Variability of HOMA and QUICKI insulin sensitivity indices.
Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.


When you hear hoofbeats, think horses before zebras - a case of recurrent small bowel obstructions with a twist.
Mechanical small bowel obstructions (SBOs) account for a considerable proportion of hospital admissions for acute abdominal pain. SBOs are most frequently caused by adhesions; and very few SBOs are associated with intraperitoneal devices. An 84-year-old man was admitted to our tertiary institution with recurrent SBOs that were initially believed to be caused by his implantable cardioverter defibrillator which had undergone intraperitoneal migration. However, this was later found to be a misguided 'zebra'; as the cause was revealed to be a common 'horse' - adhesions. This article shares our key learnings from this diagnostic dilemma.


Anti-/pro-apoptotic effects of hesperetin against 7,12-dimetylbenz(a)anthracene-induced alteration in animals.
This study investigated the anticancer effects of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA)-treated animals and explored its anticancer mechanism. The experiment consisted of two parts. First, Sprague-Dawley rats were given hesperetin daily at a dose of 50 mg/kg for 8 weeks after a single dose of DMBA (100 mg/kg). As controls, rats were divided into vehicle alone and DMBA alone groups. Secondly, ICR mice were given hesperetin daily at a dose of 10 and 50 mg/kg BW/day for 7 weeks before a single dose of DMBA (34 mg/kg/week). In rats with DMBA-induced mammary gland tumors, hesperetin pretreatment significantly reduced the tumor burden and PCNA overexpression. The administration of hesperetin significantly inhibited mammary gland carcinoma from developing by restoring the decreased Bcl-2 and increased Bax expression. By contrast, in the livers of mice treated with DMBA, obvious DNA fragmentation was observed. Moreover, apoptosis-related gene expression in the livers of the mice differed from that in mammary gland carcinomas in rats. These changes were restored in mice treated with hesperetin, indicating the inhibition of apoptosis. Based on these results, hesperetin may act not only as a proapoptotic agent, but also as an antiapoptotic agent, depending on the circumstance.


Molecular Probe Data Base (MPDB).
This paper provides an update on the contents and structure, forms and mode of data distribution of the Molecular Probe Data Base (MPDB), a database that collects and provides on-line information on the sequence, target gene, applications and bibliographic references of synthetic oligonucleotides. The recent data extension and the new means of accessing the database are discussed.


Association between opium abuse and comorbidity in diabetic men.
The aims of this study were to determine the prevalence of opium abuse in diabetic men and to investigate its association with comorbidity. The study population was comprised of 312 consecutive diabetic men aged 20 years or older residing in the study area in 2005. The prevalence of self-reported opium abuse was 11.2%. Opium use was associated with low socioeconomic status, smoking, tea consumption, and a higher prevalence of erectile dysfunction (ED) and severe depression. The prevalence of severe depression was 22.8% among 35 men who used opium and 13.4% among 277 who did not use it. The prevalence of moderate or severe ED was 85.7% among opium users and 66.1% among non-users. The risk of ED was two times (95% CI 1.0-7.4) higher in opium users compared with nonusers.


Association of Epigenetic Age and p16INK4a With Markers of T-Cell Composition in a Healthy Cohort.
How the measurement of aging biomarkers in peripheral blood T-lymphocytes (PBTLs) is influenced by cell composition is unclear. Here, we collected peripheral blood and isolated CD3+ PBTLs from 117 healthy couples between the ages of 21 and 72. Each sample was profiled for Horvath epigenetic clock (DNAm), p16INK4a expression, cytomegalovirus (CMV) seropositivity and 74 mRNA markers of PBTL subtype, differentiation, immune checkpoints, and cytokine production. Correlations between individual aging biomarkers (DNAm or p16INK4a) and PBTL mRNAs were corrected for chronological age, sex, and couple. DNAm measurements correlated with CMV seropositivity as well as PBTL mRNAs indicative of effector function (CD8A, EOMES, TBX21, GZMB), poor proliferative capacity (KLRG1, CD57), differentiation (CD45RO, CD45RA), and immune checkpoints (PDCD1, TIGIT, LAG3, CD160, CD244). In contrast, only three PBTL mRNAs, CD28, CD244, and p14ARF, showed a significant association with p16INK4a. p16INK4a expression also showed a weaker association with immunosenescent PBTL subsets than DNAm in flow cytometry analyses. These data suggest that PBTL composition has a greater influence on DNAm than p16INK4a and link accelerated epigenetic aging to immunosenescent phenotypes.


Myopericytoma of the liver hilus: a case report.
Pericytic tumours is a new category recently introduced in soft tissue pathology describing those entities sharing evidence of myoid differentiation and a tendency of spindle or more rounded cells to grow in a perivascular fashion. The great majority of pericytic tumours are benign but recurrence has been described as well as very rare malignant cases with an aggressive behaviour. Although pericytic tumours arise most commonly in the subcutaneous tissue of distal extremities in middle age patients, additional cases have been recently described in many other organs. Here we describe a case of a 57-year-old man with an 8.5 cm mass of the liver hilus diagnosed as myopericytoma, with particular reference to its biological potential and differential diagnosis. It is important for the pathologists to take this diagnosis into consideration as well for a better management of patient care.


Corneal transplant rejection rate and severity after endothelial keratoplasty.
To examine the corneal transplant rejection rate and the rate of graft failure subsequent to rejection in the first 2 years after endothelial keratoplasty (EK) and to compare this to background data for similar cases of penetrating keratoplasty (PK). Anonymized data from consecutive cases of EK [deep lamellar (DLEK) or Descemet stripping (DSEK)] for Fuchs corneal endothelial dystrophy or pseudophakic bullous keratopathy operated on before August 2004 were collected in 4 participating centers. The number and timing of rejection episodes and cases of subsequent graft failure were recorded, together with the time to cessation of topical steroid medication. Two-year postoperative findings were compared with background data for similar patients undergoing PK recorded in the Swedish Corneal Transplant Registry. Rejection episodes were less frequent after EK than PK (P = 0.035). Fifteen (7.5%) of 199 EK cases had a rejection episode in the first 2 years after surgery versus 92 (13%) of 708 PK cases. Graft failure after rejection in EK may have been less frequent than in PK (P = 0.063), with only 1 (6.7%) case of rejection after EK versus 26 (28.3%) cases of rejection after PK proceeding to graft failure. A strong trend toward continued use of low-dose topical steroid medication was observed in the EK group. Eighty percent of EK patients were still taking topical steroid medication 2 years after surgery, whereas topical steroid medication had been ceased within a year of surgery in almost all PK patients in the comparator group. Corneal transplant rejection is less frequent and may be less severe after EK than after PK. It is not yet clear whether these apparent differences are simply a product of relatively prolonged postoperative topical steroid cover in EK patients.


NADPH oxidases-do they play a role in TRPC regulation under hypoxia?
In the lung, acute alveolar hypoxia causes hypoxic pulmonary vasoconstriction (HPV) to maintain ventilation perfusion matching and thus optimal oxygenation of blood. In contrast, global chronic hypoxia triggers a pathological thickening of pulmonary arterial walls, called pulmonary vascular remodelling, leading to persistence of pulmonary hypertension (PH). Moreover, ischaemia or hypoxia can lead to a damage of pulmonary endothelial cells with subsequent oedema formation. Alterations in reactive oxygen species (ROS) have been suggested as a crucial mediator of such responses. Among the various sources of cellular ROS production, NADPH oxidases (NOXs) have been found to contribute to these physiological and pathophysiological signalling processes. NOXs are the only known examples that generate ROS as the primary function of the enzyme system. However, the downstream targets of NOX-derived ROS signalling in hypoxia are still not known. Canonical transient receptor potential (TRPC) channels recently have been recognised as directly or indirectly ROS-activated channels and have been shown to be essential for hypoxia-dependent vascular regulatory processes in the lung. Against this background, we here summarise the current knowledge on NOX-mediated TRPC channel signalling during hypoxia in the pulmonary circulation.


Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-1,4,7-trisacetic Acid (DO3A)-Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent.
We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high r1 relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging.


Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity.
Aptamers are single-stranded RNA or DNA molecules that specifically recognize their targets and have proven valuable for functionalizing sensitive biosensors. α-thrombin is a trypsin-like serine proteinase which plays a crucial role in haemostasis and thrombosis. An abnormal activity or overexpression of this protein is associated with a variety of diseases. A great deal of attention was devoted to the construction of high-throughput biosensors for accurately detect thrombin for the early diagnosis and treatment of related diseases. Herein, we propose a new approach to modulate the interaction between α-thrombin and the aptamer TBA15. To this end, TBA15 was chemically conjugated to two peptide sequences (TBA-G3FIE-Ac and TBA-G3EIF-Ac) corresponding to a short fragment of the acidic region of the human factor V, which is known to interact directly with exosite I. Surface Plasmon Resonance (SPR) results showed enhanced analytical performances of thrombin with TBA-G3EIF-Ac than with TBA wild-type, reaching a limit of detection as low as 44.9 pM. Electrophoresis mobility shift assay (EMSA) corroborated the SPR results. Molecular dynamics (MD) simulations support experimental evidences and provided further insight into thrombin/TBA-peptide interaction. Our findings demonstrate that the combination of TBA15 with key interacting peptides offers good opportunities to produce sensitive devices for thrombin detection and potential candidates to block thrombin activity.


Simultaneous multiparametric PET/MRI for the assessment of therapeutic response to chemotherapy or concurrent chemoradiotherapy of cervical cancer patients: Preliminary results.
To assess the response to initial treatment strategies of cervical cancer using multiparametric-PET/MRI. PET/MR-derived morphological (tumor size), functional (DWI, DCE-MRI) and metabolic (18F-FDG PET) parameters were acquired in pre- and posttreatment examinations of 8 patients. Besides RECIST- and PERCIST-criteria, functional quantitative parameters were used to assess therapeutic response. RECIST- and PERCIST-response criteria demonstrated high correlations for the differentiation between therapy-responders and non-responders, which was additionally reflected by functional (DWI, DCE-MRI) quantitative imaging parameters. Multiparametric-PET/MRI bears the potential of a more comprehensive response assessment of initial treatment strategies in cervical cancer patients.


