Reactions of CO2 on solid and liquid Al100+.
The reactions of CO(2) on the Al(100)(+) cluster have been investigated as a function of cluster temperature (300-1100 K) and relative kinetic energy (0.2-10 eV). Two main products are observed at low cluster temperature: Al(100)O(+) (which is believed to result from a stripping reaction) and Al(100)CO(2)(+) from complex formation. As the cluster temperature is raised, both products dissociate by loss of Al(2)O. Al(100)O(+) forms Al(98)(+), while Al(100)CO(2)(+) forms Al(98)CO(+) and Al(96)C(+). In both cases, loss of Al(2)O turns-on above the melting temperature of Al(100)(+). This presumably occurs because the overall reaction leading to the loss of Al(2)O is significantly less endothermic for the liquid cluster than for the solid.


The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.
Actin is an important cytoskeletal protein involved in signal transduction, cell structure and motility. Actin regulators include actin-monomer-binding proteins, Wiskott-Aldrich syndrome (WAS) family of proteins, nucleation proteins, actin filament polymerases and severing proteins. This group of proteins regulate the dynamic changes in actin assembly/disassembly, thus playing an important role in cell motility, intracellular transport, cell division and other basic cellular activities. Lymphocytes are important components of the human immune system, consisting of T-lymphocytes (T cells), B-lymphocytes (B cells) and natural killer cells (NK cells). Lymphocytes are indispensable for both innate and adaptive immunity and cannot function normally without various actin regulators. In this review, we first briefly introduce the structure and fundamental functions of a variety of well-known and newly discovered actin regulators, then we highlight the role of actin regulators in T cell, B cell and NK cell, and finally provide a landscape of various diseases associated with them. This review provides new directions in exploring actin regulators and promotes more precise and effective treatments for related diseases.


Pancreatic polypeptide response to insulin in duodenal ulcer. Different levels in accordance with ulcer activity and its response to treatment.
Pancreatic polypeptide is said to be a marker of vagal tone in duodenal ulcer. To determine whether pancreatic polypeptide levels are related to the course of duodenal ulcer, we studied acid and pancreatic polypeptide responses to insulin in 80 patients with duodenal ulcer disease: 40 with unoperated duodenal ulcer and 40 with proximal vagotomy. Data were analysed in accordance with the presence of an ulcer (active disease) and, when present, in accordance with the ulcer healing on medical treatment (cimetidine, 1 g/day for 4 weeks). In both groups acid and pancreatic polypeptide responses to hypoglycaemia were slightly correlated (r = 0.38) (p less than 0.05). The basal pancreatic polypeptide level was higher in patients with active disease than in those with inactive disease, who had a basal level similar to that of normal subjects of the same age range. Like the insulin-stimulated acid secretion, the pancreatic polypeptide response to insulin hypoglycaemia was higher in patients with active disease than in those with inactive disease (p less than 0.05): 26.1 +/- 3.9 versus 20.1 +/- 4 nmol/l/120 min, respectively, in unoperated patients and 34.8 +/- 2.2 versus 24.3 +/- 2.5 nmol/l/120 min, respectively, after proximal vagotomy. In active disease the pancreatic polypeptide response to insulin hypoglycaemia was higher in subjects whose ulcer did not heal further after cimetidine therapy than in those whose ulcer did. These data suggest that the pancreatic polypeptide response to insulin is an indicator of duodenal ulcer activity and is related to the treatment efficacy. These relationships are partly mediated by increased vagal tone.


Preventing Falls Among Behavioral Health Patients.
Inpatient falls are among the most common hospital incidents reported. Fall-related injuries have significant implications for patients, staff, and organizations. Adult behavioral health inpatients are responsible for higher rates of injurious falls and challenge traditional fall prevention methods. An inpatient behavioral health unit in an acute care hospital identified an increased rate of injury from falls per 1,000 patient-days in three months; three falls resulted in major injury. The purpose of this quality improvement (QI) report is to describe the redesign of a fall prevention program for adult behavioral health inpatients using evidence-based practice (EBP) and QI methods. Root cause analyses (RCAs) were conducted on all three fall-related major injuries. Concurrently, a literature review identified EBP recommendations for fall prevention on behavioral health units. A fall prevention action program was developed consisting of four elements: RN education to improve Morse Fall Scale scoring, individualized fall prevention patient plans, revised staff workflow, and improved fall prevention communication. There were no fall-related injuries for six months and no fall-related major injuries for 12 months following implementation of the fall prevention program. Overall, this reduction in fall-related major injuries was sustained over a 21-month period. An interprofessional team approach using EBP and RCA is effective in redesigning and implementing a fall prevention program for the adult inpatient behavioral health population.


Acute interstitial nephritis and drug rash with secondary to Linezolid.
Linezolid, a member of oxazolidinone antibiotic class, is a relatively well-tolerated drug with few side effects. It is active against gram-positive cocci, including multidrug resistant staphylococci and enterococci. We report a case of a 54-year-old diabetic male with alcoholic cirrhosis admitted in intensive care unit with altered sensorium. He was diagnosed as a case of hepatic failure secondary to hepatitis E infection and enterococcal urosepsis. He was started on linezolid based on the urine culture sensitivity report. On day three of linezolid treatment, he developed severe pruritus, macular rash, eosinophilia, and renal dysfunction. Renal biopsy showed acute tubulointerstitial nephritis. Renal functions improved on discontinuation of linezolid and short course of steroid therapy.


Case Of Xanthogranulomatous Oophoritis.
Xanthogranulomatous inflammation is characterized by destruction of the tissues of the organ involved and replacement by chronic inflammatory cells such as lymphocytes, plasma cells, occasional neutrophils with or without multinucleated or Touton giant cells. Exact aetiology is not known but the theory of infection with organisms like Proteus, E coli, and Bacteroides fragilis is most popular. Xanthogranulomatous inflammation of the female genital tract is not common and usually involves the endometrium; however, xanthogranulomatous inflammation of the ovaries is a rare entity.


Diffuse reflectance and machine learning techniques to differentiate colorectal cancer ex vivo.
In this study, we used machine learning techniques to reconstruct the wavelength dependence of the absorption coefficient of human normal and pathological colorectal mucosa tissues. Using only diffuse reflectance spectra from the ex vivo mucosa tissues as input to algorithms, several approaches were tried before obtaining good matching between the generated absorption coefficients and the ones previously calculated for the mucosa tissues from invasive experimental spectral measurements. Considering the optimized match for the results generated with the multilayer perceptron regression method, we were able to identify differentiated accumulation of lipofuscin in the absorption coefficient spectra of both mucosa tissues as we have done before with the corresponding results calculated directly from invasive measurements. Considering the random forest regressor algorithm, the estimated absorption coefficient spectra almost matched the ones previously calculated. By subtracting the absorption of lipofuscin from these spectra, we obtained similar hemoglobin ratios at 410/550 nm: 18.9-fold/9.3-fold for the healthy mucosa and 46.6-fold/24.2-fold for the pathological mucosa, while from direct calculations, those ratios were 19.7-fold/10.1-fold for the healthy mucosa and 33.1-fold/17.3-fold for the pathological mucosa. The higher values obtained in this study indicate a higher blood content in the pathological samples used to measure the diffuse reflectance spectra. In light of such accuracy and sensibility to the presence of hidden absorbers, with a different accumulation between healthy and pathological tissues, good perspectives become available to develop minimally invasive spectroscopy methods for in vivo early detection and monitoring of colorectal cancer.


Cytokines and MicroRNAs as Candidate Biomarkers for Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with varied course and symptoms. Its etiology is very complex and not clearly understood. There is growing evidence of the important role of cytokines in SLE pathogenesis, as well as their utility as biomarkers and targets in new therapies. Other potential new SLE biomarkers are microRNAs. Recently, over one hundred different microRNAs have been demonstrated to have a significant impact on the immune system. Various alterations in these microRNAs, associated with disease pathogenesis, have been described. They influence the signaling pathways and functions of immune response cells. Here, we aim to review the emerging new data on SLE etiology and pathogenesis.


Regenerative effects of hyperbaric oxygen therapy and platelet-rich plasma on the osteochondral defects of rats.
This study aims to investigate the effects of hyperbaric oxygen (HBO) therapy and platelet-rich plasma (PRP) on the regeneration of osteochondral defects of the rats, and the synergistic effect of this combined treatment. This randomized, controlled, and interventional animal study was conducted between May 2014 and August 2014 Osteochondral regeneration was evaluated in four treatment groups (control, PRP, HBO, and HBO+PRP groups) at the 30th day after iatrogenic injury. Thirty-two female Wistar albino rats (weighing 248-305 g) underwent arthrotomy and osteochondral surgery on left knees. The regenerations of defects were then examined histologically by the modified version of O'Driscoll score. Groups that were treated with either HBO or PRP alone regenerated significantly better than the control group (p=0.01), while no significant difference was found between the HBO- and PRP-treated groups (p>0.05). The defects in group 4 (treated with both HBO and PRP) regenerated significantly better than the control group, the HBO-treated group alone, and the PRP-treated group alone (p=0.01). The results of this study showed a synergistic effect of HBO and PRP on knee cartilage regeneration. However, the possible underlying mechanisms should be the subject of future researches. The aggregation and activation of growth factors released from platelets whose activation is increased in the hyperbaric environment may explain this effect. This may result in a better regeneration than the effect of PRP or HBO alone.


Stratospheric measurements of continuous absorption near 2400 cm(-1).
Solar occultation spectra obtained with a balloon-borne interferometer have been used to study continuous absorption by N(2) and CO(2) near 2400 cm(-1) in the lower stratosphere. Synthetic continuum transmittances, calculated from published coefficients for far-wing absorption by CO(2) lines and for pressure-induced absorption by the fundamental band of N(2), are in fair agreement with the observed stratospheric values. The continuum close to the nu(3) R-branch band head of CO(2) is sensitive to the CO(2) far-wing line shape. Therefore, given highly accurate knowledge of the N(2) continuum from laboratory data, high-resolution stratospheric spectra provide a sensitive means for in situ testing of various air-broadened CO(2) line shapes at low temperatures.


