Epigallocatechin-3-gallate inhibits VCAM-1 expression and apoptosis induction associated with LC3 expressions in TNFα-stimulated human endothelial cells.
Tumor necrosis factor alpha (TNF-α) promotes the expression of adhesion molecules and induces endothelial dysfunction, a process that can lead to atherosclerosis. Green tea consumption can inhibit endothelial dysfunction and attenuate the development of arteriosclerosis. The purpose of this study was to examine whether epigallocatechin-3-gallate (EGCG) prevents TNF-α-dependent endothelial dysfunction. Here, we compared the regulatory effects of the green tea components EGCG and L-theanine against TNF-α-induced stimulation of adhesion molecule expression and apoptosis induction, which is associated with autophagy. Monocytic cell adhesion to human endothelial cells was measured using a fluorescently-labeled cell line, U-937. Caspase 3/7 activity was examined with a fluorescent probe and fluorescence microscopy. In addition, we analyzed the expression of several genes by RT-PCR. TNF-α-modulation of LC3 and VCAM1 protein levels were investigated by Western blot (WB). TNF-α induced adhesion of U937 cells to endothelial cells, and gene expression associated with adhesion molecules and apoptosis. On the other hand, EGCG and L-theanine inhibited TNF-α-induced adhesion of U937 cells to endothelial cells and inhibited increases in ICAM1, CCL2 and VCAM1 expression. Furthermore, EGCG and L-theanine inhibited TNF-α-induced apoptosis-related gene expression (e.g., CASP9), and caspase activity while inhibiting TNFα-induced VCAM1, LC3A and LC3B protein expression. Meanwhile, treatment of endothelial cells with autophagy inhibitor 3-methyladenine (3-MA) blocked EGCG-induced expression of CASP9. Together, these results indicate that EGCG can modulate TNF-α-induced monocytic cell adhesion, apoptosis and autophagy. We thus conclude that EGCG might be beneficial for inhibiting TNF-α-mediated human endothelial disorders by affecting LC3 expression-related processes.


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Defect-Enhanced CO2 Reduction Catalytic Performance in O-Terminated MXenes.
Electrochemical carbon dioxide reduction reaction (CO2 RR) represents a promising way to generate fuels and chemical feedstock sustainably. Recently, studies have shown that two-dimensional metal carbides and nitrides (MXenes) can be promising CO2 RR electrocatalysts due to the alternating -C and -H coordination with intermediates that decouples scaling relations seen on transition metal catalysts. However, further by tuning the electronic and surface structure of MXenes it should still be possible to reach higher turnover number and selectivities. To this end, defect engineering of MXenes for electrochemical CO2 RR has not been investigated to date. In this work, first-principles modelling simulations are employed to systematically investigate CO2 RR on M2 XO2 -type MXenes with transition metal and carbon/nitrogen vacancies. We found that the -C-coordinated intermediates take the form of fragments (e. g., *COOH, *CHO) whereas the -H-coordinated intermediates form a complete molecule (e. g., *HCOOH, *H2 CO). Interestingly, the fragment-type intermediates become more strongly bound when transition-metal vacancies are present on most MXenes, while the molecule-type intermediates are largely unaffected, allowing the CO2 RR overpotential to be tuned. The most promising defective MXene is Hf2 NO2 containing Hf vacancies, with a low overpotential of 0.45 V. More importantly, through electronic structure analysis it could be observed that the Fermi level of the MXene changes significantly in the presence of vacancies, indicating that the Fermi level shift can be used as an ideal descriptor to rapidly predict the catalytic performance of defective MXenes. Such an evaluation strategy is applicable to other catalysts beyond MXenes, which could enhance high throughput screening efforts for accelerated catalyst discovery.


MSCs exosomal miR-1470 promotes the differentiation of CD4+CD25+FOXP3+ Tregs in asthmatic patients by inducing the expression of P27KIP1.
Exosomes derived from Mesenchymal Stem Cells (MSCs) possesses similar immunomodulatory effect as MSCs. It had been suggested that MSCs exosomes contain higher level of miR-1470 compared to exosomes derived from fibroblast. Here, we show that MSCs exosomal miR-1470 can elevate the proportion of CD4+CD25+FOXP3+ regulatory T cells (Tregs) in asthmatic patients. Moreover, mechanistic studies revealed that miR-1470 can promote the upregulation of P27KIP1 by directly targeting the 3' region of c-Jun mRNA. Furthermore, miR-1470 mimic transfection could significantly upregulate the proportion of CD4+CD25+FOXP3+ Tregs in CD4+ T cells. P27KIP1 knockdown via siRNA silencing significantly inhibited the proportion of CD4+CD25+FOXP3+ Tregs with over-expression of miR-1470, which indicates that miR-1470 induces the differentiation of CD4+CD25+FOXP3+ Tregs through P27KIP1.


Use of both cumulus cells' transcriptomic markers and zona pellucida birefringence to select developmentally competent oocytes in human assisted reproductive technologies.
Selection of the best oocyte for subsequent steps of fertilization and embryo transfer was shown to be the crucial step in human infertility treatment procedure. Oocyte selection using morphological criteria mainly Zona pellucida (ZP) has been the gold standard method in assisted reproductive technologies (ART) clinics, but this selection approach has limitations in terms of accuracy, objectivity and constancy. Recent studies using OMICs-based approaches have allowed the identification of key molecular markers that quantitatively and non-invasively predict the oocyte quality for higher pregnancy rates and efficient infertility treatment. These biomarkers are a valuable reinforcement of the morphological selection criteria widely used in in vitro fertilization (IVF) clinics. In this context, this study was designed to investigate the relationship between transcriptomic predictors of oocyte quality found by our group and the conventional morphological parameters of oocyte quality mainly the ZP birefringence. Microarray data revealed that 48 and 27 differentially expressed candidate genes in cumulus cells (CCs) were respectively overexpressed and underexpressed in the ZGP (Zona Good Pregnant) versus ZBNP (Zona Bad Non Pregnant) groups. More than 70% of previously reported transcriptomic biomarkers of oocyte developmental competence were confirmed in this study. The analysis of possible association between ZP birefringence versus molecular markers approach showed an absence of correlation between them using the current set of markers. This study suggested a new integrative approach that matches morphological and molecular approaches used to select developmentally competent oocytes able to lead to successful pregnancy and the delivery of healthy baby. For each ZP birefringence score, oocytes displayed a particular CCs' gene expression pattern. However, no correlations were found between the 7 gene biomarkers of oocyte developmental potential and the ZP birefringence score. Further studies using larger lists of candidate markers are required to identify suitable genes that are highly correlated with the morphological criteria, and therefore able to reinforce the accuracy of oocyte selection and the effectiveness of infertility treatment.


Identification of the effector cells in human blood displaying spontaneous cytotoxicity to chicken erythrocytes.
By combining velocity and linear density fractionations as well as target cell rosetting techniques we have isolated and morphologically identified the human effector cell type responsible for spontaneous, trypsin-augmentable cytotoxicity against chicken red cells and human myeloma cell line targets. This cell is a large lymphoid cell with strong alpha-naphthyl esterase activity concentrated in a limited area in the cytoplasm usually at the indentation site of a slightly reniform nucleus. Cells with this morphology also formed plaques on chicken erythrocyte monolayers. The cell is nonphagocytic and nonadherent, it carries Fc receptors but no complement receptors on its surface, and shows a weak affinity to sheep red blood cells (SRBC). The frequency of these cells based on morphological analysis is 3 x 10(4)--6 x 10(4)/ml in normal human blood. This cell shows similarities (surface Ig-, Fc+, C3-) with the human natural killer (NK) cells lytic to hematopoetic target cell lines but differs in that the cytotoxicity is augmentable by trypsin and the affinity to SRBC is lower. Therefore, we postulate that these two killer populations represent different subpopulations of human NK cells.


Possible involvement of oxidative stress as a causative factor in blood-brain barrier dysfunction in stroke-prone spontaneously hypertensive rats.
To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier (BBB) dysfunction, we compared the chronological changes of oxidative stress in blood and cerebral tissue between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age, but not in WKY. There were no significant differences in 8-OHdG or lipid peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by the biological antioxidant potential test, was similar between SHRSP and WKY at all ages examined. The changes in plasma and tissue d-ROM levels coincided with changes in glucose transporter-1 and aquaporin-4 expression, as functional constituents of the BBB. These results indicate that plasma oxidative stress increases before the onset of tissue damage, and plays an important role in BBB dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test appears to be useful for predicting vasogenic cerebral edema in severe hypertension.


Clinical application of EEG topography in cerebral ischemia: detection of functional reversibility and hemodynamics.
To detect the functional reversibility and hemodynamic process in cerebral ischemia, the EEG topography cased on % time and amplitude was applied. % time and amplitude were obtained by the wave-form recognition method/EEGs were recorded under the resting state and during drug-induced conditions in 18 patients with steno-occlusion of main cerebral artery. The type of ischemic attack was TIA in 2 patients, RIND in 4, minor stroke in 7 and major stroke in 5. Six of 11 patients showed the improvement of EEG under induced hypertension. Four of those 6 patients were operated on ECIC bypass surgery, and all of them showed the improvement of clinical and EEG findings postoperatively. Twelve patients showed the deterioration of EEG under induced hypotension. Eight of them were operated on ECIC bypass surgery, and none of them suffered from reattack of cerebral ischemia postoperatively. Those preoperative EEG changes were observed mainly on the EEG topography of % time. And, the analysis of the EEG topography of % time under drug-induced conditions was available to study the pathophysiology of cerebral ischemia for selecting the suitable treatment.


