'I wasn't made to feel like a nut case after all': A qualitative story completion study exploring healthcare recipient and carer perceptions of good professional caregiving relationships.
Professional caregiving relationships are central to quality healthcare but are not always developed to a consistently high standard in clinical practice. Existing literature on what constitutes high-quality relationships and how they should be developed is plagued by dyadic conceptualisations; discipline, context and condition-specific research; and the absence of healthcare recipient and informal carer voices. This study aimed to address these issues by exploring how healthcare recipients and carers conceptualise good professional caregiving relationships regardless of discipline, care setting and clinical condition. A qualitative story completion approach was used. Participants completed a story in response to a hypothetical stem that described a healthcare recipient (and, in some instances, carer) developing a good relationship with a new healthcare provider. Stories were analysed using reflexive thematic analysis. Participants were 35 healthcare recipients and 37 carers (n = 72 total). Participants' stories were shaped by an overarching discourse that seeking help from new providers can elicit a range of unwanted emotions for both recipients and carers (e.g., anxiety, fear, dread). These unwanted emotions were experienced in relation to recipients' presenting health problems as well as their anticipated interactions with providers. Specifically, recipient and carer characters were fearful that providers would dismiss their concerns and judge them for deciding to seek help. Good relationships were seen to develop when healthcare providers worked to relieve or minimise these unwanted emotions, ensuring healthcare recipients and carers felt comfortable and at ease with the provider and the encounter. Participants positioned healthcare providers as primarily responsible for relieving recipients' and carers' unwanted emotions, which was achieved via four approaches: (1) easing into the encounter, (2) demonstrating interest in and understanding of recipients' presenting problems, (3) validating recipients' presenting problems and (4) enabling and respecting recipient choice. Participants' stories also routinely oriented to temporality, positioning relationships within recipients' and carers' wider care networks and biographical and temporal contexts. The findings expand our understanding of professional caregiving relationships beyond dyadic, static conceptualisations. Specifically, the findings suggest that high-quality relationships might be achieved via a set of core healthcare provider behaviours that can be employed across disciplinary, context and condition-specific boundaries. In turn, this provides a basis to support interprofessional education and multidisciplinary healthcare delivery, enabling different healthcare disciplines, specialties, and teams to work from the same understanding of what is required to develop high-quality relationships. The findings are based on stories from 72 healthcare recipient and carer participants, providing rich insight into their conceptualisations of high-quality professional caregiving relationships.


Cephamycins, a new family of beta-lactam antibiotics: antibacterial activity and resistance to beta-lactamase degradation.
The susceptibility to some cephalosporin antibiotics and to cephamycin C, a member of a new family of beta-lactam antibiotics, was evaluated for 466 cultures representing 11 different genera or species of gram-negative clinical isolates. The susceptibility of 39 gram-negative cultures known to produce beta-lactamase was also determined. The beta-lactamase activity of a representative group of the clinical isolates and the 39 enzyme producers was studied with the cephalosporins (cephalothin and cephaloridine) and cephamycin C as substrates and was related to the in vitro disc susceptibility to these same antibiotics. The significant resistance to beta-lactamase displayed by the cephamycins is reflected in the kinetics of enzyme activity (K(m) and V(max)) that are reported for the cephalosporins and the cephamycins. Resistance to beta-lactamase is probably one of the reasons that many cephalosporin-resistant cultures are susceptible to cephamycin C.


Efficacy of continuous neuromonitoring in thyroid surgery: preliminary report of a single-center experience.
The continuous intraoperative nerve monitoring (CIONM) technique seems to be acknowledged as a useful tool to prevent impending nerve injury, because it constantly provides valuable real-time information. Aim of the study is to evaluate the impact of the CIONM technique on functional outcome i.e., recurrent laryngeal nerve (RLN) palsy, compared to the traditional surgical procedure. From January to December 2016, 197 patients who underwent thyroid surgery were included in this retrospective study: 94 patients had CIONM procedure and 103 traditional technique, according to the order of the operating room list. A total of 8 patients showed a damage to left or right vocal cord: 3 patients after CIONM procedure, and 5 patients after traditional surgical procedure. After matching for propensity score, 188 patients were eventually considered and 7 RLN palsy were identified: 3 in CIONM and 4 in traditional surgical procedure. The analysis performed on the matched propensity score sample showed a non-significant difference between the two procedures. In our experience no significant differences in functional outcomes were found between the use of CIONM and the standard technique.


A description method of handprinted chinese characters.
A description method of handprinted Chinese characters is presented. In the method, a Chinese character is composed of some partial patterns which are constructed using the concatenate relation, cross relation, and near relation. The relations of relative location among partial patterns are used for categorization of the partial pattems. A Chinese character is expressed from the results of categorization.


Endoanal ultrasound in perirectal abscesses.
Transrectal ultrasound is a useful exploration in the assessment of local spread of rectal tumors. The aim of this study has been the knowledge of the results of transrectal ultrasound in perirectal abscesses. Forty patients suffering from perianal septic disease were examined with endoanal echography before surgical approach. The endorectal probe used was initially of 5 MHz and in the last 25 patients of 7.5 MHz. The examination could not be done in 8 patients because severe pain originated by the introduction of the probe in the anal canal. The echographic findings show the exact location and extension of the abscesses as confirmed by the surgical exploration. In three patients we suspected a perirectal abscess due to fever and anal pain but the anal exploration was normal; the ultrasonography showed the collection in all patients and two of them were treated by echoguided drainage. Transrectal ultrasonography localizes and defines the extension of perirectal abscesses. It is a very important diagnostic and therapeutic tool in patients with clinical presumption, but not confirmation, of what kind of abscesses.


[Myocardial myoglobin in some types of cardiac pathology in the far northeastern USSR].
Immunomorphological and biochemical study of the myoglobin in the myocardium of 118 males at the age of from 30 to 55 years who died suddenly from coronary insufficiency, chronic pulmonary-cardiac insufficiency and from alcoholic cardiomyopathy in Magadan and Moscow is described. A decrease of the myoglobin concentration is revealed in the myocardium of the practically healthy Magadan citizeus as compared to that of moscovites. When the death occurred suddenly reduction of the myoglobin content is noted in the left ventricle simultaneously with its hypertrophy. It is shown immunomorphologically that myoglobin in the cytoplasm of cardiomyocytes is observed in the form of dense foci, granules and streaks. The myoglobin concentration tend to the reduction when there was hypertrophy of the right ventricle in patients dying from chronic pulmonary-cardiac insufficiency. Almost two-fold decrease of the myoglobin concentration in the left ventricle without its visible hypertrophy was observed in alcoholic cardiomyopathy, this may serve as a complementary test in the diagnosis of this disease.


Effect of vanadium on tissue respiration in organs and on cholesterol metabolism in guinea pigs with experimental atheroclerosis.
In experiments on guinea pigs with experimental atherosclerosis, vanadium pentoxide retarded the development of vascular pathomorphological changes, supported cholesterol metabolism, and activated oxidoreductive processes. Correlation and regression analyses proved that vanadium pentoxide has a beneficial effect on the course of experimental atherosclerosis in guinea pigs to the influence of this drug on oxido-reductive processes.


Inpatient views and experiences before and after implementing a totally smoke-free policy in the acute psychiatry hospital setting.
In the present study, we examined the views and experiences of patients admitted to an acute psychiatry unit before and after the implementation of a totally smoke-free policy. Forty-six inpatients completed a questionnaire assessing their views before the smoking ban. Another 52 inpatients completed a questionnaire assessing their views and experiences after the smoking ban. Before the totally smoke-free policy, 69.6% smoked, with 67.7% smoking more when admitted to the psychiatry ward. Before the smoking ban, 54.4% reported that the totally smoke-free policy would be 'negative' or 'very negative,' and 30.5% said it would be 'positive' or 'very positive.' After the totally smoke-free policy, 57.7% smoked heavily before hospital (mean cigarettes/day = 24.9), with consumption dramatically reducing following admission to a totally smoke-free psychiatric unit (mean cigarettes/day = 8.3). After the totally smoke-free policy, 36.5% reported that it was 'negative' or 'very negative,' and 50% reported that it was 'positive' or 'very positive.' Overall, inpatients reported improved acceptance of the policy following implementation. Inpatients stated that the most difficult thing about the smoking ban was experiencing increased negative emotions, while the most positive aspect was the improved physical environment of the ward. Inpatients who smoke must be appropriately supported using a range of strategies, and in the present study, we suggest relevant clinical implications.


The impact of COVID-19 and the COVID-19 pandemic on hospitalized patients with STEMI in the United States: insights from the National Inpatient Sample.
It is unclear how COVID-19 pandemic affected care and outcomes among patients who are diagnosed with ST-elevation myocardial infarction (STEMI) in the USA. We analyzed the data from National Inpatient Sample from 2016 to 2020 and assessed the impact of COVID-19 infection and the COVID-19 pandemic (year 2020) on in-hospital mortality, length of stay (LOS) and hospitalization costs.P. There were 1 050 905 hospitalizations with STEMI, and there was an 8.2% reduction in admissions in 2020. Patients with COVID-19 versus those without had significantly greater in-hospital mortality (45.2% vs. 10.7%; P < 0.001). In 2020, 3.0% of hospitalizations had a diagnosis of COVID-19, and the mortality was 11.5% compared to 10.7% for patients admitted in 2016-2019 period. There was a significantly increased mortality (OR 6.25, 95% CI 5.42-7.21, P < 0.001), LOS (coefficient 3.47, 95% CI 3.10-3.84, P < 0.001) and cost (coefficient 10.69, 95% CI 8.4-12.55, P < 0.001) with COVID-19 infection compared with no infection. There was a borderline difference in mortality (OR 1.04, 95% CI 1.00- 1.09, P = 0.050) but LOS (coefficient -0.21, 95% CI-0.28 to -0.14, P < 0.001) and costs (3.14, 95% CI 2.79 to 3.49, P < 0.001) were reduced in 2020 compared to 2016-2019 period. In conclusion, in patients hospitalized with STEMI, COVID-19 infection was associated with increased mortality, LOS, and cost but during the pandemic year of 2020 there was a small trend for increased mortality for patients with a diagnosis of STEMI.


