Escalating teniposide systemic exposure to increase dose intensity for pediatric cancer patients.
The primary objective for this study was to determine whether controlling pharmacokinetic variability, by designing patient-specific dosage regimens for teniposide using a Bayesian estimation control strategy, would permit an increase in dose intensity without increased toxicity. Twenty patients with relapsed acute lymphocytic leukemia were given teniposide as part of their induction and maintenance therapy. Before beginning reinduction therapy, an intensive pharmacokinetic study was performed based on 12 measured teniposide plasma concentrations. Doses were determined to achieve a targeted systemic exposure defined by an area under the plasma concentration time curve (AUC) beginning at an AUC consistent with that predicted for a patient with average pharmacokinetic parameters receiving the currently accepted maximal-tolerated dose. The targeted systemic exposure was then escalated in increments of 25% in cohorts of at least three patients until unacceptable toxicity occurred. In 36 follow-up studies, when teniposide was administered during maintenance therapy, a Bayesian strategy based on only three or five measured drug concentrations was evaluated for precision and bias for achieving the targeted systemic exposure against the full pharmacokinetic study. Teniposide clearance varied over a fivefold range (3.7 to 21.6 mL/min/m2). With the use of the patient-specific dosage regimens, the intensity of systemic exposure was increased 50% (1,656 mumol.h v 1,060 mumol/L.h) over that previously possible with standard fixed doses, with no increase in acute, nonhematologic toxicity. Teniposide concentrations (n = 265) were well predicted (R2 = .82) with as few as three measured values from the initial study. Targeting systemic exposure is clinically feasible, precise, and allows increased dose intensity for teniposide without increased risk of acute, nonhematologic toxicity, when compared with fixed-dose regimens.


Serum Levels of TNF-, IL-6, and Selenium in Patients with Acute and Chronic Coronary Artery Disease.
Selenium (Se) is part of the glutathione peroxidase enzyme complex (GSH-PX) that plays an important role in antioxidant mechanisms in body, also it has been demonstrated that populations with low Se intake have 2-3 times greater risk of ischemic heart disease. To determine the circulating levels of IL- 6, TNF-alpha, Cu, Zn, and Se in patients with chronic coronary artery disease (CCAD), acute myocardial infarction (AMI), and normal individuals. Patients were divided into two groups: 25 subjects with CCAD and 25 patients with AMI. The control group included 50 normal individuals who did not have any history of ischemic heart disease, and were sex and age matched with the patients. Blood samples were collected during the first hours after the onset of chest pain in AMI group. Serum concentration of Se, Cu, and Zn were determined by atomic absorption spectrometry and TNF-alpha and IL-6 levels were measured using ELISA method. In both groups of patients there was a significant reduction in serum Se levels (82.36 + 11.31 g/L in CCAD, 74.08+11.31g/L in AMI, and 105+32.52g/L in the control group, p=0.03). TNF-alpha titers were increased in AMI patients compared with CCAD and control group. Mean TNF-alpha levels were 37.44 pg/ml in CCAD, 914.32 pg/ml in AMI, and 4.80 pg/ml in the control group (p=0.01). Serum levels of IL-6 in CCAD and AMI patients were 3.28 15.55 pg/ml and 472207.88 pg/ml, respectively, and 1.28 pg/ml in the control group (p=0.001). These findings confirm previous studies and demonstrate that patients suffering from AMI exhibit lower plasma concentrations of Se and higher concentrations of pro-inflammatory cytokines of TNF-alpha and IL-6.


Iodine deficiency disease in the GDR.
In the last decade several epidemiologic surveys were carried out in the GDR. The findings of all studies indicate consistently that the goiter is existing in the whole country increasing from the north to the south. Inhabitants of all ages are involved. The main cause appears to be an iodine deficiency of grade II. In the south of the GDR more than 90% of the groups examined are subjected to it. The introduction of iodinated salt prophylaxis is going on. An Interdisciplinary Iodine Commission has been established to control and coordinate these measures.


Bariatric Surgery for Type 2 Diabetes Mellitus in Patients with BMI <30 kg/m2: A Systematic Review and Meta-Analysis.
The role of bariatric surgery in non-obese patients with type 2 diabetes (T2DM) remains unclear, and its use in clinical practice is controversial. We conducted a systemic review and meta-analysis to investigate the metabolic changes after surgical treatment in diabetic patients with body mass index (BMI) <30 kg/m2. We conducted a comprehensive search in MEDLINE (PubMed), EMBASE and the Cochrane Library of published articles from January 2000 to April 2013 reporting the clinical outcome changes in various metabolic outcomes in diabetic patients with BMI <30 kg/m2. Ten prospective studies including 290 patients were included in the meta-analysis. Bariatric surgery led to an overall 2.79 kg/m2 [95%CI 2.05~3.53, P<0.00001] reduction in BMI, a 1.88%[95%CI 1.32~2.43, P<0.00001] reduction in glycosylated hemoglobin, a 3.70 mmol/L [95%CI, 1.93~5.47, P<0.00001] reduction in fasting blood glucose, a 6.69 mmol/L [95%CI, 2.29~11.08, P=0.003] reduction in postprandial glucose, anda 3.37 [95%CI 0.55~6.18, P=0.02] reduction in homeostasis model assessment of insulin resistance (HOMA-IR). After surgical treatment, 76.2% of the patients were insulin free, and 61.8% patients were off medication. In total, 90(42.4%), 10(37%) and 34(37.2%) patients had post-surgical HbA1c levels of <6%,<6.5% and<7%, respectively. No deaths were observed in the included studies, and the major complication rate was 6.2%. Based on the currently available data, bariatric surgery might improve glycemic control and weight loss in a very limited range with a doubled surgical complication rate in drug-refractory T2DM patients with BMI <30 kg/m2. It remains too premature to suggest bariatric surgery for non-obese T2DM patients.


Psychology of the injured athlete.
The current interest in physical fitness has had a profound effect on all facets of society, especially on the field of sports medicine. Although scientific needs result in rapidly changing technology, patients' psychological needs never change. PACU nurses are still the first line of support for the injured athlete. The authors review the emotional needs and guidelines for care of the patient in the PACU.


The immunobiology of murine interleukin-1 alpha encoded by recombinant vaccinia virus.
Recombinant vaccinia viruses were constructed which encoded murine interleukin-1 alpha (IL-1 alpha) (VV-IL1). One virus also encoded the hemagglutinin (HA) gene of influenza virus (VV-HA-IL1). Mice were infected with these viruses and the effects of co-expressed IL-1 on various immune parameters were assessed. The growth of VV-IL1 in vivo was less than that of the control virus, and this was reflected in the reduced virus-induced cell-mediated immune responses. However, specific antibody responses generated after challenge with vaccinia or influenza viruses were significantly higher when VV-HA-IL1 was used to prime mice, compared to the control virus (VV-HA-TK). This study demonstrates that co-expressed cytokines may be useful for selective alteration of immune reactivity.


Six chloroplast genes (ndhA-F) homologous to human mitochondrial genes encoding components of the respiratory chain NADH dehydrogenase are actively expressed: determination of the splice sites in ndhA and ndhB pre-mRNAs.
Sequences (ndhA-F) homologous to human mitochondrial genes for components of the respiratory chain NADH dehydrogenase have been found in the chloroplast DNA of tobacco. The ndhA, D, E and F sequences corresponding to the mitochondrial URF1, 4, 4L and 5 are located in the small single copy region, the ndhB sequence corresponding to URF2 in the inverted repeat and the ndhC sequence corresponding to URF3 in the large single copy region of the chloroplast DNA. Northern blot hybridization revealed that all six ndh sequences are actively expressed in the chloroplasts. The ndhA and ndhB sequences contain single introns and the splice sites of their pre-mRNAs were determined by reverse transcription analysis. These findings suggest that potential components of an NADH dehydrogenase are synthesized in the chloroplasts.


Delayed onset of fatal basilar thrombotic embolus after whiplash injury.
Whiplash injuries are generally seen after rear-end rather than frontal car collisions. Previous reports have documented death up to 8 days after serious whiplash injury. We report a case of lethal basilar thrombotic embolus that occurred 2 months after the patient's injury in a collision. After whiplash trauma in a car accident, a 50-year-old taxi driver suffered from headache and episodic visual disturbances. Two months after the accident he suddenly lost consciousness and was admitted to the hospital. A CT scan performed at that time was indicative of basilar thrombosis. The patient died 3 days later. The autopsy revealed a thrombosis in the right vertebral artery and a thrombotic embolus in the basilar artery. Microscopically, a lesion of the right vertebral artery was found at the level of the atlantoaxial joint. We conclude that the whiplash injury caused a lesion of the right vertebral artery, leading to repeated transient ischemic attacks and finally to a fatal basilar thrombotic embolus. We suggest that in patients with disturbances of the vertebrobasilar circulation, attention should be paid to occurrence of neck trauma in the preceding 3 months. Further, anticoagulant therapy should particularly be considered in patients who after suffering neck injuries develop signs of transient ischemic attacks with origin from the posterior cerebral circulation.


Group-specific component subtyping in semen and seminal stains by conventional isoelectric focusing.
Group-specific component (GC) subtyping in semen and seminal stains was carried out using isoelectric focusing in carrier ampholyte-generated pH gradients and immunoblotting. In serum samples the anodal bands of GC 1F and of GC 1S disappeared by neuraminidase treatment, but in semen samples these bands remained unchanged after such treatment. The GC 2 type in semen exhibited two bands: the main GC 2 band and another fast band which focused at the position of the cathodic band of GC 1F. These seminal GC bands were unaffected by enzyme digestion. Reliable subtyping was possible in seminal stains stored at 4 degrees C for up to 10 weeks, at room temperature for up to 8 weeks, and at 37 degrees C for up to 5 weeks. The GC subtyping by conventional isoelectric focusing after neuraminidase treatment is simple, economical and useful in medicolegal examination of seminal stains.


