central venous catheter complications that required line removal occurred in 37% (n=13) of the patients. No patient died of toxicity. Overall, the ECF regimen showed high anti-tumor activity with a tolerable toxicity pattern.


Relationship between growth and plasma concentrations of ghrelin and growth hormone in juvenile beagle dogs.
Although the release of growth hormone (GH) is known to be regulated mainly by GH-releasing hormone (GHRH) and somatostatin (SRIF) secreted from the hypothalamus, ghrelin also may be involved in GH release during juvenile period. We have examined plasma concentrations of acylated ghrelin, desacyl ghrelin, and GH in juvenile beagle dogs. Plasma acylated and desacyl ghrelin levels changed through aging; however, there was no closely correlation between ghrelin, body weight and circulating GH levels during juvenile period. The increase in body weight was essentially linear until 8 months of age, whereas plasma GH concentrations exhibited bimodal peaks for the meanwhile. The results suggest that ghrelin may not play internal cueing in GH secretion in juvenile beagle dogs.


[Enteral nutrition in cancer patients].
The significance of nutritional management in patients with malignant tumors is under-recognized due to the lack of clear evidence of a direct link with survival rate. However, for cancer patients, with markedly reduced food intake continuing for≥7 days or intake of under 60% of estimated energy expenditure for≥10 days, as referred to in the European Society for Clinical Nutrition and Metabolism, rapid implementation of nutritional support constitutes a clinically appropriate intervention. With regard to route of administration, as with other conditions, enteral nutritional management is recommended if the gastrointestinal tract is available. The utility of enteral immunonutrition formulae containing eicosapentaenoic acid and other forms of nutritional management has also recently been reported and further studies are anticipated. However, the principles of nutritional management for cancer patients comprise not simply weight increase or improvement in nutritional markers but the maintenance of patient QOL in ways that include alleviation of symptoms and antitumor therapy side-effects, and decreased risk of infection. Administration routes such as percutaneous endoscopic gastrostomy should therefore also be discussed from this perspective.


Structural organization and chromosomal assignment of the human 14-3-3 eta chain gene (YWHAH).
14-3-3 protein, a brain-specific protein, is thought to be a multifunctional protein involved in the activation of tyrosine and tryptophan hydroxylases, the inhibition or activation of protein kinase C, and the activation of signal transduction. The human 14-3-3 eta chain gene was isolated and its structure was determined. It is composed of two exons separated by one long intron (approximately 8 kb) and spans about 10 kb. A transcription initiation site was identified by a combination of S1 nuclease mapping, primer extension analysis, and RACE methods. In the 5'-flanking region, we found four GC box sequences, four anti-GC box sequences, a TATA box-like sequence, CAAT box-like sequences, a C/EBP element, two AP-2 sequences, an AP-3 sequence, an Oct-6-like sequence, six E boxes, and a CRE sequence. FISH with DNA probes of the human 14-3-3 eta chain gene mapped the 14-3-3 eta chain gene to chromosome 22q12.1-q13.1.


Fibrosing colonopathy revealing cystic fibrosis in a neonate before any pancreatic enzyme supplementation.
Although its pathogenesis remains still unknown, fibrosing colonopathy (FCP) is considered to be the result of prolonged treatment by high doses of pancreatic enzyme preparations, in a small proportion of patients who present with cystic fibrosis (CF). We present the case of a newborn with meconium ileus (treated by conservative measures), in which, at the age of 3 weeks, the features of intestinal obstruction made necessary the removal of 15 cm of the proximal large intestine. Macroscopical and especially microscopical appearances typical for FCP were found, despite the absence of any enzymatic treatment. These findings raised the suspicion of CF, which was confirmed 4 weeks later at necropsy by the presence of characteristic pancreatic lesions. This case and another similar report in the literature suggest that the mechanism of FCP must be linked with the disease itself, at least in some patients. Thus, for us, FCP is not a "closed subject" and we sustain the importance of continuing studies, which will shed light on its etiopathogenesis.


Range resolution and the possible use of spectral information in the echolocating bat, Eptesicus fuscus.
Individuals of the echolocating bat Eptesicus fuscus were trained to discriminate simulated two-wave-front targets with internal time delays of 0 to 100 microns between the wave fronts from a one-wave-front target. The ability of bats to discriminate between such targets can be referred to as range resolution. In Eptesicus fuscus, this ability is limited to distinct internal time delays (12, 32-40, and 52-100 microns) between the two wave fronts of a double-wave-front target. Analysis of the simulated two-wave-front echoes reveals periodic frequency minima in the spectrum. Position and separation of these spectral minima depend on the time delay between the two wave fronts. The occurrence of spectral minima within the frequency range of the first harmonic in the echo of the bats' echolocation call correlates to the bats' ability to discriminate a one-wave-front echo from two-wave-front echoes, suggesting that Eptesicus fuscus uses spectral differences within the first harmonic in echoes for range resolution.