Real-time intraoperative monitoring during neurosurgical and neuroradiological procedures.
A real-time intraoperative evoked potential (EP) monitoring system is described and evaluated. Unique features include (1) online artifact rejection to reduce noise contamination, (2) optimum digital filtering to improve the signal-to-noise ratio of the EP signal, (3) statistically defined confidence intervals to determine significant EP peak latency deviations, and (4) sliding windows of EP subaverages of various sizes to minimize feedback time to the surgeon. The reliability and validity of this system were determined by comparison with conventional intraoperative EP averaging and by examining the correlation of EP parameter changes with concurrent surgical and radiological manipulations. This system was clearly superior to conventional averaging systems. Reliable EPs could be obtained from neurologically compromised patients within the electrically hostile operating room environment, in cases in which conventional averaging failed to extract a stable EP signal. EP update times of 10-20 s were quite common and allowed direct moment-to-moment correlations with surgical and radiological events. Case histories are presented that show the utility of this system for aiding in the prevention of neurological complications. This utility is examined for neurosurgical and neuroradiological procedures involving spinal cord, brainstem, midbrain, and cortical structures, and affecting the somatosensory, motor, auditory, and visual system pathways.


Synthesis of partially modified retro-inverso substance P analogues and their biological activity.
Partial retro-inverso modification of a single peptide bond was applied to pGlu-Phe-Phe-Gly-Leu-Met-NH2 (I), a C-terminal hexapeptide analogue of the neuropeptide substance P. Two analogues with reversed peptide bonds, between the pGlu-Phe and Phe-Gly residues, were prepared, purified and characterized. The analogue gpGlu-(RS)-mPhe-Phe-Gly-Leu-Met-NH2 (II) was devoid of either agonistic or antagonistic activity. The second pseudopeptide analogue, i.e., pGlu-Phe-gPhe-mGly-Leu-Met-NH2 (III), was found to be a full agonist with 22% of the potency of I in the guinea pig ileum assay.


Higher readability of institutional websites drives the correct fruition of the abortion pathway: A cross-sectional study.
In Italy, abortion services are public: therefore, health Institutions should provide clear and easily readable web-based information. We aimed to 1) assess variation in abortion services utilisation; 2) analyse the readability of institutional websites informing on induced abortion; 3) explore whether easier-to-read institutional websites influenced the correct fruition of abortion services. We identified from the 2021 administrative databases of Tuscany all women having an abortion, and-among them-women having an abortion with the certification provided by family counselling centres, following the pathway established by law. We assessed variation in total and certified abortion rates by computing the Systematic Component of Variation. We analysed the readability of the Tuscan health authorities' websites using the readability assessment tool READ-IT. We explored how institutional website readability influenced the odds of having certified abortions by running multilevel logistic models, considering health authorities as the highest-level variables. We observed high variation in the correct utilization of the abortion pathway in terms of certified abortion rates. The READ-IT scores showed that the most readable text was from the Florence Teaching Hospital website. Multilevel models revealed that higher READ-IT scores, corresponding to more difficult texts, resulted in lower odds of certified abortions. Large variation in the proper fruition of abortion pathways occurs in Tuscany, and such variation may depend on readability of institutional websites informing on induced abortion. Therefore, health Institutions should monitor and improve the readability of their websites to ensure proper and more equitable access to abortion.


The Seniors Quality Leap Initiative (SQLI): An International Collaborative to Improve Quality in Long-Term Care.
To describe an innovative Canadian and US community of practice that employs empirical evidence based on risk-adjusted indicators to guide collaborative initiatives to improve the quality of care in nursing homes. Ongoing study of quality of care related to pain management in nursing home residents using clinical assessment records. and Participants: Nursing home residents in 14 organizations in Canada and the United States between 2014 and 2017. The most recent analytic samples for quality indicator calculation involve 11,123 unique residents in 68 homes associated with 12 different long-term care organizations. Assessment data on pain and associated risk adjusters were obtained from the RAI/MDS 2.0 and MDS 3.0 assessments in Canadian and US nursing homes, respectively. The Seniors Quality Leap Initiative has been functioning as an active community of practice for almost a decade with the aim of demonstrating leadership in the use of collaborative approaches to drive evidence-informed improvements in the quality of long-term care. Initiatives with a specific emphasis on improving care related to pain resulted in notable improvements in quality of clinical care in specific homes as well as within the network as a whole. The Seniors Quality Leap Initiative demonstrates that a partnership between organizations in 2 countries can foment quality transitions through a shared commitment to identifying needs; employing flexible, but practical initiatives; and evaluating the impact of those initiatives through a transparent reporting mechanism.


Symptoms of mast cell activation syndrome in functional gastrointestinal disorders.
Objectives: Mast cell involvement is evident in functional gastrointestinal disorders (FGID). FGID and mast cell activation syndrome (MCAS) are associated with multi-organ symptoms. An overlap has not been assessed.Methods: MCAS symptoms were determined by questionnaires in 2083 FGID patients.Results: The median number of MCAS symptoms ([IQR] (range 0-16)) was 6 [4-8] in all FGID, and in functional dyspepsia (FD) patients, 7 [5-9] in overlapping irritable bowel syndrome and FD (IBS+FD), 5 [3-8] in IBS and 5 [3-6] in non-IBS/non-FD (p < .001 vs. FD and IBS + FD) patients. MCAS symptoms in ≥2 organ-systems existed in 1773 (85%) of all patients.Conclusions: MCAS symptoms are common in FGID warranting further mechanistic investigation.


Putative floral brood-site mimicry, loss of autonomous selfing, and reduced vegetative growth are significantly correlated with increased diversification in Asarum (Aristolochiaceae).
The drivers of angiosperm diversity have long been sought and the flower-arthropod association has often been invoked as the most powerful driver of the angiosperm radiation. We now know that features that influence arthropod interactions cannot only affect the diversification of lineages, but also expedite or constrain their rate of extinction, which can equally influence the observed asymmetric richness of extant angiosperm lineages. The genus Asarum (Aristolochiaceae; ∼100 species) is widely distributed in north temperate forests, with substantial vegetative and floral divergence between its three major clades, Euasarum, Geotaenium, and Heterotropa. We used Binary-State Speciation and Extinction Model (BiSSE) Net Diversification tests of character state distributions on a Maximum Likelihood phylogram and a Coalescent Bayesian species tree, inferred from seven chloroplast markers and nuclear rDNA, to test for signal of asymmetric diversification, character state transition, and extinction rates of floral and vegetative characters. We found that reduction in vegetative growth, loss of autonomous self-pollination, and the presence of putative fungal-mimicking floral structures are significantly correlated with increased diversification in Asarum. No significant difference in model likelihood was identified between symmetric and asymmetric rates of character state transitions or extinction. We conclude that the flowers of the Heterotropa clade may have converged on some aspects of basidiomycete sporocarp morphology and that brood-site mimicry, coupled with a reduction in vegetative growth and the loss of autonomous self-pollination, may have driven diversification within Asarum.


Hormonal regulation of lymphocyte functions.
The role of hormones in regulating the complex network of immune responses has lately been emphasized. In particular, glucocorticoids and sex hormones have been shown to modulate both cellular and humoral immunity. Reports concerning the mechanisms of hormonal action are still somewhat conflicting, and there are reports of both inhibitory and stimulatory effects on various phases of the immune response.


Multiple digital glomus tumors.
In 28 patients with glomus tumors of the digits, 21 were relieved of symptoms by excision of a solitary tumor. Seven other patients had multiple tumors, four of which were the cause of recurrent symptoms. Three patients had multiple tumors--five in one patient, four in another, and two in a third, which had been found at the time of the first operation. A 25% incidence of multiple tumors and a 15% incidence of recurrent symptoms indicates that a careful search should be made for additional tumors.


Congenital lipoma of the tongue. Report of a case.
A case of a congenital lipoma of the tongue in a 20-day old female infant is reported. The tumor was completely removed and follow-up showed excellent healing without recurrence.


Magnetofection is superior to other chemical transfection methods in a microglial cell line.
Microglia, the resident phagocytic cells of the brain, have recently been the subject of intense investigation given their role in pathology and normal brain physiology. In general, phagocytic cells are hard to transfect with plasmid DNA. The BV2 cell line is a murine cell line of microglial origin which is often used to study this cell type in vitro. Unfortunately, this microglial cell line is, like other phagocytic cells, resistant to transfection. Magnetofection is a well-established transfection method that combines DNA with magnetic particles which, under the influence of a magnetic field, ensures a high concentration of particles in proximity of cultured cells. Only recently, Glial-Mag was specifically developed for efficient transfection of microglia and microglial cell lines. Magnetofection with Glial-Mag yielded a transfection efficiency of 34.95% in BV2 cells, 24h after transfection with an eGFP-expressing plasmid. Efficient gene delivery caused a modest and short-lived cell activation (as measured by IL6 secretion) that ceased by 24h after transfection. Here we show that Glial-Mag magnetofection of BV2 cells yielded a significantly higher transfection efficiency (34.95%) compared to other chemical transfection methods including calcium-phoshate precipication (0.34%), X-tremeGENE (3.30%) and Lipofectamine 2000 (12.51%). Transfection of BV2 cells using Glial-Mag magnetofection is superior compared to other chemical transfection methods and could be considered as the method of choice to chemically transfect microglial cell lines.


Increased visual impairment after exercise (Uhthoff's phenomenon) in multiple sclerosis: therapeutic possibilities.
The Uhthoff symptom, a transient impairment of visual function after exercise, is demonstrated in 2 multiple sclerosis patients. Following exercise, impairment of visual function, as documented most clearly by the testing of contrast sensitivity, was less obvious after body surface cooling and after treatment with orally administered 4-aminopyridine. It is hypothesized that both treatment modalities improve the nerve conduction safety factor and thereby prevent the occurrence of a conduction block, which is believed to be the mechanism underlying the Uhthoff symptom.