Reconstructing asymmetrical reproductive character displacement in a periodical cicada contact zone.
Selection against costly reproductive interactions can lead to reproductive character displacement (RCD). We use information from patterns of displacement and inferences about predisplacement character states to investigate causes of RCD in periodical cicadas. The 13-year periodical cicada Magicicada neotredecim exhibits RCD and strong reproductive isolation in sympatry with a closely related 13-year species, Magicicada tredecim. Displacement is asymmetrical, because no corresponding pattern of character displacement exists within M. tredecim. Results from playback and hybridization experiments strongly suggest that sexual interactions between members of these species were possible at initial contact. Given these patterns, we evaluate potential sources of selection for displacement. One possible source is 'acoustical interference', or mate-location inefficiencies caused by the presence of heterospecifics. Acoustical interference combined with the species-specificity of song pitch and preference appears to predict the observed asymmetrical pattern of RCD in Magicicada. However, acoustical interference does not appear to be a complete explanation for displacement in Magicicada, because our experiments suggest a significant potential for direct sexual interactions between these species before displacement. Another possible source of selection for displacement is hybrid failure. We evaluate the attractiveness of inferred hybrid mating signals, and we examine the viability of hybrid eggs. Neither of these shows strong evidence of hybrid inferiority. We conclude by presenting a model of hybrid failure related to life cycle differences in Magicicada.


A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis.
Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic myelofibrosis refractory to treatment, developing EMH after splenectomy in various organs, exceptionally the skin and the heart. Along with the case, the clinical presentations, treatment options, prognostic significance of EMH and the role of cytogenetics is discussed in the light of the literature.


Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease.
Right ventricular (RV) dysfunction determines prognosis in patients with chronic pulmonary disease. We examined the relative prognostic potential of measures of systolic, diastolic, and global RV function in 87 patients with chronic pulmonary disease. Systolic function was evaluated by measuring RV dimensions, diastolic function by pulsed wave Doppler of the tricuspid flow profile, and global function by the Tei index. After 15.5 months follow-up, 47 patients had died. Univariate analysis demonstrated that both clinical and echocardiographic variables predicted survival. In the multivariate model both RV end-diastolic diameter index and velocity of late diastolic filling were independent predictors of survival. Receiver operator characteristic analysis demonstrated that a composite model combining these 2 measures provided the most powerful prognostic information. Echocardiographic indices of RV function identify patients with pulmonary disease at high risk and provide incremental prognostic information over and above that supplied by clinical data.


ABCC6 is a basolateral plasma membrane protein.
ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation.


Effect of diet on plasma tryptophan and serotonin in trained mares and geldings.
Concentrations of tryptophan (TRP) and serotonin (5-HT) in plasma were measured in 36 moderately trained Dutch warmblood horses after eight weeks on a high fibre (n=18) or high starch (n=18) diet. Samples were taken three hours after feeding, when the horse was at rest, either at 11.00 or 14.00 hours. Plasma 5-HT and pH were significantly higher in horses fed a high fibre diet than those fed a high starch diet (P<0.05 and P<0.01, respectively), and significantly higher levels of TRP were found in mares than geldings (P<0.05). Plasma 5-HT may therefore be a good marker of serotonergic activity.


Seroepidemiology of Varicella zoster in Israel prior to large-scale use of varicella vaccines.
This large-scale study provides up-to-date estimates of Varicella zoster virus (VZV) age-specific seroprevalence and characteristics of VZV transmission in a representative sample of the Israeli population. In 2000-2001, 1,642 sera collected from an agestratified general population sample were tested for VZV antibodies using an indirect IgG ELISA system. The age-weighted VZV overall estimate was 90.2%. Seropositivity increased rapidly with age, from 68.9% at age 4 to 94.4% at age 7 and 96.6% at age 12 years. The highest force of infection was in the 4-5 years age group (0.548 per susceptible year) followed by the 6-9 years age group. Multivariate analysis revealed that VZV seroprevalence estimates were significantly associated with age and place of origin. The highest seroprevalence estimate was found among subjects of Eastern origin. The seroepidemiology of VZV in Israel shows a pattern corresponding to that described for developed European countries. This study indicates that the highest force of infection is in pre-school children. Knowledge of pre-vaccination seroepidemiology is important to evaluate the effect of vaccination programs on the epidemiology of the disease.


Characterization and immunolocalization of an oocyst wall antigen of Cryptosporidium parvum (Protozoa: Apicomplexa).
A monoclonal antibody (OW-IGO) raised against purified excysted oocysts of Cryptosporidium parvum reacted in an immunofluorescence assay with the oocyst wall. The corresponding antigen was localized by immunoelectron microscopy in fibrillous material present in the parasitophorous vacuole of developing macrogametes and in the wall of both single and double layered sporulating oocysts. Gold particles were also detected over electron-lucent vesicles of the macrogametes by immunoelectron microscopy. On Western blotting of C. parvum oocyst extracts, major bands at 250 and 40 kDa and several minor components were recognized by Mab OW-IGO. Almost complete abolition of Western blot reactivity occurred after periodate oxidation of oocyst antigen, suggesting that monoclonal antibody OW-IGO reacts with a carbohydrate epitope. Taken together, our results suggest that a fibrillous glycoproteinic material is released in the parasitophorous vacuole from electron-lucent vesicles during gametogenesis, and later condensed in the oocyst wall.


Pro-con debate: Inhaled corticosteroids should not be prescribed in primary care to children under two years of age - the case for.
Inhaled corticosteroids (ICS) are effective treatment for older children and adults with asthma. Pathological studies have established that eosinophilic inflammation is important especially in mild to moderate asthma, thus providing a rationale for ICS treatment. However, we have wrongly concluded in the past that early and aggressive treatment of asthma is needed to prevent irreversible scarring and airflow obstruction. We have increasing evidence from all age groups that there are non-eosinophilic asthma phenotypes, that remodelling is independent of inflammation, and that steroids do not prevent children developing progressive airflow obstruction. Asthma treatments that are valuable in adults may not be effective in children, and safe prescribing requires paediatric clinical trials. In young preschool children, the evidence for any eosinophilic airway inflammation is scant, the symptomatic benefit of inhaled steroids is meagre, and there is clear evidence that ICS do not modify the natural history. There is also the potential for steroids to interfere with the developing lung. Thus, we believe that ICS should not be prescribed in primary care for children under two years of age, and that if these children are thought to need more than intermittent therapy with beta-agonists or possibly leukotriene antagonists, specialist referral is mandatory.


Spectrophotometric determination of leukocytes in blood.
The determination of leukocyte concentration in human blood depending on the detection of oxidized o-dianisidine in acidic solution is studied. The oxidation of o-dianisidine was carried out by peroxidase enzymes found in leukocytes. The reaction was stopped by the addition of 4N H(2)SO(4) to the solution, and a very stable, colored o-dianisidine derivative was obtained. The calibration graph was plotted with the recorded absorbance values at 400 nm assigned to the y-axis, and leukocyte counts in 1-mL blood samples to the x-axis. The equation of the calibration graph was y=0.0025 x +0.0904, with a correlation coefficient of R=0.994. The coefficient of variation and P-value of the method were 4.00% and 0.05%, respectively.


Coexistence of T-Large Granular Lymphocyte Leukemia and Peripheral T Cell Lymphoma-NOS with Indolent Behavior.
T-cell lymphomas and leukemias are highly heterogeneous groups of rare disorders. We report a case of a 68-year-old man patient who developed two different T-cell neoplasms (Large Granular Lymphocyte Leukemia [LGLL] in 2018 and Peripheral T-cell non-Hodgkin lymphoma not otherwise specified [PTCL-NOS] in 2019) with a previous diagnosis of B-cell marginal zone lymphoma in 2010, treated with two lines of chemo-immunotherapy. The coexistence of these different T-cell neoplasms is rarely reported in the literature. Moreover, it is usually described as an LGLL transformation into PTCL-NOS; differently from these examples, herein, the simultaneous conditions appear to be driven by different T-cell clones. Furthermore, the PTCL-NOS had quite unusual behavior, with good disease control without intensive treatment. Because of these features, it could belong to a subgroup of indolent PTCL-NOS, not yet described in the WHO classification of T-cell neoplasms, which could benefit from less aggressive treatment.


Quantitative determination of a novel enantiomeric tropane analog, (-)-satropane, in biological fluids using liquid chromatography/tandem mass spectrometry.
A sensitive, accurate and precise liquid chromatography-tandem mass spectrometry method was developed for the determination of (-)-satropane (3alpha-paramethyl-benzenesulfonyloxy-6beta-acetoxy-tropane) in rabbit aqueous humor. Since (-)-satropane may be absorbed from the aqueous humour with resultant systemic side effects, the LC-MS/MS method was also evaluated for its applicability in analyzing plasma samples containing this compound. (-)-Satropane and phentolamine (the internal standard, represented as IS) were detected by multiple reaction monitoring using the transitions m/z 354-182 and 282-212, respectively. The calibration curve was linear over the ranges 2-500 and 5-1000 ng/mL, and the values of the lower limit of quantification were 2 and 5 ng/mL for the microdialysis dialysate and rat plasma samples, respectively. The intra-day and inter-day precision and accuracy were better than 8.6 and 6.00%, respectively, in both matrices investigated. The absolute recovery of the plasma samples was more than 76.30%. The average matrix effects of (-)-satropane were 91.72 and 83.05% in the microdialysis dialysate and plasma samples, respectively. The validated method was successfully applied to analyze (-)-satropane in microdialysis dialysate and rat plasma samples, and this assay has been used to quantify (-)-satropane in the pharmacokinetic and toxicokinetic studies in our laboratory.


