Lack of glucocorticoids sustains the stress-induced release of noradrenaline in the anterior hypothalamus.
The release of endogenous noradrenaline in the anterior hypothalamus was studied with microdialysis perfusion in freely moving rats that were subjected to immobilization stress. Experiments were carried out in sham-adrenalectomized and adrenalectomized rats that were first given drinking water containing corticosterone for 5 days following surgery and then switched to a corticosterone-free diet the day before stress application. One group of these adrenalectomized animals was injected with dexamethasone. Basal release of noradrenaline collected in 20-min fractions was similar in the three groups of animals and averaged 24 fmol. The recovery of the probe was about 10%. In sham-adrenalectomized rats application of 20-min immobilization stress increased noradrenaline release to 310% of baseline in the sample collected during stress application. A significant increase (+ 175% of baseline) was still observed in the next 20-min sample. Subsequent values were all identical to baseline. In adrenalectomized rats lacking exogenous corticosterone the stress-induced release of noradrenaline was prolonged with noradrenaline levels remaining elevated for 2 h after the onset of stress. The total noradrenaline release during this entire period was about 2.5 times higher in adrenalectomized than in sham-operated rats. However, the maximal increase during the period of immobilization was not significantly affected. Treatment with dexamethasone prevented the prolonged increase in noradrenaline release but did not affect the increase during the period of stress. While glucocorticoids do not appear to affect the increased release of NA in the anterior hypothalamus during the period of stress, they act to limit the duration of this activation after the application of stress.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolated assessment of translation or rotation severely underestimates the effects of subject motion in fMRI data.
Subject motion has long since been known to be a major confound in functional MRI studies of the human brain. For resting-state functional MRI in particular, data corruption due to motion artefacts has been shown to be most relevant. However, despite 6 parameters (3 for translations and 3 for rotations) being required to fully describe the head's motion trajectory between timepoints, not all are routinely used to assess subject motion. Using structural (n = 964) as well as functional MRI (n = 200) data from public repositories, a series of experiments was performed to assess the impact of using a reduced parameter set (translationonly and rotationonly) versus using the complete parameter set. It could be shown that the usage of 65 mm as an indicator of the average cortical distance is a valid approximation in adults, although care must be taken when comparing children and adults using the same measure. The effect of using slightly smaller or larger values is minimal. Further, both translationonly and rotationonly severely underestimate the full extent of subject motion; consequently, both translationonly and rotationonly discard substantially fewer datapoints when used for quality control purposes ("motion scrubbing"). Finally, both translationonly and rotationonly severely underperform in predicting the full extent of the signal changes and the overall variance explained by motion in functional MRI data. These results suggest that a comprehensive measure, taking into account all available parameters, should be used to characterize subject motion in fMRI.


Modified sequential multiplex PCR for determining capsular serotypes of invasive pneumococci recovered from Seville.
The heptavalent pneumococcal vaccine's introduction resulted in a decline in invasive disease caused by Streptococcus pneumoniae, but was accompanied by an increase in non-vaccine serotypes. We evaluated a modified scheme of the sequential multiplex PCRs adapted to the prevalence of serotypes in Seville (Spain) for determining capsular serotypes of S. pneumoniae invasive clinical isolates. In adults, the modified scheme allowed us to type 73% with the first three reactions, and 92% with two additional PCRs. In paediatric patients, it allowed us to type 73.5% with the first three reactions, and 90% with the two additional PCRs. The multiplex PCR approach was successfully adapted to target the serotypes most prevalent in Seville.


Entrainment in a chemical oscillator chain with a pacemaker.
Entrainment by a pacemaker was investigated experimentally and numerically in a chain of chemical oscillators using coupled discrete Belousov-Zhabotinsky reaction oscillators. The spontaneous frequency of each oscillator depended on the concentration of catalyst ions. The coupling strengths among the nearest neighbor oscillators were controlled by changing the spacing distance (d) between beads. When the coupling strength was sufficiently strong, the pacemaker entrained other oscillators in the chain. Subsequently, the trigger waves propagating from a pacemaker were observed. The range of trigger wave propagation area, i.e., the number of entrained oscillators, depended on d. Numerical simulation for the system described the experimental results well. Furthermore, photic noise maximized the strength of entrainment at an optimal noise intensity.


A comparative study of the bell-bottom technique vs hypogastric exclusion for the treatment of aneurysmal extension to the iliac bifurcation.
A significant proportion of patients undergoing endovascular aneurysm repair (EVAR) have common iliac artery aneurysms (CIAA). Aneurysmal involvement at the iliac bifurcation potentially undermines long-term durability. Patients with CIAA who underwent EVAR were identified in two teaching hospitals. Bell-bottom technique (BBT; iliac limb ≥20 mm) or internal iliac artery embolization and limb extension to the external iliac artery (IIE + EE) were used. Outcome between these two approaches was compared. We identified 185 patients. Indication for EVAR included asymptomatic abdominal aortic aneurysm (AAA) in 157, symptomatic or ruptured aneurysm in 19, and CIAA in nine. Mean AAA diameter was 59 mm. Among 260 large CIAAs that were treated, BBT was used to treat 166 CIAA limbs, and 94 limbs underwent IIE + EE. Total reintervention rates were 11% for BBT (n = 19) and 19.1% for IIE + EE (n = 18; P = .149). Rates of reintervention for type Ib or III endoleak were 4% for BBT (n = 7) and 4% for IIE + EE (n = 4; P > .99). The difference in limb patency rates was not significant. The 30-day mortality rate was 1%. Median follow-up was 22 months. Complications did not differ significantly between the two groups; however, the combined incidence of perioperative complications and reinterventions was higher in the IIE + EE group (49% vs 22%; P = .002). The combined incidence of perioperative complications and reinterventions is significantly higher with IIE + EE than with BBT; therefore, when feasible, BBT is desirable.


Population Age Structure and Greenhouse Gas Emissions from Road Transportation: A Panel Cointegration Analysis of 21 OECD Countries.
Using panel data from 21 Organization for Economic Cooperation and Development (OECD) countries collected between 2000 and 2016, this study analyzes the effect of age structure on greenhouse gas (GHG) emissions from road transportation. Previous studies have failed to reflect the driver's behavior patterns, especially by age group. We apply the Fully-Modified Ordinary Least Squares (FMOLS) method, including the age structure effect by reorganizing 17 age groups into a polynomial structure. The age structure exhibits an asymmetric inverted U-shaped effect on GHG emissions. Initially, people emit more GHGs as they age, and reach peak emissions in their late 20s, after which emissions fall until around the age of 70, when GHG emissions remain constant because of minimum mobility demand. Factors, such as higher income, increased vehicle ownership, and raised transport volumes increase emission rates. On the other hand, fuel transition and increased fuel price, population density, urbanization rate, and fuel economy reduce GHG emissions. Furthermore, we perform a projection of GHG emissions until 2050, and conclude that the effect of age structure is limited because of the minimum mobility demand of the elderly. We conclude that various policy measures, such as increased fuel economy and urbanization, must be considered in order to achieve sustainable transport.


[Promotion of home medical care and ways to provide medicines to patients at home].
The Medicare Security Law and Fee Schedule for Medical Services have undergone revisions in accordance with the changes in society, and these were introduced on the premise that home medical care be promoted. If home medical care is promoted, it is expected that a considerable proportion of persons who are now hospitalized and depend heavily on medicare will be transferred home, partly because of the shortening of the maximum insured hospitalization time. Thus, it will become necessary to provide medicines including injectables such as TPN to patients at home. Generally speaking, medicines for patients at home are provided by nearby pharmacists based on prescriptions written by the physician in charge of a patient. However, with regard to injectables such as TPN that require aseptic environments for preparation, such requirements can not yet be met satisfactorily owing to a shortage of sufficient provisions at pharmacies and of sufficient technical skills on the part of pharmacists. Currently, there are only 27 pharmacies which are officially recognized as being sufficiently equipped to prepare injectables in aseptic environments, and pharmacists who actually prepare TPN drugs in aseptic environments account for about one third of this number. The current number of pharmacists will obviously not meet the demand for medicines from patients at home, which will undergo a sharp rise in the near future. Accordingly, it is essential to increase the number of pharmacists nationwide who are sufficiently equipped to manage injectables such as TPN in aseptic conditions.


Scanning electron microscopy of early microbial colonization of human enamel and root surfaces in vivo.
This study describes the pattern of microbial colonization in six dental students, who carried test pieces of enamel and root surface in intraoral acrylic appliances for 4, 8, 12, 24, and 48 h, respectively. Oral hygiene was discontinued during the experimental periods. The results showed that oral microorganisms colonized enamel and root surfaces individually. The pattern of colonization mimicked the surface structure of the tooth; on enamel surfaces the first bacteria appeared in pits and surface irregularities followed by proliferation along the perikymata, while on root surfaces bacterial colonization was characterized by a haphazard distribution. Within the initial 24-h period root surfaces were more heavily colonized than were enamel surfaces. This pattern was characteristic irrespective of differences in the intra- and interindividual rates of bacterial coverage. It is concluded that early microbial colonization in vivo is determined by the surface structure of the tooth. Consequently, natural tooth surfaces should not be replaced by artificial surfaces in structural studies of microbial deposits in the oral cavity.


[Comparative study of lysosomal and cytosolic catabolisms of oligomannosidic-type glycans].
In order to study the substrate specificities of the enzymes implicated in the catabolism of oligomannosidic-type glycans, the oligosaccharides Man9GlcNAc and Man5GlcNAc were incubated with rat liver lysosomal and cytosolic alpha-D-mannosidases and the hydrolysis products were characterized by 400 MHz 1H-NMR spectroscopy. Although they both occur in an ordered way, the two catabolic pathways are quite different. The lysomal pathway is realized in two stages: the first leads from Man9GlcNAc to Man5GlcNAc by preferential cleavage of the four alpha-1,2-linked mannose residues, and the second, Zn(2+)-dependent, leads from Man5GlcNAc to Man (beta 1-4) GlcN Ac by hydrolysis of alpha-1, 3- and alpha-1,6-linked residues. On the contrary, the cytosolic pattern leads by a pathway quite different to a unique hexasaccharide Man5GlcNAc which has, curiously, the same structure as one of the polyprenolic intermediates occurring in the cytosol during the biosynthesis of N-glycosylprotein glycans: Man (alpha 1-2) Man (alpha 1-2) Man (alpha 1-3) [Man (alpha 1-6)] Man (beta 1-4) GlcN Ac (beta 1-4) GlcNAc alpha 1-P-P-Dol.