Common complaints in the first 30 days of life.
Visits to the emergency department (ED) by neonates and their parents can cause anxiety for parents and the ED staff. Many of the presenting complaints are unique to the neonatal population, and an understanding of both common problems and true medical emergencies is paramount. This article discusses the complaints the EDs have seen more frequently as a result of earlier newborn discharges from hospitals.


Prohaptoglobin is a possible prognostic biomarker for colorectal cancer.
Fucosylated haptoglobin is a novel glycan biomarker for colorectal and other cancers, while the significance of its precursor, prohaptoglobin (proHp), remains to be elucidated. In this study, we investigated whether proHp can be a colorectal cancer (CRC) biomarker and the biological functions of proHp in CRC using 10-7G, a monoclonal antibody recently developed in our laboratory. Serum proHp level in 74 patients with CRC was semi-quantified by western blotting, and 5-year recurrence-free survival and overall survival were analyzed for groups stratified by proHp status (high vs. low). We also performed immunohistochemical analyses of 17 CRC tissue sections using 10-7G mAb. The biological functions of proHp were evaluated by overexpressing proHp in CRC cell lines. Serum proHp correlated with the clinical stage and poorer prognosis of CRC. In the primary CRC sections, immune cells were stained positive for 10-7G in ∼50% of the cases. Overexpression of proHp in HCT116 human CRC cells induced epithelial-mesenchymal transition-like changes and promoted cell migration in CRC cells. We provide evidence for the first time that proHp has potential as a prognostic biomarker for CRC and demonstrated specific biological activities of proHp.


Exposure to environmental tobacco smoke as a risk factor for recurrent acute otitis media in children under the age of five years.
Exposure to environmental tobacco smoke (ETS) has remained a controversial risk factor for otitis media in children. This study evaluates the association between exposure to ETS and recurrent acute otitis media (RAOM) in 85 cases and 85 age and gender matched controls under the age of 5 years. Cases and controls were obtained from outpatient otolaryngology and ophthalmology clinics, respectively, at the Children's Hospital of Eastern Ontario. Cases were defined as having four or more physician documented AOM episodes in the preceding 12 months and controls were otitis free in the prior 12 months. Exposure status was assessed via parental questionnaire. Controlling for other risk factors (via conditional logistic regression), such as daycare attendance, socioeconomic status, prematurity and family history of otitis media, a significant association between ETS and RAOM was evident (odds ratio = 2.68, 95% CI = 1.27-5.65). When categorized, a significant exposure response relationship between increasing level of exposure to ETS and increased risk of RAOM was evident. The population etiologic fraction indicated that up to 34% of RAOM cases may be accounted for by ETS exposure. We conclude that exposure to ETS is an important and modifiable risk factor for RAOM in children under the age of 5 years.


[Effects on micro-vessel density after pre-operative intra-arterial infusion chemotherapy in colorectal cancer].
To evaluate the effects of pre-operative intra-arterial infusion chemotherapy on colorectal cancer. Twenty-eight patients with colorectal cancer, treated by surgery from February to October 2000, were divided into two groups randomly. There were 12 patients in group A (pre-operative intra-arterial infusion chemotherapy) and 16 in group B (control). Arterial contrast technique was used in group A, then mitromycin 10 mg, 5-Fu 1,000 mg, epirubicin 60 mg were given through Weidner's way. Micro-vessel density in the center, surface of the tumor and adjacent tissue around the tumor were 40.46 +/- 7.06, 52.27 +/- 18.40, 49.92 +/- 8.15 in group A, and 46.09 +/- 12.21, 73.44 +/- 22.06, 51.94 +/- 12.64 in group B. Micro-vessel density on the surface in group A was significantly lower than that of group B (P < 0.05), with no significance between the center and the adjacent tissue. Pre-operative intra-arterial infusion chemotherapy is able to reduce micro-vessel density on the surface of colorectal tumor.


Identification of acetylcholinesterase-reactive neurons and neuropil in neostriatal transplants.
To identify and describe neurons in neostriatal transplants that synthesize acetylcholinesterase (AChE), the present study has utilized the irreversible AChE inhibitor diisopropylfluorophosphate (DFP) combined with AChE histochemistry. Dissociated suspensions of tissue taken from the striatal ridge of embryos at 14 days of gestation were transplanted into the neostriatum of adult rats 5 days after intrastriatal kainic acid lesions. Two types of AChE neurons have been identified in transplants treated with DFP. One type resembled the large intensely reactive AChE neuron that is thought to be a cholinergic interneuron of the normal neostriatum. The other type resembled smaller, less reactive AChE neurons of the neostriatum, as well as medium-sized, lightly reactive AChE neurons of the globus pallidus. Qualitative observations suggest that these less reactive AChE neurons were more numerous in transplants compared to the normal neostriatum. Both AChE neuronal types were found in segregated clusters throughout the grafts. Transplants processed for AChE histochemistry without DFP treatment contained two types of AChE neuropil. Dark areas of AChE neuropil similar in intensity to the normal neostriatum were found between larger areas of lighter AChE neuropil. These results demonstrate that neostriatal transplants contain AChE neurons and suggest that these neurons contribute to the AChE reactivity within the graft.


In vivo measures of monoamines during amphetamine-induced behaviors in rats.
1. Using a removable in vivo microdialysis probe, and remote sample collection, the temporal and dose-related behavioral and monoamine response to amphetamine (AMPH) were examined in freely-moving rats. Extracellular dopamine, serotonin and their metabolites were monitored concomitant with detailed characterization of the locomotor and stereotypy profiles. Consistent with previous results, AMPH (0.5-5.0 mg/kg) induced a rapid dose-dependent increase in dopamine concentration and decrease in the concentrations of the dopamine metabolites. Dopamine and metabolites exhibited contrasting temporal and dose-related patterns, suggesting that the decline in dopamine metabolites is functionally dissociated from the AMPH-enhanced dopamine release, and that metabolite levels do not provide an accurate index of functional dopaminergic activity. 2. Dose response comparisons revealed a significant relationship between AMPH-induced increases in behavioral perseveration and the magnitude and duration of the dopamine release. However, the temporal patterns of the neurotransmitter response and individual components of stereotypy were not parallel, suggesting that the presence of stereotypies is not associated simply with quantitative differences in striatal dopamine release. 3. Consistent with this interpretation, we found that a variety of manipulations including reserpine, apomorphine, and chronic amphetamine pretreatment, produced a dissociation between the alterations in the behavioral and dopaminergic responses to amphetamine. The behavioral response to amphetamine may be influenced by the interaction between levels of dopamine and serotonin, by the state of their respective receptors, and by the relative contributions of additional dopaminergic systems.


Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection.
The novel Malawi polyomavirus (MWPyV) was initially detected in stool specimens from healthy children and children with gastrointestinal symptoms, mostly diarrhea, indicating that MWPyV might play a role in human gastroenteric diseases. Recently, MWPyV sequences were additionally identified in respiratory secretions from both healthy and acutely ill children suggesting that MWPyV may have a tropism for different human tissues. This study was designed to investigate the possible sites of latency/persistence for MWPyV in a cohort of healthy Italian children. Specimens (n° 500) of tonsils, adenoids, blood, urines and feces, from 200 healthy and immunocompetent children (age range: 1-15 years) were tested for the amplification of the MWPyV LT antigen sequence by quantitative real-time PCR. Samples (n° 80) of blood and urines from 40 age-matched children with autoimmune diseases, were screened for comparison. Polyomaviruses JC/BK and Epstein-Barr Virus (EBV) were also tested as markers of infection in all samples using the same molecular technique. In our series of healthy children, MWPyV was detected only in the lymphoid tissues showing a prevalence of 6 % in tonsils and 1 % in adenoids, although with a low viral load. No JCPyV or BKPyV co-infection was found in MWPyV positive samples, while EBV showed a similar percentage of both in tonsils and adenoids (38 and 37 %). Conversely, no MWPyV DNA was detected in stool from babies with gastroenteric syndrome. With regards to autoimmune children, neither MWPyV nor BKPyV were detected in blood, while JCPyV viremia was observed in 15 % (6/40) of children treated with Infliximab. Urinary BKPyV shedding was observed in 12.5 % (5/40) while JCPyV in 100 % of the samples. The detection of MWPyV sequences in tonsils and adenoids of healthy children suggests that secondary lymphoid tissues can harbour MWPyV probably as transient sites of persistence rather than actual sites of latency.


Identification of the mineralization front: comparison of a modified toluidine blue stain with tetracycline fluorescence.
A modified toluidine blue method for identification of the mineralization front at the zone of demarcation between bone and osteoid in undecalcified, plastic-embedded sections of bone is described. The intensity of staining is increased both by increasing the pH of the solution and by increasing the duration of staining. The method is reproducible, since measurements of the extent of mineralization front on two nonadjacent sections from the same biopsy in 20 cases had a correlation coefficient of 0.98. The identification of the mineralization front by toluidine blue agrees closely with identification by means of in vivo tetracycline uptake, with a correlation coefficient of 0.97 between measurements of its extent using the two methods on adjacent sections from the same biopsy. It is likely that both toluidine blue staining at pH 6.5 and tetracycline uptake depend on some property of the most recently deposited bone mineral. With either method we find low values for the extent of mineralization front as a fraction of osteoid surface in many patients with osteoporosis. The uniformly normal values for this quantity in osteoporosis reported by other investigators may reflect different criteria for distinguishing osteoid-covered from quiescent bone surfaces.


Sex and season-related differences of basic haematological values in the mountain reedbuck (Reduncula fulvorufula).
1. Basic haematological values in the peripheral blood of four male and 13 female mountain reedbucks (Reduncula fulvorufula) have been repeatedly estimated. 2. Comparing these results for both sexes, we noted pronouncedly lower haematocrit values and haemoglobin contents in females (statistical significance less than or greater than 1%). In the white blood cells only an increased proportion of neutrophils in females was apparent. 3. We have been unable to find seasonal related differences in the red and white blood overall picture of the cells during the summer and winter seasons with the exception of raised red cell counts and increased proportion of monocytes in the winter. The presented findings are compared and discussed with those abstracted from the literature.