[Genome of influenza virus: organization, function, evolution].
Basic features of influenza virus genome structure, replication and evolution are reviewed with a special emphasis upon the segmentary structure of the genome and the use of cell mRNA as primer in virus-specific transcription. The structural and functional autonomy of virus genomic segments and the selection of the segments in the process of viral genome assembly is considered to be the basis for the gene reassortment and the appearance of recombinants. The reassortment of genes is discussed in relation to the nature of "new" antigenic subtypes of human influenza A virus, that is, to the orivin of antigenic shifts and pandemic strains. Another kind of antigenic variation (antigenic drift) is produced by the accumulation of mutations under the conditions of selection pressure in an immune population. Together with the conservation of earlier antigenic subtypes in animal populations these two types of evolutionary changes produce a complex pattern of influenza virus evolution. The prospects of influenza control are briefly discussed in connection with the characteristics of influenza virus genome structure and evolution.


Lipoprotein interconversions in an insect, Manduca sexta. Evidence for a lipid transfer factor in the hemolymph.
Hemolymph lipoproteins (lipophorins) of adult Manduca sexta are disinct from larval forms in density, lipid content, composition, and the presence of a third, low molecular weight apoprotein. Generally, only one lipoprotein species exists in M. sexta hemolymph during any given life stage. Progression through the life cycle results in alterations of existing lipoproteins to produce new forms, without new protein synthesis. The observed alterations in lipoprotein density could result from facilitated lipid transfer in insect hemolymph. An in vitro assay of facilitated lipid transfer was developed which employs a high density lipophorin from the wandering larva (density = 1.18 g/ml) as acceptor and adult low density lipophorin (density = 1.03 g/ml) as donor. Adult lipophorin-deficient hemolymph was shown to catalyze a time-dependent equilibration of the starting lipoproteins to produce a new intermediate lipophorin, Lp-I. Hydrodynamic experiments on the donor, acceptor, and product lipoproteins excluded fusion as the mechanism whereby Lp-I is produced. Thus, it is concluded that Lp-I results from facilitated net lipid transfer from low to high density lipoprotein. Furthermore, experiments conducted with radioiodinated donor and radioiodinated acceptor lipoproteins demonstrated that apoprotein exchange does not occur during the lipid transfer reaction. When donor lipoprotein was labeled in the lipid moiety with carbon-14, evidence of diacylglycerol and phospholipid exchange was obtained. Partial characterization of the lipid transfer factor revealed a relationship between incubation time, donor concentration, acceptor concentration, lipophorin-deficient hemolymph concentration, and transfer activity, as measured by Lp-I production. It is concluded that lipophorin-deficient hemolymph contains one or more factor(s) that catalyze net lipid transfer as well as diacylglycerol and phospholipid exchange between lipophorins to produce a single form at equilibrium.


The Therapeutic Landscape of Renal Cell Carcinoma: From the Dark Age to the Golden Age.
Oncologic treatments for renal cell carcinoma (RCC) have undergone a major revolution in the past 2 decades, moving away from the pre-2004 Dark Age during which interleukin 2 and interferon-α were the only therapeutic options and induced treatment responses in only 5% to 10% of patients with metastatic disease. The development of anti-angiogenic tyrosine kinase inhibitors against vascular endothelial growth factor receptor 2 and inhibitors of mammalian target of rapamycin complex 1 in 2005 introduced the Modern Age with better overall and progression-free survival and a greater number of patients (30%-40%) responding to and (∼80%) benefiting from these targeted therapeutic agents. The coming of age of the immuno-oncology era with the use of immune checkpoint inhibitors (ICIs) have ushered us into the Golden Age of metastatic RCC care, in which combined administrations of two ICIs (anti-programmed cell death protein 1/programmed death-ligand 1 and anti-cytotoxic T-lymphocyte-associated protein 4 or one tyrosine kinase inhibitor plus one ICI (anti-programmed cell death protein 1/programmed death-ligand 1) have recast the treatment landscape of clear cell RCC, the most common RCC subtype, with an approximately 60% response rate and an approximately 90% disease control rate that further improves metastatic RCC survival. Exciting clinical trials are in the pipeline investigating complementary/synergistic molecular mechanisms, based on studies investigating the biology, pathology, and genomics of renal carcinoma and the respective treatment outcome. This will enable us to enter the Diamond Age of precision medicine in which a specific treatment can be tailored to the specific biological and pathologic circumstance of an individual kidney tumor to offer more effective yet less toxic therapy.


Neural crest progenitors and stem cells: from early development to adulthood.
In the vertebrate embryo, the neural crest forms transiently in the dorsal neural primordium to yield migratory cells that will invade nearly all tissues and later, will differentiate into bones and cartilages, neurons and glia, endocrine cells, vascular smooth muscle cells and melanocytes. Due to the amazingly diversified array of cell types it produces, the neural crest is an attractive model system in the stem cell field. We present here in vivo and in vitro studies of single cell fate, which led to the discovery and the characterization of stem cells in the neural crest of avian and mammalian embryos. Some of the key issues in neural crest cell diversification are discussed, such as the time of segregation of mesenchymal vs. neural/melanocytic lineages, and the origin and close relationships between the glial and melanocytic lineages. An overview is also provided of the diverse types of neural crest-like stem cells and progenitors, recently identified in a growing number of adult tissues in animals and humans. Current and future work, in which in vivo lineage studies and the use of injury models will complement the in vitro culture analysis, should help in unraveling the properties and function of neural crest-derived progenitors in development and disease.


Feasibility of simultaneous pre- and postfilter transcranial Doppler monitoring during carotid artery stenting.
Carotid artery stenting (CAS) is emerging as an acceptable treatment alternative to surgery for patients with carotid artery stenosis. The major risk of CAS is cerebral embolization of plaque and thrombus causing stroke or asymptomatic brain infarction. Use of embolic protection devices (EPD) to trap emboli before they reach the brain is now standard practice in CAS. The pore size of the currently available filters is >100 microns and emboli smaller than the EPD pores can still reach the brain. While the use of EPD is widespread, little evidence exists of their in vivo efficacy in preventing distal embolization. Our aim was to quantify the number of emboli reaching the brain with the device in place. Therefore, the expected value of this report is in its description of a novel application of transcranial Doppler (TCD). Due to the limited number of cases, it is not intended to support the use of one EPD over another. Six patients were monitored with ipsilateral simultaneous dual probe TCD during CAS. Two types of cerebral protection systems were evaluated: FilterWire EZ System (FW; Boston Scientific, Santa Clara, Calif) and GORE Neuro Protection System (NPS; W.L. Gore and Associates, Flagstaff, Ariz). By placing TCD probes both proximal and distal to the filterwire EPD, we quantified the microembolic signals before the EPD as well as those, which reached the intracranial circulation after the EPD. One probe was placed submandibularly to monitor the ICA (SICA), while another was placed transtemporally to monitor the middle and anterior cerebral artery (MCA + ACA). We compare the number of extracranial emboli prior to the EPD with the number of intracranial emboli after the EPD. Dual probe monitoring was successful during the five stages of the CAS: lesion crossing (LC), predilatation (PreD), stent placement (SP), postdilatation (PostD), and filter/device removal (FR/DR). Using FW during LC by probe 1 (SICA)/probe 2 (MCA + ACA): (18 [range, 15-22]/15 [range, 11-20]), PreD (111 [range, 101-121]/101 [range, 90-111]), SP (68 [range, 60-76]/42 [range, 30-53]), PostD (27 [range, 25-30]/24 [range, 22-27]), FR (0.3 [range, 0-1]/0.7 [range, 0-1]) average number of microembolic signals were detected. Using NPS during LC (1.7 [range, 0-3]/1 [range, 0-2]), PreD (0/1.7 [range, 0-4]), SP (0/0), PostD (0/0), DR (18 [range, 0-18]/6.7 [range, 1-13]) average number of microembolic signals were detected. EPD significantly reduces but does not eliminate the number of microemboli reaching the brain during carotid artery angioplasty and stenting. We propose monitoring of CAS with submandibular and transtemporal TCD probes to further evaluate the practice of distal embolization protection. Although our study is not powered to make any recommendations about EPDs, we believe that sequential dual probe TCD monitoring is a worthy tool with the potential to give vital information to assess the various devices and the techniques of utilization.


Exercise protects against insulin-dependent diabetes-induced osteoarthritis in rats: A scanning electron microscopy study.
We tested the hypothesis that swim exercise can protect the articular cartilage from damages induced secondary to insulin-dependent diabetes mellitus in rats using the scanning electron microscopy and to monitor the blood levels of oxidative and antioxidative stress biomarkers that are known to be modulated in osteoarthritis (OA). A profound damage to the cartilage was observed in the diabetic rats. Our findings also show that swim exercise protects the knee joints from damage induced by diabetes as well as significantly inhibiting OA-induced upregulation of thiobarbituric acid reactive substances (TBARS) and tumor necrosis factor alpha (TNF-α) and augmented superoxide dismutase (SOD) inhibition by OA. Thus, we demonstrated an effective protection by swim exercise against diabetes-induced OA in a rat model of the disease.


Pig manure contamination marker selection based on the influence of biological treatment on the dominant fecal microbial groups.
The objective of this study was to identify a microbial marker for pig manure contamination. We quantified the persistence of four dominant bacterial groups from the pig intestinal tract throughout manure handling at 10 livestock operations (including aerobic digestion) by using molecular typing. The partial 16S rRNA genes of Bacteroides-Prevotella, Eubacterium-Clostridiaceae, Bacillus-Streptococcus-Lactobacillus (BSL), and Bifidobacterium group isolates were amplified and analyzed by capillary electrophoresis single-strand conformation polymorphism. The most dominant bacterial populations were identified by cloning and sequencing their 16S rRNA genes. The results showed that Bifidobacterium spp. and, to a lesser extent, members of the BSL group, were less affected by the aerobic treatment than either Eubacterium-Clostridiaceae or Bacteroides-Prevotella. Two Bifidobacterium species found in raw manure were still present in manure during land application, suggesting that they can survive outside the pig intestinal tract and also survive aerobic treatment. The 16S-23S rRNA internal transcribed spacer of one species, Bifidobacterium thermacidophilum subsp. porcinum, was sequenced, and a specific pair of primers was designed for its detection in the environment. With this nested PCR assay, this potential marker was not detected in samples from 30 bovine, 30 poultry, and 28 human fecal samples or in 15 urban wastewater effluents. As it was detected in runoff waters after spreading of pig manure, we propose this marker as a suitable microbial indicator of pig manure contamination.