An optimal host response to a bacterium may require the interaction of leukocytes and resident host cells.
Bacterial infection results in inflammatory responses that may lead to soft-tissue damage and bone resorption. However, the mechanisms by which different bacteria contribute to lesions of endodontic origin are not fully understood. This study examined the response to Streptococcus mutans and Porphyromonas endodontalis in two cell types that are involved in periapical pathology, mononuclear and osteoblastic cells. This was accomplished by measuring the induction of chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-2) and proinflammatory cytokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, interferon-gamma). The results demonstrated that S. mutans more efficiently stimulate inflammatory cytokine production by mononuclear cells, whereas P. endodontalis is relatively more potent in activating osteoblastic cells. Moreover, optimal activation of osteoblastic cells by S. mutans requires soluble mediators produced by mononuclear cells, whereas P. endodontalis does not. These results suggest that the association of different bacteria with specific pathologic processes may be partially explained by their capacities to activate specific host cells.


Evaluation of a home-based exercise and training programme to improve sit-to-stand in patients with chronic stroke.
To investigate the feasibility and efficacy of a task-specific home-based exercise protocol for improving sit-to-stand (STS), with additional exercises to strengthen lower limb extensor muscles in patients with chronic stroke. A pre-test, post-test design was used. Six subjects at least one year post stroke and discharged from all rehabilitation services for at least six months participated in the study. Functional performance of sit-to-stand was evaluated using the Standing Up item of the Motor Assessment Scale (MAS). Peak vertical ground reaction force, walking speed over 10 m and grip strength were also measured. Group MAS score was significantly higher at post-test than at pre-test with two subjects reaching the highest point on the scale and three subjects reaching the second highest point. Time-to-peak vertical ground reaction force occurred significantly closer to thighs-off, the critical time when the body mass is propelled into standing. Walking speed increased significantly over 10 m from a mean of 0.86 m/s to 1.10 m/s. Grip strength, which was not trained, did not change. This study demonstrates that a home-based task-specific exercise and training protocol for STS can induce improved performance of STS and increase walking speed more than one year after stroke.


Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs.
The anti-neoplastic sphingolipid analog SH-BC-893 starves cancer cells to death by down-regulating cell surface nutrient transporters and blocking lysosomal trafficking events. These effects are mediated by the activation of protein phosphatase 2A (PP2A). To identify putative PP2A substrates, we used quantitative phosphoproteomics to profile the temporal changes in protein phosphorylation in FL5.12 cells following incubation with SH-BC-893 or the specific PP2A inhibitor LB-100. These analyses enabled the profiling of more than 15,000 phosphorylation sites, of which 958 sites on 644 proteins were dynamically regulated. We identified 114 putative PP2A substrates including several nutrient transporter proteins, GTPase regulators (e.g. Agap2, Git1), and proteins associated with actin cytoskeletal remodeling (e.g. Vim, Pxn). To identify SH-BC-893-induced cell signaling events that disrupt lysosomal trafficking, we compared phosphorylation profiles in cells treated with SH-BC-893 or C2-ceramide, a non-vacuolating sphingolipid that does not impair lysosomal fusion. These analyses combined with functional assays uncovered the differential regulation of Akt and Gsk3b by SH-BC-893 (vacuolating) and C2-ceramide (non-vacuolating). Dynamic phosphoproteomics of cells treated with compounds affecting PP2A activity thus enabled the correlation of cell signaling with phenotypes to rationalize their mode of action.


Circadian rhythms.
Circadian rhythms are a ubiquitous adaptation of eukaryotic organisms to the most reliable and predictable of environmental changes, the daily cycles of light and temperature. Prominent daily rhythms in behavior, physiology, hormone levels and biochemistry (including gene expression) are not merely responses to these environmental cycles, however, but embody the organism's ability to keep and tell time. At the core of circadian systems is a mysterious mechanism, located in the brain (actually the suprachiasmatic nucleus of the hypothalamus) of mammals, but present even in unicellular organisms, that functions as a clock. This clock drives circadian rhythms. It is independent of, but remains responsive to, environmental cycles (especially light). The interest in temporal regulation--its organization, mechanism and consequences--unites investigators in diverse disciplines studying otherwise disparate systems. This diversity is reflected in the brief reviews that summarize the presentations at a meeting on circadian rhythms held in New York City on October 31, 1992. The meeting was sponsored by the Fondation pour l'Etude du Système Nerveux (FESN) and followed a larger meeting held 18 months earlier in Geneva, whose proceedings have been published (M. Zatz (Ed.), Report of the Ninth FESN Study Group on 'Circadian Rhythms', Discussions in Neuroscience, Vol. VIII, Nos. 2 + 3, Elsevier, Amsterdam, 1992). Some speakers described progress made in the interim, while others addressed aspects of the field not previously covered.


[Medical treatment of urinary lithiasis].
Urinary stone disease is frequent, and characterized by a high recurrence rate. Prevention of recurrent urolithiasis is possible using an appropriate diet with or without medications. Patients should be encouraged to have a high fluid intake. For an adult, urine volume should exceed 2000 ml/day. Diet modification should be done according to the various metabolic factors contributing to the formation of the stone (ie, hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricuria, and so forth). Calcium intake should be around 1000 mg/day, protein intake limited to 1.2 g/kg/day, and salt intake kept to less than 100-150 mEq/jour. For uric acid urolithiasis, patient should limit uric acid intake to less than 500 mg/day. If these dietary manoeuvers fail, one can use thiazide diuretics to treat hypercalciuria, potassium citrate to correct hypocitraturia or sodium bicarbonate to alkalanize urine and prevent uric acid stone formation.


Fluorescence lidar detection with shot noise and sky radiance.
Rank annihilation-factor analysis is potentially the best method of analyzing fluorescence lidar returns because of the following capability. Rank annihilation can recognize a fluorescence signal of a component that is hidden by a large fluorescence background without a spectrum of that background. Theoretical models were developed to analyze the effectiveness of rank annihilation-factor analysis in the interpretation of lidar returns. Interferents such as background fluorescence, photon-counting noise, sky radiance, and atmospheric extinction degraded the lidar-return spectra in numerical simulations. The rank annihilation-factor analysis detection algorithm was most severely biased by the combination of photon-counting noise and sky radiance. Rank annihilation calculations were also compared with calculations done by two other detection algorithms: finding peak wavelengths and the least-squares technique. Rank annihilation is better than both techniques.


Functional Aromatic Polyamides.
We describe herein the state of the art following the last 8 years of research into aromatic polyamides, wholly aromatic polyamides or aramids. These polymers belong to the family of high performance materials because of their exceptional thermal and mechanical behavior. Commercially, they have been transformed into fibers mainly for production of advanced composites, paper, and cut and fire protective garments. Huge research efforts have been carried out to take advantage of the mentioned characteristics in advanced fields related to transport applications, optically active materials, electroactive materials, smart materials, or materials with even better mechanical and thermal behavior.


Recovery of Burkholderia cenocepacia strain PHDC from cystic fibrosis patients in Europe.
Burkholderia cenocepacia can cause life threatening respiratory tract infections in patients with cystic fibrosis (CF) and has a significant impact on survival. There is extensive evidence for patient to patient spread and nosocomial transmission of this organism, and several widespread B cenocepacia strains have been described including the transatlantic ET12 clone. A study was performed to compare B cenocepacia isolates recovered from CF patients receiving care in several European countries and strains isolated from other clinical samples and the environment, with reference isolates from the epidemic B cenocepacia strain PHDC which has so far only been recovered from CF patients and soil in the USA. A large collection of B cenocepacia isolates, including a large number recovered from CF patients receiving care in several European countries, Canada and the USA, were genotyped by means of randomly amplified polymorphic DNA typing (RAPD) and rep-PCR using the BOX-A1R primer (BOX-PCR). Nineteen Burkholderia cenocepacia isolates cultured from clinical samples in Europe (18 recently recovered from CF patients in France and Italy and one recovered in 1964 from urine in the UK) showed RAPD fingerprinting patterns that were similar to patterns obtained from isolates of B cenocepacia strain PHDC. Subsequent analysis of these isolates using BOX-PCR confirmed that the European isolates and strain PHDC represent the same clone. Strain PHDC represents a second transatlantic B cenocepacia clone capable of colonising patients with CF.


Acquired von Willebrand Syndrome Complicating Nephrotic Syndrome: A Case of a Patient With Membranous Nephropathy.
Acquired von Willebrand syndrome (AVWS) is a rare clinical entity presenting with heterogeneous hemorrhagic manifestations, although some subsets of patients with AVWS may be asymptomatic until they are exposed to major trauma, an invasive procedure, or surgery. We herein report one such case in a 73-year-old male patient with nephrotic syndrome with a prolonged active partial thromboplastin time. We initially did not deal with this distinct abnormal clotting profile seriously, but persistent bleeding after a retroperitoneoscopic-assisted renal biopsy that allowed us to ascribe his nephrotic syndrome to membranous nephropathy fortuitously led to the discovery of concurrent AVWS. We feel that an accurate and prompt diagnosis as well as awareness of the disease remain a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own in a prospective manner. This report underscores the pitfalls associated with determining the bleeding risk, including an insufficient assessment and improper weighting of an abnormal clotting profile prior to the invasive procedure. Several management concerns that emerged in the current case are also discussed.