[A fully enzymatic triglyceride determination in a continuous flow 12-channel analyzer (author's transl)].
A fully enzymatic triglyceride determination utilizing enzymatic hydrolysis with a lipase-esterase mixture and subsequent enzymatic glycerol determination, has been adapted for use in a continuous flow 12-channel-analyzer. The method is linear up to 7.9 mmol/l (700 mg/100 ml). The analytical precision in the concentration range of 1.5 to 5.4 mmol/l (133 to 478 mg/100 ml) is characterized by relative standard deviations of 0.8 to 4.8%. In the lower measuring range at concentrations around 0.7 mmol/l (62 mg/100 ml) a mean relative standard deviation of 7.2% is found for 1140 measurements under routine conditions. For triglyceride concentrations of 0.9 to 7.7 mmol/80 to 680 mg/100 ml) a mean relative coefficient of verspill Q = 2.0 is determined. Bilirubin caused no observable interference in the determination. In comparison with the manual method by Eggstein & Kreutz (1966) Klin. Wochenschr. 44, 262-267) the results from the fully enzymatic method on the 12-channel-analyzer were lower by approximately 16%, corrected by an additive factor of 0.029 mmol/l (2.59 mg/100 ml). The accuracy controls with controls sera showed a difference of 10%.


A multisensor evaluation of the asymmetric convective model, version 2, in southeast Texas.
There currently exist a number of planetary boundary layer (PBL) schemes that can represent the effects of turbulence in daytime convective conditions, although these schemes remain a large source of uncertainty in meteorology and air quality model simulations. This study evaluates a recently developed combined local and nonlocal closure PBL scheme, the Asymmetric Convective Model, version 2 (ACM2), against PBL observations taken from radar wind profilers, a ground-based lidar, and multiple daytime radiosonde balloon launches. These observations were compared against predictions of PBLs from the Weather Research and Forecasting (WRF) model version 3.1 with the ACM2 PBL scheme option, and the Fifth-Generation Meteorological Model (MM5) version 3.7.3 with the Eta PBL scheme option that is currently being used to develop ozone control strategies in southeast Texas. MM5 and WRF predictions during the regulatory modeling episode were evaluated on their ability to predict the rise and fall of the PBL during daytime convective conditions across southeastern Texas. The MM5 predicted PBLs consistently underpredicted observations, and were also less than the WRF PBL predictions. The analysis reveals that the MM5 predicted a slower rising and shallower PBL not representative of the daytime urban boundary layer. Alternatively, the WRF model predicted a more accurate PBL evolution improving the root mean square error (RMSE), both temporally and spatially. The WRF model also more accurately predicted vertical profiles of temperature and moisture in the lowest 3 km of the atmosphere. Inspection of median surface temperature and moisture time-series plots revealed higher predicted surface temperatures in WRF and more surface moisture in MM5. These could not be attributed to surface heat fluxes, and thus the differences in performance of the WRF and MM5 models are likely due to the PBL schemes. An accurate depiction of the diurnal evolution of the planetary boundary layer (PBL) is necessary for realistic air quality simulations, and for formulating effective policy. The meteorological model used to support the southeast Texas 03 attainment demonstration made predictions of the PBL that were consistently less than those found in observations. The use of the Asymmetric Convective Model, version 2 (ACM2), predicted taller PBL heights and improved model predictions. A lower predicted PBL height in an air quality model would increase precursor concentrations and change the chemical production of O3 and possibly the response to control strategies.


Combination of Brachytherapy and Intravitreal Chemotherapy in the Treatment of Retinoblastoma with Vitreous Seeding.
The aim of this study was to report the efficacy of combined intravitreal chemotherapy (IVC) and ruthenium-106 brachytherapy in retinoblastoma, either as first-line or second-line treatment, following systemic chemoreduction or intra-arterial chemotherapy. Retrospective data of 18 eyes from 18 patients treated with IVC and brachytherapy from August 2014 to December 2019 were collected. The method described was our first-line therapy in 6 patients, whereas it was used as second-line treatment after chemoreduction in the remaining 12 patients. The eyes showed the following classification at initial presentation: 2 group B eyes, 3 group C eyes, and 13 group D eyes. The mean follow-up was 19.5 months (range 2-53 months). The mean patient age at brachytherapy was 34.0 months (range 15-83 months). The median prescribed dose at the tumour base and apex was 574.5 ± 306.7 Gy and 88.5 ± 12.2 Gy, respectively. The ocular retention rate was 66.7%. Six eyes had to be enucleated due to uncontrollable subretinal and recurrent vitreous seeding, tumour relapse, recurrence of a solid tumour elsewhere in the eye, and persistent vitreous bleeding with loss of tumour control. The mean number of intravitreal injections of melphalan was 5.0. Two patients received a simultaneous injection of topotecan for insufficient therapeutic response. With regard to radiogenic complications, we could observe temporary retinal and vitreous bleeding (27.8%), serous retinal detachment (44.4%), and radiogenic maculopathy and retinopathy (11.1%). None of the children showed metastatic disease during follow-up. Ruthenium-106 plaque therapy in combination with IVC is an effective local therapy with good tumour control rates even in advanced eyes. Overall, the analysed therapeutic approach shows an acceptable side-effect profile, especially when considering that external-beam radiation therapy and systemic polychemotherapy or at least the number of cycles needed, with their increased incidence of adverse events, can thus be avoided.


Growth hormone deficiency after localized ganglioneuroblastoma: A case report.
Growth hormone deficiency (GHD) related to standard dose chemotherapy has rarely been described. We report on a case of localized ganglioneuroblastoma treated by carboplatin/etoposide for 2 courses and surgery, which developed a serious GHD after 56 months. At present, the child is growing on by GH replacement therapy. We discuss about the hypothesis that GHD may be related to chemotherapy and we report a review of previous published cases.


[Microcontact printing and its application prospect in bone tissue engineering].
The application of bone tissue engineering regeneration technology is expected to repair maxillofacial bone tissue defects caused by tumors, trauma, etc. Surface patterning occupies an important position in bone tissue engineering. Microcontact printing is an emerging technology through which the elastic stamp contacts with the substance and materials used as ink can be transferred from stamp to substance to form patterns. The biggest characteristic of the technology is to fabricate high-throughput and high-accuracy patterned surface, making it widely applied. This review summarized the application and optimization of microcontact printing, and prospected its application in bone tissue engineering.


Imaging the liver.
Imaging of the liver is undertaken for the detection and characterization of suspected primary or secondary neoplasms, prior to planning a surgery or chemotherapy pump placement, for assessing treatment response, for evaluating biliary pathology, and for screening for liver neoplasms in high-risk groups. In this article, we review the advantages and disadvantages of various imaging modalities in the evaluation of the liver and formulate guidelines for the imaging of common clinical indications. A brief review of imaging findings in focal and diffuse liver disease is also presented.


PKCepsilon activation augments cardiac mitochondrial respiratory post-anoxic reserve--a putative mechanism in PKCepsilon cardioprotection.
Modest cardiac-overexpression of constitutively active PKCepsilon (aPKCepsilon) in transgenic mice evokes cardioprotection against ischemia. As aPKCepsilon interacts with mitochondrial respiratory-chain proteins we hypothesized that aPKCepsilon modulates respiration to induce cardioprotection. Using isolated cardiac mitochondria wild-type and aPKCepsilon mice display similar basal mitochondrial respiration, rate of ATP synthesis and adenosine nucleotide translocase (ANT) functional content. Conversely, the aPKCepsilon mitochondria exhibit modest hyperpolarization of their inner mitochondrial membrane potential (DeltaPsi(m)) compared to wild-type mitochondrial by flow cytometry. To assess whether this hyperpolarization engenders resilience to simulated ischemia, anoxia-reoxygenation experiments were performed. Mitochondria were exposed to 45 min anoxia followed by reoxygenation. At reoxygenation, aPKCepsilon mitochondria recovered ADP-dependent respiration to 44 +/- 3% of baseline compared to 28 +/- 2% in WT controls (P = 0.03) in parallel with enhanced ATP synthesis. This preservation in oxidative phosphorylation is coupled to greater ANT functional content [42% > concentration of atractyloside for inhibition in the aPKCepsilon mitochondria vs. WT control (P < 0.0001)], retention of mitochondrial cytochrome c and conservation of DeltaPsi(m). These data demonstrate that mitochondria from PKCepsilon activated mice are intrinsically resilient to anoxia-reoxygenation compared to WT controls. This resilience is in part due to enhanced recovery of oxidative phosphorylation coupled to maintained ANT activity. As maintenance of ATP is a prerequisite for cellular viability we conclude that PKCepsilon activation augmented mitochondrial respiratory capacity in response to anoxia-reoxygenation may contribute to the PKCepsilon cardioprotective program.


Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials.
We review factors impacting ipilimumab-associated adverse events through the experience from National Cancer Institute (NCI)-sponsored phase I immunotherapy clinical trials. Attributable ipilimumab-related adverse events from NCI-sponsored phase I immunotherapy clinical trials were queried retrospectively by anonymized patient experience reports for observed adverse events like decreased hematological cell counts, blood electrolytes or proteins, or reduced patient performance status. The prevalence of ipilimumab-related toxicity was associated by patient to the duration of ipilimumab exposure, radiographic responses, progression-free survival, and overall survival. 373 patients from 11 phase 1 ipilimumab clinical trials were analyzed. Patients experiencing at least one grade 3 or 4 adverse event associated with observed radiographic response were included. The average number of grade 3/4 adverse events in responders was 1.167 versus 0.645 in non-responders (p = 0.001). Patient performance status did not significantly impact observed toxicity grade. Pretherapy lymphocyte count or chemistries were not associated with ipilimumab-associated toxicity. The number of agents combined with ipilimumab on trial was associated with average number of grade 3/4 toxicities-ipilimumab monotherapy (0.631) versus ipilimumab + 1 agent (0.877) versus ipilimumab + 2 agents (1.408) (p = 0.014). Number of low grade (grade 1/2) toxicities was associated with duration of treatment, Pearson correlation coefficient r = 0.456 (p < 0.0001); whereas the number of high grade (grade 3/4) toxicities was not, r = 0.032 (p = 0.546). Ipilimumab-attributed grade 3/4 toxicity was associated with therapeutic response. The number of co-administered agents added to ipilimumab significantly raised the likelihood of toxicity. Extended duration of treatment increased the incidence of low but not high-grade toxicity.


