High normal albuminuria is associated with arterial stiffness and carotid atherosclerosis in Korean patients with type 2 diabetes.
Current evidence suggests that high normal albuminuria is significantly associated with increased cardiovascular risk. This study investigated the association between urine albumin-to-creatinine ratio (ACR) within the normal range and subclinical atherosclerosis in Korean patients with type 2 diabetes. This cross-sectional study involved 521 type 2 diabetic patients with normoalbuminuria. Brachial-ankle pulse wave velocity (baPWV) measurement and ultrasound assessment of carotid atherosclerosis was done. Subclinical atherosclerosis was assessed by the presence of high baPWV (>1682 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50% of luminal narrowing). Across the tertiles of ACR, there was a trend for an increasing prevalence of high baPWV (16.8%, 20.0%, and 38.2%, P < 0.001), carotid atherosclerosis (46.9%, 55.4%, and 64.7%, P < 0.001), and carotid stenosis (12.7%, 16.0%, and 30.1%, P < 0.001). In multivariate analysis, patients in the highest ACR tertile had an odds ratio of 2.05 (95% confidence interval [CI], 1.13-3.72, P = 0.019) for high baPWV, 1.78 (95% CI, 1.08-2.93, P = 0.024) for carotid atherosclerosis, and 2.72 (95% CI, 1.44-5.11, P = 0.002) for carotid stenosis compared to those in the lowest tertile. The relation of ACR with carotid atherosclerosis and stenosis remained significant even in patients without diabetic retinopathy. High normal albuminuria was significantly associated with atherosclerotic vascular changes, independent of retinopathy and other cardiovascular risk factors. High normal albuminuria may be an early marker for subclinical atherosclerosis in type 2 diabetes.


Phosphoproteomics Enables Molecular Subtyping and Nomination of Kinase Candidates for Individual Patients of Diffuse-Type Gastric Cancer.
The diffuse-type gastric cancer (DGC) constitutes a subgroup of gastric cancer with poor prognosis and no effective molecular therapies. Here, we report a phosphoproteomic landscape of DGC derived from 83 tumors together with their nearby tissues. Based on phosphorylation, DGC could be classified into three molecular subtypes with distinct overall survival (OS) and chemosensitivity. We identified 16 kinases whose activities were associated with poor OS. These activated kinases covered several cancer hallmark pathways, with the MTOR signaling network being the most frequently activated. We proposed a patient-specific strategy based on the hierarchy of clinically actionable kinases for prioritization of kinases for further clinical evaluation. Our global data analysis indicates that in addition to finding activated kinase pathways in DGC, large-scale phosphoproteomics could be used to classify DGCs into subtypes that are associated with distinct clinical outcomes as well as nomination of kinase targets that may be inhibited for cancer treatments.


Placental gene expression and pre-eclampsia.
Pre-eclampsia and related syndromes, such as the HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome, have a strong genetic component, although the nature, origin and recurrence rate of the genetic risks involved are not necessarily the same for each form of pregnancy-induced hypertension or population. This review addresses these items in the context of the recent understanding that (a) common diseases can be caused by common genetic variations, (b) the placental genotype can control the maternal phenotype, (c) epistasis and epigenetics are involved, and (d) a conserved pathway shared between organs is possible as well as a common, pathophysiological pathway is shared between syndromes.


Nomogram based on MRI for preoperative prediction of Ki-67 expression in patients with intrahepatic mass cholangiocarcinoma.
To validate a new nomogram based on magnetic resonance imaging (MRI) for pre-operative prediction of Ki-67 expression in patients with intrahepatic mass cholangiocarcinoma (IMCC). A total of 78 patients with clinicopathologically confirmed IMCC who underwent pre-operative gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI between 2016 and 2022 were enrolled in the training and validation group (53 patients and 25 patients, respectively). Images including qualitative, quantitative MRI features and clinical data were evaluated. Univariate analysis and multivariate logistic regression were used to select the independent predictors and establish different predictive models. The predictive performance was validated by operating characteristic curve (ROC) analysis, calibration curve, and decision curve analysis (DCA). The validation cohort was used to test the predictive performance of the optimal model. The nomogram was constructed with the optimal model. In the training cohort, independent predictors obtained from the combined model were DWI (OR 1822.741; 95% CI 6.189, 536,781.805; P = 0.01) and HBP enhancement pattern (OR 14.270; 95% CI 1.044, 195.039; P = 0.046). The combined model showed the good performance (AUC 0.981; 95% CI 0.952, 1.000) for predicting Ki-67 expression. In the validation cohort, The combined model (AUC 0.909; 95% CI 0.787, 1.000)showed the best performance compared to the clinical model (AUC 0.448; 95% CI 0.196, 0.700) and MRI model (AUC 0.770; 95% CI 0.570, 0.970). This new nomogram has a good performance in predicting Ki-67 expression in patients with IMCC, which could help the decision-making of the patients' therapy strategies.


Assessment of knowledge, attitude and practice of food allergies among food handlers in the state of Penang, Malaysia.
Food handler's knowledge, attitude and practice regarding food allergies are important to prevent debilitating and sometimes fatal reactions. This study aimed to assess their food allergy knowledge, attitude and practice, which could help to maintain the safety and hygiene of food consumed by the public. Cross-sectional survey. A cross-sectional survey involving 121 conveniently sampled (81.76% response rate) respondents among the food handlers in the state of Penang, Malaysia, was conducted using a validated self-administered questionnaire. Their knowledge, attitude and work practice were captured using a 37-item questionnaire that elicited their responses using a mixture of closed-ended and Likert scale techniques. The mean knowledge score for respondents was 50.23 (SD = 14.03), attitude score was 54.26 (SD = 11.67) and practice score was 45.90 (SD = 24.78). Only 1.79% of the respondents were considered to have excellent knowledge, 21.37% had a low risk practice and 4.27% had positive attitudes towards food allergies. Most of the respondents (70%) knew about food allergies and their seriousness. There was a statistically significant correlation between the attitude and practice of respondents (r = 0.51). The type of establishment was the only characteristic significantly associated (P < 0.05) with food handler allergy knowledge, attitude and practice. More than half of food handlers in Penang have moderate levels of food allergy knowledge, practice and attitude. Only a small proportion of them have excellent food allergy knowledge, practice and attitude. Integration of food allergy training into compulsory food safety training programmes is needed to reduce food allergy risks and prevent fatal allergic reactions to food among their customers.


Lysozyme release and polymer erosion behavior of injectable implants prepared from PLGA-PEG block copolymers and PLGA/PLGA-PEG blends.
We evaluated the controlled release of lysozyme from various poly(D,L-lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers relative to PLGA 50/50. Lysozyme was encapsulated in cylindrical implants (0.8 mm diameter) by a solvent extrusion method. Release studies were conducted in phosphate buffered saline +0.02% Tween 80 (PBST) at 37°C. Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was evaluated by kinetics of polymer molecular weight decline, water uptake, and mass loss. Lysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG, PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27 kDa) showed release profiles similar to PLGA. We achieved continuous lysozyme release for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore-forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3 and blending AB15 with PLGA. Lysozyme activity was mostly recovered during 4 weeks. These block co-polymers may have utility either alone or as PLGA blends for the controlled release of proteins.


NAD+ metabolism and eye diseases: current status and future directions.
Currently, there are no truly effective treatments for a variety of eye diseases, such as glaucoma, age-related macular degeneration (AMD), and inherited retinal degenerations (IRDs). These conditions have a significant impact on patients' quality of life and can be a burden on society. However, these diseases share a common pathological process of NAD+ metabolism disorders. They are either associated with genetically induced primary NAD+ synthase deficiency, decreased NAD+ levels due to aging, or enhanced NAD+ consuming enzyme activity during disease pathology. In this discussion, we explore the role of NAD+ metabolic disorders in the development of associated ocular diseases and the potential advantages and disadvantages of various methods to increase NAD+ levels. It is essential to carefully evaluate the possible adverse effects of these methods and conduct a more comprehensive and objective assessment of their function before considering their use.


[Use of an immunofluorescence micromethod for determining the antigens of the influenza and tick-borne encephalitis viruses].
The diagnostic possibilities of several variants of the solid-phase immunofluorescent micromethod (requiring 100-200 microliter of the reaction mixture), intended for the determination of influenza virus and tick-borne encephalitis virus antigens in material obtained from patients and ticks, have been studied. A high degree of correlation between the results obtained by the methods under investigation and the control methods has been established.


Supporting Data for Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs.
Although nanoparticulate drug delivery systems (NDDSs) can preferentially accumulate in tumors, active targeting by targeting ligands (e.g. monoclonal antibody) is necessary for increasing its targeting efficacy in vivo. We conjugated mAb198.3 on the SiO2@AuNP system surface to make it obtain active targeting efficacy. The FAT1 targeting capability of SiO2@AuNP system is the first issue to be solved. Thus, flow cytometry analysis was attempted to demonstrate that the SiO2@AuNP system could bind to native FAT1 molecules on the surface of Colo205 cells. Also, together with the drug release behavior study of self-decomposable SiO2 NPs, the continuous morphological evolution needed to be clarified. Therefore, to characterize the morphological evolution in vitro, we analyzed the morphology of inner self-decomposable NPs in different time intervals using transmission electron microscopy (TEM). A more comprehensive analysis of this data may be obtained from the article "Multifunctional all-in-one drug delivery systems for tumor targeting and sequential release of three different anti-tumor drugs" in Biomaterials.