Formation of gapless Fermi arcs and fingerprints of order in the pseudogap state of cuprate superconductors.
We use angle-resolved photoemission spectroscopy and a new quantitative approach based on the partial density of states to study properties of seemingly disconnected portions of the Fermi surface (FS) that are present in the pseudogap state of cuprates called Fermi arcs. We find that the normal state FS collapses very abruptly into Fermi arcs at the pseudogap temperature (T*). Surprisingly, the length of the Fermi arcs remains constant over an extended temperature range between T* and T(pair), consistent with the presence of an ordered state below T*. These arcs collapse again at the temperature below which pair formation occurs (T(pair)) either to a point or a very short arc, whose length is limited by our experimental resolution. The tips of the arcs span between points defining a set of wave vectors in momentum space, which are the fingerprints of the ordered state that causes the pseudogap.


Hydrogen peroxide-induced cytotoxicity in cultured epithelial cells (WISH): A functional and morphological study.
The effect of hydrogen peroxide on cultured epithelial cells (WISH) was investigated with particular emphasis on cell functions: cell morphology and cytoskeletal components were also studied. The presence of low concentrations of H(2)O(2) (0.1-0.4 mM) in the culture medium markedly inhibited cell growth, although WISH contained catalase and glutathione-peroxidase activities. After 1 hr of incubation with H(2)O(2) up to 5 mM, the majority of the cells were still alive, but reincubation in normal medium for 24 hr clearly reduced cell viability. Cell adhesion was dose-dependently reduced by H(2)O(2) treatment (0.1-0.5 mM) for 4 hr. Incubation with 1.5 mM-H(2)O(2) gave rise to a bleb appearance on the cell surface and to mitochondrial swelling, as shown, respectively, by scanning and transmission electron microscopy. Immunofluorescence studies revealed changes in microtubules and microfilaments, which are two of the main cytoskeletal components. The modification of microtubules was also confirmed by Western blot analysis of WISH protein homogenates submitted to SDS-PAGE. WISH treated with 1.5 mM-H(2)O(2) showed decreased levels of GSH compared with control cells: glutathione transferase activity was reduced, whereas other enzymes of the glutathione cycle were unchanged.


View-Based 3-D Model Retrieval: A Benchmark.
View-based 3-D model retrieval is one of the most important techniques in numerous applications of computer vision. While many methods have been proposed in recent years, to the best of our knowledge, there is no benchmark to evaluate the state-of-the-art methods. To tackle this problem, we systematically investigate and evaluate the related methods by: 1) proposing a clique graph-based method and 2) reimplementing six representative methods. Moreover, we concurrently evaluate both hand-crafted visual features and deep features on four popular datasets (NTU60, NTU216, PSB, and ETH) and one challenging real-world multiview model dataset (MV-RED) prepared by our group with various evaluation criteria to understand how these algorithms perform. By quantitatively analyzing the performances, we discover the graph matching-based method with deep features, especially the clique graph matching algorithm with convolutional neural networks features, can usually outperform the others. We further discuss the future research directions in this field.


[Impact of Helicobacter pylori infection on the risk of gastro-duodenal ulcer in patients treated with nonsteroidal antiinflammatory drugs].
The interaction of Helicobacter pylori (H. pylori) and non steroidal anti-inflammatory drugs (NSAIDs) on the development of gastro-duodenal ulcers and their complications is complex and controversial. From a clinical point of view, the question is whether or not H. pylori infection should be tested and eradicated in patients treated or about to be treated by NSAIDs or low-dose aspirin. Contradictory results have been reported in epidemiological studies. Recent data suggest that H. pylori-NSAID interaction may be different depending on the type of treatment, non aspirin NSAIDs or low-dose aspirin, the gastric or duodenal localization of ulcer and the strains of H. pylori. Controlled randomized studies suggest that eradication of H. pylori may be beneficial in NSAID-naïve patients but not in those already on long term NSAID therapy. Recommendations are proposed for different subgroups of patients. In NSAID users presenting with gastro-duodenal ulcer or complications, H. pylori screening and eradication are indicated. In patients treated or about to be treated by NSAIDs, the "test and treat" H. pylori strategy is recommended if there is a history of gastroduodenal ulcer or complications. Whether this strategy should be generalized preventively in patients without ulcer history is still controversial and deserves further studies.


Epigenetics of programmed obesity: alteration in IUGR rat hepatic IGF1 mRNA expression and histone structure in rapid vs. delayed postnatal catch-up growth.
Maternal food restriction (FR) during pregnancy results in intrauterine growth-restricted (IUGR) offspring that show rapid catch-up growth and develop metabolic syndrome and adult obesity. However, continued nutrient restriction during nursing delays catch-up growth and prevents development of obesity. Epigenetic regulation of IGF1, which modulates growth and is synthesized and secreted by the liver, may play a role in the development of these morbidities. Control (AdLib) pregnant rats received ad libitum food through gestation and lactation, and FR dams were exposed to 50% food restriction from days 10 to 21. FR pups were nursed by either ad libitum-fed control dams (FR/AdLib) or FR dams (FR/FR). All pups were weaned to ad libitum feed. Maternal FR resulted in IUGR newborns with significantly lower liver weight and, with the use of chromatin immunoprecipitation, decreased dimethylation at H3K4 in the IGF1 region was observed. Obese adult FR/AdLib males had decreased dimethylation and increased trimethylation of H3K4 in the IGF1 region. This corresponded to an increase in mRNA expression of IGF1-A (134 ± 5%), IGF1-B (165 ± 6%), IGF1 exon 1 (149 ± 6%), and IGF1 exon 2 (146 ± 7%) in the FR/AdLib compared with the AdLib/AdLib control group. In contrast, nonobese FR/FR had significantly higher IGF1-B mRNA levels (147 ± 19%) than controls with no difference in IGF1-A, exon 1 or exon 2. Modulation of the rate of IUGR newborn catch-up growth may thus protect against IGF1 epigenetic modifications and, consequently, obesity and associated metabolic abnormalities.


Effects of Nt-truncation and coexpression of isolated Nt domains on the membrane trafficking of electroneutral Na+/HCO3- cotransporters.
The SLC4 genes are all capable of producing multiple variants by alternative splicing or using alternative promoters. The physiological consequences of such diversity are of great interest to investigators. Here, we identified two novel variants of the electroneutral Na(+)/HCO3- cotransporter NBCn1, one full-length starting with "MIPL" and the other Nt-truncated starting with "MDEL". Moreover, we identified a new promoter of Slc4a10 encoding NBCn2 and a novel type of Nt-truncated NBCn2 starting with "MHAN". When heterologously expressed, the new NBCn1 variants were well localized to the plasma membrane and exhibited characteristic NBCn1 activity. However, MHAN-NBCn2 was poorly localized on the plasma membrane. By deletion mutations, we identified the Nt regions important for the surface localization of NBCn2. Interestingly, coexpressing the full-length NBCn2 greatly enhances the surface abundance of the Nt-truncated NBCn2. Co-immunoprecipitation and bimolecular fluorescence complementation studies showed that the full-length and Nt-truncated NBCn2 interact with each other to form heterodimers in neuro-2A cells. Finally, we showed that the isolated Nt domain interacts with and enhances the surface abundance of the Nt-truncated NBCn2. The present study expands our knowledge of the NBCn1 and NBCn2 transcriptome, and provides insights into how the Nt domain could affect transporter function by regulating its membrane trafficking.


Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.
Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Chronic corticosterone-induced deterioration in rat behaviour is not paralleled by changes in hippocampal NF-kappaB-activation.
We investigated whether long-lasting stress induced by chronic glucocorticoid (GC) exposure affects activation of brain NF-kappaB and whether these changes are related to functional deterioration and structural changes in the rat hippocampus. Psychometric investigations were conducted using a holeboard test system in 28 one-year-old male Wistar rats. Thereafter, rats were divided into three groups for daily administration of 10 mg corticosterone (treatment) or sesame oil (placebo = sham control for effects of the vehicle) for 60 days. Additional control rats did not receive any treatment or handling until the end of the experiment. Behavioural and cognitive changes were tested again in the holeboard system. Rat body weights and corticosterone concentrations in plasma, hippocampus and urine were determined and adrenal glands were investigated histopathologically. Hippocampal concentrations of corticosterone, NF-kappaB and I-kappaBalpha were determined using RIA, EMSA and Western blotting techniques, respectively. Structural changes in rat hippocampus were measured using magnetic resonance imaging techniques. High peripheral corticosterone concentrations after chronic treatment led to significant reductions in rat body weight. Significant atrophy of both adrenal glands with marked histological deterioration was detected. Furthermore, an increase in hippocampal corticosterone concentrations was observed after chronic administration. Chronic corticosterone treatment also significantly altered behaviour and working and reference memory capacity without changing hippocampal structure. Daily injections of sesame oil in the placebo group, however, were also sufficient to reduce the pellet-finding time. However, neither in the corticosterone group nor in the placebo group were behavioural changes paralleled by significant changes in brain NF-kappaB activation and I-kappaBalpha expression. Thus, cognitive alterations in rats seen after chronic corticosterone exposure are not paralleled by hippocampal NF-kappaB modulation.


