Idiopathic premature ventricular complexes treatment: Comparison of flecainide, propafenone, and sotalol.
Beta-blockers (BB) or dihydropyridine calcium channel blockers (CCBs) are still the first choices in the treatment of idiopathic premature ventricular complexes (PVCs), with low-modest efficacy. Antiarrhythmic drugs (AADs) of Ic class are moderate to highly efficient but the evidence on their benefits is still limited. To compare effectiveness and safety of flecainide, propafenone, and sotalol in the treatment of symptomatic idiopathic PVCs. Our single-center retrospective study analyzed 104 consecutive patients with 130 medication episodes of frequent idiopathic PVCs treated with AADs flecainide, propafenone (Ic class) or sotalol (III class). The primary outcome was complete/near complete reduction of PVCs after medication episode (PVCs burden reduction >99%), and the secondary outcome was significant PVC burden reduction (≥80%). The complete/near complete PVCs burden reduction occurred in 31% and was significant in 43% of treated patients. A reduction of PVC burden for >99% was achieved in 56% of patients on flecainide, in 11% of patients on propafenone (p = .002), and in 21% of patients receiving sotalol (p = .031). There was no difference between propafenone and sotalol (p = .174). A reduction of PVC burden for ≥80% was achieved in 64% of patients on flecainide, in 30% of patients on propafenone (p = .009), and 33% of patients on sotalol (p = .020). There was no difference between propafenone and sotalol (p = .661). The efficacy of AADs class Ic and III in the treatment of idiopathic PVCs was modest. Flecainide was the most effective AAD in the achievement of complete/near complete or significant PVC burden reduction, compared to propafenone and sotalol.


Ifosfamide and VP-16213 combination chemotherapy combined with ablative chemotherapy and autologous marrow transplantation as salvage treatment for malignant lymphoma.
Eighteen patients with high-grade malignant lymphoma were treated with ifosfamide-VP16213 combinations after failing to respond completely or after relapsing on CHOP-like therapy. Responders to the salvage therapy were subsequently treated with ablative chemotherapy (BCNU, VP-16213, Ara-C and melfalan) and autografted. Of these 18 patients six were in relapse, six were partial responders and six failed CHOP-like therapy. There were two complete remissions and seven partial responses to the ifosfamide-VP-16213 combinations. Of them, eight patients were transplanted, together with one non-responder. Four of these nine patients were disease-free survivors 18-34 months after autografting. There were two early deaths: one before and one during the autografting procedure. Using one of the best salvage therapy combinations followed by high-dose chemotherapy and autografting is feasible. The results in this pilot study suggest that an appreciable number of patients may be cured by this procedure.


Associations between environmental covariates and temporal changes in malaria incidence in high transmission settings of Uganda: a distributed lag nonlinear analysis.
Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in malaria incidence. The study investigated the effect of environmental covariates on malaria incidence in high transmission settings of Uganda. This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period. Estimates of monthly malaria incidence (MI) were derived from MRCs' catchment areas. Environmental data including monthly temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed lag nonlinear model was used to investigate the effect of environmental covariates on malaria incidence. Overall, the median (range) monthly temperature was 30 °C (26-47), rainfall 133.0 mm (3.0-247), NDVI 0.66 (0.24-0.80) and MI was 790 per 1000 person-years (73-3973). Temperature of 35 °C was significantly associated with malaria incidence compared to the median observed temperature (30 °C) at month lag 2 (IRR: 2.00, 95% CI: 1.42-2.83) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 8.16 (95% CI: 3.41-20.26) at lag-month 4. Rainfall of 200 mm significantly increased IRR of malaria compared to the median observed rainfall (133 mm) at lag-month 0 (IRR: 1.24, 95% CI: 1.01-1.52) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 1.99(95% CI: 1.22-2.27) at lag-month 4. Average NVDI of 0.72 significantly increased the cumulative IRR of malaria compared to the median observed NDVI (0.66) at month lags 2-4, with the highest cumulative IRR of 1.57(95% CI: 1.09-2.25) at lag-month 4. In high-malaria transmission settings, high values of environmental covariates were associated with increased cumulative IRR of malaria, with IRR peaks at variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.


Microvascular density of breast cancer in bone metastasis: influence of therapy.
Bone is the most frequent site of systemic progression of breast cancer (BRC). Angiosuppressive therapy has now entered the management of progressing cancers, therefore it is clinically important to obtain information on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) of bone metastasis of BRC. VEGF expression and MVD were evaluated in bone metastases of BRC immunohistochemically in paraffin samples of 18 patients and compared to their primary tumors. MVD was determined by using the hot-spot method and the endothelial marker, CD34. Chemo- and/or endocrine therapy-naïve BRC cases progressed to the bone with a concomitant increase in their angiogenic potential, suggesting that this is the "natural history" of BRC progression. On the other hand, this study revealed that vascularization of the bone metastases of BRC patients that had received adjuvant (chemo- and/or endocrine) therapy was significantly decreased compared to the corresponding primary tumors, also supported by a decreased VEGF expression in metastases, both suggesting that the treatment significantly affected the angiogenic phenotype of the progressing disease. Angiosuppressive therapy is a new approach to cancer management including BRC and is frequently applied in the advanced stage of disease. Tumors with a prominent angiogenic phenotype (high MVD and VEGF) are primary candidates for such regimes. The fact that chemo-endocrine adjuvant therapy of BRC resulted in a weaker angiogenic phenotype in bone metastases compared to non-treated cases may suggest that these latter patients are better candidates for angiosuppressive interventions.


A fuzzy-based shared controller for brain-actuated simulated robotic system.
The primary problems of brain-computer interface (BCI) are the low channel capacity and high error rate. Therefore, an assistive motion control method is important for the brain-actuated robot to realize real-time and reliable control. To make the brain-actuated robot respond to the external environments with more flexibility, a shared control method based on fuzzy logic is proposed. Experimental results obtained with ten healthy voluntary subjects show that the proposed fuzzy-based shared controller has improved performance compared with direct control approach.


The detection of intracytoplasmic interleukin-2 in Jurkat E6.1 and human peripheral blood mononuclear cells using direct conjugate, two-colour, immunofluorescent flow cytometry.
The most commonly used approaches for the estimation of cytokine protein production involve the quantification of cytokines produced, and accumulated, in a complex body fluid or supernatant of cultured cells, by means of a bioassay or immunoassay, but these techniques do not permit an estimation of the frequency or phenotype of cytokine-producing cells. Traditional methods use immunohistochemical based techniques which can be difficult to perform and interpret, whereas flow cytometry has the advantage of objective assessment and standardisation and is less labour intensive. In this study we have established a rapid and sensitive technique for the simultaneous detection of intracellular IL-2 in conjunction with CD3. Polyclonal goat anti-IL-2 and control goat IgG were conjugated to FITC and then separated from free fluorochrome using column chromatography. PHA activated PBMC or Jurkat E6.1 cells were fixed in paraformaldehyde and permeabilised with saponin, followed by the addition of directly conjugated antibodies (FITC anti-IL-2 or PE anti-CD3) alone or in combination. Samples were then analysed using a flow cytometer and the percentage of dual labelled cells calculated. Several methods have been previously established for the detection of intracellular cytokines using flow cytometry and employing multiple layers of antibodies in the detection steps. By using direct conjugates the technique is less time consuming, requires fewer controls and can be used to examine cytokine production by identifiable cell phenotypes in a mixed cell population.


Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance.
To clarify the relationship between diabetes mellitus and carbohydrate digestion, the activities of sucrase and isomaltase, which form a complex enzyme (SI complex) on the brush border membranes, were compared in the progression of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resistance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic controls. Until 40 weeks of age, OLETF rats were obese and had a high plasma glucose level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM became very severe with advancing insulin resistance in OLETF rats. In OLETF rats, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrease in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF rats; however, at 40 and 48 weeks of age, the plasma insulin level in the non-fasting state in OLETF rats was not significantly different from that in LETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level.


WAIS-III General Ability Index in neuropsychiatry and forensic psychiatry inpatient samples.
The purpose of this study is to examine the WAIS-III General Ability Index (GAI) in a sample of 33 neuropsychiatry inpatients and 47 forensic psychiatry inpatients. The GAI is comprised of the six subtests that form the Verbal Comprehension and the Perceptual Organization Indexes. The GAI, although highly correlated with the FSIQ, was on average 5.3 points higher in the neuropsychiatry sample and 4.2 points higher in the forensic psychiatry sample. The GAI was significantly higher than the Working Memory and the Processing Speed Indexes in both groups. The GAI, a composite measure of verbal and nonverbal intellect, appears to be an appropriate measure for use in day-to-day clinical practice in neuropsychology. To facilitate clinical use, statistically reliable difference scores between the GAI and the WMI and PSI, for the 95% confidence interval, are presented.


Threshold nonlinearities and signal detection theory.
The review summarizes Kulikowski's contributions to the mechanisms involved in visual detection and discrimination. His findings provide strong evidence for the existence of 'barriers' which block weak activity in the visual system. It is proposed that the properties of these barriers may underlie near-optimal detection in conditions of signal uncertainty.


PS-5, a new beta-lactam antibiotic. I. Taxonomy of the producing organism, isolation and physico-chemical properties.
Antibiotic PS-5 is a new beta-lactam antibiotic isolated from fermentation broths of Streptomyces sp. strain A271. The strain was considered to be a new subspecies of Streptomyces cremeus and the name, Streptomyces cremeus subsp. auratilis, was proposed. Fermentative production, isolation and physico-chemical properties of PS-5 are described.


Local direction of edge motion causes and abolishes the barberpole illusion.
The perceived direction of motion of a one-dimensional grating is measured in straight-edged rectangular and indented rectangular apertures. It is shown that the perceived direction of motion of the pattern is largely determined by the directions of motion at the edges, rather than by the aspect ratio or global shape of the aperture. The edge motion vectors appear to be calculated at a remarkably local scale. The barberpole illusion is abolished when indentation size equals or exceeds one-quarter of the grating period. This critical size is scale invariant with grating period and corresponds well with a quadrature model of motion perception.


A proposal for standardized grading of chronic changes in native kidney biopsy specimens.
Chronic changes represent an important component of native kidney biopsy evaluation and have a major bearing on predicting prognosis and guiding treatment. We propose here a uniform, semiquantitative approach to assessing such changes, which include glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis, and we report these findings as an overall chronicity grade.