The D-amino acid oxidase-carbon nanotubes: evaluation of cytotoxicity and biocompatibility of a potential anticancer nanosystem.
The 'enzyme prodrug therapy' represents a promising strategy to overcome limitations of current cancer treatments by the systemic administration of prodrugs, converted by a foreign enzyme into an active anticancer compound directly in tumor sites. One example is D-amino acid oxidase (DAAO), a dimeric flavoenzyme able to catalyze the oxidative deamination of D-amino acids with production of hydrogen peroxide, a reactive oxygen species (ROS), able to favor cancer cells death. A DAAO variant containing five aminoacidic substitutions (mDAAO) was demonstrated to possess a better therapeutic efficacy under low O2 concentration than wild-type DAAO (wtDAAO). Recently, aiming to design promising nanocarriers for DAAO, multi-walled carbon nanotubes (MWCNTs) were functionalized with polyethylene glycol (PEG) to reduce their tendency to aggregation and to improve their biocompatibility. Here, wtDAAO and mDAAO were adsorbed on PEGylated MWCNTs and their activity and cytotoxicity were tested. While PEG-MWCNTs-DAAOs have shown a higher activity than pristine MWCNTs-DAAO (independently on the DAAO variant used), PEG-MWCNTs-mDAAO showed a higher cytotoxicity than PEG-MWCNTs-wtDAAO at low O2 concentration. In order to evaluate the nanocarriers' biocompatibility, PEG-MWCNTs-DAAOs were incubated in human serum and the composition of protein corona was investigated via nLC-MS/MS, aiming to characterize both soft and hard coronas. The mDAAO variant has influenced the bio-corona composition in both number of proteins and presence of opsonins and dysopsonins: notably, the soft corona of PEG-MWCNTs-mDAAO contained less proteins and was more enriched in proteins able to inhibit the immune response than PEG-MWCNTs-wtDAAO. Considering the obtained results, the PEGylated MWCNTs conjugated with the mDAAO variant seems a promising candidate for a selective antitumor oxidative therapy: under anoxic-like conditions, this novel drug delivery system showed a remarkable cytotoxic effect controlled by the substrate addition, against different tumor cell lines, and a bio-corona composition devoted to prolong its blood circulation time, thus improving the drug's biodistribution. The online version contains supplementary material available at 10.1007/s13205-023-03568-1.


Metabolic risk factors attributed burden in Iran at national and subnational levels, 1990 to 2019.
Metabolic risk factors (MRFs) predispose populations to a variety of chronic diseases with a huge burden globally. With the increasing burden of these risk factors in Iran, in this study, we aimed to report the estimated burden attributed to MRFs at national and subnational scales in Iran, from 1990 to 2019. Based on the comparative risk assessment method of the Global Burden of Disease (GBD) Study 2019, data of deaths and disability-adjusted life years (DALYs) attributable to four top MRFs in Iran including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body mass index (BMI), and high low-density lipoprotein (LDL) for the 1990-2019 period, were extracted. The socio-demographic index (SDI) was used to report the data based on the corresponding socio-economic stratifications. The results were reported in national and subnational 31 provinces of Iran to discover disparities regarding the attributable burden to MRFs. Furthermore, we reported the causes of diseases to which the attributable burden to MRFs was related. Overall, the age-standardized high LDL, high SBP, high BMI, and high FPG-attributed death rate changed by -45.1, -35.6, +2.8, and +19.9% from 1990 to 2019, respectively. High SBP was the leading risk factor regarding attributed age-standardized death rates reaching 157.8 (95% uncertainty interval: 135.3-179.1) and DALY rates reaching 2973.4 (2652.2-3280.2) per 100,000 person-years, in 2019. All rates increased with aging, and men had higher rates except for the +70 years age group. At the subnational level, provinces in the middle SDI quintile had the highest death and DALY rates regarding all four MRFs. Total deaths, DALYs, YLLs and YLDs number by the causes of diseases linked to MRFs increased over the study period. Cardiovascular diseases, diabetes mellitus, and kidney diseases were the main causes of burden of disease attributable to MRFs. Herein, we found divergent patterns regarding the burden of MRFs as well as disparities in different regions, sex, and age groups for each risk factor and related causes. This could provide policymakers with a clearer vision toward more appropriate decision-making and resource allocation to prevent the burden of MRFs in Iran.


Behavioural recovery from unilateral vestibular lesion is facilitated by GM1 ganglioside treatment.
Exogenously administered gangliosides function in vivo to facilitate survival and repair of damaged neurones in both central and peripheral nervous systems. These effects have been attributed to their neuritogenic and neuronotrophic properties. In this investigation the effects of ganglioside treatment have been studied on the compensation that follows a unilateral labyrinthectomy, considering that the vestibular recovery is supposed to be achieved through a mechanism of sprouting acting on the deafferented neurones. Hemilabyrinthectomized guinea pigs were given a daily injection of either GM1 ganglioside (30 mg/kg, i.p.) or saline for 21 days. As regards postural symptoms, the GM1 group more quickly restored a posture of the head non-deviated in the horizontal plane, while the remaining postural symptomatology was not significantly affected by the treatment. Furthermore, the GM1-treated group attained more rapidly an ocular position characterized by very slow drifts (or by no drift at all), directed towards the side of the intact labyrinth. Ganglioside treatment did not reduce the severity of the initial hemilabyrinthectomy impairments and the effect of the treatment became evident with time. This result is consistent with the hypothesis that also in this model of neuronal plasticity, gangliosides act by enhancing reactive synaptogenesis on the deafferented vestibular neurones.


Acute Myocardial Infarction Secondary to Triple Coronary Arteries Dissection in a Patient With Takayasu Vasculitis.
Synchronous spontaneous triple coronary artery dissection with Takayasu arteritis has not been previously reported in the literature. We describe the case of a young man with acute inferior wall myocardial infarction secondary to triple-vessel coronary artery dissection. Takayasu arteritis was diagnosed upon further investigation. (Level of Difficulty: Intermediate.).


The immunopharmaceutical effects and mechanisms of herb medicine.
In recent years, studies on evaluation of the therapeutic and toxic activity of herbal medicinal products became available and popular. The advances in modern biotechnology have led to discovery of many new active constituents. However, it is a constant challenge to establish the pharmacological basis for efficacy and safety of herbal medicinal products. A better understanding of the effects and bioavailability of phytopharmaceuticals can help in discovering suitable and rational therapies. In this review, we present the bioavailability studies in immune system that has been conducted for some of the more important or widely used phytopharmaceuticals. Furthermore, various new drug targets worthy of using for drug development in immunomodulating herbal medicine area and their regulatory mechanisms are also discussed. Adverse effects, drug interactions, and contraindications are also discussed which show that caution should be exercised when combining phytopharmaceuticals with chemically derived pharmaceutical components.


[Retracted] SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells.
Following the publication of this paper, and subsequently to a corrigendum that was published to take account of errors that had been made concerning the Transwell invasion assay data in Fig. 4B (doi: 10.3892/ijo.2022.5463), it was drawn to the Editor's attention by a concerned reader that the western blots shown in Figs. 3C and 6B shared the same control data; moreover, potential anomalies were identified in the flow cytometric plots shown in Fig. 2A. Although the authors proposed to publish a corrigendum to account for these errors, including new data after having performed certain of the experiments again, given the number of problems that have been identified concerning the assembly of various of the figures in the published paper, the Editor of International Journal of Oncology has decided not to publish a further corrigendum, and has, in fact, determined that this paper should be retracted from the Journal on account of an overall lack of confidence in the originally presented data. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 50: 893-902, 2017; DOI: 10.3892/ijo.2017.3871].


Epidermal growth factor stimulates prostacyclin production by cultured human vascular endothelial cells.
Epidermal growth factor (EGF) stimulated prostacyclin (PGI2) production by cultured human umbilical vein endothelial cells, as measured by radioimmunoassay of its stable metabolite 6-keto-prostaglandin F1 alpha. This effect of EGF was dose-dependent, the lowest stimulatory concentration of EGF was 1.0 ng/ml and 100 ng/ml caused a 2.7 +/- 0.3 (mean +/- SEM) fold increase in the PGI2 synthesis. The stimulation appeared at 3-6 h of incubation and lasted at least 24 h. It was suppressed by EGF antibodies and blocked by protein synthesis inhibitor cycloheximide. Cells preincubated 12 h with EGF released also higher amounts of PGI2 when incubated with thrombin for 5 min. It is concluded that EGF liberated from platelets during aggregation may prevent local thrombogenesis and atherogenesis by stimulating the release of the antiaggregatory, vasodilatory PGI2 from vascular endothelial cells.


Clinical implications of shared genetics and pathogenesis in autoimmune diseases.
Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the presence of autoreactive T cells. They are caused by a complex genetic predisposition that is attributable to multiple genetic variants, each with a moderate-to-low effect size. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. Here, we review the shared and specific genetic background of autoimmune diseases, summarize their treatment options and discuss how identifying the genetic and environmental factors that predispose patients to an autoimmune disease can help in the diagnosis and monitoring of patients, as well as the design of new treatments.


Temporal changes in myocardial endothelial nitric oxide synthase expression following human heart transplantation.
The incidence of cardiac allograft vasculopathy increases with time after heart transplantation. Allograft vasculopathy is associated with endothelial dysfunction and reduced endothelium-dependent nitric oxide-mediated vascular effects. In this study, temporal changes in endothelial nitric oxide synthase (NOS3) expression in human myocardial biopsies were investigated during the first 3 years after heart transplantation. In each patient (n = 7), the immunohistochemical presence of NOS3 and inducible nitric oxide synthase were examined in serial biopsies taken at 1, 4, and 26 weeks and at 1, 2, and 3 years after transplantation. Endothelial nitric oxide synthase was present in vascular endothelial cells in all biopsies at the time of transplantation. A rapid fall within the first months in the number of NOS3-positive biopsies was observed, with a possible difference in the rate of disappearance among the capillaries, the arterial endothelium, and the venous endothelium. After 2 years, very little NOS3 could be detected. Inducible nitric oxide synthase was present in vascular smooth muscle cells throughout the study period and did not change. Endothelial nitric oxide synthase immunoreactivity is gradually lost after heart transplantation. These changes may be responsible for the coronary endothelial dysfunction often seen after human cardiac transplantation.


Operant conditioning of trigeminally-evoked cortical potentials: correlated effects on facial nociception.
The effects of operant conditioning somatosensory evoked potential (SEP) amplitude on nociceptive sensitivity were studied in albino rats. SEPs were evoked by stimulation to the descending trigeminal tract. Rewarding medial forebrain bundle stimulation (at intensities predetermined to sustain bar pressing) was made contingent upon the animal making the amplitude of the SEP 0.5 standard deviation (S.D.) large (uptraining) or 0.5 S.D. smaller (downtraining) than the predetermined mean value. Nociceptive sensitivity was measured immediately following the conditioning session by heating the rat's face and noting the latency of a defensive face rubbing response directed at that area of the face. Increasing the amplitude of the SEP (uptraining) was associated with a decrease in noxious sensitivity. Decreasing the amplitude of the SEP (downtraining) was associated with an increase in noxious sensitivity.