Drought stress does not protect Quercus ilex L. from ozone effects: results from a comparative study of two subspecies differing in ozone sensitivity.
Long-term effects of ozone (O3) exposure and drought stress were assessed on two subspecies of Quercus ilex: ssp. ilex and ssp. ballota. Two-year-old seedlings were continuously exposed for 26 months in open-top chambers to three O3 treatments: charcoal filtered air, non-filtered air and non-filtered air supplemented with 40 nl · l(-1) O3. Additionally, two irrigation regimes were adopted: half of the plants were well-watered and the others received half of the water supplied to control plants. Growth, shoot water potential and gas exchange rates were assessed seasonally, and biomass accumulation was determined at the end of the experiment. Drought stress caused higher reductions of gas exchange, growth and biomass accumulation than O3 exposure in both subspecies. The combination of O3 and drought stress caused further decreases of accumulated aboveground biomass but no additive effects were observed on gas exchange rates or root biomass. Thus, drought stress did not protect Q. ilex from O3 effects on biomass when the response of the whole plant was considered. Q. ilex ssp. ballota was more sensitive to O3 and ssp. ilex was more affected by drought stress. The different O3 sensitivity was not only related to pollutant uptake but also to the ability of plants for resource acquisition and allocation. Based on biomass dose-response functions, Q. ilex is more resistant to O3 than other European evergreen tree species, however, O3 represents an additional stress factor that might be impairing plant ability to withstand current and future climate change.


Why chemotherapy can fail?
There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.


The effect of the odor of breast milk on the time needed for transition from gavage to total oral feeding in preterm infants.
The aim of this study was to investigate the effect of the application of the odor of breast milk in preterm infants during gavage feeding on the period of transition to total oral feeding. This prospective experimental study was performed on a total of 80 preterm infants: 40 infants in the study group and 40 in the control group. This experimental study was performed in eastern Turkey at the Neonatal Intensive Care and Premature Unit of a university hospital between September 2007 and December 2008. The demographic data were collected via a questionnaire, and an intervention and follow-up table was prepared by the researcher based on relevant literature. The study was approved by the local institution, and written informed consent was obtained from all parents. The findings of the study indicated that the preterm infants who were stimulated by the odor of breast milk during gavage feeding transitioned to oral feeding 3 days earlier than control subjects. Moreover, the mean hospitalization time of these infants was 4 days shorter. The results show that stimulation with breast milk odor is an effective method for decreasing transition of preterm infants from gavage to oral feeding. Nurses can train mothers to pump their breast milk, stimulate their infants with the odor of their breast milk, and feed it to their infants in the premature unit. This may lead to a quicker transition to oral feeding.


AI-Enabled Algorithm for Automatic Classification of Sleep Disorders Based on Single-Lead Electrocardiogram.
Healthy sleep is an essential physiological process for every individual to live a healthy life. Many sleep disorders both destroy the quality and decrease the duration of sleep. Thus, a convenient and accurate detection or classification method is important for screening and identifying sleep disorders. In this study, we proposed an AI-enabled algorithm for the automatic classification of sleep disorders based on a single-lead electrocardiogram (ECG). An AI-enabled algorithm-named a sleep disorder network (SDN)-was designed for automatic classification of four major sleep disorders, namely insomnia (INS), periodic leg movement (PLM), REM sleep behavior disorder (RBD), and nocturnal frontal-lobe epilepsy (NFE). The SDN was constructed using deep convolutional neural networks that can extract and analyze the complex and cyclic rhythm of sleep disorders that affect ECG patterns. The SDN consists of five layers, a 1D convolutional layer, and is optimized via dropout and batch normalization. The single-lead ECG signal was extracted from the 35 subjects with the control (CNT) and the four sleep disorder groups (seven subjects of each group) in the CAP Sleep Database. The ECG signal was pre-processed, segmented at 30 s intervals, and divided into the training, validation, and test sets consisting of 74,135, 18,534, and 23,168 segments, respectively. The constructed SDN was trained and evaluated using the CAP Sleep Database, which contains not only data on sleep disorders, but also data of the control group. The proposed SDN algorithm for the automatic classification of sleep disorders based on a single-lead ECG showed very high performances. We achieved F1 scores of 99.0%, 97.0%, 97.0%, 95.0%, and 98.0% for the CNT, INS, PLM, RBD, and NFE groups, respectively. We proposed an AI-enabled method for the automatic classification of sleep disorders based on a single-lead ECG signal. In addition, it represents the possibility of the sleep disorder classification using ECG only. The SDN can be a useful tool or an alternative screening method based on single-lead ECGs for sleep monitoring and screening.


Protective effects of chlorogenic acid on the meat quality of oxidatively stressed broilers revealed by integrated metabolomics and antioxidant analysis.
Oxidation is a major cause of meat quality deterioration during broiler production, which leads to undesirable meat color and impaired water holding capacity (WHC), thereby impacting consumer appeal and satisfaction. Chlorogenic acid (CGA), a natural phenolic acid, is regarded as a potential, safer and healthier antioxidant to improve meat quality. To investigate the protective effects of CGA on the meat quality of oxidatively stressed broilers, 240 one-day-old male Cobb broiler chickens were allocated to four treatments: basal diet (control group), basal diet + dexamethasone (DEX) injection (DEX group), basal diet containing 500 mg kg-1 CGA (CGA group), and basal diet containing 500 mg kg-1 CGA + DEX injection (DEX_CGA group). Meat quality, antioxidant capacity, the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and metabolomic profile were detected in the breast muscle of broilers. Then, correlation analysis between meat quality and antioxidant capacity, antioxidant-related genes, and metabolites was performed. The results indicated that CGA supplementation improved the growth performance and meat quality traits (pH, WHC, and meat color) and enhanced the antioxidant enzyme activity by activating the Nrf2 pathway in the breast muscle of oxidatively stressed broilers. A total of 619 metabolites were identified, among which 93 differential metabolites were found between control and DEX groups, and 65 differential metabolites were observed between DEX and DEX_CGA groups. Breast metabolic profiles were changed by DEX treatment, while CGA supplementation could normalize the metabolic changes in DEX-challenged broilers. Metabolic pathway analysis revealed that most of the differential metabolites between DEX and DEX_CGA groups were involved in pyrimidine/purine, propanoate and phenylalanine metabolism, primary bile acid biosynthesis, and lysine metabolism, which may contribute to explain the protective effects of CGA on meat quality. Moreover, according to the correlation analysis, four metabolites were identified as potential biomarkers to predict the meat quality. In conclusion, our findings demonstrate that CGA is an effective, natural and safe antioxidant to enhance the quality of meat from intensive industrial poultry production.


Distribution and organoleptic impact of ethyl 2-hydroxy-4-methylpentanoate enantiomers in wine.
The enantiomers of ethyl 2-hydroxy-4-methylpentanoate (ethyl dl-leucate) were assayed in several wines using chiral gas chromatography (γ-cyclodextrin). Analyses of 55 commercial wines from various vintages and origins revealed different distributions. Generally, white wines presented only the R form, whereas red wines contained both enantiomers, in various ratios according to aging. The highest levels of the S form were found in the oldest samples. The R/S average enantiomeric ratio of this compound in red wine was approximately 95:5 with an average total concentration of ∼400 μg/L. The olfactory threshold of R-ethyl 2-hydroxy-4-methylpentanoate (126 μg/L) in hydroalcoholic solution was almost twice that of the S form (55 μg/L). The olfactory threshold of a mixture of R- and S-ethyl 2-hydroxy-4-ethylpentanoate (95:5, m/m) in hydroalcoholic solution was 51 μg/L, suggesting that both enantiomeric forms contribute to perception of this compound in wine, resulting in a synergistic effect. Both enantiomers have quite similar aromatic nuances. Sensory analysis was employed to demonstrate a synergistic effect of this ethyl ester on the perception of fruity aromas in wine: in hydroalcoholic solution supplemented with R- or S-ethyl 2-hydroxy-4-methylpentanoate or a mixture of the R and S forms (95:5, m/m) at their average concentrations in red wines, fruity character was perceived at concentrations 2.2, 4.5, and 2.5 times lower, respectively, than in hydroalcoholic solution alone. Sensory profiles of aromatic reconstitutions, using HPLC fruity fractions, highlighted the contribution of this compound to blackberry fruit and fresh fruit descriptors.


Establishing correspondence in wood: the challenge and some solutions?
Establishing correspondence between the upper portion of a white birch sapling, a suspected weapon, and a potential source from a stand of trees was posed to one of us (GMC). A bending force shattered the sapling, precluding physical matching. Three white birch saplings were taken from the same stand of trees in a similar manner. Correspondence was achieved by measuring the width of the annual rings along four radii from a disk cut above and below the break. The regression coefficient of the data from the two disks from the same sapling was r(2) = 0.95. Regressing the upper disk against the lower disk of two other saplings resulted in r(2) values of 0.26 and 0.17, respectively. The various characteristics that are confined to a wood stem as part of its normal process of growth can be used to eliminate candidate saplings and establish correspondence between two pieces of wood.


IFN-λ-mediated IL-12 production in macrophages induces IFN-γ production in human NK cells.
With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although the antiviral activity of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production.


The Pd(4)(dppm)(4)(H)(2)(2+) cluster: a precatalyst for the homogeneous hydrogenation of alkynes.
The catalytic properties of the title cluster toward the homogeneous hydrogenation of phenylacetylene, diphenylethyne and phenyl-1-propyne have been investigated as a function of temperature, pressure, solvents, substrate and cluster concentrations, and counterions. The title cluster is a precatalyst that exhibits a good catalytic activity under mild conditions (1 atm of H(2) at 20 degrees C) for the hydrogenation of alkynes and alkenes. For the alkyne substrates, the turnover frequencies (tof's) range between 200 and 500 h(-)(1), and the product distribution varies as: cis-products, 75-90%; trans-products; 0-8% after 3 h of reaction. Based on the graphs -d[substrate]/dt vs [Pd(4)](1/2), the mechanism indicates a cluster dissociation into two dimers (presumably of the type Pd(2)(dppm)(2)(H)(solvent)(+)). The variations of tof (or -d[substrate]/dt) as a function of [substrate] and pressure of H(2) are linear. At 1600 psi of H(2), the tof can reach 2500-3000 h(-)(1) (in THF). The tof also increases with temperature reaching a maximum at approximately 35 degrees C (tof: 1000-1300 h(-)(1)), but at higher temperatures cluster decomposition begins to occur, leading to a rapid decrease in rates of catalysis. At 50 degrees C, no catalysis is observed. The hydrogenation reaction can be stopped at the corresponding cis-alkenes with approximately 95% yields, depending on the substrate and experimental conditions used. The tof's also vary with the solvent, where stronger coordinating solvent molecules give higher tof's. In addition, the tof's do not change with the nature of the counterion, which acts as "spectator" in the catalysis.