A DFT investigation of the potential of porous cages for the catalysis of ammonia borane dehydrogenation.
Full DFT based quantum mechanical studies reveal that zero dimensional porous structures, especially the newly proposed phosphorus incorporated organic cages, can be excellent catalysts for the dehydrogenation of ammonia borane.


Nurses' stories: the search for a relational ethic of care.
The author begins by telling "Mike's story," a personal narrative account of an interaction with a patient. "Mike's story" provides a lens through which the author explores an alternative paradigm for nursing ethics--a paradigm grounded in a relational ethic of care. Mike's case is used to demonstrate how the moral experience of the nurse is distorted by the standard of moral rationality in traditional biomedical ethics. An interpretive analysis of "Mike's story" attempts to capture some of the fundamental assumptions of a relational ethic of care. The author identifies the benefits of grounding a theory of nursing ethics in nurses' conflicting stories of caregiving and encourages nurses to claim those stories that reflect the moral foundation of nursing.


Effects of danazol, gonadotropin-releasing hormone agonist, and a combination of danazol and gonadotropin-releasing hormone agonist on experimental endometriosis.
Effects of danazol, gonadotropin-releasing hormone agonist (leuprolide), and danazol-leuprolide combination on experimental endometriosis were evaluated in female rats. A complete resorption of the fluid and a marked decrease in the volume of endometrium autotransplanted under the renal capsule were found after castration (1.4 +/- 0.1 mm3 in castrated, n = 14, vs 26.7 +/- 5.6 mm3 in intact control, n = 16). Histologic examination indicated atrophy and regression of the endometrial explant. These atrophic changes of endometrial explant were also induced by danazol, leuprolide, and the combination treatment. However, the volume of explants after combination therapy with danazol and leuprolide (1.8 +/- 1.0 mm3, n = 17) was significantly less than that after therapy with danazol (11.6 +/- 2.8 mm3, n = 20) or leuprolide alone (5.9 +/- 1.4 mm3, n = 24). The combination therapy (16/17) was also shown to be superior to danazol (9/20) or leuprolide alone (14/24) to induce the regression of fluid in experimental endometriosis. As expected, administration of leuprolide decreased the serum estradiol level, but use of danazol did not. These findings suggest that a combination therapy of danazol and gonadotropin-releasing hormone agonist, which show different modes of action, may be a potential modality in treatment of patients with advanced endometriosis.


A Benzophenone-Based Photocaging Strategy for the N7 Position of Guanosine.
Selective modification of nucleobases with photolabile caging groups enables the study and control of processes and interactions of nucleic acids. Numerous positions on nucleobases have been targeted, but all involve formal substitution of a hydrogen atom with a photocaging group. Nature, however, also uses ring-nitrogen methylation, such as m7 G and m1 A, to change the electronic structure and properties of RNA and control biomolecular interactions essential for translation and turnover. We report that aryl ketones such as benzophenone and α-hydroxyalkyl ketone are photolabile caging groups if installed at the N7 position of guanosine or the N1 position of adenosine. Common photocaging groups derived from the ortho-nitrobenzyl moiety were not suitable. Both chemical and enzymatic methods for site-specific modification of N7G in nucleosides, dinucleotides, and RNA were developed, thereby opening the door to studying the molecular interactions of m7 G and m1 A with spatiotemporal control.


Lead-Free KNN-Based Textured Ceramics for High-Frequency Ultrasonic Transducer Application.
Environment-friendly lead-free piezoelectric materials with excellent piezoelectric properties are needed for high-frequency ultrasonic transducer applications. Recently, lead-free 0.915(K0.45Na0.5Li0.05)NbO3-0.075BaZrO 3-0.01(Bi0.5Na0.5)TiO3 (KNLN-BZ-BNT) textured piezo- electric ceramics have high piezoelectric response, superior thermal stability, and excellent fatigue resistance, which are promising for devices applications. In this work, the KNLN-BZ-BNT textured ceramics were prepared by the tape-casting method. Microstructural morphology, phase transition, and electrical properties of KNLN-BZ-BNT textured ceramics were investigated. High-frequency needle-type ultrasonic transducers were designed and fabricated with these textured ceramics. The tightly focused transducers have a center frequency higher than 80 MHz and a -6-dB fractional bandwidth of 52%. Such transducers were built for an f -number close to 1, and the desired focal depth was achieved by press-focusing technology associated with a set of customer design fixture. Its lateral resolution was better than [Formula: see text] by scanning a 15- [Formula: see text] tungsten wire target. These promising results demonstrate that the lead-free KNLN-BZ-BNT textured ceramic is a good candidate for high-frequency ultrasonic transducer applications.


Chronic alcohol exposure alters action control via hyperactive premotor corticostriatal activity.
Alcohol use disorder (AUD) alters decision-making control over actions, but disruptions to the responsible neural circuit mechanisms are unclear. Premotor corticostriatal circuits are implicated in balancing goal-directed and habitual control over actions and show disruption in disorders with compulsive, inflexible behaviors, including AUD. However, whether there is a causal link between disrupted premotor activity and altered action control is unknown. Here, we find that mice chronically exposed to alcohol (chronic intermittent ethanol [CIE]) showed impaired ability to use recent action information to guide subsequent actions. Prior CIE exposure resulted in aberrant increases in the calcium activity of premotor cortex (M2) neurons that project to the dorsal medial striatum (M2-DMS) during action control. Chemogenetic reduction of this CIE-induced hyperactivity in M2-DMS neurons rescued goal-directed action control. This suggests a direct, causal relationship between chronic alcohol disruption to premotor circuits and decision-making strategy and provides mechanistic support for targeting activity of human premotor regions as a potential treatment in AUD.


Prenatal Activation of Glucocorticoid Receptors Induces Memory Impairment in a Sex-Dependent Manner: Role of Cyclooxygenase-2.
Prenatal exposure to dexamethasone (DEX) results in long-lasting effects on cognitive functions such as learning and memory impairment. However, the mechanisms underlying these DEX-induced deleterious effects are not well known. Here, we assessed whether cyclooxygenase-2 (COX-2) is involved in the impact of prenatal exposure to DEX on learning and memory during adulthood. Pregnant Sprague-Dawley rats received daily injections of either DEX (0.2 mg/kg; i.p.) or saline from gestation day (GD) 14 until GD21. Gene and protein expression of COX-2, as well as presynaptic (synaptophysin) and postsynaptic (postsynaptic density protein-95) proteins, were monitored in the dorsal and ventral hippocampi of adult male and female offspring. A different cohort of adult male and female rat offspring was given daily injections of either vehicle or a specific COX-2 inhibitor (celecoxib 10 mg/kg, i.p.) for 5 consecutive days and was subsequently subjected to Morris water maze memory test. Prenatal DEX enhanced the expression of COX-2 protein and cox-2 mRNA in the dorsal hippocampus of adult female but not male rats. This enhanced COX-2 expression was associated with reduced expression in pre- and postsynaptic proteins and altered memory acquisition and retention. Administration of COX-2-specific inhibitor alleviated prenatal DEX-induced memory impairment in adult female rats. This study suggests that prenatal activation of glucocorticoid receptors stimulates COX-2 gene and protein expression and impairs hippocampal-dependent spatial memory in female but not male rat offspring. Furthermore, COX-2 selective inhibitors can be used to alleviate the long-lasting deleterious effects of corticosteroid medication during pregnancy.


Increased oscillatory theta activation evoked by violent digital game events.
The authors examined electroencephalographic (EEG) oscillatory responses to two violent events, the player character wounding and killing an opponent character with a gun, in the digital game James Bond 007: NightFire. EEG was recorded from 25 (16 male) right-handed healthy young adults. EEG data were segmented into one 1-s baseline epoch before each event and two 1-s epochs after event onset. Power estimates (microV(2)) were derived with the fast Fourier transform (FFT) for each artefact free event. Both of the studied events evoked increased occipital theta (4-6Hz) responses as compared to the pre-event baseline. The wounding event evoked also increased occipital high theta (6-8Hz) response and the killing event evoked low alpha (8-10Hz) asymmetry over the central electrodes, both relative to the pre-event baseline. The results are discussed in light of facial electromyographic and electrodermal activity responses evoked by these same events, and it is suggested that the reported EEG responses may be attributable to affective processes related to these violent game events.


Performance study of biofilter developed to treat H2S from wastewater odour.
Biofiltration is an efficient biotechnological process used for waste gas abatement in various industrial processes. It offers low operating and capital costs and produces minimal secondary waste streams. The objective of this study was to evaluate the performance of a pilot scale biofilter in terms of pollutants' removal efficiencies and the bacterial dynamics under different inlet concentrations of H2S. The treatment of odourous pollutants by biofiltration was investigated at a municipal wastewater treatment plant (WWTP) (Charguia, Tunis, Tunisia). Sampling and analyses were conducted for 150 days. Inlet H2S concentration recorded was between 200 and 1300 mg H2S.m(-3). Removal efficiencies reached 99% for the majority of the running time at an empty bed retention time (EBRT) of 60 s. Heterotrophic bacteria were found to be the dominant microorganisms in the biofilter. The bacteria were identified as the members of the genus Bacillus, Pseudomonas and xanthomonadacea bacterium. The polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) method showed that bacterial community profiles changed with the H2S inlet concentration. Our results indicated that the biofilter system, containing peat as the packing material, was proved able to remove H2S from the WWTP odourous pollutants.