[Pharmacological research on ophthalmic drug lamellae containing gentamycin sulfate in laboratory and agricultural animals].
The in vitro and in vivo solubility of ocular drug lamellae, containing 1.5 and 3 mg gentamycin sulphate, was followed up. It was found that those that contained lower amount of the antibiotic disintegrated in the eyes of rabbits, lambs, and sheep for 30-40 minutes, while lamellae having 3 mg gentamycin disintegrated for 45-50 minutes. It is stated that such ocular lamellae are well tolerated by the conjunctiva of the animal species referred to. With the application of one lamella with 3 mg gentamycin sulphate therapeutic concentrations of the antibiotic in the lacrimal secretion are found up to the 24 th hour with cows, sheep, and lambs, and up to the 48h hour with rabbits.


[The application of cryogenic temperatures in medicine].
An increased interest in effects of low temperatures on human organisms has been observed during last years. Low temperatures have been applied in cryotherapy and cryosurgery. In our article we show the influence of low temperatures on different physiological mechanisms and the possibility of their application in the therapy.


The dilemma of Crohn's disease: ileoduodenal fistula complicating Crohn's disease.
Nine cases of duodenal fistula complicating Crohn's disease are reported. All nine patients were male. Four patients had Crohn's disease of the ileum and five had ileocolitis. No patient had primary duodenal Crohn's disease. Because attempt at primary closure of the duodenal defect may fail, our treatment of choice has been formal cross cut two-layered duodenojejunal anastomostis with extensive drainage of the area postoperatively. This treatment has been associated with no mortality and little morbidity, and no late recurrence of duodenal fistula.


Prompt cooling of burned areas: a review of benefits and the effector mechanisms.
Arguably one of the oldest recorded methods of treating burns is still recommended today, namely prompt cooling of the injured part, usually in cold water. Such therapy was recommended by Galen (AD 129-199) and Rhazes (AD 852-923) Earle (1799) and by Sorensen (1967). As a first aid measure it has numerous advocates in the 1970s and 1980s. Almost certainly subjective considerations initiated this form of treatment and only within recent times have objective studies confirmed the beneficial effects of a more rapid reduction in tissue temperature and thus severity of injury.


Optimization of pectinase-assisted extraction of Annona muricata L. juice and the effect of liquefaction on its pectin structure.
Soursop (Annona muricata L.) is an underutilized tropical and subtropical fruit with high nutritional and therapeutic benefits. This fruit is faced with enormous post-harvest losses due to its high perishability. This work was aimed to optimize the pectinase-assisted extraction conditions of soursop juice using Doehlert design and to study the effect of pectinase on its pectin structure. The predicted models were validated for all the responses studied and the regression coefficients ranged from 0.905 to 0.987 (P ≤ 0.05). An incubation time of 172 min, enzyme concentration of 0.04% (w/w) and incubation temperature at 42.9 °C were found to be the optimal conditions for soursop juice extraction, which resulted in 75.20%, 3.74, 7.35 °Brix, 87.06%T, and 0.44% MAE for soursop juice yield (%), pH, total soluble solids (TSS) (°Brix), clarity (%T) and titratable acidity (% malic acid equivalent, MAE), respectively. Morphologically, untreated soursop pulp presented a non-uniform spherical surface; enzyme hydrolyzed soursop exhibited ruptured and wrinkled surface; meanwhile for the different pectin obtained, untreated soursop pectin depicted porous surface and enzyme hydrolyzed soursop pectin showed whirling rough surface. Fourier-transform infrared (FTIR) confirmed the presence of similar chemical group stretching and vibrations in commercial pectin and soursop pectin. Under the optimum conditions, the numerical predictions were similar to the experimental data obtained, thus confirming the validity of the models. Application of enzyme treatment caused the breakdown of pectin structure as illustrated by scanning electron microscopy (SEM) and FTIR analyses.


Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate.
The survival of 90% of a tumor-bearing population treated with the complex Rh(2) (CF(3)CONH)(4) was examined and the pharmacological parameter Surv(90) determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv(90) dose of 3.8x 10(-5) mol/kg was found.


Levofloxacin susceptibility testing against Helicobacter pylori: evaluation of a modified disk diffusion method compared to E test.
We compared levofloxacin (1 μg/disk) disk diffusion method to E test against 212 Helicobacter pylori strains. Using diameter breakpoints for susceptibility (≥15 mm) and resistance (≤9 mm), very major error, major error rate, and categoric agreement were 0.0%, 0.6%, and 93.9%, respectively. The method may be useful in low-resource laboratories.


Water relations of stem succulent trees in north-central Baja California.
Water relations of several stem succulent trees were measured in north-central Baja California in comparisons to other growth forms in the same habitat. Our research concentrated on three stem succulent species (Idria collumnaris, Pachycormus discolor and Bursera microphylla) each with a different succulent stem morphology. The stem succulent trees had 1 to 4 kg H2O/m3 of trunk while the other trees and shrubs in the same habitat had 0.6 to 0.8 kg H2O/m3. The diurnal and seasonal variation in leaf water potential was small for the stem succulent species in comparison to deciduous and evergreen species as a consequence of the stem-water, buffering capacity. In addition, the leaf conductance of the stem succulent species was low (60 mmol m-2 s-1) and yet, the leaf conductance decreased through the day similar to adjacent evergreen and deciduous species. The leaves of the stem succulent trees lost turgor at low saturated water deficits (0.06 to 0.14), had comparatively high osmotic potentials, and high values of elastic modulus in comparison to adjacent evergreen and deciduous species. The stem acts as an important buffering mechanism allowing for the maintenance of leaf turgor in these stem succulent trees. The low transpiration rates of the stem succulent trees may be a mechanism to minimize leaf saturated water deficit and extend leaf longevity.


A Twisted Thieno[3,4-b]thiophene-Based Electron Acceptor Featuring a 14-π-Electron Indenoindene Core for High-Performance Organic Photovoltaics.
With an indenoindene core, a new thieno[3,4-b]thiophene-based small-molecule electron acceptor, 2,2'-((2Z,2'Z)-((6,6'-(5,5,10,10-tetrakis(2-ethylhexyl)-5,10-dihydroindeno[2,1-a]indene-2,7-diyl)bis(2-octylthieno[3,4-b]thiophene-6,4-diyl))bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (NITI), is successfully designed and synthesized. Compared with 12-π-electron fluorene, a carbon-bridged biphenylene with an axial symmetry, indenoindene, a carbon-bridged E-stilbene with a centrosymmetry, shows elongated π-conjugation with 14 π-electrons and one more sp3 carbon bridge, which may increase the tunability of electronic structure and film morphology. Despite its twisted molecular framework, NITI shows a low optical bandgap of 1.49 eV in thin film and a high molar extinction coefficient of 1.90 × 105 m-1 cm-1 in solution. By matching NITI with a large-bandgap polymer donor, an extraordinary power conversion efficiency of 12.74% is achieved, which is among the best performance so far reported for fullerene-free organic photovoltaics and is inspiring for the design of new electron acceptors.


Analysis of recreational off-road vehicle accidents resulting in spinal cord injury.
Twelve cases of spinal cord injury (SCI) resulting from recreational off-road vehicle (ORV) accidents seen during a three-year period at a spinal cord injury center were analyzed using structured interviews and record reviews. Seven accidents involved three-wheel all-terrain vehicles (ATVs), one involved a four-wheel ATV, and four involved two-wheel trailbikes. The analysis of accident victim characteristics showed that all age groups are at risk, and that most victims were young adult men vehicle drivers with experience and wearing helmets. Spinal injury levels were cervical, three; thoracic, three; and thoracolumbar, six. Categorized accident hazard patterns were loss of control, six; tipover, four; and hidden obstacle, two. Contributing causative factors to the accident occurrence were poor driver judgment, seven, and vehicle instability, eight. Speeding was the most frequent primary cause of ORV accidents. We discuss vehicle and driver performance characteristics as they relate to risk of accident occurrence. The frequency of ORV accidents as an etiology of traumatic SCI at our center was 8%, compared to 8% for diving accidents and 11% for motorcycle accidents. We recommend, in view of the high risk of severe injury, widespread public education about ORV accident prevention.


Comparison of coupling of impulse activity of cerebral cortical neurons and spatial synchronicity of the EEG.
The coherence of the EEG and the coupling of the impulse activity of neurons of the visual and sensorimotor areas of the neocortex of rabbits, recorded simultaneously from the same electrodes, were compared under chronic experimental conditions. An association was found between the presence and properties of the conjugated functioning of neurons and the coherence of the EEG at various frequencies. Greater coherence of the EEG was observed during the correlated functioning of neurons at frequencies of 3-4.5 Hz than during independent functioning. The neurons discharged in pairs, with a smaller delay between them at the highest level of EEG coherence, and a common source participating more often in their synchronization than at the lowest level of EEG coherence.


Model-based total evidence phylogeny of Neotropical electric knifefishes (Teleostei, Gymnotiformes).
This study provides the most comprehensive Model-Based Total Evidence (MBTE) phylogenetic analyses of the clade Gymnotiformes to date, reappraising relationships using a dataset comprised of six genes (5277bp) and 223 morphological characters, and an ingroup taxon sample including 120 of 212 valid species representing 34 of the 35 extant genera. Our MBTE analyses indicate the two main gymnotiform clades are Gymnotidae and Sternopygoidei, the latter comprised of Rhamphichthyoidea (Rhamphichthyidae+Hypopomidae) and Sinusoidea (Sternopygidae+Apteronotidae). Within Gymnotidae, Electrophorus and Gymnotus are sister taxa, and Gymnotus includes the following six clades: (i) G. pantherinus clade, (ii) G. coatesi clade, (iii) G. anguillaris clade, (iv) G. tigre clade, (v) G. cylindricus clade, and (vi) G. carapo clade. Within Rhamphichthyoidea, Steatogenae (Steatogenys+Hypopygus) is a member of Rhamphichthyidae, and Hypopomidae includes the following clades: (i) Akawaio, (ii) Hypopomus, (iii) Microsternarchini, and (iv) Brachyhypopomus. Within Sternopygidae, Sternopygus and Eigenmanninae are sister groups, Rhabdolichops is the sister to other Eigenmanninae, Archolaemus+Distocyclus is the sister to Eigenmannia, and Japigny is nested within Eigenmannia. Within Apteronotidae, Sternarchorhamphinae (Sternarchorhamphus+Orthosternarchus) is the sister to Apteronotinae, Adontosternarchus is the sister group to other Apteronotinae, Sternarchorhynchini (Sternarchorhynchus+Platyurosternarchus) is the sister to Navajini, and species assigned to Apteronotus are members of two separate clades: (i) A. sensu stricto in the Apteronotini, and (ii) the "A." bonapartii clade in the Navajini.