Complex DNA nanostructures from oligonucleotide ensembles.
The first synthetic DNA nanostructures were created by self-assembly of a small number of oligonucleotides. Introduction of the DNA origami method provided a new paradigm for designing and creating two- and three-dimensional DNA nanostructures by folding a large single-stranded DNA and 'stapling' it together with a library of oligonucleotides. Despite its power and wide-ranging implementation, the DNA origami technique suffers from some limitations. Foremost among these is the limited number of useful single-stranded scaffolds of biological origin. This report describes a new approach to creating large DNA nanostructures exclusively from synthetic oligonucleotides. The essence of this approach is to replace the single-stranded scaffold in DNA origami with a library of oligonucleotides termed "scaples" (scaffold staples). Scaples eliminate the need for scaffolds of biological origin and create new opportunities for producing larger and more diverse DNA nanostructures as well as simultaneous assembly of distinct structures in a "single-pot" reaction.


Elevated D-Dimer Combined with Persistent Acupuncture-like Chest Pain in An Elderly Patient Misdiagnosed as Pulmonary Embolism Finally Proved as Lung Hamartoma with Secondary Lung Infection by Bronchoscopy Biopsy: a Case Report and Literature Review.
Pulmonary hamartoma is one of the most common benign tumors of the lung, the symptoms are often atypical, so its diagnosis is not so easy. We presented an elderly man with elevated D-dimer combined persistent acupuncture-like chest pain misdiagnosed as pulmonary embolism finally proved as lung hamartoma with secondary lung infection by bronchoscopy biopsy. Appropriate laboratory tests were carried out. The chest computed tomography (CT) scan and bronchoscopy were performed for diagnosis. Laboratory tests showed D-dimer was 2,615.88 ng/mL, the chest CT scan showed the right lung portal occupying lesions accompanied by obstructive changes in the middle of the right lung and mediastinal lymphade-nopathy with partial calcification. Bronchoscopy showed the new spherical neoplasm in the middle of the right lung completely blocked the opening of the bronchus, the surface of the neoplasm was smooth and blood vessels were abundant, pathological result was lung hamartoma. Elevated D-dimer is not a specific index of pulmonary embolism. When a patient's D-dimer rise combined with severe chest pain, the physician should be wary of pulmonary embolism, myocardial infarction, aortic dissection, and other emergencies, and should also take into account serious infections, tumors, and other diseases. Diagnosis needs further related examination. Chest CT scan has guidance function, and when the chest CT scan suggests the occupying lesion, the pathology examination is the key to identify the benign tumor.


Molecular and functional characterization of allogantigen-specific anergic T cells suitable for cell therapy.
CD4(+) regulatory T cells are a specialized subset of T cells that actively control immune responses. Several experimental protocols have been used to expand natural regulatory T cells and to generate adaptive type 1 regulatory T cells for regulatory T-cell-based therapies. The ability of exogenous recombinant human interleukin-10 to induce alloantigen-specific anergy in T cells was investigated and compared to that of interleukin-10 derived from tolerogenic dendritic cells, in mixed lymphocyte cultures. A detailed characterization of the effector functions of the resulting anergized T cells is reported. Interleukin-10, whether exogenous or derived from tolerogenic dendritic cells, induces a population of alloantigen-specific T cells (interleukin-10-anergized T cells) containing type 1 regulatory T cells, which are anergic and actively suppress alloantigen-specific effector T cells present within the mixed population. Interleukin-10-induced anergy is transforming growth factor-β independent, and is associated with a decreased frequency of alloantigen-specific cytotoxic T lymphocyte precursors, but interleukin-10-anergized T cells are still responsive to third-party, bacterial, and viral antigens. Tolerogenic dendritic cells are more powerful than exogenous interleukin-10 in generating type 1 regulatory T-cell precursors, and are also effective in the context of HLA-matched donors. Based on these studies, we have developed an efficient and reproducible in vitro method to generate antigen-specific type 1 regulatory T-cell precursors starting from total peripheral blood cells with minimal cell manipulation and suitable for generating type 1 regulatory T cells for regulatory T-cell-based therapies.


Use of quantitative brain water imaging as concentration reference for J-edited MR spectroscopy of GABA.
To compare two different methods of obtaining the water reference for determination of quantitative water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA). Water-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of brain water content. J-difference edited MR spectroscopy data were combined with quantitative brain water measures, which provided individual water density references and T1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific water content and relaxation values. Occipital GABA concentration values obtained from individual water and T1 maps were 1.64±0.35mM in controls, and significantly higher (P<0.01) than in mHE (1.15±0.28mM) and HE 1 patients (1.18±0.09mM). Results from the tissue-dependent approach (1.58±0.30mM (controls), 1.10±0.27mM (mHE) and 1.12±0.12mM (HE 1)) were slightly lower (P<0.05 in each group). Water-scaled in vivo GABA estimates can be obtained with individual water density and T1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial brain water content or relaxation changes.


Comparative analysis of the fecal microbiota from different species of domesticated and wild suids.
Most of the microorganisms living in a symbiotic relationship in different animal body sites (microbiota) reside in the gastrointestinal tract (GIT). Several studies have shown that the microbiota is involved in host susceptibilities to pathogens. The fecal microbiota of domestic and wild suids was analyzed. Bacterial communities were determined from feces obtained from domestic pigs (Sus scrofa) raised under different conditions: specific-pathogen-free (SPF) pigs and domestic pigs from the same bred, and indigenous domestic pigs from a backyard farm in Kenya. Secondly, the fecal microbiota composition of the African swine fever (ASF) resistant warthogs (Phacochoerus africanus) from Africa and a European zoo was determined. African swine fever (ASF) is a devastating disease for domestic pigs. African animals showed the highest microbial diversity while the SPF pigs the lowest. Analysis of the core microbiota from warthogs (resistant to ASF) and pigs (susceptible to ASF) showed 45 shared OTUs, while 6 OTUs were exclusively present in resistant animals. These six OTUs were members of the Moraxellaceae family, Pseudomonadales order and Paludibacter, Anaeroplasma, Petrimonas, and Moraxella genera. Further characterization of these microbial communities should be performed to determine the potential involvement in ASF resistance.


Thyroid stimulating hormone suppression time on cardiac function of patients with differentiated thyroid carcinoma.
This study was to investigate the influence of thyroid stimulating hormone (TSH) suppression time on the cardiac function of differentiated thyroid carcinoma (DTC) patients. 105 DTC patients were divided into strict TSH suppression group (model group, TSH ≤ 0.1 mU/L) and general TSH suppression group (control group, TSH > 0.1 mU/L). According to the suppression time, these two groups were respectively divided into three groups: group within half a year, group between half a year and a year and group more than a year. Gated myocardial perfusion imaging was applied to observe differences of left ventricle (LV) myocardial perfusion, LV diastolic and systolic function and LV systolic synchrony in every group. The left ventricular diastolic function, systolic synchrony and myocardial perfusion level of model group decreased with prolonged suppression time. The values of left ventricular EF, PFR and BPM in patients less than half a year were higher than those in 6 months to 1 year for control group. Thyroid stimulating hormone suppression can influence the cardiac function of patients and with the prolongation of suppression time, regardless of the level of TSH suppression, the possibility of cardiac function depression in patients will increase. TSH may lower the risk of cardiovascular disease in high-risk patients than those in TSH patients with moderate or low risk. The drugs improving cardiac function should be used cooperatively in different suppression period to decrease the occurrence rate of cardiac adverse reactions.


Novel immunosuppressive strategies for composite tissue allografts.
Vascularized composite tissue allografts (CTAs) provide excellent restorative options for patients with limb loss and other deformities. Acute rejection remains common with CTA and immunosuppression is used in an attempt to prevent rejection. This has created ethical debates regarding the use of intensive immunosuppression for a nonlife-saving procedure. This highlights the need for newer immunosuppressive strategies for CTA, which are described in this review. Recent studies have looked into immunomodulation and tolerance to decrease toxicity of immunosuppression. Both strategies have had some success but have their own limitations. Although immunomodulation and decrease in immunosuppression decreases toxicity, it has been associated with higher rates of rejection. Induction of tolerance has achieved some initial success, but the initial conditioning regimens are associated with significant morbidity. Although recent advancements have been made in the immunosuppressive strategies in CTA, the ideal immunosuppression strategy with low toxicity and infection risk but with the ability to prevent acute and chronic rejection is yet to be discovered.


Pyrene-terminated phenylenethynylene rigid linkers anchored to metal oxide nanoparticles.
Phenylenethynylene (PE) rigid linkers (para and meta) were used to anchor pyrene to the surface of TiO2 (anatase) and ZrO2 nanoparticle thin films through the two COOH groups of an isophthalic acid (Ipa) unit. Four chromophore-linker models were studied in solution and bound. Two are novel meta-pyrene-PE linker systems: dimethyl 5-(3-(1-pyrenylethynyl)phenylethynyl)-isophthalate, carrying one pyrene, and dimethyl 5-(bis-3,5-(1-pyrenylethynyl)phenylethynyl)-isophthalate, carrying two. These were compared with para rigid-rods dimethyl 5-(1-pyrenylethynyl)isophthalate and dimethyl 5-(4-(1-pyrenylethynyl)phenylethynyl)-isophthalate, each carrying one pyrene but varying in length. The length of the PE linkers and the para or meta substitution influence the photophysical properties of the compounds. The extinction coefficient increased, and the long wavelength absorbance of the pyrene chromophore was shifted to the red with increasing conjugation. Compared to unsubstituted pyrene, the pyrene-linker systems were characterized by short fluorescence lifetimes (tau approximately 2 ns in tetrahydrofuran solutions), but quantum yields were close to unity. ZINDO/S CI calculations attribute this effect to a switching in the order of the two lowest-lying singlet states of pyrene. High surface coverages, approximately 10(-8) mol/cm2, and carboxylate binding modes on nanostructured TiO2 films were obtained in all cases. The appearance of a pyrene excimer emission on ZrO2, an insulator, indicates that the pyrene-linker system is closely packed (Py-Py < 4 A) on the surface. The fluorescence emission on TiO2 was completely quenched, consistent with quantitative and rapid electron injection into the semiconductor indicating that the pyrene excimer acts as a sensitizer. Photoelectrochemical studies in regenerative solar cells with I3-/I- as the redox mediator indicated near-quantitative conversion of absorbed photons into an electrical current.