The food retail environment and its use in a deprived, urban area of Scotland.
This study sought to describe the food retail environment and its use in a deprived urban area in Scotland by mapping all food outlets and determining where residents do their main food shopping as well as investigating the availability of fresh fruit and vegetables (F&V) (as an indicator of healthy eating) and takeaway food. Cross-sectional study. The food retail environment, the number, size and food availability of all food outlets, was mapped in Viewpark, a small community located to the east of Glasgow. Subsequently a validated questionnaire was used to determined food shopping usage and habits. There was high availability of common fresh fruit and vegetables (F&V) and very high availability of fast food outlets. Only 9% of the sample shopped solely at local food outlets within Viewpark whilst 91% shopped at a large supermarket outside Viewpark (n = 106). Walking was significantly negatively associated (B = -3.555, P = 0.008) with shopping outside the community. The majority of respondents (80%) reported buying F&V weekly and 57% purchased takeaways at least once a week - these individuals were employed, over 45 years old and had at least one child. The use of the local retail environment in a deprived community is influenced by car accessibility.


Silanized fiberglass modified by carbon dots as novel and impressive adsorbent for aqueous heavy metal ion removal.
This work discusses the application of a silanized fiberglass (SFG) modified by carbon dots (CDs) as an effective adsorbent for up-taking some heavy metal ions including lead (Pb2+), chromium (Cr3+), cadmium (Cd2+), cobalt (Co2+), and nickel (Ni2+) as pollutant in the aqueous solution by batch method. Removal tests were carried out after optimization of pH, contact time, initial concentration of metal ions, and CDs amount. The SFG modified with CDs (CDs-SFG) was applied for the removal of 10 ppm of each metal ion solution after 100 min and the corresponding results showed the removal efficiencies of 100, 93.2, 91.8, 90, and 88.3% for Pb2+, Cd2+, Cr3+, Co2+, and Ni2+, respectively. The adsorption capacity of CDs-SFG in the metal ion mixed solution was also evaluated, and the results indicated the same trend in the adsorption capacity for metal ions in the mixed solution, though with lower absolute values compared to the single metal solutions. Moreover, the selectivity of this adsorbent for the adsorption of Pb2+ was almost twice of other tested metal ions. The regeneration of the CDs-SFG showed that its adsorption capacity after five cycles was reduced about 3.9, 6.0, 6.8, 6.7, and 8.0% for Pb2+, Cd2+, Cr3+, Co2+, and Ni2+, respectively. Finally, the applicability of the CDs-SFG adsorbent was examined with the analysis of the metal ions in water and wastewater samples.


Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo.
Eleven healthy volunteers received a single intravenous dose of diazepam (0.15 mg/kg), midazolam (0.1 mg/kg), and placebo by 1-minute infusion in a double-blind, three-way crossover study. Plasma concentrations were measured during 24 hours after dosage, and the electroencephalographic (EEG) power spectrum was simultaneously computed by fast-Fourier transform to determine the percentage of total EEG amplitude occurring in the 13 to 30 Hz range. Both diazepam and midazolam had large volumes of distribution (1.2 and 2.3 L/kg, respectively), but diazepam's half-life was considerably longer (33 versus 2.8 hours) and its metabolic clearance lower (0.5 versus 11.0 ml/min kg) than those of midazolam. EEG changes were maximal at the end of the diazepam infusion and 5 to 10 minutes after midazolam infusion. Percent 13 to 30 Hz activity remained significantly above baseline until 5 hours for diazepam but only until 2 hours for midazolam. For both drugs, EEG effects were indistinguishable from baseline by 6 to 8 hours, suggesting that distribution contributes importantly to terminating pharmacodynamic action. The relationship of EEG change to plasma drug concentration indicated an apparent EC50 value of 269 ng/ml for diazepam as opposed to 35 ng/ml for midazolam. However, Emax values were similar for both drugs (+19.4% and +21.3%, respectively).


[Risk assessment of human exposure to pesticides in food].
This review presents methods for the assessment of acute and chronic risk from pesticide residues in food. Multiple pesticide residues can often be found in food. Currently, there is no internationally accepted procedure for the assessment of cumulative exposure to multiple pesticide residues in food. Therefore, risk assessment is based on toxicological evaluation of single compounds in a food matrix. The international estimation of short-term intake model (IESTI) has been used to calculate acute intake. IESTI is based on "the worst-case scenario" and addresses the possibility that consumers sometimes eat large amounts of a food item, and such a large amount might contain residues at highest levels. However, it should take into account uneven distribution of pesticide residues in food. Chronic exposure is based on a deterministic approach, analogous to the calculation of the theoretical maximum daily intake.


Akinesia due to catecholamine depletion in mice is prevented by caffeine. Further evidence for an involvement of adenosinergic system in the control of motility.
The administration of reserpine with alpha-methyl-p-tyrosine (2.5 and 200 mg kg-1 i.p., 24 and 3 h before the test, respectively) induced a marked akinesia in mice. This effect was significantly and dose-dependently reversed by the methylxanthine, caffeine. The anti-akinetic effect of caffeine within a pattern of catecholamine depletion has been interpreted as a dopamine mimetic activity of this drug. The possible involvement of the adenosine system in this effect of caffeine is discussed.


Effect of pre-injection opioid use on post-injection patient-reported outcomes following epidural steroid injections for radicular pain.
Chronic opioid therapy is associated with worse patient-reported outcomes (PROs) following spine surgery. However, little literature exists on the relationship between opioid use and PROs following epidural steroid injections for radicular pain. We evaluated the association between pre-injection opioid use and PROs following spine epidural steroid injection. This study is a retrospective analysis of a prospective longitudinal registry database. A total of 392 patients within our database who were undergoing epidural steroid injections (ESIs) at our institution for degenerative structural spine diagnoses and met our inclusion criteria were included in this study. Patient-reported outcomes for disability (Oswestry Disability Index/Neck Disability Index [ODI/NDI)]), quality of life (EuroQol-5D [EQ-5D]), and pain (Numerical Rating Scale scores for back pain, neck pain, leg pain, and arm pain [NRS-BP/NP/LP/AP]) were assessed at baseline and at 3 and 12 months post-injection. Multivariable proportional odds logistic regression models were created to examine the relationship between pre-injection opioid use and post-injection PROs. A logistic regression with Bayesian Markov chain Monte Carlo parameter estimation was used to investigate a possible cutoff value of pre-injection opioid use above which the effectiveness of ESI (as measured by minimum clinically important difference [MCID] for ODI/NDI) decreases. A total of 276 patients with complete 12-month follow-up following ESI were analyzed. The mean pre-injection daily morphine equivalent amount (MEA) was 14.7 mg (95% confidence interval [CI] 12.4 mg-19.1 mg) for the cohort. Pre-injection opioid use was associated with slightly higher odds of worse disability (odds ratio [OR] 1.03, p=.03) and leg/arm pain (OR 1.01, p=.04) scores at 3 months post-injection only. No significant association between pre-injection opioid use and MCID for ODI/NDI was found, although a cutoff of 55.5 mg/day might serve as a significant threshold. Increased pre-injection opioid use does not impact long-term outcomes after ESIs for degenerative spine diseases. A pre-injection MEA around 50 mg/day may represent a threshold above which the 3-month effectiveness of ESI for back- and neck-related disability decreases. Epidural steroid injection is an effective treatment modality for pain in patients using opioids, and can be part of a multimodal strategy for opioid independence.


A large accessory protein interactome is rewired across environments.
To characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in the yeast Saccharomyces cerevisiae across nine growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a threefold increase over PPIs identified in one condition. A few 'immutable' PPIs are present across all conditions, while most 'mutable' PPIs are rarely observed. Immutable PPIs aggregate into highly connected 'core' network modules, with most network remodeling occurring within a loosely connected 'accessory' module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.


Adverse effects of neutrophils on the lung.
Studies of both emphysema and adult respiratory distress syndrome (ARDS) support the premise that lung injury is due to unregulated host defense mechanisms. A major mediator of host defense and injury is the neutrophil, which is relatively incapable of regulating its own function. Accordingly, defects in regulatory mechanisms allow neutrophils to damage the lungs. Emphysema serves as a prime example of this link between host defense and injury. Hereditary emphysema is caused by a deficiency in alpha 1-antitrypsin (alpha 1-AT), a protease inhibitor. The decreased levels of this enzyme in affected individuals result in inadequate protection against neutrophil elastase and other proteolytic enzymes, leading to lung damage. Patients with acquired emphysema, associated with cigarette smoking, have normal levels of alpha 1-AT in their lungs. However, the alpha 1-AT in these patients has a reduced ability to associate with and inhibit the action of neutrophil elastase. Thus, both types of emphysema involve an alteration in the balance between proteases and antiproteases. The lung damage observed in patients with ARDS also appears to involve neutrophils, but in this case elastase may not be the culprit. In these patients, neutrophil elastase appears to be inactivated by high levels of alpha 1-AT, thus preventing excess protease action. It is hoped that a more complete understanding of the mechanisms involved in host defense and injury will enable the development of specific therapeutic interventions, such as the alpha 1-AT replacement therapy that is being used to treat patients with hereditary emphysema.


Early Pregnancy-Associated Plasma Protein A Concentrations Are Associated With Third Trimester Insulin Sensitivity.
First or early second trimester pregnancy-associated plasma protein A (PAPP-A) concentrations have previously been shown to be lower in women who subsequently develop gestational diabetes mellitus (GDM) and gestational hypertension. We therefore sought to investigate why circulating PAPP-A concentrations are related to the subsequent risk of GDM and gestational hypertension. We measured serum PAPP-A concentrations around week 15 of pregnancy and related these to indices derived from week 28 oral glucose tolerance tests and blood pressures across pregnancy in the Cambridge Baby Growth Study cohort. Increased PAPP-A concentrations were associated with reduced GDM risk [odds ratio 0.623 (0.453, 0.856), P = 3.5 × 10-3, n = 777] and reduced mean arterial blood pressures (β = -0.202 to -0.177, P = 1.7 to 6.9 × 10-3, n = 347 to 355). They were also negatively associated with week 28 fasting (β = -0.149, P = 6.6 × 10-4, n = 777) and 60-minute (β = -0.188, P = 1.5 × 10-5, n = 777) oral glucose tolerance test glucose concentrations. These associations were underpinned by the strong associations between increased week 15 PAPP-A concentrations and decreased week 28 insulin resistance (homeostasis model assessment of insulin resistance: β = -0.319, P = 1.7 × 10-13, n = 768), as well as increased insulin secretion relative to insulin sensitivity (insulin disposition index: β = 0.202, P = 6.5 × 10-6, n = 731). These results suggest that links between PAPP-A concentrations in early pregnancy and subsequent glucose concentrations and blood pressures may be mediated by changes in insulin sensitivity (and secretion).