Low doses of lithium carbonate reduce melatonin light sensitivity in healthy volunteers.
Sensitivity of the pineal hormone melatonin to bright light at night has been posited as a putative marker of affective disorders. Research demonstrates melatonin supersensitivity to light in bipolar disorder, however the role that lithium carbonate plays in this response is unclear. This study assessed the effect of lithium on nocturnal melatonin secretion and sensitivity to light in healthy adults. Ten participants, tested on two nights, had blood samples drawn between 20:00 and 02:30 hours. On testing nights participants were exposed to 200 lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium daily for 5 d between testing nights. The results indicated that lithium had a significant effect on sensitivity to light but not on overall melatonin synthesis. This finding has implications on the true magnitude of the melatonin light response in people with bipolar disorder and may elucidate possible mechanisms of action of lithium.


KETCH1 imports HYL1 to nucleus for miRNA biogenesis in Arabidopsis.
MicroRNA (miRNA) is processed from primary transcripts with hairpin structures (pri-miRNAs) by microprocessors in the nucleus. How cytoplasmic-borne microprocessor components are transported into the nucleus to fulfill their functions remains poorly understood. Here, we report KETCH1 (karyopherin enabling the transport of the cytoplasmic HYL1) as a partner of hyponastic leaves 1 (HYL1) protein, a core component of microprocessor in Arabidopsis and functional counterpart of DGCR8/Pasha in animals. Null mutation of ketch1 is embryonic-lethal, whereas knockdown mutation of ketch1 caused morphological defects, reminiscent of mutants in the miRNA pathway. ketch1 knockdown mutation also substantially reduced miRNA accumulation, but did not alter nuclear-cytoplasmic shuttling of miRNAs. Rather, the mutation significantly reduced nuclear portion of HYL1 protein and correspondingly compromised the pri-miRNA processing in the nucleus. We propose that KETCH1 transports HYL1 from the cytoplasm to the nucleus to constitute functional microprocessor in Arabidopsis This study provides insight into the largely unknown nuclear-cytoplasmic trafficking process of miRNA biogenesis components through eukaryotes.


Diffusible factors in anuran fertilization.
Anuran eggs are shed surrounded by a jelly material which is deposited by the oviduct as they descend through it. As soon as they come in contact with water, some components are released from the jelly coats into the inseminating inedium. The present review summarizes the information bearing on the problem of these diffusible factor involvement in fertilization. Evidence exists indicating that they are likely to exert some specific as well as protective influence on the spermatozoon. Their activity is discussed in connection to the acrosome reaction and the role of the jelly in the fertilization process. Attention is also drawn to some adaptive features of anuran fetrillization, suggesting that they would represent a transitional form between typically external and internal fertilization.


Role of enzymatic N-hydroxylation and reduction in flutamide metabolite-induced liver toxicity.
Flutamide is used for prostate cancer therapy but occasionally induces severe liver injury. Flutamide is hydrolyzed in the body into 5-amino-2-nitrobenzotrifluoride (FLU-1) and then further oxidized. In our previous study, N-hydroxy FLU-1 (FLU-1 N-OH) was detected in the urine of patients and exhibited cytotoxicity in rat primary hepatocytes. In the present study, we have assessed the roles of FLU-1 N-oxidation and hepatic glutathione (GSH) depletion in liver injury. FLU-1 (200 mg/kg p.o.) was administered to C57BL/6 mice for 5 days together with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) (3 mg/kg i.p.) for the first 3 days. Mice were fasted for the last 2 days to deplete hepatic GSH. Administration of FLU-1 alone did not affect serum alanine aminotransferase activities (ALT), whereas coadministration of FLU-1 and TCPOBOP significantly increased ALT in fasted mice but not in nonfasted mice. Microsomal FLU-1 N-hydroxylation was enhanced approximately 5 times by TCPOBOP treatment. Flutamide metabolite-protein adducts were detected in liver microsomes incubated with FLU-1 N-OH, but not with FLU-1 and flutamide, by immunoblotting using antiflutamide antiserum. In the presence of mouse liver cytosol, FLU-1 N-OH was reduced back into FLU-1. This enzymatic reduction required NAD(P)H as a cofactor. The reduction was enhanced by the coexistence of NAD(P)H and GSH, whereas it was markedly inhibited by allopurinol (20 microM). By using purified bovine xanthine oxidase, the reduction was observed in the presence of NAD(P)H. These results suggest that FLU-1 N-OH is involved in flutamide-induced hepatotoxicity and that cytosolic reduction of FLU-1 N-OH plays a major role in protection against flutamide-induced hepatotoxicity.


Evaluation of plakophilin-3 mRNA as a biomarker for detection of circulating tumor cells in gastrointestinal cancer patients.
This study aims to assess Plakophilin-3 (PKP3) as a surrogate biomarker of circulating tumor cells in patients with gastrointestinal cancer. The primary aim is to estimate the diagnostic accuracy of PKP3 real-time reverse transcriptase-PCR in blood. Receiver operating characteristic curves were constructed. Correlations between the blood PKP3 levels and the clinicopathologic features of the study subjects were analyzed. Logistic regression was used to predict outcomes based on PKP3. Sixty-four patients with gastrointestinal cancer and 23 controls were included. The mean relative PKP3 mRNA expression was 48.45 in cancer patients and 2.8 in controls (P < 0.0001). Comparing the PKP3 levels in patients and controls, the area under the curve was 0.852 (95% confidence interval, 0.76-0.94; P < 0.0001) in receiver operating characteristic analysis. A higher blood level of PKP3 mRNA was associated with a more advanced stage (P = 0.025), pT(3-4) tumors (P = 0.028), metastasis (P = 0.021), and residual (R2) disease (P = 0.037). Higher PKP3 mRNA was associated with the risk of cancer progression and death (odds ratio, 3.875; 95% confidence interval, 1.781-8.430; P = 0.001). Increased PKP3 mRNA was detected in the blood of gastrointestinal cancer patients. Significant correlations were found with advanced stage, pT(3-4), metastatic disease, and the residual disease status. PKP3 mRNA in blood was associated with the risk of cancer progression and death. PKP3 mRNA can be used as a marker of subclinical disease in gastrointestinal cancer and thus holds potential clinical relevance as a predictor for disease outcome.


Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease.
Alzheimer's disease is associated with a disruption of amyloid β (Aβ) homeostasis, resulting in the accumulation and subsequent deposition of Aβ peptides within the brain. The peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor that acts in a coupled metabolic cycle with Liver X Receptors (LXRs) to increase brain apolipoprotein E (apoE) levels. apoE functions to promote the proteolytic clearance of soluble forms of Aβ, and we found that the synthetic PPARγ agonist, pioglitazone, stimulated Aβ degradation by both microglia and astrocytes in an LXR and apoE-dependent manner. Remarkably, a brief 9 d oral treatment of APPswe/PS1Δe9 mice with pioglitazone resulted in dramatic reductions in brain levels of soluble and insoluble Aβ levels which correlated with the loss of both diffuse and dense-core plaques within the cortex. The removal of preexisting amyloid deposits was associated with the appearance of abundant Aβ-laden microglia and astrocytes. Pioglitazone treatment resulted in the phenotypic polarization of microglial cells from a proinflammatory M1 state, into an anti-inflammatory M2 state that was associated with enhanced phagocytosis of deposited forms of amyloid. The reduction in amyloid levels was associated with a reversal of contextual memory deficits in the drug-treated mice. These data provide a mechanistic explanation for how PPARγ activation facilitates amyloid clearance and supports the therapeutic utility of PPARγ agonists for the treatment of Alzheimer's disease.


S-nitrosylation of the transcription factor MYB30 facilitates nitric oxide-promoted seed germination in Arabidopsis.
The gaseous signaling molecule nitric oxide (NO) plays an important role in breaking seed dormancy. NO induces a decrease in abscisic acid (ABA) content by transcriptionally activating its catabolic enzyme, the ABA 8'-hydroxylase CYP707A2. However, the underlying mechanism of this process remains unclear. Here, we report that the transcription factor MYB30 plays a critical role in NO-induced seed germination in Arabidopsis (Arabidopsis thaliana). MYB30 loss-of-function attenuates NO-mediated seed dormancy breaking. MYB30 triggers a NO-induced decrease in ABA content during germination by directly promoting CYP707A2 expression. NO induces S-nitrosylation at Cys-49 of MYB30 and enhances its transcriptional activity. Conversely, the ABA receptors PYRABACTIN RESISTANCE1 (PYR1)/PYR1-LIKE (PYL)/REGULATORY COMPONENTS OF ABA RECEPTORS (RCAR) interact with MYB30 and repress its transcriptional activity. ABA promotes the interaction between PYL4 and MYB30, whereas S-nitrosylation releases the PYL4-mediated inhibition of MYB30 by interfering with the PYL4--MYB30 interaction. Genetic analysis showed that MYB30 functions downstream of PYLs during seed dormancy and germination in response to NO. Furthermore, MYB30 mutation significantly represses the reduced dormancy phenotype and the enhanced CYP707A2 expression of the pyr1 pyl1 pyl2 pyl4 quadruple mutant. Our findings reveal that S-nitrosylation of MYB30 precisely regulates the balance of seed dormancy and germination, providing insights into the underlying mechanism of NO-promoted seed germination.


Pre-validation of a reporter gene assay for oxidative stress for the rapid screening of nanobiomaterials.
Engineered nanomaterials have been found to induce oxidative stress. Cellular oxidative stress, in turn, can result in the induction of antioxidant and detoxification enzymes which are controlled by the nuclear erythroid 2-related factor 2 (NRF2) transcription factor. Here, we present the results of a pre-validation study which was conducted within the frame of BIORIMA ("biomaterial risk management") an EU-funded research and innovation project. For this we used an NRF2 specific chemically activated luciferase expression reporter gene assay derived from the human U2OS osteosarcoma cell line to screen for the induction of the NRF2 mediated gene expression following exposure to biomedically relevant nanobiomaterials. Specifically, we investigated Fe3O4-PEG-PLGA nanomaterials while Ag and TiO2 "benchmark" nanomaterials from the Joint Research Center were used as reference materials. The viability of the cells was determined by using the Alamar blue assay. We performed an interlaboratory study involving seven different laboratories to assess the applicability of the NRF2 reporter gene assay for the screening of nanobiomaterials. The latter work was preceded by online tutorials to ensure that the procedures were harmonized across the different participating laboratories. Fe3O4-PEG-PLGA nanomaterials were found to induce very limited NRF2 mediated gene expression, whereas exposure to Ag nanomaterials induced NRF2 mediated gene expression. TiO2 nanomaterials did not induce NRF2 mediated gene expression. The variability in the results obtained by the participating laboratories was small with mean intra-laboratory standard deviation of 0.16 and mean inter laboratory standard deviation of 0.28 across all NRF2 reporter gene assay results. We conclude that the NRF2 reporter gene assay is a suitable assay for the screening of nanobiomaterial-induced oxidative stress responses.