[Monofascicular nerve rotation].
In case of the loss of one single muscle function in the hand, the possibility of a neurogenic cause should not be overlooked. The differential diagnosis includes: 1. Partial compression; 2. anatomical variation; 3. monofascicular rotational distorsion. Rotational distorsion of a nerve has previously been described by A. Wilhelm (1976). This type of compression syndrome occurs after repeated forceful muscle contractions and may involve for example either exclusively those fascicles in the main trunk of the median nerve, forming the anterior interosseous nerve or the deep branch of the radial nerve. We report a series of six patients in whom torsional nerve injury was found.


Probiotic alternatives to reduce gastrointestinal infections: the poultry experience.
The intestinal mucosa represents the most active defense barrier against the continuous challenge of food antigens and pathogenic microorganisms present in the intestinal lumen. Protection against harmful agents is conferred by factors such as gastric acid, peristalsis, mucus, intestinal proteolysis, and the intestinal biota. The establishment of beneficial bacterial communities and metabolites from these complex ecosystems has varying consequences for host health. This hypothesis has led to the introduction of novel therapeutic interventions based on the consumption of beneficial bacterial cultures. Mechanisms by which probiotic bacteria affect the microecology of the gastrointestinal tract are not well understood, but at least three mechanisms of action have been proposed: production/presence of antibacterial substances (e.g., bacteriocins or colicins), modulation of immune responses and specific competition for adhesion receptors to intestinal epithelium. The rapid establishment of bacterial communities has been thought to be essential for the prevention of colonization by pathogenic bacteria. Some animal models suggest that the reduction in bacterial translocation in neonatal animals could be associated with an increase in intestinal bacterial communities and bacteriocin-like inhibitory substances produced by these species. This review emphasizes the role of the intestinal microbiota in the reduction of the gastrointestinal infections and draws heavily on studies in poultry.


Increased serum levels of C-terminal parathyroid hormone-related protein in different diseases associated with HTLV-1 infection.
We analyzed the serum levels of C-terminal parathyroid hormone-related protein (C-PTHrP) in asymptomatic carriers of human T lymphotropic virus type 1 (HTLV-1) and patients with three HTLV-1 related diseases; adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU). Serum C-PTHrP levels were significantly elevated in HTLV-1-infected individuals, irrespective of whether they were symptomatic or asymptomatic, when compared with that of the seronegative controls. In ATL patients, a good correlation was demonstrated between the serum C-PTHrP level and serum calcium or lactic dehydrogenase (LDH) level. Thus the elevated serum C-PTHrP level could be a characteristic marker of HTLV-1 carrier state, and the determination of its level in ATL patients could be useful for the assessment of the prognosis and as one of the tumor markers. The determination of the serum level of C-PTHrP in various stages of the HTLV-1 carrier state would help to understand the mechanism of the development of hypercalcemia in ATL.


Binding energy of hydrogenic impurities in quantum dots under intense laser radiation.
We calculate the binding energy of on- and off-center hydrogenic impurities in a parabolic quantum dot subjected to an intense high-frequency laser field. An exactly solvable model that replaces the actual Coulomb interaction with the donor by a non-local separable potential is introduced for calculating the binding energy. The separable potential allows us to solve the problem exactly and all calculations are carried out analytically. The action of the laser irradiation results in dressed Coulomb and confinement potentials. At low laser intensity the binding energy is found to decrease when the impurity is shifted away from the origin. At high laser intensity and strong confinement the opposite behavior is observed. We propose a simple one-dimensional model that explains the observed crossover.


Iron toxicity protection by truncated Ras2 GTPase in yeast strain lacking frataxin.
Yeast strain deleted for the YFH1 gene, which encodes the orthologue of human frataxin, accumulates iron in mitochondria, constitutively activates the high-affinity iron import system in the plasma membrane, and is sensitive to high iron media. We have performed a genetic screen for mutants of a yfh1 deleted strain with increased resistance to high levels of iron. One of the identified mutations caused the deletion of the hypervariable C-terminal region of Ras2p GTPase. The effect of ras2 mutation on the growth of yfh1 null strain was masked by the addition of caffeine. We found that the ras2 mutation does not alter the expression of the iron regulon nor prevent mitochondrial iron accumulation in a yfh1 mutant context. The double yfh1 ras2 mutant has increased mRNA levels of CIT2 gene and augmented catalase activity.


Alpha-glucosidase mutant catalyzes "alpha-glycosynthase"-type reaction.
Replacement of the catalytic nucleophile Asp481 by glycine in Schizosaccharomyces pombe alpha-glucosidase eliminated the hydrolytic activity. The mutant enzyme (D481G) was found to catalyze the formation of an alpha-glucosidic linkage from beta-glucosyl fluoride and 4-nitrophenyl (PNP) alpha-glucoside to produce two kinds of PNP alpha-diglucosides, alpha-isomaltoside and alpha-maltoside. The two products were not hydrolyzed by D481G, giving 41 and 29% yields of PNP alpha-isomaltoside and alpha-maltoside, respectively. PNP monoglycosides, such as alpha-xyloside, alpha-mannoside, or beta-glucoside, acted as the substrate, but PNP alpha-galactoside and maltose could not. No detectable product was observed in the combination of alpha-glucosyl fluoride and PNP alpha-glucoside. This study is the first report on an "alpha-glycosynthase"-type reaction to form an alpha-glycosidic linkage.


Beta-N-methylamino-L-alanine: LC-MS/MS optimization, screening of cyanobacterial strains and occurrence in shellfish from Thau, a French Mediterranean lagoon.
β-N-methylamino-L-alanine (BMAA) is a neurotoxic non-protein amino acid suggested to be involved in neurodegenerative diseases. It was reported to be produced by cyanobacteria, but also found in edible aquatic organisms, thus raising concern of a widespread human exposure. However, the chemical analysis of BMAA and its isomers are controversial, mainly due to the lack of selectivity of the analytical methods. Using factorial design, we have optimized the chromatographic separation of underivatized analogues by a hydrophilic interaction chromatography coupled to tandem mass spectrometry (HILIC-MS/MS) method. A combination of an effective solid phase extraction (SPE) clean-up, appropriate chromatographic resolution and the use of specific mass spectral transitions allowed for the development of a highly selective and sensitive analytical procedure to identify and quantify BMAA and its isomers (in both free and total form) in cyanobacteria and mollusk matrices (LOQ of 0.225 and 0.15 µg/g dry weight, respectively). Ten species of cyanobacteria (six are reported to be BMAA producers) were screened with this method, and neither free nor bound BMAA could be found, while both free and bound DAB were present in almost all samples. Mussels and oysters collected in 2009 in the Thau Lagoon, France, were also screened, and bound BMAA and its two isomers, DAB and AEG, were observed in all samples (from 0.6 to 14.4 µg/g DW), while only several samples contained quantifiable free BMAA.


[Effect of methisoprinol on postoperative immunodepression in subjects with malignant neoplasms].
The authors investigated the state of immunity, before and after surgery, in a group of 6 methisoprinol-treated patients and in a 10-patient control group both affected by malignant neoplasia. All the patients exhibited various degrees of immuno-depression. Versus the control group the group treated with 1-g methisoprinol injections at the dosage of 4 g daily for 7 days after surgery showed a positive effect on post-surgical immuno-depression.


Unique Considerations for Paediatric Proximal Phalanx Fractures.
Paediatric hand fracture care presents unique considerations and challenges. The proximal phalanx is the most injured location. This review details pearls for the examination of the injured paediatric hand, immobilisation considerations and treatment strategies. Over-treatment can lead to unnecessary stiffness, missed activities, increased healthcare costs or unnecessary surgical morbidity. Undertreatment can promote malunion and dysfunction. Fracture patterns discussed include those of the phalangeal head, neck, shaft and base. The concepts covered will help optimise the evaluation and treatment of children with injured proximal phalanges. Level of Evidence: Level V (Therapeutic).


Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient.
Human cytomegalovirus infections are still significant causes of morbidity and mortality in transplant recipients. The use of antiviral agents is limited by toxicity and evolving resistance in immunocompromised patients with ongoing viral replication during therapy. Here, we present the first documented case of genotypic resistance against maribavir in a bone marrow transplant (BMT) recipient. The female 13-year-old patient was suffering from a refractory cytopenia. Ganciclovir, foscarnet, cidofovir, leflunomide and maribavir, an inhibitor of the cytomegalovirus UL97 protein, were administered to treat a therapy-resistant cytomegalovirus infection. Viral mutations conferring resistance against nucleotide and pyrophosphate analogs as well as maribavir (MBV) have evolved sequentially. Particularly, impressive was the fast emergence of multiple mutations T409M, H411Y and H411N conferring maribavir resistance after less than 6 weeks. We describe the fast emergence of cytomegalovirus variants with different maribavir resistance associated mutations in a bone marrow transplant recipient treated with MBV 400 mg p.o. twice per day. The results suggest that a high virus load permitted a selection of several but distinct therapy-resistant HCMV mutants. Since a phase II study with MBV is intended for the treatment of resistant or refractory HCMV infections in transplant recipients this has to be kept in mind in patients with high viral loads during therapy (NCT01611974).