Effectiveness of a School-Based Tobacco Prevention Program for Middle School Students in Saudi Arabia: A Quasi-Experimental Controlled Trial.
To evaluate the effect of a school-based tobacco program in preventing initiation of tobacco use among adolescents in Saudi Arabia. We used a quasi-experimental controlled design. Four intervention and four control schools were selected from the regional education registry. A baseline questionnaire was administered to all grade 7 students before implementing the tobacco prevention program, Dentists Fighting Nicotine Dependence (DFND). The intervention group (n =379) received the DFND program whereas the control group (n = 255) received the regular tobacco program administered by the Department of Education. The program was delivered by trained health educators over 5 weeks. Pre- and post-test surveys (immediate and 2-year post-intervention) were collected. Study outcomes were current tobacco use, tobacco knowledge, attitude towards not using tobacco, and perceived behavioral control (PBC) of tobacco use. Covariates included sex, parent education, academic performance, absenteeism, student allowance, and religiosity. Data were analyzed using a two-level hierarchical mixed models. In the immediate post-test, 597 participants (intervention, n = 366; control, n = 231) were surveyed. There was no difference in tobacco use between intervention and control schools, however, the intervention group had significantly higher mean scores for knowledge (β = 1.27, SE = 0.27, P < .01) and attitude toward not using tobacco (β = 5.17, SE = 2.48, P < .05) after adjusting for covariates. At 2-year post-intervention, 463 participants (intervention, n = 289; control, n = 173) were surveyed. There were no differences in tobacco use, knowledge, attitude or PBC between intervention and control groups. Our program did not impact tobacco use. In the short-term, the program significantly improved knowledge and attitude towards not using tobacco. These effects decayed 2 years post-intervention without additional programming. Increasing the effectiveness of DFND may be achieved by expanding curriculum content and practice time throughout the school years and by targeting high-risk adolescents within the program.


NO-donor phenols: a new class of products endowed with antioxidant and vasodilator properties.
The synthesis and study of the antioxidant and vasodilator properties of a new class of phenols able to release nitric oxide are described. The products were designed through a symbiotic approach using selected phenols and selected nitrooxy and furoxan NO-donors as reference models. The antioxidant activities of the hybrid products were assessed by detecting the 2-thiobarbituric acid reactive substances (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids present in microsomial membranes of rat hepatocytes. The vasodilator activity was assessed on rat aortic strips precontracted with phenylephrine. Some of the products (13, 35, 37, 60-62, 64) behave principally as vasodilators and others as antioxidants (24, 32, 72), and the two properties are relatively balanced in 19, 41, and 68. Further in vivo studies should clarify whether some of these products may become preclinical candidates for the treatment of cardiovascular disease underpinned by atheroma.


Choline [Amino Acid] Ionic Liquid/Water Mixtures: A Triple Effect for the Degradation of an Organophosphorus Pesticide.
A series of ionic liquids (ILs) composed by choline (Ch) as a cation and different amino acids (AA) as anions and their respective aqueous mixtures were prepared using different [Ch][AA] contents in a range of 0.4-46 mol % IL. These solvents were used for the first time to achieve an eco-friendlier Paraoxon degradation. The results show that [Ch][AA]/water mixtures are an effective reaction medium to degrade Paraoxon, even when the IL content in the mixture is low (0.4 mol % IL) and without the need of an extra nucleophile. Both the kinetics and the degradation pathways of pesticides depend on the nature of the AA on [Ch][AA] and the amount of an IL present in the mixture. We have demonstrated that in those mixtures with a low amount of [Ch][AA], the hydrolysis reaction is the main pathway for Paraoxon degradation, showing a catalytic effect of the IL. However, as the percentage of [Ch][AA] increases in the mixture, the nucleophilic attack of [Ch][AA] is evident. Finally, the aim of this study was to provide evidence of a promising and biocompatible methodology to degrade a toxic compound (Paraoxon) using a minimal quantity of an IL designed totally from natural resources.


Impact of the carbon flux regulator protein pirC on ethanol production in engineered cyanobacteria.
Future sustainable energy production can be achieved using mass cultures of photoautotrophic microorganisms such as cyanobacteria, which are engineered to synthesize valuable products directly from CO2 and sunlight. For example, strains of the model organism Synechocystis sp. PCC 6803 have been generated to produce ethanol. Here, we performed a study to prove the hypothesis that carbon flux in the direction of pyruvate is one bottleneck to achieve high ethanol titers in cyanobacteria. Ethanol-producing strains of the cyanobacterium Synechocystis sp. PCC 6803 were generated that bear mutation in the gene pirC aiming to increase carbon flux towards pyruvate. The strains were cultivated at different nitrogen or carbon conditions and the ethanol production was analysed. Generally, a clear correlation between growth rate and ethanol production was found. The mutation of pirC, however, had only a positive impact on ethanol titers under nitrogen depletion. The increase in ethanol was accompanied by elevated pyruvate and lowered glycogen levels indicating that the absence of pirC indeed increased carbon partitioning towards lower glycolysis. Metabolome analysis revealed that this change in carbon flow had also a marked impact on the overall primary metabolism in Synechocystis sp. PCC 6803. Deletion of pirC improved ethanol production under specific conditions supporting the notion that a better understanding of regulatory mechanisms involved in cyanobacterial carbon partitioning is needed to engineer more productive cyanobacterial strains.


Synthesis and Characterization of BaTiO₃/Polypyrrole Composites with Exceptional Dielectric Behaviour.
Higher concentrations of ceramic fillers induce brittleness in the ceramic/polymer hybrids which restrict their applications to limited fields especially when such hybrids are prepared for their use as dielectrics. We have synthesized and characterized different BaTiO₃-polypyrrole (PPy) composites by changing the concentration of BaTiO₃ from 1% by weight of PPy taken to 5 wt % to explore its effect on the dielectric parameters of the final product and found that the BaTiO₃-polypyrrole composite with weight ratio of 0.05:1 exhibited highest dielectric constant, lowest dielectric loss and thermally most stable. All the composites were prepared using in-situ polymerization of pyrrole in an aqueous dispersion of low content of BaTiO₃ in the presence of small amount of Hydrochloric acid. These composites were characterized for their microstructure and crystallinity by X-ray diffractometer (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) while thermal stability by thermo gravimetric (TGA) analysis. An impedance analyser (LCR meter) was utilized to investigate the dielectric parameters. FT-IR data confirmed the presence of the two phases and their interaction, inferred from the shifting of normal PPy peaks. The data obtained from XRD confirmed the presence of crystallites of 2.8 to 5 nm with dominant crystallinity of the filler, TGA analysis (25 to 600 °C) confirmed the higher thermal stability induced on successive addition of the filler into the prepared composites as compared to that of pure PPy in a wide temperature range which is unusual for such a low % age addition of the filler. The SEM analysis together with XRD results reveal that the successive introduction of BaTiO₃ particles produced crystallites of 2 to 5 nm size which bonded together and changed the hemispherical shaped larger grains of the matrix to regular shaped smaller grains. The dielectric constant of the composites was enhanced with filler contents from 178 to 522 at 1 MHz for 1 wt % and 5 wt % BaTiO₃ respectively. It was concluded that the introduction of BaTiO₃ into the polymer matrix with this new procedure has greatly affected the polymerization process, thermal stability, morphology and dielectric properties of the host matrix and has resulted in a novel series of the composites which may have broad applications.


Influence of hepatic cells on allogeneic islet transplantation in rats without immunosuppressive drugs.
With the hypothesis of a possible helpful effect of the liver on islets transplanted into it, we have performed experiments that suggest some effect of hepatic cells for islet tolerance. We have studied 6 groups of Wistar rats made diabetic with streptozotocin and transplanted in sham conditions and with a mixture of islets and hepatic cells (allo-co-transplantation) in several conditions, all of them via the portal vein, and observed them over 30 days. Groups were as follows: Group A had a sham transplantation with saline. Group B was transplanted with hepatic cells alone. Group C was transplanted with islets alone without hepatic cells. Group D was co-transplanted with cultured islets and fresh hepatic cells (ratio 1:100). Group E was as group D with a ratio of 1:200. Group F also had co-transplantation, but after co-culture of islets and hepatic cells for 24 hours. Results show reversion of diabetes in group D for 4-5 days, and thereafter, a fall of blood glucose during the period observed. The effect was less marked in group F after co-culture of islets and hepatic cells. Paradoxically, when the ratio of islets and hepatic cell were 1:200, the results were not so good. These results suggest that hepatic cells have some helpful effect on islets when co-transplanted in the liver via the portal vein. More studies are needed to clarify if this effect can be related to some hepatic cell subpopulation; also if the effect is a membrane one, cell-to-cell contact, or through some secreted product.