Investigation of photocatalytic effect of SnO2 nanoparticles synthesized by hydrothermal method on the decolorization of two organic dyes.
Tin oxide nanoparticles about 4 nm in size were successfully synthesized using hydrothermal method. The photocatalytic activity of the particles was determined by the decolorization of malachite green (MG) and titanium yellow (TY) under UV light. 12 ppm of MG and TY were used for the solution with an initial volume of 100 mL. The amounts of catalysts were 10, 30 and 50 mg. The effect of the catalyst loading on the reaction kinetic parameters and the decolorization rate constants (k) were determined. In order to reveal the photocatalytic efficiency of the nano particles, further experiments were conducted with bulk SnO(2). The oxygen species registered no observable effect on the reaction mechanism as nitrogen bubbling leads to no change in decolorization rates. Results showed that the synthesized nano tin oxide particles represent excellent photocatalytic activity for the decolorization of 12 ppm MG under UV light with 150 min of irradiation time. The energies of the highest occupied molecular orbital (HOMO) E(HOMO) of the dyes were also calculated by using the quantum chemical software in order to discuss the differences for the decolorization of two dyes. Electrical energy efficiency values for the decolorization of two dyes were also calculated.


Platelet lysate embedded scaffolds for skin regeneration.
The work presents the development of acellular scaffolds extemporaneously embedded with platelet lysate (PL), as an innovative approach in the field of tissue regeneration/reparation. PL embedded scaffolds should have a tridimensional architecture to support cell migration and growth, in order to restore skin integrity. For this reason, chondroitin sulfate (CS) was associated with sodium alginate (SA) to prepare highly porous systems. The developed scaffolds were characterized for chemical stability to γ-radiation, morphology, hydration and mechanical properties. Moreover, the capability of fibroblasts and endothelial cells to populate the scaffold was evaluated by means of proliferation test 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and confocal laser scanning microscopy study. The scaffolds, not altered by sterilization, were characterized by limited swelling and high flexibility, by foam-like structure with bubbles that formed a high surface area and irregular texture suitable for cell adhesion. Cell growth and scaffold population were evident on the bubble surface, where the cells appeared anchored to the scaffold structure. Scaffold network based on CS and SA demonstrated to be an effective support to enhance and to allow fibroblasts and endothelial cells (human umbilical vein endothelial cells, HUVEC) adhesion and proliferation. In particular, it could be hypothesized that cell adhesion was facilitated by the synergic effect of PL and CS. Although further in vivo evaluation is needed, on the basis of in vitro results, PL embedded scaffolds seem promising systems for skin wound healing.


Defect annihilation and proliferation in active nematics.
Liquid crystals inevitably possess topological defect excitations generated through boundary conditions, through applied fields, or in quenches to the ordered phase. In equilibrium, pairs of defects coarsen and annihilate as the uniform ground state is approached. Here we show that defects in active liquid crystals exhibit profoundly different behavior, depending on the degree of activity and its contractile or extensile character. While contractile systems enhance the annihilation dynamics of passive systems, extensile systems act to drive defects apart so that they swarm around in the manner of topologically well-characterized self-propelled particles. We develop a simple analytical model for the defect dynamics which reproduces the key features of both the numerical solutions and recent experiments on microtubule-kinesin assemblies.


The lack of response of broiler chickens to supplemental niacin when fed a corn-soybean meal diet from 3 to 7 weeks of age.
An experiment involving 1296 Cobb feather-sexed broiler chickens was conducted to determine their need for supplemental niacin from 3 to 7 wk of age when fed a corn-soybean meal diet. Birds were raised in litter floor pens to 3 wk of age and fed a diet that met or exceeded the 1984 National Research Council nutritional requirements. From 3 to 7 wk of age, birds were assigned to six dietary treatments consisting of 0, 3, 6, 12, 24, and 36 mg of supplemental niacin/kg of feed. Twelve replicate pens (six per sex) were fed each dietary treatment. The corn-soybean meal basal diet (unsupplemented with niacin) contained by analysis 21.3% crude protein, 23% tryptophan, and 22 mg of niacin/kg of feed. Birds were weighed at 3 and 7 wk of age on a per pen basis. The body weight gain, total feed intake, and feed conversion were determined for male and female chickens between 3 and 7 wk of age. There were no significant differences in body weight gain (P = .67), feed intake (P = .36), and feed conversion (P = .12) due to dietary treatments. Treatment by sex interaction was not significant for body-weight gain (P = .53), feed intake (P = .76), and feed conversion (P = .53). It was concluded that a corn-soybean meal diet containing 22 mg of niacin/kg (from corn and soybean meal) and .23% tryptophan was adequate for optimum growth and feed conversion of broiler chickens from 3 to 7 wk.


[Current aspects of ovarian carcinoma].
Ovarian cancer is still an unsolved therapeutical problem in gynaecology. Inspite the occasional use of therapies exercising a great strain, the resulting overall 5-year survival is hardly unchanged. Genetic factors are probably involved in the origin of the cancer. Vaginal sonography and CA-125 screening determination have not yet been routinely established. Primary cytoreductive surgery is meanwhile a cornerstone of the treatment of advanced stages of ovarian cancer. In contrast, secondary cytoreduction is restricted to individual cases. For the second line-chemotherapy taxol was introduced. This substance has a new principle of efficacy and can obtain response rates in cisplatinum-nonresponders. An efficient treatment of ovarian cancer can only be carried out by a systemic approach involving immunological and genetic methods.


A unified computational framework for modeling genome-wide nucleosome landscape.
Nucleosomes form the fundamental building blocks of eukaryotic chromatin, and previous attempts to understand the principles governing their genome-wide distribution have spurred much interest and debate in biology. In particular, the precise role of DNA sequence in shaping local chromatin structure has been controversial. This paper rigorously quantifies the contribution of hitherto-debated sequence features-including G+C content, 10.5 bp periodicity, and poly(dA:dT) tracts-to three distinct aspects of genome-wide nucleosome landscape: occupancy, translational positioning and rotational positioning. Our computational framework simultaneously learns nucleosome number and nucleosome-positioning energy from genome-wide nucleosome maps. In contrast to other previous studies, our model can predict both in vitro and in vivo nucleosome maps in Saccharomyces cerevisiae. We find that although G+C content is the primary determinant of MNase-derived nucleosome occupancy, MNase digestion biases may substantially influence this GC dependence. By contrast, poly(dA:dT) tracts are seen to deter nucleosome formation, regardless of the experimental method used. We further show that the 10.5 bp nucleotide periodicity facilitates rotational but not translational positioning. Applying our method to in vivo nucleosome maps demonstrates that, for a subset of genes, the regularly-spaced nucleosome arrays observed around transcription start sites can be partially recapitulated by DNA sequence alone. Finally, in vivo nucleosome occupancy derived from MNase-seq experiments around transcription termination sites can be mostly explained by the genomic sequence. Implications of these results and potential extensions of the proposed computational framework are discussed.


Immunity in chimpanzees chronically infected with hepatitis C virus: role of minor quasispecies in reinfection.
We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.


Characterization of imaging performance in differential phase contrast CT compared with the conventional CT--noise power spectrum NPS(k).
The differential phase contrast CT is emerging as a new technology to improve the contrast sensitivity of the conventional CT. Via system analysis, modeling, and computer simulation, the authors study the noise power spectrum (NPS)--an imaging performance indicator-of the differential phase contrast CT and compare it with that of the conventional CT. The differential phase contrast CT is implemented with x-ray tube and gratings. The x-ray propagation and data acquisition are modeled and simulated with Fourier analysis and Fresnel analysis. To avoid any interference caused by scatter and beam hardening, a monochromatic x-ray source (30 keV) is assumed, which irradiates the object to be imaged by 360 degrees so that no weighting scheme is needed. A 20-fold up-sampling is assumed to simulate x-ray beam's propagation through the gratings Gl and G2 with periods 8 and 4 microm, respectively, while the intergrating distance is 193.6 mm (1/16 of the Tabolt distance). The dimension of the detector cell for data acquisition ranges from 32 x 32 to 128 x 128 microm2, while the field of view in data acquisition is 40.96 x 40.96 mm2. A uniform water phantom with a diameter 37.68 mm is employed to study the NPS, with its complex refraction coefficient n = 1 - delta + ibeta = 1 - 2.5604 x 10(-7) + i1.2353 x 10(-10). The x-ray flux ranges from 10(6) to 10(8) photon/cm2.projection and observes the Poisson distribution, which is consistent with that of micro-CT in preclinical applications. The image matrix of reconstructed water phantom is 1280 x 1280, and a total of 180 regions at 128 x 128 matrix are used for NPS calculation via 2D Fourier Transform in which adequate zero padding is applied to avoid aliasing. The preliminary data show that the differential phase contrast CT manifests its NPS with a l/|k| trait, while the distribution of the conventional CTs NPS observes |k|. This accounts for the significant difference in their noise granularity and the differential phase contrast CTs substantial advantage in noise over the conventional CT, particularly, in the situations where the detector cell size for data acquisition is smaller than 100 microm. The differential phase contrast CT detects the projection of refractive coefficient's derivative and uses the Hilbert filter for image reconstruction, which leads to the radical difference in its NPS and the advantage in noise in comparison to that of the conventional CT.