A Cross-Sectional Comparative Study of the Performance of the Widal Test and the Typhidot Immunoassay for Typhoid Fever Diagnosis in the West Region of Cameroon.
The diagnosis of typhoid fever based on the Widal slide agglutination test remains a major hurdle in developing countries due to varied perceptions of the value of the Widal test in determining clinical decision-making. We undertook a study to evaluate the diagnostic performance of the Widal test and the Typhidot immunoassay in patients suspected of having typhoid fever in the Menoua division, West Region of Cameroon. Blood and stool samples were collected from 558 consenting febrile patients on the basis of suspicion of typhoid fever. These patients attended three district health services of the Menoua division between April 2018 and September 2019. These patients had clinical symptoms suggestive of typhoid fever as determined by their consultant. Serum was used for the Widal slide agglutination test and for the Typhidot rapid immunoassay test based on manufacturer's guidelines. A composite reference of fever plus positive coproculture for Salmonella typhi and Salmonella paratyphi was used as the reference. The sensitivity, specificity, and predictive values of the positive and negative tests were calculated as well as Cohen's kappa for agreement between the two tests. Of 558 patients, 12.90% tested positive for the reference method, 57.17% tested positive for the Widal slide agglutination test, while 15.59% were positive for Typhidot-IgM. The overall sensitivity, specificity, and predictive values of the positive and negative tests were 80.56%, 94.03%, 66.6%, and 97.03% for Typhidot-IgM and 94.44%, 48.35%, 21.32%, and 98.33% for the Widal slide agglutination test, respectively. Cohen's kappa estimates were 0.1660 (0.121-0.211) and 0.386 (0.312-0.460) for the Widal test and Typhidot immunoassay for 53.6% and 76.16% agreements of all observations, respectively. The Widal test was found to have a lower predictive value for the diagnosis of typhoid fever in our setting. However, the Typhidot test, although better, was not ideal. Diagnosis of typhoid fever should therefore rely on adequate clinical suspicion and a positive Typhidot test to improve the clinical management of typhoid fever in our setting.


Localized periodontal defect associated with unusual furcation involvement on a mandibular incisor.
A localized periodontal defect associated with an unusual furcation on a mandibular central incisor and its treatment sequences are presented. A 54-year-old woman presented with a persistent localized periodontal defect, which was not responsive to nonsurgical periodontal therapy. An exploratory surgery revealed complete through and through furcation involvement on the right mandibular central incisor, resulting in a three-walled infrabony defect. Following thorough mechanical debridement and root planing, the infrabony aspect of the defect was grafted with freeze-dried bone allograft combined with the recombinant human platelet-derived growth factor-BB. The flaps were positioned to enable patient's home care and professional dental cleaning. Follow-up examination revealed uneventful healing and resolution of the infrabony periodontal defect. Clinicians should be aware of this unusual condition and consider it as a potential etiology when dealing with a persistent localized periodontal defect in the mandibular anterior sextant, which may not respond to the conventional nonsurgical periodontal therapy. Eliminating the active disease as well as enabling careful maintenance and oral hygiene may prevent further deterioration and result in a stable long-term outcome preserving the compromised tooth.


Interleukin (IL)-1, 4, 6, 7, 8, 10 Appearance in Congenital Intra-Abdominal Adhesions in Children Under 1 Year of Age.
Several cytokines have been studied for their potential role in adhesion formation. Regulatory role between the cytokine pathways has not yet to be defined. This study was designed to investigate the relation between proinflammatory and anti-inflammatory cytokines in congenital intra-abdominal adhesions. Tissue samples used for research were obtained from abdominal surgery due to obstructive gut malrotation and several additional pathologies (rectal atresia without perforation, omphalocele). All tissue specimens were stained with hematoxylin and eosin and by immunohistochemistry for interleukin-1 (IL-1), IL-4, IL-6, IL-7, IL-8, and IL-10. The number of immunoreactive structures was graded semiquantitatively. Occasionally to moderate number of IL-1, IL-4, and IL-8 positive inflammatory cells and fibroblasts were observed in tissue. Few to moderate connective tissue cells contained IL-6, but moderate to numerous-IL-7 and IL-10. Statistically significant correlation was found between IL-7 and IL-1 (rs=0.471, P=0.001), IL-4 (rs=0.491, P<0.001), IL-8 (rs=0.440, P=0.001), IL-10 (rs=0.433, P=0.002). The relatively common finding of IL-6 in adhesions points out the relevance of lymphocyte balance regulation of an ongoing inflammation and regenerative processes. The coherence between the inflammation mediator IL-7 and other proinflammatory/anti-inflammatory cytokines suggests about activation of macrophages and chronic inflammatory aggregate formation. The essential IL-10 and less distinct IL-1 findings in the adhesion material points out strong local defense reactions.


Effects of epanolol, a selective beta1-blocker with intrinsic sympathomimetic activity, in patients with ischemic left ventricular dysfunction.
Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.


Does multidisciplinary rehabilitation benefit whiplash recovery?: results of a population-based incidence cohort study.
Population-based, incidence cohort. To evaluate a government policy of funding community and hospital-based fitness training and multidisciplinary rehabilitation for whiplash. Although insurance benefits commonly include rehabilitation for whiplash, its effectiveness is unknown. All Saskatchewan adults treated for whiplash (n = 6,021) over a 2-year period were followed up at 6 weeks, 3, 6, 9, and 12 months. Recovery was defined by self-report of improvement. Recovery times were compared between those attending fitness training at health clubs (n = 833), multidisciplinary outpatient rehabilitation (n = 468), and multidisciplinary inpatient rehabilitation (n = 135) to those receiving usual insured individual care. Recovery was 32% slower in those receiving fitness training within 69 days of injury (P = 0.001) and 19% slower when received within 119 days of injury (P = 0.041). Recovery was 50% slower in those receiving outpatient rehabilitation within 119 days of injury (P = 0.001). Attending inpatient rehabilitation did not influence recovery rates during the follow up (P = 0.131). Multivariable adjustment for important prognostic factors did not change these results. We found no evidence to support the effectiveness of a population-based program of fitness training and multidisciplinary rehabilitation for whiplash. Rehabilitation programs should be tested in randomized trials before being recommended to injured populations.


Comparison of cigarette, little cigar, and waterpipe tobacco smoke condensate and e-cigarette aerosol condensate in a self-administration model.
The pharmacological effects of tobacco products are primarily mediated by nicotine; however, research suggests that several non-nicotine tobacco constituents may alter the reinforcing effects of nicotine. This study evaluated the reinforcing effects of aqueous solutions of smoke/aerosol condensate from cigarettes, little cigars, electronic cigarettes (e-cigarettes), and waterpipe tobacco in a self-administration procedure to determine if abuse liability of these tobacco products differed. Adult male Sprague-Dawley rats (n = 64 total) were trained to self-administer intravenous nicotine (30 μg/kg/infusion) on a fixed ratio 5 schedule of reinforcement. Following nicotine dose-effect assessment (1, 7.5, 15, and 30 μg/kg/infusion), rats were given access to smoke/aerosol condensate derived from their assigned tobacco product. Rats responded for smoke/aerosol condensate containing 1, 7.5, 15, and 30 μg/kg/infusion nicotine, with the ratio of nicotine:non-nicotine constituents held constant across doses for each tobacco product. Responding for nicotine or smoke/aerosol condensate was also assessed on a progressive ratio schedule of reinforcement. Cigarette, little cigar, and e-cigarette smoke/aerosol condensates shifted the nicotine dose-effect curve leftward, whereas waterpipe tobacco smoke condensate shifted the dose-effect curve rightward. Smoke/aerosol condensate from all tobacco products produced similar levels of responding compared to nicotine alone during the progressive ratio phase. Results suggest that non-nicotine constituents in cigarettes, little cigars, and e-cigarettes differentially enhance nicotine's reinforcing potency. In contrast, waterpipe tobacco blunted nicotine's reinforcing potency, suggesting that it may contain unique constituents that dampen nicotine's reinforcing effects.


Fluorescence-activated cell sorting analysis of the induction and expression of acute thermal tolerance within the cell cycle.
We have examined the cell cycle specificity of 45.5 degrees heat-induced toxicity and the induction and expression of thermal tolerance. Ultrapure populations of G1-, S-, and G2-M-phase cells were obtained through sequential centrifugal elutriation and flow cytometric cell sorting of Hoechst 33342-stained cells. We found no interaction of Hoechst 33342 with hyperthermia under staining conditions that gave good cytometric resolution of DNA distributions. Single dose-response survival curves indicated that S phase was the most sensitive to 45.5 degrees hyperthermia (Do = 1.97, 1.26, and 1.95 min for G1, S, and G2-M, respectively). Both S and G2-M phases exhibited a decreased ability from G1 to accumulate sublethal heat lesions as evidenced by decreased heat survival curve shoulders (Dq) = 13.7, 9.51, and 8.39 min for G1, S, and G2-M, respectively). Thermal tolerance, as measured by the decreased inactivation slope of the split-dose treatment, could be induced and expressed in G1, S, and G2-M phases. However, both the magnitude and temporal expression of tolerance were dependent on the position of the cell within the cell cycle at the time of the initial heat treatment. S-phase cells exhibited slightly less thermal tolerance as compared to G1 cells given isosurvival thermal induction doses as measured by the split-dose inactivation rate constants (heated/control = 8.37 and 5.62 for G1 cells at 12 and 24 hr and 7.68 and 5.27 for S-phase cells at 12 and 28 hr). Also, split-dose survival curves for cells heated in G2-M indicated a near total inability to accumulate heat-induced sublethal damage. Simultaneous bivariate (90 degrees light scatter and DNA content) progression analysis of heated replicates indicated that tolerance could probably be expressed in those cells which moved into other cycle compartments following the initial heat treatment. For instance, G1-phase cells preheated for 20 min began progression into normally heat-sensitive S phase between 24 and 28 hr after the heat treatment. This corresponded to approximately the time of maximal thermal tolerance expression. [3H]Thymidine suicide experiments also indicated that the ultimately clonogenic cells began movement into S phase at or near the time of maximal tolerance. In this case then, tolerance expression appeared to supersede the S-phase acute heat sensitivity. Heated S-phase cells began progression into G2-M between 4 and 12 hr, which corresponded temporally to large amounts of tolerance expression4 +


[The nervous system in rheumatic diseases].
Underlying the pain in rheumatic diseases are interactive effects between tissues, the extracellular environment and the nervous system, complex interactions within the nervous system itself, and changes in the properties of nerve cells. These phenomena and their effects as reflected in the treatment of rheumatic diseases are summarised in this review.