The Illegal Immigration Reform and Immigrant Responsibility Act of 1996: an overview.
"On September 30, 1996, President Clinton signed the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (1996 Act), Pub. L. No. 104-208, 110 Stat. 3009. After an intense lobbying effort by the business community, most provisions relating to legal immigration were omitted from the final bill. Instead, the 1996 Act focuses on illegal immigration reform and includes some of the toughest measures ever taken against illegal immigration." Aspects considered include border enforcement, penalities against alien smuggling and document fraud, deportation and exclusion proceedings, employer sanctions, welfare provisions, and changes to existing refugee and asylum procedures.


Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.
Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection.


Management of Western North American Bark Beetles with Semiochemicals.
We summarize the status of semiochemical-based management of the major bark beetle species in western North America. The conifer forests of this region have a long history of profound impacts by phloem-feeding bark beetles, and species such as the mountain pine beetle (Dendroctonus ponderosae) and the spruce beetle (D. rufipennis) have recently undergone epic outbreaks linked to changing climate. At the same time, great strides are being made in the application of semiochemicals to the integrated pest management of bark beetles. In this review, we synthesize and interpret these recent advances in applied chemical ecology of bark beetles for scientists and land managers.


Feature Pyramid Nonlocal Network With Transform Modal Ensemble Learning for Breast Tumor Segmentation in Ultrasound Images.
Automated breast ultrasound image segmentation is essential in a computer-aided diagnosis (CAD) system for breast tumors. In this article, we present a feature pyramid nonlocal network (FPNN) with transform modal ensemble learning (TMEL) for accurate breast tumor segmentation in ultrasound images. Specifically, the FPNN fuses multilevel features under special consideration of long-range dependencies by combining the nonlocal module and feature pyramid network. Additionally, the TMEL is introduced to guide two iFPNNs to extract different tumor details. Two publicly available datasets, i.e., the Dataset-Cairo University and Dataset-Merge, were used for evaluation. The proposed FPNN-TMEL achieves a Dice score of 84.70% ± 0.53%, Jaccard Index (Jac) of 78.10% ± 0.48% and Hausdorff distance (HD) of 2.815 ± 0.016 mm on the Dataset-Cairo University, and Dice of 87.00% ± 0.41%, Jac of 79.16% ± 0.56%, and HD of 2.781±0.035 mm on the Dataset-Merge. Qualitative and quantitative experiments show that our method outperforms other state-of-the-art methods for breast tumor segmentation in ultrasound images. Our code is available at https://github.com/pixixiaonaogou/FPNN-TMEL.


The effect of a short voice training program in future teachers.
The purpose of this study was to investigate if a module consisting of 6 hours of voice training is effective in future teachers. Sixty-five students, enrolled in the academic teaching program at the Vrije Universiteit Brussel, participated in this study. The trained group (n=35) received 6 hours of voice training, whereas the control group (n=30) received no voice training. A multidimensional test battery containing subjective judgments and objective measurements was applied in both groups at the study onset and after 4 months to evaluate the training outcome. No significant differences were observed for the subjective judgments. For the objective measurements, by contrast, several significant differences between the trained and the control groups were found. This outcome favors the systematic introduction of voice training during the schooling of future teachers.


An exploration of the leadership attributes and methods associated with successful lean system deployments in acute care hospitals.
The lean system has been shown to be a viable and sustainable solution for the growing number of cost, quality, and efficiency issues in the health care industry. While there is a growing body of evidence to support the outcomes that can be achieved as a result of the successful application of the lean system in hospital organizations, there is not a complete understanding of the leadership attributes and methods that are necessary to achieve successful widespread mobilization and sustainment. This study was an exploration of leadership and its relevant association with successful lean system deployments in acute care hospitals. This research employed an exploratory qualitative research design encompassing a research questionnaire and telephonic interviews of 25 health care leaders in 8 hospital organizations across the United States. The results from this study identified the need to have a strong combination of personal characteristics, learned behaviors, strategies, tools, and tactics that evolved into a starting adaptable framework for health care leaders to leverage when starting their own transformational change journeys using the lean system. Health care leaders could utilize the outcomes reported in this study as a conduit to enhance the effective deployment, widespread adoption, and sustainment of the lean system in practice.


[Is psychoanalytic psychotherapy an "alternative treatment method"?].
Psychoanalytic psychotherapy is a controversial treatment method even though it has an extensive theory and is widely used. Its assumptions continue to be challenged, especially by psychiatrists with a biologic-scientific orientation. Hence it is an appropriate model for examining the transitional area between textbook medicine and what are referred to as "alternative" treatment approaches. The historical development of psychiatry from the end of the 18th century was characterized on the one hand by the increasing influence of biological and technical methods of investigation and on the other by the increasing independence of the citizenry and societal acceptance of subjective emotional experience. The special contribution of Freudian psychoanalytic theory lies in its function as a medicator between these two approaches, whereby it develops analogies between the scientific knowledge of the time and psychic processes. At the same time it provides explanations of emotional illness that the individual can comprehend. This is what is unique about classical psychoanalysis and at the same time makes it problematic, as evidenced, for example, by the fact that so many different schools have developed. The integration of psychoanalysis in the form of psychoanalytic psychotherapy into textbook medicine gives the latter the advantage of being able to reach a clientele that in addition to wanting scientific-causal explanations also has a desire for existential interpretations of psychopathological states.