A new acetonitrile-free mobile phase method for LC-ELSD quantification of fructooligosaccharides in onion (Allium cepa L.).
Onion soluble non-structural carbohydrates consist of fructose, glucose and sucrose plus fructooligosaccharides (FOS) with degrees of polymerisation (DP) in the range of 3-19. In onion, sugars and FOS are typically separated using liquid chromatography (LC) with acetonitrile (ACN) as a mobile phase. In recent times, however, the production of ACN has diminished due, in part, to the current worldwide economic recession. A study was therefore undertaken, to find an alternative LC method to quantify sugars and FOS from onion without the need for ACN. Two mobile phases were compared; the first taken from a paper by Vågen and Slimestad (2008) using ACN mobile phase, the second, a newly reported method using ethanol (EtOH). The EtOH mobile phase eluted similar concentrations of all FOS compared to the ACN mobile phase. In addition, limit of detection, limit of quantification and relative standard deviation values were sufficiently and consistently lower for all FOS using the EtOH mobile phase. The drawback of the EtOH mobile phase was mainly the inability to separate all individual sugar peaks, yet FOS could be successfully separated. However, using the same onion extract, a previously established LC method based on an isocratic water mobile phase could be used in a second run to separate sugars. Although the ACN mobile phase method is more convenient, in the current economic climate a method based on inexpensive and plentiful ethanol is a valid alternative and could potentially be applied to other fresh produce types. In addition to the mobile phase solvent, the effect of extraction solvents on sugar and FOS concentration was also investigated. EtOH is still widely used to extract sugars from onion although previous literature has concluded that MeOH is a superior solvent. For this reason, an EtOH-based extraction method was compared with a MeOH-based method to extract both sugars and FOS. The MeOH-based extraction method was more efficacious at extracting sugars and FOS from onion flesh, eluting significantly higher concentrations of glucose, kestose, nystose and DP5-DP8.


Differential responses of corticotropin-releasing factor and urocortin 1 to acute pain stress in the rat brain.
It has been hypothesized that corticotropin-releasing factor (CRF) and its related neuropeptide urocortin 1 (Ucn1) play different roles in the initiation and adaptive phases of the stress response, which implies different temporal dynamics of these neuropeptides in response to stressors. We have tested the hypothesis that acute pain stress (APS) differentially changes the dynamics of CRF expression in the paraventricular nucleus of the hypothalamus (PVN), oval subdivision of the bed nucleus of the stria terminalis (BSTov) and central amygdala (CeA), and the dynamics of Ucn1 expression in the midbrain non-preganglionic Edinger-Westphal nucleus (npEW). Thirty minutes after APS, induced by a formalin injection into the left hind paw, PVN, BSTov, CeA and npEW all showed a peak in cFos mRNA expression that was followed by a robust increase in cFos protein-immunoreactivity, indicating a rapid increase in (immediate early) gene expression in all four brain nuclei. CRF-dynamics, however, were affected by APS in a brain nucleus-specific way: in the PVN, CRF-immunoreactivity was minimal at 60 min after APS and concomitant with a marked increase in plasma corticosterone, whereas in the BSTov not CRF peptide but CRF mRNA peaked at 60 min, and in the CeA a surge of CRF peptide occurred as late as 240 min. The npEW differed from the other centers, as Ucn1 mRNA and Ucn1 peptide peaked at 120 min. These results support our hypothesis that each of the four brain centers responds to APS with CRF/Ucn1 dynamics that are specific as to nature and timing. In particular, we propose that CRF in the PVN plays a major role in the initiation phase, whereas Ucn1 in the npEW may act in the later, termination phase of the adaptation response to APS.


[Effect of fundus vagotomy on the gastric emptying of the solids and liquids of a meal in patients with and without postoperative duodenal ulcer recurrence].
The effects of fundic vagotomy (FV) on gastric emptying in the solid and liquid phases of a meal were studied by an isotopic technique in 12 patients with duodenal ulcer. Postoperative results were compared with those obtained in the same subjects before FV and with control values obtained in an identical group of healthy subjects. Early gastric emptying (perprandial) of the two phases of the meal was enhanced by FV but the results failed to reach statistical significance. Gastric emptying of liquids, measured during the 3 h following the end of the meal, was not significantly modified by FV (half-emptying times: 62 +/- 5 min before FV, 75 +/- 8 min after and 65 +/- 7 min for controls). That of solids was significantly delayed by FV (per cent emptied by min: 0.50 +/- 0.02 p. 100 before FV, 0.40 +/- 0.03 p. 100 after, and 0.49 +/- 0.02 p. 100 for controls); this delay was found in all but one patient, but the difference was very slight. Eleven of the 12 investigated patients cured by the operation, were compared with 6 subjects presenting with post FV recurrence: gastric emptying rates of solids (0.41 +/- 0.02 p. 100/min and 0.47 +/- 0.07 p. 100/min) and half emptying times of liquids (72 +/- 10 min and 61 +/- 10 min) were not significantly different. Thus, the gastric emptying rate of an ordinary meal remains practically unchanged by FV and postoperative recurrences of duodenal ulcer cannot be explained by alteration of gastric evacuation.


Characterization of a novel microcin that kills enterohemorrhagic Escherichia coli O157:H7 and O26.
A novel phenotype was recently identified in which specific strains of Escherichia coli inhibit competing E. coli strains via a mechanism that was designated "proximity-dependent inhibition" (PDI). PDI-expressing (PDI(+)) E. coli is known to inhibit susceptible (PDI(-)) E. coli strains, including several enterohemorrhagic (EHEC) and enterotoxigenic (ETEC) E. coli strains. In this study, every strain from a genetically diverse panel of E. coli O157:H7 (n = 25) and additional strains of E. coli serovar O26 were susceptible to the PDI phenotype. LIVE/DEAD staining was consistent with inhibition by killing of susceptible cells. Comparative genome analysis identified the genetic component of PDI, which is composed of a plasmid-borne (Incl1) operon encoding a putative microcin and associated genes for transport, immunity, and microcin activation. Transfer of the plasmid to a PDI(-) strain resulted in transfer of the phenotype, and deletion of the genes within the operon resulted in loss of the inhibition phenotype. Deletion of chromosomally encoded tolC also resulted in loss of the inhibitory phenotype, and this confirmed that the putative microcin is most likely secreted via a type I secretion pathway. Deletion of an unrelated plasmid gene did not affect the PDI phenotype. Quantitative reverse transcription (RT)-PCR demonstrated that microcin expression is correlated with logarithmic-phase growth. The ability to inhibit a diversity of E. coli strains indicates that this microcin may influence gut community composition and could be useful for control of important enteric pathogens.


[The role of deep cerebral structures in the regulation of intracerebral microcirculation].
Changes of the diameter of microvessels of the rabbit cortex, thalamus, hypothalamus, septum pellucidum, amygdala, hippocampus and globus pallidus were studied during electrical stimulation of these structures. The stimulation of amygdala elicited vasoconstrictive reactions, the stimulation of hypothalamus and septum--vasodilative reactions, the stimulation of thalamus, hippocampus and globus pallidus caused a vasoconstriction in the motor cortex and a vasodilatation in the subcortex. These results suggest participation of the deep brain structures in the regulation of brain microcirculation.


Anti-stress effect of the Lactobacillus pentosus strain S-PT84 in mice.
We investigated if the orally administered Lactobacillus pentosus strain S-PT84 (S-PT84) might show anti-stress activity and ameliorate stress-induced immune suppression in mice. Stress of mice induced an increase in serum corticosterone and a decrease in splenic natural killer activity and in the number of splenocytes versus control mice. However, these changes were not observed in stressed mice that had been administered S-PT84. Furthermore, interleukin (IL)-12 and IL-10 production, which was downregulated in lipopolysaccharide-activated macrophages from stressed mice, was maintained at control levels in the macrophages of stressed mice that had been fed S-PT84. Interferon-γ production, which was downregulated in concanavalin A-activated splenocytes from stressed mice, tended to be maintained at control levels in stressed mice that had been fed S-PT84, although IL-4 production by these cells was not influenced by S-PT84 administration. Additionally, reduced glutathione (GSH) levels were decreased in serum and peritoneal macrophages from stressed mice versus controls, but these GSH levels were significantly higher in stressed animals that had been administered S-PT84 compared with those that had not. These results suggest that S-PT84 exerts anti-stress activity through immune modulation and/or antioxidative activity.


The Characterization of the Th1/Th2 Ratio in Moderate-Severe Alzheimer's Disease Patients and Its Response to an Aloe Polymannose-Based Dietary Supplement.
Alzheimer's disease (AD) is a leading killer of Americans, imparting a tremendous societal toll. Relationships between immune function and inflammation with cognition are well-established in AD, but the Th1/Th2 ratio of immune function is unknown. Describing the Th1/Th2 ratio and its relationship with cognition may shed light on the disease's clinical context. How the Th1/Th2 ratio responds to dietary supplementation is another unknown question in this population. The objectives of the study were to: 1) characterize the Th1/Th2 ratio according to IL-2/IL-10, IFN-γ/IL-10, IL-2/IL-4, IFN-γ/IL-4, IL-2/TNF-α, and IFN-γ/TNF-α in subjects with moderate-to-severe AD and in comparison to healthy adults; 2) investigate the effect of an aloe polymannose multinutrient complex (APMC) dietary supplement on the Th1/Th2 ratios over 12 months; and 3) compare the changes in the Th1/Th2 ratios with the changes in cognition from baseline to 12 months. Subjects consumed 2.5 g of the APMC four times per day for 12 months, and they were assessed on cognition and cytokines at baseline and 12 months. The Th1/Th2 ratios in AD patients were significantly higher than the healthy controls, and five of the six ratios decreased from baseline to 12 months follow-up (other than IL-2/TNF-α). Several significant relationships were noted between the changes in Th1/Th2 ratios with cognitive assessments. Our results showed an overall rebalancing of the Th1/Th2 ratio in response to APMC, these changes were related to improved cognition in subjects with moderate-to-severe AD, and the APMC supplement was safely tolerated.


Influencing prescribing practices and associated outcomes utilizing the drug use evaluation process.
Influencing prescribing practices and the implementation of pharmaceutical care utilizing the drug use evaluation (DUE) process at a 891-bed teaching hospital are described. The DUE program has been structured to provide for significant pharmacy involvement while maintaining medical staff responsibility as outlined by the Joint Commission on Accreditation of Healthcare Organizations. A multidisciplinary approach is used to identify problems and develop prescribing criteria and educational initiatives. Pharmacists provide drug therapy monitoring and engage in clinical interventions and documentation of outcomes on a daily basis. DUE program pharmacists help target possible interventions, assure monitoring and outcome documentation, and compile results of all initiatives for reporting purposes to the medical staff and quality assessment program. Specific performance compliance and problems are identified and incorporated into the credentialing process. Corrective measures are determined by the Pharmacy and Therapeutics (P&T) Subcommittee with subsequent actions carried out by peer physicians. The net result is a positive influence on prescribing practices that improves the appropriate and effective use of drugs and improves patient outcomes.