Existence of an energy function for three-dimensional chaotic "sink-source" cascades.
This paper is a continuation of research in the direction of energy function (a smooth Lyapunov function whose set of critical points coincides with the chain recurrent set of a system) construction for discrete dynamical systems. The authors established the existence of an energy function for any A-diffeomorphism of a three-dimensional closed orientable manifold whose non-wandering set consists of a chaotic one-dimensional canonically embedded surface attractor and repeller.


Interaction of chlamydiae with host cells and mucous surfaces.
For chlamydiae, as obligate intracellular parasites, attachment to and ingestion by host cells are essential steps in reproduction. Their attachment site appears to be heat-sensitive; it has not been correlated with any morphological entity. Antibody blocks chlamydial attachment to cells and, for certain chlamydia psittaci and chlamydia trachomatis strains which are highly infective for cell cultures, N-acetylglucosamine appears to contribute to cell receptor specificity. Sialic acid residues have been suggested as receptors for other C. trachomatis strains. The guinea-pig inclusion conjunctivitis strain of C. psittaci becomes associated with the conjunctiva during incubation of inoculated tissue fragments in vitro. However, although antibody from tears neutralizes infectivity of this strain in vivo, association of the organism with tissue fragments is not inhibited, suggesting that antibody neutralization in vivo is not mediated by prevention of attachment to cells. Chlamydial infectivity for cell monolayers is greatly increased by centrifugation. The process is temperature-dependent and involves cooperative interactions between direction force and the pressure generated during centrifugation. Enhanced infectivity appears to result from changes induced in the cell surface. These changes may favour nonspecific interactions in attachment, since antibody inhibition of infectivity on static cell monolayers is overcome by centrifugation.


Toward a national policy on Alcohol: A complex public health issue in need of urgent action.
Alcohol use is a major public health issue. It is also associated with a range of family, social, and economic problems. This led multiple countries worldwide to adopt national policies for alcohol regulation. Over the years, alcohol use and related problems have increased in India. The existing regulatory framework on alcohol varies greatly across states in terms of government sanctions, pricing, and legal drinking age, resulting in variations in its availability and prevalence of alcohol use disorder and related harms. Despite alcohol use being mentioned in several national policies and plans, a comprehensive national policy addressing alcohol is lacking. In this manuscript, the need for a dedicated national alcohol policy is underscored, emphasizing its potential to mobilize resources, prioritize interventions, and guide various stakeholders. The timely implementation of such a policy is crucial to address the multifaceted challenge of alcohol use effectively.


Revealing the Genetic Impact of the Ottoman Occupation on Ethnic Groups of East-Central Europe and on the Roma Population of the Area.
History of East-Central Europe has been intertwined with the history of Turks in the past. A significant part of this region of Europe has been fallen under Ottoman control during the 150 years of Ottoman occupation in the 16-17th centuries. The presence of the Ottoman Empire affected this area not only culturally but also demographically. The Romani people, the largest ethnic minority of the East-Central European area, share an even more eventful past with Turkish people from the time of their migration throughout Eurasia and they were a notable ethnic group in East-Central Europe in the Ottoman era already. The relationship of Turks with East-Central European ethnic groups and with regional Roma ethnicity was investigated based on genome-wide autosomal single nucleotide polymorphism data. Population structure analysis, ancestry estimation, various formal tests of admixture and DNA segment analyses were carried out in order to shed light to the conclusion of these events on a genome-wide basis. Analyses show that the Ottoman occupation of Europe left detectable impact in the affected East-Central European area and shaped the ancestry of the Romani people as well. We estimate that the investigated European populations have an average identity-by-descent share of 0.61 with Turks, which is notable, compared to other European populations living in West and North Europe far from the affected area, and compared to the share of Sardinians, living isolated from these events. Admixture of Roma and Turks during the Ottoman rule show also high extent.


Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones.
Gatifloxacin, gemifloxacin, and moxifloxacin are the newest fluoroquinolones and show excellent in vitro activity against a wide variety of respiratory tract pathogens, many gram-negative aerobic organisms, and Bacteroides fragilis. These agents may be administered as oral and/or intravenous formulations with excellent bioavailability. The pharmacodynamics of these 3 new fluoroquinolones is more favorable than that of levofloxacin or ciprofloxacin for Streptococcus pneumoniae. All 3 agents are approved for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia. In addition, gatifloxacin and moxifloxacin are approved for the treatment of sinusitis. The toxicity of these 3 agents appears to be similar to that of the other fluoroquinolones in terms of gastrointestinal and central nervous system disturbances. All 3 agents have a low risk of phototoxicity, but gemifloxacin is associated with an increased risk of skin rash that is not a photoreaction. These agents can be useful for treatment of bacterial respiratory tract infections in patients who are allergic to beta-lactams, but caution must be exercised to avoid the potential for selection of widespread resistance, which may occur with indiscriminate use.


Inferior rectus paresis after secondary blepharoplasty.
A 52-year-old woman underwent a secondary cosmetic blepharoplasty for repair of residual dermatochalasis. After this procedure vertical diplopia was noted. Ultrasound examination and the findings at operation were consistent with trauma to the inferior rectus muscle. We present this as an additional complication of cosmetic blepharoplasty.


CRISPR/Cas9-Mediated SlMYC2 Mutagenesis Adverse to Tomato Plant Growth and MeJA-Induced Fruit Resistance to Botrytis cinerea.
Methyl jasmonate (MeJA), a natural phytohormone, played a critical role not only in plant growth but also in plant defense response to biotic and abiotic stresses. MYC2, a basic helix-loop-helix transcription factor, is a master regulator in MeJA signaling pathway. In the present work, slmyc2 mutants were generated by the clustered regularly interspaced short palindromic repeats and associated Cas9 protein (CRISPR/Cas9) system to investigate the role of SlMYC2 in tomato plant growth and fruit disease resistance induced by exogenous MeJA. The results showed that slmyc2 mutants possessed a higher number of flowers and a lower fruit setting rate in comparison with wild-type plants. In addition, the fruit shape of slmyc2 mutant was prolate, while the control fruits were oblate. Knockout of SlMYC2 significantly decreased the activities of disease defensive and antioxidant enzymes, as well as the expression levels of pathogen-related (PR) genes (SlPR-1 and SlPR-STH2) and the key genes related to jasmonic acid (JA) biosynthesis and signaling pathway including allene oxide cyclase (SlAOC), lipoxygenase D (SlLOXD), SlMYC2, and coronatine insensitive 1 (SlCOI1), and consequently aggravated the disease symptoms. By contrast, the disease symptoms were largely reduced in MeJA-treated fruit that possessed higher activities of these enzymes and expression levels of genes. However, the induction effects of MeJA on fruit disease resistance and these enzymes' activities and genes' expressions were significantly attenuated by knockout of SlMYC2. Therefore, the results indicated that SlMYC2 played positive regulatory roles not only in the growth of tomato plants but also in MeJA-induced disease resistance and the antioxidant process in tomato fruits.


Gender disparity in patients undergoing percutaneous coronary intervention for acute coronary syndromes - does it still exist in contemporary practice?
Prior studies have demonstrated evidence of a disparity in the treatment and outcome of male compared to female patients undergoing percutaneous coronary intervention (PCI). From a dedicated database, we retrospectively analysed all consecutive patients with acute coronary syndrome (ACS) admitted to our institution for PCI in 2008. Baseline and procedural characteristics as well as complications were then evaluated for male patients (n = 331) as compared with female patients (n = 137). Women were noted to be older at the time of presentation (66.1 +/- 10.0 vs 60.7 +/- 11.6 years, P <0.00001), the groups were otherwise well matched in terms of baseline characteristics. Female patients were treated with significantly smaller diameter stents (2.86 +/- 0.44 vs 2.96 +/- 0.50 mm, P = 0.04), though the proportion of drug-eluting stents was similar (53.7% vs 50.5%, P = 0.5). Female patients were significantly less likely to receive optimal medical therapy with lesser use of glycoprotein IIb/IIIa inhibitor (26.3% vs 55.3%, P <0.0000001), and beta-blockers (83.9% vs 90.9%, P = 0.04). At 30 days, there were no differences in the rate of major adverse cerebrovascular or cardiac events (2.9% vs 3.9%, P = 0.8), though females had a significantly higher rate of femoral access site pseudoaneurysm (4.4% vs 0.9%, P = 0.02). There remains evidence for continued gender disparity in contemporary practice; despite evidence for efficacy in ACS patients, females received a notably lower use of glycoprotein IIb/IIIa inhibitors and beta-blockers. Women are also significantly more likely to develop femoral access site complications with pseudoaneurysm development; it is important therefore to optimise procedures for sheath removal in female patients or give strong consideration to the use of radial access site.