The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells.
Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU). We also demonstrated that metformin inhibits the opening of mPTP and induces mitochondrial biogenesis. Altogether, the inhibition of mPTP and the increase in mitochondrial biogenesis may account for the poor pro-apoptotic effect of metformin in cancer cells.


Gallium-68 labelled RGD PET/CT imaging of endothelial activation in COVID-19 patients.
In coronavirus disease 2019 (COVID-19), endothelial cells play a central role and an inadequate response is associated with vascular complications. PET imaging with gallium-68 labelled RGD-peptide (68Ga-RGD) targets αvβ3 integrin expression which allows quantification of endothelial activation. In this single-center, prospective observational study, we included ten hospitalized patients with COVID-19 between October 2020 and January 2021. Patients underwent 68Ga-RGD PET/CT followed by iodine mapping of lung parenchyma. CT-based segmentation of lung parenchyma, carotid arteries and myocardium was used to quantify tracer uptake by calculating standardized uptake values (SUV). Five non-COVID-19 patients were used as reference. The study population was 68.5 (IQR 52.0-74.5) years old, with median oxygen need of 3 l/min (IQR 0.9-4.0). 68Ga-RGD uptake quantified as SUV ± SD was increased in lungs (0.99 ± 0.32 vs. 0.45 ± 0.18, p < 0.01) and myocardium (3.44 ± 1.59 vs. 0.65 ± 0.22, p < 0.01) of COVID-19 patients compared to reference but not in the carotid arteries. Iodine maps showed local variations in parenchymal perfusion but no correlation with SUV. In conclusion, using 68Ga-RGD PET/CT in COVID-19 patients admitted with respiratory symptoms, we demonstrated increased endothelial activation in the lung parenchyma and myocardium. Our findings indicate the involvement of increased and localized endothelial cell activation in the cardiopulmonary system in COVID-19 patients.Trail registration: NCT04596943.


Molecular Mechanisms of Bipolar Disorder: Progress Made and Future Challenges.
Bipolar disorder (BD) is a chronic and progressive psychiatric illness characterized by mood oscillations, with episodes of mania and depression. The impact of BD on patients can be devastating, with up to 15% of patients committing suicide. This disorder is associated with psychiatric and medical comorbidities and patients with a high risk of drug abuse, metabolic and endocrine disorders and vascular disease. Current knowledge of the pathophysiology and molecular mechanisms causing BD is still modest. With no clear biological markers available, early diagnosis is a great challenge to clinicians without previous knowledge of the longitudinal progress of illness. Moreover, despite recommendations from evidence-based guidelines, polypharmacy is still common in clinical treatment of BD, reflecting the gap between research and clinical practice. A major challenge in BD is the development of effective drugs with low toxicity for the patients. In this review article, we focus on the progress made and future challenges we face in determining the pathophysiology and molecular pathways involved in BD, such as circadian and metabolic perturbations, mitochondrial and endoplasmic reticulum (ER) dysfunction, autophagy and glutamatergic neurotransmission; which may lead to the development of new drugs.


Genetic heterogeneity of histamine H2-receptors in the mouse vas deferens.
The ability of histamine to inhibit the overall contractile ('twitch') response of the isolated vas deferens of the mouse to electrical field stimulation (64 V pulse, 1 ms pulse width, frequency 0.2 Hz) was studied in nine inbred mouse strains. The strains were also characterized in terms of the potency of the histamine H2-receptor antagonist cimetidine in its inhibition of histamine-mediated effects. An apparently bimodal inter-strain variation (8-10 fold) in both characteristics was encountered, with three strains (SWR, A2G and C57BL/10ScSn) relatively sensitive (S) to both agonist and antagonist actions, and six (C3H, A, C57/BL6, DBA/2, Balb/C and 129/Sv) relatively insensitive (IS). These strain differences were independent of extracellular calcium concentration in the range 1.25-5 mM, and also independent of the frequency of tissue stimulation over the range 0.2-6.4 Hz. Representative S (SWR and A2G) and IS (DBA/2 and C3H) mouse vasa were also characterized in terms of their sensitivity to the agonist actions of dimaprit and the antagonist actions of tiotidine. In the S strain tissues, dimaprit produced 50% inhibition of the twitch response at 4.6-1.8 microM (mean +/- s.d.) and was able to elicit complete inhibition of the twitch response at concentrations greater than 100 microM, whereas 48.7 +/- 11.9 microM dimaprit was required to produce 50% inhibition of the twitch response in tissues from IS mice. In addition, the agonist actions of dimaprit were incomplete in the latter tissues, the drug eliciting no more than 75% inhibition of the twitch response at concentrations in the range 300-1000 microM. Tiotidine produced competitive antagonism of the actions of both histamine and dimaprit, the strain differences being of the same magnitude as those observed for cimetidine. 4 Mating of a representative S (SWR) and IS (129/Sv) strain produced F, mice with intermediate histamine and cimetidine sensitivities relative to the parental strains. A backcross of male F1 to female IS mice produced progeny displaying a range of histamine and cimetidine sensitivities representative of those seen in tissues from F1 and IS parental animals, however, the data were not bimodal. Thus, the backcross data provided no evidence to support single gene inheritance of histamine sensitivity and might suggest that more than one gene is responsible for these differences between S and IS mice.


[New breaths of foreign medical culture in the Leibniz's literary production].
This short composition is referred to the famous Leopoldian society, founded in Germany, in which illustrious Italian men were welcome. Some social, historical and medical considerations underline the great attraction that the philosopher Leibniz showed for the international cultural exchanges, by safeguarding the ancient tradition.


Elucidation of bacterial trehalose-degrading trehalase and trehalose phosphorylase: physiological significance and its potential applications.
Bacteria possess diverse metabolic and genetic processes, resulting in the inability of certain bacteria to degrade trehalose. However, some bacteria do have the capability to degrade trehalose, utilizing it as a carbon source, and for defense against environmental stress. Trehalose, a disaccharide, serves as a carbon source for many bacteria, including some that are vital for pathogens. The degradation of trehalose is carried out by enzymes like trehalase (EC 22.214.171.124) and trehalose phosphorylase (EC 188.8.131.52/184.108.40.206), which are classified under the glycoside hydrolase families GH37, GH15, and GH65. Numerous studies and reports have explored the physiological functions, recombinant expression, enzymatic characteristics, and potential applications of these enzymes. However, further research is still being conducted to understand their roles in bacteria. This review aims to provide a comprehensive summary of the current understanding of trehalose degradation pathways in various bacteria, focusing on three key areas: (i) identifying different trehalose-degrading enzymes in Gram-positive and Gram-negative bacteria, (ii) elucidating the mechanisms employed by trehalose-degrading enzymes belonging to the glycoside hydrolases GH37, GH15, and GH65, and (iii) discussing the potential applications of these enzymes in different sectors. Notably, this review emphasizes the bacterial trehalose-degrading enzymes, specifically trehalases (GH37, GH15, and GH65) and trehalose phosphorylases (GH65), in both Gram-positive and Gram-negative bacteria, an aspect that has not been highlighted before.


The novel multitarget iron chelating and propargylamine drug M30 affects APP regulation and processing activities in Alzheimer's disease models.
In many of the neurodegenerative diseases, such as Alzheimer's disease (AD) and AD-related disorders, as well as in the regular ageing process, excessive generation of oxidative stress (OS) and accumulation of iron levels and deposition have been observed in specific affected-brain regions and thus, regarded as contributing factors to the pathogenesis of the diseases. In AD, iron promotes amyloid β (Aβ) neurotoxicity by producing free radical damage and OS in brain areas affected by neurodegeneration, presumably by facilitating the aggregation of Aβ. In addition, it was shown that iron modulates intracellular levels of the holo amyloid precursor protein (APP) by iron-responsive elements (IRE) RNA stem loops in the 5' untranslated region (5'UTR) of the APP transcript. As a consequence of these observations, iron chelation is one of the major new therapeutic strategies for the treatment of AD. This review describes the benefits and importance of the multimodal brain permeable chimeric iron-chelating/propargylamine drug M30, concerning its neuroprotective/neurorestorative inter-related activities relevant of the pathological features ascribed to AD, with a special focus on the effect of the drug on APP regulation and processing.


Thoracoscopic surgery for lung cancer is associated with improved survival and shortened admission length: a nationwide propensity-matched study.
Population-based studies comparing long-term survival after minimally invasive and open surgery for lung cancer are lacking. The aim of this study was to compare long-term survival rates between minimally invasive [video-assisted thoracoscopic surgery (VATS)] and open surgery for lung cancer in an unselected nationwide setting. Patients undergoing minimally invasive (n = 710) or open (n = 2814) lung resection for lung cancer between 2004 and 2014 were identified from nationwide complete registries in Finland. Propensity score matching resulted in groups of 632 patients who had VATS and 632 who had a thoracotomy. The primary outcome was the 1-year survival rate. Secondary outcomes were 30-day, 90-day and 5-year survival rates and the length of surgical admission. Cox models were adjusted for sex, age, comorbidity, centre size, year of surgery, histological diagnosis, stage and adjuvant therapy. In the propensity-matched cohort, the 1-year survival rate was 90.8% [confidence interval (CI) 88.3-92.8%] after VATS and 87.1% (CI 84.3-89.6%) after open surgery. The 5-year survival rate in the propensity-matched cohort was 59.6% (CI 54.9-63.9%) after VATS and 53.3% (CI 48.6-57.7%) after open surgery. The 30-day mortality rates showed no differences between approaches, but the 90-day mortality rate was better after VATS when adjusted for patient-, tumour- and operation-specific features (hazard ratio 0.56, 95% CI 0.30-0.92; P = 0.024). According to this population-based nationwide study from Finland, minimally invasive surgery for lung cancer is associated with improved long- and short-term survival rates, supporting the use of VATS as a primary surgical method for treating lung cancer. Due to the complexity of confounding factors in this study, one should, however, interpret the results critically. Additional studies are needed.