Rare Osteochondroma of the Posterior Talar Process: A Case Report.
Osteochondromas are benign bone tumors that arise from divergent cartilage formation, most commonly in childhood versus adulthood. We report the case of a healthy 42-year-old woman who presented with an unusual solitary posterolateral ankle mass with associated pain and ankle impingement with 6-week follow-up. The patient was successfully treated with open surgical excision, with bone sent for pathologic diagnosis of benign osteochondroma. The patient returned to normal baseline function with no pain at 6-week follow-up. An open posterior ankle incision approach was performed to remove suspicious enlarged bony growth from the posterior talar process to be sent for pathologic evaluation. Pathologic evaluation reported benign osteochondroma of the posterior talar process, and the patient subsequently had routine healing of the postoperative incision site and return to full function without pain or disability at 6-week follow-up. This case study adds to the current understanding, incidence, occurrence, and treatment of rare osteochondromas occurring in the posterior talar process.


Construction and validation of a predictive nomogram for ferroptosis-related genes in osteosarcoma.
Ferroptosis is a new type of cellular regulation of necrosis that has attracted great attention in recent years, which is different from the traditional mode of autophagy, apoptosis, and necrosis. Studies suggest that ferroptosis is key to the occurrence and development of tumors. Here, we investigated the prognostic significance of ferroptosis-related genes (FRGs) in osteosarcoma (OS) using RNA transcriptome data from 88 OS samples collected from the UCSC Xena platform. We defined the OS sample from the UCSC platform as the training cohort and the GEO dataset (GSE21257 and GSE16091) as the validation cohorts. We assessed 73 up-regulated and 63 down-regulated FRGs. We divided patients from the UCSC database into groups at high risk and low risk and built a prognostic risk model to assess prognosis using five FRGs: MT1G, G6PD, ARNTL, BNIP3, and SQLE. High-risk OS patients presented a lower survival rate. These results were confirmed in the validation groups. In the training group, the areas under the ROC curves (AUC) were as follows: 0.880 for 1 year, 0.833 for 3 years, and 0.818 for 5 years. In the GSE21257 validation cohort, the AUC were as follows: 0.770 for 1 year, 0.641 for 3 years, and 0.632 for 5 years survival, and in the GSE16091 were 0.729 for 1 year, 0.663 for 3 years, and 0.735 for 5 years survival. These findings suggest that FRGs are associated with the prognosis of osteosarcoma. Moreover, our prognostic risk model can predict overall survival in osteosarcoma. This provides new ideas for the clinical diagnosis and personalized treatment of osteosarcoma.


Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure.
Although it is widely accepted that clinical trials in heart failure may not apply to older populations, the magnitude of the discrepancy between trial populations and patients seen in community-based practice are not known. Our objective was to determine the proportion of older persons meeting enrollment criteria of randomized controlled trials of agents that prolong life in heart failure. We conducted a cross-sectional study of Medicare beneficiaries >64 years old with the principal diagnosis of heart failure who were discharged from acute care hospitals in the United States between April 1998 and March 1999. Enrollment criteria of the Studies of Left Ventricular Dysfunction (SOLVD), Metroprolol CR/LX Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), and Randomized Aldactone Evaluation Study (RALES) trials were applied to the population, and the proportions meeting the criteria were determined by subgroups of age and sex. Of the 20,388 patients studied, 18%, 13%, and 25% met the enrollment criteria of the SOLVD, MERIT-HF, and RALES trials, respectively. Although trial eligibility was less than a third for any sex or age group, significantly fewer women than men met trial criteria (13% vs 23% for SOLVD, 11% vs 17% for MERIT-HF, and 21% vs 32% for RALES, P <.0001 for all). The oldest patients were also less likely to fulfill enrollment criteria. The proportion of all patients not included because of preserved left ventricular systolic function was twice as large as the proportion meeting the inclusion criteria for any trial. A minority of hospitalized older persons with heart failure fit the profile of populations of clinical trials. There is an urgent need for research in heart failure for typical heart failure patients, including the very old, women, and patients with preserved left ventricular systolic function.


[Influence of the blight of Morinda officinalis How on microscopic structure and constituents of the host].
The results showed that microscopic structure in biennial roots, the contents of B and Mn in nutritive organ and beta-sitosterol content in roots, stems of Morinda officinalis were affected markedly. The total sugar content in the roots and aerial stems was decreased by 5.42%-15.29%.


Thorough survey and analysis of pulmonary lymphoepithelioma-like carcinoma in Macau and multimodality treatment for advanced disease.
Pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. The clinical course and prognosis of advanced LELC are largely unknown. Few reports have discussed multimodality treatment for LELC. This retrospective study identified records from 2007 to 2018 of pulmonary LELCs and other lung cancer subtypes from hospital information systems and collected demographic, treatment, and survival data. In this cohort of 69 LELCs (median age: 55.4), more female, non-smokers, and fewer right upper lobe tumors (4.3%) were observed in the LELC subgroup compared with others. The median overall survival (OS) of LELCs was 40 months, superior to other subtypes (p < 0.05), except adenocarcinoma (p = 0.062). Patients with early stage disease and primary tumor resection tended to have better OS in univariate analysis, but surgery was the independent predictor in multivariate analysis (0.042). The median OS of 52 advanced LELCs was 22.7 months. Platinum-based chemotherapy and radiotherapy with curative purpose were independent predictors for OS of advanced LELCs (p = 0.004 and 0.003, respectively). For patients who received multimodality treatment in advanced setting, the median line of treatments was two. The overall response and disease-control rates were 61.8% and 80.6%, respectively. There were no differences in response or survival between patients receiving taxane-combined and non-taxane-combined chemotherapy. However, patients treated with radiotherapy in upfront settings had significantly favorable response and progression-free survival compared with those without. One case with PD-L1 positivity had pembrolizumab in the 4th line and achieved tumor shrinkage and stable disease for 12 months. Patients who underwent radical resection of primary tumors had better prognoses. Patients with advanced LELC could achieve satisfactory survival by receiving multimodality treatment, including platinum-based chemotherapy and/or radiotherapy. Immune checkpoint inhibitors may be part of future therapies. A well-organized clinical trial should be performed to determine the optimal treatment regimen.


Toxins as tools in the study of sodium channel distribution in the muscle fibre membrane.
The number of tetrodotoxin molecules bound to the membrane of the fibres of muscles in normal conditions and after detubulation produced by glycerol-induced osmotic shock pointed to a higher sodium channel density at the surface membrane than at the membrane in the transverse tubules. Study of the maximum rate of rise of the action potential at the junctional and nonjunctional regions of the muscle fibre membrane suggested that the Na+ channel density is also not the same along the muscle fibre membrane, being higher at the junctional region. Further studies on the distribution of the Na+ channel along the muscle fibre membrane were carried out with the use of (1) the loose patch voltage-clamp technique, (2) labelling the Na+ channels with fluorescently labelled scorpion toxins, (3) autoradiography of localized Na+ channels with 125I-labelled scorpion toxins, and (4) toxins that induce persistent activation of the Na+ channel. The studies referred to in (1), (2) and (3) demonstrate that the density of the Na+ channel is much higher at the junctional region than elsewhere in the membrane of the muscle fibre. On the other hand, in experiments carried out on curarized rat diaphragms several sodium channel activating toxins (crotamine, Phoneutria nigriventer venom, its toxin PhTx2, veratrine) were found to produce a much greater depolarization of the membrane at the junctional region than at nonjunctional regions. However, it was also found that some toxins (veratridine, batrachotoxin) depolarized equally well the junctional and nonjunctional regions. Two alternative hypotheses to explain the uniform depolarization of the muscle fibre membrane induced by these toxins are suggested.


Soil gross nitrogen transformations along the Northeast China Transect (NECT) and their response to simulated rainfall events.
Climate changes are predicted to increase extreme rainfall events in semiarid and arid region in Northern Hemisphere. Nutrient cycles will be affected by the precipitation changes but so far only very little is known how soil N transformations may respond. Here we investigated gross soil N transformation rates and their response to simulated rainfall events across Northeast China Transect (NECT). The results showed that gross N mineralisation rate, nitrification rate and nitrification to mineralisation ratio significantly increased as the humidity index decreased along NECT, resulting in NO3(-) as the predominant inorganic N form. These characteristics could increase the risk of NO3(-) losses but at the same time reduce the risk of N losses via volatilization in the semiarid and arid region. The soil-plant ecosystems have developed effective N conservation strategies in the long term with respect to the prevailing climate in arid region. However, compared to humid soils more dramatic changes of soil N transformation rates are likely to occur in arid soils, after sudden soil moisture increases. Soil N conservation mechanisms in arid regions were drastically affected when the heavy rainfall frequently occurred. Arid ecosystems are expected to be more vulnerable than humid ecosystems in response to extreme rainfall events.


Simultaneous bioremediation of petroleum hydrocarbons and production of biofuels by the micro-green alga, cyanobacteria, and its consortium.
There are two major problems in the world, fuel deficiency and environmental pollution by fossil fuels. Microalgae are regarded as one of the most feasible feedstocks for the manufacturing of biofuels and are used in the degradation of fossil fuel spills. The present study was possessed to investigate the ability of green alga Chlorella vulgaris, blue-green alga Synechococcus sp, and its consortium to grow and degrade hydrocarbon such as kerosene (k) with different concentrations (0, 0.5, 1, and 1,5%), and also using algal biomasses to produce biofuel. The algal growth was estimated by optical density (O.D) at 600 nm, pigment contents such as Chlorophyll a,b carotenoid, and dry weight. The kerosene degradation was estimated by FT-IR analysis after and before the cultivation of algae and its consortium. The components of the methanol extract were determined by GC-MS spectroscopy. The results denote the best growth was determined by O.D, algae consortium with 1.5% Kerosene after ten days, meanwhile, the highest dry weight was with C. vulgaris after ten days of cultivation. The FT-IR demonstrated the algae and consortium possessed high efficacy to degrade kerosene. After 15 days of algae cultivation with 1% K, C.vulgaris produced the maximum amount of lipids (32%). The GC-MS profile of methanol extract of two algae and consortium demonstrated that Undecane was presented in high amounts, C.vulgaris (19.9%), Synechococcussp (82.16%), algae consortium (79.51%), and also were presented moderate amounts of fatty acid methyl ester in Synechococcus sp. Overall, our results indicate that a consortium of algae can absorb and remove kerosene from water, and at the same time produce biofuels like biodiesel and petroleum-based fuels.