Mechanically stimulated TCH3 gene expression in Arabidopsis involves protein phosphorylation and EIN6 downstream of calcium.
Mechanical signals are important both as environmental and endogenous developmental cues in plants. Among the quickest measurable responses to mechanical stimulation (MS) in plants is the up-regulation of specific genes, including TCH3, in Arabidopsis. Little is known about the signaling events and components that link perception of mechanical signals to gene expression in plants. Calcium has been identified previously as being potentially involved, and a role for ethylene has also been suggested. Using the protein kinase inhibitor staurosporine, we determined that MS up-regulation of TCH3 expression requires protein kinase activity in young Arabidopsis seedlings. Our data from studies on the Arabidopsis ein6 mutant demonstrate that the EIN6 protein is also required, but that its role in mechanically induced TCH3 expression appears to be independent of ethylene. Challenge of seedlings with protein phosphatase inhibitors calyculin A and okadaic acid stimulated TCH3 expression even in the absence of MS, implying protein phosphatase activity acting to negatively regulate TCH3 gene expression. This phosphatase activity acts either downstream or independently of EIN6. EIN6 and protein kinase activity, on the other hand, operate downstream of calcium to mediate mechanically stimulated TCH3 expression.


The potential protein kinase A (Pka) phosphorylation site is required for the function of FgSge1 in Fusarium graminearum.
The new transcription factor Sge1 has garnered much attention in filamentous fungi recently, which highlights its role in pathogenicity, conidiation, and the production of secondary metabolites. In this study, we demonstrated that FgSge1 is localized in the nucleus in Fusarium graminearum using fluorescent protein GFP. Mutants containing a T67A mutation within the potential protein kinase A (Pka) phosphorylation site of FgSge1 exhibited a significant decrease in conidiation and dramatically impaired virulence on both wheat head and non-host tomato. These results indicated that the Pka phosphorylation site is required for the function of FgSge1 in F. graminearum. In addition, we characterized the FgSGE1 deletion mutants and found that the mutants showed increased sensitivity to osmotic stress mediated by NaCl or KCl, and to cell wall damaging agent congo red (CR). Real-time PCR assays revealed increased transcription levels of FgSGE1 with the treatment of NaCl or CR, and decreased FgSGE1 transcription in the FgOS-2 deletion mutant ΔFgOs-2. Based on the transcription levels, it can be concluded that FgSge1 is a downstream target of the mitogen-activated protein kinase FgOs-2.


Effect of posttranslational modifications on enzyme function and assembly.
The detailed examination of enzyme molecules by mass spectrometry and other techniques continues to identify hundreds of distinct PTMs. Recently, global analyses of enzymes using methods of contemporary proteomics revealed widespread distribution of PTMs on many key enzymes distributed in all cellular compartments. Critically, patterns of multiple enzymatic and nonenzymatic PTMs within a single enzyme are now functionally evaluated providing a holistic picture of a macromolecule interacting with low molecular mass compounds, some of them being substrates, enzyme regulators, or activated precursors for enzymatic and nonenzymatic PTMs. Multiple PTMs within a single enzyme molecule and their mutual interplays are critical for the regulation of catalytic activity. Full understanding of this regulation will require detailed structural investigation of enzymes, their structural analogs, and their complexes. Further, proteomics is now integrated with molecular genetics, transcriptomics, and other areas leading to systems biology strategies. These allow the functional interrogation of complex enzymatic networks in their natural environment. In the future, one might envisage the use of robust high throughput analytical techniques that will be able to detect multiple PTMs on a global scale of individual proteomes from a number of carefully selected cells and cellular compartments. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.


Surface-Triggered Tandem Coupling Reactions of Cyclic Azasilanes.
Cyclic azasilanes have been synthesized for the purpose of developing coupling agents appropriate for a variety of nanotechnologies including surface modification of nanoparticles, nanocrystals, mesoporous materials and substrates. N-Methyl-aza-2,2,4-trimethylsilacyclopentane is representative of this class of compounds. Preliminary data for the treatment of inorganic surfaces, including nanoparticles and oxidized silicon wafers, with cyclic azasilanes suggest high-density monolayer deposition by a ring-opening reaction. Cyclic azasilanes contain a cryptic amine functionality that can perform a subsequent tandem coupling reaction with functional molecules after the surface-triggered ring-opening reaction, allowing for a one-pot self-assembly route on nanostructures. Tandem coupling reactions are demonstrated via addition reactions of the cryptic amine with epoxy and acrylate systems.


Direct nucleophilic and electrophilic activation of alcohols using a unified boron-based organocatalyst scaffold.
Organocatalytic strategies for the direct activation of hydroxy-containing compounds have paled in comparison to those applicable to carbonyl compounds. To this end, boronic acids have emerged as valuable catalysts for the functionalization of hydroxy groups in a mild and selective fashion. Distinct modes of activation in boronic acid-catalyzed transformations are often accomplished by vastly different catalytic species, complicating the design of broadly applicable catalyst classes. Herein, we report the use of benzoxazaborine as a general scaffold for the development of structurally related yet mechanistically divergent catalysts for the direct nucleophilic and electrophilic activation of alcohols under ambient conditions. The utility of these catalysts is demonstrated in the monophosphorylation of vicinal diols and the reductive deoxygenation of benzylic alcohols and ketones respectively. Mechanistic studies of both processes reveal the contrasting nature of key tetravalent boron intermediates in the two catalytic manifolds.


Microsurgical anatomy of the extra-articular segment of middle genicular artery.
Knowledge of the incompletely studied microsurgical anatomy of the extracapsular part of the middle genicular artery (MGA) could imply an educational value and clinical significance because of the possible risk of injury during knee surgery. Thirty formol-fixed cadaveric lower limbs in full extension were dissected and used for the measurements of MGA parameters. A second group of measurements was performed on distal ends of 30 adult femurs. Two fresh injected cadaveric lower limbs were explored by means of multidetector computed tomographic angiography (MDCTA). The MGA originated from the popliteal artery (PA), facing the lateral half of the intercondylar fossa in 16 (53.4 %) specimens, together with the superior lateral genicular artery (SLGA) in ten (33.3 %) cases, or from the same point of origin with SLGA and superior medial genicular artery (SMGA) in 4 (13.3 %) cases. The MGA averaged 15.6 mm in length and 1.8 mm in the outer diameter. After its curved direction the MGA entered the posterior capsule. The average distances of the point of MGA entrance into the joint capsule were as follows: to the lateral femoral epicondyle it was 34.88 mm, to the medial femoral epicondyle 46.38 mm, 5.74 mm lateral to the posterior midline, with an average vertical distance to the femoral subcondylar plane of 28.73 mm. This detailed anatomical examination with measurements of the extracapsular part of a MGA could be of clinical importance and useful in knee surgery for the prevention of vascular injury of MGA and PA, as well as in radiological examination of the knee region.


The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain.
We have identified and sequenced cDNA clones that encode for the human beta-subunit of rod cGMP phosphodiesterase (PDEB). A single 2565-bp open reading frame that codes for an 854-amino-acid protein was identified. The human beta-subunit protein is 90% identical to the bovine beta-subunit and 91% identical to the mouse protein. Northern blot analysis indicates that the gene is expressed as an abundant 3.5-kb transcript in retina and as a rare 2.9-kb transcript in brain. The isolation of cDNAs from human brain cDNA libraries confirms the brain as a site of expression for this gene. The molecular defect underlying retinal degeneration in the rd mouse has been found to be a nonsense mutation in the beta-subunit of the mouse cGMP PDE, resulting in a truncated protein (Pittler et al., 1991b, Proc. Natl. Acad. Sci. USA. 88: 8322-8326). The molecular cloning of the cDNA encoding for the PDEB represents the first step in establishing whether this gene plays a causative role in any one of the several human hereditary retinopathies or, based on its localization to chromosome 4p 16.3, in the pathogenesis of Huntington disease.


In vitro and in vivo inhibition of [3H]imipramine binding by cadmium.
Chronic exposure of rats to CdCl2 altered the specific binding of [3H]imipramine to membranes from platelets and hypothalamus. There was a decrease in Bmax of 10-40% and a decrease in KD values of 30-40% as compared to the control group. In vitro studies on the inhibition of [ 3H ]imipramine binding to membranes from human and rat platelets and hypothalamus by CdCl2 corroborate the in vivo results which imply that the imipramine binding protein contains Cd2+-sensitive groups.


In vivo antiplasmodial activities of aqueous extract of Bridelia ferruginea stem bark against Plasmodium berghei berghei in mice.
Bridelia ferruginea Benth (Euphorbiaceae) is an indigenous medicinal plant in Nigeria. It is usually a gnarled shrub which sometimes reaches the size of a tree in suitable condition. Decoctions of parts of this plant have been employed in ethno medicine in many parts of Africa for treatment of many ailments including malaria fever. In vivo antiplasmodial activity of aqueous stem bark extract of BF was investigated against Plasmodium berghei-infected mice. The aqueous stem bark extract of BF (100-400 mg/kg) was administered orally to P. berghei-infected mice in both early and established models of antiplasmodial studies. The extract exhibited significant (p < 0.05) antiplasmodial activity in early and established infection tests with a considerable mean survival time comparable to that of chloroquine, 10 mg/kg. The oral LD(50) obtained was greater than 5000 mg/kg in mice. The findings show that aqueous stem bark extract of Bridelia ferruginea possesses considerable antiplasmodial activity which can be developed in malaria therapy.