Auricular reconstruction: an update.
One of the greatest challenges in facial plastic surgery is total auricular reconstruction. The ability to construct a fully satisfactory complete external ear has for centuries been an elusive goal. With advancing standards and expectations in plastic surgery, greater focus is being directed to this arena of reconstruction as well. With advances both in surgical technique and biotechnology, an expanding range of options is available to the reconstructive surgeon who is willing to take on this still formidable task. While progress continues to be made in the detailing of costal cartilage grafts and soft-tissue rearrangement, it is also being made with the use of alloplastic implants and prostheses. The most promising field of advances, with the hope of eventual clinical utility, lies in the realm of bioengineering with cultured cartilage. Review of the literature over the past year reveals several reports describing advances made in the development of cultured chondrocytes with attempts to direct special shape to the manufactured neocartilage. Though advances continue to be made, actual clinical applicability of this technology is still insufficient while expectation continues that this will eventually become integral to total auricular reconstruction.


Septicemia due to a non-0:1, non-0:139 Vibrio cholerae.
We describe a patient with a non-0:1, non-0:139 Vibrio cholerae septicemia associated with ecythema gangrenosa-like skin lesions. The patient acquired the infection in Puerto Rico. Given the high fatality rate, it is important for the medical community to consider the diagnosis in high risk patients with exposures in Puerto Rico tropical waters.


Association of Intron Microsatellite Instability and Exon Mutational Profile of TP53 in Human Gastric Cancers.
Microsatellite instability (MSI) is a hallmark of genomic instability. In gastric cancer (GC), MSI phenotype is an important molecular subgroup that is often closely correlated with elevated mutation rates on the whole genome level. However, on a single gene level, it is still unknown whether the MSI status of a gene is correlated with the mutational profile of the gene itself. We analyzed intron MSI status and exon mutational profile of TP53 through short tandem repeat (STR) scanning and direct sequencing respectively in gastric cancers and their matched normal tissues. MSI status of the TP53 intron was significantly associated with the mutational profile of seven TP53 exon positions (p=0.0416), male patients (p=0.0095), and drinking (p=0.0474), and showed a mild correlation with longer survival time (p=0.0584) and increasing age (p=0.0611). TP53 exons tended to mutation in the status of TP53 intron MSI.


Social drug use in the parturient: implications for the management of obstetrical anaesthesia.
Maternal use of social drugs in pregnancy continues to increase--worldwide. Although a great deal has been learned regarding the implications of illicit drug abuse in pregnancy (cocaine, amphetamines, hallucinogens), the use of social drug in pregnancy has received far less attention. This article reviews the consequences of the social drug use in pregnancy including ethanol, tobacco and caffeine and offers recommendation for anaesthetic management of these potentially complicated pregnancies.


Reduced Heartbeat-Evoked Responses in a Near-Death Case Report.
Whether brain-heart communication continues under ventricular fibrillation (VF) remains to be determined. There is weak evidence of physiological changes in cortical activity under VF. Moreover, brain-heart communication has not previously been studied in this condition. We aimed to measure parallel changes in heart-rate variability (HRV), cortical activity, and brain-heart interactions in a patient who experienced VF. The EEG and EKG signals for the case report were acquired for approximately 20 h. We selected different 1-min-long segments based on the changes in the EKG waveform. We present the changes in heartbeat-evoked responses (HERs), HRV, and EEG power for each selected segment. The overall physiological activity appeared to deteriorate as VF proceeded. Brain-heart interactions measured using HERs disappeared, with a few aberrant amplitudes appearing occasionally. The parallel changes in EEG and HRV were not pronounced, suggesting the absence of bidirectional neural control. Our measurements of brain-heart interactions suggested that the evolving VF impairs communication between the central and autonomic nervous systems. These results may support that reduced brain-heart interactions reflect loss of consciousness and deterioration in the overall health state.


A Replication-Defective Influenza Virus Vaccine Confers Complete Protection against H7N9 Viral Infection in Mice.
Avian influenza H7N9 viruses continue to pose a great threat to public health, which is evident by their high case-fatality rates. Although H7N9 was first isolated in humans in China in 2013, to date, there is no commercial vaccine available against this particular strain. Our previous studies developed a replication-defective influenza virus through mutation of the hemagglutinin (HA) cleavage site from a trypsin-sensitive to an elastase-sensitive motif. In this study, we report the development of a reassortant mutant influenza virus derived from the human isolate A/British Columbia/01/2015 (H7N9) [BC15 (H7N9)], which is the QVT virus. The HA gene of this virus possesses three mutations at the cleavage site, Lys-Gly-Arg were mutated to Gln-Thr-Val at amino acid (aa) positions 337, 338, and 339, respectively. We report this virus to rely on elastase in vitro, possess unaltered replication abilities when elastase was provided compared to the wild type virus in vitro, and to be non-virulent and replication-defective in mice. In addition, we report this virus to induce significant levels of antibodies and IFN-γ and IL-5 secreting cells, and to protect mice against a lethal challenge of the BC15 (H7N9) virus. This protection is demonstrated through the lack of body weight loss, 100% survival rate, and the prevention of BC15 (H7N9) viral replication as well as the reduction of proinflammatory cytokines induced in the mouse lung associated with the influenza disease. Therefore, these results provide strong evidence for the use of this reassortant mutant H7N9 virus as a replication-defective virus vaccine candidate against H7N9 viruses.


Diet regulates membrane extension and survival of niche escort cells for germline homeostasis via insulin signaling.
Diet is an important regulator of stem cell homeostasis; however, the underlying mechanisms of this regulation are not fully known. Here, we report that insulin signaling mediates dietary maintenance of Drosophila ovarian germline stem cells (GSCs) by promoting the extension of niche escort cell (EC) membranes to wrap around GSCs. This wrapping may facilitate the delivery of bone morphogenetic protein stemness factors from ECs in the niche to GSCs. In addition to the effects on GSCs, insulin signaling-mediated regulation of EC number and protrusions controls the division and growth of GSC progeny. The effects of insulin signaling on EC membrane extension are, at least in part, driven by enhanced translation of Failed axon connections (Fax) via Ribosomal protein S6 kinase. Fax is a membrane protein that may participate in Abelson tyrosine kinase-regulated cytoskeletal dynamics and is known to be involved in axon bundle formation. Therefore, we conclude that dietary cues stimulate insulin signaling in the niche to regulate EC cellular structure, probably via Fax-dependent cytoskeleton remodeling. This mechanism enhances intercellular contact and facilitates homeostatic interactions between somatic and germline cells in response to diet.


Fungi as mutualistic partners in ant-plant interactions.
Associations between fungi and ants living in mutualistic relationship with plants ("plant-ants") have been known for a long time. However, only in recent years has the mutualistic nature, frequency, and geographical extent of associations between tropical arboreal ants with fungi of the ascomycete order Chaetothyriales and Capnodiales (belonging to the so-called "Black Fungi") become clear. Two groups of arboreal ants displaying different nesting strategies are associated with ascomycete fungi: carton-building ants that construct nest walls and galleries on stems, branches or below leaves which are overgrown by fungal hyphae, and plant-ants that make their nests inside living plants (myrmecophytes) in plant provided cavities (domatia) where ants cultivate fungi in small delimited "patches". In this review we summarize the current knowledge about these unsuspected plant-ant-fungus interactions. The data suggest, that at least some of these ant-associated fungi seem to have coevolved with ants over a long period of time and have developed specific adaptations to this lifestyle.


Perceptions, attitudes and factors that influence prescribing by general dentists in Australia: A qualitative study.
Longitudinal studies of dental prescribing in Australia show that dentists make some inappropriate prescribing choices; literature has shown that dentists tend to overprescribe antibiotics and prescribe for incorrect indications. The unnecessary use of antibiotics is a contributing factor towards the development of antibiotic resistance. The aims of the study were to obtain a greater understanding of the perceptions, attitudes and factors that influence dental prescribing for all major relevant drug classes. Semi-structured interviews of 15 purposively sampled dentists practising in Victoria, Australia were conducted from June-September 2018. Two dentists practised in rural areas and the remainder in urban locations. The range of clinical experience varied from 2.5 to 37 years, with a mean of 13 years. The transcripts were analysed thematically. Dentists generally preferred amoxicillin as first-line therapy for odontogenic infections, with some confusion about the spectrum and uses of antibiotics. Overprescribing was evident, mostly due to basing judgement for use of antibiotics on symptoms rather than clinical signs. Other factors, such as time pressure, patient expectations, pressure from assistant staff, concern about online criticism and medico-legal considerations, influenced prescribing. Of the dentists who prescribed anxiolytics, most did not have a care protocol for their sedated patients. A variety of prescribing practices were described, and future interventions should target misconceptions around the appropriate use and choice of antibiotics, resources to address the shortfall in knowledge of therapeutics, patient education and staff training, as well as appropriate care and monitoring of sedated patients.


Age Effects on Visuo-Haptic Length Discrimination: Evidence for Optimal Integration of Senses in Senior Adults.
Demographic changes in most developed societies have fostered research on functional aging. While cognitive changes have been characterized elaborately, understanding of perceptual aging lacks behind. We investigated age effects on the mechanisms of how multiple sources of sensory information are merged into a common percept. We studied visuo-haptic integration in a length discrimination task. A total of 24 young (20-25 years) and 27 senior (69-77 years) adults compared standard stimuli to appropriate sets of comparison stimuli. Standard stimuli were explored under visual, haptic, or visuo-haptic conditions. The task procedure allowed introducing an intersensory conflict by anamorphic lenses. Comparison stimuli were exclusively explored haptically. We derived psychometric functions for each condition, determining points of subjective equality and discrimination thresholds. We notably evaluated visuo-haptic perception by different models of multisensory processing, i.e., the Maximum-Likelihood-Estimate model of optimal cue integration, a suboptimal integration model, and a cue switching model. Our results support robust visuo-haptic integration across the adult lifespan. We found suboptimal weighted averaging of sensory sources in young adults, however, senior adults exploited differential sensory reliabilities more efficiently to optimize thresholds. Indeed, evaluation of the MLE model indicates that young adults underweighted visual cues by more than 30%; in contrast, visual weights of senior adults deviated only by about 3% from predictions. We suggest that close to optimal multisensory integration might contribute to successful compensation for age-related sensory losses and provides a critical resource. Differentiation between multisensory integration during healthy aging and age-related pathological challenges on the sensory systems awaits further exploration.