Ethnic differential item functioning in the assessment of quality of life in cancer patients.
Past research has shown that Filipino cancer patients report lower levels of quality of life (QoL) than other ethnic groups. One possible explanation for this is that Filipinos do not define QoL in the same manner as others, resulting in bias in their assessments. Hence, Filipinos would not necessarily have lower QoL. Item response theory methods were used to assess differential item functioning (DIF) in the quality of life (measured by the EORTC QLQ-C30) of cancer patients across four ethnic groups (Caucasian, Filipino, Hawaiian, and Japanese). The sample consisted of 359 cancer patients. Results showed the presence of DIF on several items, indicating ethnic differences in the assessment of quality of life. Relative to the Caucasian and Japanese groups, items related to physical functioning, cognitive functioning, social functioning, nausea and vomiting, and financial difficulties exhibited DIF for Filipinos. On these items Filipinos exhibited either higher or lower QoL scores, even though their overall QoL was the same. This evidence may explain why Filipinos have previously been found to have lower overall QoL. Although Filipinos score lower on QoL than other groups, this may not reflect lower QoL, but rather differences in how QoL is defined. The presence of DIF did not appear, however, to alter the psychometric properties of the QLQ-C30.


Late thrombotic occlusion of saphenous vein grafts: successful recanalization using thrombolytic therapy.
We report two cases in which thrombosis was the primary cause of vein graft occlusion many years after bypass surgery. Both displayed minimal thrombolysis immediately after a selective infusion of streptokinase but were patent when reimaged hours later. Such therapy may be helpful when graft occlusions are associated with a large volume of thrombus.


A model to calculate the average interaction energy and adhesion force between petroleum asphaltenes and some metallic surfaces.
A model is proposed to account for the interaction energy and adhesion force between petroleum asphaltenes and metallic surfaces. It is assumed that the total molecule-surface interaction potential may be constructed through superposition of corresponding interactions with a relevant number of atomic layers forming the substrate and resorting to the Lindhard continuum planar potential (CPP) approximation, which requires only of knowledge of binary molecule-atom interactions. Molecular mechanics (MM) calculations are performed to generate the average binary interaction between the asphaltene molecule and an atom in the substrate, which in turn is represented by a parameterized analytical--physically sound--expression. The resulting CPP yields an analytical expression representing the interaction between the asphaltene molecule and each substrate layer. To validate the method, pilot calculations are performed for a sample asphaltene molecule with a fixed orientation relative to metallic surfaces of iron, aluminum, and chromium. Comparison between corresponding CPP and MM calculations for the asphaltene-plane (A-P) and asphaltene-substrate (A-S) interactions indicate reasonable agreement pointing to the adequacy of the CPP method to represent molecule-surface interactions. Also, the effect of a surrounding (i.e., solvent) medium is addressed with the use of a dielectric constant, epsilon, incorporated in the molecule-atom potential. Finally, a discussion is presented on the applicability of the method to generate an analytical universal expression for asphaltene-metallic wall interactions.


Effect of treatment delay on outcome of patients with early-stage head-and-neck carcinoma receiving radical radiotherapy.
Access to radiotherapy (RT) has been considerably reduced in Quebec since the late 1980s. The aim of the present study was to analyze the impact of delaying treatment on the outcome of patients with early head-and-neck squamous cell carcinomas. This retrospective analysis examined the outcome for all 623 patients with early-stage disease (T1-2, N0-1) who received radical RT between 1988 and 1997 at the Hotel Dieu of Quebec Hospital. Delay was defined as the time from initial evaluation by a radiation oncologist to the beginning of RT. Delay intervals were divided as follows: <30 days, 31-40 days, and >40 days. A delay of >40 days was significantly associated with an increased risk of local and neck failure and poorer survival relative to patients treated in <30 days or between 31 and 40 days. The adjusted hazard ratio and (in parentheses) the 95% confidence interval was 2.6 (1.07-6.4), 2.73 (1.38-5.4), and 1.7 (1.1-2.6), respectively, for local failure, neck failure, and survival. In the subgroup of patients with T2N0 disease, delaying RT for >30 days was associated with a poor outcome, as measured by the same end points. Delaying RT had a deleterious effect on these patients. RT should be started as soon as possible in patients with squamous cell carcinoma of the head and neck, preferably within 20-30 days after evaluation by a radiation oncologist.


Recent concepts in the conservative treatment of intracranial tumours in children.
The role of radiotherapy for certain intracranial tumours, given either postoperatively or as the sole treatment in inoperable cases, is discussed, principally in relation to medulloblastoma, ependymoma, cerebral astrocytoma, brain-stem glioma and craniopharyngioma. Methods of increasing the response of gliomas to irradiation are mentioned and reference is made to the possible value of chemotherapy and of immunotherapy as adjuvants against such tumours. Treatment results are reported and consideration given to the quality of long-term survival.


Breaking the cycle of excessive conservatism: Evaluating the γ-radiation dose from building materials.
Radionuclide content in building materials is regulated in most European countries by calculating the activity concentration index. The I-index does not account for the properties nor the application of the material but provides a conservative evaluation of the annual γ-radiation dose. Using a Monte Carlo toolkit, EGSnrc, this study calculated doses from building materials in less conservative set-ups by focusing on materials with a potential for recycling NORM residues, such as Portland cement, ceramics, gypsum, and mineral insulation. It was observed that proper consideration of building material geometry strongly affected the indoor dose rate. Regulating low-density materials and finishing materials such as gypsum and insulation under the same framework as high-density and high-bulk materials proved problematic because the doses differ by orders of magnitude. The current reference values for radionuclide concentrations used in calculating the I-index do not apply to most construction materials. For many types of building materials, higher radionuclide concentrations in the material could be allowed without contradicting the annual effective dose reference for the public. This illustrates the potential for boosting the use of NORM residues in various construction applications.


Inhibition of benzo[a]pyrene metabolism by insulin, FITC-insulin and an FITC-insulin-antibody conjugate in the human hepatoma cell line HepG2.
Benzo[a]pyrene (BaP) can be metabolically activated to an ultimate carcinogen, (+)-anti-BaP-7,8-dihydrodiol-9,10-epoxide [(+)-anti-BaPDE] by cells in culture. This activation involves oxidation by specific isoforms of cytochrome P450s such as CYP1A1. The human hepatoma cell line, HepG2, was used to examine the effect of inhibition of CYP1A1 activity by anti CYP1A1 specific antibodies on BaP metabolism. Metabolism of BaP to water-soluble metabolites by HepG2 cells in culture was 50% lower in fluorescein isothiocyanate (FITC)-insulin-CYP1A1-antibody-conjugate-treated cells than in control cells. However, FITC-insulin (lacking anti CYP1A1 conjugates) or insulin alone also decreased BaP metabolism by 50%. This insulin-induced inhibition of BaP metabolism was observed for cultures treated with a concentration range of FITC-insulin from 50-1000 nM. FITC-conjugated gamma-globulin showed no significant binding to HepG2 cells by fluorescence microscopy, however, FITC-insulin-antibody conjugates bound extensively, suggesting that FITC-insulin conjugates still retain the ability to bind insulin receptors. These results demonstrate that free insulin, FITC-insulin or FITC-insulin conjugated to antibodies are effective inhibitors of BaP metabolism in cells in culture.


A radiolabel-release microwell assay for proteolytic enzymes present in cell culture media.
A modified method for the measurement of proteolytic enzyme activity in cell culture-conditioned media has been developed. Using the release of 3H-labeled peptides from 3H-labeled gelatin the method is performed in microwell plates. The substrate is insolubilized and attached to the wells by glutaraldehyde treatment, thus eliminating the need for a precipitation step at the end of the assay. The assay is sensitive, reproducible, and convenient for small sample volumes. The effect of different protease inhibitors on activity can be assessed rapidly allowing an early characterization of the enzyme. It can also be adapted to microplate spectrophotometric analysis by staining residual substrate with Coomassie blue.


Sequences of the genes encoding argininosuccinate synthetase in Escherichia coli and Saccharomyces cerevisiae: comparison with methanogenic archaebacteria and mammals.
The nucleotide (nt) sequences of the genes encoding argininosuccinate synthetase from Escherichia coli K-12 (argG) and Saccharomyces cerevisiae (ARG1) were determined. The deduced amino-acid sequences were compared to each other and to their counterparts in two methanogens and in mammals. Three regions are highly conserved. Two of them appear to contain possible Walker-type nt-binding sites [Walker et al., EMBO J. 1 (1982) 945-951] and are therefore candidates for ATP-binding sites. The third region shows some similarity to a short portion of the N-proximal part of the PurA enzyme which catalyses an analogous reaction.


Analysis of respiratory events in obstructive sleep apnea syndrome: Inter-relations and association to simple nocturnal features.
This study carefully evaluates the association of different respiration-related events to each other and to simple nocturnal features in obstructive sleep apnea-hypopnea syndrome (OSAS). The events include apneas, hypopneas, respiratory event-related arousals and snores. We conducted a statistical study on 158 adults who underwent polysomnography between July 2012 and May 2014. To monitor relevance, along with linear statistical strategies like analysis of variance and bootstrapping a correlation coefficient standard error, the non-linear method of mutual information is also applied to illuminate vague results of linear techniques. Based on normalized mutual information weights (NMIW), indices of apnea are 1.3 times more relevant to AHI values than those of hypopnea. NMIW for the number of blood oxygen desaturation below 95% is considerable (0.531). The next relevant feature is "respiratory arousals index" with NMIW of 0.501. Snore indices (0.314), and BMI (0.203) take the next place. Based on NMIW values, snoring events are nearly one-third (29.9%) more dependent to hypopneas than RERAs. 1. The more sever the OSAS is, the more frequently the apneic events happen. 2. The association of snore with hypopnea/RERA revealed which is routinely ignored in regression-based OSAS modeling. 3. The statistical dependencies of oximetry features potentially can lead to home-based screening of OSAS. 4. Poor ESS-AHI relevance in the database under study indicates its disability for the OSA diagnosis compared to oximetry. 5. Based on poor RERA-snore/ESS relevance, detailed history of the symptoms plus polysomnography is suggested for accurate diagnosis of RERAs.