Manganese ion concentration affects production of human core 3 O-glycan in Saccharomyces cerevisiae.
Production of various mucin-like glycoproteins could be useful for development of antibodies specific to disease-related glycoproteins as well as for the biosynthesis of clinically useful glycoproteins. A Saccharomyces cerevisiae strain capable of in vivo production of mucin-type core 1 structure (Galβ1-3GalNAcα1-O-Ser/Thr) has been reported, but a strain producing core 3 structure (GlcNAcβ1-3GalNAcα1-O-Ser/Thr) has not been constructed. To generate core 3-producing strain, genes encoding uridine diphosphate (UDP)-Gal-4-epimerase, UDP-GalNAc transporter, UDP-GlcNAc transporter, and two glycosyltransferases were integrated into the genome. A Mucin-1-derived acceptor peptide (MUC1ap) was expressed as an acceptor. The amount of the resulting modified peptide was analyzed by HPLC. Introduction of a codon-optimized UDP-GlcNAc:βGal β-1,3-N-acetylglucosaminyltransferase 6 (β3Gn-T6) gene yielded increases in β3Gn-T6 activity but did not alter the level of core 3 production. The highest in vitro activity of β3Gn-T6 was observed at Mn(2+) concentrations of 10mM and above. Supplementation of MnCl2 to the culture medium yielded increases of up to 25% in the accumulation of core 3 on the MUC1ap. The yeast invertase from the core 3-producing strain was less extensively N-glycosylated; however, it was partially restored by the addition of MnCl2 to the medium. Physiological Mn(2+) concentration in S. cerevisiae was insufficient to facilitate optimal synthesis of core 3. Mn(2+) supplementation led to up-regulation of reaction of glycosylation in the Golgi, resulting in increases of core 3 production. This study reveals that control of Mn(2+) concentration is important for production of specific mammalian-type glycans in S. cerevisiae.


Serotonin immunoreactivity in the peripheral nervous system of oligochaeta.
The distribution of serotonin immunoreactive elements in the peripheral nervous system of three earthworm species (Lumbricus terrestris, Eisenia fetida and Tubifex tubifex) was studied using the peroxidase-antiperoxidase method. Most parts of the peripheral nervous system contain immunoreactive fibers. All segmental nerves as well as branches of the prostomial nerves show strong immunoreactivity. Muscles of the body wall contain serotonergic fibers, mostly between the circular and longitudinal layers. The best supplied area is the buccal musculature. All parts of the enteric nervous system contain serotonergic fibers, strongest staining was observed in the buccal and pharyngeal walls. Along the wall of the calciferous glands thin immunoreactive fibers were found. The excretory system, the metanephridial tubules also display immunoreactivity. Under the surface epithelium, a serotonergic subepidermal plexus was observed. No significant differences were observed between the species studied. On the basis of our morphological findings and functional studies performed by other authors it is suggested that serotonin plays an essential role in the function of the peripheral nervous system in Oligochaeta.


Isozyme selective arylation of cytosolic glutathione S-transferase by [14C]bromobenzene metabolites.
[14C]Bromobenzene was incubated with NADPH-fortified liver homogenates from phenobarbital-treated rats, after which the glutathione S-transferases were isolated from the incubation mixture. Glutathione S-transferase activity, with 1-chloro-2,4-dinitrobenzene as the substrate, in the homogenate was unchanged after incubation with bromobenzene. Radioactivity derived from the [14C]bromobenzene remained associated with the cytosolic glutathione S-transferases after DE52 and Sephadex G-100 chromatography. Further purification of the cytosolic glutathione S-transferase by CM52 and hydroxylapatite chromatography showed that bromobenzene metabolites were bound to fractions containing glutathione S-transferase subunits 4, 5, and 1. The primary site of arylation appeared to be subunit 1, as indicated by autoradiography and hydroxylapatite chromatography. [14C]Bromobenzene metabolites were not bound to microsomal glutathione S-transferases. These data show that hepatic cytosolic glutathione S-transferases, especially glutathione S-transferases 4-4/5-5, 3-4, and 1-1 may act as trapping or scavenger proteins for reactive metabolites and that this effect is not associated with a loss of catalytic activity.


An evaluation of craniofacial growth pattern in North Indian children.
The aim of this study was to assess craniofacial growth pattern in children with generalized decreased skeletal age and compare it with the children having normal skeletal age. Lateral cephalograms and hand wrist radiographs of 40 patients (age group 3-14 years) were taken and skeletal age assessment was done with hand wrist radiographs according to Greulich and Pyle, based on which two groups were made, Group A - Control group (normal skeletal age) and Group B - study group (decreased skeletal age). Group A had a sample size of 21 and Group B, a sample size of 19. These were further divided into subgroups according to age: subgroup (a) - 3 to 6 years, subgroup (b) - 7 to 11 years and subgroup (c) - 12 to 14 years. The skeletal and dental patterns were analyzed with Down's Cephalometric analysis. Student "t" test was used to verify comparisons in all the subgroups of patients of Group A and Group B. The facial angle and Cant of occlusal plane exhibited maximum difference between the two groups which indicated that mandibular growth was affected more than other bones in diseased child patients. The present study led to the conclusion that craniofacial growth was retarded in children with generalized decreased skeletal age in comparison to healthy child patients.


Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction.
Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock. Retrospective, clinical study in the medical intensive care unit of a university hospital. 17 patients with septic shock and 19 control subjects. Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days. In septic shock we found a significant increase in ANP (82.7+/-9.9 vs. 14.9+/-1.2 pg/ml) and BNP (12.4+/-3.6 vs. 5.5+/-0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=-0.56; p<0.05). ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.


Maximum Lyapunov exponent-based multiple chaotic slime mold algorithm for real-world optimization.
Slime mold algorithm (SMA) is a nature-inspired algorithm that simulates the biological optimization mechanisms and has achieved great results in various complex stochastic optimization problems. Owing to the simulated biological search principle of slime mold, SMA has a unique advantage in global optimization problem. However, it still suffers from issues of missing the optimal solution or collapsing to local optimum when facing complicated problems. To conquer these drawbacks, we consider adding a novel multi-chaotic local operator to the bio-shock feedback mechanism of SMA to compensate for the lack of exploration of the local solution space with the help of the perturbation nature of the chaotic operator. Based on this, we propose an improved algorithm, namely MCSMA, by investigating how to improve the probabilistic selection of chaotic operators based on the maximum Lyapunov exponent (MLE), an inherent property of chaotic maps. We implement the comparison between MCSMA with other state-of-the-art methods on IEEE Congress on Evolution Computation (CEC) i.e., CEC2017 benchmark test suits and CEC2011 practical problems to demonstrate its potency and perform dendritic neuron model training to test the robustness of MCSMA on classification problems. Finally, the parameters' sensitivities of MCSMA, the utilization of the solution space, and the effectiveness of the MLE are adequately discussed.


Heart rate variability in the irritable bowel syndrome: a review of the literature.
Patients with irritable bowel syndrome (IBS) often present with disturbances of bowel habits (diarrhea, constipation) and abdominal pain/discomfort that are modulated by the autonomic nerve system (ANS). In this narrative review, we analyzed studies that measured ANS functioning in IBS by means of heart rate variability (HRV). The PUBMED was searched with the keywords 'irritable bowel syndrome' AND ('heart rate variability' OR 'autonomic function'). We included only papers that used 'traditional' HRV indices and diagnosed IBS based on Manning or Rome criteria. Studies were sub-grouped according to methodological features of HRV analysis (24-h monitoring, short-term laboratory records, records during sleep). Most studies reported no difference in HRV when the IBS population was compared to healthy controls. Dividing the IBS sample into subgroups--according to their predominant bowel symptoms, the severity of clinical course, the presence of depressive symptoms, or a history of abuse in the past--revealed changes in autonomic functioning. Patients with IBS appear to experience symptoms that may be the result of changes in ANS functioning. HRV measures in clinical routine may allow assessing these changes, but further studies performed in a standardized fashion should improve the validity of HRV measures for clinical research first.


The clinical usefulness of central hemodynamics to evaluate diastolic dysfunction in subjects without hypertension.
Diastolic dysfunction is associated with increased arterial stiffness in patients with hypertension. However, the role of arterial stiffness in diastolic dysfunction in subjects without hypertension has not been fully established. A total of 287 subjects (male:female ratio 121:166, mean age 53.0±14.4 years) without hypertension or any heart disease who simultaneously received transthoracic echocardiography and noninvasively semiautomated radial artery applanation tonometry (with an Omron HEM-9000AI) in the Department of Internal Medicine, St Vincent's Hospital, from July 2011 to September 2012, were enrolled in this study. A total of 147 subjects (male:female ratio 59:88, mean age 61.7±9.9 years), representing 51.2% of the 287 subjects, had diastolic dysfunction (defined as abnormal relaxation pattern of mitral inflow). There were significant differences in systolic blood pressure (BP), pulse pressure, late systolic peak pressure (SBP2), and radial augmentation index (RaAIx) between normal diastolic function and diastolic dysfunction. ΔBP was defined as systolic BP minus SBP2, because of the difference in systolic BP between the two groups. ΔBP (odds ratio [OR] 1.059, 95% confidence interval [CI] 1.005-1.115; P=0.032) and RaAIx (odds ratio 1.027, 95% CI 1.009-1.044, P=0.003) were associated with diastolic dysfunction. A receiver operating-characteristic curve showed that ΔBP (area under the curve 0.875, 95% CI 0.832-0.911) and RaAIx (area under the curve 0.878, 95% CI 0.835-0.914) were associated with diastolic dysfunction. We found that ΔBP and increased RaAIx were associated with diastolic dysfunction in subjects without hypertension after adjustment for age and sex. Therefore, it is suggested that noninvasive estimation of central BP may be useful to reflect diastolic dysfunction in subjects with normal peripheral BP.


Role of cyclic AMP in differentiation of human neuroblastoma cells in culture.
The inhibitors of cyclic AMP phosphodiesterase (papaverine and 4-(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone), serum-free medium, and x irradiation caused cell death and neurite formation in human neuroblastoma cells in culture (IMR-32), whereas theophylline was ineffective. Prostaglandin (PG) E1, N6O'2-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) induced neurites without causing cell lethality. Inhibitors of phosphodiesterase and PGE1 increased the intracellular level of cAMP by about 2- and 4-fold respectively, whereas serum-free medium and x irradiation did not. The combination of PGE1 and phosphodiesterase inhibitor was more effective in causing morphological differentiation and in increasing the cAMP level than the individual agent. Sodium butyrate induced cell death and neurites, probably in part by increasing the cAMP level. cAMP, guanosine 3',5'-cyclic monophosphate, and adenosine had no detectable effect on the growth or morphology of neuroblastoma cells in culture. Adenosine 5'-monophosphate produced cell death without causing neurite formation. DbcAMP, and to a much lesser degree, sodium butyrate increased the tyrosine hydroxylase activity.