Trial of a new operative method for recurrent chronic subdural hematoma.
A new operative method for treating recurrent chronic subdural hematoma is presented. This method consists of complete obliteration of the subdural hematoma cavity and conversion of the hematoma cavity into epidural space. The procedure was carried out in three patients with recurrent chronic subdural hematoma, all of whom made a complete recovery.


New Culicoides Latreille of the subgenus Mataemyia Vargas from Pará, Brazil (Diptera: Ceratopogonidae).
Two new species of Culicoides Latreille of the Neotropical subgenus Mataemyia Vargas are described and illustrated based on female specimens from Juruti, Pará, Brazil and compared with their similar congeners. This paper also presents a diagnosis of the subgenus Mataemyia and a systematic key for the identification of the 19 species of the subgenus.


How early should ankylosing spondylitis be treated with tumour necrosis factor blockers?
Recognition and treatment of ankylosing spondylitis (AS) in the early stages of the disease has yet to be established. This paper considers the evidence available and the questions that need to be answered regarding the benefits of early diagnosis and treatment with tumour necrosis factor (TNF) blockers in AS. The authors conclude that AS can and has to be diagnosed earlier than is being done at present, before radiological changes are evident, and the potential of TNF blockers to induce long term remission if given early enough needs to be clarified.


Brain magnetic resonance imaging findings in postpartum headache.
The objectives were to determine the frequency of abnormal magnetic resonance imaging findings in patients with postpartum headache and related factors. A total of 102 patients with postpartum headache underwent brain magnetic resonance imaging study. The images were examined by a blinded radiologist. The related demographic, obstetric and headache-related factors were recorded. The multiple logistic regression model was used to determine the predictive factors. Abnormal magnetic resonance imaging findings were observed in 42 of 102 patients (41.2%, 95% confidence interval = 31.6 to 50.7%). The most common finding was sinusitis (10 of 42 patients, 23.8%, 95% confidence interval = 15.5 to 32%). Then, posterior reversible encephalopathy syndrome (six of 42 cases, 14.2%, 95% confidence interval = 7.4 to 20.9%), cerebral venous thrombosis (four of 42 cases, 9.5%, 95% confidence interval = 3.8 to 15.1%), and subarachnoid hemorrhage (four of 42 cases, 9.5%, 95% confidence interval = 3.8 to 15.1%) were most prevalent findings. Convulsions (odds ratio of 3.39) and initiation of headache earlier than 5 days postpartum (odds ratio of 0.29) were significant predictive factors. Abnormal brain magnetic resonance imaging findings were seen in a considerable number of patients with postpartum headache. When headache starts in the first 5 days postpartum and accompanied by convulsions, there are likely to be abnormal magnetic resonance imaging findings.


Coping with negative symptoms of schizophrenia: patient and family perspectives.
An exploratory study was conducted of the strategies that schizophrenia patients and their relatives employ to cope with negative symptoms. Coping strategies and their perceived efficacy were elicited in semistructured interviews conducted separately with patients and relatives. Coping responses were coded according to the following dimensions: behavioral-cognitive, social-nonsocial, and problem focused-emotion focused. Overall, the number of coping strategies was related to perceived coping efficacy for both patients and relatives, regardless of the type of strategy. Perceived coping efficacy tended to be highest for apathy; intermediate for alogia, anhedonia, and inattention; and lowest for blunting. Relatives with more knowledge about schizophrenia used more coping strategies and reported higher levels of coping efficacy. Patient rejection by relatives and distress (either patient or relative) tended to not be related to coping strategies. The findings suggest that patients and relatives use a wide variety of strategies to cope with negative symptoms of schizophrenia. Future clinical work and research need to evaluate whether families may benefit from psychoeducational approaches to teaching them how to better manage negative symptoms.


Influence of Pall Pl-50 platelet filters on lactate dehydrogenase, platelet factor 4, and complement factor 3 in stored platelet concentrates.
The study examines Pall Pl-50 platelet filters with respect to their influence on some biochemical properties of platelet concentrates. Ten pairs of pooled platelet preparations, each consisting of 3 platelet concentrates, were studied. On day 1, one of the preparations was filtered and the other served as an identical non-filtered control. Immediately after filtration platelet counts, the levels of desarginated activated complement factor 3 (C3a), extracellular levels of lactate dehydrogenase (LDH) and extracellular and total concentrations of platelet factor 4 (PF4) were determined in both concentrates. After 5 days sterility testing and determination of extracellular levels of PF4 and LDH were performed. Extracellular concentrations of PF4 and C3a decreased immediately after filtration (p < 0.01). Furthermore, Pall Pl-50 filters caused cellular instability reflected by an increased release of PF4 (p < 0.01) during subsequent storage. Platelet concentrates filtered with Pall Pl-50 would not appear suitable for storage.


Enhancement of juvenile Caribbean spiny lobsters: an evaluation of changes in multiple response variables with the addition of large artificial shelters.
Shortage of natural crevice shelters may produce population bottlenecks in juvenile Caribbean spiny lobsters (Panulirus argus), a socially gregarious species. We conducted a field experiment to test enhancement of a local population of juvenile P. argus with the addition of artificial shelters ("casitas") that mimic large crevices (1.1 m(2) in surface area and 3.8 cm in height). Changes in density and biomass of juvenile lobsters 15-50 mm carapace length (CL) were assessed with a multiple before-after control-impact (MBACI) analysis. Separate analyses were also conducted on small (15-35 mm CL) and large (35.1-50 mm CL) juveniles to assess size-related effects. First, we carried out 13 lobster surveys on nine fixed 1-ha sites over a shallow reef lagoon ("before" period). Then, we deployed ten casitas in each of five sites and left four sites as controls, and conducted 22 further surveys ("after" period). Deployment of casitas resulted in a sixfold increase in juvenile density (76% contributed by small and 24% by large juveniles) and a sevenfold increase in biomass (40 and 60%, respectively). Capture-recapture results revealed that enhancement was achieved not by promoting individual growth but by increasing survival, persistence, and foraging ranges of small and large juveniles. Casitas both mitigated shortage of natural shelter and increased sociality, allowing for cohabitation of smaller, more vulnerable juveniles with larger conspecifics that have greater defensive abilities. Casitas may help enhance local populations of juvenile P. argus in Caribbean seagrass habitats, typically poor in natural crevice shelters. The use of MBACI and the simultaneous assessment of multiple interrelated response variables may be a powerful analytical approach to test shelter limitation in other species and to examine the function of structural habitat in other systems.


High serum allopregnanolone levels in girls with precocious puberty.
Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.


The promoters of two carboxylases in a C4 plant (maize) direct cell-specific, light-regulated expression in a C3 plant (rice).
C4 plants have two carboxylases which function in photosynthesis. One, phosphoenolpyruvate carboxylase (PEPC) is localized in mesophyll cells, and the other, ribulose bisphosphate carboxylase (RuBPC) is found in bundle sheath cells. In contrast, C3 plants have only one photosynthetic carboxylase, RuBPC, which is localized in mesophyll cells. The expression of PEPC in C3 mesophyll cells is quite low relative to PEPC expression in C4 mesophyll cells. Two chimeric genes have been constructed consisting of the structural gene encoding beta-glucuronidase (GUS) controlled by two promoters from C4 (maize) photosynthetic genes: (i) the PEPC gene (pepc) and (ii) the small subunit of RuBPC (rbcS). These constructs were introduced into a C3 cereal, rice. Both chimeric genes were expressed almost exclusively in mesophyll cells in the leaf blades and leaf sheaths at high levels, and no or very little activity was observed in other cells. The expression of both genes was also regulated by light. These observations indicate that the regulation systems which direct cell-specific and light-inducible expression of pepc and rbcS in C4 plants are also present in C3 plants. Nevertheless, expression of endogenous pepc in C3 plants is very low in C3 mesophyll cells, and the cell specificity of rbcS expression in C3 plants differs from that in C4 plants. Rice nuclear extracts were assayed for DNA-binding protein(s) which interact with a cis-regulatory element in the pepc promoter. Gel-retardation assays indicate that a nuclear protein with similar DNA-binding specificity to a maize nuclear protein is present in rice.(ABSTRACT TRUNCATED AT 250 WORDS)


Antiphospholipid Antibodies and Heart Valve Disease in Systemic Lupus Erythematosus.
Evaluation of antiphospholipid antibodies (aPL) and correlation with heart valve abnormalities among patients with systemic lupus erythematosus (SLE). Nested case-control study was conducted with 70 patients with SLE selected from a longitudinal database based on levels of aPL and presence or absence of valve disease by echocardiogram. Valvular abnormalities observed were regurgitation (52), other (14), artificial valves (4), stenosis (2), thickening (2) and no Libman-Sacks endocarditis (0). The mitral valve was the most commonly affected (30 abnormalities), followed by the tricuspid (20 abnormalities). Multivariate logistic regression for those with and without an aPL value ≥20 units/mL, adjusted for disease duration and age, showed significant differences for any valve abnormality (odds ratio [OR] = 3.1; 95% CI: 1.0-8.9; P = 0.041) and individually for the tricuspid valve (OR = 3.3; 95% CI: 1.0-11.1; P = 0.052) but not for the mitral valve (OR = 2.1; 95% CI: 0.68-6.45; P = 0.195). Levels of aPL ≥20 units/mL showed no association with aortic (P = 0.253), pulmonic (P = 1.000), tricuspid (P = 0.127), or mitral (P = 0.249) valve abnormalities. Levels of aPL correlate with certain valvular abnormalities among patients with SLE.


Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases.
Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or histologically mature teratoma. However, lesions with the morphology of atypical carcinoid can occasionally exhibit metastatic spread.


In silico metagenomes mining to discover novel esterases with industrial application by sequential search strategies.
We present here an in silico search of fungal sterol-esterase/lipase and bacterial depolymerase sequences from environmental metagenomes. Both enzyme types contain the α/β-hydrolase protein fold. Analysis of DNA conserved motifs, protein homology search, phylogenetic analysis, and protein 3D modeling have been used, and the efficiency of these screening strategies is discussed. The presence of bacterial genes in the metagenomes was higher than those from fungi, and the sequencing depth of the metagenomes seemed to be crucial to allow finding enough diversity of enzyme sequences. As a result, a novel putative PHA-depolymerase is described.


Algorithms for exact multi-object muscle wrapping and application to the deltoid muscle wrapping around the humerus.
Lines of action of muscle forces imply the function and performance of muscles acting around joints. It is not always possible to determine muscle force lines of action in vivo, and so computational techniques are often used to predict them. It is common to model a muscle as a taut elastic string that follows the shortest geodesic path between attachments over the wrapping geometry. A number of studies have been concerned with wrapping paths over single wrapping objects, and those that have considered more objects have applied the single-object solutions with iterative approaches to the search for a solution. This study presents a more efficient methodology for finding the exact solutions to a certain class of wrapping problems in which the path is constrained by multiple surfaces. It also introduces a more general wrapping technique based on the idea of energy minimization, which has been successfully validated against the exact solution. These methods are applied to the case of an element of the deltoid wrapping around the humerus modelled as a composite sphere-cylinder. Comparison of results with those obtained from approximated single-object solutions demonstrates the need to include correct multi-object wrapping algorithms in biomechanical models.


Symptom Frequency Characteristics of the Hamilton Depression Rating Scale of Major Depressive Disorder in Epilepsy.
Depressive disorders are common among patients with epilepsy (PWE). The aim of this study was to explore symptom frequencies of 17-item Hamilton Depression Rating Scale (HDRS-17) and recognize the clinical characteristics of Major Depressive Disorder in PWE. A sample of 40 adults outpatients with epilepsy and depression was diagnosed using SCID-I for DSM-IV-TR and HDRS-17. The total HDRS-17 score was analysed followed by the exploratory analysis based on the hierarchical model. The frequencies of HDRS-17 items varied widely in this study. Insomnia related items and general somatic symptoms items as well as insomnia and somatic factors exhibited constant and higher frequency. Feeling guilty, suicide, psychomotor retardation and depressed mood showed relatively lower frequencies. Other symptoms had variable frequencies across the study population. Depressive disorders are common among PWE. In the study group insomnia and somatic symptoms displayed highest values which could represent atypical clinical features of mood disorders in PWE. There is a need for more studies with a use of standardized approach to the problem.


Five-grass pollen immunotherapy tablet: an update on the latest findings from clinical trials: an interview with Olivier de Beaumont.
Interview by Jonathan Wilkinson (Managing Commissioning Editor, Future Science Group). Olivier de Beaumont became Doctor of Medicine at the University of Paris Descartes in 1993. In the same year, he also took a Master of Health Economics degree at Paris Dauphine University. He is also a Master of Business Administration, ESCP Paris, 1999. At Stallergenes, he has been serving as Vice President/Head of Corporate Clinical Development since 2005, responsible for the clinical development plan, clinical operations, biometry and pharmacovigilance. In 2011, he took the responsibility of Senior Vice President Global Medical Affairs responsible for medical information and education, medical communication and nonregistration clinical studies. In 2014 he became Senior Vice President Global Scientific and Medical Affairs. From 2002 to 2005 he led the European business development of the world's leading clinical research organization Quintiles, developing Phase I-IV clinical trial programs for pharmaceutical companies. Previous roles included: Chief Scientific Officer and cofounder of Direct Medica (2000-2002), product champion and lifecycle management at Aventis (1998-2000), medical affairs manager in oncology and respiratory diseases at corporate Rhone-Poulenc Rorer (1993-1998).


Activity-dependent neuroprotective protein (ADNP): a case study for highly conserved chordata-specific genes shaping the brain and mutated in cancer.
The recent finding of activity-dependent neuroprotective protein (ADNP) as a protein decreased in serum of patients with Alzheimer's disease (AD) compared to controls, alongside with the discovery of ADNP mutations in autism and coupled with the original description of cancer mutations, ignited an interest for a comparative analysis of ADNP with other AD/autism/cancer-associated genes. We strive toward a better understanding of the molecular structure of key players in psychiatric/neurodegenerative diseases including autism, schizophrenia, and AD. This article includes data mining and bioinformatics analysis on the ADNP gene and protein, in addition to other related genes, with emphasis on recent literature. ADNP is discovered here as unique to chordata with specific autism mutations different from cancer-associated mutation. Furthermore, ADNP exhibits similarities to other cancer/autism-associated genes. We suggest that key genes, which shape and maintain our brain and are prone to mutations, are by in large unique to chordata. Furthermore, these brain-controlling genes, like ADNP, are linked to cell growth and differentiation, and under different stress conditions may mutate or exhibit expression changes leading to cancer propagation. Better understanding of these genes could lead to better therapeutics.


Modulation of cellular immunity by antibodies against calreticulin.
Although caltreticulin (CRT) is mainly a residential ER protein, it is also expressed on the membrane surface of various types of cells exhibiting multiple functions. We report here that intraperitoneal administration of a soluble recombinant CRT fragment (rCRT/39-272) led to a substantial decrease in delayed type hypersensitivity (DTH) responses in BALB/c mice and EAE in C57BL/6 mice. In the recall response against keyhole limpet hemocyanin (KLH) in vitro, draining lymph node cells from the rCRT/39-272-treated mice produced less IFN-γ but more IL-4 as compared with the cells from the control group. The immunomodulating effect of intraperitoneally administered rCRT/39-272 was attributed to anti-CRT Abs thereby induced, because, in passive transfer experiments, the CRT-specific antiserum could suppress DTH in BALB/c mice. B-cell-deficient μMT mice were not susceptible to rCRT/39-272-mediated DTH suppression. Furthermore, CRT appears on the surface of murine T cells soon after activation and remains detectable (at relatively low level) by flow cytometry for approximately 5 days in vitro. Anti-CRT Abs were able to inhibit AKT phosphorylation, proliferation, and cytokine production by activated murine T cells. We propose that cell surface CRT could play a role in the function of effector T cells and may be considered a target for immunological manipulation.


Antibiotic sensitivity and proticine typing of Proteus mirabilis strains associated with rheumatoid arthritis.
Urinary isolates of Proteus mirabilis, obtained from 49 RA patients and 44 healthy controls, were tested for susceptibility to antibiotics by the disc diffusion method. In addition, P. mirabilis isolates were also tested for proticine production and sensitivity (p/s) typing by the inhibition of growth of each test isolate against 13 reference strains of P. mirabilis. The P. mirabilis isolates from both RA patients and healthy controls were highly susceptible to norfloxacin, ciprofloxacin and trimethoprim, but less to minocycline. The urine of RA patients contained fewer different types of P. mirabilis strains than those isolated from healthy controls. All of the strains found in the RA patients were proticine producers (P < 0.001), mostly of proticine 3 (P < 0.005). The presence of such strains provides evidence of a sub-clinical upper urinary tract infection with P. mirabilis in some RA patients. Therapeutic intervention in RA with relevant antibiotics requires evaluation.


Continuous single pass perfusion of the isolated kidney.
The use of continuous single pass perfusion to study the metabolism of isolated kidneys reveals that active metabolic processes continue in the hypothermically preserved kidney. These preliminary experiments described demonstrated a rapid uptake of substrates from the perfusion media in the first 24 hrs of storage, followed by a release of organic acids in the subsequent 24 to 72 hrs. Urea was found to be easily eliminated from the kidney. This technique may be useful for studying events related to loss of renal function by pinpointing specific residual biochemical activity and lesions that occur during prolonged preservations. An eventual correction or prevention of such lesions might be feasible in order to improve preservation techniques.


Analysis of radiological measurement parameters that can predict the type of treatment to be applied in odontoid fractures: Clinical research.
Although various conservative and surgical treatment methods have been proposed, treatment options for patients with odontoid fractures remain controversial. This study was conducted to determine some demographic and radiological measurement parameters that can predict treatment options in patients with odontoid fractures. The patients were separated into the surgery (-) group (n = 9) and the surgery (+) group (n = 10). Patient data were recorded of age, gender, type of odontoid fracture, morphological measurement results obtained from computed tomography images, treatment regimens, duration of stay in the hospital, and mortality rate. In the operating room, a halo-vest corset or Philadelphia-type cervical collar was applied to the surgery (-) patients after the reduction of the fracture under fluoroscopy. Anterior odontoid lag screw fixation was performed on surgery (+) patients. The amount of displacement of the fractured odontoid, the distance between the C1 vertebra and the odontoid process, the angle between the posterior wall of the odontoid process and the posterior wall of the clivus, the slip angle, and the anterior to posterior width of the spinal canal were not different between the groups. No difference was determined between the groups in respect of the amount of lateral displacement of the odontoid process in the spinal canal in the axial plane and the angle of the fractured odontoid process with the C2 vertebral body. This preliminary study showed that the demographic data and radiological measurement parameters analyzed in the present study could not be used as predictive markers either in decision-making for treatment modality or mortality risk.


Immunization with oral poliovirus vaccine in China.
China began to produce oral, live poliovirus vaccine ( OPV ) in 1960. During 1960-1964, OPV was introduced in major cities only and subsequently was used throughout the country. Since that time the incidence of poliomyelitis has dropped dramatically, and the percentage of the healthy population with antibody has clearly risen. Data from many observations showed a high rate of isolation of other enteroviruses in the healthy population and in individuals with poliomyelitis. These findings indicate that some paralytic cases may be caused by other enteroviruses. Localized outbreaks of poliomyelitis still occur, however, and their elimination will require a campaign to ensure that greater than 90% of susceptible individuals are immunized.