Bcl6 middle domain repressor function is required for T follicular helper cell differentiation and utilizes the corepressor MTA3.
T follicular helper (Tfh) cells are essential providers of help to B cells. The transcription factor B-cell CLL/lymphoma 6 (Bcl6) is a lineage-defining regulator of Tfh cells and germinal center B cells. In B cells, Bcl6 has the potential to recruit distinct transcriptional corepressors through its BTB domain or its poorly characterized middle domain (also known as RDII), but in Tfh cells the roles of the Bcl6 middle domain have yet to be clarified. Mimicked acetylation of the Bcl6 middle domain (K379Q) in CD4 T cells results in significant reductions in Tfh differentiation in vivo. Blimp1 (Prdm1) is a potent inhibitor of Tfh cell differentiation. Although Bcl6 K379Q still bound to the Prdm1 cis-regulatory elements in Tfh cells, Prdm1 expression was derepressed. This was a result of the failure of Bcl6 K379Q to recruit metastasis-associated protein 3 (MTA3). The loss of Bcl6 function in Bcl6 K379Q-expressing CD4 T cells could be partially rescued by abrogating Prdm1 expression. In addition to Prdm1, we found that Bcl6 recruits MTA3 to multiple genes involved in Tfh cell biology, including genes important for cell migration, cell survival, and alternative differentiation pathways. Thus, Bcl6 middle domain mediated repression is a major mechanism of action by which Bcl6 controls CD4 T-cell fate and function.


Pelvic floor muscle function differs between supine and standing positions in women with stress urinary incontinence: an experimental crossover study.
In women with stress urinary incontinence, how does pelvic floor muscle (PFM) function differ between supine and standing when assessed using manometry, vaginal palpation, dynamometry and electromyography? An experimental crossover study. A total of 101 women with stress urinary incontinence were included. The PFM evaluations were performed and compared in supine and standing positions. The participants were assigned to either Group 1 (assessments in supine followed by standing) or Group 2 (assessments in standing followed by supine). The primary outcome was the PFM pressure during the maximum voluntary contraction (MVC). Secondary outcomes were the measures of PFM pressure at rest; PFM function (PERFECT scheme); active and passive forces (dynamometry); and PFM electromyography (EMG) activity. The mean MVC pressure was significantly lower in standing (MD -7 cmH2O, 95% CI -10 to -4). The mean PFM resting pressure was higher in standing (7 cmH2O, 95% CI 5 to 10). Three measures of PFM function derived from vaginal palpation were better in supine than in standing. The PFM active and the passive forces measured using dynamometry were higher in standing (0.18 kgf, 95% CI 0.16 to 0.20). The resting EMG activity was higher in standing than in supine (MD 3.6 μV, 95% CI 2.6 to 4.5), whereas EMG activity during MVC was higher in supine than standing (MD -8.7 μV, 95% CI -12.5 to -4.8). The pressure and EMG activity during MVC, and PFM function were lower in standing. The resting pressure, the passive and active forces of the PFM and the resting EMG activity of the PFM were higher in standing.


The CAIX inhibitor SLC-0111 exerts anti-cancer activity on gastric cancer cell lines and resensitizes resistant cells to 5-Fluorouracil, taxane-derived, and platinum-based drugs.
Gastric cancer (GC) is the fifth most frequent malignancy and the fourth leading cause of worldwide cancer-related death. Despite the usage of multimodal perioperative chemotherapy (pCT), GC progressively gains chemoresistance, thereby, the identification of suitable targets to overcome drug resistance is fundamental. Amongst the potential biomarkers, carbonic anhydrase IX (CAIX) - associated with a poor prognosis of several solid cancers - has gained the most attention. In a cohort of GC patients who received perioperative FLOT (i.e., Leucovorin, 5-Fluouracil, Docetaxel, and Oxaliplatin) or FOLFOX (i.e., Leucovorin, 5-Fluouracil, and Oxaliplatin), non-responder patients showed an increased expression of tumor CAIX compared to responder group. Moreover, GC cell lines induced to be resistant to 5-Fluouracil, Paclitaxel, Cisplatin, or the combination of 5-Fluorouracil, Oxaliplatin, and Docetaxel, overexpressed CAIX compared to the control. Accordingly, CAIX-high-expressing GC cells showed increased therapy resistance compared to low-expressing cells. Notably, SLC0111 significantly improved the therapy response of both wild-type and resistant GC cells. Overall, these data suggest a correlation between CAIX and GC drug resistance highlighting the potential of SLC-0111 in re-sensitizing GC cells to pCT.


Brain noradrenaline and varieties of alternation learning.
Depletion of noradrenaline from the locus coeruleus system was effected by intraperitoneal injection of 6-hydroxydopamine to neonatal rat pups. Spontaneous, and two paradigms of rewarded alternation behaviour were examined in a T-maze. No change was seen in spontaneous alternation but marked impairment in acquisition of one of the two rewarded alternation tasks was found. It is concluded that powerful support is offered to previous results using intracerebral adult 6-hydroxydopamine administration.


[Problems caused by asbestos].
Asbestos has become a pollutant of ambiant air and there is a lack of informations allowing a reliable evaluation of the health risk related to the levels of concentrations found in the community. Biological significance of short fibres, analytical methodology and permissible levels are discussed under the view of the future needs for research.


A follow-up study of adiposity and growth of Jerusalem schoolchildren from age 6 to 14 years.
This study evaluated growth and change in adiposity from childhood to early adolescence in 587 Jerusalem schoolchildren examined in both the first and eighth grades. Mean body mass index, height, and weight were determined according to demographic variables and menstrual status and were compared to international reference populations. Menstruating females were taller and heavier than nonmenstruating females at both ages and were more overweight at age 14 years. Height and weight were positively correlated with social class for boys, and few differences were found among ethnic groups. Study subjects were shorter than reference subjects, and study girls were more overweight than reference girls at age 14 years. Our findings suggest that previously demonstrated ethnic differences in growth and adiposity among Israeli children are disappearing. Adolescent girls appear to be at greatest risk for developing obesity. The relationship of pubertal status to body size and obesity at and between the two ages is discussed.


T lymphoblastic lymphoma with LEU-7 positive phenotype and unusual clinical course: a multiparameter study.
Immunologic phenotype studies were performed on cells and on frozen sections of involved tissue from a 20 year old female with typical T-cell lymphoblastic (convoluted) lymphoma. The cells demonstrated a thymic phenotype but in addition marked with Leu-7 (HNK-1)--an antibody reported to identify human natural killer/killer (NK/K) cells. Normal or neoplastic cells with this phenotype have not been previously reported. These findings support the existence of a thymic precursor for a T-cell subset of Leu-7 + cells. The unusual clinical response to therapy is another feature of this unique case.


Reliability of video-based identification of footstrike pattern and video time frame at initial contact in recreational runners.
Two-dimensional video recordings are used in clinical practice to identify footstrike pattern. However, knowledge about the reliability of this method of identification is limited. To evaluate intra- and inter-rater reliability of visual identification of footstrike pattern and video time frame at initial contact during treadmill running using two-dimensional (2D) video recordings. Thirty-one recreational runners were recorded twice, 1 week apart, with a high-speed video camera. Two blinded raters evaluated each video twice with an interval of at least 14 days. Kappa values for within-day identification of footstrike pattern revealed intra-rater agreement of 0.83-0.88 and inter-rater agreement of 0.50-0.63. Corresponding figures for between-day identification of footstrike pattern were 0.63-0.69 and 0.41-0.53, respectively. Identification of video time frame at initial contact ranged from five frames to 12 frames (95% limits of agreement). For clinical use, the intra-rater within-day identification of footstrike pattern is highly reliable (kappa>0.80). For the inter-rater between-day identification inconsistencies may, in worst case, occur in 36% of the identifications (kappa=0.41). The 95% limits of agreement for identification of video time frame at initial contact may, at times, allow for different identification of footstrike pattern. Clinicians should, therefore, be encouraged to continue using clinical 2D video setups for intra-rater identification of footstrike pattern, but bear in mind the restrictions related to the between day identifications.


Five-year survival does not equal cure in non-small cell lung cancer: a Surveillance, Epidemiology, and End Results-based analysis of variables affecting 10- to 18-year survival.
Five-year survival after the diagnosis of non-small cell lung cancer is the most common benchmark used to evaluate long-term survival. Data on survival beyond 5 years are sparse. We sought to elucidate variables affecting 10- to 18-year survival. A total of 31,206 patients alive at least 5 years after diagnosis of non-small cell lung cancer who were registered in the Surveillance, Epidemiology, and End Results database from 1988 to 2001 were examined. Primary end points were disease-specific survival and overall survival. Survival analysis was performed with Kaplan-Meier estimates, multivariable Cox proportional hazards regression, and competing risk models. Overall survival at 10, 15, and 18 years was 55.4%, 33.1%, and 24.3%, respectively. Disease-specific survival at 10, 15, and 18 years was 76.6%, 65.4%, and 59.4%, respectively. In multivariable regression analysis, squamous cell cancers had a disease-specific survival advantage (hazard ratio, 0.88; P < .0001) but an overall survival disadvantage (hazard ratio, 1.082; P = .0002) compared with adenocarcinoma. Pneumonectomy (hazard ratio, 0.44) and lobectomy (hazard ratio, 0.474) had improved disease-specific survival compared with no surgery (P < .0001). Left-sided tumors (hazard ratio, 0.723; P = .036) and node-negative cancers (hazard ratio, 0.562; P < .001) also had a better disease-specific survival and, to a lesser extent, overall survival advantage. Five-year survivors of non-small cell lung cancer have a persistent risk of death from lung cancer up to 18 years from diagnosis. More than one half of all deaths in 5-year survivors are related to lung cancer. In multivariable regression analysis, age, node-negative disease, and lobar or greater resection were strong predictors of long-term survival (ie, 10-18 years).


Quality of acute asthma care: an audit of clinical practice in a Victorian health service.
Gaps in the treatment of patients with acute asthma have been repeatedly described in Australia. We conducted a retrospective audit of acute asthma care at a Victorian tertiary institution. To describe acute asthma care at a large health network in metropolitan Melbourne, and evaluate the extent to which Emergency Department (ED) care was consistent with National Asthma Council guidelines. A retrospective audit was performed of medical records between July 2017 and June 2019. We included adult patients admitted to campuses within the Western Health network in Melbourne, Victoria, where the length of stay was at least 12 h, and the primary discharge diagnosis was asthma. Four hundred and ninety-three admissions were included in the analysis, representing 392 individual patients. Seventy-one percent of patients were female and 27% were current smokers. Ninety-six percent of patients had a prior asthma diagnosis, 63% had a previous hospital presentation and 75% were prescribed an inhaled preventer. In the ED, systemic corticosteroids and inhaled salbutamol were prescribed in 65% and 82% admissions respectively; adjunctive treatments included ipratropium (67% of admissions), magnesium sulfate (30%), adrenaline (11%) and non-invasive ventilation (9%). Overall, ED care was guideline concordant in 59% of admissions. On the wards, treatments prescribed within 24 h of admission included corticosteroids (90% of admissions), salbutamol (84%), ipratropium (64%) and inhaled preventers (63%). The proportion of patients prescribed these treatments, as well as documented follow up (e.g. asthma action plans), varied significantly depending on the treating specialty. The emergency treatment of patients with acute asthma frequently deviated from guidelines and there was significant variation in inpatient treatment. Quality improvement initiatives that incorporate structural changes are required to improve asthma care.