Salmonella Surveillance by the Food and Drug Administration: A Review 1974-1985.
Since 1974, the Food and Drug Administration's (FDA's) Minneapolis Center for Microbiological Investigations has been responsible for confirmation and serotyping of Salmonella cultures originally isolated by FDA field laboratories. The data have subsequently been entered into FDA's Microbial Information System for storage and analysis. A summary of the data accumulated from 1974 to 1985 is provided as an overview of FDA's Salmonella surveillance activities for the period.


[Specifics of reproductive disorders and hormonal sensitivity of tumors in patients with "hormone-related neoplastic syndrome"].
Blood-serum levels of gonadotrophins and estradiol were assayed alongside with those of estradiol and progesterone receptors in the tissue of tumors of the breast, uterus, ovary and large bowel to establish general regularities of reproductive homeostasis in patients. The study was based on the assumption that risk of secondary tumor development is considerable in a patient who bears one of said malignancies. The effect of estrogen hormones was shown to be one of general causes of tumorigenesis. This is corroborated by enhanced hyperestrinism observed in cases of carcinoma of the corpus uteri as well as by certain data pointing to a reliable correlation between estrogen-stimulated synthesis of progesterone receptors and prognosis in patients with tumors of the breast, uterus and ovary. No estrogen dependence, however, was registered in patients with tumors of the bowel. Pathogenetic features shared by tumors of the large bowel and those of the reproductive system should probably be accounted for by disorders in metabolism.


Kinetic proofreading of gene activation by chromatin remodeling.
Gene activation in eukaryotes involves the concerted action of histone tail modifiers, chromatin remodelers, and transcription factors, whose precise coordination is currently unknown. We demonstrate that the experimentally observed interactions of the molecules are in accord with a kinetic proofreading scheme. Our finding could provide a basis for the development of quantitative models for gene regulation in eukaryotes based on the combinatorical interactions of chromatin modifiers.


Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease.
Mild elevation of plasma homocysteine is an independent risk factor for vascular disease. We studied the role of 5-methyltetrahydrofolate (5-MTHF), the folate form directly involved in homocysteine metabolism, in contrast to previous studies, which used total folate measurements, in 70 coronary artery disease (CAD) patients and control subjects. We also measured S-adenosylmethionine (SAM), which controls the activity of critical enzymes of homocysteine metabolism. Fasting plasma total homocysteine was elevated (> 12.4 mumol/L for women, > 13.3 mumol/L for men) in 17% of patients, in accordance with earlier studies. These patients showed lower 5-MTHF (12.4 +/- 1.0 mumol/L, mean +/- SD) than control subjects (24.2 +/- 15.0, P < .001), and there was a clear correlation (multiple linear regression analysis: P = .002) of this relevant form of folate with homocysteine. However, 37% of the normohomocysteinemic patients also revealed similarly low 5-MTHF levels, suggesting that a decrease of 5-MTHF does not necessarily cause hyperhomocysteinemia. SAM was significantly decreased in patients (1.4 +/- 0.4 mumol/L) compared with control subjects (1.8 +/- 0.3, P < .001) but was not correlated to homocysteine or 5-MTHF. The correlation between homocysteine and 5-MTHF that was found in CAD patients but not in control subjects confirms the direct relationship between these compounds in vivo. The new finding of low SAM in patients demands further studies, since it might indicate that low levels pose risk and that SAM might be a protective factor against the development of CAD.


The More Who Die, the Less We Care: Evidence from Natural Language Analysis of Online News Articles and Social Media Posts.
Considerable amount of laboratory and survey-based research finds that people show disproportional compassionate and affective response to the scope of human mortality risk. According to research on "psychic numbing," it is often the case that the more who die, the less we care. In the present article, we examine the extent of this phenomenon in verbal behavior, using large corpora of natural language to quantify the affective reactions to loss of life. We analyze valence, arousal, and specific emotional content of over 100,000 mentions of death in news articles and social media posts, and find that language shows an increase in valence (i.e., decreased negative affect) and a decrease in arousal when describing mortality of larger numbers of people. These patterns are most clearly reflected in specific emotions of joy and (in a reverse fashion) of fear and anger. Our results showcase a novel methodology for studying affective decision making, and highlight the robustness and real-world relevance of psychic numbing. They also offer new insights regarding the psychological underpinnings of psychic numbing, as well as possible interventions for reducing psychic numbing and overcoming social and psychological barriers to action in the face of the world's most serious threats.


The role of the allantoin in promoting fracture healing in osteoclast-deficient zebrafish.
Fracture healing is a rigorous and orderly process with multiple steps that are mediated by multiple cells. During this process, osteoclast-mediated bone remodeling plays a critical role, and its abnormal activity leads not only to fracture susceptibility but also to impaired fracture healing. However, few studies have focused on impaired healing caused by osteoclast defects, and clinical drugs for this type of impaired fracture healing are still lacking. The cell types and regulatory pathways in the zebrafish skeletal system are highly similar to those of mammals, making the zebrafish skeletal system being widely used for skeletal-related studies. To study the process of fracture healing disorders caused by osteoclast defects and discover potential therapeutic drugs, we established an in vivo osteoclast-deficient fracture model using a previously generated fms gene mutant zebrafish (fmsj4e1). The results showed that reduced functional osteoclasts could affect fracture repair in the early stages of fracture. Then we applied an in vitro scale culture system to screen for osteoclast-activating drugs. We found the small molecule compound allantoin (ALL) being able to activate osteoclasts. Subsequently, we verified the activation role of ALL on osteoclasts and the promotion of fracture repair in an in vivo fmsj4e1 fracture defect model. Finally, by examining the osteoclastogenesis and maturation process, we found that ALL may promote osteoclast maturation by regulating RANKL/OPG, thus promoting fmsj4e1 fracture healing. Our study provides a potential new approach for the future improvement of fracture healing disorders caused by osteoclast defects.


Short-term hemodynamic changes in episcleral arteriovenous anastomoses correlate with venous pressure and IOP changes in the albino rabbit.
In the present study we have determined the effects of acute diameter changes in the recently discovered episcleral arteriovenous anastomoses (AVA) on episcleral venous pressure and intraocular pressure (IOP) in the rabbit eye. The pressure was measured in episcleral arterioles, AVA and veins (vascular pressure) with a pressure chamber mounted on the tip of a microendoscope. After constriction of the AVA following topical administration (100 micrograms) of epinephrine we observed a decrease in the episcleral vascular pressure as well as in the IOP. Acute widening of the AVA after topical administration of 5mg nitroprusside led to a significant increase in the pressure of arterioles, AVA, veins and IOP which lasted several min. After 0.5mg topical nitroprusside the blood flow in the AVA increased. No significant effects were seen in the intravascular pressures; the IOP had a tendency to decrease. Experimental lowering of the IOP to 10mmHg caused an increase of vascular diameters and of blood flow in the AVA. It is assumed that-at least in drastic hemodynamic disorders-the degree of the AVA-perfusion might influence aqueous humor outflow and IOP due to changes of the episcleral venous pressure.


Thalamic processing of vibrissal information in the rat. I. Afferent input to the medial ventral posterior and posterior nuclei.
Retrograde tracing with true blue (TB) and diamidino yellow (DY) and anterograde tracing with either wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L) were employed to investigate the projections from trigeminal nucleus principalis (PrV) and trigeminal subnucleus interpolaris (SpI) to their targets in the medial ventral posterior (VPM) and posterior (POm) nuclei of the thalamus. Many more cells in both PrV and SpI were labeled by tracer injections into VPM than into POm. Only a very small number of double-labeled neurons were observed in either PrV or SpI. However, a significantly higher percentage of SpI cells projected to POm or to both POm and VPM than was the case for PrV. Anterograde tracing with WGA-HRP showed that the projections from both PrV and SpI to VPM were much denser than those from the same nuclei to POm. Small injections of PHA-L into either PrV or SpI produced a focus of fairly dense labeling in VPM and much more diffuse terminal labeling in POm. These anatomical data provide evidence for two separate trigeminothalamic pathways, one originating from PrV and the second originating from SpI. Both of these pathways converge and diverge at the thalamic level. That is, information from the PrV pathway and from the SpI pathway are both provided to VPM in a morphologically restricted fashion and to POm in a morphologically widespread fashion.


Neural control of penile erection.
Filling of the sinusoidal spaces with blood due to smooth muscle relaxation results from parasympathetic neural pathway activation and probably simultaneous inhibition of sympathetic outflow. The final common pathway for proerectile fibers is represented by the cavernous nerves and fibers controlling detumescence and flaccidity originating in the sympathetic chain. The hypogastric nerve could represent an accessory proerectile pathway unmasked by a sacral spinal cord lesion. Nitric oxide, which can be colocalized with VIP and acetylcholine, is the main proerectile neurotransmitter and noradrenaline is considered to be the major antierectile agent. Reflexive erection elicited by recruitment of penile afferents involves both autonomic and somatic efferents. This reflex is mediated at the spinal cord level and modulated by supraspinal influences. Serotonergic pathways originating in the raphe nuclei may mediate inhibitory control on reflexive erections. The hypothalamic medial preoptic area is an important integrating center and dopamine may regulate penile erection at this level. Neuroendocrine regulation may vary depending on the context in which erection occurs, for example, coitus, in response to extrinsic or psychogenic stimuli, and rapid eye movement sleep.