Present state-of-the-art in elbow arthroplasty.
Prosthetic joint replacement of the elbow is, with some delay in comparison with the shoulder, the finger joints and especially the hip and knee joint, becoming a routine operation at least in more specialised orthopedic and trauma centers. In the seventies and eighties, more than 80% of the indications were in patients affected by rheumatoid arthritis, in which both sides were typically affected, seriously jeopardising their independence in activities of daily living. In the last decade an increasing number of posttraumatic osteoarthritic cases were included in the indications. Among the numerous prosthetic devices, only a few have stood the test of time (> 10 years); a meta-analysis of the world literature shows an average follow-up of less than 5 years. Two main types of prostheses must be distinguished, linked and non-linked. The linked prostheses are, with few exceptions, so-called sloppy hinges with a clearance between both components, permitting movement in the sagittal plane and in the frontal plane and also some rotation. Using the normal anatomical stabilising structures, the stresses on the interface are reduced. This type of linked prostheses has a wider range of possible indications than the non-linked resurfacing prostheses, which require a largely preserved bone stock and intact ligaments in order to avoid instability with subluxations or even dislocations. Resurfacing prostheses can be more or less constrained according to the degree to which they mimic normal elbow anatomy. In order to reduce the stresses on the interface, the more constrained resurfacing prostheses make additional use of an intramedullary stem. The fixation of the device in the bone is achieved with bone cement in nearly all the linked and non-linked prostheses. Sloppy hinges with condylar configurations (as the GSB III elbow prosthesis) or an anterior flange (Coonrad-Morrey) further reduce the stresses on the interface and have better long-term results. Special instruments help to place the prosthesis in correspondence to the normal center of rotation and to minimise the bone resection needed and the risk of intra-operative complications (condyle fractures, shaft perforation). The results concerning pain relief and mobility are, for all properly placed prostheses, very satisfactory in the first years. A reliable account of long-term results (> 10 years of non-interrupted series of elbow prostheses) has so far been given only by a few authors. In cases with rheumatoid arthritis the survival rate at 10 years reaches 90%; the complication rate however is still definitely larger than with hip, knee and shoulder prostheses. This is particularly true for posttraumatic OA cases. Aseptic loosening, infection, instability and ulnar nerve lesions are at the fore and about twice as frequent as in RA, especially in patients below 60 years of age. In order to keep a safe retreat possibility open, we insist on the best possible preservation or reconstruction of normal anatomy (e.g. condyle reconstruction) when implanting an elbow prosthesis.


An immunohistochemical study of the expression of the hypoxia markers Glut-1 and Ca-IX in canine sarcomas.
Tumor hypoxia has been associated with increased malignancy, likelihood of metastasis, and increased resistance to radiotherapy and chemotherapy in human medicine. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that is induced by tumor hypoxia and regulates the pathways involved in cellular response and adaptation to the hostile tumor microenvironment. HIF-1 induces transcription of different proteins, including Ca-IX and Glut-1, which are considered endogenous markers of chronic hypoxia in solid tumors in humans. In this study, sections from 40 canine sarcomas (20 histiocytic sarcomas and 20 low-grade soft-tissue sarcomas) were immunostained for these markers. Expression of Glut-1 was scored based on percentage of positive staining cells (0 = <1%; 1 = 1%-50%; 2 = >50%) and intensity of cellular staining (1 = weak; 2 = strong); Ca-IX was scored based on percentage of positive cells (0 = <1%; 1 = 1%-30%; 2 = >30%). Intratumoral microvessel density was measured using CD31 to assess intratumoral neoangiogenesis. Histiocytic sarcomas showed statistically significant higher Glut-1 immunoreactivity and angiogenesis than did low-grade soft-tissue sarcomas. Intratumoral microvessel density in histiocytic sarcomas was positively associated with Glut-1 immunoreactivity score. These findings suggest a potential role of hypoxia in the biology of these tumors and may provide a base for investigation of the potential prognostic use of these markers in naturally occurring canine tumors.


[Combination of endoscopic mucosal resection and full-thickness resection in the treatment of local residual neoplasia of the colon two case reports].
We present the case of a 61-year-old patient with local residual neoplasia (LRN) of the rectum and the case of a 65-year-old patient with LRN of the cecum. In both cases, the lesion measured 25 mm in diameter and its center was fixed by submucosal fibrosis causing the non-lifting sign. For endoscopic treatment, which was uneventful,a combination of endoscopic mucosal resection (EMR) and full-thickness resection (FTR) was used. In both cases, histological examination showed completely resected tubular adenoma with HGIN.Key words: colorectal carcinoma local residual neoplasia full-thickness resection endoscopic mucosal resection.


Neuroprotective effect of pretreatment with Lavandula officinalis ethanolic extract on blood-brain barrier permeability in a rat stroke model.
To evaluate the protective effect of Lavandula officinalis (L. officinalis) extract against blood-brain barrier (BBB) permeability and its possible mechanisms in an experimental model of stroke. Focal cerebral ischemia was induced by the transient occlusion of the middle cerebral artery for 1 h in rats. Lavender extract (100, 200 mg/kg i.p.) was injected for 20 consecutive days. BBB permeability and oxidative stress biomarkers were evaluated using standard methods. The results of this study showed that L. officinalis ethanolic extract significantly reduced the BBB permeability in experimental groups when compared with ischemia group. The lavender extract significantly reduced malondialdehyde levels of plasma and brain tissue in intact group when compared with control group. L. officinalis extract reduced blood brain barrier permeability and alleviated neurological function in rats, and the mechanism may be related to augmentation in endogenous antioxidant defense and inhibition of oxidative stress in the rat brain.


Olfactory Stimulation and the Diagnosis of Patients With Disorders of Consciousness: A Double-Blind, Randomized Clinical Trial.
The aim of this study was to determine whether behavioral responses elicited by olfactory stimulation are a predictor of conscious behavioral response and prognosis of patients with disorders of consciousness (DOC). Twenty-three DOC patients (8 unresponsive wakefulness syndrome [UWS]; 15 minimally conscious state [MCS]) were recruited for this study in which 1-Octen-3-ol (familiar neutral odor) and pyridine were used to test odor behavioral responses, and water was used as an odorless stimulus. One rater presented the three odors in front of each patient's nose randomly, and another one videotaped all behavioral responses (e.g., pouting, wrinkling nose, slightly shaking head, frowning, etc.). Two independent raters, blind to the stimuli and the patient's diagnosis, gave the behavioral results according to the recorded videos. One-, 3-, and 6-month follow-up evaluations were conducted to obtain a good prognostic value. All MCS patients showed behavioral responses to the 1-Octen-3-ol stimulus; nine MCS and one UWS showed olfactory emotional responses to the pyridine, and two MCS showed olfactory emotional responses to the water stimulus. The incidence of behavioral response was significantly higher using 1-Octen-3-ol than it was for water by McNemar test (p < 0.001), significantly higher using pyridine than it was for water (p < 0.01). The χ2 test results indicated that there were significant differences between MCS and UWS to 1-Octen-3-ol (p < 0.001). For MCS patients, the incidence of behavioral response was no different between using 1-Octen-3-ol and pyridine (p > 0.05). There was no significant relationship between the olfactory behavioral response and the improvement of consciousness based on the χ2 test analysis (p > 0.05). Olfactory stimuli, especially for the familiar neutral odor, might be effective for eliciting a conscious behavioral response and estimating the clinical diagnosis of DOC patients. [https://clinicaltrials.gov/ct2/show/NCT03732092], [identifier NCT03732092].


Effectiveness of different acupuncture therapies for chronic cancer pain: A protocol for systematic review and Bayesian network meta-analysis.
Pain is a common and distressing symptom experienced by cancer patients. Previous research found acupuncture was associated with significant reductions in pain intensity and opioid use. Acupuncture therapies are various, and the difference in efficacy and safety has never been assessed. This paper aims to assess and rank the effectiveness of the different acupuncture methods and provide an acupuncture treatment guideline for relieving chronic pain in cancer survivors. Four English databases (PubMed, Embase, Cochrane library, and Web of Science) and 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Data, and Chinese Biomedical Literature Database) will be searched for randomized controlled trials (RCTs) published from the database inception to November 30, 2021. The primary outcomes will be patient-reported pain intensity measured by the Brief Pain Inventory, Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale, and other valid outcome measures. The Grading of Recommendations Assessment, and Development and Evaluation System will evaluate the quality of evidence. Bayesian network meta-analysis will be performed in WinBUGS V.1.4.3 to determine the comparative effectiveness of the acupuncture therapies. This study will quantify the effectiveness of each acupuncture intervention for chronic cancer pain with pain scores and the use of analgesics. The adverse events of acupuncture treatment for cancer pain will also be reported. The conclusion of our study will help physicians and patients choose suitable acupuncture methods to manage cancer pain.


Web-based interactive 2D/3D medical image processing and visualization software.
There are many medical image processing software tools available for research and diagnosis purposes. However, most of these tools are available only as local applications. This limits the accessibility of the software to a specific machine, and thus the data and processing power of that application are not available to other workstations. Further, there are operating system and processing power limitations which prevent such applications from running on every type of workstation. By developing web-based tools, it is possible for users to access the medical image processing functionalities wherever the internet is available. In this paper, we introduce a pure web-based, interactive, extendable, 2D and 3D medical image processing and visualization application that requires no client installation. Our software uses a four-layered design consisting of an algorithm layer, web-user-interface layer, server communication layer, and wrapper layer. To compete with extendibility of the current local medical image processing software, each layer is highly independent of other layers. A wide range of medical image preprocessing, registration, and segmentation methods are implemented using open source libraries. Desktop-like user interaction is provided by using AJAX technology in the web-user-interface. For the visualization functionality of the software, the VRML standard is used to provide 3D features over the web. Integration of these technologies has allowed implementation of our purely web-based software with high functionality without requiring powerful computational resources in the client side. The user-interface is designed such that the users can select appropriate parameters for practical research and clinical studies.


Prevalence and associated factors of burnout among family medicine residents in Al Madina, Saudi Arabia.
Burnout is a common problem for interns and residents. It has been associated with physical and mental health of health care providers as well as low job satisfaction and medical errors. Few studies have investigated this problem among residents. This study aimed to determine the prevalence of burnout and its associated factors among family residents in Al Madina city, Saudi Arabia. This cross-sectional study was conducted among 75 residents in the family medicine residency programs in Al Madina, Saudi Arabia. A self-administered questionnaire was used that includes questions on sociodemographic characteristics and sources of stress and burnout. T test, analysis of variance (ANOVA) test, and multiple linear regression analysis were employed. Majority were female (54.7%) and aged 26 to 30 years (84.0%). The significant predictors of burnout in the final model were "tests/examinations" (P = 0.014), "large amount of content to be learnt" (P = 0.016), "unfair assessment from superiors" (P = 0.001), "work demands affect personal/home life" (P = 0.001), and "lack of support from superiors" (P = 0.006). Burnout is present among family medicine residents at a relatively high percentage. This situation is strongly triggered by work-related stressors, organizational attributes, and system-related attributes, but not socio-demographics of the respondents. Systemic changes to relieve the workload of family medicine residents are recommended to promote effective management of burnout.