Refractory hypotension secondary to chronic treatment with high doses of quetiapine.
Quetiapine is an atypical antipsychotic used in the treatment of depressive, schizophrenic, or bipolar disorders. It acts on dopamine D1 and D2, histamine, and 5HT1A and 5HT2 receptors. However, it also acts as an antagonist for α1 receptors causing cardiovascular side effects, including hypotension. We present the case of a patient chronically medicated with Quetiapine who developed hypotension refractory to vasoconstrictors and intraoperative fluid therapy. Noradrenalin has a strong α1 effect with lower affinity for β2 receptors unlike adrenalin. This translates into peripheral vasoconstriction and an improved clinical picture. Therefore, it should be considered the vasoactive drug of choice in patients on high doses of Quetiapine.


Vascular cognitive impairment: A preventable component of dementia.
For many decades during the 20th century, the common belief was that the slow strangulation of the brains' blood supply from hardening of the brain arteries led to chronic brain ischemia and neuronal death. Not surprisingly, to counter this, vasodilators rapidly became one of the most commonly used and profitable medications worldwide; however, no clinical benefits were ever proven. In the 1970s and early 1980s cerebral blood flow studies strongly disproved the idea of brain failure due to chronic ischemia. It was also shown that infarcts and not chronic ischemia caused dementia, leading to the concept of multiinfarct dementia. In addition to infarcts, it was then realized that other vascular lesions can also cause cognitive decline. Gradually, as "atherosclerotic dementia" lost ground, Alzheimer's disease (AD) that once had been considered a presenile dementia and rare, became almost synonymous with dementia. Subsequent memory-based definitions and evaluations of dementia led to a bias in favor of diagnosing AD, overshadowing vascular contributions. The widespread use of brain imaging in the 1980s and 1990s contributed to the resurgence of evidence of cerebrovascular diseases. Moreover, it was shown that most cognitive impairment of the elderly results from mixed pathologies, emphasizing the need for a change in the traditional categorical diagnosis of dementia, e.g., AD vs vascular dementia. The alternative diagnostic method was named the vascular cognitive impairment approach, meaning identifying any impairment caused by or associated with vascular factors. The importance of this approach is that vascular lesions are currently the most important treatable and preventable components of dementia, even before any symptoms manifest, i.e., at the brain at risk stage. This chapter provides a summary of the vascular cognitive impairment approach to diagnosis, treatment, and prevention of cognitive decline.


Proton pump inhibitors and odds of cholangiocarcinoma: A retrospective case-control study.
Proton pump inhibitors (PPIs) have been reported to be associated with cholangitis and might possibly be carcinogenic. However, few studies have been conducted to investigate the association of PPIs with cholangiocarcinoma (CCA). Thus, a hospital-based case-control study was carried out in China to explore the association between PPIs and CCA. In this study, 1468 CCA cases (826 intrahepatic cholangiocarcinoma (ICC) and 642 extrahepatic cholangiocarcinoma (ECC)) were included, which were observed at Beijing Friendship Hospital, from February 2002 to October 2018. We retrospectively extracted PPI use and other possible risk factors from clinical records, followed by an investigation of the relationship with CCA via calculation of odds ratios (ORs), adjusted odds ratios (AORs), and 95% confidence intervals (CIs) using logistic regression analysis. PPIs were used by 135 (9.2%) CCA cases and 173 (5.9%) controls. We found that PPI use was associated with a 1.61-fold elevated CCA odds (P < .001) (AOR = 1.61, 95% CI = 1.28-2.05; P < .001). After stratification by CCA subtypes, the AORs of PPIs were consistent for both CCA subtypes, with ORs of 1.36 (AOR = 1.36, 95% CI = 1.02-1.83; P = .003) and 1.95 (AOR = 1.95, 95% CI = 1.46-2.62; P < .001) for ICC and ECC respectively. Our results also showed that PPI use was slightly linked to the odds of CCA in a dose-dependent manner. PPI use was correlated with a significant 61% increased odds of CCA, particularly in the ECC. However, the retrospective design and observational nature cannot establish causation. Larger scale, multi-centre prospective studies are required for further validation.


Influence of data sampling methods on the representation of neural spiking activity in vivo.
In vivo single-unit recordings distinguish the basal spiking properties of neurons in different experimental settings and disease states. Here, we examined over 300 spike trains recorded from Purkinje cells and cerebellar nuclei neurons to test whether data sampling approaches influence the extraction of rich descriptors of firing properties. Our analyses included neurons recorded in awake and anesthetized control mice, and disease models of ataxia, dystonia, and tremor. We find that recording duration circumscribes overall representations of firing rate and pattern. Notably, shorter recording durations skew estimates for global firing rate variability toward lower values. We also find that only some populations of neurons in the same mouse are more similar to each other than to neurons recorded in different mice. These data reveal that recording duration and approach are primary considerations when interpreting task-independent single neuron firing properties. If not accounted for, group differences may be concealed or exaggerated.


Preparation of paramagnetic ferroferric oxide-calcined layered double hydroxide core-shell adsorbent for selective removal of anionic pollutants.
Adsorption is one of the most common methods of pollution treatment. The selectivity for pollutants and recyclability of adsorbents are crucial to reduce the treatment cost. Layered double hydroxide (LDH) materials are one type of adsorbent with poor recyclability. Prussian blue (PB) is a sturdy and inexpensive metal-organic framework material that can be used as the precursor for synthesizing paramagnetic ferroferric oxide (Fe3O4). It is intriguing to build some reusable adsorbents with magnetic separation by integrating LDH and PB. In this work, paramagnetic Fe3O4-calcined LDH (Fe3O4@cLDH) core-shell adsorbent was designed and prepared by the calcination of PB-ZnAl layered double hydroxide (PB@LDH) core-shell precursor, which exhibits high anionic dyes selectivity in wastewater solutions. The paramagnetism and adsorption capability of Fe3O4@cLDH come from the Fe3O4 core and calcined ZnAl-LDH shell, respectively. Fe3O4@cLDH shows an adsorption capacity of 230 mg g-1 for acid orange and a high selectivity for anionic dyes in cation-anion mixed dye solutions. The regeneration process indicates that the high selectivity for anions is related to the specific hydration recovery process of ZnAl-LDH. The synergistic effect of the paramagnetic Fe3O4 core and calcined ZnAl-LDH shell makes Fe3O4@cLDH an excellent magnetic separation adsorbent with high selectivity to anions.


Intestinal responses to hyperosmolar glucose infusion in dogs.
Physiological and morphological changes of small intestine after hyperosmolar glucose infusions into canine jejunum were studied using in vivo perfusion model. Infusions of 40 ml of 50% and 20% glucose solution into the jejunal loops induced biphasic osmolar degression in the lumen. Osmolarity of jejunal venous blood was rapidly increased and maintained the maximal level (approximately 320 mOM/L). Blood flow to the jejunal loop was significantly increased after 50% glucose infusion compared to 5% glucose infusion. Most characteristic electron microscopic change of jejunal epithelial cell was pseudo-pod like process projected into the jejunal lumen, which was very similar to that of cholera.


Modulation of quinolinic acid-induced depletion of striatal NADPH diaphorase and enkephalinergic neurons by inhibition of nitric oxide synthase.
The present study was designed to examine the role of nitric oxide (NO) in quinolinic acid (QUIN)-induced depletion of rat striatal nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and enkephalinergic neurons. Intrastriatal injection of QUIN produced a dose-dependent decrease in NADPH diaphorase and enkephalin positive cells, with cell loss being evident following the injection of 6 and 18 nmol QUIN, respectively. To evaluate the role of NO in QUIN-induced toxicity, animals were pretreated with the non-specific nitric oxide synthase (NOS) inhibitor, Nomega-nitro-l-arginine (l-NAME) or the selective neuronal NOS inhibitor, 7-nitro indazole (7-NI). l-NAME (2x250 mg/kg, i.p. 8 h apart) maximally inhibited striatal NOS activity by 85%, while 7-NI (50 mg/kg, i.p.) maximally inhibited striatal NOS activity by 60%. Pretreatment with l-NAME or 7-NI potentiated the loss of NADPH diaphorase neurons resulting from intrastriatal injection of low doses of QUIN (18 nmol). Neither NOS inhibitor had any effect on the loss of striatal NADPH diaphorase neurons induced by a higher dose of QUIN (24 nmol). In contrast, 7-NI partially prevented the QUIN (18 and 24 nmol)-induced loss of enkephalinergic neurons, while l-NAME had no effect. These results indicate that NO formation may play a role in QUIN-induced loss of enkephalinergic neurons, but not in the loss of NADPH diaphorase neurons.


Grit Levels of Graduate Nursing Students: Why Grit Is Needed in Nursing.
The coronavirus disease 2019 (COVID-19) pandemic has created a need for nurses who are perseverant and passionate, the definition of grit. This study examined grit levels in Master in Nursing (MSN) and Doctor of Nursing Practice (DNP) students. MSN and DNP students were surveyed using the Grit-S scale, which is composed of two parts: Grit-CI (consistency of interest) and Grit-PE (perseverance of effort). Overall, graduate nursing students had high levels of grit as measured by the Grit-S (M = 3.9, SD = 0.5). Perseverance was higher for both MSN and DNP students than passion (M = 4.2, SD = 0.5 vs. M = 3.6, SD = 0.7). There was no difference in Grit-S levels related to program type. Graduate nursing students had high levels of grit. With the challenges faced by nursing professionals during the COVID-19 pandemic, nurses with high grit levels may avoid burnout and persevere though challenges. [J Nurs Educ. 2022;61(4):197-200.].


m6A-mediated upregulation of lncRNA RMRP boosts the progression of bladder cancer via epigenetically suppressing SCARA5.
Aim: This study aimed to elucidate the relationship between SCARA5 and RMRP in bladder cancer and their underlying mechanism. Methods: Biological functions were evaluated using cell-counting kit 8 assay, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays. RNA immunoprecipitation, RNA pull-down and chromatin immunoprecipitation were employed. A xenograft tumor model in nude mice was also conducted. Results & conclusion: RMRP and SCARA5 exhibited an inverse correlation. Downregulation of RMRP significantly suppressed bladder cancer cell proliferation, migration and invasion, which was reversed by SCARA5 overexpression. RMRP recruited DNA methyltransferases to the promoter region of SCARA5, thereby triggering the methylation of the SCARA5 promoter to epigenetically suppress its expression. Our findings elucidate the machinery by which RMRP, stabilized by METTL3, exerts a promoter role in bladder cancer tumorigenesis by triggering SCARA5 methylation.