Unveiling the Atomic Structure and Growth Dynamics of One-Dimensional Water on ZnO(10-10).
The adsorption and organization state of water on the metal oxide surface is of critical importance for wide fields where interface chemistry dominates. On the technically important ZnO(10-10) surface, we found water assembles into an one-dimensional (1D) chain structure at submonolayer coverage instead of the well-known half-dissociated two-dimensional (2D) island. With a combination of high resolution scanning tunneling microscopy (STM) and density functional theory (DFT) calculations, we clearly distinguished the single and double water chains, which are composed of dissociated monomers and half-dissociated dimers, respectively. Moreover, we unambiguously determined that single water molecules dissociate spontaneously before agglomerating into ordered phase, which is contrary to the proposition of previous studies. These results have deepened our understandings of the adsorbed water species on the ZnO surface, which may bring new insights into the mechanisms of water-stimulated surface reactions.


Regulation of human cytotoxic lymphocyte responses. II. Suppression by a soluble factor produced by primed lymphocytes.
A soluble supernatant factor is elaborated from in vitro primed human allogeneic lymphocytes which suppresses the development of alloreactive cytotoxic lymphocytes (CTL). In contrast, supernatants obtained from primary mixed lymphocyte cultures (MLC) and primed autologous cultures were unable to suppress CTL activation, indicating that antigen restimulation was required to elicit the factor. The suppressor factor (SF) functioned in a dose-dependent manner. When the SF was added 24 or 48 hr after MLC initiation it was ineffective. However, adding the SF at culture initiation significantly reduced CTL activity, suggesting that suppression occurs either during antigen recognition or early in the CTL differentiation pathway. The SF did not function by altering the kinetics of the CTL response. Preincubation experiments showed that the SF operates by partially inactivating both MLC responder and stimulator cell populations.


Kidney disease and cognitive function: African American-diabetes heart study MIND.
Albuminuria and reduced estimated glomerular filtration rate (eGFR) are linked with poorer cognitive performance in European-ancestry populations with advanced nephropathy; relationships in African Americans (AAs) with type 2 diabetes (T2D) are less clear. Tests of cognitive performance, urine albumin:creatinine ratio (UACR), and CKD-EPI eGFR were performed in unrelated AAs with T2D to determine relationships. Cross-sectional analysis of 263 unrelated AAs with T2D recruited in the African American-Diabetes Heart Study (AA-DHS) MIND. Global cognitive function (mini-mental state exam [3MSE] and Montreal Cognitive Assessment [MoCA]), memory (Rey Auditory Verbal Learning Test [RAVLT]), executive function (Stroop, verbal fluency for animals, and Digit Symbol Copy [DSC]), UACR, and eGFR were determined. Relationships between cognitive tests and renal parameters were assessed using multivariate models, adjusted for age, gender, body mass index, hemoglobin A1c, level of education, hypertension, and LDL cholesterol. Participants had a mean ± SD age of 60.2 ± 9.7 years, 62.7% were female, T2D duration was 14.3 ± 8.9 years, eGFR 86.0 ± 23.2 ml/min/1.73 m(2), and UACR 155.8 ± 542.1 (median 8.1) mg/g. In adjusted models, higher UACR was associated with worse 3MSE (p = 0.014), MoCA (p = 0.0089), DSC (p = 0.0004), Stroop performance time (p = 0.003), Stroop errors (p = 0.032), and Stroop interference (p = 0.026). Higher eGFR was associated with better performance on DSC (p = 0.0071). In AAs with T2D, albuminuria and eGFR were associated with cognitive function, even in mild kidney disease. These data stress the need for interventions to prevent cognitive decline well before the late stages of kidney disease.


Percutaneous mitral annular reduction provides continued benefit in an ovine model of dilated cardiomyopathy.
Functional mitral valve regurgitation plays a key role in the symptomatic severity and progression of heart failure. In an ovine model of dilated cardiomyopathy, we examined the chronic functional consequences of mitral regurgitation reduction using a recently developed novel percutaneous mitral annular reduction (PMAR) device. Fourteen adult sheep were paced right ventricularly at 180 to 190 bpm for 5 weeks, leading to the development of moderate mitral valve regurgitation. After echocardiographic, hemodynamic, and neurohormonal analysis, 9 animals underwent PMAR. All animals were subsequently paced for another 28 days, and a final echocardiographic and hemodynamic study was conducted. Animals that had undergone PMAR showed significantly increased negative and positive dP/dt, whereas pulmonary capillary wedge pressure and mitral valve regurgitation were significantly reduced compared with those at device implant despite continued pacing. In conjunction, significant improvements in plasma norepinephrine and brain natriuretic peptide were apparent. The application of PMAR in animals with pacing-induced dilated cardiomyopathy and functional mitral valve regurgitation resulted in continued improvements in hemodynamic and neurohormonal parameters.