Differential effects of noradrenaline on evoked, spontaneous and miniature IPSCs in rat cerebellar stellate cells.
1. The modulation by noradrenaline (NA) of synapses among stellate cells was investigated in rat cerebellar slices by using presynaptic loose cell-attached recording and postsynaptic whole-cell recording. 2. NA increased the frequency of spontaneous IPSCs recorded from stellate cells without changing their mean amplitude. 3. NA increased the firing rate of stellate cells. This effect persisted after blocking ionotropic glutamate receptors and GABA receptors, indicating that it was independent of synaptic input. 4. The effects of NA on action potential frequency were mimicked by the beta-receptor agonist isoprenaline but not by the alpha-receptor agonist 6-fluoro noradrenaline, and they were not blocked by the alpha-receptor antagonist phentolamine, indicating that they were mediated by beta-receptors. 5. In paired recordings of connected stellate cells, NA slightly decreased the success rate of synaptic transmission. A small decrease in mean IPSC amplitude (excluding failures) and a slight increase in latency were also observed in NA. 6. These results show that, while NA increases the number of action potential-dependent IPSCs by increasing the firing rate of stellate cells, it actually reduces the probability of evoked release. Since previous studies showed that NA increases the rate of miniature IPSCs in this preparation, we conclude that different mechanisms underly the modulation by NA of action potential-dependent and action potential-independent transmitter release.


Energy-flow dynamics in the molecular channel of propanal photodissociation, C2H5CHO --> C2H6 + CO: direct ab initio molecular dynamics study.
Direct ab initio molecular dynamics calculations have been carried out for the molecular channel of the photodissociation of propanal, C2H5CHO --> C2H6 + CO, at the RMP2(full)/cc-pVDZ level of ab initio molecular orbital theory. The initial conditions were generated using the microcanonical sampling to put the excess energy randomly into all vibrational modes of the TS. Starting from the TS, a total of approximately 700 trajectories were numerically integrated for 100 fs. The obtained final energy distributions for the C2H6 and CO fragments and their relative translational motion were found to be quite similar to those obtained for the acetaldehyde reaction, CH3CHO --> CH4 + CO, in our previous study (Chem. Phys. Lett. 2006, 421, 549) despite the fact that the number of degree of freedom for C2H6 is larger than that for CH4. The coupling between the intrinsic reaction coordinate and one of the generalized normal modes orthogonal to it was predicted substantially strong around s = 1.4 amu(1/2) bohr, and it is expected that the energy flow out of C2H6 proceeds through this coupling. However, the obtained energy distributions strongly suggest that the coupling among the modes in C2H6 is quite small and the intramolecular energy redistribution does not occur efficiently in this molecule.


Differential expression of multiple somatostatin receptors in the rat cerebellum during development.
The present study describes the expression pattern of somatostatin receptor genes during the development of rat cerebellum. Characterization of somatostatin receptors was carried out by binding studies using receptor subtype-selective ligands in the germinative epithelium and granule cell layer of the cerebellum from postnatal day 4 (P4) to P21 and in granule cell cultures. Quantitative reverse transcription-PCR carried out for the five receptor subtype mRNAs in cerebellar extracts showed that sst1 mRNAs are predominant at the end of gestation. A transient high expression of the sst2 gene was observed from P7 to P14. In parallel, high levels of binding sites sensitive to sst2 ligands were detected in the granule cell germinative epithelium and in granule cell cultures. sst3 mRNAs rapidly increased from P14 and became the predominant form at P21, but respective binding sites were not detected. Whereas sst4 mRNA levels were generally low, those of sst5 were nearly undetectable. Reverse transcription-PCR carried out in granule cell cultures revealed the relative abundance of sst mRNAs as follows: sst2 > sst1 > sst3 = sst4. sst5 mRNA was undetectable. The results show the expression of four somatostatin receptor genes, but only three receptors (sst1, sst4, and mainly sst2) were detected as binding sites during cerebellar development.


Stochastic optimal velocity model and its long-lived metastability.
In this paper, we propose a stochastic cellular automaton model of traffic flow extending two exactly solvable stochastic models, i.e., the asymmetric simple exclusion process and the zero range process. Moreover, it is regarded as a stochastic extension of the optimal velocity model. In the fundamental diagram (flux-density diagram), our model exhibits several regions of density where more than one stable state coexists at the same density in spite of the stochastic nature of its dynamical rule. Moreover, we observe that two long-lived metastable states appear for a transitional period, and that the dynamical phase transition from a metastable state to another metastable/stable state occurs sharply and spontaneously.


Nucleic acid therapeutics: concepts for targeted delivery to solid tumors.
Solid tumors form a heterogeneous group of diseases, although common features such as hyperproliferation, overexpression of certain growth factor receptors and deregulated vessel formation including leaky vasculature give the opportunity to target macromolecular drug and nucleic acid carriers to tumor tissue. Similar to other macromolecular drugs, nucleic acid carriers have to be designed to enable tumor targeting after systemic injection. Chemical modification of nucleic acids makes them resistant towards enzymatic degradation. Cationic lipids or polycations condense nucleic acids into small, virus-like structures and the surface modification with hydrophilic polymers allows passive accumulation in tumor tissue; tumor cell binding ligands allow cellular targeting. To avoid toxic side effects, biodegradable and biocompatible carriers were designed. The design of thermoresponsive gene carriers allowed their selective tumor accumulation by locoregional hyperthermia. As a therapeutic concept, tumor-specific delivery of antitumoral RNA was realized in an orthotopic brain tumor model. The combination of gene- and radio-therapy enabled selective accumulation of radionuclides in tumors and boosted antitumoral effects. Hence, combining a smart delivery concept for nucleic acids with a suitable therapeutic strategy will allow successful treatment of otherwise incurable malignant diseases.


Molecular characterization of Shigella species isolated from diarrheal patients in Tehran, Iran: phylogenetic typing and its association with virulence gene profiles and a novel description of Shigella invasion associated locus.
The present study aims to employ a multiplex PCR-based method for phylogenetic typing of Shigella and determine the frequency of several virulence genes among Shigella phylogenetic clades and species. Species identification, phylogenetic typing of 44 previously diagnosed Shigella isolates, and frequency of virulence genes and loci, virA, virB, virF, ipaBCD, ial, sen, and set1A were investigated through performing several PCR assays. Distribution of virulence genes among Shigella phylogenetic clades and species was determined by the statistical analysis. The identities of 40 isolates out of 44 were confirmed as Shigella, and these isolates were classified in four phylogenetic clades, S1 (7.5%), S2 (52.5%), S3 (20%), and S5 (20%) and 4 species, S. sonnei (52.5%), S. flexneri (22.5%), S. dysenteriae (20%), and S. boydii (5%). The prevalence of virA, virB, virF, ipaBCD, ial, sen, and set1A was determined as 67.5%, 72.5%, 72.5%, 65%, 75%, 40%, and 5%, respectively. The presence of sen, uidA, or set1A was found to be statistically correlated with either of Shigella phylogenetic clades or species. A significant statistically association was also determined between set1A and Shigella phylogenetic clades. Furthermore, the nucleotide sequence of invasion-associated locus (ial) was determined and mapped on Shigella genome through in silico analysis. The current study shows the distribution of Shigella isolates and its key virulence genes within the five recently described phylogenetic clades for the first time in the Asia. This is also the first description of ial nucleotide sequence and its exact location on Shigella genome after its initial identification.


Critical relevance of genomic gains of PRL-3/EGFR/c-myc pathway genes in liver metastasis of colorectal cancer.
The PRL-3 gene is involved in the liver metastasis of colorectal cancer (CRC) and oncogene addiction to anticancer therapy. In the present study genomic gains in PRL-3 and its pathway genes, c-myc and EGFR, were investigated in order to determine their clinical relevance during metastatic formation in primary CRC and corresponding liver metastases. The genomic gain statuses of PRL-3, EGFR, and c-myc were investigated using quantitative polymerase chain reaction (qPCR) analysis in 35 samples of CRC and corresponding liver metastases. In the primary CRC specimens, genomic gains in PRL-3, c-myc, and EGFR were observed in 4, 4, and 13 cases, respectively. A genomic gain in one gene was observed in 18 cases, and these genomic gains were mutually exclusive. In the liver metastasis specimens, genomic gains were observed in 14, 8, and 13 cases, respectively. The copy numbers of PRL-3 and c-myc were significantly higher in the liver metastases than in the primary CRC specimens (P=0.03, P=0.009, respectively). A genomic gain in PRL-3 was the most frequent gain in the liver metastases (P=0.004) and was partially redundant with a c-myc genomic gain. EGFR genomic gains were consistent between the primary CRC and the liver metastases (P=0.0000008). In addition, a genomic gain in any of the 3 genes was observed in 23 cases (66%). Among the clinicopathological factors that were assessed, an EGFR genomic gain was significantly associated with tumour size in the primary CRC and the liver metastases (P=0.04). A c-myc genomic gain was also significantly associated with the v factor of the primary tumours in the liver metastases (P<0.01). In conclusion, the genomic copy numbers of PRL-3, c-myc and EGFR were frequently characterised by aberrations in genomic gain in liver metastases from CRC; thus, these gene statuses exhibit potential for the identification of patients who are likely to respond positively to anticancer therapies.