Antiarrhythmic effects of intravenous timolol in supraventricular arrhythmias.
The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias. In our double-blind, randomized, parallel, multiclinic study, subjects received timolol, 1 mg iv, or matching placebo as a starting dose, followed by a second and third dose of 1 mg each (or matching placebo) at 20-min intervals if the arrhythmia did not convert to sinus rhythm. Subjects in whom the sinus rhythm returned or the ventricular rate decreased to less than 100 bpm were transferred to a dosing regimen of timolol in 10-mg tablets twice a day by mouth, 1 hr after the last intravenous dose. Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo. The overall proportion of responders (either conversion to sinus rhythm or a decrease in ventricular rate to less than 100 bpm) was 68% after timolol and 7% after placebo. The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia (26 of 32 subjects and two of 38 subjects), atrial fibrillation (17 of 29 subjects and three of 32 subjects), and atrial flutter (seven of 11 subjects and one of nine subjects). The most common adverse effects were bradycardia and hypotension.


Motor and somatosensory evoked potentials in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) linked to chromosome 2p, SPG4.
The aim of our study was to evaluate Motor Evoked Potentials (MEPs) and cortical excitability, using Transcranial Magnetic Stimulation (TMS) as well as short latency Somatosensory Evoked Potentials (SEPs) in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) patients. MEPs were recorded from upper and lower limb muscles in 12 patients (7 m and 5f) affected by ADHSP with spastin mutation (SPG4). We measured: (i) motor threshold (MTh); (ii) total motor conduction time (TMCT); (iii) direct and indirect central motor conduction time (d-CMCT and i-CMCT) calculated by subtracting from the cortical latency those obtained on magnetic spinal stimulation (d-PMCT) and via the F-wave method (i-PMCT); (iv) MEP amplitude (MEP/Mmax ratio%) and (v) duration of the cortical silent period (CSP). Latency, amplitude and persistence of the F-wave obtained with electrical nerve stimulation were also considered; H reflex was also tested from lower extremities. SEPs were recorded from spine and scalp sites following median and posterior tibial nerve stimulation; conventional latency and amplitude measurements were performed. In a comparison with the control group, the MTh recording from lower limbs was significantly higher (67.5 +/- 7.7% versus 52.5 +/- 6.9%), MEPs were absent in one case and showed reduced amplitude in the remainders (22.9 +/- 12.6% versus 66.3 +/- 25.9% of M wave); TMCT resulted to be abnormal (36.5 +/- 3.9 ms versus 27.1 +/- 1.4 ms) and d-CMCT as well as i-CMCT were significantly prolonged (23.1 +/- 3.5 ms versus 13.8 +/- 1.3 ms; and 20.1 +/- 3.4 ms versus 10.6 +/- 1.3 ms, respectively). The CSP, which was normal from the hands, was significantly shortened from the legs and correlated with spasticity scoring (Ashworth scale). Cortical SEPs from lower limbs were abnormal in all cases, whereas SEPs by stimulation of median nerves were normal; F-wave parameters from upper limbs showed no abnormalities, whereas an increased persistence was detected from lower limbs; H reflex amplitudes resulted larger compared with controls. Moreover, shortening of the CSP, being correlated with the Ashworth scale, can be considered an electrophysiological marker of spasticity that seems to arise from impairment of the supraspinal or intracortical inhibitory pathways with an additional contribution of increased segmental motor neuron excitability. These data prove the existence of comparable neurophysiological abnormalities in ADHSP with spastin mutation (SPG4) when long ascending and descending pathways are involved.


A collaborative study to establish the first National Standard for HIV-1 RNA nucleic acid amplification techniques (NAT) in Taiwan.
The World Health Organization (WHO) International Standard (IS) for human immunodeficiency virus type 1 (HIV-1) RNA is only available in limited amounts. It is critical to use the most common HIV-1 genotype as source for secondary standards, e.g. a National Standard for Taiwan. The objective of this study was to establish the first National Standard for HIV-1 RNA NAT assays in Taiwan. A collaborative study, including eleven laboratories from five different countries, was carried out to establish the HIV-1 RNA National Standard by calibration, in International Units (IU), against the WHO HIV-1 RNA IS. The HIV-1 RNA content for the candidate was quantitated by each laboratory in three independent assays and the results were collected and analyzed statistically. Overall, a high level of agreement among results was achieved from different laboratories. In addition, the stability study indicated that the candidate was stable for 24 months at -80±5°C. In conclusion, the candidate standard was established as the first National Standard for HIV-1 RNA for use in NAT assays in Taiwan. The standard is intended to be used for the quality control of HIV-1 NAT assays and as a quantitative reference material for HIV-1 NAT assays.


A general method for selecting strains of Escherichia coli having altered spontaneous or induced mutabilities.
A simple method is described for selecting mutant strains of E. coli differing from their parent in the ability to spontaneously mutate via any mechanism. The method detects hypo- and hyper-mutators. It relies on the detection as papillae on thy colonies of second mutations either at the dra or drm locus.


Characterization of differential ripening pattern in association with ethylene biosynthesis in the fruits of five naturally occurring banana cultivars and detection of a GCC-box-specific DNA-binding protein.
MA-ACS1 and MA-ACO1 are the two major ripening genes in banana and play crucial role in the regulation of ethylene production during ripening. Here, we report a comparative ripening pattern in five different naturally occurring banana cultivars namely Cavendish (AAA), Rasthali (AAB), Kanthali (AB), Poovan (AAB) and Monthan (ABB), which have distinct genome composition. We found a distinct variation in the climacteric ethylene production and in-vivo ACC oxidase activity level during the ripening stages in the five cultivars. We identified the cDNAs for MA-ACS1 and MA-ACO1 from the five cultivars and studied the transcript accumulation patterns of the two genes, which correlated well with the differential timing in the expression of these two genes during ripening. The GCC-box is one of the ethylene-responsive elements (EREs) found in the promoters of many ethylene-inducible genes. We have identified a GCC-box motif (putative ERE) in the promoters of MA-ACS1 and MA-ACO1 in banana cultivars. DNA-protein interaction studies revealed the presence of a GCC-box-specific DNA-binding activity in the fruit nuclear extract and such DNA-binding activity was enhanced following ethylene treatment. South-Western blotting revealed a 25-kDa nuclear protein that binds specifically to GCC-box DNA in the climacteric banana fruit. Together, these results indicate the probable involvement of the GCC-box motif as the cis-acting ERE in the regulation of MA-ACS1 and MA-ACO1 during ripening in banana fruits via binding of specific ERE-binding protein.


Risk of Relapse in Patients With Ulcerative Colitis With Persistent Endoscopic Healing: A Durable Treatment Endpoint.
Deep remission in patients with UC has relied on initial achievement of biochemical, endoscopic, and/or histological remission. We evaluated persistent symptomatic remission and endoscopic healing (EH: Mayo endoscopy score [MES] 0 or 1) on consecutive endoscopic examinations as a durable treatment endpoint. In a retrospective cohort study, we estimated and compared cumulative risk of clinical relapse in patients with persistent EH, with and without persistent histological remission and depth of EH, among adults with active UC treated-to-target of symptomatic remission and EH who achieved and maintained symptomatic remission and EH over two serial endoscopic assessments. We also explored risk of relapse in patients with persistent EH whose therapy was de-escalated. Of 270 patients who initially achieved EH with treatment-to-target, 89 maintained symptomatic remission and EH on follow-up endoscopy [interval between EH1 and EH2, 16 months]. On follow-up after EH2 [median, 19 months], 1-year cumulative risk of relapse in patients with persistent EH was 11.5%, and with persistent histological remission was 9.5%. Seventeen patients with persistent EH, who underwent de-escalation of therapy, did not have an increased risk of relapse as compared with patients who continued index therapy [5.3% vs 14%, p = 0.16]. Patients with active UC treated-to-target of clinical remission, who achieve and maintain symptomatic remission and EH over consecutive endoscopies, have a low risk of relapse, particularly in a subset of patients who simultaneously achieve histological remission. Persistent EH should be examined as a treatment endpoint suggestive of deep remission.


Deciphering the substrate specificity of housekeeping sortase A and pilus-specific sortase C of probiotic bacterium Lactococcus lactis.
Several strains and species of lactic acid bacteria (LAB) are widely used in fermented foods, including dairy products and also as probiotics, because of their contribution to various health benefits in humans. Sortase enzymes decorate the bacterial cell wall with different surface proteins and pili for facilitating the interactions with host and environment for the colonization and beneficial effects. While the sortases and sortase anchored proteins from pathogens have been the prime focus of the research in the past, sortases from many non-pathogenic bacteria, including LAB strains, have attracted attention for their potential applications in vaccine delivery and other clinical interventions. Here, we report the purification and functional characterization of two sortases (housekeeping SrtA and pilus-specific SrtC) from a probiotic Lactococcus lactis. The purified sortases were found to be active against the putative LPXTG motif-based peptide substrates, albeit with differences. The in-silico analysis provides insights into the residues involved in substrate binding and specificity. Overall, this study sheds new light on the aspects of structure, substrate specificity, and function of sortases from non-pathogenic bacteria, which may have physiological ramifications as well as their applications in sortase-mediated protein bioconjugation.


A hyperelastic model for simulating cells in flow.
In the emerging field of 3D bioprinting, cell damage due to large deformations is considered a main cause for cell death and loss of functionality inside the printed construct. Those deformations, in turn, strongly depend on the mechano-elastic response of the cell to the hydrodynamic stresses experienced during printing. In this work, we present a numerical model to simulate the deformation of biological cells in arbitrary three-dimensional flows. We consider cells as an elastic continuum according to the hyperelastic Mooney-Rivlin model. We then employ force calculations on a tetrahedralized volume mesh. To calibrate our model, we perform a series of FluidFM[Formula: see text] compression experiments with REF52 cells demonstrating that all three parameters of the Mooney-Rivlin model are required for a good description of the experimental data at very large deformations up to 80%. In addition, we validate the model by comparing to previous AFM experiments on bovine endothelial cells and artificial hydrogel particles. To investigate cell deformation in flow, we incorporate our model into Lattice Boltzmann simulations via an Immersed-Boundary algorithm. In linear shear flows, our model shows excellent agreement with analytical calculations and previous simulation data.