Spectroscopic Ellipsometry Characterization of As-Deposited and Annealed Non-Stoichiometric Indium Zinc Tin Oxide Thin Film.
A spectroscopic ellipsometry study on as-deposited and annealed non-stoichiometric indium zinc tin oxide thin films of four different compositions prepared by RF magnetron sputtering was conducted. Multi-sample analysis with two sets of samples sputtered onto glass slides and silicon wafers, together with the analysis of the samples onto each substrate separately, was utilized for as-deposited samples. Annealed samples onto the glass slides were also analyzed. Spectroscopic ellipsometry in a wide spectral range (0.2-6 eV) was used to determine optical constants (refractive index n and extinction coefficient k) of these films. Parameterized semiconductor oscillator function, together with Drude oscillator, was used as a model dielectric function. Geometrical parameters (layer thickness and surface roughness) and physical parameters (direct optical bandgap, free carrier concentration, mobility, and specific electrical resistivity) were determined from spectroscopic ellipsometry data modeling. Specific electrical resistivity determined from the Drude oscillator corresponds well with the results from electrical measurements. Change in the optical bandgap, visible especially for annealed samples, corresponds with the change of free carrier concentration (Moss-Burstein effect). Scanning electron microscope did not reveal any noticeable annealing-induced change in surface morphology.


Exploring the Potential of Cell-Free-DNA Measurements After an Exhaustive Cycle-Ergometer Test as a Marker for Performance-Related Parameters.
Intensive exercise is known to be accompanied by a rapid release of cell-free DNA (cfDNA). The physiological significance of cfDNA release for performance diagnostics has not been studied. The authors analyzed the release of cfDNA during bicycle exercise and its correlation with physiological parameters. Eleven male athletes performed an incremental cycling test. Venous blood was collected before and immediately after exercise and after 90 min of recovery. Since the amount of cfDNA is influenced by preanalytical parameters like DNA extraction and quantification method, the authors applied different measurement approaches based on quantitative real-time polymerase chain reaction. They compared a direct measurement procedure not requiring cfDNA extraction for a short (L1PA290) and a long fragment (L1PA2222) and a procedure for extracted cfDNA for a short (LTR570) and long fragment (LTR5323) with primers targeting the repetitive sequences L1PA2 and LTR5 in both assays, respectively. With the exception of LTR5323, the procedures revealed significant increases of cfDNA postexercise, whereas the direct approach showed lower interindividual variance in cfDNA values. When linking cfDNA levels to parameters of exercise performance the authors observed that, especially, the measurement based on L1PA2222 correlated significantly with exercise markers. These correlations were similar to the relationship of the performance markers among themselves. cfDNA is a possible physiological marker to assess and predict exercise performance in athletes. In addition, the results indicate that using cfDNA as a marker in exercise physiology requires careful selection of a suitable measurement technique, whether it is eluted DNA or directly quantified.


Novel Biocompatible with Animal Cells Composite Material Based on Organosilicon Polymers and Fullerenes with Light-Induced Bacteriostatic Properties.
A technology for producing a nanocomposite based on the borsiloxane polymer and chemically unmodified fullerenes has been developed. Nanocomposites containing 0.001, 0.01, and 0.1 wt% fullerene molecules have been created. It has been shown that the nanocomposite with any content of fullerene molecules did not lose the main rheological properties of borsiloxane and is capable of structural self-healing. The resulting nanomaterial is capable of generating reactive oxygen species (ROS) such as hydrogen peroxide and hydroxyl radicals in light. The rate of ROS generation increases with an increase in the concentration of fullerene molecules. In the absence of light, the nanocomposite exhibits antioxidant properties. The severity of antioxidant properties is also associated with the concentration of fullerene molecules in the polymer. It has been shown that the nanocomposite upon exposure to visible light leads to the formation of long-lived reactive protein species, and is also the reason for the appearance of such a key biomarker of oxidative stress as 8-oxoguanine in DNA. The intensity of the process increases with an increase in the concentration of fullerene molecules. In the dark, the polymer exhibits weak protective properties. It was found that under the action of light, the nanocomposite exhibits significant bacteriostatic properties, and the severity of these properties depends on the concentration of fullerene molecules. Moreover, it was found that bacterial cells adhere to the surfaces of the nanocomposite, and the nanocomposite can detach bacterial cells not only from the surfaces, but also from wetted substrates. The ability to capture bacterial cells is primarily associated with the properties of the polymer; they are weakly affected by both visible light and fullerene molecules. The nanocomposite is non-toxic to eukaryotic cells, the surface of the nanocomposite is suitable for eukaryotic cells for colonization. Due to the combination of self-healing properties, low cytotoxicity, and the presence of bacteriostatic properties, the nanocomposite can be used as a reusable dry disinfectant, as well as a material used in prosthetics.