Temporal changes in the incidence and 30-day mortality associated with bacteremia in hospitalized patients from 1992 through 2006: a population-based cohort study.
Little is known about temporal trends in the incidence and mortality associated with bacteremia in the general population. We conducted a population-based cohort study in Northern Denmark to examine changes in bacteremia occurrence and 30-day mortality from 1992 through 2006. All patients who received a diagnosis of bacteremia were identified in a population-based bacteremia database and followed up for mortality through the Danish Civil Registry System. We determined the overall annual age- and sex-standardized rates of bacteremia episodes, the incidence of first-time episodes, and the adjusted 30-day mortality by place of acquisition and study period. We identified 14,303 bacteremia episodes, 11,703 (81.8%) of which were incident. The age- and sex-standardized overall rate of bacteremia increased by 68% from 1992 through 2006, and the incidence increased by 46% (from 114 to 166 episodes per 100,000 person-years). Community-acquired and nosocomial bacteremia incidence rates peaked at 92.1 and 77.2 episodes per 100,000 person-years in 2004 and 2002, respectively, whereas the incidence of health care-associated bacteremia increased steadily from 2.9 to 39.8 episodes per 100,000 person-years. Total number of deaths increased from 742 during 1992-1996 to 926 during 2002-2006. The 30-day mortality decreased in patients with community-acquired bacteremia (19.0% during 1992-1996 vs 15.4% during 2002-2006) but remained nearly unchanged for health care-associated (23.4% and 22.0%, respectively) and nosocomial bacteremia (27.9% and 27.7%, respectively). The occurrence of bacteremia in Northern Denmark, regardless of the place of acquisition, increased considerably in the past 15 years, and bacteremia was associated with persistently high 30-day mortality. Thus, bacteremia remains a clinical and public health concern.


Ethanol in low doses augments calcium-mediated mechanisms measured intracellularly in hippocampal neurons.
The electrophysiological effects of ethanol in low doses (5 to 20 millimoles per liter or 23 to 92 milligrams per 100 milliliters) were examined intracellularly in CA1 cells of rat hippocampus in vitro. Inhibitory and excitatory postsynaptic potentials were increased when ethanol was applied to the respective synaptic terminal regions. Postsynaptically, ethanol caused a moderate hyperpolarization with increased membrane conductance, even when synaptic transmission was blocked. Ethanol augmented the hyperpolarization that followed repetitive firing or that followed the eliciting of calcium spikes in the presence of tetrodotoxin, but not the rapid afterhyperpolarization in calcium-free medium. Ethanol appears to augment calcium-mediated mechanisms both pre- and postsynaptically.


[Neuromuscular syndromes of the critically ill].
With the continuous improvement in the survival of critical patients, new neuromuscular syndromes are being described. The clinical finding is an acute-subacute onset of generalised weakness with difficulty in weaning the patient from the ventilator, due to polyneuropathy, myopathy, prolonged neuromuscular blockade or a combination of these disorders. Although having a multifactorial ethiopathology, the major risk factors in the development of these disorders are multiple organ failure and sepsis for polyneuropathy; corticosteroids and neuromuscular junction blocking agents (NMB) for myopathy; and NMB and renal and liver failure for prolonged neuromuscular blockade. No specific treatment exists, which is why--due to the high incidence of these syndromes and their poor prognosis, with a mortality rate higher than 50%--we should recognise, diagnose and avoid, where possible, the conditions that help the development of these disorders.


Novel technology to help understand the context of physical activity and sedentary behaviour.
When used in large, national surveillance programmes, objective measurement tools provide prevalence estimates of low physical activity guideline compliance and high amounts of sedentary time. There are undoubtedly a plethora of reasons for this but one possible contributing factor is the current lack of behavioural context offered by accelerometers and posture sensors. Context includes information such as where the behaviour occurs, the type of activity being performed and is vital in allowing greater refinement of intervention strategies. Novel technologies are emerging with the potential to provide this information. Example data from three ongoing studies is used to illustrate the utility of these technologies. Study one assesses the concurrent validity of electrical energy monitoring and wearable cameras as measures of television viewing. This study found that on average the television is switched on for 202 min d-1 but is visible in just 90 min of wearable camera images with a further 52 min where the participant is in their living room but the television is not visible in the image. Study two utilises indoor location monitoring to assess where older adult care home residents accumulate their sedentary time. This study found that residents were highly sedentary (sitting for an average of 720 min d-1) and spent the majority of their time in their own rooms with more time spent in communal areas in the morning than in the afternoon. Lastly, study three discusses the use of proximity sensors to quantify exposure to a height adjustable desk. These studies are example applications of this technology, with many other technologies available and applications possible. The adoption of these technologies will provide researchers with a more complete understanding of the behaviour than has previously been available.


Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11.
Anti-liver kidney microsomes (anti-LKM2) autoantibodies, appearing in patients treated with tienilic acid and suffering from hepatitis, react with proteins in rat liver sections. The nature of the rat proteins responsible for this recognition and detection of anti-LKM2 has been investigated. Immunoblot testing of the anti-LKM2 with liver microsomes from diversely treated rats and with purified rat liver cytochromes P450 (IA1, IA2, IIB1, IIB2, IIC6, IIC11 and IVA1) showed that these antibodies cross-reacted with cytochrome P450IIC11 and also with phenobarbital-induced cytochromes P450IIB1 and IIB2. Moreover, metabolic activation of tienilic acid and of a tienilic acid isomer by untreated rat liver microsomes was partially inhibited by anti-LKM2. On the other hand, monospecific polyclonal anti-rat P450IIC11 antibodies cross-reacted with human microsomal cytochromes P450 and recognized the same cytochromes P450 as anti-LKM2. This antibody also gave an immunofluorescence pattern on rat and mouse liver and kidney sections very similar to anti-LKM2. The data presented here show that anti-LKM2 recognize epitopes shared by rat P450 IIC11, and a human P450 of the family IIC. All the results indicate rat P450 IIC11, the major isoenzyme present in normal adult male rat liver, as the main antigen recognized by human anti-LKM2 autoantibodies; this is the basis of the immunofluorescence test for detection of these antibodies.


Chemical design of biocompatible iron oxide nanoparticles for medical applications.
Iron oxide nanoparticles are one of the most versatile and safe nanomaterials used in medicine. Recent progress in nanochemistry enables fine control of the size, crystallinity, uniformity, and surface properties of iron oxide nanoparticles. In this review, the synthesis of chemically designed biocompatible iron oxide nanoparticles with improved quality and reduced toxicity is discussed for use in diverse biomedical applications.


[Connection of endothelial dysfunction and level of blood leukocytes with clinical course of stable angina pectoris in patients with ischemic heart disease].
The authors presents in the article information on influence of endothelial dysfunction and level of blood leukocytes with clinical course of stable angina pectoris in patients with ischemic heart disease (IHD). 104 male patients aged from 36 to 69 (on average 54.9+/-2.1 years) with IHD and stage I-III stable angina pectoris have been observed. The level of leukocytes, ECG daily monitoring, endotelial function with the help of Celermaera-Sorensena test and plasma concentration of endothelin I have been studied in patients. It was established that there is no significant different (P>0.05) in the level of leukocytes between health persons and patients with IHD independently of functional class of angina pectoris. Patients with IHD had higher level of endothelin I in their blood serum than those in a control group. Patients with IHD have a complicated endothelial-non-dependent vasodilation and an increased thickness of the complex intima-media, there is a negative correlation bond between these characteristics. Patients III functional class of angina pectoris has also reliably decreased endothelial-dependent vasodilation by 37%. Frequency of ventricular extrasystoles in patients with IHD and endothelial dysfunction increases by 12 times.


Extracellular matrix proteins in epiretinal membranes and in diabetic retinopathy.
Non-vascular epiretinal membranes (ERM) and neovascular membrane in proliferative diabetic retinopathy (PDR) are recognized causes of visual impairment. Both ERMs and neovascular membranes in PDR consist of cellular components and extracellular matrix (ECM) proteins such as fibronectin (FN) and collagen. Transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) regulate ECM protein production. In this study, we investigated ECM proteins and their regulators in ERMs and vitreous from PDR subjects and non-diabetic subjects undergoing vitrectomy. ERMs from non-diabetic subjects undergoing membrane peeling were collected. Vitreous samples from non-diabetic and PDR subjects undergoing vitrectomy were also collected and separated into solid pellets consisting of fibrovascular tissue and vitreous fluid. Real-time PCR was done for estimating mRNA levels of extracellular matrix proteins like collagen, FN, its splice variant extra-domain B containing FN (EDBFN), and their regulators, TGF-beta and ET-1. ELISA was done to detect the EDBFN level in blood and vitreous from non-diabetic and PDR subjects undergoing vitrectomy. ECM proteins, including FN, its splice variant EDBFN, and collagen were significantly upregulated in the ERMs and PDR compared to vitreous from both other two group. The levels were, however, higher in the ERM. ECM protein regulators like TGF-beta and ET-1 were also elevated. FN and EDBFN show significant correlation with TGF-beta in vitreous but not in ERMs. Plasma and vitreous EDBFN were elevated in the PDR subjects compared to non-diabetic subjects. Data from these studies show that ECM proteins such as EDBFN and collagen are upregulated in ERM and PDR, and are regulated by TGF-beta. Elevated serum EDBFN in the PDR may potentially be further explored as a possible molecular marker for the early detection of diabetic end organ damages.