Combined weightbearing CT and MRI assessment of flexible progressive collapsing foot deformity.
The objective of this study was to evaluate the correlation between Weightbearing CT (WBCT) markers of pronounced peritalar subluxation (PTS) and MRI findings of soft tissue insufficiency in patients with flexible Progressive Collapsing Foot Deformity (PCFD). We hypothesized that significant correlation would be found. Retrospective comparative study with 54 flexible PCFD patients. WBCT and MRI variables deformity severity were evaluated, including markers of pronounced PTS, as well as soft tissue degeneration. A multiple regression analysis and partition prediction models were used to evaluate the relationship between bone alignment and soft tissue injury. P-values of less than .05 were considered significant. Degeneration of the posterior tibial tendon was significantly associated with sinus tarsi impingement (p = .04). Spring ligament degeneration correlated to subtalar joint subluxation (p = .04). Talocalcaneal interosseous ligament involvement was the only one to significantly correlate to the presence of subfibular impingement (p = .02). Our results demonstrated that WBCT markers of pronounced deformity and PTS were significantly correlated to MRI involvement of the PTT and other important restraints such as the spring and talocalcaneal interosseus ligaments. Level III, Retrospective comparative study.


Motion artifacts in quantitative magnetic resonance imaging.
Several investigators have emphasized the potential value of quantitative relaxation times in the assessment of diseases. In performing such measurements using the spin-echo technique, we have encountered several anomalous results, whereby the intensity of the organ parenchyma on second-echo images is greater than on first echo images. This is most likely a result of respiratory motion, and it occurs only rarely. Several volunteers were studied before and after exercise to see if respiratory motion could reproduce the anomalous intensity reverse; a reversal of intensities in renal parenchyma was observed in two of five individuals. We conclude that respiratory motion artifacts will seriously limit quantitative magnetic resonance imaging of the upper abdomen if respiratory gating during imaging is not used.


Longitudinal study of dietary patterns and hypertension in adults: China Health and Nutrition Survey 1991-2018.
China is undergoing the nutrition transition that may explain partly the high prevalence of hypertension. We aimed to investigate the longitudinal association between dietary patterns and hypertension in Chinese adults over 28 years of follow-up. We used data collected in the China Health and Nutrition Survey from 1991 to 2018. Adults aged 18 years and above (n = 15,929) were included in the analysis, for whom questionnaires and anthropometric data were collected during at least two waves. Factor analysis was conducted to derive food patterns based on 18 foods or food groups. We constructed three-level mixed-effect linear regression models to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP) in relation to quartiles of dietary pattern score and performed three-level mixed-effect logistic regression models to assess the risk of hypertension. Participants in the top quartile of the modern pattern had a decrease in SBP (β = - 0.51; 95% CI -0.86, -0.16; P < 0.01) when adjusted for all potential confounders, whereas participants in the top quartile of the meat pattern had an increase in DBP (β = 0.31; 95% CI 0.08, 0.53; P < 0.01). Participants in the highest quartile of the meat pattern were more likely to have hypertension (OR = 1.14; 95% CI 1.03, 1.24; P < 0.01). Adherence to the modern pattern characterized by high intake of fruits and dairy products was inversely associated with SBP, whereas the meat pattern was positively associated with DBP and the risk of hypertension. These findings may well have important public health implications.


Immunoglobulin allotypes Gm and Km in hematologic malignancies.
Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.


[The invasive ability of bladder cancer].
To find a direct method for testing the invasive ability of bladder cancer. The invasive ability of 49 specimens of primarily cultured bladder cancer, transfected BIU-87 cells with pcDNA3-E1AF and untransfected BIU-87 cells was evaluated by Matrigel invasion assay. Sixteen of the 49 specimens were found to penetrate the matrigel barrier, and the result of the Matrigel invasion was related to the grade of the tumor cells. The number of positive cells of transfected BIU-87 was remarkably larger than that of untransfected BIU-87. Matrigel invasion assay is a simple, direct and dependable method, and could be used clinically to test the invasive ability of bladder cancer.


Sinonasal primitive neuroectodermal tumor arising in a long-term survivor of heritable unilateral retinoblastoma.
Patients who survive retinoblastoma (RB) are at risk for having second nonocular tumors, usually osteosarcomas, which often are fatal. Such patients almost always have bilateral RB. This article reports a woman who, at the age of 1 year had been cured of a unilateral RB by radiation therapy and enucleation. Eighteen years later, she had a sinonasal small cell tumor that rapidly recurred and proved fatal 2 months after surgical debulking. The tumor was studied by immunohistochemistry and electron microscopic (EM) examination. It showed diffuse neuron-specific enolase staining, focal weak staining for chromogranin, synaptophysin, and Leu-7 monoclonal antibodies in paraffin-embedded, B5-fixed tissue (Great Lakes Diagnostics, Troy, MI). EM study showed an undifferentiated primitive neuroectodermal tumor with many polyribosomes, simple cell junctions, few microtubules, and rare dense core granules. The combined immunohistochemical, ultrastructural, and clinical features of the tumor were interpreted as a sinonasal primitive neuroectodermal tumor with early neuronal differentiation. The tumor was pathologically indistinguishable from poorly differentiated olfactory neuroblastoma (ONB) and Ewing sarcoma.


Mechanism of synergistic action on behavior, oxidative stress and inflammation following co-treatment with ketamine and different antidepressant classes.
Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist. Wistar rats were acutely treated with fluoxetine (1.25mg/kg), quetiapine (5mg/kg), and lamotrigine (5.0mg/kg) alone or in combination with ketamine (5.0mg/kg), and then subjected to behavioral tests. In addition, oxidative damage and antioxidant capacity were assessed in the rat brain, and pro-inflammatory cytokines levels were evaluated in the serum. It was observed a synergistic effect of ketamine in combination with fluoxetine on the immobility time in the forced swimming test, indicating an antidepressant effect. Other antidepressant did not show effects when administrated alone or joint to ketamine. The combination of ketamine with other antidepressants, particularly quetiapine, in some brain regions induced an increase in damage to lipids and proteins. However, the combination of ketamine with fluoxetine increased the antioxidant activity of superoxide dismutase, and decreased oxidative damage, thus suggesting a neuroprotective effect of the combination of these drugs. The combination of ketamine with fluoxetine or lamotrigine reduced pro-inflammatory cytokines levels. In conclusion, ketamine induced antioxidant or pro-antioxidant effects dependent of antidepressant classes or brain area.


Probes for narcotic receptor mediated phenomena. 47. Novel C4a- and N-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols.
A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found to have modest receptor affinity both at μ- (K(i)=60 nM) and δ-opioid receptors (K(i)=64 nM). The N-methyl substituent of 2a and that of other ligands in the series was then modified to obtain compounds with different N-substituents that might provide higher affinity at both receptors. A number of compounds differently substituted at C4a and N were synthesized and evaluated. Binding studies and functional assays revealed a moderately selective δ-antagonist (2l), selective μ-δ antagonists (3d, 3g), and a μ-κ antagonist (3f).


Immunohistochemical localization of Na+/Ca2+ exchanger in human retina and retinal pigment epithelium.
Impaired calcium (Ca2+) metabolism has been implicated in the pathogenesis of various ocular diseases, suggesting that regulation of Ca2+ homeostasis in the retina is of major significance for normal function. There are known families of transport proteins that can catalyze net Ca2+ efflux across the plasma membrane, one of which is the Na+/Ca2+ exchanger. Using immunohistochemistry, we have investigated the human retina and retinal pigment epithelium (RPE) for the presence and distribution of the so-called cardiac-type Na+/Ca2+ exchanger. Paraffin sections of ten eyes enucleated for various disease processes were incubated according to the ABC method with a polyclonal antibody (pi) produced against the canine cardiac sarcolemmal Na+/Ca2+ exchanger. The reaction was visualized with aminoethylcarbazole. There was a positive reaction with anti-Na+/Ca2+ exchanger in the retina and RPE in all eyes, but the labeling varied among the different specimens. In neural retina, staining was most intense in Mueller cells, in cells of the inner nuclear layer, and in cone inner segments. Immunoreactivity was less pronounced in ganglion cells, nerve fibers, the outer nuclear layer and in rod inner segments. Outer segments appeared mostly negative. In the RPE, positive staining was present but the intensity of staining varied both within and among the specimens. Reactive RPE cells revealed the most intense labeling. Na+/Ca2+ exchanger of the cardiac type is present in human retina and RPE. The variation in immunoreactivity among the different specimens may reflect the different diseases of these eyes and their different metabolic states. A specific relation between certain diseases and malfunction of the Na+/Ca2+ exchanger could have a major impact on therapeutic regimens.


Salted food preferences in rats (Rattus norvegicus): responses to liquid milk products.
Sprague-Dawley rats do not prefer salted (NaCl) solid food when it is presented with its unsalted counterpart but prefer isotonic saline when it is presented with plain water. Preferences in liquid foods were examined by giving rats one-hour choices between various salted liquid milk products and their unsalted counterparts. When heavy cream and half and half were tested, rats consumed either equal amounts of the salted and unsalted food, or more of the unsalted food. The absence of salt preference in heavy cream and half and half was evident using other testing procedures and, with heavy cream, additional salt concentrations. In contrast, rats consumed more skin milk containing 0.150 M NaCl than plain skim milk. The role of fat content in modulating the expression of these salt preferences was examined in tests using whole milk and low-fat milk, both of which have water, protein and carbohydrate contents similar to skim milk, but a greater fat content. Unlike skim milk, preferences for 0.150 M NaCl in whole milk and low-fat milk were approximately 50%. The role of solidity in salted food preferences was also investigated by adding gelatin to salted (0.150 M NaCl) and unsalted skim milk. Whereas the rats ate equal quantities of salted and unsalted gelled skim milk, they preferred salted skim milk when it was a liquid. Results from these experiments suggest that several cues contained within food influence the expression of rats' salt preferences.


Pressing on: the legacy of Percy W. Bridgman.
A hundred years ago, Percy Bridgman invented mechanical devices that dramatically expanded the high-pressure range available for carrying out physics and chemistry experiments into an unprecedented regime of high densities. His pioneering work revolutionized condensed matter research. His spirit remains alive today as researchers continue to push back the boundaries of high-pressure science.