The molecular basis of multiple vector insertion by gene targeting in mammalian cells.
Gene targeting using sequence insertion vectors generally results in integration of one copy of the targeting vector generating a tandem duplication of the cognate chromosomal region of homology. However, occasionally the target locus is found to contain >1 copy of the integrated vector. The mechanism by which the latter recombinants arise is not known. In the present study, we investigated the molecular basis by which multiple vectors become integrated at the chromosomal immunoglobulin mu locus in a murine hybridoma. To accomplish this, specially designed insertion vectors were constructed that included six diagnostic restriction enzyme markers in the Cmu region of homology to the target chromosomal mu locus. This enabled contributions by the vector-borne and chromosomal Cmu sequences at the recombinant locus to be ascertained. Targeted recombinants were isolated and analyzed to determine the number of vector copies integrated at the chromosomal immunoglobulin mu locus. Targeted recombinants identified as bearing >1 copy of the integrated vector resulted from a Cmu triplication formed by two vector copies in tandem. Examination of the fate of the Cmu region markers suggested that this class of recombinant was generated predominantly, if not exclusively, by two targeted vector integration events, each involving insertion of a single copy of the vector. Both vector insertion events into the chromosomal mu locus were consistent with the double-strand-break repair mechanism of homologous recombination. We interpret our results, taken together, to mean that a proportion of recipient cells is in a predetermined state that is amenable to targeted but not random vector integration.


Fluctuation in plasma bone metabolic markers in multiparous and primiparous Holstein cows during early to peak lactation.
Because the role of bone turnover during early to peak lactation in dairy cows is unclear, plasma levels of osteoclast- or collagen-specific bone resorption and osteoblast-specific bone formation markers from postpartum week 3 (W+3) to W+7 were compared with prepartum W-3 levels in multiparous (n = 15) and primiparous (n = 13) Holstein cows. The multiparous group showed a consistently low level of osteoclast-specific bone resorption markers, while collagen-specific resorption and osteoblast-specific formation markers decreased at postpartum W+7 and from W+5, respectively. In the primiparous group, the plasma levels of all three markers decreased from postpartum W+3. These results suggest that the calcium demand during the transition from early to peak lactation in dairy cows is less affected by bone turnover.


RNASE2 Mediates Age-Associated B Cell Expansion Through Monocyte Derived IL-10 in Patients With Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. Ribonuclease A family member 2 (RNase2) is known to have antiviral activity and immunomodulatory function. Although RNASE2 level has been reported to be elevated in SLE patients based on mRNA microarray detection, its pathologic mechanism remains unclear. Here, we confirmed that RNASE2 was highly expressed in PBMCs from SLE patients and associated with the proportion of CD11c+T-bet+ B cells, a class of autoreactive B cells also known as age-associated B cells (ABCs). We showed that reduction of RNASE2 expression by small interfering RNA led to the decrease of ABCs in vitro, accompanied by total IgG and IL-10 reduction. In addition, we demonstrated that both RNASE2 and IL-10 in peripheral blood of lupus patients were mainly derived from monocytes. RNASE2 silencing in monocytes down-regulated IL-10 production and consequently reduced ABCs numbers in monocyte-B cell co-cultures, which could be restored by the addition of recombinant IL-10. Based on above findings, we concluded that RNASE2 might induce the production of ABCs via IL-10 secreted from monocytes, thus contributing to the pathogenesis of SLE.


Temperature control and the role of supplemental oxygen.
Unrecognized and untreated intraoperative hypothermia remains a common avoidable scenario in the modern operating room. Failure to properly address this seemingly small aspect of the total operative care has been shown to have profound negative patient consequences including increased incidence of postoperative discomfort, surgical bleeding, requirement of allogenic blood transfusion, wound infections, and morbid cardiac events. All of these ultimately lead to longer hospitalizations and higher mortality. To avoid such problems, simple methods can be employed by the surgeon, anesthesiologist, and ancillary personnel to ensure euthermia. Similarly, another effortless method to potentially improve surgical outcomes is the liberal use of supplemental oxygen. Promising preliminary data suggests that high-concentration oxygen during and after surgery may decrease the rate of surgical site infections and gastrointestinal anastomotic failure. The precise role of supplemental oxygen in the perioperative period represents an exciting area of potential research that awaits further validation and analysis. In this article, the authors explore the data regarding both temperature regulation and supplemental oxygen use in an attempt to define further their emerging role in the perioperative care of patients undergoing colorectal surgery.


Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases.
Periodontal diseases, such as chronic periodontitis, share common inflammatory risk factors with other systemic and chronic inflammatory disorders. Mucosal tissues, such as oral epithelia, are exposed to environmental stressors, such as tobacco and oral bacteria, that might be involved in promoting a systemic inflammatory state. Conversely, chronic disorders can also affect oral health. This review will summarize recent evidence for the interrelationship between chronic periodontitis and other prevalent chronic diseases such as cardiovascular diseases, diabetes, cancer and chronic respiratory diseases. The association with pregnancy is also included due to possible obstetric complications. We will focus on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have been shown to be increased in patients with chronic periodontitis, in patients with chronic systemic diseases, and in patients with both chronic periodontitis and other chronic diseases. Therefore, an imbalance towards a proinflammatory immune response could underline a bidirectional link between chronic periodontitis and other chronic diseases. Finally, we highlight that a close coordination between dental and other health professionals could promote oral health and prevent or ameliorate other chronic diseases.


Nonequilibrium coupled Brownian phase oscillators.
A model of globally coupled phase oscillators under equilibrium (driven by Gaussian white noise) and nonequilibrium (driven by symmetric dichotomic fluctuations) is studied. For the equilibrium system, the mean-field state equation takes a simple form and the stability of its solution is examined in the full space of order parameters. For the nonequilbrium system, various asymptotic regimes are obtained in a closed analytical form. In a general case, the corresponding master equations are solved numerically. Moreover, the Monte Carlo simulations of the coupled set of Langevin equations of motion is performed. The phase diagram of the nonequilibrium system is presented. For the long time limit, we have found five regimes. Three of them can be obtained from the mean-field theory. One of them, the oscillating regime, cannot be predicted by the mean-field method and has been detected in the Monte Carlo numerical experiments.


Effect of glipizide on insulin secretion and insulin metabolism in obese type II diabetic patients.
This study was designed to explore the short-term effect of glipizide on insulin secretion and metabolism. Plasma insulin and C-peptide levels in the fasting state and after a 100-g oral glucose load were measured in 17 obese newly diagnosed type II (non-insulin-dependent) diabetic subjects before and after 1 mo of treatment with glipizide (15 mg/day). Plasma glucose levels decreased significantly after treatment with glipizide. Plasma insulin and C-peptide concentrations in the fasting state did not change after glipizide treatment. Also, postglucose plasma insulin levels did not change after glipizide, whereas postglucose plasma C-peptide concentrations significantly increased. A significant relationship was found between the increase in C-peptide plasma levels and the decrease in glycemic profile after glucose load following glipizide treatment. The relation between plasma C-peptide and insulin incremental areas after the oral glucose load significantly increased after treatment. These results suggest that in obese type II diabetic patients, 1 mo of treatment with glipizide potentiates the beta-cell response to oral glucose load and increases insulin metabolism, probably within the liver.


A Case of Hand-Foot-and-Mouth Disease in an Adult Male.
Hand-foot-and-mouth disease (HFMD) is commonly seen in infants and children; less frequently, it may be seen in adults as well. The disease is usually associated with viral infections, including many variants of enteroviruses and coxsackieviruses. We discuss the case of a 39-year-old male who presented with constitutional symptoms, fever, and lesions on his hands, feet, and mouth. His children, who had been recently diagnosed with HFMD, were likely the source of his infection. A comprehensive history and physical examination enabled us to identify the lesions, some of which were faint and difficult to visualize. Viral panel testing indicated positive results for human rhinovirus/enterovirus. Treatment and testing associated with the patient's condition were supportive, largely based on the history and physical findings which helped us narrow down our differential diagnoses. Complete resolution of the symptoms within one to two weeks is generally expected in these patients.


AMPK inhibitor BML-275 induces neuroprotection through decreasing cyt c and AIF expression after transient brain ischemia.
Stroke is a major public health problem with an imperative need for a more effective and tolerated therapy. Neuroprotective therapy may be an effective therapeutic intervention for stroke. The morbidity and mortality of stroke-induced secondary brain injury is mainly caused by neuronal apoptosis, which can be executed in a caspase-dependent or apoptosis inducing factor (AIF)-dependent manner. As apoptosis is an energy-dependent process with a relative time delay, abnormal energy metabolism could be a significant and fundamental pathophysiological basis of stroke. To our knowledge, convincible evidences that AMPK inhibition exerts neuroprotection in cerebral ischemia injury via anti-apoptosis remain to be investigated. Accordingly, the aims of this study were to investigate the protective effects of AMPK inhibitor BML-275 on cerebral ischemic/reperfusion (I/R) injury and to elucidate the underlying mechanisms. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) in male C57BL/6 mice. The therapeutic effects of BML-275 were evaluated by infarct sizes, neurological scores and the proportion of apoptotic neurons after 24 h of reperfusion. The cell apoptosis markers cyt c and AIF were also evaluated. The results showed that intraperitoneally administration of BML-275 alleviate the cerebral infarction, neurological deficit and neuronal apoptosis induced by MCAO. BML-275 simultaneously induces anti-apoptosis and decreases the expression of cyt c and AIF. This study supports the hypothesis that anti-apoptosis is one of potential neuroprotective strategies for the treatment of stroke.