Determining the presence of chemicals with suspected endocrine activity in drinking water from the Madrid region (Spain) and assessment of their estrogenic, androgenic and thyroidal activities.
Endocrine disruptors (EDs) are natural or man-made chemicals that can affect the health of organisms by interfering with their normal hormonal functions. Many of these substances can cause their effects at very low doses and, considering the key role played by the endocrine system on development, organisms in early phases of growth (foetal, childhood, puberty) are especially sensitive to the action of EDs. In addition, when combined, they can show additive, antagonistic and synergistic activities. Taking all this into account it is essential to determine the presence of this kind of compounds in drinking water. Thus the main aim of the present study was to monitor the presence of substances with suspected or known endocrine activity in drinking water of the Madrid Region (MR) (Central Spain) and determine possible estrogenic, androgenic, or thyroidal activities. Water samples were collected at different times from a number of supply points that received water from reservoirs or rivers. The sampling point with the highest concentration of the analysed substances (up to 30 compounds) was DW1 (1203 ng L-1). This sampling point receives water from a drinking water treatment plant (DWTP) that serves the population from the south of the MR with treated water from the Tajuña River. DW2 was the second point with the highest concentration of the analysed substances (1021 ng L-1). DW2 receives water from one of the reservoirs in the north of the MR. The highest daily concentrations detected corresponded to the flame retardant Tris (2-chloroethyl)phosphate (TCEP) (266.55 ng L-1) and to the nonylphenol diethoxylate (188.57 ng L-1) at points DW1 and DW4, respectively, both of which are supplied with treated river water. None of the water samples exhibited androgenic, oestrogenic, or thyroidal activities in in vitro assays based on cells stably transfected with the receptors of interest and luciferase as reporter gene. These results demonstrate that water quality in the MR is high and does not present a health risk for the population, although the concentrations of some substances justify the need for local authorities to continually monitor the presence of these contaminants in order to implement any corrective measures if necessary.


[Headache as a warning symptom].
Chronic headache is an independent clinical picture. Headaches are to be interpreted as a warning sign from the body until this is excluded through differential diagnostics. The clarification and the initial treatment should be carried out by a neurologist to ensure sufficient diagnostic certainty.


Dr Eliza Foster McDonogh Frikart: advertiser.
Eliza Frikart was the first woman doctor registered in New Zealand. She moved round Australia and New Zealand and advertised her presence wherever she went. She was struck off the British register.


Evaluating the impact of the National Healthy School Standard: using national datasets.
An evaluation of the National Healthy School Standard (NHSS) was undertaken by the authors on behalf of the Department of Health and the Department for Education and Skills. One part of the evaluation involved gaining access to a number of datasets derived from previous research and analysing the health-related outcomes of schools which had attained Level 3 of the NHSS, compared with those of other schools. The sources which provided the most interesting findings were the Health-Related Behaviour Questionnaire (HRBQ) survey and the Ofsted database of school inspection ratings. This paper describes the statistical methods used, and the results of the HRBQ and Ofsted analyses. Using HRBQ data, many pupil-level outcomes were explored, but relatively few indicated significant differences and even those tended to be quite small. The Ofsted school-level data yielded stronger evidence of NHSS impact. The paper concludes by suggesting possible reasons for these findings.


Parental perceptions and acceptance of silver diamine fluoride staining.
The caries arrest that can be achieved by using silver diamine fluoride (SDF) offers a minimally invasive and inexpensive alternative to traditional restorative caries treatment. The authors evaluated how the dentinal staining that is associated with SDF influences the acceptance of this treatment among parents of young children in the New York City metropolitan area. The authors invited the parents of children who had experienced dental caries and who had appointments at the New York University Pediatric Dentistry Clinic and at several private clinics in New Jersey to participate in a Web-based survey designed to assess parents' demographics, perceptions of photographs of SDF-treated carious teeth, and acceptability of treatment in different behavior management scenarios. Ninety-eight mothers and 22 fathers from diverse backgrounds participated. Most parents (67.5%) judged SDF staining on the posterior teeth to be esthetically tolerable, but only 29.7% of parents made this same judgment about anterior teeth (P < .001). In the absence of their child having behavioral barriers to conventional restorations, 53.6% of parents reported that they were likely to choose SDF to treat their child's posterior teeth, but only 26.9% of parents were likely to choose SDF to treat their child's anterior teeth. As the number of children's behavioral barriers increased, so did the parents' level of acceptance. In extreme cases, in which parents had to decide whether their children should undergo general anesthesia during treatment, parents' acceptance rate of SDF as a treatment method increased to 68.5% on posterior teeth and to 60.3% on anterior teeth. Parents' acceptance of the treatment also varied according to their socioeconomic status. Staining on posterior teeth was more acceptable than staining on anterior teeth. Although staining on anterior teeth was undesirable, most parents preferred this option to advanced behavioral techniques such as sedation or general anesthesia. Clinicians need to understand parental sensitivities regarding the staining effect of SDF to plan adequately for the use of SDF as a method of caries management in pediatric patients.


Coupling FeCo atomic pair to promote the selective reduction of nitroaromatics under mild conditions.
Selectively reducing nitroaromatics into aromatic amines will not only remove nitroaromatic pollutants in waste effluents to reduce environmental risks, but also yield important feedstocks for chemical industrial manufactures. In this study, a FeCo-co-embedded N-doped Carbon (FeCo-N-C) catalyst with FeCo atomic pair has been identified with favorable activity, superior selectivity, excellent reusability, as well as outstanding performance in the treatment of real water. The combined results from theoretical study and experimental tests indicate that the improved catalytic performance of FeCo-N-C is owing to the narrowed band gap and electron delocalization caused by the FeCo atomic pair which can improve electron transport in its catalytic reaction. The results of isotope experiments and H* quenching experiments confirm that H2O is the source of hydrogen in catalytic reduction of PNP. FeCo-N-C is identified as a superior catalyst to replace multitudinous currently used noble-metal catalysts for the selective catalytic reduction of nitroaromatics in wastewater treatment.


Integrin Alpha-2 as a Potential Prognostic and Predictive Biomarker for Patients With Lower-Grade Glioma.
Diffuse gliomas are the most common malignant brain tumors with the highest mortality and recurrence rate in adults. Integrin alpha-2 (ITGA2) is involved in a series of biological processes, including cell adhesion, stemness regulation, angiogenesis, and immune/blood cell functions. The role of ITGA2 in lower-grade gliomas (LGGs) is not well defined. Firstly, we downloaded RNA sequencing and relevant clinical information from The Cancer Genome Atlas cohort, the Chinese Glioma Genome Atlas cohort, and related immune cohorts. Next, prognosis analysis, difference analysis, clinical model construction, enrichment analysis, and immune infiltration analysis are performed for this study. These analyses indicated that ITGA2 may have clinical application value and research value in LGG immunotherapy. We also detected the mRNA and protein expression of ITGA2 in three LGG cell lines and normal glial cells using quantitative real-time polymerase chain reaction assay and western blot assay. Our study not only offers a novel target for LGG immunotherapy but also can better comprehend the mechanism of the development and progression of patients with LGG. This study revealed that ITGA2 may be a potential prognostic and predictive biomarker for LGG, which can bring new insights into targeted immunotherapy.


Regulatory Role of RNA Chaperone TDP-43 for RNA Misfolding and Repeat-Associated Translation in SCA31.
Microsatellite expansion disorders are pathologically characterized by RNA foci formation and repeat-associated non-AUG (RAN) translation. However, their underlying pathomechanisms and regulation of RAN translation remain unknown. We report that expression of expanded UGGAA (UGGAAexp) repeats, responsible for spinocerebellar ataxia type 31 (SCA31) in Drosophila, causes neurodegeneration accompanied by accumulation of UGGAAexp RNA foci and translation of repeat-associated pentapeptide repeat (PPR) proteins, consistent with observations in SCA31 patient brains. We revealed that motor-neuron disease (MND)-linked RNA-binding proteins (RBPs), TDP-43, FUS, and hnRNPA2B1, bind to and induce structural alteration of UGGAAexp. These RBPs suppress UGGAAexp-mediated toxicity in Drosophila by functioning as RNA chaperones for proper UGGAAexp folding and regulation of PPR translation. Furthermore, nontoxic short UGGAA repeat RNA suppressed mutated RBP aggregation and toxicity in MND Drosophila models. Thus, functional crosstalk of the RNA/RBP network regulates their own quality and balance, suggesting convergence of pathomechanisms in microsatellite expansion disorders and RBP proteinopathies.


The measurement of backscatter coefficient from a broadband pulse-echo system: a new formulation.
A new formulation for obtaining the absolute backscatter coefficient from pulse-echo measurements is presented. Using this formulation, performing the diffraction correction and system calibration is straightforward. The diffraction correction function for the measurement of backscatter coefficient and the acoustic coupling function for a pulse-echo system are defined. Details of these functions for two very useful cases are presented: a flat disk transducer and a spherically focused transducer. Approximations of these functions are also provided. For a flat disk transducer, the final formulation appears as a modification to the established Sigelmann-Reid formulation. For a focused transducer, the final correction is a weak function of frequency when the scattering volume is near the focal area, rather than the frequency squared dependence proposed by earlier investigators.


Human T-lymphotropic virus type 1 open reading frame I p12(I) is required for efficient viral infectivity in primary lymphocytes.
Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus encoding regulatory and accessory genes in four open reading frames (ORF I to IV) of the pX region. Emerging evidence indicates an important role for the pX ORF I-encoded accessory protein p12(I) in viral replication, but its contribution to viral pathogenesis remains to be defined. p12(I) is a conserved, membrane-associated protein containing four SH3-binding motifs (PXXP). Its interaction with the interleukin-2 (IL-2) receptor beta- and gamma-chains implies an involvement of p12(I) in intracellular signaling pathways. In addition, we have demonstrated that expression of pX ORF I p12(I) is essential for persistent infection in rabbits. In contrast, standard in vitro systems have thus far failed to demonstrate a contribution of p12(I) to viral infectivity and ultimately cellular transformation. In this study we developed multiple in vitro coculture assays to evaluate the role of p12(I) in viral infectivity in quiescent peripheral blood mononuclear cells to more accurately reflect the virus-cell interactions as they occur in vivo. Using these assays, we demonstrate a dramatic reduction in viral infectivity in quiescent T lymphocytes for a p12 mutant viral clone (ACH.p12) in comparison to the wild-type clone ACH. Moreover, addition of IL-2 and phytohemagglutinin during the infection completely rescued the ability of ACH.p12 to infect primary lymphocytes. When newly infected primary lymphocytes are used to passage virus, ACH.p12 also exhibited a reduced ability to productively infect activated lymphocytes. Our data are the first to demonstrate a functional role for pX ORF I in the infection of primary lymphocytes and suggest a role for p12(I) in activation of host cells during early stages of infection.