Global mRNA decay analysis at single nucleotide resolution reveals segmental and positional degradation patterns in a Gram-positive bacterium.
Recent years have shown a marked increase in the use of next-generation sequencing technologies for quantification of gene expression (RNA sequencing, RNA-Seq). The expression level of a gene is a function of both its rate of transcription and RNA decay, and the influence of mRNA decay rates on gene expression in genome-wide studies of Gram-positive bacteria is under-investigated. In this work, we employed RNA-Seq in a genome-wide determination of mRNA half-lives in the Gram-positive bacterium Bacillus cereus. By utilizing a newly developed normalization protocol, RNA-Seq was used successfully to determine global mRNA decay rates at the single nucleotide level. The analysis revealed positional degradation patterns, with mRNAs being degraded from both ends of the molecule, indicating that both 5' to 3' and 3' to 5' directions of RNA decay are present in B. cereus. Other operons showed segmental degradation patterns where specific ORFs within polycistrons were degraded at variable rates, underlining the importance of RNA processing in gene regulation. We determined the half-lives for more than 2,700 ORFs in B. cereus ATCC 10987, ranging from less than one minute to more than fifteen minutes, and showed that mRNA decay rate correlates globally with mRNA expression level, GC content, and functional class of the ORF. To our knowledge, this study presents the first global analysis of mRNA decay in a bacterium at single nucleotide resolution. We provide a proof of principle for using RNA-Seq in bacterial mRNA decay analysis, revealing RNA processing patterns at the single nucleotide level.


Unfulfilled Needs in the Detection, Diagnosis, Monitoring, Treatment, and Understanding of Glaucoma in Blacks Globally.
Glaucoma is an ophthalmic disorder that affects a significant number of Blacks globally. A leading cause of this condition is an age-related enlargement of the lens and increased intraocular pressure. Although Blacks are affected by glaucoma at a higher rate than their Caucasian counterparts, there remains a lack of emphasis placed on the detection, diagnosis, monitoring, and treatment of glaucoma in this population. Education regarding glaucoma in the African and African American populations is essential to reducing rates of glaucoma-related visual impairment and improving treatment success. In this article, we highlight specific issues and limitations to the management of glaucoma, which affects Blacks at a higher rate. In addition, we also review the backgrounds of Blacks globally and examine historical events that have contributed to financial inequality and wealth/health disparities affecting glaucoma management. Lastly, we suggest reparations and solutions that health care professionals can use to improve glaucoma screening and management.


Mapping the experiences of people with achalasia from initial symptoms to long-term management.
Achalasia is a rare motility disorder affecting the oesophagus, which is associated with a range of symptoms and different treatment strategies. Currently, little is known about people's experiences with achalasia and its management. This study aimed to understand the experiences of people living with achalasia, from the initial onset of symptoms to long-term management. This qualitative study explored the journey of people living with achalasia and outlined the care pathway using a process map. Ten female and five male participants living with achalasia (age range: 40-73) took part, and all aspects of their diagnosis, treatment and management were discussed. A process map showing people's experiences by separating the management of their condition into a series of steps was developed to present the pathway in the participants' journey. The analysis involved discussing the process map within the research team. The process map comprised of 10 steps, which occurred before and after diagnosis. The developed map indicates that most participants managed their on-going symptoms through stress management techniques and dietary changes. Key issues that participants highlighted about their journey managing achalasia were misdiagnosis, delay in diagnosis and lack of support in the long-term management of achalasia. This research was a novel study exploring patients' experiences and management of achalasia and mapping their journey. Two distinct phases to their journeys were identified: before and after diagnosis. Areas highlighted by this study can provide a basis for future research, in particular behaviour change to support the long-term management of achalasia.


Quantitative Infrared Pupillometry in Nonconvulsive Status Epilepticus.
Nonconvulsive status epilepticus (NCSE) is a frequent disorder in neurocritical care and diagnosing it can be challenging. NCSE patients often show altered pupil function, but nature and extent may vary. Infrared pupillometry allows detection of subtle changes of pupil function. The neurological pupil index (NPi) is considered a surrogate marker of global pupil function which is supposed to be independent of absolute parameters such as the pupil diameter. Cross-sectional observational study to assess whether NPi is altered in NCSE. 128 consecutive adult emergency patients who had experienced a suspected seizure, have not reached their prior functional level regarding level of consciousness, mental status or focal deficits, had no obvious clinical signs of status epilepticus and had an EEG indication as determined by the treating clinician for exclusion of NCSE were examined by routine EEG and pupillometry. Exclusion criteria were ocular comorbidity (n = 21) and poor EEG quality (n = 4). Pupillometry was performed once directly before the beginning of EEG recording. NCSE diagnosis (no NCSE, possible NCSE and confirmed NCSE) was established according to Salzburg consensus criteria blinded to pupillometry results. Group comparison was performed for right NPi, left NPi, lowest NPi of both sides (minNPi) and the absolute difference of both sides (diffNPi) applying non-parametric testing. In post-hoc analysis, receiver operating characteristics (ROC) of NCSE diagnosis (combined confirmed NCSE and possible NCSE) were performed for minNPi and diffNPi. From 103 patients included in the final analysis, 5 (4.9%) had confirmed NCSE, 7 (6.8%) had possible NCSE. Right NPi (p = 0.002), left NPi (p < 0.001) and minNPi (p < 0.001) were significantly lower in "confirmed NCSE" and "possible NCSE" compared to "no NCSE"; diffNPi was significantly higher in "confirmed NCSE" and "possible NCSE" compared to "no NCSE" (p < 0.001). There was no significant difference of minNPi and diffNPi between "confirmed NCSE" and "possible NCSE". ROC analysis showed an optimal cut-off of minNPi for NCSE diagnosis of 4.0 (AUC = 0.93, 95% CI 0.86-0.99). Optimal ROC analysis cut-off of diffNPi for NCSE diagnosis was 0.2 (AUC = 0.89, 95% CI 0.80-0.99). NPi was significantly reduced and the difference between left and right NPi was significantly higher in confirmed NCSE. An NPi < 4.0 on either side as well as an NPi difference of both sides > 0.2 may be potential indicators of NCSE. Infrared pupillometry may be a helpful diagnostic tool in the assessment of NCSE and should be studied further in larger populations.


Integrated omics approaches provide strategies for rapid erythromycin yield increase in Saccharopolyspora erythraea.
Omics approaches have significantly increased our understanding of biological systems. However, they have had limited success in explaining the dramatically increased productivity of commercially important natural products by industrial high-producing strains, such as the erythromycin-producing actinomycete Saccharopolyspora erythraea. Further yield increase is of great importance but requires a better understanding of the underlying physiological processes. To reveal the mechanisms related to erythromycin yield increase, we have undertaken an integrated study of the genomic, transcriptomic, and proteomic differences between the wild type strain NRRL2338 (WT) and the industrial high-producing strain ABE1441 (HP) of S. erythraea at multiple time points of a simulated industrial bioprocess. 165 observed mutations lead to differences in gene expression profiles and protein abundance between the two strains, which were most prominent in the initial stages of erythromycin production. Enzymes involved in erythromycin biosynthesis, metabolism of branched chain amino acids and proteolysis were most strongly upregulated in the HP strain. Interestingly, genes related to TCA cycle and DNA-repair were downregulated. Additionally, comprehensive data analysis uncovered significant correlations in expression profiles of the erythromycin-biosynthetic genes, other biosynthetic gene clusters and previously unidentified putative regulatory genes. Based on this information, we demonstrated that overexpression of several genes involved in amino acid metabolism can contribute to increased yield of erythromycin, confirming the validity of our systems biology approach. Our comprehensive omics approach, carried out in industrially relevant conditions, enabled the identification of key pathways affecting erythromycin yield and suggests strategies for rapid increase in the production of secondary metabolites in industrial environment.


Per-rectal portal scintigraphy with technetium-99m pertechnetate for the early diagnosis of cirrhosis in patients with chronic hepatitis.
We evaluated the role of per-rectal portal scintigraphy with 99m-technetium pertechnetate (99m-Tc test) for early diagnosis of cirrhosis. Forty patients with biochemical evidence of chronic liver disease were studied. Laparobiopsy documented chronic active hepatitis (CAH) without cirrhosis in 22 of the patients and CAH with cirrhosis (CAHc) in 18 patients. Clinical or laboratory findings could not differentiate between CAH and CAHc. Twelve healthy volunteers served as controls. The results, expressed as shunt index (SI), i.e., the ratio between heart radioactivity and the sum of heart and liver radioactivity in the first 30 s of observation, were: controls 5.66 +/- 1.66, CAH 15.27 +/- 2.83 and CAHc 24.88 +/- 3.95. A significant difference between the mean SI values in the three groups studied (F = 142.71, p less than 0.0001) was observed. At values less than 17, our test showed a predictivity of 100% for cirrhosis exclusion, while at values higher than 19 the predictive positive value for a diagnosis of cirrhosis was 100%. Invasive diagnostic procedures should be performed only in patients with SI values between 17-19.


Normally sulphated and highly sulphated glycosaminoglycans (GAG) affecting fibrillogenesis of type I and type II collagen in vitro.
Proteoglycans (PG) and glycosaminoglycans (GAG) influence the aggregation of collagen molecules during fibrillogenesis and the ultimate fibril width. The current in vitro experiments suggest that collagen type II may interact more strongly with highly sulphated GAG than type I collagen. Electron microscopic investigations indicate that, after addition of highly sulphated GAG, the fibrils of type II collagen become significantly (p less than 0.001) thicker than fibrils of a control experiment.