Adverse events and stroke prevention by interventional left atrial appendage occlusion in patients with low CHA2 DS2 -VASc score-results from the multicenter German LAARGE registry.
Interventional left atrial appendage occlusion (LAAO) is routinely performed in patients with nonvalvular atrial fibrillation and contraindications to standard anticoagulation. We investigated its role in patients at low stroke risk, and compared the effectiveness and safety in patients with low versus high risk. LAARGE is a prospective registry depicting the clinical reality of LAAO. LAAO was conducted with different standard commercial devices, and follow-up period was 1 year. Patients with started procedure and documented CHA2 DS2 -VASc score were selected from the whole database. A total of 638 patients from 38 centers were divided into CHA2 DS2 -VASc score ≤2, i.e., low-risk group (10.2%), and >2, i.e., high-risk group (89.8%). The latter had a pronounced cardiovascular risk profile and preceding strokes (0% vs. 23.9%; p < 0.001). Implantation success was consistently high (97.6%), frequencies of intrahospital major adverse cardiac and cerebrovascular events (0% vs. 0.5%) and other major complications (4.6% vs. 4.0%) were low (each p = not significant [NS]). Numerous moderate complications were also observed in the low-risk patients (12.3% vs. 9.4%; p = NS). Frequencies of nonfatal strokes (0% vs. 0.7%) and severe bleedings (0% vs. 0.7%) were low (each p = NS). In a specific analysis, patients at very high risk of stroke (i.e., CHA2 DS2 -VASc score >4) did not have increased rates of complications or nonfatal strokes in the first year after the procedure. Low-risk patients had no nonfatal strokes and major bleedings within 1 year after hospital discharge but had unexpectedly high rates of moderate procedural complications. The indication in these patients should be strictly defined based on an individual benefit-risk assessment.


Gastric mucosal damage induced by local intra-arterial administration of Paf in the rat.
1. A technique for the close-arterial administration of substances to the rat stomach in vivo has been developed. 2. Intra-arterial infusion of platelet-activating factor (Paf, 10-50 ng kg-1 min-1 for 10 min) induced macroscopically assessed damage in the corpus mucosa, characterized as vasocongestion and necrosis. 3. The threshold intra-arterial doses of Paf that induced histologically assessed damage in the antrum and corpus of the stomach (10 and 5 ng kg-1 min-1, respectively) produced minimal systemic hypotension (less than 20 mmHg) suggesting a dissociation between these events. 4. Pretreatment with the Paf-antagonist, L-652,731 (2.5 mg kg-1 i.v.) prevented the gastric damage induced by local infusion of Paf. 5. Intravenous infusion of Paf (25 ng kg-1 min-1) did not significantly damage the gastric mucosa, in contrast to the same dose infused locally, yet Paf administered by either route produced a comparable degree of hypotension. Such findings suggest minimal metabolism of Paf during its passage through the gastric circulation. 6. Local intra-arterial infusion of Paf in doses as low as 0.25 ng kg-1 min-1, which had no systemic hypotensive actions, significantly induced gastric damage in the presence of intragastric 20% ethanol. 7. These observations support a local role for Paf in the pathogenesis of gastric irritation and ulceration, such as that observed during endotoxin shock or bacterial infection. The present technique is thus useful for the study of locally administered substances on gastric function and integrity.


Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet.
Resveratrol, a polyphenolic activator of the silent information regulation 2 homolog 1 (SIRT1), is known to extend lifespan and improve metabolic disease. The aim of the present study is to test whether resveratrol protects against metabolic steatohepatitis through the modulation of lipid metabolism-related genes. We used a mouse model in which steatohepatitis can be induced by an atherogenic diet (Ath diet) to evaluate the effects of resveratrol on steatotic hepatitis and hepatic gene expression. The Ath diet induced excessive weight gain, hepatomegaly, dyslipidemia, and steatohepatitis after 8 weeks. The addition of resveratrol protected against Ath diet-induced changes and also alleviated steatohepatitis. Whole-genome expression analysis revealed that an Ath diet altered the hepatic expression of genes involved in lipid metabolism, and the addition of resveratrol to the diet reversed that effect. Real-time PCR and Western blot analysis confirmed the Ath diet up-regulated the levels of genes related to lipogenesis and down-regulated genes involved in lipolysis. Resveratrol clearly suppressed the Ath diet-induced alterations of the expression of genes related to lipid metabolism. Resveratrol ameliorated dyslipidemia and steatohepatitis induced by the Ath diet, and its beneficial effects were associated with the altered expression of hepatic genes involved in lipid metabolism.


Statistical inference of mass channel purity from Fisher ratio analysis using comprehensive two-dimensional gas chromatography with time of flight mass spectrometry data.
Tile-based Fisher ratio (F-ratio) analysis has recently been developed and validated for discovery-based studies of highly complex data collected using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS). In previous studies, interpretation and utilization of F-ratio hit lists has relied upon manual decomposition and quantification performed by chemometric methods such as parallel factor analysis (PARAFAC), or via manual translation of the F-ratio hit list information to peak table quantitative information provided by the instrument software (ChromaTOF). Both of these quantification approaches are bottlenecks in the overall workflow. In order to address this issue, a more automatable approach to provide accurate relative quantification for F-ratio analyses was investigated, based upon the mass spectral selectivity provided via the F-ratio spectral output. Diesel fuel spiked with 15 analytes at four concentration levels (80, 40, 20, and 10 ppm) produced three sets of two class comparisons that were submitted to tile-based F-ratio analysis to obtain three hit lists, with an F-ratio spectrum for each hit. A novel algorithm which calculates the signal ratio (S-ratio) between two classes (eg., 80 ppm versus 40 ppm) was applied to all mass channels (m/z) in the F-ratio spectrum for each hit. A lack of fit (LOF) metric was utilized as a measure of peak purity and combined with F-ratio and p-values to study the relationship of each of these metrics with m/z purity. Application of a LOF threshold coupled with a p-value threshold yielded a subset of the most pure m/z for each of the 15 spiked analytes, evident by the low deviations (< 5%) in S-ratio relative to the true concentration ratio. A key outcome of this study was to demonstrate the isolation of pure m/z without the need for higher level signal decomposition algorithms.


Multimodal data-driven prognostic model for predicting new-onset ST-elevation myocardial infarction following emergency percutaneous coronary intervention.
We developed a nomogram model derived from inflammatory indices, clinical data, and imaging data to predict in-hospital major adverse cardiac and cerebrovascular events (MACCEs) following emergency percutaneous coronary intervention (PCI) in patients with new-onset ST-elevation myocardial infarction (STEMI). Patients with new-onset STEMI admitted between June 2020 and November 2022 were retrospectively reviewed. Data pertaining to coronary angiograms, clinical data, biochemical indices, and in-hospital clinical outcomes were derived from electronic medical records. Lasso regression model was employed to screen risk factors and construct a prediction model. Overall, 547 patients with new-onset STEMI who underwent PCI were included and assigned to the training cohort (n = 384) and independent verification cohort (n = 163). Six clinical features (age, diabetes mellitus, current smoking, hyperuricemia, neutrophil-to-lymphocyte ratio, and Gensini score) were selected by LASSO regression to construct a nomogram to predict the risk of in-hospital MACCEs. The area-under-the-curve (AUC) values for in-hospital MACCEs risk in the training and independent verification cohorts were 0.921 (95% CI 0.881-0.961) and 0.898 (95% CI 0.821-0.976), respectively. It was adequately calibrated in both training cohort and independent verification cohorts, and predictions were correlated with actual outcomes. Decision curve analysis demonstrated that the nomogram was capable of predicting in-hospital MACCEs with good clinical benefit. Our prediction nomogram based on multi-modal data (inflammatory indices, clinical and imaging data) reliably predicted in-hospital MACCEs in new-onset STEMI patients with emergency PCI. This prediction nomogram can enable individualized treatment strategies.


Patient outcomes and cost analysis associated with an outpatient deep venous thrombosis treatment program.
Low-molecular-weight heparins are safe and effective for outpatient treatment of deep vein thrombosis (DVT). An outpatient DVT treatment program was established in a 532-bed nonprofit teaching hospital. With the cooperation and skills of a multidisciplinary team, 125 patients were treated for acute DVT primarily at home over 26 months. Preliminary results demonstrated a drop in average length of hospitalization from 5.4 days before the program to 0.97 days. All patients successfully completed a course of enoxaparin, averaging 5.23 days, with 4.26 days of treatment as outpatients. One hundred twenty-two patients (97.6%) required no rehospitalization for any reason, including recurrence of DVT and bleeding complications, throughout the 90-day anticoagulation treatment course. The hospital achieved a cost avoidance of $2470.68/patient. For all 125 patients, total cost avoidance was $308,835.17.


Evaluation of bacterial communities of Grana Padano cheese by DNA metabarcoding and DNA fingerprinting analysis.
The composition of the bacterial community of Grana Padano (GP) cheese was evaluated by an amplicon-based metagenomic approach (DNA metabarcoding) and RAPD-PCR fingerprinting. One hundred eighteen cheeses, which included 118 dairies located in the production area of GP, were collected. Two hundred fifty-four OTUs were detected, of which 82 were further discriminated between dominant (32 OTUs; > 1% total reads) and subdominant (50 OTUs; between 0.1% and 1% total reads) taxa. Lactobacillus (L.) delbrueckii, Lacticaseibacillus (Lact.) rhamnosus, Lact. casei, Limosilactobacillus fermentum, Lactococcus (Lc.) raffinolactis, L. helveticus, Streptococcus thermophilus, and Lc. lactis were the major dominant taxa ('core microbiota'). The origin of samples significantly impacted on both richness, evenness, and the relative abundance of bacterial species, with peculiar pattern distribution among the five GP production regions. A differential analysis allowed to find bacterial species significantly associated with specific region pairings. The analysis of pattern similarity among RAPD-PCR profiles highlighted the presence of a 'core' community banding pattern present in all the GP samples, which was strictly associated with the core microbiota highlighted by DNA metabarcoding. A trend to group samples according to the five production regions was also observed. This study widened our knowledge on the bacterial composition and ecology of Grana Padano cheese.