Mixed Solvent Electrolyte Solutions: A Review and Calculations with the eSAFT-VR Mie Equation of State.
In this work, mixed-solvent mean ionic activity coefficients (MIAC), vapor-liquid equilibrium (VLE), and liquid-liquid equilibrium (LLE) of electrolyte solutions have been addressed. An extended literature review of existing electrolyte activity coefficient models (eGE) and electrolyte equations of state (eEoS) for modeling mixed solvent electrolyte systems is first presented, focusing on the details of the models in terms of physical and electrolyte terms, relative static permittivity, and parameterization. The analysis of this literature reveals that the property predictions can be ranked, from the easiest to the most difficult, in the following order: VLE, MIAC, and LLE. We have then used our previously developed eSAFT-VR Mie model to predict MIAC, VLE, and LLE in mixed solvents without fitting any new adjustable parameters. The model was parameterized on MIAC of aqueous electrolyte solutions and successfully extended to nonaqueous, single solvent electrolyte solutions without any new adjustable parameters by using a salt-dependent expression for the relative static permittivity. Our approach yields excellent results for MIAC and VLE of mixed solvent electrolyte solutions, while being fully predictive. LLE is significantly more challenging, and an accurate model for the salt-free solution is crucial for accurate calculations. When the compositions of the two phases in the binary salt-free system are accurately captured, then the electrolyte extension of our model shows a lot of potential and is currently among the best eEoS for LLE prediction in the literature.


TLR3-mediated synthesis and release of eotaxin-1/CCL11 from human bronchial smooth muscle cells stimulated with double-stranded RNA.
Respiratory infections with RNA viruses, such as rhinovirus or respiratory syncytial virus, are a major cause of asthma exacerbation, accompanied by enhanced neutrophilic and/or eosinophilic inflammation of the airways. We studied the effects of dsRNA synthesized during RNA virus replication, and of its receptor, TLR3, on the synthesis of eosinophilic chemokines in bronchial smooth muscle cells (BSMC). Synthetic dsRNA, polyinosinic-cystidic acid (poly(I:C)), induced the synthesis of eosinophilic chemokines, eotaxin-1/CCL11 and RANTES/CCL5, from primary cultures of human BSMC, and IL-4 increased synergistically the synthesis of poly(I:C)-induced CCL11. A robust eosinophil chemotactic activity was released from BSMC stimulated with poly(I:C) and IL-4, which was mostly inhibited by preincubation with an anti-CCL11, but not with an anti-CCL5 Ab. Although the immunoreactivity of TLR3 was detectable on the cellular surface of BSMC by flow cytometric analysis, pretreatment with an anti-TLR3-neutralizing Ab failed to block the poly(I:C)-induced synthesis of CCL11. We have determined by confocal laser-scanning microscopy that the immunoreactivity of TLR3 was aggregated intracellularly in poly(I:C)-stimulated BSMC, colocalizing with fluorescein-labeled poly(I:C). The synthesis of CCL11 was prominently inhibited by the transfection of TLR3-specific small interfering RNA or by bafilomycin A1, an endosomal acidification inhibitor, further supporting the essential role played by intracellular TLR3 in the synthesis of poly(I:C)-induced CCL11 in BSMC. In conclusion, these observations suggest that, by activating intracellular TLR3 in BSMC, respiratory RNA virus infections stimulate the production of CCL11 and enhance eosinophilic inflammation of the airways in the Th2-dominant microenvironment.


Impulsivity and alexithymia predict early versus subsequent relapse in patients with alcohol use disorder: A 1-year longitudinal study.
Longitudinal psychopathological predictors of relapse in alcohol use disorder are unclear. Relapses, sociodemographic and psychopathological risk factors were assessed in 171 alcohol use disorder outpatients within a 1-year follow up. Impulsivity and alexithymia were evaluated using the Barratt Impulsiveness Scale and the Toronto Alexithymia Scale, respectively. At endpoint, 39% of patients maintained abstinence, 30.9% relapsed at ≤1 month from detoxification (early), 30.1% at >1 month (subsequent). Baseline Barratt Impulsiveness Scale score was predictive of early versus subsequent relapse (odds ratio 1.12, p = 0.005) and versus abstinence (odds ratio 1.17, p < 0.001). Toronto Alexithymia Scale score was a risk factor for subsequent versus early relapse (odds ratio 1.13, p = 0.003) and versus abstinence (odds ratio 1.21, p < 0.001). Impulsivity predicted relapse within the first 4-weeks; alexithymia showed delayed effects. Time-varying effects of specific relapse factors emphasise the need for preliminary careful assessment and personalised interventions to promote long-term abstinence.


In-vitro activity of vancomycin, teicoplanin, daptomycin, ramoplanin, MDL 62873 and other agents against staphylococci, enterococci and Clostridium difficile.
The minimum inhibitory concentrations (MICs) of different antibiotics were determined by a broth microdilution method for staphylococci, enterococci and Clostridium difficile. The antimicrobial agents tested were vancomycin, teicoplanin, daptomycin, ramoplanin, MDL 62873, rifampicin and piperacillin, the latter limited to enterococci. In terms of MIC90S, daptomycin (0.89 mg/l). MDL 62873 (0.99 mg/l), and teicoplanin (1.50 mg/l) were found to be highly active against methicillin-resistant Staphylococcus aureus (MRSA). Daptomycin (MIC90 0.48 mg/l), MDL 62873 (0.95 mg/l) and ramoplanin (1.45 mg/l) were the most active drugs against methicillin-resistant S. epidermidis (MRSE). Teicoplanin (MIC90 0.45 mg/l) was the most active agent against enterococci, followed by MDL 62873 (0.65 mg/l) and daptomycin (1.60 mg/l). MDL 62873 gave the lowest MIC90 (0.17 mg/l) for C. difficile. Teicoplanin (MIC90 0.42 mg/l), daptomycin (0.87 mg/l) and ramoplanin (0.98 mg/l) were also very active. Our results indicate that teicoplanin, daptomycin, ramoplanin and MDL 62873, a teicoplanin derivative, are potentially effective alternative antibiotics for treatment of infections caused by staphylococci, enterococci and C. difficile.


The Mitsunobu reaction: origin, mechanism, improvements, and applications.
The Mitsunobu reaction is a widely used and versatile method for the dehydrative oxidation-reduction condensation of an acid/pronucleophile usually with a primary or secondary alcohol that requires the combination of a reducing phosphine reagent together with an oxidizing azo reagent. The utility of this reaction stems from the fact that it is generally highly stereoselective and occurs with inversion of the stereochemical configuration of the alcohol starting material. Furthermore, as carboxylic acids, phenols, imides, sulfonamides, and other compounds can be used as the acid/pronucleophile, this reaction is useful for the preparation of a wide variety of functional groups. This Focus Review of the Mitsunobu reaction summarizes its origins, the current understanding of its mechanism, and recent improvements and applications.


Simultaneous detection and differentiation of Mycobacterium tuberculosis and nontuberculous mycobacteria coexisting in patients with pulmonary tuberculosis by single-tube multiplex PCR.
In clinical diagnostics, molecular methods are used to detect Mycobacterium tuberculosis bacilli (MTB) and to distinguish them from non-tuberculous mycobacteria (NTM). They are also used to make the right treatment decision for the patient as soon as possible. The aim of this study was to establish a rapid and novel multiplex PCR (mPCR) assay for the detection and differentiation of MTB and NTM in a single tube. 100 sputum samples positive for acid-fast bacilli (AFB) were included in this study. Mycobacterial culture, biochemical tests, and antibiotic susceptibility testing were performed on samples. After alkaline decontamination, total DNA was extracted from the samples. A primer pair targeting the rpoB gene, encoding the beta-subunit of RNA polymerase, was used to detect MTB and NTM, amplifying a 235-bp fragment of MTB and a 136-bp sequence of NTM. A pair of primers targeting a 190-bp fragment of the IS6110 region of MTB was also used to confirm the results. The sensitivity and specificity of the mPCR assay were evaluated using DNA extracted from standard strains. The amplified products were then analyzed by conventional agarose gel electrophoresis. Of 100 AFB smear-positive sputum samples, 92 MTB DNA, 7 NTM DNA, and one mixed-infection sample were identified in a single tube using mPCR assay. There was no correlation between the AFB degree of smear positivity and PCR results. Of seven NTM isolates, 6 (86%) were resistant to rifampin, isoniazid, and ethambutol, the three first-line anti-tuberculosis drugs. A single-tube mPCR assay based on the rpoB gene provides a rapid and reliable means of detecting and differentiating MTB and NTM in sputum specimens.


"Here's egg in your eye": a prospective study of blunt ocular trauma resulting from thrown eggs.
To see if a public awareness campaign might be justified around Halloween with regard to the dangers of egg throwing. A prospective study was carried out of all patients who attended the St Paul's Eye Unit's Primary Care Department with ocular injuries resulting from a thrown egg over a 14-month period from November 2004. All injuries were classified as minor, intermediate or major and patients were followed up until discharge. 13 ocular injuries that were attributed to assault with a raw egg were reported. In all the 13 cases, the eggs had been thrown by strangers. 12 of the patients were men and the average age of the victims was 27.9 years. 9 patients were injured in the left eye and there were no bilateral injuries. On presentation, only 1 patient had a visual acuity of 6/6, 7 presented at 6/9, with the remainder having 6/18 or worse. All the patients had closed globe injuries. 8 injuries were classified as major injuries. 4 patients had permanent sequelae, with one suffering permanent, severe visual loss. Although most of our patients showed improvement in visual acuity, there were severe injuries, with the potential for severe ocular morbidity. We conclude that there is sufficient injury caused by this prank to warrant a public health message. At the least this practice should not be promoted by the press.