Spiro rhodamine-coumarin compact electron donor-acceptor dyads: synthesis and spin-orbit charge transfer intersystem crossing.
We prepared spiro rhodamine (RB)-coumarin (Cou) compact electron donor-acceptor dyads (RB-Cou-CF3 and RB-Cou-CN), to study the charge transfer (CT) and spin-orbit CT intersystem crossing (SOCT-ISC). The π-conjugation planes of the rhodamine and coumarin units in both dyads are in nearly orthogonal geometry (dihedral angle: 86.3°). CT state emission was observed for RB-Cou-CF3 (at 550 nm) and RB-Cou-CN (at 595 nm). Although the fluorescence of the pristine coumarin units (fluorescence quantum yields ΦF = 59%) was quenched in the dyads (ΦF = 0.5 ~ 1.1% in n-hexane), the triplet state quantum yields of the dyads are also low (singlet oxygen quantum yield, ΦΔ = 2.3-7.5% in n-hexane). Nanosecond transient absorption spectra show that the 3Cou* state was formed, which shows a triplet state lifetime of 11-15.6 μs. The proposed photophysical path for the dyads is as follows: RB-1Cou* → RB+•-Cou-• → RB-3Cou*. The low SOCT-ISC yield is attributed to the slightly lower charge-transfer state energy (1.94 eV in toluene) as compared to the 3Cou* state energy (2.23 eV) and the shallow potential energy curve (PEC) at energy minima of the dyads. This work indicates that orthogonal conformation of donor-acceptor units is inadequate for achieving efficient SOCT-ISC. These results are useful for studying charge separation and intersystem crossing of electron donor/acceptor dyads.


Evaluation of Right Ventricular Function in the Management of Patients Referred for Left Ventricular Assist Device Therapy.
Speckle tracking echocardiography analysis (STE) has recently allowed an in-depth analysis of right ventricular (RV) performance. The aim of the study was to observe RV function by STE in patients with advanced heart failure before and after left ventricular assist device (LVAD) implantation. A transthoracic echocardiogram was performed in 19 patients referred for LVAD implant at baseline and with serial echocardiograms after LVAD implantation (Jarvik 2000). All echocardiographic images were analyzed off line by an independent operator to calculate with STE the RV free wall longitudinal strain (RVLS). All the patients, except 4, showed a progressive increase of RVLS after LVAD implant. However, 4 patients, who presented the lowest RVLS values at baseline, presented a further RV failure in the postoperative. The value of -11% represented the empirical preoperative cutoff able to identify patients at greater risk of postimplant RV failure. RV myocardial deformation may have important clinical implications for the selection and management of LVAD patients. It can be used to evaluate RV function before LVAD implantation, to drive decisional strategy regarding the management of this type of patients, and after LVAD implant for the follow-up.


Iranian Women and Health Care Providers' Perception of Oral Health in Pregnancy: A Qualitative Research.
Periodontal diseases during pregnancy are associated with adverse outcomes. This study aimed to explain the perception of healthcare providers and pregnant women about oral health during pregnancy. This qualitative study was conducted with the approach of conventional content analysis in health centers of Hamadan, Iran, in 2020. To collect the data, semi-structured in-depth interviews with sixteen pregnant women and eight healthcare providers (gynecologist, midwife, and dentist) were used. Pregnant women with a singleton fetus, lack of chronic diseases and complications of pregnancy, willingness to participate in the study, and the ability to communicate properly were included in the study. Sampling was done purposefully with maximum variety. Data analysis accomplished according to the proposed steps by Graneheim and Lundman using MAXQDA 10 software. "Belief in the importance of oral health in pregnancy," "Lack of a coherent structure for oral care," "Accepting the negative effect of pregnancy on oral health," and "The dilemma of treatment and non-treatment in pregnancy" were four categories extracted from the data. The theme of "Ignoring the mother for the fetus" was obtained as the main theme of the present study. The findings suggest that although mothers and healthcare providers have recognized the importance of oral health in pregnancy, underlying factors in society have led them to understand the mother's oral health should be neglected because of the fetus. This perception can have a negative impact on their behavior, performance, and the oral health of mothers.


Sedative-hypnotic properties of a new benzodiazepine in comparison with flurazepam. Pharmacological and clinical findings.
The sedative-hypnotic effects of a new benzodiazepine, 1-(2-hydroxyethyl)-3-hydroxy-7-chloro-1,3-dihydro-5-(o-fluorophenyl)-2H-1,4-benzodiazepin-2-one (SAS 643), were compared with those of flurazepam in mice and rats as well as in a double-blind clinical trial. It was found that SAS 643 has a potency 2--4 times greater than that of flurazepam while it is about one half less toxic than the latter drug. The results of the clinical trial confirm the greater activity of SAS 643 and indicate that the new benzodiazepine causes a significantly less amount of hangover than flurazepam.


Calcium and sodium transport processes in patients with cystic fibrosis. I. A specific decrease in Mg2+-dependent, Ca2+-adenosine triphosphatase activity in erythrocyte membranes from cystic fibrosis patients.
Calcium-ATPase activity (Mg2+-dependent Ca2+-ATPase, ATP phosphohydrolase, EC 22.214.171.124) in erythrocyte membrane preparations from cystic fibrosis (CF) patients was greatly reduced compared to erythrocyte membranes from control subjects. The Km for calcium was found to be similar in the two groups; however, the Vmax, the maximal rate of activation of the Ca2+-ATPase, is reduced by 50% in the erythrocyte membrane preparations of the CF patients (P less than 0.001). In contrast, the Mg2+-ATPase activity of erythrocyte membranes from CF patients was unchanged compared to the control subjects. No difference in the Na+,K+-ATPase activity in erythrocyte membranes from CF patients compared to control patients could be observed. This indicates that the Ca2+-ATPase activity noted in CF erythrocytes is not part of a generalized membrane or membrane-bound enzyme alteration. It remains to be determined whether this alteration in Ca2+-ATPase activity is directly related to a defect in calcium transport in these cells and is a generalized phenomenon in CF present in cell types more directly involved in secretion.


Inhibitory activities and inhibition specificities of caffeic acid derivatives and related compounds toward 5-lipoxygenase.
Various caffeic acid derivatives were synthesized, and their effects on 5-lipoxygenase (5-LO), 12-lipoxygenase (12-LO) and prostaglandin (PG) synthase activities were investigated. Among them, caffeic acid octyl amide (5) and 1-(3,4-dihydroxyphenyl)-1-octen-3-one (11) showed very potent inhibitory activities toward 5-LO with IC50 values of 4.2 x 10(-8) and 3.5 x 10(-8) M, respectively. They were very selective inhibitors for 5-LO. Compound 11 showed non-competitive inhibition, and the two adjacent hydroxy groups attached to the benzene ring, as well as the hydrophobic alkyl side chain, were required for its strong binding to 5-LO.


Lenvatinib Induces Immunogenic Cell Death and Triggers Toll-Like Receptor-3/4 Ligands in Hepatocellular Carcinoma.
Immunogenic cell death (ICD) is a cell death modality that plays a vital role in anticancer therapy. In this study, we investigated whether lenvatinib induces ICD in hepatocellular carcinoma and how it affects cancer cell behavior. Hepatoma cells were treated with 0.5 μM lenvatinib for two weeks, and damage-associated molecular patterns were assessed using the expression of calreticulin, high mobility group box 1, and ATP secretion. Transcriptome sequencing was performed to investigate the effects of lenvatinib on hepatocellular carcinoma. Additionally, CU CPT 4A and TAK-242 were used to inhibit TLR3 and TLR4 expressions, respectively. Flow cytometry was used to assess PD-L1 expression. Kaplan-Meier and Cox regression models were applied for prognosis assessment. After treatment with lenvatinib, there was a significant increase in ICD-associated damage-associated molecular patterns, such as calreticulin on the cell membrane, extracellular ATP, and high mobility group box 1, in hepatoma cells. Following treatment with lenvatinib, there was a significant increase in the downstream immunogenic cell death receptors, including TLR3 and TLR4. Furthermore, lenvatinib increased the expression of PD-L1, which was later inhibited by TLR4. Interestingly, inhibiting TLR3 in MHCC-97H and Huh7 cells strengthened their proliferative capacity. Moreover, TLR3 inhibition was identified as an independent risk factor for overall survival and recurrence-free survival in patients with hepatocellular carcinoma. Our study revealed that lenvatinib induced ICD in hepatocellular carcinoma and upregulated PD-L1 expression through TLR4 while promoting cell apoptosis through TLR3. Antibodies against PD-1/PD-L1 can enhance the efficacy of lenvatinib in the management of hepatocellular carcinoma.


The role of the family in genetic testing: theoretical perspectives, current knowledge, and future directions.
This article addresses conceptual challenges and theoretical approaches for examining the role of the family in responding and adapting to genetic testing for inherited conditions. Using a family systems perspective, family-based constructs that are relevant to genetic testing may be organized into three domains: family communication, organization and structure of family relationships, and health-related cognitions and beliefs shared within families. Empirical findings are presented from key content areas in family-based genetics research, including family communication, how genetic testing affects family relationships, psychological responses to genetic testing in the family context, and family-based influences on health decisions. Future research should explore decision making about genetic testing or behavior change specifically within the context of the family system and should identify family-based determinants of genetic testing outcomes.


Developing process-support tools for patient safety: finding the balance between validity and feasibility.
The Johns Hopkins Quality and Safety Research Group, which has developed many process-support tools--three of which are reported in this issue--describes its approach to tool development.


Multiunit activity in the mesencephalic reticular formation and septal area of freely moving newborn rat.
A surgical technique to implant stereotaxically fixed probes for recording multiunit activity /MUA/ from the mesencephalic reticular formation and septal area of freely moving 6--12 hr old newborn rat is described. In both brain areas the spontaneous firing of neuron populations showed close correlation with the stages of wakefulness and sleep cycle.


[Diabetes insipidus--a rare complication post partum].
A report is made on the manifestation of diabetes insipidus (neuropituitary syndrome), observed six days after a Caesarean section (29-years old I. Gravida). The progress of pregnancy and delivery as well as the successful treatment with Desmopressin (Minirin) post partum are described. The aetiology is still obscure.