Computation of synchronized periodic solution in a BAM network with two delays.
A bidirectional associative memory (BAM) neural network with four neurons and two discrete delays is considered to represent an analytical method, namely, perturbation-incremental scheme (PIS). The expressions for the periodic solutions derived from Hopf bifurcation are given by using the PIS. The result shows that the PIS has higher accuracy than the center manifold reduction (CMR) with normal form for the values of time delay not far away from the Hopf bifurcation point. In terms of the PIS, the necessary and sufficient conditions of synchronized periodic solution arising from a Hopf bifurcation are obtained and the synchronized periodic solution is expressed in an analytical form. It can be seen that theoretical analysis is in good agreement with numerical simulation. It implies that the provided method is valid and the obtained result is correct. To the best of our knowledge, the paper is the first one to introduce the PIS to study the periodic solution derived from Hopf bifurcation for a 4-D delayed system quantitatively.


Serum Testosterone Is Associated With the Severity of COVID-19.
Coronavirus disease 2019 (COVID-19) is more likely to be severe in men than in women. Its association with sex hormones as an aggravating factor for male patients has been attracting attention. This study aimed to investigate whether serum testosterone is associated with the aggravation of COVID-19. Serum testosterone concentrations in 116 male patients with COVID-19 and residual serum were measured and examined upon their admission to Sapporo Medical University Hospital between February 1, 2020 and March 31, 2021. Blood samples collected from these patients with COVID-19 were analyzed. The serum testosterone levels were 2.19±1.35, 1.29±0.88, and 0.75±0.58 ng/ml in mild, moderate, and severe groups, respectively. Patients with severe COVID-19 on admission had lower testosterone levels (p<0.001). At a cutoff level of 1.31 ng/ml, the area under the curve for the comparison of severe with non-severe cases was 0.825. Furthermore, serum testosterone levels negatively correlated with C-reactive protein and serum amyloid A levels but positively correlated with calcium, zinc, C3, and C4. In male patients with COVID-19, low serum testosterone levels correlated with disease severity, accompanied by a strong inflammatory reaction and proportion of complement consumption.


Linking fishes to multiple metrics of coral reef structural complexity using three-dimensional technology.
Structural complexity strongly influences biodiversity and ecosystem productivity. On coral reefs, structural complexity is typically measured using a single and small-scale metric ('rugosity') that represents multiple spatial attributes differentially exploited by species, thus limiting a complete understanding of how fish associate with reef structure. We used a novel approach to compare relationships between fishes and previously unavailable components of reef complexity, and contrasted the results against the traditional rugosity index. This study focused on damselfish to explore relationships between fishes and reef structure. Three territorial species, with contrasting trophic habits and expected use of the reef structure, were examined to infer the potential species-specific mechanisms associated with how complexity influences habitat selection. Three-dimensional reef reconstructions from photogrammetry quantified the following metrics of habitat quality: 1) visual exposure to predators and competitors, 2) density of predation refuges and 3) substrate-related food availability. These metrics explained the species distribution better than the traditional measure of rugosity, and each species responded to different complexity components. Given that a critical effect of reef degradation is loss of structure, adopting three-dimensional technologies potentially offers a new tool to both understand species-habitat association and help forecast how fishes will be affected by the flattening of reefs.


[Efficacy and safety of TS-1 monotherapy for advanced/metastatic breast cancer - an observational study by the Kumamoto Breast Cancer Cooperative Group(KBCCG)].
TS-1, an oral fluoropyrimidine, is known to be effective for the treatment of various carcinomas including advanced/metastatic breast cancer.The Kumamoto Breast Cancer Cooperative Group(KBCCG)conducted an observational study, wherein, the efficacy and safety of TS-1 monotherapy was analyzed in 35 patients with recurrent or metastatic breast cancer.The median time to cancer progression was 3.7 months, overall response rate was 12%, and clinical benefit rate was 32%. Adverse events were observed in 27 patients(77%), and adverse events of Grade >3 were observed in 7 patients(20%). The rate of treatment-related Grade 3 and 4 adverse events increased, and was associated with poor levels of creatinine clearance(Ccr)ie <60mL/min.This study suggests that TS-1 monotherapy can potentially be used as a salvage treatment for advanced/metastatic breast cancer owing to its safety and efficacy.Measuring the level of Ccr before TS-1 therapy should be considered to avoid severe adverse events.


Surface Layer Fluorination-Modulated Space Charge Behaviors in HVDC Cable Accessory.
Space charges tend to accumulate on the surface and at the interface of ethylene⁻propylene⁻diene terpolymer (EPDM), serving as high voltage direct current (HVDC) cable accessory insulation, which likely induces electrical field distortion and dielectric breakdown. Direct fluorination is an effective method to modify the surface characteristics of the EPDM without altering the bulk properties too much. In this paper, the surface morphology, hydrophobic properties, relative permittivity, and DC conductivity of the EPDM before and after fluorination treatment were tested. Furthermore, the surface and interface charge behaviors in the HVDC cable accessory were investigated by the pulsed electroacoustic (PEA) method, and explained from the point of view of trap distribution. The results show that fluorination helps the EPDM polymer obtain lower surface energy and relative permittivity, which is beneficial to the interface match in composite insulation systems. The lowest degree of space charge accumulation occurs in EPDM with 30 min of fluorination. After analyzing the results of the 3D potentials and the density of states (DOS) behaviors in EPDM before and after fluorination, it can be found that fluorination treatment introduces shallower electron traps, and the special electrostatic potential after fluorination can significantly suppress the space charge accumulation at the interface in the HVDC cable accessory.


Inhibition of Tenon's fibroblast proliferation and enhancement of filtration surgery in rabbits with cytosine arabinoside.
Our purpose was to study the antiproliferative effect of cytosine arabinoside (Ara-C) on rabbit Tenon's fibroblasts and the efficacy of Ara-C as an adjunctive antifibrosis treatment for glaucoma filtration surgery in the rabbit eye. Rabbit Tenon's fibroblasts were exposed to 1 microg/ml of Ara-C for various time intervals, then cell number and viability was assessed at different time points. Following posterior lip sclerectomy, rabbit eyes were treated with 10 mg subconjunctival Ara-C daily for 7 days, then every other day for 7 days. Rabbit fibroblasts exposed to 1 microg/ml Ara-C for 1 hour showed no significant decrease in cell number compared with control. Continuous or 24-hour incubation of fibroblasts with Ara-C was lethal to the cells. Exposure of cells to Ara-C for 3-, 6-, and 9-hour intervals caused significant reduction of cell proliferation. Pulsed treatment of cells with 6 hour exposure to 1 microg/ml Ara-C every 3 days caused prolonged suppression of cell proliferation. Following posterior lip sclerectomy in rabbits, topical instillation of Ara-C drops at varying concentrations and dosing intervals did not cause any significant lowering of intraocular pressure compared with control eyes, although bleb survival was prolonged in eyes treated with Ara-C (P < 0.01). In rabbit eyes treated postoperatively with subconjunctival injections of 10 mg Ara-C every other day for two weeks, the mean intraocular pressure was significantly decreased and the bleb survival time was significantly prolonged (P < 0.0067) compared with control eyes. In conclusion, Ara-C inhibits rabbit Tenon's fibroblast proliferation in vitro. Postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit.


Analysis of enteric neurons, glia and their interactions using explant cultures of the myenteric plexus.
The enteric nervous system (ENS) of the gastrointestinal tract is the largest and most complicated division of the peripheral nervous system. The ENS possesses reflex pathways composed of motor neurons, interneurons and sensory neurons which act in an integrated fashion together with input from the central nervous system to control gut function. The neurons, morphologically and electrophysiologically a very heterogeneous group containing a large number of different proven and putative neurotransmitters, are intimately associated with enteric glia, which both at the morphological and molecular level resemble astrocytes. In this review we describe how explant cultures from the ENS have been used to investigate the neurochemical, molecular and electrophysiological characteristics of ENS neurons, the molecular properties of enteric glia and their interactions with one another.


Acute Vertigo After COVID-19 Vaccination: Case Series and Literature Review.
Objective: The aim of this study was to present some cases of acute vertigo potentially related to the coronavirus disease 2019 (COVID-19) vaccine and review the available literature about cochleovestibular dysfunction after the COVID-19 vaccination. Methods: In the period from May to July 2021, we evaluated 33 patients (mean age 54.3 ± 14.1) with "acute vertigo" post COVID-19 vaccination. A detailed medical history was taken on comorbidities, types of vaccines received, and symptoms associated. All patients underwent otoneurological evaluation, such as head impulse test, nystagmus evaluation, test of skew (HINTS) examination. Head shaking test-induced nystagmus, hyperventilation-induced nystagmus, and parossistic positional nystagmus were studied to search for vestibular impairment. Results: Symptoms included 16 patients (48.5%) with objective vertigo, 14 patients (42.4%) with subjective vertigo, and 3 patients (9.1%) with dizziness. Of the associated ear, nose, and throat (ENT) symptoms, the most expressed was tinnitus (18.2%). Bedside examination showed absent nystagmus in 7 patients (21.2%), 9 patients (27.3%) had horizontal or rotatory nystagmus, 17 patients (51.5%) had a vertical or oblique nystagmus, negative HST, or "central HINTS." Discussion and Conclusions: The 9 patients had an evoked nystagmus pathognomonic for benign paroxysmal positional vertigo; in the remaining 17 cases, peripheral vestibular dysfunction could be excluded and central disorder may be suggested. Due to the prevalence of nystagmus of non-peripheral origin, a central nervous system involvement could not be excluded. However, due to the small sample size, a definite cause-effect relationship between vaccination and vertigo cannot be inferred. In light of expected third dose, large-scale and well-designed studies are needed to better define possible adverse reactions of the COVID-19 vaccine.