Comparing stigmatising attitudes towards people with substance use disorders between the general public, GPs, mental health and addiction specialists and clients.
Substance use disorders (SUDs) are among the most severely stigmatised conditions; however, little is known about the nature of these stigmatising attitudes. To assess and compare stigmatising attitudes towards persons with SUDs among different stakeholders: general public, general practitioners (GPs), mental health and addiction specialists, and clients in treatment for substance abuse. Cross-sectional study (N = 3,326) in which stereotypical beliefs, attribution beliefs (e.g. perceptions about controllability and responsibility for having an addiction), social distance and expectations about rehabilitation opportunities for individuals with substance use disorders were assessed and compared between stakeholders. Individuals with substance use disorders elicited great social distance across all stakeholders. Stereotypical beliefs were not different between stakeholders, whereas attribution beliefs were more diverse. Considering social distance and expectations about rehabilitation opportunities, the general public was most pessimistic, followed by GPs, mental health and addiction specialists, and clients. Stereotypical and attribution beliefs, as well as age, gender and socially desirable answering, were not associated with social distance across all stakeholders. The general public and GPs expressed more social distance and were more negative in their expectations about rehabilitation opportunities, compared to mental health and addiction specialists and clients. Although stigmatising attitudes were prevalent across all groups, no striking differences were found between stakeholders.


Introducing ward-based epidural pain relief.
Epidural pain relief has advantages for postoperative patients and can be provided safely in surgical wards. Changing practice from providing epidural analgesia in high-dependency areas only to ensuring its safe provision in the wards requires a team approach.


Magnesium sulfate protects the heart against carbon monoxide-induced cardiotoxicity in rats.
Carbon monoxide (CO), a toxic gas produced via incomplete fossil fuel combustion, has several poisonous effects in the heart including induction of necrosis, apoptosis, and electrocardiogram (ECG) changes. Magnesium sulfate (MS) is a drug with cardioprotective effects especially when used after ischemia/reperfusion. In the current study, we aimed to evaluate MS cardioprotective effects following CO poisoning. Animals were exposed to CO 3000 ppm for 1 h and immediately after the exposure period and on the next 4 days (a total of 5 consecutive doses given on a daily basis), MS (75, 150 and 300 mg/kg) was injected intraperitoneally (i.p.) and ECG was recorded focusing on ST-segment, T-wave, and Q-pathologic wave changes. On day 5, animals were sacrificed and their heart was excised for determination of BAX, BCL2 and Akt expression level using western blot analysis and necrosis investigations. The results showed that MS significantly decreased necrosis and BAX/BCL2 ratio (P < 0.001) while pro-survival protein Akt was significantly increased (P < 0.001). Moreover, CO-induced ST-segment depression, T-wave inversion, and atrioventricular block (AV-block) were decreased following treatment with MS. In conclusion, our results showed that MS could decrease cardiac deleterious effects of CO poisoning including necrosis and apoptosis while increased the expression of Akt, as a cell survival protein.


Transition metal-catalyzed three-component coupling of allenes and the related allylation reactions.
The feature article surveys the transition metal-catalyzed three-component coupling of allenes and the related allylation reactions. Most of the reactions shown in the article mechanistically proceed via oxidative addition of organic electrophiles to metals, followed by carbometallation of allene and then transmetalation by main group metals or reagents and organometallic reagents. These reactions provide an efficient route for the synthesis of various substituted allyl and vinyl metal reagents and complex organic molecules in highly regio-, stereo- and chemoselective manner in one pot. The metal reagents or pi-allyl-metal intermediates obtained from the reaction are utilized for the allylation of aldehydes, ketones and imines, producing various homoallylic alcohols and amines in a highly regio- and stereoselective manner.


A monoclonal DNA-binding autoantibody causes a deterioration in renal function in MRL mice with lupus disease.
Two DNA-binding monoclonal antibodies (MoAb) derived from lupus mice were examined for their effects on kidney function. Antibody IV-228, reactive with single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) significantly altered kidney function in some MRL/Mp-lpr/lpr (MRL/lpr) mice with lupus glomerulonephritis. Antibody II-410, preferentially reactive with dsDNA, did not modify kidney function in MRL/lpr mice. Neither antibody affected normal healthy MRL/Mp- +/+ (MRL/n) mice. Not all MRL/lpr mice were equally affected by IV-228 and in some animals with clinical disease it was without effect even when high circulating antibody levels were maintained by five sequential daily injections. Its affects upon kidney function appeared to be related to its ability to localize in vivo in glomeruli. It is assumed that epitopes on trapped immune complexes are immunologically available to circulating antibodies, and in those animals where injected antibody is not captured this is because the antigen epitope is either absent or is masked by the animals' own auto-antibodies. We conclude that antibodies which bind to ssDNA contribute to lupus nephritis; that individual mice make DNA-binding antibodies of different fine specificity; and that kidney disease is not always due to the same balance of antibodies in members of a genetically homogeneous stock.


Electronic Health Record Usage Patterns Across Surgical Subspecialties.
To utilize metrics from physician action logs to analyze surgeon clinical volume, electronic health record (EHR) efficiency, EHR proficiency, and workload outside scheduled time as impacted by physician characteristics such as years of experience, gender, subspecialty, academic title, and administrative title. We selected 30 metrics from Epic Signal, an analytic tool in Epic that extracts metrics related to clinician documentation. Metrics measuring appointments, messages, and scheduled hours per day were used as a correlate for volume. EHR efficiency and proficiency were measured by scores built into Epic Signal. Metrics measuring time spent in the EHR outside working hours were used as a correlate for documentation burden. We analyzed these metrics among surgeons at our institution across four months and correlated them with physician characteristics. Analysis of 133 surgeons showed that, when stratified by gender, female surgeons had significantly higher EHR metrics for time per day, time per appointment, and documentation burden, and significantly lower EHR metrics for efficiency when compared to male surgeons. When stratified by experience, surgeons with 0-5 years of experience had significantly lower EHR metrics for volume, time per day, efficiency, and proficiency when compared to surgeons with 6-10 and >10 years of experience. On multivariate analysis, having over 10 years of experience was an independent predictor of more appointments per day, greater proficiency, and spending less time per completed message. Female gender was an independent predictor of spending more time in notes per appointment and time spent in the EHR outside of working hours. The burden associated with volume, proficiency, efficiency, and workload outside scheduled time related to EHR use varies by gender and years of experience in our cohort of surgeons. Evaluation of physician action logs could help identify those at higher risk of burnout due to burdensome medical documentation.


Transcriptional profiling of adult neural stem-like cells from the human brain.
There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.


[The study of efficiency and cost of research oriented CT system in Shanghai zone].
The paper is about the study on efficiency and operation cost of 11 research oriented CT systems in Shanghai zone. The study result include the average volume, annual operation cost, cost per scan and break-even-point. It reveals that the research oriented CT system purchase price and operation cost is high. The suggestion is that the hospital should be cautious to select the research oriented CT system with consideration of clinical research demand to avoid unsuitable investment.


Mode of action of xylogalacturonan hydrolase towards xylogalacturonan and xylogalacturonan oligosaccharides.
XGH (xylogalacturonan hydrolase; GH 28) is an enzyme that is capable of degrading XGA (xylogalacturonan), which is a polymer of alpha-D-galacturonic acid, highly substituted with beta-D-xylose. XGA is present in cell walls of various plants and exudates, such as gum tragacanth. XGA oligosaccharides were derived from an XGH digestion of gum tragacanth, then fractionated, and analysed for their sugar composition and structure by matrix-assisted laser-desorption ionization-time-of-flight MS and nanospray MS. Several oligosaccharides from XGA were identified with different galacturonic acid/xylose ratios including five oligosaccharide isomers. Although XGH can act as an endo-enzyme, product-progression profiling showed that the disaccharide GalAXyl was predominantly produced from XGA by XGH, which indicated also an exolytic action. The latter was further supported by degradation studies of purified oligosaccharide GalA4Xyl3. It was shown that XGH acted from the non-reducing end towards the reducing end of this oligosaccharide, and showed the processive character of XGH. The results from this study further show that although XGH prefers to act between two xylosidated GalA units, it tolerates unsubstituted GalA units in its -1 and +1 subsites.


Extracellular acidification induces human neutrophil activation.
In the current work, we evaluated the effect of extracellular acidification on neutrophil physiology. Neutrophils suspended in bicarbonate-buffered RPMI 1640 medium adjusted to acidic pH values (pH 6.5-7.0) underwent: 1) a rapid transient increase in intracellular free calcium concentration levels; 2) an increase in the forward light scattering properties; and 3) the up-regulation of surface expression of CD18. By contrast, extracellular acidosis was unable to induce neither the production of H2O2 nor the release of myeloperoxidase. Acidic extracellular pH also modulated the functional profile of neutrophils in response to conventional agonists such as FMLP, precipiting immune complexes, and opsonized zymosan. It was found that not only calcium mobilization, shape change response, and up-regulation of CD18 expression but also production of H2O2 and release of myeloperoxidase were markedly enhanced in neutrophils stimulated in acidic pH medium. Moreover, extracellular acidosis significantly delayed neutrophil apoptosis and concomitantly extended neutrophil functional lifespan. Extracellular acidification induced an immediate and abrupt fall in the intracellular pH, which persisted over the 240-s analyzed. A similar abrupt drop in the intracellular pH was detected in cells suspended in bicarbonate-supplemented PBS but not in those suspended in bicarbonate-free PBS. A role for intracellular acidification in neutrophil activation is suggested by the fact that only neutrophils suspended in bicarbonate-buffered media (i.e., RPMI 1640 and bicarbonate-supplemented PBS) underwent significant shape changes in response to extracellular acidification. Together, our results support the notion that extracellular acidosis may intensify acute inflammatory responses by inducing neutrophil activation as well as by delaying spontaneous apoptosis and extending neutrophil functional lifespan.