[Protective effect of CoQ 10 administration on cardial toxicity in FAC therapy].
An unique combination treatment for cancer patients has been attempted in our department. The treatment consists of 500 rad irradiation of cobalt 60 on the first day and drip infusion of mixture of 50mg adriamycin, 500mg cyclophosphamide and 500mg 5-fluorouracil on the next day. This combination therapy was repeated every 3 weeks. The myocardial intoxication may be a great problem in this therapy. Investigation was performed in 40 cancer patients in order to clarify of Coenzyme Q10 (CoQ10) could show any protecting effect upon the possible myocardial intoxication. All patients were divided into 2 groups; one with CoQ10 of 20 patients, who received CoQ10 of 90mg/day orally and the other without CoQ10 of 20 patients. In the group without CoQ10, cardiothoracic ratio (CTR) and pulse rate increased significantly in all patients and on ECG low voltage of QRS complex was seen in 2 cases, changes of ST-segment, T-wave and appearance of arrhythmia were more than frequent in the group without CoQ10 than that with CoQ10. It is concluded that CoQ10 is effective for protecting the myocardium in this cancer therapy.


Taste aversion learning in fyn mutant mice.
Conditioned taste aversion (CTA) learning is a robust form of classical conditioning in which animals rapidly associate a flavor with aversive internal symptoms. The present study assessed CTA learning in transgenic mice deficient in a specific nonreceptor tyrosine kinase (the fyn mutant). Fyn mutants show impaired long-term potentiation and marked deficits in acquisition of spatial learning tasks. To assess whether they are also impaired in CTA learning, fyn mutant and wild-type mice received 2 conditioning trials consisting of access to a flavored solution followed by administration of LiCl. Fyn mutant mice acquired significant CTAs following a single conditioning trial and these aversions were comparable to those seen in wild-type mice. These results indicate that the fyn mutation does not interfere with the acquisition of CTAs and hence that this mutation is not associated with a global learning deficit.


Interaction between human polymorphonuclear leucocytes and Chlamydia trachomatis elementary bodies: electron microscopy and chemiluminescent response.
Incubation of human polymorphonuclear leucocytes (HPMN) with highly purified Chlamydia trachomatis serotype L2/434/Bu elementary bodies (EB), in the presence and absence of specific antibody, resulted in a 10(3)-fold reduction of viable count after 24 h incubation. Electron microscopy observations indicated activation of the HPMN by the EB. Attachment of the EB to the HPMN cell membrane, formation of a cytoplasmic cup and EB-containing vacuoles were observed. In addition, two types of phagocytic vacuoles were observed after 30 min incubation; in one type, a single EB was tightly surrounded by the vacuolar membrane, while the other type was enlarged and held one or more intact EB or degenerated EB or both. A fuzzy coat was observed on EB located in the HPMN vacuoles only in the presence of specific antibody. Empty vacuoles containing degenerated EB were observed in the HPMN after 24 h incubation. HPMN exposed to EB of C. trachomatis produced a marked chemiluminescent response with a peak 14 times greater than the peak value of the control. A second stimulation with phorbol 12-myristate 13-acetate and zymosan was achieved. The chemiluminescent peak value in the presence of heat-treated EB (56 degrees C, 20 min) was 50% of that obtained in the presence of untreated EB. The significance of the chemiluminescent response in the killing mechanism of C. trachomatis EB by HPMN is discussed.


Mental health services for war-affected children: report of a survey in Kosovo.
In war-affected societies it is assumed that the major mental health problem facing the population will be stress reactions. To describe the creation of a child and adolescent mental health service (CAMHS) in Kosovo after the military conflict ended in 1999, and to establish the range of problems and diagnoses that presented. Data were collected on 559 patients over 2 years, including their referring problems and diagnoses. Stress-related disorders constituted only a fifth of the case-load in year 1. A substantial number of patients were symptom-free but attended because they had been exposed to a traumatic event, and believed it might make them ill. Non-organic enuresis and learning disability were the most common diagnoses in year 2. Many patients had a complex mix of social and psychological difficulties that did not fit conventional diagnostic categories. Mental health services that only address traumatic stress may fail to meet the needs of war-affected children. A comprehensive, culturally appropriate CAMHS is needed to address a wide range of problems including learning disability. It should be developed through local actors, and build on existing local infrastructure. Services can also have an educational role in 'depathologising' normative responses.


Recent advances in III-Sb nanowires: from synthesis to applications.
The excellent properties of III-V semiconductors make them intriguing candidates for next-generation electronics and optoelectronics. Their nanowire (NW) counterparts further provide interesting geometry and a quantum confinement effect which benefits various applications. Among the many members of all the III-V semiconductors, III-antimonide NWs have attracted significant research interest due to their narrow, direct bandgap and high carrier mobility. However, due to the difficulty of NW fabrication, the development of III-antimonide NWs and their corresponding applications are always a step behind the other III-V semiconductors. Until recent years, because of advances in understanding and fabrication techniques, electronic and optoelectronic devices based on III-antimonide NWs with novel performance have been fabricated. In this review, we will focus on the development of the synthesis of III-antimonide NWs using different techniques and strategies for fine-tuning the crystal structure and composition as well as fabricating their corresponding heterostructures. With such development, the recent progress in the applications of III-antimonide NWs in electronics and optoelectronics is also surveyed. All these discussions provide valuable guidelines for the design of III-antimonide NWs for next-generation device utilization.


Factors affecting stimulation of natural cytotoxicity to a rat lymphoma by Corynebacterium parvum.
Differences were seen in the ability of 2 strains of C. parvum to augment cytotoxicity attributable to NK cells towards a rat lymphoma. Furthermore, 2 batches of the same strain of C. parvum prepared by different methods also differed in their ability to augment cytotoxicity. Other factors influencing cytotoxicity were dose, route of inoculation and time after injection at which the assay was performed. Although all preparations of C. parvum augmented the cytotoxicity of peritoneal-exudate cells when injected i.p., only the most stimulatory preparation consistently augmented splenic cytotoxicity when given by this route. I.v. administration of 1 mg of C. parvum produced peak levels of splenic cytotoxicity 2-3 days later, but this response was strictly dose-dependent, since 1 microgram depressed splenic cytotoxicity. This dose-dependent effect also extended to ADCC, since 1 mg stimulated cytotoxicity towards antibody-coated P815 cells, whilst 1 microgram depressed it in a manner similar to its effect on natural cytotoxicity. Whilst the cytotoxic cells of stimulated rats closely resembled the NK cells of normal rats, BN rats responded differently to C. parvum from W/Fu or WAG rats, in that marked lysis of P815 or RBL-5 cells was observed, though these targets are usually resistant to lysis by rat NK cells in short-term assays.


[A Case of Hypertrophic Pachymeningitis with Symptomatic Venous Congestion due to Sinus Stenosis].
We report a patient with hypertrophic pachymeningitis and symptomatic stenosis of the superior sagittal sinus. A 71-year-old man presented with right hemiparesis, sensory-dominant aphasia, and right hemispatial neglect that had been worsening over 2 weeks. Computed tomography showed isodense crescent-shaped lesions deforming the surface of the left cerebral hemisphere, mimicking a subdural hematoma with atypical perifocal edema in the left parietal lobe. Magnetic resonance imaging showed diffuse thickening of the dura mater with contrast enhancement of his left cerebral hemisphere. Histopathological examination of the dural specimen obtained by burr-hole surgery revealed mononuclear inflammatory cell infiltration, and he was diagnosed with hypertrophic pachymeningitis. Dynamic cerebral angiography showed superior sagittal sinus stenosis with reduced venous flow through the left parietal lobe. Administration of high-dose steroid therapy led to neurological improvement. In the case of a subdural mass with atypical parenchymal edema such as a chronic subdural hematoma, other etiology should be taken into consideration.


The maternal brain: an organ with peripartal plasticity.
The time of pregnancy, birth, and lactation, is characterized by numerous specific alterations in several systems of the maternal body. Peripartum-associated changes in physiology and behavior, as well as their underlying molecular mechanisms, have been the focus of research since decades, but are still far from being entirely understood. Also, there is growing evidence that pregnancy and lactation are associated with a variety of alterations in neural plasticity, including adult neurogenesis, functional and structural synaptic plasticity, and dendritic remodeling in different brain regions. All of the mentioned changes are not only believed to be a prerequisite for the proper fetal and neonatal development, but moreover to be crucial for the physiological and mental health of the mother. The underlying mechanisms apparently need to be under tight control, since in cases of dysregulation, a certain percentage of women develop disorders like preeclampsia or postpartum mood and anxiety disorders during the course of pregnancy and lactation. This review describes common peripartum adaptations in physiology and behavior. Moreover, it concentrates on different forms of peripartum-associated plasticity including changes in neurogenesis and their possible underlying molecular mechanisms. Finally, consequences of malfunction in those systems are discussed.


Polarization dependence of the coupling ratio in LiTaO3 directional couplers.
The effect of design and fabrication parameters on the polarization dependence of the splitting ratio in directional couplers produced in LiTaO3 by Zn diffusion has been investigated experimentally at a wavelength of 1558 nm. The directional couplers featured various combinations of waveguide width, separation gaps between waveguides, bending angle, and diffusion conditions. In each case the coupling region was 3.5 mm long. Of particular interest was the identification of parameter sets for which the sum of power splitting ratios from TE and TM inputs equals unity at the output, as needed for electro-optic tunable filters with relaxed beam-splitter requirements.


[A health education program based on training and support of stakeholders in the field].
Education Santé Territoire (EST) is a health education programme for children and adolescents. It was developed on the basis of the international literature and the results of interventional studies conducted in France. It is based on local resources and develops a territorial approach centered on the school as the reference site of the "perceived territory" of children and adolescents. It therefore comprises a local environment approach (school and college) and a territorial approach, as it is centered on participation and is designed to mobilize local stakeholders involved in the education of young people. It concerns educational activities (in the schoolroom, in the institution, in the context of extracurricular activities, in leisure centres, in sports clubs); the school-community relationship; the quality of life of children and adolescents. The available results show major changes in practices and a wide range of modalities of participation. Factors that determine participation are essentially related to individual determinants (adhesion to the underlying values of the programme, compatibility of representations, perception of the relevance of the content) and contextual factors (numbers, school environment, social environment). Training and the history of involvement in the programme appear to be key elements determining participation.