Zinc alpha2 glycoprotein alleviates palmitic acid-induced intracellular lipid accumulation in hepatocytes.
Zinc alpha2 glycoprotein (ZAG) plays an important role in stimulating fat mobilization and lipolysis in adipose tissue, but its role in hepatic lipid metabolism remains unclear. Palmitic acid (PA) was used to stimulate HepG2 cells with ZAG overexpression or ZAG knock down (shRNA). Overexpression of ZAG significantly inhibited lipogenesis, promoted lipolysis and fatty acid β-oxidation, and attenuated PA-induced intracellular fat accumulation. Moreover, ZAG overexpression dramatically stimulated adiponectin expression in HepG2 cells. In contrast, knockdown of ZAG notably inhibited fatty acid β-oxidation, increased lipogenesis and lipid accumulation. Collectively, these data suggest that ZAG has the potential to alleviate hepatosteatosis, making it a promising therapeutic target for fatty liver.


Clinical utility of automated chemiluminescent antiphospholipid antibody assay.
The threshold for clinically relevant levels of antiphospholipid (aPL) antibodies for the diagnosis of antiphospholipid syndrome (APS) remains a matter of debate. As new technologies for antibody detection are introduced, their performance characteristics must be clearly understood and compared to traditional assays. To assess the analytical performance and clinical utility of fully automated anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) chemiluminescent immunoassays (CIA) in comparison to the traditional ELISA tests. Samples from 220 autoimmune patients were studied (primary APS - 74; secondary APS - 47, systemic lupus erythematosus (SLE) without APS - 99). All samples were tested for IgG and IgM aCL and β2GPI antibodies using both CIA and ELISA, and for lupus anticoagulant (LAC). Good qualitative agreement and quantitative correlation were found between methods in regard to individual antibodies and their categories (profiles). All assays showed good clinical performance in APS, and strong correlation with APS-related clinical symptoms. Importance of determining individual laboratory 99 percentile values for a healthy population as normal cut-off values was shown. Additionally, based on a clinical approach, this study has established the low/medium threshold for QUANTA Flash aCL IgG and IgM assays. This study showed good clinical performance and strong correlation of the new automated CIA aPL assays with APS clinical symptoms. It also enabled us to determine the corresponding low/medium antibody threshold for the aCL antibody methods with different unit types.


Celestin tube use: radiographic manifestations of associated complications.
Celestin intubation of the esophagus is occasionally employed in the palliation of unresectable esophageal carcinoma and in the obturation of malignant tracheoesophageal fistulas. Fourteen of 192 patients with carcinomas of the esophagus had Celestin tubes inserted at our institution between October 1977 and October 1982. Although tube insertion carries a low operative risk, there is significant subsequent morbidity associated with its use. Complications were identified radiographically in 11 of the 14 patients. Gastroesophageal reflux with aspiration pneumonia, tube obstruction, and tube migration were demonstrated most often. When Celestin tube use is deemed appropriate, the clinician and radiologist should be aware of the possible complications.


Lipase turbidimetric assay and acute pancreatitis.
The simplified turbidimetric assay for lipase activity was used for the differential diagnosis of acute pancreatitis. Serum lipase levels were found to be increased in a group of 17 patients in whom acute pancreatitis was clinically suspected and confirmed by a high ACCR and decreased uptake of the radionuclide in the pancreas scan. The lipase levels were within normal limits in a control group of 14 patients suffering from diseases other than acute pancreatitis. The turbidimetric test was helpful for rapid quantitative determination of serum lipase and thus for the early and accurate diagnosis of acute pancreatitis.


Spinal Arteriovenous Fistula, A Manifestation of Hereditary Hemorrhagic Telangiectasia: A Case Report.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by arteriovenous malformations (AVM). HHT can have neurological manifestations. A 32-year-old woman with a history of HHT presented to the emergency department with acute partial paralysis of the right leg, urinary retention, and right-sided back and hip pain. Magnetic resonance imaging of the spine demonstrated multiple, dilated blood vessels along the cervical spine, diffuse AVMs in the lumbar and thoracic spine, and a new arteriovenous fistula at the twelfth thoracic (T12) vertebral level. Her symptoms improved after endovascular embolization of the fistula. Spinal AVMs are thought to be more prevalent in patients with HHT. Given the high morbidity of arteriovenous fistulas, early recognition and intervention are critical.


Biliary fascioliasis: Management in a child using endoscopic retrograde cholangio pancreatography.
A 9-year-old boy presented with right upper abdominal pain and fever. The radiologic investigations revealed multiple cholangitic abscesses with cholangitis and worms in common bile duct. Endoscopic retrograde cholangio pancreatographic (ERCP) sphincterotomy, basketing, ballooning and extraction of Fasciola hepatica worms from the common bile duct were done.


Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy.
Invasive cribriform and intraductal carcinoma in radical prostatectomy specimens have been associated with an adverse clinical outcome. Our objective was to determine the prognostic value of invasive cribriform and intraductal carcinoma in pre-treatment biopsies on time to disease-specific death. We pathologically revised the diagnostic biopsies of 1031 patients from the first screening round of the European Randomized Study of Screening for Prostate Cancer (1993-2000). Ninety percent of all patients (n=923) had received active treatment, whereas 10% (n=108) had been followed by watchful waiting. The median follow-up was 13 years. Patients who either had invasive cribriform growth pattern or intraductal carcinoma were categorized as CR/IDC+. The outcome was disease-specific survival. Relationships with outcome were analyzed using multivariable Cox regression and log-rank analysis. In total, 486 patients had Gleason score 6 (47%) and 545 had ≥7 (53%). The 15-year disease-specific-survival probabilities were 99% in Gleason score 6 (n=486), 94% in CR/IDC- Gleason score ≥7 (n=356) and 67% in CR/IDC+ Gleason score ≥7 (n=189). CR/IDC- Gleason score 3+4=7 patients did not have statistically different survival probabilities from those with Gleason score 6 (P=0.30), while CR/IDC+ Gleason score 3+4=7 patients did (P<0.001). In multivariable analysis, CR/IDC+ status was independently associated with a poorer disease-specific survival (HR 2.6, 95% CI 1.4-4.8, P=0.002). We conclude that CR/IDC+ status in prostate cancer biopsies is associated with a worse disease-specific survival. Our findings indicate that men with biopsy CR/IDC- Gleason score 3+4=7 prostate cancer could be candidates for active surveillance, as these patients have similar survival probabilities to those with Gleason score 6.


The evolution of prey-attraction strategies in spiders: the interplay between foraging and predator avoidance.
Lures and other adaptations for prey attraction are particularly interesting from an evolutionary viewpoint because they are characterized by correlational selection, involve multicomponent signals, and likely reflect a compromise between maximizing conspicuousness to prey while avoiding drawing attention of enemies and predators. Therefore, investigating the evolution of lure and prey-attraction adaptations can help us understand a larger set of traits governing interactions among organisms. We review the literature focusing on spiders (Araneae), which is the most diverse animal group using prey attraction and show that the evolution of prey-attraction strategies must be driven by a trade-off between foraging and predator avoidance. This is because increasing detectability by potential prey often also results in increased detectability by predators higher in the food chain. Thus increasing prey attraction must come at a cost of increased risk of predation. Given this trade-off, we should expect lures and other prey-attraction traits to remain suboptimal despite a potential to reach an optimal level of attractiveness. We argue that the presence of this trade-off and the multivariate nature of prey-attraction traits are two important mechanisms that might maintain the diversity of prey-attraction strategies within and between species. Overall, we aim to stimulate research on this topic and progress in our general understanding of the diversity of predator and prey interactions.


Size-tunable Synthesis of Silver Nanobelts Using a Polyaniline Derived Polymer as a Template.
Silver nanobelts (AgNBs) have attracted a great interest due to their excellent electrical conductivity and mechanical strength, leading a facile synthesis of these AgNBs in great demand. In here, we are reporting a simple, aqueous phase, size tunable synthesis of smooth surfaced 1D-silver nanobelts using a Polyaniline (PANi) derived polymer at room temperature. The specifically designed PANi polymer, comprising a pendant carboxyl group in the chain, acted as both a reducing agent and template. The resulting Ag nanobelts have more than 10 μm of length, mean width values ranging from 41.1 (11.5) nm to 118.5 (8.8) nm and a mean thickness value of 36.7 (12.5) nm. The UV-Visible spectrum of the AgNBs has shown two Surface Plasmon Resonance peaks at 352 nm and 383 nm.


Inhibition of mitochondrial succinate oxidation--similarities and differences between N-methylated beta-carbolines and MPP+.
N-Methylated beta-carbolinium compounds (N-Me-BCs), including 2-N-methyl and 2,9-N,N-dimethyl analogs, structural analogs of 1-methyl-4-phenylpyridinium (MPP+), may be endogenously bioactivated, MPP(+)-like toxins, capable of inducing parkinsonism. Both MPP+ and selected N-Me-BCs inhibit NADH-linked mitochondrial respiration (Complex I). We now show that both also inhibit succinate-supported (Complex II) respiration, the greatest inhibition (80%) being seen for 2,9-dimethylharmanium. Complex I inhibition occurs at MPP+ concentrations (IC50 = 0.17 mM) about one order of magnitude lower than Complex II inhibition (greater than 1.2 mM). In contrast, Complex I and Complex II inhibition by the N-Me-BCs tested occurred at similar concentrations (I, 0.1 mM; II, 0.25 mM) and concentrations similar to Complex I inhibition by MPP+. 2,9-N,N-Dimethyl-BCs, which are the permanently charged BC analogs of MPP+, show inhibitory characteristics similar to MPP+: slow onset of inhibition, potentiation by TPB, and reversal by DNP. The fact that succinate oxidation cannot bypass the Complex II inhibition by N-Me-BCs could enhance any chronic neurotoxicity of N-Me-BCs.


Microarray analysis of peroxisome proliferator-activated receptor-gamma induced changes in gene expression in macrophages.
We used a combination of expression microarray and Northern blot analyses to identify target genes for peroxisome proliferator-activated receptor (PPAR) gamma in RAW264.7 macrophages. PPARgamma natural ligand 15-deoxy-Delta(12,14) prostaglandin and synthetic ligands ciglitazone and rosiglitazone increased the expression of scavenger receptor CD36 and ATP-binding cassette transporter A1, as well as adipophilin (a lipid droplet coating protein involved in intracellular lipid storage and transport), calpain (a protease implicated in ABCA1 protein degradation), and ADAM8 (a disintegrin and metalloprotease protein involved in cell adhesion). These findings are relevant to understanding the effect of PPARgamma activation on gene expression and cognate pathways in macrophages.