Development of a Bioinformatics Framework for the Detection of Gene Conversion and the Analysis of Combinatorial Diversity in Immunoglobulin Heavy Chains in Four Cattle Breeds.
We have developed a new bioinformatics framework for the analysis of rearranged bovine heavy chain immunoglobulin (Ig) variable regions by combining and refining widely used alignment algorithms. This bioinformatics framework allowed us to investigate alignments of heavy chain framework regions (FRHs) and the separate alignments of FRHs and heavy chain complementarity determining regions (CDRHs) to determine their germline origin in the four cattle breeds Aubrac, German Black Pied, German Simmental, and Holstein Friesian. Now it is also possible to specifically analyze Ig heavy chains possessing exceptionally long CDR3Hs. In order to gain more insight into breed specific differences in Ig combinatorial diversity, somatic hypermutations and putative gene conversions of IgG, we compared the dominantly transcribed variable (IGHV), diversity (IGHD), and joining (IGHJ) segments and their recombination in the four cattle breeds. The analysis revealed the use of 15 different IGHV segments, 21 IGHD segments, and two IGHJ segments with significant different transcription levels within the breeds. Furthermore, there are preferred rearrangements within the three groups of CDR3H lengths. In the sequences of group 2 (CDR3H lengths (L) of 11-47 amino acid residues (aa)) a higher number of recombination was observed than in sequences of group 1 (L≤10 aa) and 3 (L≥48 aa). The combinatorial diversity of germline IGHV, IGHD, and IGHJ-segments revealed 162 rearrangements that were significantly different. The few preferably rearranged gene segments within group 3 CDR3H regions may indicate specialized antibodies because this length is unique in cattle. The most important finding of this study, which was enabled by using the bioinformatics framework, is the discovery of strong evidence for gene conversion as a rare event using pseudogenes fulfilling all definitions for this particular diversification mechanism.


Synthesis and Evaluation of 11C-Labeled Triazolones as Probes for Imaging Fatty Acid Synthase Expression by Positron Emission Tomography.
Cancer cells require lipids to fulfill energetic, proliferative, and signaling requirements. Even though these cells can take up exogenous fatty acids, the majority exhibit a dependency on de novo fatty acid synthesis. Fatty acid synthase (FASN) is the rate-limiting enzyme in this process. Expression and activity of FASN is elevated in multiple cancers, where it correlates with disease progression and poor prognosis. These observations have sparked interest in developing methods of detecting FASN expression in vivo. One promising approach is the imaging of radiolabeled molecular probes targeting FASN by positron emission tomography (PET). However, although [11C]acetate uptake by prostate cancer cells correlates with FASN expression, no FASN-specific PET probes currently exist. Our aim was to synthesize and evaluate a series of small molecule triazolones based on GSK2194069, an FASN inhibitor with IC50 = 7.7 ± 4.1 nM, for PET imaging of FASN expression. These triazolones were labeled with carbon-11 in good yield and excellent radiochemical purity, and binding to FASN-positive LNCaP cells was significantly higher than FASN-negative PC3 cells. Despite these promising characteristics, however, these molecules exhibited poor in vivo pharmacokinetics and were predominantly retained in lymph nodes and the hepatobiliary system. Future studies will seek to identify structural modifications that improve tumor targeting while maintaining the excretion profile of these first-generation 11C-methyltriazolones.


Effects of alpha-adrenergic blockade on cardiovascular responses to static exercise in cats.
Static exercise performed by conscious cats elicits increases in heart rate (HR), left ventricular systolic pressure (LVSP), and the maximal rate of left ventricular pressure development [LV(dP/dt)max]. The increased HR is mediated primarily by withdrawal of parasympathetic tone, whereas a beta-adrenergic mechanism is responsible for the LV(dP/dt)max increase. In the present study the cardiovascular responses to static exercise in awake cats was recorded before and after alpha-adrenergic blockade. Pressure transducers were implanted into the left ventricle of cats who had been trained operantly to perform static exercise. Significant increases in LVSP, LV(dP/dt)max and HR occurred in all cats during static exercise before blockade. In contrast, alpha-adrenergic blockade (phentolamine, 2.5 mg/kg iv) abolished the exercise-induced increase in LVSP but did not prevent increases in HR and LV(dP/dt)max. The cats performed fewer exercise bouts per day during alpha-blockade than when unblocked. We conclude that an alpha-adrenergic mechanism mediates the increase in LVSP in response to static exercise in conscious cats.


Life after coronary stent thrombosis.
Coronary stent thrombosis is a catastrophic complication of percutaneous coronary intervention. There is a paucity of long-term data regarding the clinical outcome of patients who have suffered stent thrombosis. We sought to assess the long-term clinical outcome of patients who suffered de novo ST-segment elevation myocardial infarction as well as those who suffered ST-segment elevation myocardial infarction as a result of stent thrombosis. In both patient groups, major cardiac adverse events were studied during a 1-year follow-up period. A total of 1890 consecutive patients who presented with ST-segment elevation myocardial infarction during the period January 2003 to December 2005 were studied: 1843 (97.5%) suffered de novo ST-segment elevation myocardial infarction, and 47 (2.5%) suffered ST-segment elevation myocardial infarction as a consequence of stent thrombosis. The rate of cardiogenic shock was significantly higher in the stent thrombosis group than in the de novo thrombosis group (21.3% vs 4.8%, respectively) (P<0.001). Mortality rates at 30 days (6.4% vs 8.8%) and at 1 year (17.0% vs 14.9%) showed no significant difference between the 2 groups. The repeat revascularization rate was higher among patients with post-stent thrombosis (35.7% vs 9.1%) (P<0.001), as was the major cardiovascular event rate (57.1% vs 31.2%) (P<0.001). The long-term clinical outcome of patients who have suffered stent thrombosis is poor. Additional research is warranted to further improve therapeutic measures associated with stent thrombosis.


Spatially resolved rotation of the broad-line region of a quasar at sub-parsec scale.
The broadening of atomic emission lines by high-velocity motion of gas near accreting supermassive black holes is an observational hallmark of quasars1. Observations of broad emission lines could potentially constrain the mechanism for transporting gas inwards through accretion disks or outwards through winds2. The size of regions for which broad emission lines are observed (broad-line regions) has been estimated by measuring the delay in light travel time between the variable brightness of the accretion disk continuum and the emission lines3-a method known as reverberation mapping. In some models the emission lines arise from a continuous outflow4, whereas in others they arise from orbiting gas clouds5. Directly imaging such regions has not hitherto been possible because of their small angular size (less than 10-4 arcseconds3,6). Here we report a spatial offset (with a spatial resolution of 10-5 arcseconds, or about 0.03 parsecs for a distance of 550 million parsecs) between the red and blue photo-centres of the broad Paschen-α line of the quasar 3C 273 perpendicular to the direction of its radio jet. This spatial offset corresponds to a gradient in the velocity of the gas and thus implies that the gas is orbiting the central supermassive black hole. The data are well fitted by a broad-line-region model of a thick disk of gravitationally bound material orbiting a black hole of 3 × 108 solar masses. We infer a disk radius of 150 light days; a radius of 100-400 light days was found previously using reverberation mapping7-9. The rotation axis of the disk aligns in inclination and position angle with the radio jet. Our results support the methods that are often used to estimate the masses of accreting supermassive black holes and to study their evolution over cosmic time.


Microarrays as a tool to investigate the biology of aging: a retrospective and a look to the future.
The use of microarrays as a tool to investigate fundamental biological questions has become ubiquitous over the past several years. Microarrays are becoming as common as the polymerase chain reaction or any of the other tools in the molecular biologist's armory. Unlike experiments involving other tools, however, the design and analysis of microarray experiments present some unique problems to molecular biologists, problems with which statisticians have long been familiar. In this overview of microarrays and aging-related research, we will review selected highlights of microarray studies that have been carried out to study aging to date, as well as discuss some of the potential problems that routinely arise during these types of experiments, especially in the context of aging.


Duration of action of atracurium when given by infusion to critically ill children.
The aim of the study was to investigate the offset time of atracurium when given by continuous infusion on a paediatric intensive care unit and to look for evidence of tolerance. Over a period of 8 months, 20 mechanically ventilated children had a steady-state infusion of atracurium discontinued to enable the assessment of their level of sedation. The offset time of atracurium was assessed by train-of-four (TOF) stimulation of the ulnar nerve. The initial TOF reading was documented as was the time taken to reach a TOF ratio of 0.9. Thirty-five assessments were carried out. The mean offset time of atracurium was 28.7 min (SEM 1.76 min, range 8-56 min). There was no correlation between the dose of atracurium at discontinuation and the offset time of the infusion. The duration of infusion was negatively correlated with the offset time of atracurium, and this effect was most prominent in children who had received infusions for longer than 48 h. When given by continuous infusion, the offset time of atracurium is very variable between individual patients. Infusions administered for longer than 48 h are associated with a significant reduction in the offset time as a result of increasing tolerance.


Expression of endothelial monocyte-activating polypeptide II in the rat dental follicle and its potential role in tooth eruption.
Endothelial monocyte-activating polypeptide II (EMAP-II) is an inflammatory cytokine with chemotactic activity. Because the dental follicle (DF) recruits mononuclear cells (osteoclast precursors) to promote the osteoclastogenesis needed for tooth eruption, it was the aim of this study to determine if EMAP-II contributes to this recruitment. Using a DNA microarray, EMAP-II was found to be highly expressed in vivo in the DFs of day 1 to day 11 postnatal rats, with its expression elevated on days 1 and 3. Use of a short interfering RNA (siRNA) to knock down EMAP-II expression resulted in a reduction in the expression of colony-stimulating factor-1 (CSF-1) and monocyte chemoattractant protein-1 (MCP-1) in the DF cells. Addition of EMAP-II protein to the DF cells partially restored the expression of CSF-1 and MCP-1. In chemotaxis assays using either conditioned medium of the DF cells with anti-(EMAP-II) immunoglobulin G added or conditioned medium of DF cells with EMAP-II knocked down by siRNA, migration indexes of bone marrow mononuclear cells were significantly reduced. These results suggest that EMAP-II is another chemotactic molecule in the dental follicle involved in the recruitment of mononuclear cells, and that EMAP-II may exert its chemotactic function directly by recruiting mononuclear cells and indirectly by enhancing the expression of other chemotactic molecules (CSF-1 and MCP-1).