Learning to represent continuous variables in heterogeneous neural networks.
Animals must monitor continuous variables such as position or head direction. Manifold attractor networks-which enable a continuum of persistent neuronal states-provide a key framework to explain this monitoring ability. Neural networks with symmetric synaptic connectivity dominate this framework but are inconsistent with the diverse synaptic connectivity and neuronal representations observed in experiments. Here, we developed a theory for manifold attractors in trained neural networks, which approximates a continuum of persistent states, without assuming unrealistic symmetry. We exploit the theory to predict how asymmetries in the representation and heterogeneity in the connectivity affect the formation of the manifold via training, shape network response to stimulus, and govern mechanisms that possibly lead to destabilization of the manifold. Our work suggests that the functional properties of manifold attractors in the brain can be inferred from the overlooked asymmetries in connectivity and in the low-dimensional representation of the encoded variable.


Comparison of surgical stress between laparoscopic and open appendectomy in children.
The present study aimed to evaluate laparoscopic appendectomy (LA) in comparison with conventional open appendectomy (OA) in children, with special emphasis on the extent of surgical trauma after LA and OA, and to assess whether LA had any clear advantages compared with conventional OA. A total of 160 patients with a median age of 7.9 years (range 3-15 years) were studied. Sixty-nine of them underwent LA, and the remaining 91 underwent OA. Serum interleukin (IL) 6 and C-reactive protein (CRP) levels which are thought to play a pivotal role in the pathogenesis of surgical trauma and can also be used to monitor the magnitude of surgical trauma were measured using an enzyme-linked immunosorbent assay before surgery and 12 hours after surgery. In addition, we compared operating time, hospital stay, incidence of wound infection, and incidence of intra-abdominal infection. The operative time of normal and suppurative appendix in the laparoscopic group was significantly shorter than that in the open group, respectively, but the operative time of gangrenous appendix was not different between the laparoscopic group and open group. The hospital stay in the laparoscopic group was also significantly shorter than that in the open group. Postoperatively, 1 patient had port-site infection in the laparoscopic group, whereas 10 had wound infection in the open group; this difference was highly significant (chi2 = 4.19, P < .05). Three patients in the open group and 2 patients in the laparoscopic group had intra-abdominal infection, and the difference had no statistically significant difference (chi2 = 0.10, P < .05). Preoperative IL-6 levels were not different between the 2 groups, but the rise (preoperative vs postoperative) of IL-6 in the laparoscopic group was remarkably less than that in the open group. Similar results were obtained for CRP; serum CRP levels in the basal state were not different between the 2 groups, but the rise (preoperative vs postoperative) of CRP in the laparoscopic group was also substantially less compared with that in the open group. LA for children was as safe and effective as the open procedure and had significant advantages over OA because of less operating time, less postoperative complications, less surgical trauma, and more rapid postoperative recovery.


Computed tomography application to lumbar epidurography.
The application of current-generation computed tomography scanning to lumbar epidurography has resulted in a better appreciation of epidural anatomy and improved ease of interpretation of non-ionic contrast material within the epidural space. The development of extended window width has greatly improved imaging of the more variable levels of attenuation encountered in contrast material within the epidural space. The procedure of distribution of contrast material by catheter technique via the sacral canal approach is described. The experience obtained on examination of 24 patients is discussed, along with the possible adjunctive and primary roles of this type of imaging in evaluation of the lumbar spine.


How to optimise patient and public involvement in your research: Doing science.
This paper considers how best to achieve patient and public involvement in research and how to get the most out of it http://ow.ly/R0hwV.


Greenhouse gas emissions of an outpatient care service: a cost-based approach.
Climate change is already having an impact on global health and will continue to do so even more. Heat waves and extreme weather events are only part of the impact. Adapting health services to these threats is only partially possible, so another focus should be on mitigating climate change by minimising greenhouse gas emissions. In this context, health care can play an important role. However, evidence about greenhouse gas emission hotspots and alternative action to mitigate greenhouse gas emissions is needed for the shift to a climate-friendly health system. In this paper, the greenhouse gas emissions of an outpatient care service will be calculated. On the one hand, focal points of the emissions will be identified and the effects of climate-friendly measures calculated. In order to calculate a comprehensive footprint, a hybrid approach was chosen in which emissions from electricity, gas and fuels are determined on the basis of quantities, and emissions resulting from the production of consumer goods are calculated using cost-based emission factors. The expenditure and consumption data required come from a care service in Lower Saxony providing for 132 people in need of care. The outpatient care service emitted a total of 37,258 kg CO2eq in 2018, i.e. roughly 282 kg CO2eq per year and person in need of care. The production (15%) and combustion of fuels (68%) accounted for the largest share of 73%. By switching to diesel vehicles, the care service could save 7% of the annual greenhouse gas emissions and by switching to electric vehicles up to 30%. The study shows that the outpatient care service produces greenhouse gas emissions of about 282 kg CO2eq per year and person in need of care, which is a relevant amount given the average per capita emission of 7.9 kg CO2 in Germany. However, these emissions can be reduced by more than half by making the relatively easy switch to electric cars. Limitations of the study relate to potential inaccuracies of the cost-based emission factors and the lack of information about the kilometers driven and the fuel consumed. The majority of the emissions of an ambulatory care service comes from the production and combustion of fuels. However, this source can be significantly reduced by switching to modern technologies. To validate the results of this study, further studies should be conducted, preferably with a bottom-up methodology.


Timing of life cycles in a seasonal environment: the temperature-dependence of embryogenesis and diapause in a grasshopper (Chorthippus brunneus Thunberg).
The durations of the stages in the embryonic development of Chorthippus brunneus (Thunberg) have been estimated at constant temperatures of 20° C and 30° C. There was stage-dependent variation in the temperaturedependence of morphogenesis-a pattern apparently not previously described. The earliest and latest stages of morphogenesis proceeded relatively rapidly at higher temperatures. But intermediate stages, which would tend to occur around the diapause stage in a temperate winter, proceeded relatively rapidly at lower temperatures, as did diapause development. At a given temperature, there was individual variation between eggs such that some developed consistently faster than others. However, these intrinsic differences could be altered by exposure to diapause-breaking conditions at different morphological stages. The results are discussed in terms of their adaptive significance, their effect on population dynamics in a seasonal environment, and their implications for the nature of diapause in insects generally.


Ruffus: a lightweight Python library for computational pipelines.
Computational pipelines are common place in scientific research. However, most of the resources for constructing pipelines are heavyweight systems with graphical user interfaces. Ruffus is a library for the creation of computational pipelines. Its lightweight and unobtrusive design recommends it for use even for the most trivial of analyses. At the same time, it is powerful enough to have been used for complex workflows involving more than 50 interdependent stages. Ruffus is written in python. Source code, a short tutorial, examples and a comprehensive user manual are freely available at http://www.ruffus.org.uk. The example program is available at http://www.ruffus.org.uk/examples/bioinformatics


[Disorder in the ratio of cortisol and insulin secretion in peptic ulcer and following vagotomy].
It was established that non-operated patients with duodenal ulcer and patients after organ-saving operations associated with vagotomy show an essential increase of insulin and cortisol secretion and reveal a strict dependence of hormonal secretion on the severity of the pathological process and time after operation. The increased cortisol/insulin ratio correlated with a reduction of the body mass of patients.


Gas-containing renal stones: a red flag for renal infection.
Gas in the renal excretory system is described as a consequence of recent procedures but it can be a sign of severe conditions such as fistulas or infections; however, gas-containing renal stones are only rarely encountered. To describe the association of gas-containing renal stones and urinary tract infection. We performed a retrospective evaluation of the clinical and imaging findings in a series of six patients with gas-containing renal stones and compared our findings with those of patients with gas-containing renal stones reported in the literature. Urine and stone cultures were used as a diagnostic standard for urinary tract infection. Including the present series, there is a total of 21 patients with gas-containing renal stones in the literature. Based on clinical presentation, urinary tract infection could be suspected in 10 (57%) patients, while urine and/or stone cultures showed infection in 18 of 19 (95%) patients, with only one case with no bacterial growth in both (5%); in the remaining patient the information was not available. Gas-containing renal stones are a rarely reported entity usually diagnosed with computed tomography. They are a radiological sign often associated with urinary tract infection that can also be encountered in patients with non-specific renal symptoms.