Painful knee prosthesis: can we help with bone SPECT/CT?
The aim of the study was to evaluate the value of single-photon emission computerized tomography/computed tomography (SPECT/CT) in the clinical assessment of painful knee prostheses. Between 2009 and 2011 we identified 105 patients who had undergone Tc-hydroxydiphosphonate SPECT/CT for painful knee prosthesis. Complete follow-up data were available for 69 patients (50 women and 19 men; mean age, 71 years) with painful knee prostheses (59 total, nine unicompartmental, one patellofemoral) and clinical suspicion of infection or loosening. The imaging test report in conjunction with the clinical data from the patient's notes was used to gauge how useful the test had been in terms of patient management. SPECT/CT confirmed the suspected clinical diagnosis of loosening in nine patients (13%) and of infection in two (2.9%) and identified other causes in 43 patients (62.3%). In 85.5% of patients, SPECT/CT was clinically useful (both positive and negative results), whereas in 14.5% it had no clinical impact on patient management. Revision surgery was performed in 24/69 (34.8%) patients and confirmed the SPECT/CT diagnosis in 21 patients (seven loosening, one infection, two subchondral fractures, two postoperative inflammation and nine patellofemoral osteoarthritis). SPECT/CT is a useful tool for the evaluation of painful knee prosthesis in 85.5% of cases and helps in confirming mechanical loosening and in excluding other causes such as infection and patellofemoral osteoarthritis.


Validity and inter-rater reliability of inertial gait measurements in Parkinson's disease: a pilot study.
Walking models driven by centre of mass (CoM) data obtained from inertial measurement units (IMU) or optical motion capture systems (OMCS) can be used to objectively measure gait. However current models have only been validated within typical developed adults (TDA). The purpose of this study was to compare the projected CoM movement within Parkinson's disease (PD) measured by an IMU with data collected from an OMCS after which spatio-temporal gait measures were derived using an inverted pendulum model. The inter-rater reliability of spatio-temporal parameters was explored between expert researchers and clinicians using the IMU processed data. Participants walked 10 m with an IMU attached over their centre of mass which was simultaneously recorded by an OMCS. Data was collected on two occasions, each by an expert researcher and clinician. Ten people with PD showed no difference (p=0.13) for vertical, translatory acceleration, velocity and relative position of the projected centre of mass between IMU and OMCS data. Furthermore no difference (p=0.18) was found for the derived step time, stride length and walking speed for people with PD. Measurements of step time (p=0.299), stride length (p=0.883) and walking speed (p=0.751) did not differ between experts and clinicians. There was good inter-rater reliability for these parameters (ICC3.1=0.979, ICC3.1=0.958 and ICC3.1=0.978, respectively). The findings are encouraging and support the use of IMUs by clinicians to measure CoM movement in people with PD.


Whole cow's milk in infancy.
Early introduction of whole cow's milk may lead to iron deficiency anemia. From a nutritional point of view, it is best to delay the introduction of whole cow's milk until the infant is one year old. While there is no evidence to suggest adverse clinical sequelae associated with the increased renal solute load in healthy infants, feeding with whole cow's milk would narrow the margin of safety in situations that may lead to dehydration. Early exposure to cow's milk proteins increases the risk of developing allergy to milk proteins. Because of the possible association between early exposure to cow's milk proteins and risk for type 1 diabetes mellitus, breast-feeding and avoidance of commercially available cow's milk and products containing intact cow's milk protein during the first year of life are strongly encouraged in families with a strong history of insulin dependent diabetes mellitus. The authors suggest that the optimal food in infancy is human breast milk. If human milk is not available, it is preferred that iron-fortified formulas rather than whole cow's milk be used during the first year of life.