The effect of temporal placement on gap detectability.
The detectability of a masked sinusoid increases as its onset approaches the temporal center of a masker. This study was designed to determine whether a similar change in detectability would occur for a silent gap as it was parametrically displaced from the onset of a noise burst. Gap thresholds were obtained for 13 subjects who completed five replications of each condition in 3 to 13 days. Six subjects were inexperienced listeners who ranged in age from 18 to 25 years; seven subjects were highly experienced and ranged in age from 20 to 78 years. The gaps were placed in 150-ms, 6-kHz, low-passed noise bursts presented at an overall level of 75 dB SPL; the bursts were digitally shaped at onset and offset with 10-ms cosine-squared rise-fall envelopes. The gated noise bursts were presented in a continuous, unfiltered, white noise floor attenuated to an overall level of 45 dB SPL. Gap onsets were parametrically delayed from the onset of the noise burst (defined as the first nonzero point on the waveform envelope) by 10, 11, 13, 15, 20, 40, 60, 110, 120, and 130 ms. Results of ANOVAs indicated that the mean gap thresholds were longer when the gaps were proximal to signal onset or offset and shorter when the gaps approached the temporal center of the noise burst. Also, the thresholds of the younger, highly experienced subjects were significantly shorter than those of the younger, inexperienced subjects, especially at placements close to signal onset or offset. The effect of replication (short-term practice) was not significant nor was the interaction between gap placement and replication. Post hoc comparisons indicated that the effect of gap placement resulted from significant decreases in gap detectability when the gap was placed close to stimulus onset and offset.


Transmission of Helicobacter pylori.
The epidemiology of Helicobacter pylori has been the attention of a great deal of study. The age and geographical distribution of infection is rapidly changing with improvements in living conditions, particularly in the childhood period. More than one mode and route of transmission is possible varying with local custom and practices. Infection may be acquired from environmental sources in certain parts of the developing world, but in most circumstances it is probably acquired interpersonally. Interpersonal transmission may be by either fecal-oral or oral-oral routes, depending on circumstances, but the former is likely to be the most important. The life-long chronic active gastritis associated with H pylori may have other consequences for health, such as growth in childhood and coronary heart disease.


The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo.
Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts (hNF), human TGF-β-activated fibroblasts (hAF), and human localized scleroderma-derived fibroblasts (hLSF) after direct CAP treatment, co-cultured with plasma-treated human epidermal keratinocytes (hEK) and with an experimental murine model of scleroderma. In hAF and hLSF, 2 min CAP treatment with the MicroPlaSterβ® plasma torch did not affect pro-fibrotic gene expression of alpha smooth muscle actin, fibroblast activating protein, and collagen type I, however, it promoted re-expression of matrix metalloproteinase 1. Functionally, CAP treatment reduced cell migration and stress fiber formation in hAF and hLSF. The relevance of CAP treatment was confirmed in an in vivo model of bleomycin-induced dermal fibrosis. In this model, CAP-treated mice showed significantly reduced dermal thickness and collagen deposition as well as a decrease in both alpha smooth muscle actin-positive myofibroblasts and CD68-positive macrophages in the affected skin in comparison to untreated fibrotic tissue. In conclusion, this study provides the first evidence for the successful use of CAP for treating LS and may be the basis for clinical trials including patients with LS.


Ictal deafness in drug-resistant MRI-negative epilepsy.
Ictal clinical semiology indicates where the patient's seizure arises from and how it progresses. A patient's description of a focal sensory seizure may support a surgical decision even when MRI and PET abnormalities are absent. Ictal deafness is a focal auditory seizure characterized by suppression of hearing, presumably originating from the auditory cortex in the temporal lobe. However, the precise localization has not been confirmed with surgical cases. We present a case in which the region from where ictal deafness arose was confirmed by intracranial electroencephalography, with successful epilepsy surgery and review other published cases.


Distribution of delta activity across nonrapid eye movement sleep episodes in healthy young men.
The distribution of delta activity across successive nonrapid eye movement (NREM) sleep episodes and its night-to-night stability across three consecutive nights were investigated by studying delta power with spectral analysis in 31 healthy young men. Repeated-measures analysis of variance (ANOVA) with polynomial contrast was applied to grouped data of absolute delta power and three indexes: (1) the rate of delta power per NREM episode to its duration, 2) the standardized rate for the last NREM episode, and 3) the logarithm of the standardized rate. A significant linear decrease across NREM episodes was observed for each variable in each successive night. In addition, using night as a second within-subjects factor, no night effect was observed. Yet, the subsequent analysis of the logarithmic data yielded greater F values in all three nights' data as well as a linear function that accounted for a greater proportion of total variance than the analysis of the nonlogarithmic data. Since a linear decline for the logarithm of a variable implies an exponential distribution for that variable, we conclude that delta activity is distributed exponentially across NREM episodes, and this finding shows a remarkable night-to-night stability.


Transcriptome sequencing and gene expression profiling of Pinus sibirica under different cold stresses.
Cold stress is a major abiotic factor that affects plant growth and geographical distribution. Pinus sibirica is extremely frigostable tree species. To understand the molecular mechanisms of cold tolerance by P. sibirica, physiological responses were analyzed and transcriptome profiling was conducted to the plants treated by cold stress. The physiological data showed that membrane permeability relative conductivity (REC), reactive oxygen species (ROS), malonaldehyde (MDA) content, peroxidase (POD) and catalase (CAT) activity, soluble sugar, soluble protein and proline contents were increased significantly (p < 0.05) in response to cold stress. Transcriptome analysis identified a total of 871, 1397 and 872 differentially expressed genes (DEGs) after cold treatment for 6 h, 24 h and 48 h at -20°C, respectively. The signaling pathway mediated by Ca2+ as a signaling molecule and abscisic acid pathways were the main cold signal transduction pathways in P. sibirica. The APETALA2/Ethylene-Responsive Factor (AP2/ERF) and MYB transcription factor families also play an important role in the transcriptional regulation of P. sibirica. In addition, many genes related to photosynthesis were differentially expressed under cold stress. We also validated the reliability of transcriptome data with quantitative real-time PCR. This study lays the foundation for understanding the molecular mechanisms related to cold responses in P. sibirica.


Direct muscle neurotization after end-to-side neurorrhaphy.
Over the recent years, end-to-side neurorrhaphy has reemerged in the literature for reconstructive nerve surgery. Another technique, in which interest has remained continuous during the last century, is direct nerve implantation into muscle belly, so-called direct muscle neurotization (DMN). In this work, the authors present a new technique to recover muscle innervation through direct nerve implantation into muscle belly, by means of a nerve graft, and sutured with end-to-side neurorrhaphy. They carried out experiments on 20 Wistar rats divided into two groups. In Group 1 (10 rats), on the right side, the peroneal nerve was sutured to the tibial nerve with end-to-side neurorrhaphy. Subsequently, the terminal branches of the same nerve were implanted in the anterior tibial muscle (ATM). On the left side, the peroneal nerve was severed, and the ATM completely denervated. In Group 2 (10 rats), on the right side, the same technique was used as in first group. On the left side, the normal innervation of the ATM was maintained. After 4 months, all muscles and nerves were harvested and evaluations carried out on the morphologic aspect, weight, and histology of the ATM, as well as the histology of the nerves. The authors analyzed the results, which demonstrated good reinnervation of the muscles deprived of any nerve connection.


Predictors of Treatment Response and Long-Term Outcomes in Young Children with Steroid-Dependent Nephrotic Syndrome Treated with High-Dose Mizoribine as First-Line Steroid-Sparing Agent.
Mizoribine may be a safe and effective treatment for children with steroid-dependent nephrotic syndrome (SDNS). However, predictors of treatment response and long-term outcomes after mizoribine discontinuation remain unknown. We retrospectively reviewed the clinical course of 22 children aged ≤ 10 years (median age, 5.3 years) with SDNS who received high-dose mizoribine as the initial steroid-sparing agent (SSA). Mizoribine was administered at a single daily dose of 10 mg/kg (maximum, 300 mg/day) after breakfast. The dose was adjusted to maintain 2-h post-dose mizoribine levels of > 3 μg/mL and was tapered off after 12 months of steroid-free remission. Patients who regressed to SDNS were switched from mizoribine to other SSAs. The primary endpoint was probability of survival without regression to SDNS after mizoribine initiation. Ten patients were able to discontinue SDNS (response group), whereas twelve were switched from mizoribine to other SSAs (non-response group) during a median observation period of 6.0 years after mizoribine. The steroid-dependent dose prior to mizoribine was significantly lower in the response group than in the non-response group (p < 0.05). The Kaplan-Meier analysis revealed that the probability of regression-free survival was significant higher in patients with steroid-dependent dose of < 0.25 mg/kg/day than in those with steroid-dependent dose of ≥ 0.25 mg/kg/day (p < 0.05). During a median follow-up of 5.5 years after mizoribine discontinuation, all but one patient did not develop SDNS. High-dose mizoribine may be an attractive treatment option as initial SSA in young children with low steroid-dependent dose for improved long-term outcomes.


Fraction of uninfected walkers in the one-dimensional Potts model.
The dynamics of the one-dimensional q-state Potts model, in the zero-temperature limit, can be formulated through the motion of random walkers which either annihilate (A+A-->Phi) or coalesce (A+A-->A) with a q-dependent probability. We consider all of the walkers in this model to be mutually infectious. Whenever two walkers meet, they experience mutual contamination. Walkers which avoid an encounter with another random walker up to time t remain uninfected. The fraction of uninfected walkers is known to obey a power-law decay U(t) approximately t(-phi(q)), with a nontrivial exponent phi(q) [C. Monthus, Phys. Rev. E 54, 4844 (1996); S. N. Majumdar and S. J. Cornell, ibid. 57, 3757 (1998)]. We probe the numerical values of phi(q) to a higher degree of accuracy than previous simulations and relate the exponent phi(q) to the persistence exponent theta(q) [B. Derrida, V. Hakim, and V. Pasquier, Phys. Rev. Lett. 75, 751 (1995)], through the relation phi(q)=gamma(q)theta(q) where gamma is an exponent introduced in [S. J. O'Donoghue and A. J. Bray, preceding paper, Phys. Rev. E 65, 051113 (2002)]. Our study is extended to include the coupled diffusion-limited reaction A+A-->B, B+B-->A in one dimension with equal initial densities of A and B particles. We find that the density of walkers decays in this model as rho(t) approximately t(-1/2). The fraction of sites unvisited by either an A or a B particle is found to obey a power law, P(t) approximately t(-theta) with theta approximately 1.33. We discuss these exponents within the context of the q-state Potts model and present numerical evidence that the fraction of walkers which remain uninfected decays as U(t) approximately t(-phi), where phi approximately 1.13 when infection occurs between like particles only, and phi approximately 1.93 when we also include cross-species contamination. We find that the relation between phi and theta in this model can also be characterized by an exponent gamma, where similarly, phi=gamma(theta).