Barriers to Disclosure of Disability and Request for Accommodations Among First-Year Resident Physicians in the US.
Ensuring access to accommodations is critical for resident physicians and their patients. Studies show that a large proportion of medical trainees with disabilities do not request needed accommodations; however, drivers of nonrequests are unknown. To assess the frequency of accommodation requests among first-year resident physicians (ie, interns) with disabilities and to identify possible drivers of nonrequest for needed accommodations. As part of the Intern Health Study, a longitudinal cohort study of first-year resident physicians, residents at 86 surgical and nonsurgical residency programs in 64 US institutions provided demographic and training characteristics 2 months prior to matriculation (April-May 2021). At the end of their intern year (June 2022), participants completed a new survey with questions about disability-related information, including disability status, disability type, whether they received accommodations, and if not, reasons for nonaccommodation. Poststratification and attrition weights were used to estimate the frequency of accommodation requests and reasons for not requesting accommodations. Interns reporting at least 1 disability were included in the analysis. Prevalence of reported disabilities, residency specialties distribution, frequency of accommodation requests, and reasons for nonaccommodation among resident physicians with disabilities. Among the 1486 resident physicians who completed the baseline survey, 799 (53.8%) replied to the disability questions. Of those, 94 interns (11.8%; weighted number, 173 [11.9%]) reported at least 1 disability and were included in the present study (weighted numbers, 91 [52.6%] men, 82 [47.4%] women, mean [SD] age, 28.6 [3.0] years). Among interns with reported disability and need for accommodations (83 of 173 [48.0%]), more than half (42 [50.6%]) did not request them. The most frequently reported reasons for not requesting needed accommodations were fear of stigma or bias (25 [59.5%]), lack of a clear institutional process for requesting accommodations (10 [23.8%]), and lack of documentation (5 [11.9%]). Program directors should investigate cultural and structural factors within their programs that contribute to an environment where residents do not feel safe or supported in disclosing disability and requesting accommodation and review their disability policies for clarity.


Sirt1 mediates the effects of a short-term high-fat diet on the heart.
High-fat diet leads to development of cardiac dysfunction through molecular mechanisms poorly known. The aim of this study is to elucidate the early events in cardiac dysfunction caused by a high-fat diet, before massive alterations due to obesity and indirect mechanisms of heart damage take place. Moreover, we analyzed the role of Sirt1, a major mediator of cardiac gene regulation, in these effects. Short-term high-fat feeding (5 weeks) caused a similar mild increase in body weight and triglyceridaemia in wild-type (wt) and Sirt1(+/-) mice. The high-fat diet suppressed the expression of lipid catabolism (PPARα target) gene expression in the hearts of wt mice, but not Sirt1(+/-) mice. Pro-inflammatory genes were induced and estrogen-related receptor-alpha (ERRα) target genes was suppressed in the hearts of wt fed the high-fat diet, but not in Sirt1(+/-) mice. We found the formation of a complex between PPARα and Sirt1 in wt mice under high-fat diet conditions which might account for suppression of the ERRα pathway. Sirt1 haploinsufficiency impairs the formation of this complex and promotes the binding of PPARα to the p65 subunit of NF-κB, thereby mediating inhibition of pro-inflammatory pathways and induction of PPARα target genes. Short-term high-fat diet causes metabolic and inflammatory alterations in heart, and Sirt1 is critical for mediating these cardiac alterations. The capacity of Sirt1 to interact with transcriptional regulators such as NF-κB and PPARα appears to be involved in the cardiac responsiveness to a high-fat diet.


Thoracolumbar flexion-distraction injuries: associated morbidity and neurological outcomes.
Retrospective study, prospectively gathered databases. To assess abdominal comorbidities, missed injuries, and complications associated with thoracolumbar flexion-distraction injuries (FDI). From 1989 to 2003, 153 patients with flexion-distraction type injuries were identified. Predominant injury mechanisms consisted of motor vehicle crashes, falls, and motorcycle crashes. Spinal injuries were categorized by region, injury pattern, American Spinal Injury Association grade, and motor score. Diagnostic methods, delayed diagnoses, and complications were recorded and compared with variables of spinal injury, abdominal injury, and neurologic outcome. Treatment variables included nonoperative care, posterior surgery alone, anterior surgery alone, or combination treatment. Primary outcomes were neurologic status, unintended secondary procedures, complications, and kyphosis angle. Spinal cord injury (SCI) was found in 37 of 151 patients (25%). SCI was correlated with high-grade posterior element dissociation. Intra-abdominal injury (IAI) was found in 46 of 151 of patients (30%). There was a statistically significant correlation between presence of FDI and IAI in the lumbar (L2-L4) region. There was a 3.9% incidence of delayed diagnosis of FDI and a 0.9% incidence of delayed diagnosis of IAI. Presence of a "lapbelt-sign" had a positive predictive value of 0.69 and a negative predictive value of 0.91 for IAI. Presence of a lumbar injury due to a motor vehicle crash in the presence of a lapbelt sign was positively associated with IAI. There was no increase in complications in the subpopulation of patients with concurrent SCI and FDI. Both IAI and SCI remain commonly associated with FDI of the thoracolumbar spinal column. The presence of an abdominal wall contusion (lapbelt sign) is a strong indicator of IAI. Adherence to an established trauma algorithm can minimize the risk of delayed diagnosis. Disruption of an established work-up paradigm, however, can lead to potentially life and spinal cord threatening complications.


99mTc-labeled nanocolloid drugs: development methods.
The work considers the problem of obtaining nanocolloid radiopharmaceuticals (RPs) and studying their functional suitability for diagnosing sentinel lymph nodes (SLN) in cancer patients. Two principal approaches to the formation of technetium-99m-labeled particles based on inorganic and organic matrices were considered when carrying out research to develop methods for the production of nanocolloid RPs. The composition of the reagents and the conditions for obtaining nanocolloid radiopharmaceuticals were determined. The functional suitability of new RPs for scintigraphic diagnostics of sentinel lymph nodes has been studied.


Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.
The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.


JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells.
Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.


Purification and characterization of two kinds of low molecular weight kininogens from rat (non-inflamed) plasma. One resistant and the second sensitive to rat glandular kallikreins.
Two kinds of low molecular weight kininogens (identified as A and B) were isolated from pooled plasma of Sprague-Dawley rats. They show a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol, and the molecular weights are 68,000 for low Mr kininogen A and 73,000 for low Mr kininogen B. Although the molecular weights and amino acid compositions of the low Mr kininogens are similar, rat submaxillary and urinary kallikreins released bradykinin from low Mr kininogen B, whereas low Mr kininogen A was resistant to these enzymes. The COOH-terminal portion of low Mr kininogen A was isolated after cyanogen bromide treatment, and the amino acid sequence of the COOH-terminal 55 residues including the T-kinin (Ile-Ser-bradykinin) was determined. The COOH-terminal portion consists of two sequences with substitution of 4 residues. One peptide corresponds to alpha 1-major acute phase protein (Cole, T., Inglis, A. S., Roxburgh, C. M., Howlett, G. J., and Schreiber, G. (1985) FEBS Lett. 182, 57-61) and the other to the TI-kininogen predicted from a cDNA study (Furuto-Kato, S., Matsumoto, A., Kitamura, N., and Nakanishi, S. (1985) J. Biol. Chem. 260, 12054-12059). The results demonstrate that there exist at least two kinds of low Mr kininogens with clearly different function in rat plasma: one of them, low Mr kininogen A, is a precursor of T-kinin and is resistant to kallikreins, and the second, low Mr kininogen B, is sensitive to tissue kallikreins and shares properties with bovine and human low Mr kininogens. The results also demonstrate that T-kininogen is a mixture of two isoproteins which correspond to alpha 1-major acute phase protein or TI-kininogen, respectively. We could not detect the low Mr kininogen corresponding to the TII-kininogen predicted from the cDNA study of Furuto-Kato et al.


Modulation of the frequency of human cytomegalovirus-induced chromosome aberrations by camptothecin.
The effects of selected DNA repair inhibitors on the frequency of human cytomegalovirus (HCMV)-induced chromosome aberrations were evaluated in human peripheral blood lymphocytes (PBLs). Treatment of HCMV-infected PBLs with camptothecin (0.05 to 0.3 micrograms/ml), an inhibitor of topoisomerase I, for 30 hr resulted in a significant (P less than 0.01) synergistic enhancement of the frequency of HCMV-induced chromosome damage. On the other hand, a significant increase in the frequency of chromosome damage was not noted for infected PBLs treated with either 3-aminobenzamide (3-AB; 3 to 30 micrograms/ml), an inhibitor of poly(ADP-ribose) polymerase, or novobiocin (3 to 30 micrograms/ml), an inhibitor of topoisomerase II or excision repair processes, for 30 hr. Chromatid-type breaks and exchanges were the predominant type of chromosome aberrations observed in the HCMV-infected cells treated with camptothecin, suggesting that HCMV infection is associated with the induction of single-strand DNA breaks. Furthermore, these findings suggest that HCMV infection does not inflict direct DNA damage which is repaired through 3-AB- or novobiocin-sensitive pathways.


High-throughput fluorescence-based screen to identify factors involved in nuclear receptor recruitment to response elements.
The glucocorticoid receptor is an inducible transcription factor which plays important roles in many -physiological processes. Upon activation, GR interacts with regulatory elements and modulates the expression of genes. Although GR is widely expressed in multiple tissues, its binding sites within chromatin and the genes it regulates are tissue specific. Many accessory proteins and cofactors are thought to play a role in dictating GR's function; however, mechanisms involved in targeting GR to specific sites in the genome are not well understood. Here we describe a high-throughput fluorescence-based method to identify factors involved in GR loading at response elements. This screen utilizes a genetically engineered cell line that contains 200 repeats of a glucocorticoid response promoter and expresses GFP-tagged GR. Upon treatment with corticosteroids, GFP-GR forms a steady-state distribution at the promoter array, and its concentration at this focal point can be quantitatively determined. This system provides a novel approach to identify activities important for GR loading at its response element using siRNA libraries to target factors that enhance or inhibit receptor localization.