Assessing the need for developing a comprehensive content-validated pressure ulcer guideline.
Healthcare professionals need evidence-based strategies and guidelines for care to optimize pressure ulcer prevention and management. Differences among pressure ulcer guidelines confuse caregivers, reducing consistency of care. To assess the need for a comprehensive content-validated guideline document, the Association for the Advancement of Wound Care Guideline Subcommittee evaluated current pressure ulcer guideline recommendations by compiling 10 pressure ulcer-specific guidelines existing before June 2008 on the National Guideline Clearinghouse website along with the National Pressure Ulcer Advisory Panel (draft), European Pressure Ulcer Advisory Panel (draft), and Wound Healing Society guidelines. Steps for each aspect of pressure ulcer management were compiled and inconsistent recommendations identified. Currently available pressure ulcer guidelines were found to differ in definitions, aspects of care, validation, evidence criteria, and procedural recommendations, potentially affecting consistency and quality of all aspects of pressure ulcer management, including diagnosis, prevention, treatment, and outcomes measurement. To address these inconsistencies, a comprehensive list of Pressure Ulcer Care Initiative (PUCI) steps was prepared for content validation and posted on www.aawconline.org, enabling healthcare professionals interested in improving the consistency and quality of pressure ulcer prevention and care to participate in this process. All steps with a content validity index > 0.75 (rated clinically relevant by survey respondents) and/or with A-level standardized clinical evidence support will be included in the comprehensive PUCI guideline. Content validation of recommendations is an important first step to improving the consistency of pressure ulcer care.


Complete oral rehabilitation in a case with severe dental fluorosis.
The authors have presented a technique of full occlusal rehabilitation in a case of severe dental fluorosis. In this technique, maxillary and mandibular anterior teeth were simultaneously prepared and restored first. This was followed by simultaneous preparation of maxillary and mandibular posterior teeth that were restored in canine guided occlusion. The technique and sequence followed here is unique and is not available in dental literature. This technique reduces number of appointments while fulfilling all objectives. Periodontal follow-up over 3 years was satisfactory. A restorative treatment protocol has been devised for fluorosis which will act as a guide for the dental practitioners.


Different Exercise Time on 5-HT and Anxiety-like Behavior in the Rat With Vascular Dementia.
Previous studies have demonstrated that pre-exercise suppresses anxiety-like behavior, but the effects of different exercise times on vascular dementia induced anxiety-like behavior have not been well investigated. The present study aims to investigate the underlying neurochemical mechanism of different pre-vascular-dementia exercise times on 5-HT and anxiety-like behavior in rats with vascular dementia. 32 Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group (S group, n = 8), vascular dementia group (VD group, n = 8), 1-week physical exercise and vascular dementia group (1WVD group, n = 8), and 4 weeks physical exercise and vascular dementia group (4WVD group, n = 8). 1 week and 4 weeks of voluntary wheel running were used as pre-exercise training. The vascular dementia model was established by bilateral common carotid arteries occlusion (BCCAo) for 1 week. But bilateral common carotid arteries were not ligated in the sham group. The level of hippocampal 5-HT was detected with in vivo microdialysis coupled with high-performance liquid chromatography (MD-HPLC). Elevated plus maze (EPM), open field (OF), and light/dark box test were used to test anxiety-like behavior. Compared with the C group, the hippocampal 5-HT was significantly decreased in the VD group after 1 week of ligated operation. The hippocampal 5-HT levels in 1WVD and 4WVD groups were substantially higher than the level in the VD group. The hippocampal 5-HT level has no significant difference among C, 1WVD, and 4WVD. Behavioral data suggested that the rats in the VD group developed obvious anxiety-like behavior after 1 week of ligation surgery. Still, the rats in 1WVD and 4WVD groups did not show significant anxiety-like behavior. Both 1 week and 4 weeks of voluntary running wheel exercise can inhibit the anxiety-like behavior in rats with vascular dementia by upregulating 5-HT levels in the hippocampus in the VD model.


The influence of antiestrogens on the release of plasminogen activator (uPA) by MDA-MB-231 and MCF-7 breast cancer cells.
Plasminogen activators are known to be involved in the metastatic spread of breast cancer. In the present study we examined the effects of antiestrogens [Analog II (1,1-dichloro-cis-2,3-diphenyl cyclopropane) (AII), ICI-182,780 (ICI) and tamoxifen (TAM)], on the in vitro release of uPA from estrogen receptor (ER)-positive MCF-7 (MCF) and ER-negative MDA-MB-231 (MDA) human breast cancer cell lines. Using a solid-phase radioassay, uPA activity was found to be higher in the culture medium from MDA cells compared to MCF cells. Aminocaproic acid, a specific plasmin inhibitor, produced a 50-60% reduction in the degradation of labeled substrate, in the solid phase assay, using culture medium from both cell lines, thus indicating that most of the proteolysis observed was due to uPA-mediated plasmin generation from plasminogen. In the absence of plasminogen, the enzyme activity was not detected in either the quantitative assay or by zymography. In MDA cells, uPA release was not altered by any of the antiestrogens used alone or in the presence of estradiol. In contrast, in MCF cells, ICI alone produced maximal inhibition (40%) of enzyme release, while estradiol alone produced a 120% increase in enzyme activity. When co-administered with estradiol, in MCF cultures, each antiestrogen reduced enzyme activity to control levels. Substrate gel zymography revealed that the urokinase-type PA is the predominant form of PA released by both cell lines. Comparison of the activity of all three antiestrogens used in this study indicates that ICI is the most potent inhibitor of enzyme activity in ER-positive MCF cells.


Removal of nitriles from synthetic wastewater by acrylonitrile utilizing bacteria.
This study describes the ability of two bacteria strains, isolated from an ABS resin manufacturing wastewater treatment system, to remove high acrylonitrile concentrations. Straight chain aliphatic nitrile compound (propionitrile, allyl cyanide); branch chain aliphatic nitrile compound (isobutyronitrilc) and aromatic nitrile compound (benzonitrile) removal by Comamonas testosteroni and Acidovorax sp. was also investigated. The results are: Comamonas testosteroni and Acidovorax sp. can remove acrylonitrile completely up to 1904.8 mg/L within 66.6 h and 1538.5 mg/L within 143.3 h, respectively. Comamonas testosteroni degraded acrylonitrile faster than Acidovorax sp., and accumulated much more acrylic acid in the medium than Acidovorax sp. The addition of acrylamide to the medium was removed by Comamonas testosteroni and Acidovorax sp. Both strains utilized acrylic acid, a metabolic by-product of acrylonitrile, as a carbon source and ammonium nitrogen, a metabolic by-product of acrylonitrile, as a nitrogen source for growth. Comamonas testosteroni and Acidovorax sp. removed propionitrile completely up to 1352.8 mg/L and 975.7 mg/L within 166.9 h, respectively. With isobutyronitrile as a substrate, more than 97.8% could be removed within 169.8 h by Comamonas testosteroni up to 1352.8 mg/L, and by Acidovorax sp. up to 975.7 mg/L. These two strains could remove allyl cyanide completely up to 775 mg/L within 49.1 h and benzonitrile completely up to 442.7 mg/L within 31.1 h. Because Comamonas testosteroni and Acidovorax sp. have good degrading ability for removing nitrile compounds they are expected to play an important role in the treatment of nitrile compounds.


Expressive metaphors in cancer narratives.
This article presents and interprets illness narratives, told by patients treated for cancer. The aim is to discuss the meaning of cancer metaphors. The interpretation focuses on the relationships of metaphors to bodily experience and to social and cultural levels. The experience of cancer and cancer therapy obviously involve the patient's body. To comprehend what is happening is a process full of uncertainty and obscurity. Metaphors, such as cancer "eating," are widespread and persistent while the meaning of that metaphor today mirrors new scientific and lay explanations of cancer and cancer treatment. Personal newly created metaphors express threatening experiences in which fear of losing oneself and fear of death are involved. Ambivalent hope in relation to treatment and caregivers is expressed. Creating new metaphors involves imaginatively using the available concepts and metaphors. Narrative communication gives access to patients' experiences of an unwanted and painful physiologic process leading to forced embodiment of sickness. Patients want consolation and must overcome solitude by articulating experience, being listened to, and, in this way, recreating and strengthening identity.


Safety and feasibility of esophageal self- expandable metal stent placement without the aid of fluoroscopy.
Self-expandable metal stents (SEMSs) are used for the management of certain esophageal conditions such as strictures, perforations, and fistulae. These can be placed using fluoroscopic control, endoscopic control, or a combination of both. We evaluated our institutional experience of placing a SEMS using only endoscopy without the aid of fluoroscopy to determine safety and feasibility using this technique. A retrospective review was performed to identify all patients who underwent esophageal SEMS from January 2010 to June 2015. Placement of SEMS was accomplished under direct endoscopic visualization without the aid of fluoroscopy. Esophageal lesion was initially identified during endoscopy and a fully covered SEMS was passed over the guide wire and deployed under direct vision. Misplacement of the SEMS during the procedure that required replacement with another new SEMS was considered as a failed procedure. Other periprocedural complications caused by placement of SEMS were noted. A total of 172 patients underwent 280 procedures for SEMS placement. Mean age was 66 years. The most common indication for SEMS placement was stricture in 248 (88%) procedures. Periprocedure SEMS misplacement occurred in 12 (4%) patients. However, only 8 (3%) patients needed to have a new SEMS placed during the same procedure. A total of 64 (23%) patients had migration of SEMS. There were no other periprocedure complications leading to adverse events. Self-expandable metal stent can be placed accurately and safely under direct endoscopic visualization without the aid of fluoroscopy.


Quantitative assessment of long-term changes in insulin secretion after canine duct-obliterated pancreas transplantation.
In this study, we have quantitatively assessed the changes in insulin-secreting capacity after duct-obliterated segmental pancreatic autotransplantation in dogs. To this end, we have used a technique for the sampling of the complete and undiluted pancreatic venous blood with simultaneous flow measurement, by which means the actual insulin-secreting capacity was determined in a direct fashion. Histologic changes were analyzed in addition in order to address the underlying mechanisms of the changes in insulin-secreting capacity. Intraoperative glucose-stimulated insulin secretion of the left pancreatic lobe was measured before (group I, n = 8), at 6 weeks (group II, n = 5), and at 18-24 months (group III, n = 7) after duct-obliterated segmental pancreatic autotransplantation. At all 3 intervals, histologic analysis was performed. Since the experiments in groups I-III were performed under general anesthesia, a 4th group of dogs (group IV, n = 6) was studied in addition in order to determine the effect of general anesthesia on glucose metabolism. K-values appeared to be reduced to 1/5 and peripheral insulin response (AUC) to about 1/3 of the values obtained from fasting conscious dogs. Although all animals in groups I-III had normal fasting glucose levels and normal K-values at each test interval, a 75% reduction of insulin secretion after duct-obliterated transplantation was observed. Insulin secretion not only showed marked quantitative changes but significant qualitative alterations in glucose-stimulated insulin response were found. Disturbance of functional islet architecture appears to be the main causative factor in the decrease in insulin secretion. If applicable to man, our results indicate that especially the duct-obliterated graft, with its borderline endocrine capacity, is prone to loss of sufficient graft function by the damage induced by eventual rejection crises.