The Dilemma of Diagnosing Hemophagocytic Lymphohistiocytosis in Sickle Cell Disease.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder due to uncontrolled activation of macrophage and cytokine release, which can be due to either genetic causes (familial) or secondary to infections malignancy and other less common cause. Parvovirus B19 rarely causes HLH. Diagnosing HLH in sickle cell disease, which inherently has high ferritin levels and pancytopenia, is particularly challenging. We are reporting HLH as a complication with parvovirus B19 infection in the background of sickle beta-thalassemia. Based on our search of available medical literature, this is the first case of HLH complicating parvovirus B19 infection in a pediatric age group with sickle beta-thalassemia.


Oncogenic codon 13 NRAS mutation in a primary mesenchymal brain neoplasm and nevus of a child with neurocutaneous melanosis.
A 28-month female with a clinical diagnosis of neurocutaneous melanosis and numerous intracranial abnormalities (including a right choroid plexus tumor and left hemimegalencephaly) presented with a rapidly expanding tumor in the left occipital cerebrum. Microscopic examination of the resected specimen revealed a myxoid mesenchymal neoplasm consisting of fusiform cells that were immunoreactive for vimentin, CD34, and P53 but no melanocyte markers. Focused amplicon deep sequencing on DNA extracted from the brain tumor and a cutaneous nevus revealed a heterozygous (c.37G>C; p.G13R) substitution in the NRAS gene. DNA sequencing of "normal" skin and buccal swab showed the identical NRAS change albeit at lower allelic frequency. Her parents did not harbor the NRAS mutation. The skin lesion, but not the brain tumor, had a BRAF mutation (c.1397G>T; p.G466V). A germline single nucleotide polymorphism in MET was found in the child and her father (c.3209C>T; p.T1010I). The findings suggest NRAS mosaicism that occurred sometime after conception and imply an oncogenic role of the activating NRAS mutation in both the brain and skin lesions in this child.


Shear stress distribution in arterial tree models, generated by constrained constructive optimization.
Models of arterial trees are generated by the algorithm of Constrained Constructive Optimization (CCO). Straight cylindrical, binary branching tubes are arranged in an optimized fashion so as to convey blood to the terminal sites of the tree, which are distributed over a predefined area, representing the tissue to be perfused. All terminal segments supply equal flows at a unique terminal pressure, and the radii of parent and daughter segments are related via a bifurcation law. The connective structure and geometry of the model are optimized according to a target function such as total intravascular volume. The shear rate between blood and the vessel walls is computed in each segment and a new method is presented for rescaling a given CCO tree to a desired value of shear rate in the root segment. The effect of viscosity varying with shear rate is evaluated and a new method is presented for rescaling a CCO-tree segment by segment to consistent values of radii and variable viscosity. Shear stress is evaluated for its deviation from being proportional to shear rate and then subjected to various types of analyses. Usually both, shear stress and its variability, are found to be larger in the smaller than in the larger segments of the CCO-model trees. However, it is shown how the shear-stress distribution can be reshuffled between small and large segments when rescaling a CCO tree to obey a different bifurcation law, while its whole geometry remains unchanged and all boundary conditions remain fulfilled. The selection of optimization target is found to drastically affect shear-stress variability within bifurcations, which reaches a distinct minimum if the model is optimized according to intravascular volume. Finally, a rank-analysis of shear stress within each bifurcation shows that only two out of six possible rank patterns actually occur: the parent segment always experiences medium shear stress while minimum shear stress resides mostly in the larger, less frequently in the smaller daughter.


Microorbitalism: a technique for orbital rim expansion.
A simple technique for orbital aperture expansion to facilitate placement of ocular prostheses is described. Both superolateral and inferolateral orbital margins are released by means of a single burr hole craniectomy of the frontosphenoid bone behind the orbital process of the frontal bone. Vertical and horizontal marginal lengthenings are performed by a rotatory displacement of one bone segment alongside the other. The expanded osseous aperture is secured with wire and plate-and-screw fixation following a supraorbital rim craniectomy to allow an adequate fit. The result provides for easier access of ocular prostheses and tissue expanders. The method has been applied to a series of patients with microorbitalism due to unilateral or bilateral congenital anophthalmia over the past 3 years without complication and with excellent results. Three-dimensional re-formatted CT reconstructions of the craniofacial skeleton are shown preoperatively and postoperatively.


Complement Protein C3 Suppresses Axon Growth and Promotes Neuron Loss.
The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3-/- mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3+/+ mice. In vitro, addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone, and ELISA experiments revealed that myelin serine proteases cleave C3 to generate active fragments. Addition of purified C3 cleavage products to cultured neurons suggested that C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3. These data indicate that C3 reduces neurite outgrowth and neuronal viability in vitro and restricts axon regeneration in vivo, and demonstrate a novel, non-traditional role for this inflammatory protein in the central nervous system.


Effects of acupuncture anesthesia on the pituitary gland.
The skin pain threshold was elevated significantly by weak and nonstressful acupuncture stimulation. Although an analgesic effect was obtained by acupuncture stimulation, the beta-E, ACTH, GH and TSH levels were not changed. These findings indicate that these hormone levels were not necessarily related to the skin pain threshold elevation. It is concluded therefore that an analgesic effect was induced without involving the pituitary gland by the weak acupuncture stimulation employed in our study. However, the magnitude of the stimulation may determine whether or not an analgesic effect is mediated by the pituitary gland. The possibility remains that strong acupuncture stimulation produces stress-induced analgesia (SIA). Further detailed research should be attempted.


Burnout in Palliative Care Nurses, Prevalence and Risk Factors: A Systematic Review with Meta-Analysis.
Palliative care nurses are exposed to hard situations, death, and duel feelings in their daily practice. These, and other work stressors, can favor burnout development. Thus, it is important to analyze the prevalence and risk factors of burnout in palliative care nurses and estimate its prevalence. A systematic review and meta-analysis was done with quantitative primary studies. n = 15 studies were included with n = 6 studies including information for the meta-analysis. The meta-analytic prevalence estimation of emotional exhaustion was 24% (95% CI 16-34%), for depersonalization was 30% (95% CI 18-44%) and for low personal accomplishment was 28% with a sample of n = 693 palliative care nurses. The main variables related with burnout are occupational variables followed by psychological variables. Some interventions to improve working conditions of palliative care nurses should be implemented to reduce burnout.


[Molluscicidal effect of 10% LDS in fields].
To evaluate the molluscicidal effects of 10% salt of quinoid-2', 5-dichloro-4'-nitrosalicylanilide (LDS) on Oncomelania hupensis in the fields, so as to provide the evidence for the application of LDS in the fields. The fields where O. hupensis density was relative high were selected as the experimental area and the different concentrations of LDS were used for molluscicidal effects with the immersion, insufflation and powdering methods, and 50% wettable powder of niclosamide ethanolamine salt (WPN) was used as the control. With the immersion method for 3 days, the snail death rates of LDS (0.1, 0.2 g/m3) were lower than those of WPN (2 g/m3, P < 0.01), but the snail death rates of LDS (0.4, 0.6, 0.8 g/m3) were similar with those of WPN (2 g/m3, P > 0.05). With the insufflation and powdering methods for 7 days, the snail death rates of LDS (0.2, 0.4 g/m2) were lower than those of WPN (2 g/m2, P < 0.01), but the snail death rates of LDS (0.6, 0.8, 1.0 g/m2) were similar with those of WPN (2 g/mI2, P > 0.05). LDS has some molluscicidal effect.


Sequence analysis and function of mosquito aeCCC2 and Drosophila Ncc83 orthologs.
Dipteran insects have genes that code for two different Na+-dependent cation-chloride cotransporter (CCC) paralogs. Aedes aegypti aeNKCC1 is an ortholog of Drosophila melanogaster Ncc69, a bumetanide-sensitive Na+-K+-2Cl- cotransporter (NKCC). Aedes aegypti aeCCC2 and aeCCC3 are orthologs of Drosophila Ncc83. Prior work suggests that the transport properties of aeCCC2 differ from canonical NKCCs. In particular, Xenopus oocytes expressing aeCCC2 have increased Na+-dependent membrane currents compared to controls, whereas NKCCs are electroneutral. Here, we further evaluated the function and localization of aeCCC2 and Ncc83. In oocytes expressing aeCCC2 or Ncc83, membrane potential (Vm) hyperpolarized upon Na+ removal; following hypotonic exposure the change in Vm was greater than it was in controls. In voltage-clamp experiments, membrane currents were concentration dependent on Na+ with an apparent affinity (Km) of approximately 4.6 mM. In Malpighian tubules of larval and adult mosquitoes, aeCCC2 was localized along the basolateral aspect of principal cells. Sequence comparisons among transporters from Drosophila, Aedes, Anopheles, and Culex revealed 33 residues within the transmembrane domains (TMDs) that are fully conserved within paralogs but that differ between orthologs of NKCC1 and orthologs of aeCCC2/Ncc83. These residues are distributed across all 12 TMDs. Our results provide a foundation for further exploration of the structural basis for functional differences between insect Na+-dependent CCCs.


Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model.
We earlier provided evidence that oral consumption of pomegranate fruit extract (PFE) inhibits prostate cancer (PCa) cell growth in nude mice. To ascertain convincing evidence of chemopreventive effects of PFE against PCa, its efficacy requires to be evaluated in animal models that closely emulate human disease. Here, we provide evidence of remarkable tumor growth inhibitory effects of PFE using the TRAMP model. Mice received 0.1 and 0.2% PFE, equivalent to 250 and 500 ml of pomegranate juice, in drinking water, starting at 6 weeks and examined at 12, 20 and 34 weeks of age. In water-fed group, 100% mice developed palpable tumors by 20 weeks compared with only 30 and 20% in the 0.1 and 0.2% PFE-supplemented groups, respectively. At 34 weeks, palpable tumors were observed in 70 of 0.1% and only 50 of 0.2% PFE-supplemented mice. Compared with median survival of 43 weeks in water-fed mice, 0.1 and 0.2% PFE-supplemented mice exhibited median life expectancy of 73 and 92 weeks, respectively. Compared with respective water-fed groups, none of the mice in PFE-supplemented groups exhibited metastases to any of the distant organs at 20 weeks and only 20% mice exhibited metastasis at 34 weeks of age. Many of the PFE-supplemented animals had multiple foci of well-differentiated carcinoma but no evidence of poorly differentiated carcinoma. PFE supplementation resulted in simultaneous and significant inhibition of IGF-I/Akt/mTOR pathways in the prostate tissues and tumors. We suggest that pomegranate juice be evaluated in clinical trials in patients at high risk for developing PCa.


Body posture in children with obesity - the relationship to physical activity (PA).
The modern world of electronic devices offers children and young people various forms of leisure activities, while reducing the need for natural movement, necessary for normal psychomotor development. Sedentary life contributes to an increased body weight and, thereby, to the development of body posture abnormalities. The aim of the study was to evaluate body posture, leisure activities, and the number of hours spent using electronic devices among children with obesity. The study involved 51 children with obesity (BMI above 95 percentile) - A group, and 69 children with normal body weight at the age of 9-13 years (10.98 ± 1.29) - B group (control). Body posture has been evaluated with the scoliometer, the digital inclinometer and the plumb line. The hump ratio has been calculated on the basis of SOSORT recommendations. Time spent in front of electronic devices based on a questionnaire results has also been calculated. Children with obesity have more body posture defects in the sagittal plane than children with normal z-scores (p<0.001). 46.8% of children in group A have distorted depth of the two curvatures of the spine. In the control group, the majority of deviations have been observed in the evaluation of the ATR (Angle Trunk Rotation) at the lumbar spine (p<0.05), while in group A, at the level of the thoracic spine (40.42% vs. 23.07%). Both groups of respondents use electronic devices at least 3 days a week (p>0.05). Obese children often use mobile devices, while children with normal body weight often use desktop equipment. Definitely more body posture abnormalities are found in the group of obese children. Children use electronic devices regardless of weight. It is worth to expand educational activities with programs that improve the quality of body posture through a daily change of abnormal patterns.


[Bettolepsy as a variant of transient ischemic attacks].
Bettolepsy (B) refers to episodes of fainting of abrupt onset in patients with nonspecific pulmonary diseases, occurring at the paroxysm of coughing. The authors conducted a comprehensive evaluation in 12 patients liable to B attacks, that incorporated study of the state of the vegetative nervous system, EEG, REG, ultrasonic dopplerography of major vessels of the brain, computerized tomography to the brain, echocardioscopy, roentgenography of the spinal column. The data obtained allow B episodes to be regarded as an acute disturbance in cerebral bloodflow in vascular beds of the vertebrobasilar system of transient ischemic attacks type, which fact leads to derangement in the ascending impacts of the reticular formation, and is a syncopal state.


Preoperative Estimation of Endodontic Working Length with Cone-Beam Computed Tomography and Standardized Paralleling Technique in comparison to Its Real Length.
An accurate estimation of the working canal length is essential for successful root canal treatment. This study is aimed at investigating the diagnostic accuracy of root canal length estimation on cone-beam computed tomography (CBCT) scans and digital paralleling radiographs (PAs), using the real canal length as a gold standard, and at evaluating the influence of canal curvature on this estimation. Sixty extracted human premolar teeth were selected for this study. Root canal length measurement was performed on CBCT scans (NewTom, Giano, Verona, Italy) and digital paralleling radiography (EzRay Air W; Vatech, Korea). The real working length was established by subtracting 0.5 mm from the actual canal length. No significant difference was found between CBCT and digital paralleling radiography. There was a tendency for underestimation of the root canal length measured on the CBCT images in 52 (86.7%) of the examined teeth and overestimation in 5 teeth (8.3%). All the digital radiographs slightly overestimated the real canal length. The analysis revealed a strong correlation between the estimation from moderate to severe curvature for digital radiography and CBCT images. Preoperative working length estimation can be made closest to its real clinical canal length on the standardized paralleling technique, using a long (16-inch) target-receptor distance.


Restricted development of mouse triploid fetuses with disorganized expression of imprinted genes.
Eukaryotic species commonly contain a diploid complement of chromosomes. The diploid state appears to be advantageous for mammals because it enables sexual reproduction and facilitates genetic recombination. Nonetheless, the effects of DNA ploidy on mammalian ontogeny have yet to be understood. The present study shows phenotypic features and expression patterns of imprinted genes in tripronucleate diandric and digynic triploid (DAT and DGT) mouse fetuses on embryonic day 10.5 (E10.5). Measurement of crown-rump length revealed that the length of DGT fetuses (1.87 ± 0.13 mm; mean ± standard error of the mean) was much smaller than that of diploid fetuses (4.81 ± 0.05 mm). However, no significant difference was observed in the crown-rump length between diploid and DAT fetuses (3.86 ± 0.43 mm). In DGT fetuses, the expression level of paternally expressed genes, Igf2, Dlk1, Ndn, and Peg3, remained significantly reduced and that of maternally expressed genes, Igf2r and Grb10, increased. Additionally, in DAT fetuses, the Igf2 mRNA expression level was approximately twice that in diploid fetuses, as expected. These results provide the first demonstration that imprinted genes in mouse triploid fetuses show distinctive expression patterns independent of the number of parental-origin haploid sets. These data suggest that both DNA ploidy and asymmetrical functions of parental genomes separately influence mammalian ontogeny.


Structure bound guide to access cavity preparation for molar root canal treatment.
A good access cavity preparation is the gateway to success in endodontic treatment. This article presents occlusal landmarks that can be used as the boundary for the endodontic access at the occlusal surfaces of maxillary and mandibular molars. Further this article gives a structure or landmark guided three simple stages of preparation to reach the pulp chamber. This assures an ideal access cavity reducing the risk of dentin gouging and eliminating iatrogenic deleterious events. All canal orifices will be within this boundary and can often be located easily.


Hemocytes of bivalve mollusks as cellular models in toxicological studies of metals and metal-based nanomaterials.
Understanding the impacts of environmental pollutants on immune systems is indispensable in ecological and health risk assessments due to the significance of normal immunological functions in all living organisms. Bivalves as sentinel organisms with vital ecological importance are widely distributed in aquatic environments and their innate immune systems are the sensitive targets of environmental pollutants. As the central component of innate immunity, bivalve hemocytes are endowed with specialized endolysosomal systems for particle internalization and metal detoxification. These intrinsic biological features make them a unique cellular model for metal- and nano-immunotoxicology research. In this review, we firstly provided a general overview of bivalve's innate immunity and the classification and immune functions of hemocytes. We then summarized the recent progress on the interactions of metals and nanoparticles with bivalve hemocytes, with emphasis on the involvement of hemocytes in metal regulation and detoxification, the interactions of hemocytes and nanoparticles at eco/bio-nano interface and hemocyte-mediated immune responses to the exposure of metals and nanoparticles. Finally, we proposed the key knowledge gaps and future research priorities in deciphering the fundamental biological processes of the interactions of environmental pollutants with the innate immune system of bivalves as well as in developing bivalve hemocytes into a promising cellular model for nano-immuno-safety assessment.


Dynamics of molecular adsorption and rotation on nonequilibrium sites.
It is generally accepted that important events on surfaces such as diffusion and reactions can be adsorption site dependent. However, due to their short lifetime and low concentration in most systems, adsorbates on nonequilibrium adsorption sites remain largely understudied. Using low-temperature scanning tunneling microscopy, site-dependent adsorption is shown for the molecule butyl methyl sulfide, which is trapped in multiple metastable adsorption sites upon deposition onto a Au(111) surface at 5 K. As this molecule does not have enough energy to diffuse to its preferred adsorption site on the surface, it is possible to study the behavior of individual molecules in a variety of nonequilibrium sites. Here we present atomic-scale data of the same chemical species in three independent, metastable adsorption sites and equilibration to a single equilibrium site as a function of either electrical or thermal excitation. Butyl methyl sulfide exhibits distinctly different physical properties at all four adsorption sites, including rotational dynamics and appearance in scanning tunneling microscopy (STM) images. An energy profile is proposed for the adsorption and equilibration of these species, and a correlation is drawn between rotational barrier and adsorption energy.


Atypical PKCs activate Vimentin to facilitate prostate cancer cell motility and invasion.
Atypical protein kinase C (aPKC) are involved in progression of many human cancers. Vimentin is expressed during epithelial to mesenchymal transition (EMT). Molecular dynamics of Vimentin intermediate filaments (VIFs) play a key role in metastasis. This article is an effort to provide thorough understanding of the relationship between Vimentin and aPKCs . We demonstrate that diminution of aPKCs lead to attenuate prostate cellular metastasis through the downregulation of Vimentin expression. siRNA knocked-down SNAIL1 and PRRX1 reduce aPKC activity along with Vimentin. Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells. Understanding the aPKC related molecular mechanisms may provide a novel therapeutic path for prostate carcinoma.


FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability.
Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and promotes CFS gene stability. Mechanistically, we demonstrate that the mitochondrial stress-dependent induction of CFS genes is mediated by ubiquitin-like protein 5 (UBL5), and that a UBL5-FANCD2 dependent axis regulates the mitochondrial UPR in human cells. We propose that FANCD2 coordinates nuclear and mitochondrial activities to prevent genome instability.