Neuronal nitric oxide synthase inhibition decreases cocaine self-administration behavior in rats.
Inhibitors of nitric oxide synthase (NOS) have been shown to alter behaviors related to cocaine addiction, including its self-administration. However, previous studies have largely used mixed-action NOS inhibitors and have not examined the effects of a neuronal NOS inhibitor on cocaine self-administration. Pretreatment with the neuronal NOS inhibitor 7-nitroindazole (7-NI) was used and its effects on cocaine self-administration were compared with those produced by pretreatment with an indirect dopamine receptor agonist (cocaine) and a D(1)-like dopamine receptor antagonist (SCH 23390). Rats were trained to self-administer 1 mg/kg cocaine under a second-order schedule of drug delivery, which measures drug-seeking behavior independently from drug intake. Pretreatment with various doses of 7-NI, cocaine, and SCH 23390 were tested in combination with the training dose of cocaine followed by studies examining the effects of a selected dose of each pretreatment drug in combination with a range of cocaine doses. Other rats were trained under a second-order schedule of food pellet delivery and pretreated with 7-NI, cocaine, or SCH 23390 to determine the behavioral specificity of the effects of these drugs for cocaine-maintained responding. The results demonstrated that 7-NI reduced responses maintained by the cocaine training dose and produced a downward shift in the cocaine dose-response curve. Changes in drug intake were minor by comparison. Cocaine pretreatment produced effects similar to 7-NI, while the changes observed after SCH 23390 pretreatment were different from 7-NI and cocaine. The reductions in cocaine-maintained responding after 7-NI pretreatment were behaviorally specific because there was no effect of 7-NI on food-maintained responding within the dose range examined. By selectively reducing drug-seeking behavior, these data suggest that 7-NI may enhance the reinforcing effects of cocaine.


ProC-TEL: Profiling of Protein C-Termini by Enzymatic Labeling.
Proteins are frequently processed by proteases in cell signaling pathways to perform their biological functions in response to environmental stimuli. Identification of the exact cleavage sites provides necessary information for the study of their biological functions. Although proteomic approaches for profiling of protein N-termini have been developed extensively in the past few years, the N-terminal profiling strategy has its inherent disadvantages. Therefore, C-terminal profiling approaches might be a complementary approach for the identification of protein cleavages although it has similar shortcomings as N-terminal profiling methods. In this protocol, we describe an approach, termed ProC-TEL: Profiling of Protein C-Termini by Enzymatic Labeling, for affinity labeling of protein C-termini for a protein or proteome. This method uses the transpeptidase activity of carboxypeptidase Y to label protein C-termini with an affinity biotin tag for subsequent isolation with avidin beads and identification by mass spectrometer. It is complementary to the N-terminal profiling approaches and can be used to identify proteolytic cleavages for a specific protease or in cell signaling events, such as apoptosis.


Quantitative activation patterns of cerebral blood flow during mental stimulation after intravenous injection of 195mAu.
A previously reported theory for quantitative cerebral blood flow measurement for nondiffusible radiotracers has been applied to patients after stroke and to volunteers undergoing a mental stimulation exercise. Quantitative measurements of cerebral blood flow pattern in p-a and lateral projections of the brain are obtained using the short lived (30s) isotope 195mAu from the recently developed generator. The energy spectrum of the eluate from the generator shows two strong photon peaks, one at an energy level of 68 KeV and a second at 262 KeV. The low-energy peak is suitable for perfusion studies of the cerebral hemispheres in lateral projection, being without "look through" effect. The high-energy level is good for studies in the p-a-projection. Studies last less than 1 min and can be repeated after 3 min. Parametric images for quantitative regional cerebral blood flow can be generated, in which the avascular region following stroke can be detected. Quantitative activation patterns of cerebral blood flow during mental stimulation can be generated. The results show that it is possible to measure cerebral blood-flow patterns not only with freely diffusible indicators like Xenon but also with nondiffusible indicators.


Expression of the kynurenine enzymes in macrophages and microglial cells: regulation by immune modulators.
The regulation of the expression of indoleamine 2,3-dioxygenase (IDO) was studied in cloned murine macrophages (MT2) and microglial (N11) cells. Both cell lines express IDO and inducible nitric oxide synthase activity after interferon-gamma (IFN-gamma) stimulation. The regulation of IDO expression appears to differ in the two cell lines. Nitric oxide (NO) production negatively modulates the expression of IDO activity in IFN-gamma-primed macrophages, thereby indicating a cross-talk between the kynurenine and nitridergic pathways in these cells. Conversely, this down-regulation of IDO activity by NO does not occour in microglial cells. A differential regulation of IDO expression in the two cell lines was also observed with LPS and picolinic acid. Together with previous findings, these results indicate the existence of marked differences in the regulation of the expression of the kynurenine pathway enzymes between macrophages and microglial cells.


Patient Knowledge, Adherence to the Therapeutic Regimen, and Quality of Life in Hemodialysis : Knowledge, Adherence, and Quality of Life in Hemodialysis.
The aim of this study was to investigate the effect of patients' knowledge on adherence to the hemodialysis regimen and Quality of Life (QoL) of patients undergoing hemodialysis as well as the effect of adherence on QoL. Also, the effect of demographic and clinical characteristics on the above three variables was studied. In this cross-sectional study conducted between March and May 2017, 321 patients on hemodialysis from six hemodialysis units completed the Kidney Disease Questionnaire, the GR-Simplified Medication Adherence Questionnaire and the Missoula Vitas Quality of Life Index-15 to measure the patient knowledge, the adherence to hemodialysis regimen, and the QoL, respectively. The statistical analysis was performed via the Statistical Program SPSS 19.0. The statistical significance level was set up at 0.05. The knowledge was independently associated with the overall QoL and its dimension-transcendence-with total adherence and its dimension-diet/fluid adherence. The total adherence was independently associated with overall QoL and its dimensions-symptoms and interpersonal. The educational level, the type of vascular access, and the daily number of pills were independently associated with the total adherence and the overall QoL. Patient knowledge may have an important effect on adherence and QoL. Adherence may have an important effect on QoL. Demographic and clinical characteristics play, also, a crucial role in the above variables. The findings can help nephrology nurses to quantify the extent of non-adherence in hemodialysis and poor quality of life.


Evaluation of automated measurement of left ventricular volume by novel real-time 3-dimensional echocardiographic system: Validation with cardiac magnetic resonance imaging and 2-dimensional echocardiography.
Traditional 3-dimensional echocardiography (3DE) with volumetric scanning technique requires several heart cycles for full-volume acquisition and complicated manual contouring of left ventricular (LV) endocardium. The new real-time 3DE (RT3DE) system allows acquisition of an instantaneous full-volume dataset in a single heart cycle and automated measurement of LV volume by the algorithm software. However, it has not been evaluated adequately whether automated measurement by RT3DE has better agreement with cardiac magnetic resonance imaging (CMR) than 2-dimensional echocardiography (2DE) with CMR. This study aimed to evaluate the accuracy of automated measurement of LV volume using RT3DE compared with 2DE and CMR. Forty-four consecutive patients who underwent RT3DE, 2DE, and CMR were evaluated in this study. The feasibility of automated measurement by RT3DE was 93.2% and the mean operation time was 6min. LV volume and ejection fraction (EF) from semi-automated measurement [end-diastolic volume: r=0.96, limits of agreement (LOA) -30.5 to 39.3 ml; end-systolic volume: r=0.97, LOA -22.6 to 32.7 ml; EF: r=0.90, LOA -16.1 to 14.2%, respectively] had better agreement with CMR than those from 2DE (r=0.87, LOA -50.5 to 72.2 ml; r=0.93, LOA -34.1 to 65.2 ml; r=0.89, LOA -20.9 to 10.0%, respectively). Semi-automated measurement by RT3DE has better agreement with CMR than 2DE in LV volume and EF. In addition, it is simple to operate and acceptable in feasibility for the clinical setting although there may be room for further learning required to incorporate small hypertrophic LV into the automated algorithm software.


Effects of excess copper on growth of wild rice (Zizania palustris) seedlings tested in reconstituted and natural waters.
Dissolved copper was toxic to wild rice (Zizania palustris) seedlings when exposed in water from the seed collection site of Swamp Creek, Crandon, Wisconsin, USA, and in laboratory-prepared artificial or reconstituted water. Seeds for the study were harvested, then held through a portion of dormancy, in Swamp Creek. After 60 days they were shipped to a laboratory, chilled, and tested with copper after germination. The end point of the tests was net gain in wet weight of the seedlings; additionally, a pronounced reduction in root development was observed. Using measured concentrations, the lowest no-observable-effect concentration (NOEC) in our study was 37 microg/liter in Swamp Creek water and the lowest-observable-effect concentration (LOEC) was 59 microg/liter. However, it appeared that there was a point at which concentrations of copper above 400 microg/liter did not result in any measurable effect or exhibit a definitive dose-response. Because the results in Swamp Creek water were more relevant to the possibility of local metals additions and the association of reduced seedling growth by copper was more powerful in this water, we derived an equation to express the relationship between copper concentration and toxicity for Swamp Creek water. As an example, we would expect a 3.0% reduction in seedling growth at 5.0 microg/liter copper. Seedling roots were particularly affected and the resultant plants may be less well anchored and more susceptible to dislodging than plants not exposed to copper. Further refinement of the methodology may be used to address effects of other contaminants impacting rice beds in North America.


Epidemiology of orofacial herpes simplex virus infections in the general population in France: results of the HERPIMAX study.
Prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. Objectives To establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (HSV) serotype in the French general population. Subjects (N = 2796) were serotyped for HSV1 and HSV2 and provided data on herpetic symptoms by questionnaire. Subjects reporting at least one episode of orobuccal ulcerative mucosal lesions were classified as clinically manifest orofacial herpes. Lifetime prevalence of clinically manifest orofacial herpes was 38.3% (42.1% in women, 32.4% in men). Prevalence in subjects seropositive for HSV1 was 50.3%. This prevalence rate was independent of HSV2 serotype. Prevalence in subjects infected with HSV2 alone was similar to that in subjects seronegative for HSV. Lack of case ascertainment limits precision of the data. Clinically manifest orofacial herpes was reported in one third of the sample, principally associated with HSV1 infection. HSV2 infection did not produce orofacial lesions nor influence clinical manifestations of HSV1 infection.