Role of carrier ligand in platinum resistance of human carcinoma cell lines.
We have examined the effects of the cis-diammine and 1,2-diaminocyclohexane (dach) carrier ligands on cytotoxicity, platinum accumulation and efflux, platinum incorporation into DNA, cytotoxicity of Pt-DNA adducts, and repair of Pt-DNA adducts in the human ovarian carcinoma A2780 cell line, the human colon carcinoma HCT8 cell line, and their cis-diamminedichloroplatinum(II) (cisplatin)-resistant derivatives, A2780/DDP and HCT8/DDP. The A2780/DDP cell line was 7.7-fold resistant to cisplatin, and the HCT8/DDP cell line was 1.6-fold resistant to cisplatin compared to their parental cell lines. Both were considered as examples of acquired cisplatin resistance. The HCT8/S cell line was 4.6-fold resistant to cisplatin compared with the A2780/S cell line and was considered an example of intrinsic resistance. Decreased accumulation of cisplatin made a significant contribution to acquired cisplatin resistance in the A2780/DDP cell line, probably contributed to intrinsic resistance in the HCT8/S cell line, but made little or no contribution to acquired resistance in the HCT8/DDP cell line. Decreased cytotoxicity of Pt-DNA adducts made a major contribution to both acquired and intrinsic cisplatin resistance in all three cell lines. Increased repair activity made a significant contribution to the decreased cytotoxicity of Pt-DNA adducts in the HCT8/S cell line, a weak contribution in the A2780/DDP cell line, and no contribution in the HCT8/DDP cell line. Glutathione levels were elevated in all the cell lines with acquired and intrinsic resistance, but the increased glutathione levels were not associated with decreased incorporation of platinum into DNA. These data suggest that both decreased accumulation and increased repair contribute to cisplatin resistance to different degrees in these human carcinoma cell lines. In addition, mechanism(s) other than repair may contribute to the decreased cytotoxicity of cis-diammine-Pt-DNA adducts. Of the cells with acquired cisplatin resistance, the HCT8/DDP cell line showed no resistance to tetrachloro(trans-DL)1,2-diaminocyclohexaneplatinum(IV) (ormaplatin, formerly known as tetraplatin), while the A2780/DDP cell line was just as resistant to ormaplatin as to cisplatin. The intrinsically cisplatin-resistant HCT8/S cell line showed only partial cross-resistance to ormaplatin. The effects of the dach carrier ligand on both acquired and intrinsic resistance in these cell lines appeared to occur primarily at the level of cytotoxicity of dach-Pt adducts, but the differences in the cytotoxicity of cis-diammine-Pt and dach-Pt adducts could not be explained by differences in repair of those adducts.(ABSTRACT TRUNCATED AT 400 WORDS)


Terpenoid biosynthesis from 1-deoxy-D-xylulose in higher plants by intramolecular skeletal rearrangement.
The incorporation of [1-13C]- and [2,3,4,5-13C4]1-deoxy-D-xylulose into beta-carotene, lutein, phytol, and sitosterol in a cell culture of Catharanthus roseus was analyzed by NMR spectroscopy. The labeling patterns of the isoprene precursors, isopentenyl pyrophosphate and dimethylallyl pyrophosphate, were obtained from the terpenes by a retrobiosynthetic approach. 13C Enrichment and 13C13C coupling patterns showed conclusively that 1-deoxy-D-xylulose and not mevalonate is the predominant isoprenoid precursor of phytol, beta-carotene, and lutein. Label from 1-deoxyxylulose was also diverted to phytosterols to a minor extent (6% relative to carotene and phytol formation). The data demonstrate that the formation of isopentenyl pyrophosphate from pentulose occurs strictly by an intramolecular rearrangement process.


[Effect of intraperitoneal therapy in gastric cancer with peritoneal dissemination].
Eighty gastric cancer patients with peritoneal dissemination were analyzed to evaluate the effect of intraperitoneal chemo- and/or immunotherapy on abdominal ascites. Among them, 19 were treated with intraperitoneal chemo- and/or immunotherapy, and 21.1% of them showed decreased ascites and better QOL. Patients treated with intraperitoneal administration with OK-432 showed good survival. Among patients with OK-432 administration, those receiving postoperative chemotherapy showed better survival than those given immunochemotherapy. Conversely, among patients with chemotherapy, those given postoperative immunochemotherapy showed better survival than those on chemotherapy. Patients with HLA-type I and III, and those with preoperative normal immune status showed good response when they received intraperitoneal therapy.


Antifungal and antibiofilm activities of chromones against nine Candida species.
The persistence of Candida infections is due to its ability to form biofilms that enable it to resist antifungals and host immune systems. Hence, inhibitions of the biofilm formation and virulence characteristics of Candida sp. provide potential means of addressing these infections. Among various chromone derivatives tested, four chromone-3-carbonitriles showed antifungal, antibiofilm, and antivirulence activities against several Candida species. Their mode of action has been partially revealed, and their toxicity is reported here using nematode and plant models.


Neurobehavioral and transcriptional effects of acrylamide in juvenile rats.
Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in juvenile rats. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of a few genes that are involved in muscle contraction, pain, and dopaminergic neuronal pathways. First, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified a few genes previously not implicated in acrylamide neurotoxicity that might be further developed into biomarkers for assessing the risk of adverse health effects induced by acrylamide exposure.


Survey on lost and poorly controlled radioactive sources in non-medical applications in Iran.
Despite well-developed Regulatory Authority systems for radiation protection, there are some concerns about lost-controlled and poorly controlled radioactive sources owing to abundance and dispersion of the users. This survey covers the current situation of the categories 3 through 5 of radioactive sources (based on the categorisation of the IAEA) in non-medical applications in Iran. The investigation performed on a selected group of non-medical users of radioactive sources in different provinces of Iran. Findings show that unauthorised supply and legacy sources in addition to abandonment of sources under regulatory control are the main reasons for lost-controlled sources. Considering the possibility of increasing poorly controlled sources which can lead to increase in the number of lost-controlled sources, further developments are needed in national regulatory control as well as international cooperation and discipline in this regard.