Functional perfusion MRI predicts later occurrence of steroid-associated osteonecrosis: an experimental study in rabbits.
Ischemia is the defined pathway leading to steroid-associated osteonecrosis (ON). Early detection of ischemic condition may help predict later ON occurrence. Bone marrow perfusion function evaluation by perfusion magnetic resonance imaging (MRI) may be a unique modality for this application. Twenty-five adult male New Zealand white rabbits were used in this study. Lipopolysaccharide (LPS) and methylprednisolone (MPS) were administrated for ON induction based on a published protocol. T1-weighted and fat suppression T2-weighted MR imaging (conventional MRI) were performed for ON lesion detection based on the abnormal signal in the proximal femora at week 0 as the baseline (before LPS injection), and week 1 and week 2 after MPS injection. At the same time, the blood perfusion function in the proximal femora was measured by perfusion MRI. Maximum enhancement (ME)--an index of MRI perfusion function was analyzed. After MRI scanning, the proximal femora were prepared histopathologically for ON lesion analysis. The rabbit with bilateral histopathological ON lesions was defined as an ON+ rabbit and included in the ON+ group evaluated at week 1 and week 2, respectively, and the rabbit without ON lesions in bilateral femora was classified into the ON- group. For the underlying mechanism of perfusion change, the extravascular marrow fat cells were measured and the intravascular endothelium inflammation injury indicator of tissue factor (TF) expression and thrombus formation were detected. In ON+ group, ME in perfusion MRI showed a significant decrease at week 1 and week 2 as compared with the baseline (p < 0.01). There was a more than 50% decrease in ME at week 1 in ON+ group; whereas there were no detectable ON lesions by conventional MRI at week 1, though 93% (14/15) rabbits could be detected at week 2 in ON+ group. In ON- group, ME showed a slight decrease at week 1 (less than 30%), and nearly recovered to normal at week 2 as compared with the baseline. Histological results showed a much larger average marrow fat area and more severe marrow blood sinusoids compression from surrounding crowded fat cells, and stronger positive TF expression in marrow endothelium and more thrombus formation in ON+ rabbits than ON- rabbits. This study demonstrated that functional perfusion MRI could predict development of steroid-associated ON. Our experimental data suggested that perfusion MRI might be a sensitive noninvasive modality for monitoring steroid-associated ON in patients.


Human Endogenous Retroviruses in Neurological Diseases.
The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human endogenous retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively. Pathogenic HERV elements may thus provide a missing link in understanding these complex diseases. Moreover, their neutralization may represent a promising strategy to establish novel and more powerful therapeutic approaches.


Does correcting myths about the flu vaccine work? An experimental evaluation of the effects of corrective information.
Seasonal influenza is responsible for thousands of deaths and billions of dollars of medical costs per year in the United States, but influenza vaccination coverage remains substantially below public health targets. One possible obstacle to greater immunization rates is the false belief that it is possible to contract the flu from the flu vaccine. A nationally representative survey experiment was conducted to assess the extent of this flu vaccine misperception. We find that a substantial portion of the public (43%) believes that the flu vaccine can give you the flu. We also evaluate how an intervention designed to address this concern affects belief in the myth, concerns about flu vaccine safety, and future intent to vaccinate. Corrective information adapted from the Centers for Disease Control and Prevention (CDC) website significantly reduced belief in the myth that the flu vaccine can give you the flu as well as concerns about its safety. However, the correction also significantly reduced intent to vaccinate among respondents with high levels of concern about vaccine side effects--a response that was not observed among those with low levels of concern. This result, which is consistent with previous research on misperceptions about the MMR vaccine, suggests that correcting myths about vaccines may not be an effective approach to promoting immunization.


Ocular inflammation in patients using soft contact lenses.
Soft contact lenses cleaned and stored in thimerosal-containing solutions may produce an ocular inflammatory process and, if untreated, corneal neovascularization. We examined 38 patients who were using soft contact lenses and found that 31 patients had positive ocular provocation test results to a thimerosal-preserved artificial tears solution. Delayed hypersensitivity to thimerosal was demonstrated by positive patch tests in 27 patients. Avoidance of thimerosal and the use of unit-dose sterile saline solutions has resulted in complete resolution of ocular symptoms.


Evacuation of Vulnerable and Critical Patients: Multimodal Simulation for Nurse-Led Patient Evacuation.
Virtual simulation (VS) is an adaptable medium for teaching critical disaster management skills such as efficient hospital evacuation. We aimed to compare VS and prerecorded narrated multimedia lecture-based training of pediatric nurses for evacuation of a sick newborn in the neonatal intensive care unit and pediatric emergency department (ED) using live evacuation simulations. Thirty neonatal intensive care unit and 30 ED nurses enrolled with 30 randomized to multimedia lecture and 30 randomized to VS, with equal block distribution of nurses from each unit. Pretraining/posttraining surveys were administered, and live evacuation simulations were scored for time to evacuation, items collected, and communication. Overall, disaster preparation and communication improved within the VS group as compared with the multimedia lecture group. Virtual simulation rated more immersive (P < 0.001), better at safety threat identification (P < 0.05), and better at evacuation preparation compared with multimedia lecture (P < 0.01). Virtual simulation participants felt more prepared in disaster response (P < 0.001) and patient evacuation (P < 0.001). Both groups packed equal essential items, but VS participants packed more equipment (mean, 19 vs. 15, P < 0.01) with no significant evacuation time difference between the VS group (145 ± 58 seconds) and multimedia lecture group (152 ± 59 seconds, P = not significant). Virtual simulation participants had better communication ratings with the charge nurse (P < 0.05) and family (P < 0.001). Virtual simulation was well received by nurses compared with multimedia lecture and may be an effective adjunct for training nurses on infant patient evacuation during a disaster.


Computed tomography with gas cisternography for detection of small acoustic tumors. A study of five false-positive results.
Cranial computed tomography (CT) with gas cisternography is reported to be the most accurate method of detection of small acoustic tumors. However, five false-positive CT results experienced in three years are now reported. This is a false-positive rate of 22% for tumors with less than 5-mm protrusion into the cerebellopontine angle, and a false-positive rate of 50% for tumors with less than 2-mm protrusion. A false-positive result is suspected if no mass protrudes at the porus or if gas enters the lateral internal auditory canal.


Association between chronic periodontitis and serum lipid levels.
Regarding the high prevalence of hyperlipidaemia, which is one of the major risk factors of cardiovascular disease, and uncertain reports about the relation between periodontal disease and serum lipid profile, this study was conducted to assess this relation. The historical cohort study was conducted on 52 cases including 26 persons with chronic periodontitis as case group, and 26 healthy subjects as control group. Both groups had the same age and weight ranges, sex, and diet, without any periodontal treatment history in the past six months, underling systemic disease such as diabetes, anti-hyperlipidemic drugs or active tobacco smoking history. Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG) and Total Cholesterol (CHOL) were measured by direct enzymatic assay. TG level was 128.4 +/- 71.1 mg/dl in control group and 165.2 +/- 83.7 in case group indicating a significantly higher level in case group (P<0.05). In control group, 30.8 percent and in case group, 61.5 percent had abnormal serum cholesterol levels, which presents a significantly higher level in case group (P<0.03). Other serum level indices did not show any significant difference. Although it seems that patients with chronic periodontal disease are more susceptible to hyperlipidemia, it is doubtful that the former causes an increase in serum lipid levels, so we suggest studying the effects of treating chronic periodontitis on serum lipid level.


Use of surface plasmon resonance imaging to study viral RNA: protein interactions.
Surface plasmon resonance imaging (SPRi) is an emerging microarray technology that is label-free, rapid and extremely flexible. Here the capabilities of SPRi are demonstrated in results of proof-of-concept experiments detailing a method for studying viral genomic RNA:protein interactions in array format. The principal RNA is the well-characterized origin of assembly (OAS) containing region of Tobacco mosaic virus (TMV) RNA, whereas the principal protein is the primary subunit for TMV virion assembly, the 20S capsid protein aggregate. DNA probes complementary to TMV and non-TMV RNA fragments were covalently attached to a thin gold layer deposited on glass. These DNA probes were used to discreetly capture in vitro transcribed TMV and Red clover necrotic mosaic virus (RCNMV) RNA2 (used as a negative control for the subsequent protein binding). The 4S TMV capsid protein monomers were isolated from TMV particles purified from infected plants of Nicotiana tabacum L. and were induced to form 20S stacked disc aggregates. These 20S stacked disc aggregates were then injected onto the array containing the RNA fragments captured by the DNA probes immobilized on the microarray surface. The discrete and preferential binding of the 20S stacked disc aggregates to the array locations containing the TMV OAS RNA sequence was observed. The results demonstrate that SPRi can be used to monitor binding of large RNA molecules to immobilized DNA capture probes which can then be used to monitor the subsequent binding of complex protein structures to the RNA molecules in a single real-time, label-free microarray experiment. The results further demonstrate that SPRi can distinguish between RNA species that have or do not have an origin of assembly sequence specific for a particular viral capsid protein or protein complex. The broader implications of these results in virology research are found in other systems where the research goals include characterizing the specificity and kinetics of viral or host protein or protein complex interactions with viral nucleic acids.