Effect of leptin on insulin resistance of muscle--direct or indirect?
We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring glucose transport. Male Wistar rats were fed rat chow or high-fat diets for 30 days. Before sacrifice, rats fed high-fat diet were subcutaneously injected with leptin (1 mg/kg b.w.) for 3 days. The glucose transport in epitrochlearis and soleus muscles did not differ in the experimental groups under basal conditions, however these values decreased significantly in the rats fed high-fat diet under insulin stimulation (p<0.01). Leptin treatment recovered the decreased glucose transport in epitrochlearis (p<0.05) and soleus muscles (p=0.08). Triglyceride concentrations in soleus muscles were increased significantly in the rats fed high-fat diet as compared to rats fed chow diet (p<0.01), and were decreased significantly by leptin treatment (p<0.01). The glucose transport was measured under basal conditions and after 60 microU/ml of insulin treatment with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to rats fed high-fat diet recovered impaired insulin responsiveness of skeletal muscles and muscle triglyceride concentrations. However, there was no direct stimulatory effect of leptin on insulin sensitivity of skeletal muscles in vitro.


Stanniocalcin-2 May Be a Potentially Valuable Prognostic Marker in Endometrial Cancer: a Preliminary Study.
In the current study, we primarily aimed to investigate stanniocalcin-2 (STC2) protein expression pattern in hysterectomy specimens from patients with endometrioid type endometrial cancer (EC) using immunohistochemistry. Secondly, in order to clarify its prognostic impact, we examined relationships of the expression levels of STC2 with clinicopathologic features and outcome of patients. Histopathology slides of 49 patients were stained with the monoclonal mouse antibody targeting STC2 protein. The expression levels of STC2 were classified based on three-tiered semiquantitative scheme: negative expression, expression level of 0; low-expression, expression level of 1+; and high-expression, expression levels of 2+ and 3+. Recurrence-free survival (RFS) was used as the primary prognostic outcome. Immunohistochemical analysis revealed that 73.5% of tissue samples exhibited positive staining with STC2. The intensity of staining with STC2 was weak in 40.8%, moderate in 22.4%, and strong in 10.2%. Thirty-eight percent of samples showed negative expression; 18.4%, low-expression (1+); and 42.8%, high-expression (2 to 3+). High-expression of STC2 was significantly associated with grade 2-3 tumors (p = 0.026) and disease recurrence (p = 0.013). Multivariate analysis revealed that both the tumor grade and STC2 were independent predictors of disease recurrence. Kaplan-Meier analyses confirmed that patients with high-expression of STC2 had a significantly poorer RFS than those with negative or low STC2 expression (p = 0.037); although overall survival did not differ with respect to expression levels of STC2 (p = 0.148). In conclusion, high-expression of STC2 is a negative prognostic factor, associated with increased risk of recurrence in endometrioid EC.


Synthesis of 8-oxo-7,8-dihydro-2'-deoxyguanosine from 2'-deoxyguanosine using Cu(II)/H2O2/ascorbate: A new strategy for an improved yield.
The free nucleoside 2'-deoxyguanosine (dGuo) is the most susceptible to oxidation by reactive oxygen species (ROS) compared to the other free nucleosides, and its oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) has been used as a biomarker to quantify oxidative stress damage. We investigated different reactions using Fe(2+) or Cu(2+) and H2O2 in order to identify the reaction with the best yield. HPLC coupled with a UV detector and micrOTOF mass spectrometry were used to detect and confirm the identity of 8-oxodGuo. The optimized reaction synthesized 8-oxodGuo with a yield of 72.0%, much higher than that previously described in the literature. Our improved method for 8-oxodGuo synthesis could be extremely useful for assays that require the synthesis of internal standards labeled with stable isotopes.


Is communication a skill? Communication behaviors and being in relation.
Patient-physician communication has been conceptualized as both a skill and as a way of mindful "being in relation" to the other. Summarizing research and theoretical analyses, the two approaches are differentiated. The skill-focused approach to communicative competence relies heavily on observed behaviors; the mindful being-in-relation approach emphasizes the perceived effects of the relationship on the participants. The distinctions between these two approaches are important to teaching and research. Teaching can, and should, focus on both changing behaviors and on the personal development of mindfulness in the learner. Research methods should routinely include both observer and participant responses. Reconciling these two views supports the thesis that good communication is both a skill and a way of being, that it is both innate and teachable, and that it must be cultivated by integrated methods of teaching and research.


Nuclear import of prototype foamy virus transactivator Bel1 is mediated by KPNA1, KPNA6 and KPNA7.
Bel1, a transactivator of the prototype foamy virus (PFV), plays pivotal roles in the replication of PFV. Previous studies have demonstrated that Bel1 bears a nuclear localization signal (NLS); however, its amino acid sequence remains unclear and the corresponding adaptor importins have not yet been identified. In this study, we inserted various fragments of Bel1 into an EGFP-GST fusion protein and investigated their subcellular localization by fluorescence microscopy. We found that the 215PRQKRPR221 fragment, which accords with the consensus sequence K(K/R)X(K/R) of the monopartite NLS, directed the nuclear translocation of Bel1. Point mutation experiments revealed that K218, R219 and R221 were essential for the nuclear localization of Bel1. The results of GST pull-down assay revealed that the Bel1 peptide 215-221, which bears the NLS, interacted with the nucleocytoplasmic transport receptors, karyopherin alpha 1 (importin alpha 5) (KPNA1), karyopherin alpha 6 (importin alpha 7) (KPNA6) and karyopherin alpha 7 (importin alpha 8) (KPNA7). Finally, in vitro nuclear import assays demonstrated that KPNA1, KPNA6 or KPNA7, along with other necessary nuclear factors, caused Bel1 to localize to the nucleus. Thus, the findings of our study indicate that KPNA1, KPNA6 and KPNA7 are involved in Bel1 nuclear distribution.


Electronic, vibrational, and torsional couplings in N-methylpyrrole: Ground, first excited, and cation states.
The electronic spectrum associated with the S1 ← S0 (Ã1A2←X̃1A1) one-photon transition of jet-cooled N-methylpyrrole is investigated using laser-induced fluorescence (LIF) and (1 + 1) resonance-enhanced multiphoton ionization (REMPI) spectroscopy; in addition, the (2 + 2) REMPI spectrum is considered. Assignment of the observed bands is achieved using a combination of dispersed fluorescence (DF), two-dimensional LIF (2D-LIF), zero-electron-kinetic energy (ZEKE) spectroscopy, and quantum chemical calculations. The spectroscopic studies project the levels of the S1 state onto those of either the S0 state, in DF and 2D-LIF spectroscopy, or the ground state cation (D0 +) state, in ZEKE spectroscopy. The assignments of the spectra provide information on the vibrational, vibration-torsion (vibtor), and torsional levels in those states and those of the S1 levels. The spectra are indicative of vibronic (including torsional) interactions between the S1 state and other excited electronic states, deduced both in terms of the vibrational activity observed and shifts from expected vibrational wavenumbers in the S1 state, attributed to the resulting altered shape of the S1 surface. Many of the ZEKE spectra are consistent with the largely Rydberg nature of the S1 state near the Franck-Condon region; however, there is also some activity that is less straightforward to explain. Comments are made regarding the photodynamics of the S1 state.


Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability.
The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs). Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25). PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests. Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.


Communication with colleagues: frequency of collaboration regarding physical health of consumers with mental illness.
To identify how frequently nurses in mental health services communicate about physical health of consumers with other healthcare professionals, and whether such collaboration is associated with physical care actions with consumers. An online national Australian survey of nurses in mental health services. Nurses discuss physical health frequently with general practitioners, psychiatrists, and case managers, and less frequently with occupational therapists, social workers, and nurse practitioners. Interprofessional attention was positively associated with direct physical health care such as clinical screening and health education. Interprofessional communication may support nurses in direct physical healthcare actions with consumers. Increasing collaborations with nurse practitioners, social workers, and occupational therapists need to be explored as part of clinical teamwork development.


[Bone metabolism, renal function and immune structure in prostate cancer. Our experience].
Relation studies between bone and immune system converge in recent years in osteoimmunology chapter. It has been suggested that prostate cancer cells may alter bone homeostasis, renal function and the immune system. The aim of this paper is to evaluate bone metabolism, renal function and immune process in prostate cancer patients versus control. Patients with prostate malignancy and bone metastases showed a condition of hypocalcemia and hypophosphatemia associated with increased bone anabolism and lymphopenia, suggesting a possible correlation between bone metabolism and immune context in prostate cancer.


The evolution of hormonal therapy for prostatic carcinoma.
It is well recognized that testosterone has a number of untoward effects on prostatic carcinoma and that castration is associated with significant tumor shrinkage and resolution of symptoms of advanced prostatic carcinoma. Approaches to hormonal therapy have evolved significantly over the last several decades. Initially castration was utilized, which provided effective reduction of testicular androgens, but with adverse psychological factors. The next approach was utilization of diethylstilbestrol, but with significant cardiovascular toxicity in higher doses. The development of the luteinizing hormone-releasing hormone agonists provided an improvement in pharmacologic castration; however, they are associated with a transient testosterone surge and the potential for exacerbation of clinical manifestations of advanced prostate carcinoma (the so-called "testosterone flare"). Recently, gonadotropin-releasing hormone (GnRH) antagonists have been investigated. Abarelix is a pure GnRH antagonist that blocks the anterior pituitary receptor, resulting in prompt and significant reduction not only of luteinizing hormone but also follicle-stimulating hormone. This results in castrate levels of testosterone while avoiding the testosterone surge.