Opportunities on the Internet for child and adolescent psychopharmacologists: net access and mailing lists.
The Internet, a system linking computers around the world, provides clinical and research psychopharmacologists with a convenient and efficient way to exchange information and offers a growing number of services to facilitate patient care. These opportunities are not theoretical, not in the future, and not for a select few. Many patients are already benefitting from practitioners who have sought guidance for their clinical work on the Internet. This article describes, for the novice user, how to begin the Internet journey. It also discusses psychopharmacology-related mailing lists, including a site that specializes in child and adolescent psychopharmacology. Subsequent articles will (1) show how to use Medlines to conduct literature searches and retrieve abstracts and articles from the computer screen, (2) describe ways to enter and traverse the World Wide Web (the "multimedia" portion of Internet), and (3) survey the use of "Web browsers" to find specialized psychopharmacology resources and databases, electronic journals, pertinent bulletin boards, and support services for patients and families-all with an emphasis on direct benefits to the practicing psychopharmacologist.


Nonabdominal causes of abdominal pain--finding your heart in your stomach!
The diagnosis of abdominal pain is difficult and often inaccurate. Nonabdominal disease, in particular cardiac and pulmonary disease, may present with abdominal symptoms. This article provides a brief review of the neuro-anatomical basis of abdominal pain in the adult patient population. Differential diagnoses are outlined with a specific focus on time critical conditions, and clinical 'red flags' for the physician in the 'frontline' are highlighted. Physicians need a high clinical index of suspicion when the diagnosis is elusive. They must acknowledge atypical presentations are common, avoid over reliance on 'classic' presentations or the outcome of preliminary investigations, and specifically seek time critical diagnoses. A detailed history and examination remains the key to avoiding diagnostic error. The priority is not 'correct diagnosis' but 'correct patient disposition'. Options include prolonged observation, further sophisticated investigations, and early specialist referral. Physician's gestalt in elusive cases remains important.


An extremely sensitive in vitro model for elucidating structure-activity relationships of growth hormone-releasing factor analogs.
An improved rat anterior pituitary primary cell culture technique for studying GH-releasing activity of human pancreatic GH-releasing factor (hpGRF) and its analogs is described. Male pituitaries, dispersed by a combination of trypsin digestion and mechanical agitation, were plated at a density of 200,000 cells per well and cultured for 4 days. The attached cells were then stimulated with synthetic hpGRF which was comprised of the first 29 residues of the larger, originally isolated forms and which was amidated at the C-terminal (hpGRF-29). Analogs of hpGRF-29 which were modified in positions 1, 2, 3, or 7, and other secretagogues were similarly tested. Medium was collected after 3 h, and secreted hormone was measured by RIA. The cells were extremely sensitive to hpGRF-29 stimulation, and this effect was specific. The minimal effective dose of hpGRF-29 was an unprecedented 0.4 X 10(-15)M. No stimulation of LH, FSH, or PRL by hpGRF-29 was observed. Bombesin and vasoactive intestinal peptide were ineffective in stimulating GH release. [D-Trp6]LHRH (a potent LHRH agonist), also did not release GH but did stimulate secretion of LH and FSH at doses ranging from 0.4 X 10(-10)M to 1.0 X 10(-9)M. Responses of the cells to hpGRF-29 analogs were characterized by distinct heterologous dose-response curves. [D-Ala2]hpGRF-29 was 50 times more active than its parent 29-amino-acid peptide. [D-Thr7]hpGRF-29, another analog that differed from hpGRF-29 by the insertion of a D-isomer for the naturally occurring L-residue, was about 10,000 times less effective in stimulating GH secretion than was hpGRF-29 itself. Potencies of these and other analogs with respect to GH release in vitro were similar to those estimated in vivo. Thus, this primary cell culture provides an extremely sensitive, selective, and reproducible system for studying hpGRF structure-activity relationships. Further, such tremendous sensitivity to hpGRF can provide a system to study changes in pituitary sensitivity to hpGRF during different physiological states.


Association between fish intake and glioma risk: a systematic review and meta-analysis.
We investigated the association between the consumption of fresh and processed fish and glioma risk using a meta-analysis approach. We selected and analyzed observational studies that discussed the relationships between fresh and processed fish intake on glioma risk from PubMed, Web of Science, Embase, and the SinoMed and Wanfang databases from inception to 31 March 2020. Studies were selected according to pre-established eligibility criteria and data were extracted separately by two researchers. A meta-analysis was conducted based on a random-effects model to provide pooled odds ratios (OR) and 95% confidence intervals (CIs). Eight studies considered the relationship between fish intake (seven fresh and seven processed fish) and glioma risk and were included in this meta-analysis. The OR effect size for fresh fish intake and glioma risk was 0.72 (95%CI 0.53-0.97) and the overall OR effect size for processed fish intake and glioma risk was 1.88 (95%CI 1.06-3.34). Dietary intake of fresh fish may reduce the risk of glioma, but consumption of processed fish may increase the risk of glioma. This study had some limitations, and further studies are therefore required to clarify the associations between fish intake and glioma risk.


Decreased Resting State Inter- and Intra-Network Functional Connectivity Is Associated with Perceived Stress in a Sample of University Students: An eLORETA Study.
Although the study of the Triple Network (TN) model has gained attention in the exploration of stress-related processes, the neurophysiological mechanisms of TN in relation to perceived stress have been relatively understudied in nonclinical samples so far. The main objective of the present study was to investigate, in a sample of university students, the association of perceived stress with resting state electroencephalography (EEG) functional connectivity in the TN. Ninety university students (40 males and 50 females; mean age 22.30 ± 2.43 years; mean educational level 16.60 ± 1.62 years) were enrolled. EEG data were analyzed through the exact low-resolution electromagnetic tomography (eLORETA). Higher levels of perceived stress were associated with decreased delta EEG connectivity within the central executive network (CEN) and between the CEN and the salience network (SN). Higher levels of perceived stress were also associated with decreased theta EEG connectivity between the CEN and the SN. The associations between perceived stress and EEG connectivity data were significant even when relevant confounding factors (i.e., sex, age, educational level, and psychopathological symptoms) were controlled for. Taken together, our results suggest that higher levels of perceived stress are associated with a dysfunctional synchronization within the CEN and between the SN and the CEN. This functional pattern might in part reflect the negative impact of high levels of perceived stress on cognitive functioning.


Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists.
Prostate cancer is the most common visceral malignancy in men. As the tumor is testosterone dependent, a frequent treatment modality involves therapy with GnRH agonists (GnRH-a) resulting in hypogonadism. Because testosterone is essential for the maintenance of bone mass in men, we postulated that GnRH-a therapy would negatively impact skeletal integrity. We compared bone mineral density (BMD), biochemical markers of bone turnover, and body composition in 60 men with prostate cancer (19 men receiving GnRH-a therapy and 41 eugonadal men) and BMD in 197 community-living healthy controls of similar age. BMD was assessed by dual energy x-ray absorptiometry and ultrasound. Biochemical markers of bone turnover, included markers of bone resorption (urinary N-telopeptide) and bone formation markers (bone-specific alkaline phosphatase and osteocalcin). Body composition (total body fat and lean body mass) was assessed by dual energy x-ray absorptiometry. Significantly lower BMD was found at the lateral spine (0.69 +/- 0.17 vs. 0.83 +/- 0.20 g/cm(2); P < 0.01), total hip (0.94 +/- 0.14 vs. 1.05 +/- 0.16 g/cm(2); P < 0.05), and forearm (0.67 +/- 0.11 vs. 0.78 +/- 0.07 g/cm(2); P < 0.01) in men receiving GnRH-a compared with the eugonadal men with prostate cancer. Significant differences were also seen at the total body, finger, and calcaneus (all P < 0.01). BMD values in eugonadal men with prostate cancer and healthy controls were similar. Markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) were elevated in men receiving GnRH-a therapy compared with those in eugonadal men with prostate cancer. Men receiving GnRH-a also had a higher percent total body fat (29 +/- 5% vs. 25 +/- 5%; P < 0.01) and lower percent lean body weight (71 +/- 5% vs. 75 +/- 5%; P < 0.01) compared with eugonadal men with prostate cancer. In conclusion, men with prostate cancer receiving androgen deprivation therapy have a significant decrease in bone mass and increase in bone turnover, thus placing them at increased risk of fracture.


Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38 MAPK and NF-κB Pathways.
Oxymatrine (OMT) is a strong immunosuppressive agent that has been used in the clinic for many years. In the present study, by using plaque inhibition, luciferase reporter plasmids, qRT-PCR, western blotting, and ELISA assays, we have investigated the effect and mechanism of OMT on influenza A virus (IAV) replication and IAV-induced inflammation in vitro and in vivo. The results showed that OMT had excellent anti-IAV activity on eight IAV strains in vitro. OMT could significantly decrease the promoter activity of TLR3, TLR4, TLR7, MyD88, and TRAF6 genes, inhibit IAV-induced activations of Akt, ERK1/2, p38 MAPK, and NF-κB pathways, and suppress the expressions of inflammatory cytokines and MMP-2/-9. Activators of TLR4, p38 MAPK and NF-κB pathways could significantly antagonize the anti-IAV activity of OMT in vitro, including IAV replication and IAV-induced cytopathogenic effect (CPE). Furthermore, OMT could reduce the loss of body weight, significantly increase the survival rate of IAV-infected mice, decrease the lung index, pulmonary inflammation and lung viral titter, and improve pulmonary histopathological changes. In conclusion, OMT possesses anti-IAV and anti-inflammatory activities, the mechanism of action may be linked to its ability to inhibit IAV-induced activations of TLR4, p38 MAPK, and NF-κB pathways.